87 PLAGUE Causative Agent Yersinia Pestis Incubation Period 2-6 Days

PLAGUE

Causative Agent PLAGUE Yersinia pestis Causative Agent YersiniaIncubation pestis Period 2 -6 days Incubation Period Infectious2-6 days Period Throughout duration of illness (pneumonic plague is the most important infectious form).Infectious Period Throughout duration of illness (pneumonic plague is the most important infectious Tform).ransmission Transmitted from rats by flea bites, by handling infected animal tissues, or airborne Tbyransmission aerosol from animals or humans with pneumonic plague. Transmitted from rats by flea bites, by handling infected animal tissues, or airborne Epidemiologyby aerosol from animals or humans with pneumonic plague. There are natural foci of plague infection of rodents in many parts of the world. WildEpidemiology rodent plague is present in central, eastern and southern Africa, South AmeThererica, are the natural western foci part of plague of North infection America of rodentsand in large in many areas parts of Asia. of the In world. some Wildareas, contactrodent between plague iswild present and domestic in central, rats is eastern common, and resulting southern in sporadic Africa, Southcases Ameof humanrica, plague the western and occasional part of North outbreaks. America and in large areas of Asia. In some areas, contact between wild and domestic rats is common, resulting in sporadic cases ofIn humanSoutheast plague Asia, and Myanmar occasional and outbreaks.Vietnam report the highest number of cases.

ClinicalIn Southeast Features Asia, Myanmar and Vietnam report the highest number of cases. Plague should be suspected in anyone with fever and painful lymphadenopathy who hasClinical been Featuresto an endemic country. Plague should be suspected in anyone with fever and painful lymphadenopathy who Therehas been are to three an endemic principal country. clinical presentations:  Bubonic plague: initial fever, headache, myalgia followed by painful acute Thereregional are three lymphadenopathy principal clinical presentations: (pathognomonic bubo), typically involving the  inguinal,Bubonic plague axillary: initial or cervical fever, regions. headache, If left myalgia untreated, followed rapid by progression painful acute to regionalsepticaemia lymphadenopathy and secondary plague (pathognomonic pneumonia occurs bubo), (fatality typically 50 - involving60%). the  inguinal,Septicaemic axillary plague or: occurs cervical when regions. Y. pestis If left invades untreated, the bloodstream. rapid progression It can to septifollowca ebubonicmia and plaguesecondary or occurs plague without pneumonia detectable occurs lymphadenopathy(fatality 50 - 60%). (primary  Septicaemicsepticaemic plague plague).: occurs Complications when Y. pestis include invades septic the shock, bloodstream. disseminated It can fointravascularllow bubonic coagulation, plague or occursmeningitis without and multiorgandetectable lymphadenopathyfailure. (primary  septicaemicPneumonic plague: plague). the least Complications common but incl theude most septic dangerous shock, and disseminatedfatal form of ithentravascular disease. Itcoagulation, can develop meningitis as a complication and multiorgan of failure. septicaemic plague or be  Pneumonicacquired dire plague:ctly by the inhalation least common of aerosols but the most from dangerous a human and or fatal animal form with of thepne u disease.monic plague. It can The develop signs as include a complication severe pneumonia, of septicaemic fever, dyspnoea plague or and be acquired directly by inhalation of aerosols from a human or animal with pneumonic plague. The signs include severe pneumonia, fever, dyspnoea and

often haemoptysis. Patients who do not receive treatment within 18 hours of onset of respiratory symptoms are unlikely to survive. often haemoptysis. Patients who do not receive treatment within 18 hours of Investigationsonset of respiratory symptoms are unlikely to survive.  Blood, bubo aspirate, sputum/throat swab, necropsy material can be sent for Investigationsisolation of Y. pestis.  AcuteBlood, and bubo convalescent aspirate, sputum/throat serology for fourfold swab, necropsy rise in titre. material A single can titre be >1:16 sent for is suggestive.isolation of Y. pestis.  InformAcute and the convalescentlaboratory beforehand serology forso fourfoldthat arrangements rise in titre. can A besingle made titre to >1:16forward is samplessuggestive. if necessary to the Department of Pathology, Singapore General  HospInformital, the or laboratory other designated beforehand sites. so that arrangements can be made to forward samples if necessary to the Department of Pathology, Singapore General NotificationHospital, or other designated sites. A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 orNotification electronically via CD-LENS) not later than 24 hours from the time of diagnosis. ACall legally MOH notifiable Communicable disease Diseasesin Singapore. Surveillance Notify Ministry team at: of 98171463Health (Form immediately MD 131 oron electronsuspicion.ically via CD-LENS) not later than 24 hours from the time of diagnosis. Call MOH Communicable Diseases Surveillance team at: 98171463 immediately Managementon suspicion. All cases must be managed at the Communicable Disease Centre (CDC). Management AllGentamicin, cases must st reptomycin,be managed at chloramphenicol the Communicable or tetracyclineDisease Centre are (CDC). highly effective if used within hours of presentation. Gentamicin, streptomycin, chloramphenicol or tetracycline are highly effective if usedInfection within Control hours of presentation.  Patients with uncomplicated infection who are promptly treated present no Infectionhealth Control hazard to others.  PatientsThose with with cough uncomplicated and other infection signs of whopneumonia are promptly must be treated placed present in strict no respirhealtha hazardtory isolation to others. for at least 48 hours after the institution of antibiotic  therapyThose withor until cough the sputum and other culture signs is negative. of pneumonia must be placed in strict  Buborespir a aspiratetory isolation and blood for at must least be 48 handled hours with after gloves the institution and aerosolization of antibiotic of thesetherapy materials or until shouldthe sputum be avoided. culture is negative.  BuboLaboratory aspirate workers and blood must bemust alerted be handled to exercise with precautions gloves and although aerosolization standard of thesebacteriological materials techniquesshould be avoided. that safeguard against skin contact and aerosolization  Laboratoryshould be adequate. workers must be alerted to exercise precautions although standard bacteriological techniques that safeguard against skin contact and aerosolization Preventionshould beand adequate. Control  All cases will be isolated at CDC, Tan Tock Seng Hospital. Prevention Case investigations and Control will be carried out and contact tracing will be intensified.  InAll the cases event will of be death, isolated proper at CDC, disposal Tan of Tock the body Seng is Hospital. important.  CasesCase investigations and close contacts, will be including carried out their and clothing contact andtracing personal will be belongings, intensified. will  beIn thedisinfected event of withdeath, insecticide proper disposal dusting. of the body is important.  Cases and close contacts, including their clothing and personal belongings, will be disinfected with insecticide dusting.

 Anti-flea measures and rodent trapping will be increased at the focus of transmission.  AntiThe -publicflea measures and the World and rodentHealth Organisation trapping will will be be increased informed at of theall suspected focus of andtran sconfirmedmission. cases.  The public andwill thebe Worldadvised Health to step Organisation up measures will to preventbe informed rodent of infestationall suspected in theand premisesconfirmed and cases. to avoid contact with rodents (either live or dead).  The public will be advised to step up measures to prevent rodent infestation in Chemoprophylaxisthe premises and to avoid contact with rodents (either live or dead). Consider antibiotic prophylaxis for the following: Chemoprophylaxis. Persons exposed to patients with pneumonic plague. .Consider Persons antibiotic exposed prophylaxis to bites for of the wild following: rodent fleas during an outbreak or to . tiPersonsssues/fluids exposed of a to plague patients-infected with pneumonic animal. plague. . Persons travelling exposed to to highlybites endemic of wild area rodent for short fleas duration. during an outbreak or to tissues/fluids of a plague-infected animal. For. Persons adults, travelling doxycycline to highly is the endemic best choicearea for (100mgshort duration. orally bd for 7 days). Trimethoprim -sulfamethoxazole is a suitable alternative. For adults, doxycycline is the best choice (100mg orally bd for 7 days). TrimethoprimIndications for-sulfameth vaccine oxazoleusage is a suitable alternative. A formalin-killed plague vaccine has been used for the following groups: Indications Travellers for to vaccine endemic usage or hyperendemic areas. A formalinIndividuals-killed who plague must vaccine live and has work been in used close for contact the following with rodents. groups:  LaboraTravellerstory to workers endemic who or hyperendemicmust handle live areas. cultures of Y. pestis.  MilitaryIndividuals personnel who must deployed live and in workplague in- endemicclose contact areas. with rodents.  Laboratory workers who must handle live cultures of Y. pestis. This Militaryvaccine ispersonnel not routinely deployed available in plague in Singapore.-endemic areas.

This vaccine is not routinely available in Singapore.

References 1. Perry RD, Fetherston JD. Yersinia pestis-etiologic agent of plague. Clin Microbiol Rev 1997; 10:35- References66 2. CDC (Atlanta). Information on plague. Available at: 1. Perry RD, Fetherston JD. Yersinia pestis-etiologic agent of plague. Clin Microbiol Rev 1997; 10:35- http://www.cdc.gov/ncidod/dvbid/plague/info.htm. Accessed Aug 2010. 66 3. Plague as a biological weapon: medical & public health management. JAMA 2000; 283:2281-90 2. CDC (Atlanta). Information on plague. Available at: http://www.cdc.gov/ncidod/dvbid/plague/info.htm. Accessed Aug 2010. 3. Plague as a biological weapon: medical & public health management. JAMA 2000; 283:2281-90

PNEUMOCOCCAL DISEASE (INVASIVE)

Causative agent PNEUMOCOCCAL DISEASE (INVASIVE) Streptococcus pneumoniae (also known as pneumococcus) Causative agent IncubationStreptococcus Period pneumoniae (also known as pneumococcus) Not well defined as colonization usually precedes invasive disease; may be as short asIncubation 1 to 3 days Period. Not well defined as colonization usually precedes invasive disease; may be as short Infectiousas 1 to 3 days Period. Presumably as long as pneumococci are carried in oro-nasal secretions in Infectiousasymptomatic Period individuals (colonization usually lasts weeks to months); with Presumablypenicillin treat as ment,long aspersons pneumococci infected are with carried susceptible in oro -strainsnasal secretions are rendered in non- infectiousasymptomatic within individuals 24-48 hours (colonization. usually lasts weeks to months); with penicillin treatment, persons infected with susceptible strains are rendered non- Transmissioninfectious within 24-48 hours. Respiratory droplets and direct contact with respiratory secretions of an infected personTransmission (usually requires frequent or prolonged close contact). Respiratory droplets and direct contact with respiratory secretions of an infected Epidemiologyperson (usually requires frequent or prolonged close contact). S . pneumoniae is one of the most common causes of invasive infections such as Epidemiologybacteraemia, meningitis and bacteraemic pneumonia, and bacterial mucosal Sinfections. pneumoniae such asis onesinusitis of the and most otitis common media. Of causes the 91 of pneumococcal invasive infections serotypes, such 23 as accounbacteraemia,t for the meningitis vast majority and of bacteraemic invasive pneumococcal pneumonia, disease and bacterial (IPD) in humans.mucosal Theinfections world widesuch emergenceas sinusitis ofand pneumococcal otitis media. resistanceOf the 91 topneumococcal antibiotics, including serotypes, beta 23- accounlactams,t for macrolides, the vast majority tetracycline, of invasive cotrimoxazole pneumococcal and fluoroquinolones disease (IPD) hasin humans. been a Theconside worlrabledwide concer emergencen. of pneumococcal resistance to antibiotics, including beta- lactams, macrolides, tetracycline, cotrimoxazole and fluoroquinolones has been a Invasiveconsider ablepneumococcal concern. infection is defined as the isolation of S. pneumoniae from normally sterile sites such as blood, pleural fluid and cerebrospinal fluid (CSF). PneumococcalInvasive pneumococcal pneumonia infection is considered is defined an invasiveas the isolation disease ofbut S .would pneumoniae be excluded from ifnormally blood or sterile pleural sites fluid such cultures as blood, are pleural sterile. fluid Otitis and media cerebrospinal is not considered fluid (CSF). an Pneumococcalinvasive disease, pneumonia but may is be considered included if an S .invasive pneumoniae disease is isolatedbut would from be excluded normally ifsterile bloo middled or pleural ear fluid. fluid cultures are sterile. Otitis media is not considered an inv asive disease, but may be included if S. pneumoniae is isolated from normally Insterile Singapore, middle earthe fluid.mean annual hospitalisation rate for IPD from 2000-2008 was 8.9 per 100,000 population (about 380 cases per year). A total of 157 deaths from IPD wereIn Singapore, reported theduring mean this annual period, hospitalisation of which 5 were rate underfor IPD the from age of2000 5 years.-2008 In was 2009, 8.9 thereper 100,000 were 251 population reported (about cases 380of IPD. cases Of per these, year). 124 A mettotal the of 157criteria deaths for fromIPD. IPDThe highestwere reported incidence during rate this was period, in children of which < 5 years 5 were of underage and the the age elderly of 5 years. aged 65In 2009,years andthere above. were 251In children,reported serotypescases of IPD. 14, 6B,Of these, 23F, 19F,124 met 6A the and criteria 19A were for IPD. the mostThe highestcommon incidence strains isolated, rate was and in childrenaccounted < 5for years 89% of of age all andinvasive the elderly diseases aged in 65children years and<5 yea above.rs old. In However,children, serotypes in adults, 14, isolate 6B, 23F, distribution 19F, 6A was and more 19A spread were the out most and common strains isolated, and accounted for 89% of all invasive diseases in children <5 years old. However, in adults, isolate distribution was more spread out and

90 common ones were 14, 3, 6B, 8 and 19F which accounted for 51% of all invasive diseases. Mean case fatality rates for IPD in single-centre series were 6.1% in commonchildren butones rising were 14, to 303,% 6B, in 8 childrenand 19F withwhich pneumococcal accounted for meningitis; 51% of all whileinvasive in diadults,seases. this Mean was 21.4%. case fatality rates for IPD in single-centre series were 6.1% in children but rising to 30% in children with pneumococcal meningitis; while in adults,A pneumococcal this was 21.4%. polysaccharide vaccine (23-valent or serotype) has been available locally since 1988. It was recommended for children >2 years old with risk factors forA pneumococcal IPD and adults polysaccharide >65 years old, vaccinebut its immunogenicity (23-valent or serotype) was fair hasand beenits uptake available was verylocally poor. since However, 1988. It itwas would recommended cover 82.8% for children of IPD serotypes>2 years old in adults.with risk A factors highly iformmunogenic IPD and adults pneumococcal >65 years old, conjugate but its vaccineimmunogenicity (7-valent) was was fair licensed and its uptake locally was for childrenvery poor. 6 However,weeks to 9 it years would old cover since 82.8% 2002 of but IPD became serotypes commercially in adults. Aavailable highly locallyimmunogenic only since pneumococcal late 2005, conjugatewith uptake vaccine primarily (7-valent) in children was licensed <5years locally within the for prchildrenivate sector. 6 weeks In November to 9 years 2009, old it since became 2002 the but 10 th became vaccine commercially-preventable disease available to belocally included only in since the National late 2005, Childhood with uptake Immunization primarily Programme. in children <5years within the private sector. In November 2009, it became the 10th vaccine-preventable disease to beClinical included Features in the National Childhood Immunization Programme.  Typically between 40-50% of children and 20-30% of adults carry Clinicalpneum Featuresococci asymptomatically in their nasopharynx.  InfectionTypically isbetween often preceded 40-50% byof childrena respiratory and 20viral-30% illness of adults before carry local disease (frompneum congestionococci asymptomatically and concentration in their of virulent nasopharynx. pneumococci) or invasion  leadingInfection to is systemic often preceded or invasive by a diseaserespiratory viral illness before local disease  Can(from infect congestion any organ and. concentration of virulent pneumococci) or invasion  Mucosalleading to infections systemic includeor invasive acute disease otitis media, bacterial sinusitis,  conjunctivCan infect ianytis. organ.  Mucosal. Otitisinfections media include may be acute complicated otitis media, by mastoiditis bacterial sinusitis, and intrac ranial conjunctivexitistension. with abscess formation. . SinusitisOtitis media may may be complicated be complicated by periorbitalby mastoiditis or orbital and intrac cellulitis,ranial with resultantextension intracranial with abscess extension formation. .  Common. Sinusitis deep-seated may or be invasive complicated infections by periorbital include primary or orbital bacteraemia, cellulitis, with pneumoniaresultant (with orintracranial without bacteraemia extension. ; pneumonia without bacteraemia is  notCommon traditionally deep-seated classified or invasive as “invasive”), infections and include meningitis primary. bacteraemia, pneumonia. Pneumonias (with or without may be bacteraemia complicated; pneumonia by parapneumonic without effusionsbacteraemia and is not traditionallyempyemas classified. as “invasive”), and meningitis. . MeningitisPneumonias is may infrequently be complicated associated by parapneumonic with development effusions of subdural and empyemas,empyemas. intracranial abscesses and vasculitic/ thrombotic . phMeningitisenomena is. infrequently associated with development of subdural  Less commonly,empyemas, it can intracranial also cause abscesses osteomyelitis, and vasculitic/ pyogenic thromboticarthritis, endocardphitis,enomena myocarditis,. pericarditis, bacterial peritonitis, endophthalmitis  Lessand salpingitis commonly,. it can also cause osteomyelitis, pyogenic arthritis,  Inendocard some patientsitis, myocarditis, (especially pericarditis, those who bacterialare immunocompromised), peritonitis, endophthalmitis pneumand salpingitisococcal .infections may be fulminant and present with overwhelming  sepsisIn some and patients multiorgan(especially failure those. who are immunocompromised), pneumococcal infections may be fulminant and present with overwhelming sepsis and multi-organ failure.

Risk Factors: Risk FactorsAge (<5: years and >65 years)  RacialAge (<5 predisposition years and >65 (though years) not evident in local series)  ChronicRacial predisposition illnesses (chronic (though not respiratory, evident in heart,local series) renal and liver disease,  alcohoChroniclism, illnesses diabetes) (chronic respiratory, heart, renal and liver disease,  Cochlearalcoholism, implants diabetes)  CerebrospinalCochlear implants fluid leaks  FunctionalCerebrospinal or fluid anatomic leaks asplenia/ splenic dysfunction (including sickle cell  disease)Functional or anatomic asplenia/ splenic dysfunction (including sickle cell  disease)Immunocompromised —either congenital, acquired (e.g. HIV infection) or  iatrogenicImmunocompromised via immunosuppression—either congenital,. acquired (e.g. HIV infection) or iatrogenic via immunosuppression. Investigations Investigations Microbiological confirmation by culture remains the gold standard for  diagnosisMicrobiological and allows confirmation for sensitivity by culturetesting as remains well as thesubsequent gold standard serotyping; for hodiagnosiswever and the allows yield infor bloodsensitivity may testing be lowas well for as differe subsequentnt pneumococcal serotyping; hosyndromeswever the—high yield in meningitis, in blood low may (around be low 25%) for in differepneumoniant pneumococcal. .syndromes The volume—high of in inoculum meningitis, (usually low (around blood, 25%)uncommonly in pneumonia pleural. fluid or . CSF)The volume is important, of inoculum and blood (usually cultures blood, (if uncommonlypositive) are usuallypleural positivefluid or withinCSF) is 18 important, hours of inoculationand blood cultures (if positive) are usually positive  Gramwithin stains 18 and hours latex of agglutination inoculation testing of infected body fluids (e.g. CSF,  Grampleural, sta peritonealins and latex or agglutination joint fluid) should testing always of infected be performed body fluids and (e.g. may CSF, be helpful,pleural, peritoneal although orother joint streptococci fluid) should may always also be appear performed as Gram and -positive may be diplhelpful,ococci although and latex other agglutination streptococci testin g may lacks also sensitivity. appear as Gram-positive  Urinarydiplococci pneumococcal and latex agglutination cell wall polysaccharide testing lacks sensitivity. (antigen) testing is currently  availableUrinary pneumococcal and a positive cell resultwall polysaccharide is strongly suggestive (antigen) testing of pneumococcal is currently diavailablesease/ pneumonia and a positive in adults, result although is strongly it can suggestive be positive of in pneumococcal the setting of acutedisease/ nasop pneumoniaharyngeal in carriage adults, although (as often it occurs can be in positive children) in and the hencesetting the of specifiacute nasopcity isharyngeal much poorer carriage in children. (as often occurs in children) and hence the  specifiImagingcity (e.g. is much X-ray, poorer computerised in children. tomography, ultrasound, and nuclear or  magneticImaging (e.g. resonance X-ray, imaging) computerised assists tomography, in localising ultrasound, infection in and patients nuclear with or appmagneticropriate resonance clinical symptoms imaging) and assists signs in localising infection in patients with appropriate clinical symptoms and signs Notification ANotification legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 orA legallyelectronically notifiable via diseaseCD-LENS in Singapore.) not later than Notify 72 Ministryhours from of theHealth time (Form of diagnosis. MD 131 or electronically via CD-LENS) not later than 72 hours from the time of diagnosis. Management Management Appropriate resuscitation, oxygenation and invasive or supportive care as  Appropriaterequired; the resuscitation,importance of othisxygenation cannot be and overemphasized invasive or . supportive care as required; the importance of this cannot be overemphasized.

92 92

 Initial choice of empirical antibiotics should be guided by local age- appropriate guidelines for respective clinical syndromes (by institution or  Initialcollege) choice. of empirical antibiotics should be guided by local age-  appropriateOnce confirmed guidelines microbiologically, for respective appropriate, clinical syndromes targeted antibiotic (by institution treatment or coshouldllege) be. guided by susceptibility testing after the initial empirical regime.  .Once P enicillinsconfirmed (followed microbiologically, by 1st and appropriate,2nd generation targeted cephalosporins) antibiotic treatmentare the shouldpreferred be guided choice by susceptibility of antimicrobials; testing however, after the depending initial empirical on the regimesite of . . Pinfection,enicillins much (followed higher by doses 1st and may 2nd be generationrequired, or cephalosporins) 3rd generation are the preferredcephalosporins choice may of ant beimicrobials; used (e.g. meningitis) however, depending. on the site of . infection,Where pneumococci much higher are doses resistant may tobe beta required,-lactams, or 3 treatmentrd generation may be indcephividualizedalosporins with may vancomycin,be used (e.g. qmeningitis)uinolones or. tetracyclines as . appropriateWhere pneumococci. are resistant to beta-lactams, treatment may be  Sourceind controlividualized (e.g. with drainage vancomycin, of infections quinolones in closed or tetracyclines spaces like empyemas as or cerebralappropriate abscesses). are often critical to success or failure of antibiotic  Sourcetreatment control. (e.g. drainage of infections in closed spaces like empyemas or  cerebralAdjunct therapies abscesses) may are also often need critical to be to considered success or e.g. failure dexamethasone of antibiotic in treapneumococcaltment. meningitis, activated protein C in severe pneumococcal sepsis.  Adjunct therapies may also need to be considered e.g. dexamethasone in pneumococcal meningitis, activated protein C in severe pneumococcal sepsis. Prevention and Control  All children <2 years old should receive pneumococcal conjugate vaccine as Preventionrecommended and Control under the National Childhood Immunization Program.  All. childrenChildren <2 <1 years year oldold shouldshould receivereceive 2 pneumococcal primary doses conjugateat 3 months vaccine and 5 as recommendedmonths followed under the by Nationala booster Childhood at 1-2 years Immunization. Program. . Children <1>1 year old should receive 2age primary appropriate doses dosesat 3 months of and 5 monthspneumo followedcoccal conjugate by a booster vaccine at 1and-2 alsoyears depending. on whether they . haveChildren risk >1factors year forold IPD should. receive age appropriate doses of  All adultspneum ≥65ococcal years conjugate old, and vaccinepersons and2 to also 64 dependingyears with onrisk whether factors theyfor IPD (as above)have ris shouldk factors receive for IPD 23-. valent pneumococcal polysaccharide vaccine as  recommendedAll adults ≥65 byyears MOH old,. and persons 2 to 64 years with risk factors for IPD  (asAll above)childhood should vaccinations receive 23 should-valent be pneumococcal notified to the polysaccharide National Immunisation vaccine as recommendedRegistry, Health by MOH Promotion. Board. All post vaccination adverse reactions  Allshould childhood also be vaccinations notified to theshould Pharmacovigilance be notified to the Branch, National Health Immunisation Sciences RegistryAuthority., Health Promotion Board. All post vaccination adverse reactions should also be notified to the Pharmacovigilance Branch, Health Sciences Authority.

References

References1. O’Brien KL, Wolfson LJ, Watt JP et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 2009; 374:893-902 1.2. O’Brienvan der Poll KL, T, Wolfson Opal SM LJ,. Pathogenesis,Watt JP et al. treatmentBurden of and disease prevention caused ofby pneumococcal Streptococcus pneumonia.pneumoniae in Lancetchildren 2009; younger 374:1543 than 5- 56years: global estimates. Lancet 2009; 374:893-902 2.3. vanLow der S, ChanPoll T, F OpalL F, CutterSM. Pathogenesis, J et al. A national treatment study and of theprevention epidemiology of pneumococcal of pneumococcal pneumonia. disease Lancetamong 2009;hospitalised 374:1543 patients-56 in Singapore: 1995 to 2004. Singapore Med J 2007; 48:824-9 3.4. LowChong S, CY,Chan Thoon F L F, KC, Cutter Mok J etYH al. et A al. national Invasive study pneumococcal of the epidemiology disease in of Singapore pneumococcal children. disease Vaamongccine hospitalised 2008; 26:3427 patients-31 in Singapore: 1995 to 2004. Singapore Med J 2007; 48:824-9 4.5. ChongHsu LY, CY, Lui Thoon SW, Lee KC, JL Mok et al. YH Adult et al. invasive Invasive pneumococcal pneumococcal disease disease pre in- Singapore and peri-pneumococcal children. connjugateVaccine 2008; vaccine 26:3427 introduction-31 in a tertiary hospital in Singapore. J Med Microbiol 2009; 58:101-4 5.6. HsuMusher LY, DM. Lui SW,Streptococcus Lee JL et pneumoniaeal. Adult invasive. In Mandell pneumococcal GL, Bennet disease JE, Dolinpre- and R (eds).peri-pneumococcal Principles and connjugatePractice of Infectiousvaccine introduction Diseases. 7th in aed. tertiary Philadelphia, hospital PA:in Singapore. Churchill JLivingstone Med Microbiol; 2010:2623 2009; 58:101-42. -4 6.7. MusherMinistry DM. of Health. Streptococcus Vaccination pneumoniae against pneumococcal. In Mandell GL, disease. Bennet Epidemiol JE, Dolin News R (eds). Bulletin Principles 2010; and 36: 7Practice-15. of Infectious Diseases. 7th ed. Philadelphia, PA: Churchill Livingstone; 2010:2623-42. 7.8. Ministry of Health. VaccinationLaboratory-based against surveillan pneumococcalce system disease. of invasive Epidemiol pneumococcal News Bulletin diseases 2010; in 36: Singapore:7-15. a nationwide monitoring of vaccine serotype coverage. Epidemiol News Bulletin 8. 2010;36:Ministry of40 Health.-5. Laboratory-based surveillance system of invasive pneumococcal diseases in Singapore: a nationwide monitoring of vaccine serotype coverage. Epidemiol News Bulletin 2010;36: 40-5.

POLIOMYELITIS

Causative Agent POLIOMYELITIS Poliovirus, types 1, 2 and 3 Causative Agent IncubationPoliovirus, types Period 1, 2 and 3 7 -14 days (Range 5-35 days) Incubation Period Infectious7-14 days (Range Period 5 -35 days) A few days before and after onset of illness. Infectious Period ATransmission few days before and after onset of illness. Faeco-oral or respiratory transmission. Transmission EpidemiologyFaeco-oral or respiratory transmission. The last indigenous case of poliomyelitis notified in Singapore was in 1973. Epidemiology Globally,The last indigenous polio cases case have of poliomyelitis decreased by notified over in 99% Singapore since 1988, was in from 1973. estimated 350,000 cases then to 1997 reported cases in 2006. In 2008, only four countries remainGlobally, endemic polio cases(northern have India, decreased northern by Nigeriaover 99% and sinceborder 1988, between from Afghanistan estimated and350,000 Pakistan). cases then to 1997 reported cases in 2006. In 2008, only four countries remain endemic (northern India, northern Nigeria and border between Afghanistan andClinical Pakistan). Features  Disease manifestation can range from subclinical infection to severe paralysis Clinicaland death.Features  TheDisease infection manifestation should be can suspected range from in someone subclinical with infection a history to of severe an incomplete paralysis immunisationand death. against polio or recent travel to an endemic country.  ThreeThe infection forms of should paralytic be poliosuspected may bein someoneseen: with a history of an incomplete 1.immunisation Spinal Paralytic against Polio polio or recent travel to an endemic country.  ThreeThis forms is precededof paralytic by polio a “minor” may be illness seen: with fever, muscle pain, headache, 1. nausea,Spinal Paralytic vomiting Polio and stiff neck/back and less frequently, signs of aseptic meningitis.This is preceded The minor by a “minor”illness lasts illness 1- 3 with days fever, followed muscle by a pain, symptom headache,-free periodnausea, of vomiting 1-5 days and beforestiff neck/back the onset and of less “major” frequently, illness signs of of paralysis. aseptic Paralmeningitis.ysis which The variesminor fromillness single lasts muscle 1-3 days involvement followed byto aquadriplegia, symptom-free is usuallyperiod of asymmetric 1-5 days and before typically the onset flaccid of with “major” loss illness of tendon of paralysis. reflexes. ThereParaly sisis no which accompanying varies from sensory single loss. muscle involvement to quadriplegia, is 2. Bulbarusually Paralytic asymmetric Polio and typically flaccid with loss of tendon reflexes. ParalysisThere is no of accompanying the soft palate, sensory pharynx loss. and larynx resulting in dysphagia, 2. nBulbarasal speech Paralytic and Poliodyspnoea. 3. PolioencephalitisParalysis of the soft palate, pharynx and larynx resulting in dysphagia, Encephalitisnasal speech isand manifested dyspnoea. by confusion and change in sensorium. This is 3. anPolioencephalitis uncommon form of polio seen in infants. Seizures are common and thereEncephalitis may be isspastic manifested paralysis by asconfusion opposed and to flaccid change paralysis. in sensorium. This is an uncommon form of polio seen in infants. Seizures are common and there may be spastic paralysis as opposed to flaccid paralysis.

 The most common differential diagnoses are those causing acute flaccid paralysis including transverse myelitis, Guillain-Barré Syndrome, enterovirus  The71 and most West common Nile vir us differential infections. diagnoses are those causing acute flaccid paralysis including transverse myelitis, Guillain-Barré Syndrome, enterovirus Investigations71 and West Nile virus infections.  CSF findings consistent with any viral meningitis. CSF protein is minimally Investigationselevated (unlike in Guillain-Barre syndrome).  PoliovirusesCSF findings can consistent usually be with isolated any viral from meningitis. the throat CSFswab proteinin the first is minimally week of illnesselevated and (unlike stool incultur Guillaines may-Barre remain syndrome). positive for several weeks.  InPolioviruses the absence can ofusually a virus be isolate,isolated the from diagnosis the throat is confirmedswab in the by first a four week-fold of iillnessncrease and in stoolantibody cultur titrees mayof the remain acute andpositive convalescent for several sera. weeks.  In the absence of a virus isolate, the diagnosis is confirmed by a four-fold Notificationincrease in antibody titre of the acute and convalescent sera. A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 orNotification electronically via CD-LENS) not later than 72 hours from the time of diagnosis. A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 Managementor electronically via CD-LENS) not later than 72 hours from the time of diagnosis. Refer all confirmed cases to the Communicable Disease Centre (CDC), Tan Tock SengManagement Hospital, for isolation and management. Specific anti-viral therapy is not Referavailable. all confirmed Management cases is thereforeto the Communicable supportive and Disease symptomatic. Centre (CDC), Tan Tock Seng Hospital, for isolation and management. Specific anti-viral therapy is not available.Prevention Management and Control is therefore supportive and symptomatic.  Case investigation and contact tracing will be carried out to identify Preventionunrecognised and Control and unreported cases. Contacts below 12 years old without  Casecomplete investigation immunisation and will contact be referred tracing to will the nearestbe carried Polyclinic out to or identify School unrecognisedHealth Clinic for and vaccination. unreported cases. Contacts below 12 years old without  comAll plete infants im munisation are routinely will vaccinated be referred against to the poliomyelitis nearest Polyclinic as part or Schoolof the HealthChildhood Clinic Immunisation for vaccination. Programme in Singapore.  BothAll infants IPV (i nactivated are routinely polio vaccinated vaccine) and against OPV (live, poliomyelitis attenuated as vaccine) part of have the beenChild hood used Immunisation for more than Programme 30 years in in controlling Singapore. paralytic poliomyelitis. IPV  Bothshould I PVbe used (inactivated for immunocompromised polio vaccine) and children OPV and (live, adults attenuated including vaccine) travellers. have  Notifybeen used all childhood for more vaccinations than 30 years to inthe controllingNational Immu paralyticnisation poliomyelitis. Registry, Health IPV Promotionshould be used Board for immunocompromised, and post-vaccination children and adverse adults including reactions travellers. to the  NotifyPharmacovig all childhoodilance Branch, vaccinations Health to Sciences the National Authority. Immu nisation Registry, Health Promotion Board, and post-vaccination adverse reactions to the ReferencePharmacovigs ilance Branch, Health Sciences Authority. 1. Chew SK. Certification of poliomyelitis eradication in the World Health Organisation Western Pacific Region. Epidemiological News Bulletin 1997; 23:70-1 Reference2. WHO. Poliomyelitiss 2008. Available at http://www.who.int/mediacentre/factsheets/fs114/en/index.html. 1. ChewAccessed SK. August Certification 2010. of poliomyelitis eradication in the World Health Organisation Western 3. PacificWHO. WildRegion. poliovirus Epidemiological isolation fromNews a BulletinNigerian 1997; child 23:70 with -acute1 flaccid paralysis seeking medical 2. WHO.care in Singapore. Poliomyelitis Week 2008.ly E Availablepidemiological at http://www.who.int/mediacentre/factsheets/fs114/en/index.html Record 2006; 81:285-6. . 4. AccessedLiew F, August Ang LW, 2010. Cutter J et al. Evaluation on the effectiveness of the National Childhood 3. WHO.Immunisation Wild poliovirus Programme isolation in Singapore, from a 1982Nigerian-2007. child Ann with Acad acute Med flaccid Singapore paralys 2010;is seeking 39:532 medical-41. care in Singapore. Weekly Epidemiological Record 2006; 81:285-6. 4. Liew F, Ang LW, Cutter J et al. Evaluation on the effectiveness of the National Childhood Immunisation Programme in Singapore, 1982-2007. Ann Acad Med Singapore 2010; 39:532-41.

RABIES

Causative Agent RABIES Rabies virus Causative Agent RabiesIncubation virus Period 20 - 90 days (range 4 days - 19 years) Incubation Period Infectious20 - 90 days Period (range 4 days - 19 years) Throughout duration of clinical illness Infectious Period TransmissionThroughout duration of clinical illness From saliva of infected animals via bites. Rarely, contamination of mucous Transmissionmembranes by infectious material, aerosol transmission and organ transplantation. From saliva of infected animals via bites. Rarely, contamination of mucous meEpidemiologymbranes by infectious material, aerosol transmission and organ transplantation. Although reservoir is present in many mammalian species, dog bites account for the majorityEpidemiology of human infections. Rabies has not been reported locally since 1953. but Althoughremains prevalent reservoir inis present many parts in many of the mammalian region and species, the world. dog bites Recent account decrease for the in majorityhuman rabies of human cases infections. has been dueRabies to improvedhas not been post reported-exposure locally treatment since as1953. well b asut remainselimination prevalent of rabies in in many animal parts reservoirs of the via region oral andimmunisation the world. of Recent wildlife. decrease in h uman rabies cases has been due to improved post-exposure treatment as well as eliminationClinical Featur of rabieses in animal reservoirs via oral immunisation of wildlife.  The first symptoms of rabies usually begin when the virus enters the CNS. A Clinicalnon- Featurspecifices prodrome of 2-10 days includes fever, malaise, fatigue, anorexia,  cough,The first sore symptoms throat, abdominalof rabies usually pain, nausea,begin when vomiting the virus or diarrhoea. enters the TheCNS. first A rabiesnon-specific-specific prodrome symptom of is2- 10 pain days or includes paraesthesia fever, referred malaise, to fatigue, the site anorexia, of the expcough,osure. sore throat, abdominal pain, nausea, vomiting or diarrhoea. The first  Therabies acute-specific neurological symptom period is pain manifests or paraesthesia as either a referredhyperactive to the(furious site rabies) of the inexp 80%osure. or a paralytic (dumb rabies) form in 20%. Autonomic instability is often  prominentThe acute neurological(hyperthermia, period saliv ation,manifests hypertension as either aand hyperactive tachycardia). (furious rabies)  Thein 80% neurological or a paralytic phase (dumb lasts rabies)2-7 days form before in 20%. development Autonomic of coma instability then death.is often prominent (hyperthermia, salivation, hypertension and tachycardia). Investigations The neurological phase lasts 2-7 days before development of coma then death. No tests are available to diagnose human rabies during the incubation period. Investigations AfterNo tests onset are of available clinical todisease, diagnose diagnostic human rabiesmethods during include: the incubation period.  Direct fluorescent antibody staining of skin biopsy from nape of neck (50%). After Rabies onset ofneutralising clinical disease, antibodies diagnostic in serum methods or CSF. include:  RabiesDirect fluorescentvirus isolation antibody from saliva,staining CSF, of skin urine biopsy and tracheal from nape secretions of neck (low).(50%).  Rabies RTneutralising-PCR in saliva,antibodies CSF, in urine serum and or tissue.CSF.  CorticalRabies virus brain isolation biopsy. from saliva, CSF, urine and tracheal secretions (low).  Rabies. Specimens RT-PCR may in saliva, need toCSF, be senturine overseas and tissue. for tests.  Cortical brain biopsy. . Specimens may need to be sent overseas for tests.

. Post-mortem brain examination for Negri bodies and fluorescent staining for rabies antibodies. . Post-mortem brain examination for Negri bodies and fluorescent staining Notificationfor rabies antibodies. Notify all suspected and confirmed cases immediately. Call MOH Communicable NotificationDiseases Surv eillance team at 98171463 and the Agri-Food and Veterinary NotifyAuthor ity all of suspected Singapore and (AVA) confirmed for further cases investigation. immediately . Call MOH Communicable Diseases Surveillance team at 98171463 and the Agri-Food and Veterinary ManagementAuthority of Singapore (AVA) for further investigation.  There is no specific treatment for clinical human rabies. Intensive supportive Managementcare in the ICU is often used although mortality is virtually 100%.  ThereStandard is noand specific respiratory treatment precautions for clinical should human be observed rabies. by Intensive healthcare supportive workers carecaring in the for ICU such is ofte patients.n used although Pre-exposure mortality immunisation is virtually 100%. of medical staff is  geneStandardrally and not respiratory required. Routine precautions delivery should of be healthcare observed is by no healthcaret an indication workers of postcaring-exposure for such prophylaxis patients. unless Pre-exposure the healthcare immunisation worker is of reasonably medical staff certain is genethat herally or notshe was required. bitten Routine or mucous delivery membranes of healthcare or non- intact is no tskin an indicationwas exposed of topost po-exposuretentially infectious prophylaxis saliva unless or neural the healthcare tissue. worker is reasonably certain that he or she was bitten or mucous membranes or non-intact skin was exposed Preventionto potentially and Control infectious saliva or neural tissue.  In rabies-free Singapore, the AVA exercises strict control on importation and Preventionquarantine and of Control dogs, cats and wild animals and intensive control of stray dog and  Incat rabiepopulation.s-free Singapore, the AVA exercises strict control on importation and  Inquarantine the case of dogs,human cats exposure and wild to animals suspectedand intensive of having control rabies, of stray immediate dog and attemptscat population. should be made to identify, capture or kill the animal involved. The  veterinarian,In the case of AVA, human will exposure remove to the animals brain suspectedof the animal of having to examine rabies, for immediate presence ofattempts rabies virusshould antigen be made by immunofluorescence.to identify, capture or kill the animal involved. The veterinarian, AVA, will remove the brain of the animal to examine for presence Pre-Exposureof rabies virusVaccination antigen by immunofluorescence.  For travellers visiting rabies endemic countries (Central and South America, Pre-ExposureAfrica, Indian Vaccination subcontinent and Southeast Asia), pre-exposure vaccination may  beFor recommended travellers visiting depending rabies ende on mic intended countries activity, (Central duration and South of stay, America, local incAfrica,idence Indian of rabies subcontinent and availability and Southeast of appropriate Asia), preanti--exposurerabies biologicals. vaccination may  Prebe - recommendedexposure vaccination depending greatly on simplifies intended but activity, does not duration eliminate of the stay, need local for postincidence-exposure of rabies treatment. and availability of appropriate anti-rabies biologicals.  Pre-exposure vaccination greatlyconsists simplifies of 3 doses but given does onnot days eliminate 0, 7 and the 21need or for28 days.post-exposure treatment.  ThePre- exposure human diploidvaccination cell consists vaccine of (HDCV) 3 doses isgiven an on inactivated days 0, 7 virusand 21 vaccine or 28 avaidays.lable in Singapore.  The human diploid cell vaccine (HDCV) is an inactivated virus vaccine Post-avaiExposurelable in Treatment Singapore.  The most effective mechanism of protection against rabies is to wash and flush Post-aExposure wound orTreatment point of contact with soap and water, followed by application of  ethanol,The most tincture effective or aqueousmechanism solution of protection of iodine. against rabies is to wash and flush a wound or point of contact with soap and water, followed by application of ethanol, tincture or aqueous solution of iodine.

 Suturing should be postponed and where indicated, anti-tetanus toxoid and antimicrobials should be administered.  RabiesSuturing vaccine should and be postponedimmunoglobulin and where should indicated, be given anti as - soontetanus as toxoid possible and if aindntimicrobialsicated (see tableshould below). be administered. Post-exposure vaccination consists of 5 doses given  onRabies days vaccine 0, 3, 7, and 14 and immunoglobulin 28. Tan Tock should Seng Hospital, be given keeps as soon a stock as possible of rabies if vaccineindicated and (see human table rabiesbelow). immunoglobulin. Post-exposure vaccination consists of 5 doses given on days 0, 3, 7, 14 and 28. Tan Tock Seng Hospital, keeps a stock of rabies Guidevaccine for Post and- Exposurehuman rabies Treatment immunoglobulin.

Guide for PostType-Exposure of contact Treatment with a suspect or confirmed rabid domestic a Category Typeor wild of contactanimal, with or animal a suspect Recommended treatment orunavailable confirmed for rabid observation domestic ICategory Touchingor wild a animal, or feeding or animal of None,Recommended if reliable treatment case history is anunavailableimals. for observation available. I TouchingLicks on intact or feeding skin. of None, if reliable case history is II anNibblingimals. of uncovered skin. avaiAdministerlable. vaccine immediately. b LicksMinor on scratches intact skin. or abrasion Stop treatment if animal remains healthy II Nibblingwithout bleeding. of uncovered skin. Administerthroughout anvaccine observation immediately. period bc of 10 MinorLicks on scratches broken orskin. abrasion Stopdays ortreatment if animal if animalis euthanised remains and healthy without bleeding. throughoutfound to be annegative observation for rabies period by c of 10 Licks on broken skin. daysappropriate or if animal laboratory is euthanised techniques. and III Single or multiple transdermal foundAdminister to be rabiesnegative immunoglobulin for rabies by and bites or scratches. avaccineppropriate immediately laboratory b. techniques.Stop treatment if III SingleContamination or multiple of mucoustransdermal Administeranimal remains rabies healthy immunoglobulin throughout anand bitesmembrane or scratches. with saliva (i.e. vaccineobservation immediately period c ofb. Stop10 days treatment or if the if Contaminationlicks). of mucous animal remainsis euthanised healthy and throughout found to be an membrane with saliva (i.e. observationnegative for periodrabies byc of appropriate 10 days or if the licks). animallaboratory is euthanised techniques. and found to be negative for rabies by appropriate a Source: Rabies pre- and post-exposurelab prophylaxisoratory techniques. in humans (revised 15 June 2010). Dept of Neglected Tropical Diseases. Neglected Zoonotic Diseases team. a WHSource:O, Geneva. Rabies Exposurepre- and post to rodents,-exposure rabbits prophylaxis and hares in humansseldom, (revisedif ever, requires15 June 2010).specific Dept anti -ofrabies Neglected treatment. Tropical Diseases. Neglected Zoonotic Diseases team. b IfWH anO, apparently Geneva. Exposure healthy dog to rodents, or cat in rabbits or from and a hareslow- riskseldom, area ifis ever,placed requires under observation,specific anti- itrabies may treatment.be justified to delay specific treatment. cb ThisIf an obapparentlyservation healthy period appliesdog or cat only in toor dogs from and a low cats.-risk Except area is in placed the case under of threatenedobservation, or it endangered may be justified species, to delayother specificdomestic treatment. and wild animals suspected as c Thisrabid ob shouldservation be period euthanised applies and only their to dogs tissues and examined cats. Except using in appropriatethe case of threatenedlaboratory techniques.or endangered species, other domestic and wild animals suspected as rabid should be euthanised and their tissues examined using appropriate laboratory techniques.

References 1. Rupprecht CE, Hanlon CA, Hemachudha T. Rabies re-examined. Lancet Infect Dis. 2002; 2:327-43 2. Whitley RJ, Gnann JW. Viral encephalitis: familiar infections and emerging pathogens. Lancet 2002; 359:507-13 3. WHO Rabies Fact Sheet No 99 December 2008. Available at http://www.who.int/mediacentre/factsheets/fs099/en/index.html. Accessed August 2010 4. Committee on Epidemic Diseases. An imported case of human rabies in Singapore. Epidemiological News Bulletin 1999; 25:71 5. Warrell MJ, Warrell DA. Rabies and other Lyssavirus diseases. Lancet 2004; 363:959-69 6. CDC (Atlanta). Human Rabies Prevention. Recommendations of the Advisory Committee on Immunization Practices 2008

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RUBELLA

Causative Agent RUBELLA Rubella virus

Causative Agent Incubation Period Rubella virus 2 - 3 weeks

Incubation Period Infectious Period 2 - 3 weeks Few days before until seven days after onset of rash. Infants with congenital rubella syndrome may shed the virus from their body secretions for 1 year or more after Infectious Period birth. Few days before until seven days after onset of rash. Infants with congenital rubella syndrome may shed the virus from their body secretions for 1 year or more after Transmission birth. Respiratory droplets and direct contact with nasopharyngeal secretions.

Transmission Epidemiology Respiratory droplets and direct contact with nasopharyngeal secretions. Rubella immunisation was introduced in Nov 1976 for female primary school leavers at 11+ years of age. However as rubella outbreaks continued to occur in Epidemiology susceptible populations especially national servicemen (NS men), the vaccination Rubella immunisation was introduced in Nov 1976 for female primary school was extended to cover male primary school leavers in 1982. NS men were also leavers at 11+ years of age. However as rubella outbreaks continued to occur in routinely vaccinated to eliminate rubella in army camps. The programme was further susceptible populations especially national servicemen (NS men), the vaccination expanded to include children 1-2 years of age using the trivalent measles, mumps, was extended to cover male primary school leavers in 1982. NS men were also rubella (MMR) vaccine in Jan 1990. The 2nd dose of MMR was introduced in 1997 routinely vaccinated to eliminate rubella in army camps. The programme was further for secondary and junior college students in a catch-up measles vaccination expanded to include children 1-2 years of age using the trivalent measles, mumps, programme and to all primary school leavers in 1998. Since 2008, the 2nd dose of rubella (MMR) vaccine in Jan 1990. The 2nd dose of MMR was introduced in 1997 MMR vaccine is now given at 6-7 years of age (primary 1) under the revised for secondary and junior college students in a catch-up measles vaccination National Childhood Immunisation Programme. programme and to all primary school leavers in 1998. Since 2008, the 2nd dose of TheMMR rubella vaccine incidence is now peaked given at in 6 1996-7 years with of 487 age notifications (primary 1). With under the the catch revised-up measlesNational vaccinationChildhood Immunisation program, the Programme. number of rubella cases has gradually declined from 10.9 cases per 100,000 population in 1999 to 3.6 per 100,000 in 2009. The The rubella incidence peaked in 1996 with 487 notifications. With the catch-up incidence of congenital rubella is about 0-2 cases per year since 1995. measles vaccination program, the number of rubella cases has gradually declined from 10.9 cases per 100,000 population in 1999 to 3.6 per 100,000 in 2009. The Inincidence a serosurveillance of congenital study rubella of is rubella about 0 conducted-2 cases per in year 1998, since it 1995. was found that the ove rall immunity of the population to rubella was 80.2% with the lowest immunity in the 10-14 year age group (65.5%). Another survey in 2004 showed that 15.8% of In a serosurveillance study of rubella conducted in 1998, it was found that the women aged 18 to 44 years were non-immune to rubella (a relatively high level overall immunity of the population to rubella was 80.2% with the lowest immunity compared to women of reproductive age in other developed countries). in the 10-14 year age group (65.5%). Another survey in 2004 showed that 15.8% of women aged 18 to 44 years were non-immune to rubella (a relatively high level It is important to ensure that at least 95% of the children are immunised at 1-2 years compared to women of reproductive age in other developed countries). of age. Congenital rubella can only be completely eliminated if every woman in the

It is important to ensure that at least 95% of the children are immunised at 1-2 years of age. Congenital rubella can only be completely eliminated if every woman in the

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15-44 year age group is immunised against the disease. Women should be advised to be vaccinated before they are married and prior to conception. 15-44 year age group is immunised against the disease. Women should be advised to beClinical vaccinated Features before they are married and prior to conception.  Many cases are subclinical. Clinical Infection Features usually starts with a mild prodrome and appearance of tender  occipital,Many cases post are- auricularsubclinical. and cervical lymphadenopathy which precedes the  appeaInfectionrance usually of the rash. starts with a mild prodrome and appearance of tender  Prodromaloccipital, post symptoms-auricular include and cervical low grade lymphadenopathy fever, headache, which malaise, precedes anorexia, the mildappea r conjunctivitis,ance of the rash. coryza, sore throat, cough and lymphadenopathy. The  symptomsProdromal last symptoms 1 - 5 days include and subside low grade rapidly fever, after headache,the rash appears. malaise, anorexia,  Anmild enanthem conjunctivitis, consisting coryza, of reddish sore throat,spots on cough the soft and palate lymphadenopathy. may be observed The in thesymptoms prodromal last period1 - 5 days or on and the subside first day rapidly of the after rash thebut rash is not appears. diagnostic.  TheAn enanthem rash progresses consisting in aof cephaloreddish- caudalspots on direction the soft andpalate usually may be subsides observed in in 3 days.the prodromal By the period end ofor theon the first first day, day theof thebody rash is but covered is not diagnostic. with red, discrete  maculopapules.The rash progresses By the in athird cephalo day,- caudalthe rash direction disappears and without usually any subsides staining in or 3 desqudays. a mation. By the end of the first day, the body is covered with red, discrete  Themaculopapules. spleen may be By slightly the third enlarged. day, the rash disappears without any staining or  Feverdesqu aifmation. present is usually low grade and lasts 1 - 3 days.  ComplicationsThe spleen may suchbe slightly as arthralgia enlarged. and arthritis, which are more common in  adults,Fever if clear present in aboutis usually 5 - 10low days. grade Encephalitis and lasts 1 -and 3 days. thrombocytopaenia are rare  complications.Complications such as arthralgia and arthritis, which are more common in  Theadults, risk clear of in foetal about infection 5 - 10 days. and Encephalitis congenital anomaliesand thrombocytopaenia depends on stageare rare of precomplications.gnancy at which infection occurs (lower risk after 20 weeks).  The risk of foetal infection and congenital anomalies depends on stage of Differentialpregnancy diagnoses at which include: infection occurs (lower risk after 20 weeks). . Exanthem subitum (Roseola infantum) Differential. Drug diagnoses rash include: . InfectiousExanthem mononucleosissubitum (Roseola infantum) . DrugEnteroviral rash infections . InfectiousMild measles mononucleosis . EnteroviralScarlet fever infections . Mild measles Investigations. Scarlet fever  Indicate on the request form a brief clinical history, as the assays used for Investigationsimmunity screening and for diagnosing recent infection may differ.  RubellaIndicate can on the be diagnosedrequest form by a demonstrating brief clinical a history, fourfold as rise the in assay IgGs antibody used for tiimtresmunity between screening acute and forconvalescent diagnosing samples recent infection and by detecting may differ. rubella -specific  IgMRubella antibody. can be diagnosed by demonstrating a fourfold rise in IgG antibody  Rubellatitres between-specific acute IgM and antibody convalescent is usually samples detectable and by by detecting five days rubella after -onsetspecific of IgMillness antibody. and remains detectable for at least one month but commonly for two  months.Rubella- specific IgM antibody is usually detectable by five days after onset of illness and remains detectable for at least one month but commonly for two months.

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 Caution is advised in interpretation of rubella IgM antibody tests since false positive results are not uncommon. They may arise during other virus infections  suchCaution as those is advised due to inparvovirus interpretation B19, CMV of rubella or EBV. IgM antibody tests since false positive results are not uncommon. They may arise during other virus infections Notificationsuch as those due to parvovirus B19, CMV or EBV. A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 orNotification electronically via CD-LENS) not later than 72 hours from the time of diagnosis. A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 or electronically via CD-LENS) not later than 72 hours from the time of diagnosis. Management  Patient is managed symptomatically. Management If infection occurs in early pregnancy, the patient should be referred to a  gynaecologistPatient is managed or an symptomatically. infectious disease physician who can provide advice and  counsellingIf infection on occurs the possib in earlyle risks pregnancy, of congenital the patient malformation should be and referred appropriate to a gynaecologistmanagement at or that an point infectious in pregnancy. disease physician who can provide advice and  Patientscounselling should on be the isolated possible from risks non of- immune congenital persons malformation (with droplet and precautions) appropriate formanag sevenement days at after that pointonset inof pregnancy.rash.  Patients should be isolated from non-immune persons (with droplet precautions) Preventionfor seven and days Control after onset of rash.  Combined measles/ mumps/rubella (MMR) vaccine is given to all pre-school Preventionchildren and at the Control age 12 -15 months and primary school entrants at the age of 6-7  yearsCombined as part measles/ of the mumps/ru Nationalbella Childhood (MMR) vaccine Immuni issation given Programme to all pre-school (see Appechildrenndix at 2 the). age 12-15 months and primary school entrants at the age of 6-7  yearsRubella as vaccination part of the is alsoNational routinely Childhood offered Immuni at polyclinicssation Programme to non-immune (see Appemarriedndix women 2). and mothers who have just delivered their first babies.  AllRubella unimmunised vaccination children is also at routinely nurseries, offered kindergartens at polyclinics and schools to non where-immune an maoutrbreakried women is occurring and mothers should bewho immunised. have just delivered their first babies.  TheAll unimmunisedvaccine should children be avoided at nurseries,in pregnancy kindergartens and women and who schools received where rubella an vaccineoutbreak should is occurring be advised should to be avoid immunised. pregnancy for one month after vaccination.  The vaccine observed should risk forbe avoided vaccine -inassociated pregnancy congenital and women rubella who received is zero butrubella the thevaccineoretical should risk isbe as advised high as to 2%. avoid The pregnancy currently for recognised one month theoreti after calvaccination. risk does Thenot mandateobserved automatic risk for vaccine termination-associated of pregnancy congenital if rubella a woman is zero has but been the theinadvertentlyoretical risk vaccinated is as high with as 2%. rubella The vaccine. currently recognised theoretical risk does  notAll childhood mandate automaticimmunisations termination should be of notified pregnancy to the if National a woman Immunisation has been inadvertentlyRegistry, Health vaccinated Promotion with Boardrubella. Postvaccine.-vaccination adverse reactions should  Allalso childhoodbe notified immunisations to the Pharmacovigilance should be notifiedBranch, toHealth the National Sciences ImmunisationAuthority. Registry, Health Promotion Board. Post-vaccination adverse reactions should Referencesalso be notified to the Pharmacovigilance Branch, Health Sciences Authority. 1. Committee on Epidemic Disease. Serosurveillance of rubella in Singapore. Epidemiological News ReferencesBulletin 2001; 27:1-3 2. Ang LW, Chua LT, James L et al. Epidemiological surveillance and control of rubella in Singapore, 1. Committee on Epidemic Disease. Serosurveillance of rubella in Singapore. Epidemiological News 1991-2007. Ann Acad Med Singapore 2010; 39; 95-101 Bulletin 2001; 27:1-3 2. Ang LW, Chua LT, James L et al. Epidemiological surveillance and control of rubella in Singapore, 1991-2007. Ann Acad Med Singapore 2010; 39; 95-101

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SEVERE ACUTE RESPIRATORY SYNDROME (SARS) SEVERE ACUTE RESPIRATORY SYNDROME Causative Agent (SARS) SARS -associated coronavirus (SARS-CoV) Causative Agent IncubationSARS-associated Period coronavirus (SARS-CoV) Typically 2-7 days but may be prolonged up to 10-14 days Incubation Period InfectiousTypically 2 Period-7 days but may be prolonged up to 10-14 days Throughout the symptomatic phase of the disease. Infectious Period AlthoughThroughout there the maysymptomatic be persistent phase viral of the shedding disease. in the stool for up to 6 weeks after recovery from clinical illness, transmission of the disease has not been documented fromAlthough asymptomatic there may nor be convalescentpersistent viral individuals. shedding in the stool for up to 6 weeks after recovery from clinical illness, transmission of the disease has not been documented Transmissionfrom asymptomatic nor convalescent individuals. Respiratory droplets and less often by direct contact with objects contaminated by respiratoryTransmission secretions. Oral-faecal and airborne transmission may occur under spRespiratoryecial circumstances. droplets and less often by direct contact with objects contaminated by respiratory secretions. Oral-faecal and airborne transmission may occur under spEpidemiologyecial circumstances. The first outbreak of this new infectious disease occurred in Guangdong, China in EpidemiologyNovember 2002, but soon spread to several Asian countries and Canada by March 2003.The first The outbreak outbreak of this ended new on infectious 5th July disease 2003, althoughoccurred in two Guangdong, cases attrib Chinauted in to Novemberlaboratory transmission2002, but soon were spread reported to several from Singapore Asian countries and Taiwan and Canadain September by March and th 2003.December The 2003, outbreak respectively. ended on Another 5 July laboratory 2003, although associated two outbreak cases attrib occurreduted into Chinalaboratory in April transmission 2004. were reported from Singapore and Taiwan in September and December 2003, respectively. Another laboratory associated outbreak occurred in ChinaThe majority in April of 2004. transmission occurred in hospitals and other institutional healthcare settings. The majority of transmission occurred in hospitals and other institutional healthcare Bysettings. the end of the worldwide outbreak in July 2003, a total of 8096 cases were r eported, with 774 deaths and a case-fatality rate of 9.6 percent. By the end of the worldwide outbreak in July 2003, a total of 8096 cases were Betweenreported, Marchwith 774 and deaths May and2003, a case a total-fatality of 23 rate8 cases, of 9.6 with percent. 33 deaths , were reported in Singapore. 41% of the cases were healthcare workers, and 68% were females. The medianBetween age March of all and SARS May cases 2003, was a total36 (range of 23 48 to cases, 90) years. with 33 deaths, were reported in Singapore. 41% of the cases were healthcare workers, and 68% were females. The median age of all SARS cases was 36 (range 4 to 90) years.

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Clinical Features  The clinical presentation is non-specific and resembles other influenza-like Clinicalillnesses. Features  The prodrome clinical presentation is prolonged is lasting non-specific from 3 and to 7 resembles days and other is characterised influenza-like by filelver,nesses. malaise, headache and myalgia. Respiratory symptoms and diarrhoea, if  present,The prodrome typically is occur prolonged a few lastingdays after from the 3 onset to 7 of days fever. and is characterised by  Physicalfever, malaise, examination headache is not and helpful myalgia. except Respiratory as a gauge symptoms of severity and of illness.diarrhoea, if  Clinicalpresent, typicallymanifestations occur varya few from days mildafter infectionthe onset (80%)of fever. to severe disease (20%)  withPhysical respiratory examination failure is and not death.helpful except as a gauge of severity of illness.  ClinicalDeath is manifestationsusually caused varyby combination from mild infectionof respiratory (80%) and to multiorgansevere disease failure (20%).  withThe clinicalrespiratory course failure is marke and death.d by deterioration in the second week of illness and  Deathrecovery is usuallyby the thirdcaused week by combinationin the majority of respiratoryof cases. Children and multiorgan have a shorter failure and.  milderThe clinical course course of illness. is marke d by deterioration in the second week of illness and  Thererecovery is noby evidence the third atweek present in the of majorityintra-partum of cases. infection. Children have a shorter and milder course of illness. Investigations There is no evidence at present of intra-partum infection.  Chest X-ray. This may be normal early in the course of the disease. However, Investigationsthe more distinct radiographic features include:  .Chest a predominantlyX-ray. This may peripheral be normal location early in of the air course-space ofopacity the disease.; However, .the moreprogression distinct from radiographic unifocal featuresto multifocal include: or bilateral lung involvement . dua predominantlyring treatment ;peripheral and location of air-space opacity; . lackprogression of cavitation, from unifocal lymphadenopathy to multifocal and or pleural bilateral effusion. lung involvement during treatment; and Case. Definitionslack of cavitation, lymphadenopathy and pleural effusion.  At the time of and in the immediate aftermath of the SARS epidemic, both the CaseWorld Definitions Health Organization (WHO) and the US CDC issued case definitions for  SARS.At the time of and in the immediate aftermath of the SARS epidemic, both the  WorldAccording Health to the Organization WHO, a case (WHO) of SARS and theis notifiable US CDC if issued it occurs case in definitions an individual for withSARS. laboratory confirmation of infection who either meets the clinical case  Accordingdefinition orto hasthe WHO worked, a incase a of laboratory SARS is withnotifiable live SARSif it occurs coronavirus in an individual or with withclinical laboratory specimens confirmation infected with of SARS infection coro navirus who either. meets the clinical case  definitionThe clinical or case has definition worked in used a laboratory by the WHO with includes: live SARS coronavirus or with clinical. A history specimens of fever infected or documented with SARS fever coro;navirus and .  .The Oneclinical or morecase definitionsymptoms used of lower by the respiratory WHO includes: tract illness (cough, difficulty . inA historybreathing, of fevershortness or documented of breath); feverand ; and . RadiographicOne or more symptoms evidence ofof lunglower infiltrates respiratory consistent tract illness with (cough,pneumonia difficulty or acutein breathing, respiratory shortness distress of syndromebreath); and (ARDS) or autopsy findings consistent . withRadiographic the pathology evidence of pneumonia of lung infiltrates or ARDS consistent without anwith identifiable pneumonia cause or ; andacute respiratory distress syndrome (ARDS) or autopsy findings consistent . Nowith alternative the pathology diagnosis of pneumonia fully explaining or ARDS the without illness .an identifiable cause;  Laboratoryand diagnostic tests that are required include one or both of the .follo Nowing: alternative diagnosis fully explaining the illness.  Laboratory diagnostic tests that are required include one or both of the following:

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. Detection of virus (reverse transcriptase PCR) assay detecting viral RNA present in two separate samples, or virus culture from any clinical . specDetectionimen. ofThese virus two (reverse samples transcriptase can be obtaine PCRd) fromassay either detecting two viralseparate RNA sitespresent (e. gin. nasopharyngealtwo separate samples, and stool) or virus or from culture the fromsame anysite, clinical but at different timesspecimen. (e.g. Thesesequential two samplesnasopharyngeal can be obtaine aspirates)d from; and/or either two separate . sitesDetection (e.g. nasopharyngealof antibody (a rise and in stool) antibody or from titre, the either same from site, negative but at different to timespositive (e .org. sequentialat least a four nasopharyngeal-fold increase) aspirates) by enzyme; and/or-linked immunosorbent . aDetectionssay (ELISA) of antibody and/or immunofluorescent(a rise in antibody titre, assay either (IFA) from. negative to . Thesepositive are or highly at least sensitive a four-fold and increase)specific but by enzymepositive- onlylinked from immunosorbent the second aweekssay of(ELISA) illness and/oronwards. immunofluorescent assay (IFA). . These are highly sensitive and specific but positive only from the second Notificationweek of illness onwards. A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 Notificationor electronically via CD-LENS) not later than 24 hours from the time of diagnosis. ANotify legally MOH notifiable immediately disease in onSingap suspicion.ore. Notify Call Ministry MOH of Communicable Health (Form MD Diseases 131 orSu relectronicallyveillance team via at: CD 98171463-LENS) not later than 24 hours from the time of diagnosis. Notify MOH immediately on suspicion. Call MOH Communicable Diseases ManagementSurveillance team at: 98171463  All suspected and probable/confirmed cases of SARS will be isolated and Managementtreated at the Communicable Disease Centre (CDC).  SymptomaticAll suspected and and supportive probable/confirmed treatment for cases all cases. of SARS will be isolated and  Ribavirintreated at thewhich Communicable was used initially Disease during Centre the (CDC). pandemic has been shown to be  Symptomaticineffective in andvitro supportive towards SARS treatment coronavirus for all cases. and is associated with significant  Ribavirintoxicities. which was used initially during the pandemic has been shown to be  Someineffective centres in vitro recommend towards SARS a shortcoronavirus course and of is associated moderate with to highsignificant dose corticostetoxicities.r oids.  SomeThere may centres be a recommend role for treatment a short using course protease of moderate inhibitor to like highlopinavir dose, corticosteimmunoglobulinsroids. and interferon based on prior experience.  There may be a role for treatment using protease inhibitor like lopinavir, Infectionimmu Controlnoglobulins and interferon based on prior experience.  Patients with SARS should ideally be nursed in negative pressure isolation Infectionrooms. Control  RespiratoryPatients with (droplet SARS and should airborne) ideally and be contact nursed precautions in negative are pressurerequired. isolation  Proceduresrooms. which may aerosolize the virus (viz. nebulizer therapy) should be  avoidedRespiratory if possible. (droplet and airborne) and contact precautions are required.  MovementProcedures of which patients may (viz. aerosolize for scans the or virusother (viz.procedures) nebulizer within therapy) the hospital should be shouldavoided be if keptpossible. to a minimum.  Movement of patients (viz. for scans or other procedures) within the hospital Preventionshould beand kept Control to a minimum.  Public health measures to limit transmission include: Prevention. Shortening and Control the time from symptom-onset to isolation of patients (viz. early  Publiccase health detection) measures to limit transmission include: . EffectiveShortening contact the time tracing from symptom-onset to isolation of patients (viz. early case detection) . Effective contact tracing

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. Quarantine of exposed persons . Surveillance of fever clusters and atypical pneumonia cases  .A combinationQuarantine of of clinical exposed and persons relevant epidemiological features should raise .suspicions Surveillance of SARS. of fever However, clusters it is and quite atypical likely pneumonia that a de novo cases case will be  Amissed combination initially, of and clinical success and of relevant current epidemiologicalpreventive policies features will be should gauged rais bye the sizesuspicions of the consequentof SARS. However, outbreak. it is quite likely that a de novo case will be  Effortsmissed areinitially, underway and success to prepare of current a vaccine preventive but are stillpolicies at an will early be stage. gauged by the size of the consequent outbreak.  Efforts are underway to prepare a vaccine but are still at an early stage. References 1. SARS Reference. http://www.sarsreference.com. Accessed Aug 2010 References2. CDC (Atlanta) http://www.cdc.gov/ncidod/sars. Accessed Aug 2010 1.3. SARSWHO http://www.who.int/csr/sars/en/index.htmlReference. http://www.sarsreference.com.. AAccessedccessed AugAug 20120100 2.4. CDCPeiris (Atlanta)JS, Yuen http://www.cdc.gov/ncidod/sarsKY, et al. The severe acute respiratory. Accessed syndrome. Aug 201 N0 Engl J Med 2003; 349: 2431-41 3.5. WHOJernigan http://www.who.int/csr/sars/en/index.html JA, Low DE, Hefland RF. Combining clinical. Accessed and epidemiologicAug 2010 features for early 4. recoPeirisgnition JS, Yuen of SARS. KY, et Emerg al. The Infect severe Dis acute 2004; respiratory 10: 327- 33syndrome. N Engl J Med 2003; 349: 2431-41 6.5. GopaJerniganlakrishna JA, Low G, ChooDE, Hefland P, Leo YSRF. etCombining al. SARS clinicaltransmission and epidemiologic and hospital containment.features for early Emerg Infectrecognition Dis. 2004; of SARS. 10:395 Emerg-400 Infect Dis 2004; 10: 327-33 7.6. LimGopa PL,lakrishna Kurup G, A, Choo Gopalakrishna P, Leo YS G et et al. al. SARS Laboratory transmission-acquired and severe hospital acute containment. respiratory Emergsyndrome. InfectN Eng Dis. J Med. 2004; 2004; 10:395 350:1740-400 -5 7.8. LimCase PL, definition Kurups A, for Gopalakrishna the 4 diseases Grequiring et al. Laboratory notification-acquired to WHO severe in all acutecircumstances respiratory under syndrome. the IHR N(2005). Eng J Wkly Med. Epidemiol2004; 350:1740 Rec 2009;-5 84:52 9.8. TaiCase DY definition. Pharmacologics for the 4 treatment diseases requiringof SARS: notification current knowledge to WHO and in all recommendations. circumstances under Ann the Acad IHR Med(2005). Singapore. Wkly Epidemiol 2007;36:438 Rec -2009;43. 84:52 9.10. TaiStockman DY. Pharmacologic L.J., Bellamy R.,treatment Garner of P. SARS: SARS: curren systematict knowledge review ofand treatment recommendations. effects. PLoS Ann Acad Med 3.Singapore. e343.2006 2007;36:438 -43. 10.11. StockmanGoh KT, Cutter L.J., Bellamy J, Heng BHR., Garneret al. Epidemiology P. SARS: systematic and control review of SARS of treatment in Singapore. effects. Ann PLoS Acad Med SingaporeMed 3. e343.2006 2006;35:301 -6. 11. Goh KT, Cutter J, Heng BH et al. Epidemiology and control of SARS in Singapore. Ann Acad Med Singapore 2006;35:301-6.

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SEXUALLY-TRANSMITTED INFECTIONS

Causative AgentsSEXUALLY -TRANSMITTED INFECTIONS In 2009, the top 5 sexually-transmitted infections (STIs) diagnosed in Singapore Causativewere: Chlamydia Agents trachomatis (infection of the urethra, cervix, pharynx and rectum), NeisseriaIn 2009, thegonorrhoeae top 5 sexuall (infectiony-transmitted of the urethra, infections cervix, (STIs) pharynx diagnosed and rectum), in Singapore non- were:gonococcal Chlamydia urethritis trachomatis (NGU), (infection herpes simplex of the urethra, virus (HSV): cervix, pharynx types 1 and and rectum), 2 (ano- Neisseriagenital herpes), gonorrhoeae and human (infection papilloma of the urethra, virus (HPV)cervix, (anopharynx-genital and warts).rectum), Other non- gonococcalimportant STIs urethritis are (NGU),Treponema herpes pallidum simplex (syphilis), virus (HSV): Trichomonas types 1 and vaginalis 2 (ano- (trichomongenital herpes),iasis), and humanhuman immunodeficiency papilloma virus virus (HPV) infection (ano-genital (HIV). warts). Other important STIs are Treponema pallidum (syphilis), Trichomonas vaginalis Incubation(trichomoni asis),Period and human immunodeficiency virus infection (HIV). Chlamydia : 5 - 14 days GonorrhoeaIncubation Period : 3 - 5 days AnoChlamydia-genital herpes : 25 - 14 days AnoGonorrhoea-genital warts : 13- - 6 5 monthsdays (mean 3 months) SyphilisAno-genital herpes : 102 - -14 90 days days (mean 21 days) TrichomoniasisAno-genital warts : a1 -few 6 months days (mean 3 months) HIVSyphilis : mean10 - 90 of days 1 month (mean to 21acute days) HIV infection, Trichomoniasis : meana few ofdays 5 to 8 years to AIDS if untreated HIV : mean of 1 month to acute HIV infection, Infectious Period mean of 5 to 8 years to AIDS if untreated Gonorrhoea, chlamydia : active infection, symptomatic or asymptomatic InfectiousAno-genital Period herpes : presence of vesicles and erosions; asymptomatic Gonorrhoea, chlamydia : activeviral sheddinginfection, issymptomatic also an importa or asymptomaticnt route of Ano-genital herpes : transmissionpresence of vesicles and erosions; asymptomatic Ano-genital warts : higherviral shedding with presence is also of active an importa lesionsnt; route of stransmissionubclinical infections common AnoSyphilis-genital warts : duringhigher withprimary presence and secondary of active stageslesions ; Trichomoniasis : sactiveubclin infection,ical infections symptomatic common or asymptomatic SyphilisHIV infection : infectiousduring primary from andearly secondary on till demise stages if untreated Trichomoniasis : active infection, symptomatic or asymptomatic ClinicalHIV infection Features : infectious from early on till demise if untreated STI may present with: .Clinical genital Features discharges (gonorrhoea, chlamydia, trichomoniasis) STI. mayano- genitalpresent ulcers with: (herpes, syphilis) . anogenital-genital discharges growths (gonorrhoea, (warts, molluscum chlamydia, contagiosum) trichomoniasis) . rashesano-genital (syph ulcersilis, scabies) (herpes, syphilis) . pelvicano-genital inflammatory growths (warts,disease molluscum (gonorrhoea, contagiosum) chlamydia) . epididymorashes (syph-orchitisilis, scabies) (gonorrhoea, chlamydia) . HIVpelvic infection inflammatory may present disease in (gonorrhoea, several ways chlamydia) depending on the organ systems . affectedepididymo (see-orchitis chapter (gonorrhoea, on HIV). chlamydia) . HIV infection may present in several ways depending on the organ systems affected (see chapter on HIV).

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Many STIs may be asymptomatic and can be detected only if the appropriate laboratory screening tests are performed (see references). Many STIs may be asymptomatic and can be detected only if the appropriate laborInvestigationsatory screening and Guide tests are to performedDiagnosis (see references).  Ano-genital Herpes (First episode/ Recurrent) Investigations. Typical and vesicles Guide orto erosionsDiagnosis in the ano-genital area (may be severe with  Ano-ingenitalitial episode Herpes). (First episode/ Recurrent) . TypicalConfirmed vesicles by viral or isolation, erosions indirect the immunofluorescenceano-genital area (may (DIF be )severe, PCR, withEIA orini tialtype episode-specific). serological test against glycoprotein gG1 (HSV-1) & gG2 . (HSVConfirmed-2) for by HSV viral (serologyisolation, isdirect not immunofluorescence useful for first episode (DIF infection), PCR, asEIA it takesor type between-specific 6serological and 8 weeks test foragainst serological glycoprotein detection gG1 following(HSV-1) & a gG2 first ep(HSVisode)-2). for HSV (serology is not useful for first episode infection as it takes between 6 and 8 weeks for serological detection following a first  Chlamydiaepisode) Genital. Infection—(A laboratory diagnosed infectious disease) . Nucleic acid amplification test (NAAT) (e.g. PCR) positive for C.  Chlamydiatrachomatis Genital from Infection ano-genital—(A lspecaboratoryimen or diagnosed urine; or infectious disease) . AntNucleicigen detectionacid amplification (e.g. EIA, test IF) positive(NAAT) for (e.g. C. PCR)trachomatis positive from for ano C.- trgenitalachomatis specimen from. ano-genital specimen or urine; or . AntChlamydiaigen detection serology (e.g. is not EIA, useful IF) as positive it does not for distinguishC. trachomatis between from past ano or- currentgenital specimen infection;. there is also cross-reactivity with other chlamydial . spChlamydiaecies. serology is not useful as it does not distinguish between past or current infection; there is also cross-reactivity with other chlamydial  Gonorrhoeaspecies. . Purulent genital discharge (associated with dysuria in males), history of  Gonorrhoearecent unprotected sexual intercourse; or . GramPurulent-stained genital smear discharge from (associated genital with discharges dysuria with in males), Gram history-negative of intracellrecent unprotectedular diplococci sexual; or intercourse ; or . PGramositive-stained culture smearon selective from media genital for N. discharges gonorrhoeae with; or Gram-negative . Urineintracell nucleicular diplococci acid amplification; or test (NAAT) (e.g. PCR) positive for N. . Pgonorrhoeaeositive culture. on selective media for N. gonorrhoeae; or . UrineGonorrhoea nucleic serology acid amplification is not useful testdue to (NAAT) lack of (e.g.sensitivity PCR) & positive specificity. for N . gonorrhoeae.  Non. -GonorrhoeaGonococcal serology Urethritis is (NGU) not useful due to lack of sensitivity & specificity. . Mucopurulent or whitish discharge from urethra associated with dysuria or  Non-urethralGonococcal discomfort/itch Urethritis (NGU) in males, history of recent unprotected sexual . iMucopurulentntercourse; or or whitish discharge from urethra associated with dysuria or . Gramurethral-stained discomfort/itch smear showing in males, increased history pus cell of count recent (5 unprotected or more WBC sexual per highintercourse-power; field)or in absence of Gram-negative intracellular diplococci; or . VisibleGram-stained threads smear in the showing first glass increased of a 2 glass pus urinecell count test. (5 or more WBC per high-power field) in absence of Gram-negative intracellular diplococci; or  Infectious. Visible Syphilis threads in the first glass of a 2 glass urine test. . Presence of primary chancre usually solitary, indurated, non-tender (but the  Infectiousulcer maySyphilis also be atypical), inguinal lymphadenopathy; or . Presence of primary chancre usually solitary, indurated, non-tender (but the ulcer may also be atypical), inguinal lymphadenopathy; or

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. Presence of clinical features of secondary syphilis e.g. rash especially on palms and soles, ano-genital patches and growths, generalized . lymphadPresencee ofnopathy, clinical patchy features hair of loss se;condary confirmed syphilis by: e.g. rash especially on palms and. Positive soles, dark ano--genitalfield microscopic patches examination and growths, of exudate generalized from lymphadenopathy,primary patchy or secondary hair loss ;ano confirmed-genital bylesions: for spirochaetes; or . RePositiveactive darkblood-field tests microscopic for syphilis :examination of exudate from 1. Nonprimary-specific or secondary treponemal ano tests-genital (RPR/VDRL) lesions for spirochaetes ; or 2.. SpecificReactive treponemalblood tests testsfor syphilis (TPPA/TPHA,: LIA, Syphilis EIA) 1. Non-specific treponemal tests (RPR/VDRL)  Non-Infectious2. SyphilisSpecific treponemal tests (TPPA/TPHA, LIA, Syphilis EIA) . Presence of clinical features of tertiary syphilis (viz. cardiovascular  Non-syphInfectiousilis, central Syphilis nervous system syphilis); or . AsymptomaticPresence of clinical infection features with rea ctive of tertiary blood tests syphilis for syphilis (viz. cardiovascular . Notesyphi lis,- persistence central nervous of reactive system serology syphilis) in; patientsor with treated syphilis may . beAsymptomatic indicative of infection a serological with scarreactive blood tests for syphilis . Note - persistence of reactive serology in patients with treated syphilis may  Congenitalbe indicative Syphilis of a serological scar . Presence of clinical features of active disease (e.g. muco-cutaneous signs,  Congenitalbone changes Syphilis, hepatosplenomegaly ) and confirmed by reactive blood tests . forPresence syphilis of. c linical features of active disease (e.g. muco-cutaneous signs, . Asymptomaticbone changes, infectionhepatosplenomegaly in infant born) and to cinfectedonfirmed mother by rea withctive: blood tests for syphilis. . Detectable LIA IgM in infant; or . Asymptomatic. RPR/VDRL infection in titreinfant in borninfant to fourfoldinfected ormother greater with than: in mother; . orDetectable LIA IgM in infant; or . RPR/VDRL titres inshow infant serial fourfold rise; or or greater than in mother; . Reactiveor CSF-VDRL or abnormal CSF FEME in infant. . RPR/VDRL titres show serial rise; or  Trichomoniasis. Reactive CSF-VDRL or abnormal CSF FEME in infant. . Diagnosed by direct wet-mount microscopy and culture. Serology is not  Trichomoniasisuseful. . Diagnosed by direct wet-mount microscopy and culture. Serology is not  Mycoplasmauseful. : There are no clear guidelines for screening with serology.

 CandidaMycoplasma: Serology: The reis arenot nouseful clear as guidelines it is not indicative for screening of a genitalwith serology. cause/disease.

 Candida: Serology is not useful as it is not indicative of a genital cause/disease. Management  All patients with a STI should be screened for syphilis, hepatitis B and HIV Managementinfection.  PatientsAll patients shoul withd receive a STI recommended should be screened antimicrobials for syphilis, in the hepatitiscorrect dosages B and HIV(see references).infection. Test-of-cure is important to assess treatment efficacy particularly  forPatients gonorrhoea should andreceive syphilis. recommended antimicrobials in the correct dosages (see references). Test-of-cure is important to assess treatment efficacy particularly for gonorrhoea and syphilis.

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 Chlamydia: . Doxycycline 100mg bid x 7days (avoid if pregnant)  .C hlamydiaErythromycin: 500mg qid x 7 days . DErythromycinoxycycline 100mg ethylsuccinate bid x 7days 800 (avoidmg qid if x pregnant)7days . AzithromycinErythromycin 5001gmmg x 1 qid dose x 7 (useful days if adherence is an anticipated problem) . Erythromycin ethylsuccinate 800 mg qid x 7days  .G onorrhoeaAzithromycin: 1gm x 1 dose (useful if adherence is an anticipated problem) . All patients with gonorrhoea should be given concurrent treatment for  Gonorrhoeachlamydia: . . FluoroquinolonesAll patients with are gonorrhoea not recommended should be due given to high concurrent prevalence treatment (80%) for of resistancechlamydia .in N. gonorrhoeae. . RepeatFluoroquinolones smears and are cultures not recommended should be performed due to high on prevalence or around (80%) the 14th of postresistance-treatment in N. day. gonorrhoeae . . ForRepeat those smears with and penicillin cultures allergy, should IMbe performed spectinomycin on or can around be used the . 14th Or considerpost-treatment allergy day. test ing and desensitization. Specialist consultation . recoFor m thosemended. with penicillin allergy, IM spectinomycin can be used. Or . Uncomplicatedconsider allergy (pharynx/urethra/rectum/cervix): testing and desensitization . Specialist consultation recommended.. IM Ceftriaxone 250mg x 1 dose; or . Uncomplicated. Cefixime (pharynx/urethra/rectum/cervix): 400mg x 1 dose . Severe or. Disseminated IM Ceftriaxone Gonococcal 250mg Infectionsx 1 dose; or (DGI) : . IVCefixime Ceftriaxone 400mg 1x- 2g1 dose daily. Duration depending on site of . Severe or Disseminatedinfection and Gonococcal response Infections (DGI): . IV Ceftriaxone 1-2g daily. Duration depending on site of  Syphilis: infection and response . Cases of syphilis should be treated with intramuscular benzathine penicillin.  Syphilis:They should have serological tests repeated at 3 months, and then every 6 . monthsCases of for syphilis 2 years. should Suspected be treated cases with of neurintramuscularosyphilis should benzathine have penicillin.a lumbar punctureThey should performed. have serological tests repeated at 3 months, and then every 6 . Formonths late forlatent 2 years. syphilis, Suspected syphilis cases of unknown of neurosyphilis duration, should congenital have asyph lumbarilis, neurosyphilispuncture performed. or syphilis in pregnancy, the treatment recommendations are . differentFor late latentand relevant syphilis, expert syphilis advice of shouldunknown be duration,sought. congenital syphilis, . Primaryneurosyphilis and Secondary or syphilis Syphilis in pregnancy: , the treatment recommendations are different .and relevant IM Benzathine expert advice Penicillin should G 2.4 be millionsought. units x 1 dose. (Some . Primary and Secondaryauthorities Syphilisuse 2 doses: for secondary syphilis); or . IM IM AqueousBenzathine Procaine Penicillin Penicillin G 2.4 million G 600,000 units unitsx 1 dose daily. (Some x 10 daysauthorities use 2 doses for secondary syphilis); or . Penicillin. allergicIM Aqueouspatients: Procaine Penicillin G 600,000 units daily x 10 . Doxycyclinedays 100mg bid x 14 days; or . Penicillin. allergicErythromycin patients: 500mg qid x 14 days; or . AzithromycinDoxycycline 100 500mgmg bid daily x 14 x 10days; days or . Erythromycin 500mg qid x 14 days; or . Azithromycin 500mg daily x 10 days

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 Cases of first-episode genital herpes should be treated with acyclovir or related medications. Recurrent genital herpes may be treated with either episodic or  suCasesppressive of first anti-episode-viral regimensgenital herpes (see references) should be .treated with acyclovir or related  Anomedications.-genital warts Recurrent can genital be treated herpes medically may be or treated surgically; with either they episodic should be or followedsuppressive up anti till-viral all regimens visible warts(see references) are cleared.. Regular PAP smears are  recoAno-mgenitalmended warts for female can bepatients. treated medically or surgically; they should be  followedCases of trichomoniasisup till all visible are tre ated warts with are metronidazole cleared. Regular (see references). PAP smears are recommended for female patients.  Cases of trichomoniasis are treated with metronidazole (see references). Notification  Chlamydia, gonorrhoea, syphilis (infectious, non-infectious and congenital), NotificationNGU, genital herpes (first episode and recurrent) should be notified to the DSC  clinicChlamydia, by fax gonorrhoea,(62994335) using syphilis form (infectious, MD 131 or nonelectronically-infectious via and CD congenital),-LENS.  NGU,Provide genital information herpes on(first type episode of HSV and detected recurrent) where should available be notified. to the DSC  Repeatclinic by notifications fax (62994335) of recurrent using form genital MD herpes 131 or are electronically not necessary via. CD-LENS.  TheProvide name, information NRIC, address on type and of HSV telephone detected number where need available not .be completed, but  Repeatinitials, notificationssex, date of birth,of recurrent ethnicity genital and residential herpes are statusnot necessary should be. provided.  The name, NRIC, address and telephone number need not be completed, but Preventioninitials, andsex, Controldate of birth, ethnicity and residential status should be provided.  Patients with STI should be given information about their current infection. Prevention To prevent and futureControl infections, information on safer sex should be given too e.g.  Patientscorrect and with consistent STI should condom be given use. information about their current infection.  PartnerTo prevent management/contact future infections, tracinginformation should on be safer condu sexcted should to diagnose be given and too treate.g. correctinfections and in c onsistentsex partners, condom to prevent use. complications and further transmission.  AntenatalPartner management/contact mothers should be tracing routinely should screened be condu for cted syphilis, to diagnose hepatitis and B treat and HinfectionsIV infection. in sex partners, to prevent complications and further transmission.  HepatitisAntenatal B mothers vaccination should should be routinely be given screened to those for who syphilis, are negative hepatitis for B HBV and markers.HIV infection.  BrothelHepatitis-based B vaccination sex workers should are provided be given with to thoseSTI/HIV who educational are negative information for HBV andmarkers. taught negotiation skills to achieve 100% condom use; they are screened  routineBrothelly-based for syphilis, sex workers gonorrhoea, are provided chlamydia, with STI/HIV HIV and educational hepatitis B information infections. andTargeted taught STI/HIV negotiation education skills to for achieve at risk 100% groups condom e.g. youth,use; they MSM, are screened military routinepersonnel,ly for and syphilis, clients of gonorrhoea, sex workers chlamydia, should be conductedHIV and hepatitis regularly. B infections.  PatientsTargeted are STI/HIV encouraged education to seek for early at risk trea groupstment, e.g. not to youth, self- medicate MSM, military and to completepersonnel, all and prescribed clients of medications. sex workers should be conducted regularly.  SelfPatients-medication are encouraged with antibiotics to seek may early result trea tment,in the notemergence to self -ofmedicate drug-resistant and to strains.complete Medical all prescribed practitioners medications. should not dispense antibiotic chemoprophylaxis  asSelf there-medication is no one with univers antibioticsally effective may result antibiotic, in the this emergence may also of result drug in-resistant a false sensestrains. of Medical security practitionersand may be dangerous. should not dispense antibiotic chemoprophylaxis as there is no one universally effective antibiotic, this may also result in a false sense of security and may be dangerous.

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References

References1. DSC clinic website: http://www.dsc-sexualhealth.com.sg. Accessed Dec 2010. 2. STI Management Guidelines - Department of STI Control, National Skin Centre, 2007 3.1. MOHDSC clinic Clinical website: Practice http://www.dsc Guidelines-sexualhealth.com.sg on genital . Accessed ulcers Dec & 2010 discharges,. May 2009: 2. http://www.moh.gov.sg/mohcorp/publications.aspx?id=22326STI Management Guidelines - Department of STI Control, National. Accessed Skin DecCentre, 2010. 2007 3. MOH Clinical Practice Guidelines on genital ulcers & discharges, May 2009: http://www.moh.gov.sg/mohcorp/publications.aspx?id=22326. Accessed Dec 2010.

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SHIGELLOSIS (BACILLARY DYSENTERY)

Causative AgentSHIGELLOSISs (BACILLARY DYSENTERY) Shigella sonnei, S. flexneri, S. boydii and S. dysenteriae. Causative Agents IncubationShigella sonnei, Period S. flexneri, S. boydii and S. dysenteriae. Usually 1 - 3 days. Up to 1 week for S. dysenteriae type 1 Incubation Period InfectiousUsually 1 - Period3 days. Up to 1 week for S. dysenteriae type 1 Throughout duration of acute illness and until the organism is no longer present in theInfectious stool, usually Period within 4 weeks after illness. Throughout duration of acute illness and until the organism is no longer present in Transmissionthe stool, usually within 4 weeks after illness.  Direct or indirect faecal-oral transmission from a symptomatic person or short- Transmissionterm asymptomatic carrier. Also via faecally-contaminated water, milk or food.  TransmissionDirect or indirect by house faecal flies-oral has transmission also been documented.from a symptomatic person or short-  Asterm few asymptomatic as 10-100 carrier. organisms Also can via causefaecally infection,-contaminated enabling water, person milk-to or-person food. transmissionTransmission where by house hygiene flies conditionshas also been are documented. compromised.  OutbreaksAs few as have 10-100 occurred organisms in homosexual can cause men;infection, under enabling conditions person of - crowding;to-person andtransmission where personal where hygiene hygiene conditions is poor such are compromised. as in day care centres, jails, mental  insOutbreakstitutions haveand crowded occurred refugee in homosexual camps. men; under conditions of crowding; and where personal hygiene is poor such as in day care centres, jails, mental Epidemiologyinstitutions and crowded refugee camps. Endemic throughout the world with the greatest burden of disease occurring in developingEpidemiology countries afflicting children less than five years of age particularly. S. soEndemicnnei accounts throughout for the the majority world ofwith shige thellosis greatest in developed burden countries. of disease occurring in developing countries afflicting children less than five years of age particularly. S. Inso nSingapore,nei accounts a fortotal the of majority 29 sporadic of shige casesllosis of inshigellosis developed were countries. reported in 2008, as compared to 13 cases in 2007. The serotypes involved were Shigella sonnei (75.9%),In Singapore, Shigella a total dysenteriae of 29 sporadic (13.8%), cases and ofShigella shigellosis boydii were (10.3%) reported. Of thein 2008,reported as cases,compared 17 were to 13 local cases residents in 2007. comprising The serotypes 12 indigenous involved and were five Shigella imported sonnei cases. There(75.9%), were Shigella two non dysenteriae-residents (13.8%),that acquired and Shigellathe infection boydii locally. (10.3%) The. Of remaining the reported 10 casescases, comprised17 were local one residents tourist and comprising nine foreigners 12 indigenous seeking and medical five imported treatment cases. in SingThereapore. were Thetwo non five- residents imported that cases acquired acquired the theinfection infection locally. from The Bangladesh remaining (1), 10 Cambodiacases comprised (1), Hong one Kong tourist (1), andIndia nine(1) and foreigners Nepal (1). seeking medical treatment in Sing apore. The five imported cases acquired the infection from Bangladesh (1), CambodiaIncreasing (1), antibiotic Hong Kong resistance (1), India to flouroquinolones (1) and Nepal (1). (esp. in Asia), nalidixic acid, TMP/SMX, ampicillin and tetracycline, has been reported. Increasing antibiotic resistance to flouroquinolones (esp. in Asia), nalidixic acid, S.TMP/SMX, dysenteriae ampicillin type 1 (SD1) and tetracycli serotypene is, hasresponsible been reported. for epidemics and for the most severe clinical illness of Shigella species. Only SD1 elaborates true Shiga toxin—a neurotoxinS. dysenteriae and typeenterotoxin 1 (SD1) that serotyp is associatede is responsible with the for Haemolyti epidemicsc Uremic and for Syndrome the most severe clinical illness of Shigella species. Only SD1 elaborates true Shiga toxin—a neurotoxin and enterotoxin that is associated with the Haemolytic Uremic Syndrome

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(HUS). All Shigella species secrete enterotoxins responsible for the watery diarrhoea. (HUS). All Shigella species secrete enterotoxins responsible for the watery diaClinicalrrhoea. Features Causes a spectrum of illness from watery diarrhoea to classical dysentery. Clinical Features TheCauses spectrum a spectrum of diseaseof illness severity from watery varies diarrhoea according to classical to the host’sdysentery immunity. and serogroup of the infecting organism. S. sonnei commonly causes mild disease, which Themay be spectrum limited ofto disease watery diarrhoea, severity varies while accordingS. dysenteriae to th ore S. host’s flexneri immunity commonly and serogroupcauses dysenteric of the infecting symptoms. organism. In a normalS. sonnei healthy commonly host, causes the course mild disease, of disease which is maygenerally be limited self-limited, to watery lasting diarrhoea, no more whilethan sevenS. dysenteriae days when or left S. untreated.flexneri commonly causes dysenteric symptoms. In a normal healthy host, the course of disease is generally self-limited, lasting no more than seven days when left untreated.  Diarrhoea: Sudden onset; initial voluminous watery stool (small intestine phase); subsequently containing blood and mucus (colonic phase); fluid  Diarrhoea:depletion typically Sudden uncoonset;mmon. initial voluminous watery stool (small intestine  phase);Fever subsequently containing blood and mucus (colonic phase); fluid  Nauseadepletion. Occasionally typically unco vomitingmmon.  AbdominalFever cramps  TenesmusNausea. Occasionally (common) vomiting  StoolsAbdominal usually cramps contain blood and mucous (dysentery)  TenesmusPainful rectal (common) examination by proctoscopy and the rectum may be hyperaemic  Stoolsor ulcerated. usually contain blood and mucous (dysentery)  Painful rectal examination by proctoscopy and the rectum may be hyperaemic Complicationsor ulcerated.  Intestinal: Complications. Proctiti s/rectal prolapse  Intestinal:. Toxic megacolon . IntestinalProctitis/rectal obstruction prolapse . ColonicToxic megacolon perforation . ProteinIntestinal losing obstruction enteropathy  Systemic:. Colonic perforation . ReactiveProtein losing arthritis: enteropathy May follow after S. flexneri infection. Can be seen  Systemic:alone or in association with conjunctivitis and urethritis (formerly . Reactiveknown as arthritis:Reiter’s syndromeMay follow). HLA after- B27S. flexneri associated. infection. Can be seen . Haloneaemolytic or in- uremic association syndrome with in conjunctivitis Shiga toxin producing and urethritis strains. (formerly . Neurologicalknown as Reiter (seizure,’s syndrome headache,). HLA encephalopathy,-B27 associated. lethargy, confusion) . Haemolytic-uremic syndrome in Shiga toxin producing strains. Investigations. Neurological (seizure, headache, encephalopathy, lethargy, confusion)  Stool leukocytes and culture (select portion with blood or mucus) or rectal swab Investigations(if the patient is unable to provide a stool specimen). Shigella is a fastidious  Stoolorganism; leukocytes and requires and culture prompt (select handling portion. Antibioticswith blood or susceptibility mucus) or rectal testing swab is (ifneeded the patientfor all specimen is unables . to provide a stool specimen). Shigella is a fastidious organism; and requires prompt handling. Antibiotics susceptibility testing is needed for all specimens.

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 Blood cultures are usually negative

Notification Blood cultures are usually negative If two or more cases are recognised in an institution, this should be reported to the MinistryNotification of Health (Form MD 131 or electronically via CD-LENS). Shigellosis is no Iflonger two aor notifiable more cases disease are recognised. in an institution, this should be reported to the Ministry of Health (Form MD 131 or electronically via CD-LENS). Shigellosis is no Managementlonger a notifiable disease.  Mild infections are usually self-limited and most patients recover without Managementantibiotic treatment.  AnyoneMild infections whose stool are usually cultures self are- limited positive and for mShigellaost patients should recover be treated without for puantbibioticlic health treatment. reasons.  AntibioticsAnyone whose shorten stool the cultures duration are of fever, positive diarrhoea for Shigella and shedding should beof Shigella treated for in stoolpublic. health reasons.  TreatmentAntibiotics regimen shortens the include: duration of fever, diarrhoea and shedding of Shigella in stool.. Ciprofloxacin 500 mg bd x 5 days (Recommended)  Treatment. Azithromycin regimens include: 500 mg day1, then 250mg daily x 4 days (Alternative) . CiprofloxacinIV Ceftriaxone 500 1-2 mg gm bd daily x 5 fordays hospitalized (Recommended) patients  Anti-.diarrhoeal Azithromycin agents can500 make mg day1, the illness then 250mg worse dailyand should x 4 days be (Alternative)avoided. . IV Ceftriaxone 1-2 gm daily for hospitalized patients Infe ctionAnti- diarrhoealcontrol agents can make the illness worse and should be avoided. Contact precautions should be observed when nursing a patient with shigellosis. ThisInfection involves control strict hand-washing before and after handling the patient as well as wearingContact precautionsof personal should protective be observedgarments whene.g. plastic nursing aprons. a patient Proper with handling shigellosis. and disposalThis involves of stool strict is handimportant-washing as the before organism and after is present handling in the large patient amounts as well in the as stool.wearing of personal protective garments e.g. plastic aprons. Proper handling and disposal of stool is important as the organism is present in large amounts in the Foodstool. handlers infected with Shigella must be treated with antibiotics and should not be involved in preparation of food as long as their stool cultures are positive; coFoodnversion handlers of theinfected stool withto negative Shigella generally must be requirestreated with at least antibiotics 48 hours and of should antibiotic not treatment.be involved Health in preparation care and day of care food cent asre long workers as theirshould stool always cultures be treated are positivas well.e; co nversion of the stool to negative generally requires at least 48 hours of antibiotic treatment.Prevention Health and Control care and day care centre workers should always be treated as well.  The Ministry of Health will carry out epidemiological investigations to trace the Preventionsource of and infection Control when an outbreak is suspected.  ContactsThe Ministry and offood Health handlers will carrywill be out screened epidemiological for Shigella inv estigationsand those foundto trace to thebe sourceinfected of will infection be treated. when an outbreak is suspected.  ContactsA high standardand food ofhandlers personal will andbe screened food hygiene for Shigella is important and those in found preventing to be trainfectednsmission. will be treated.  A high standard of personal and food hygiene is important in preventing transmission.

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References 1. Thielman NM, Guerrant RL. Acute infectious diarrhoea. N Engl J Med 2004; 350:38-47 2Re. feCrhenceristopsh er PR, David KV, John SM et al. Antibiotic therapy for Shigella dysentery. Cochrane 1. TDhiatealbmaasen SNyMst ,R Geuve. rr20ant10 R ALu.g A 4;cut(8e) :iCnDfe0c0ti6o7u8s4 d. iAarrvhaioleaab.l eN a Et:n gl J Med 2004; 350:38-47 2. Chthtpri:/s/tiopnfhoe.or nPliRn,e Dlibarvairdy K.wVil,e Jyo.chonm S/Mus eerft ilale. sA/ccntoibicho/tificle t/hCeDra0p0y6 7fo8r4 S.phdifg.e Allac cedyssseendt eDryec. C20o1ch0r. ane Database Syst Rev. 2010 Aug 4;(8):CD006784. Available at: http://info.onlinelibrary.wiley.com/userfiles/cco ch/file/CD006784.pdf. Accessed Dec 2010.

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SMALLPOX

Causative Agent SMALLPOX Variola virus, a species of Orthopoxvirus Causative Agent IncubationVariola virus, Period a species of Orthopoxvirus 12 -14 days (range 7-17 days) Incubation Period 12Infectious-14 days Period(range 7-17 days) From fever onset (usually 2–4 days before rash) until last scab has separated; about threeInfectious weeks. Period From fever onset (usually 2–4 days before rash) until last scab has separated; about Transmissionthree weeks. Aerosols/droplets from nasopharyngeal lesions and contact with contaminated aTransmissionrticles. Aerosols/droplets from nasopharyngeal lesions and contact with contaminated aEpidemiologyrticles. Last naturally acquired human case in the world occurred in Somalia in 1977; global eradicationEpidemiology was certified two years later. Last naturally acquired human case in the world occurred in Somalia in 1977; global Thereeradication are at was least certified 2 strains, two variola years majorlater. and the variola minor.

.There Variola are at least major: 2 strains, the more variola severe major form and with the variola case fatality minor. rate up to 30-50% in susceptible populations. . Variola minor:major: themilder more form severe of the form disease with withcase morefatality diminutive rate up to pox 30 - lesions;50% in casesusceptible fatality populations. rate of 1-2% in susceptible populations. . Variola minor: milder form of the disease with more diminutive pox lesions; Clinicalcase Featuresfatality rate of 1-2% in susceptible populations.  Characteristic rash appears 2-4 days after non-specific, flu-like prodrome (fever Clinicaland headache).Features  MaculopapularCharacteristic rash rash appears begins 2 - on4 days mucosa after ofnon mouth-specific, and flu pharynx,-like prodrome face, hands,(fever fandorearms headache). and spreads to legs and centrally to trunk; lesions are more  predominantMaculopapular on the rash face begins and extremities on mucosa than of mouthon the trunk and pharynx,(centrifugal). face, hands,  Lesionsforearms progress and spreads synchronously to legs on and any centrallygiven part to of trunk;the body lesions from macules are more to ppredominantapules to vesicles on the to face pustules and extremities and to crusty than scabs. on the trunk (centrifugal).  TwoLesions rare progress forms of synchronously invariably fatal on smallpox any given have part been of the reported: body from macules to p. apulesPurpura to vesicles variolosa to pustules or hemorrhagic and to crusty type smallpoxscabs.  Two. Flat rare type forms smallpox of invariably fatal smallpox have been reported: . Purpura variolosa or hemorrhagic type smallpox Differential. Flat diagnosis type smallpox  Chickenpox, monkeypox, disseminated herpes zoster. Differential Clues to diagnosis distinguish smallpox from chickenpox:  .Chickenpox, Smallpox monkeypox, lesions are synchronousdisseminated in herpes their stagezoster of. development  Clues to distinguish smallpox from chickenpox: . Smallpox lesions are synchronous in their stage of development

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. Smallpox has many more lesions on the face and extremities than trunk (centrifugal spread) . Smallpox lesions has many are more common lesions onon thepalms face and and soles extremities than trunk . (centrifugalSmallpox lesions spread) are more deeply imbedded in the dermis compared with . Smallpoxthe superficial lesions lesions are more of chickenpox common on palms and soles . Smallpox lesions are more deeply imbedded in the dermis compared with Investigationsthe superficial lesions of chickenpox  Electron microscopy, PCR, viral isolation (culture of pharyngeal swab or Investigationslesions).  GuarnieriElectron microscopy,bodies on Giemsa PCR, or viral modified isolation silver (culturestain. of pharyngeal swab or lesions). Management Guarnieri bodies on Giemsa or modified silver stain.  Supportive care. Management Antibiotics may be used for secondary bacterial infection.  Supportive care. Prophylaxis Antibiotics may be used for secondary bacterial infection. Vaccination within 3 days of exposure may significantly ameliorate or prevent Prophylaxissmallpox. Vaccination 4 to 7 days after exposure likely still offers some protection orVaccination modification within of disease 3 days severity. of exposure may significantly ameliorate or prevent smallpox. Vaccination 4 to 7 days after exposure likely still offers some protection orNotification modification of disease severity. Notify MOH immediately on suspicion. Call MOH Communicable Diseases SuNotificationrveillance team at: 98171463 Notify MOH immediately on suspicion. Call MOH Communicable Diseases IsolationSurveillance Precautions team at: 98171463  Airborne and contact precautions. Isolate patients in negative pressure isolation Isolationroom. Precautions  PatientsAirborne should and contact be considered precautions. infectious Isolate until patients all scabs in negative separate pressu and shouldre isolation be isolatedroom. during this period.  PatientsDroplet andshould airborne be considered precaution infectious for a minimum until all of scabs 17 days separate following and should exposure be isolatedfor all persons during in this direct period. contact with the index case.  Droplet and airborne precaution for a minimum of 17 days following exposure for all persons in direct contact with the index case.

References 1. Henderson DA, Inglesby TV et al. Smallpox as a biological weapon: medical and public health management. Working group on Civilian Biodefense. JAMA 1999; 281: 2127-37 References2. Committee on Epidemic Diseases. Clinical guidelines on anthrax, botulism, plague and smallpox. 1. EpidemiologicalHenderson DA, InglesbyNews Bulletin. TV et 2001; al. Smallpox 27:61-68 as a biological weapon: medical and public health 3. CDCmanagement. (Atlanta), Working group on Smallpox Civilian Biodefense. overview. JAMA 1999; 2004. 281: 2127- Available37 from 2. http://emergency.cdc.gov/agent/smallpox/overview/diseaseCommittee on Epidemic Diseases. Clinical guidelines on -anthrax,facts.asp botulism,. Accessed plague Dec 2010. and smallpox. 4. EpidemiologicalWHO. Smallpox. News 2010. Bulletin. Available 2001; from 27:61 http://www-68 .who.int/mediacentre/factsheets/smallpox/en. 3. AccessedCDC Dec (Atlanta), 2010. Smallpox overview. 2004. Available from http://emergency.cdc.gov/agent/smallpox/overview/disease-facts.asp. Accessed Dec 2010. 4. WHO. Smallpox. 2010. Available from http://www.who.int/mediacentre/factsheets/smallpox/en. Accessed Dec 2010.

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TUBERCULOSIS (TB)

Causative Agent TUBERCULOSIS (TB) Mycobacterium tuberculosis (rarely M. bovis). Causative Agent IncubationMycobacterium Period tuberculosis (rarely M. bovis). Weeks to years Incubation Period WeeksInitial to infection years usually goes unnoticed—latent TB infection (LTBI). Appr oximately 10% of those with LTBI will eventually progress to active disease, andInitial half infection will do usually so in goes the first unnoticed 2 to— latent 3 years TB following infection infection. (LTBI). ImmunocompromisedApproximately 10% of p athosetients with (e.g. LTBI HIV willinfection, eventually diabetes progress mellitus) to active are at disease, higher riskand for half developing will do active so TB. in the first 2 to 3 years following infection. Immunocompromised patients (e.g. HIV infection, diabetes mellitus) are at higher Infectiousrisk for developing Period active TB. Sputum bacteriologically positive, drug-susceptible pulmonary TB is considered nonInfectious-infectious Period after two weeks of effective therapy. (Multi-drug resistant TB may requireSputum a bacteriologicallylonger period of effective positive ,therapy drug-susceptible before cases pulmonary become non TB-infect is consideredious). non -infectious after two weeks of effective therapy. (Multi-drug resistant TB may requireNon-pulmonary a longer periodTB (except of effective for laryngeal therapy TB before) is not cases infectious. become non-infectious). . TransmissionNon-pulmonary TB (except for laryngeal TB) is not infectious. .Airborne. Rarely through unpasteurized milk (M. bovis). Transmission Airborne.Epidemiology Rarely through unpasteurized milk (M. bovis).  The TB incidence in the local Singapore population (i.e. citizens and permanent Epidemiologyresidents) rose for the first time in ten years to 40 per 100,000 in 2008 and 39  perThe 100,000TB incidence in 2009. in the Prior local to Singapore this, the population TB rate of (i.e. the citizens local populationand permanent had declinedresidents )steadily rose for from the first57 per time 100,000 in ten yearsin 1998 to 40to 35per per 100,000 100,000 in 2008in 2007. and TB39 continueper 100,000d to be in a 2009. disease Prior of older to this, males the. The TB rateTB incidence of the local rate populationamong Malays had rdeclinedemained steadilythe highest from among 57 per the 100,000 three main in 1998 ethnic to groups. 35 per 100,000 in 2007. TB  continueThe majorityd to be(83.6%) a disease had of pulmonary older males TB.. The The TB two incidence commonest rate extrapulmonary among Malays rsitesemained were the the highest pleura andamong the thelymphatic three main system. ethnic groups.  The majority number of(83.6%) TB cases had pulmonary among foreigners TB. The in two Singapore commonest has extrapulmonary increased since 2005.sites were In 2009, the pleura long- termand theimmigration lymphatic passsystem. holders comprised 20.8% and short-  Theterm numberpass holders of TB 21.9% cases of amongall notified foreigners TB cases in in Singapore the country. has increased since  2005.In 2009, In 2009,the proportion long-term of immigration primary drug pass resistance holders comprisedamong new 20.8% pulmonary and short TB- casesterm pass in Singapore holders 21.9% residents of all examined notified TBwas cases 6.6%. in Streptomycinthe country. resistance was  theIn 2009, most commonlythe proportion encountered. of primary The drug proportion resistance of multiamong-drug new resistant pulmonary (MDR) TB tuberculosiscases in Singapore among residentsnew pulmonary examined TB was cases 6.6%. in Singapore Streptomycin residents resistance examined was hasthe most remained commonly very low,encountered. at 0.3%. The The proportion MDRTB of rate multi is, - however,drug resistant 10 or(MDR) more timestuberculosis higher amongamong newforeigners pulmonary reported TB caseswith TBin Singaporein Singapore, residents i.e. 3% examined among has remained very low, at 0.3%. The MDRTB rate is, however, 10 or more times higher among foreigners reported with TB in Singapore, i.e. 3% among

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Indonesians and those from the People’s Republic of China, 4% among Vietnamese and 6% among Burmese. Indonesians and those from the People’s Republic of China, 4% among ClinicalViet nameseFeatures and 6% among Burmese.  Pulmonary TB: Common symptoms are prolonged cough (> 3 weeks), chest Clinicalpain Featuresand haemoptysis. Patients with miliary TB may have minimal respiratory  Pulmonarysymptoms and TB: present Common with symptomssystemic complaints. are prolonged cough (> 3 weeks), chest  Extrapulmonarypain and haemoptysis. TB: LymphadenitisPatients with miliary (especially TB may cervical), have minimal pleural respiratory effusion, osymptomssteomyelitis, and menpresentingitis with or systemicgastrointestinal complaints. involvement.  PatientsExtrapulmonary often have TB: associated Lymphadenitis fever, (especiallynight sweats, cervical), loss of pleural appetite, effusion, loss of weightosteomyelitis, and fatigue. meningitis or gastrointestinal involvement.  RiskPatients factors often for have HIV associated and examination fever, night for physical sweats, loss signs of of appetite, HIV (e.g. loss oral of caweightndidiasis) and fatigue. should be sought.  Risk factors for HIV and examination for physical signs of HIV (e.g. oral Investigaticandidiasis)ons should be sought.  Chest X-Ray. All persons with chest X-ray findings suggestive of TB should Investigatihave sputumons specimens submitted for microbiological examination.  AcidChest fast X- Ray.bacilli All (AFB) persons smear with and chest TB cultureX-ray findingsof sputum suggestive and other of pathological TB should havespecimens sputum such specimens as pleural submitted fluid, CSF, for microbiological urine and pus. examination.All patients suspected of  havingAcid fast pulmonary bacilli (AFB) TB smear should and have TB culture at least of two, sputum preferably and other three, pathological sputum specimens such obtained as pleural for microscopic fluid, CSF, examinationurine and pus. and All TB patients culture suspected (with drug of suscehavingptibility pulmonary testing), TB with should at least have one atearly least morning two, specimen preferably where three, possible. sputum  specimensNucleic acid obtained amplification for microscopic tests (NAATs) examination do not and obviate TB culture the need (with for drug TB suscecultureptibility as these testing), tests with do notat least provide one early information morning on specimen the drug where susceptibility possible.  patternNucleic of acid the organism. amplification The testsNAATs (NAATs) are not sufficiently do not obviate sensitive the for need a negative for TB resultculture to asexclude these TB tests in dosmear not- negative provide sputum information samples on the drug susceptibility  HIVpattern testing of the should organism. be performed The NAATs for allare patients. not sufficiently sensitive for a negative  Screeningresult to exclude for diabetes TB in mellitus smear-negative is strongly sputum recommended. samples  HIV testing should be performed for all patients. Notification Screening for diabetes mellitus is strongly recommended.  Healthcare providers are required to notify suspected and confirmed cases to the NotificationDirector, TB Control Unit, c/o STEP Registry (Form MD 532 or electronically  viaHealthcare CD-LENS) providers within are 72 requiredhours. to notify suspected and confirmed cases to the  AttendingDirector, TB physicians Control Unit, should c/o also STEP submit Registry Form (Form MD 117,MD or532 via or CDelectronically-LENS, to updatevia CD -treatmentLENS) w ithinprogress 72 hours. and changes at each visit, preferably monthly until a  Attendingfinal outcome physicians is reached. should also submit Form MD 117, or via CD-LENS, to update treatment progress and changes at each visit, preferably monthly until a Managementfinal outcome is reached.  Any physician treating a patient for TB is assuming an important public health Managementresponsibility; he must not only prescribe an appropriate regimen but also be  Any physician treating a patient for TB is assuming an important public health responsibility; he must not only prescribe an appropriate regimen but also be

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capable of assessing adherence of the patient to the regimen, and addressing poor adherence when it occurs.  capableInitial drug of assessingtherapy for adherence new cases of should the patient consist to of the 4 first regimen,-line drugs: and addressing isoniazid (INH),poor adherence rifampicin, when pyrazinamide it occurs. and ethambutol or streptomycin. Initiating  treatmentInitial drug using therapy a quinolone for new cases as a firstshould-line consist drug isof not4 first a standard-line drugs: practice. isoniazid In u(INH),ncomplicated, rifampicin, drug pyrazinamide-susceptible TBand cases, ethambutol 6 months or streptomycin. of drug therapy Initiating is sufficient.treatment using Monotherapy a quinolone should as a firstnever-line be drug given is as not thisa standard will generate practice. drug In- resistantuncomplicated, TB. A single drug- drugsusceptible should never TB cases, be added 6 monthsto a failing of regimen. drug therapy is  Thesufficient. treating Monotherapyphysician should should be alertnever to thebe givenTB culture as this and will drug generate susceptibility drug- resultsresistant which TB. Amay single take drug several should weeks never to bebe addedavailable. to a Therefailing should regimen. be an index  ofThe suspicion treating physician for the possibilityshould be alert of drug to the-resistant TB culture TB and in patientsdrug susceptibility who were prevresultsiously which treated, may take who several fail treat weeksment, to be who available. are known There contacts should ofbe MDRTBan index cases,of suspicion or who come for the from possibility countries of with drug high-resistant prevalence TB of in TB patients drug resistance. who were  Nonprev-iadherenceously treated, because who of fail adverse treatment, reactions who and are prolonged known contacts therapy of is MDRTBa major problem.cases, or who Non come-adherence from countries leads to possiblewith high treatment prevalence failure of TB and drug acquired resistance. drug  resistance.Non-adherence because of adverse reactions and prolonged therapy is a major  Directlyproblem. observed Non-adherence therapy leads (DOT) to possible is recommended treatment forfailure all TBand patients,acquired asdrug it aresistance.llows for closer monitoring, thus ensuring adherence to treatment, preventing  Directlythe development observed of therapy drug resistance. (DOT) is DOT recommended is available for at all the TB TB patients, Control as Unit it a(TBCU)llows for and closer polyclinics. monitoring, thus ensuring adherence to treatment, preventing  Allthe developmentpatients should of be drug issued resistance. with medical DOT is leave available for at at least the TBtwo Control weeks, afte Unitr which(TBCU) they and may polyclinics. be considered non-infectious.  AllFollow patients-up appointmentsshould be issued should with be medical at no longerleave for than at least monthly two intervals weeks, afte forr pwhichatients they on may TB treatment.be considered Patient nons- infectious. should be asked about clinical response to  treatment,Follow-up adherence appointments to therapyshould be and at any no longer adverse than drug monthly effects, intervals particularly for phepatientsatitis. on Patients TB treatment. with signs Patient or s symptoms should be suggestiveasked about of clinical hepatitis response such asto jaundice,treatment, nausea, adherence loss of to appetite, therapy abdominal and any adversediscomfort, drug tea effects, coloured particularly urine and hepeasya titis.fatiguability Patients should with be signs further or symptomsevaluated with suggestive liver function of hepatitis studies. such as  Responsejaundice, nausea, to treatment loss of is appetite, best monitored abdominal bacteriologically discomfort, tea with coloured repeat urine sputum and examinationeasy fatiguability at the should very leastbe further at two evaluated months (endwith ofliver intensive function phase) studies. and at the  endResponse of treatment. to treatment Those iswho best do monitored not convert bacteriologically their sputum cultures with repeatat two sputummonths mayexamination require extensionat the very of least treatment at two duration months beyond (end of six intensive months. phase) and at the  endA recordof treatment. of all Those medications who do not given, convert bacteriological their sputum response,cultures at and two adversemonths mayreactions require should extension be maintained of treatment for allduration patients. beyond six months.  SputumA record smear of - allpositive medications cases, relapsed given, bacteriological cases and those response, with risk and factors adverse for readrugctions-resistant should TB be should maintained be referred for all to pati theents. TBCU.  NonSputum-compliance smear-positive to TB treatment cases, relapsed should casesbe detected and those promptly, with riskand these factors cases for shoulddrug-resistant be referred TB shouldto TBCU. be referred to the TBCU.  Non-compliance to TB treatment should be detected promptly, and these cases Preventionshould beand referred Control to TBCU.  In an endemic area, BCG vaccination at birth helps to reduce the incidence of Preventionmiliary andTB and Cont TBrol meningitis in childhood.  In an endemic area, BCG vaccination at birth helps to reduce the incidence of miliary TB and TB meningitis in childhood.

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 Early recognition and early appropriate treatment of TB cases. Suspect TB in any person with unexplained cough for three or more weeks.  InEarly hospitals recognition and otherand early institutions, appropriate isolation treatment of smear of TB-positive cases. Suspect patients TB for in at leastany person 2 weeks with afterunexplained initiation cough of appropriatefor three or more drug we therapyeks. will help reduce  Intran hospitalssmission. and other institutions, isolation of smear-positive patients for at  Screeningleast 2 weeks of close after contacts initiation of infectious of appropriate (i.e. sputum drug bacteriologically therapy will help posit reduceive) TBtran s casesmission. for latent TB infection (LTBI) and preventive therapy. This is  peScreeningrformed ofby close the TBCU contacts Contact of infectious Clinic. (i.e. sputum bacteriologically positive) TB cases for latent TB infection (LTBI) and preventive therapy. This is o The tuberculin skin (Mantoux) test is the standard method of LTBI performed by screening.the TBCU ContactCriteria Clinic.for a positive reaction depend on the patient’s o healthThe tuberculin status and skin TB (Mantoux) risk. test is the standard method of LTBI screening. Criteria for a positive reaction depend on the patient’s o All screened close contacts found to have LTBI should be offered treatment,health status regardless and TB risk.of age and BCG vaccination status. Before o initiatingAll screened treatment, close contacts active TB found must to be have ruled LTBI out byshould patient be history,offered physicaltreatment, examination, regardless of and age chest and X BCG-ray. vaccination status. Before o Isoniazidinitiating treatment,(INH) is the active treatment TB must of bechoice ruled for out LTBI. by patient For history, adults, thephysical recommended examination, duration and chest of X treatment-ray. is at least six, and o preferIsoniazidably (INH), nine months.is the treatment of choice for LTBI. For adults, the recommended duration of treatment is at least six, and Air Travel preferably, nine months.  According to WHO guidelines, people with infectious or potentially infectious Air TravelTB should not travel by commercial air transportation on a flight of any  Accordingduration, until to WHOthere isguidelines, no longer peoplea risk of with transmitting infectious infection or potentially to others. infectious  PhysiciansTB should shouldnot travel inform by all commercial patients with air infectioustransportation or potentially on a flight infectious of any TBdur athattion, they until pose there a isrisk no oflonger infect a ionrisk to of others, transmitting and advise infection them to thatothers. they must  Physiciansnot travel byshould any inform public all air patients transportation with infectious as long or as potentially they are considered infectious TBinfe cthattious they or potentiallypose a risk infectious. of infection to others, and advise them that they must not travel by any public air transportation as long as they are considered Referencesinfectious or potentially infectious. 1. Ministry of Health. Communicable Diseases Surveillance in Singapore 2009. References2. US Centers for Disease Control and Prevention. Treatment of tuberculosis. MMWR Recomm Rep 1. Ministry2003; 52RR(11): of Health. 1- 77.Communicable Diseases Surveillance in Singapore 2009. 3.2. SmallUS Centers PM, Fujiwara for Disease PI. ManagementControl and Prevention.of tuberculosis Treatment in the United of tuberculosis. States. N MMWREngl J Med Recomm 2001; 345:Rep 1892003;-200. 52RR(11): 1-77. 3.4. SmallTuberculosis PM, Fujiwara Coalition PI. Management for Technical of Assistance.tuberculosis International in the United StandardsStates. N Engl of Tuberculosis J Med 2001; Care345: 189(ISTC),-200. second edition.. The Hague, Tuberculosis Coalitions for Technical Assistance, 2009. 4.5. TuberculosisMinistry of Health. Coalition Multidrug for Technical-resistant Assistance. pulmonary International tuberculosis Standards in Singapore, of Tuberculosis 2000 to 2006. Care (ISTC),Epidemiological second edition.. News Bulleti The Hague,n 2007; Tuberculosis 33:50-5. Coalitions for Technical Assistance, 2009. 5.6. MinistryFern RH, Brian of Health. HN, Amiesha Multidrug SP.-resistant Identification pulmonary and management tuberculosis of latent in Singapore, tuberculosis 2000 infection. to 2006. AmericanEpidemiological Family News Physician, Bulleti Mayn 2007; 15 2009. 33:50 Available-5. at: http://www.aafp.org/afp/2009/0515/p879.html#afp20090515p879-b14. Accessed Dec 2010. 6. Fern RH, Brian HN, Amiesha SP. Identification and management of latent tuberculosis infection. rd 7. WorldAmerican Health Family Organization. Physician, MayTuberculosis 15 2009. and Available air travel at:– Guidelines for prevention and Control, 3 editionhttp://www.aafp.org/afp/2009/0515/p879.html#afp20090515p879 2008. -b14. Accessed Dec 2010. 7. World Health Organization. Tuberculosis and air travel–Guidelines for prevention and Control, 3rd edition 2008.

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TULAREMIA

Causative Agent TULAREMIA Francisella tularensis Causative Agent FrancisellaIncubation tularensisPeriod 3 - 5 days (range 1 to 14 days) Incubation Period Infectious3 - 5 days (range Period 1 to 14 days) No human-to-human transmission Infectious Period TransmissionNo human-to-human transmission Humans can become incidentally infected through diverse routes of exposures: bites ofTransmission infective arthropods (primarily ticks and mosquitoes); handling infectious animal Humanstissue or can fluids; become ingestion incidentally of contaminated infected through water, diverse or inadequately routes of cookexposures:ed meat bites of ofinfected infective animals; arthropods and (primarily inhalation ticks of and dust mosquitoes); from contaminated handling infectious soil. Laboratory animal tissueinfections or fluids; occur ingestion through of accidental contaminated inoculation water, or or inadequately by inhaling cook aerosolizeded meat of infectedorganisms. animals; and inhalation of dust from contaminated soil. Laboratory infe ctions occur through accidental inoculation or by inhaling aerosolized organisms.Inoculation or inhalation of as few as 10 organisms is needed to cause disease and is one of the most infectious pathogenic bacteria known. Inoculation or inhalation of as few as 10 organisms is needed to cause disease and is oneThe ofprimary the most concern infectious for intentional pathogenic infection bacteria known.by the organism is through inhalation after aerosol dissemination of bacteria. The primary concern for intentional infection by the organism is through inhalation afterEpidemiology aerosol dissemination of bacteria. The majority of infections in humans and animals are caused by the two species: F. Epidemiologytularensis subspecies tularensis (most virulent) and F. tularensis subspecies Theholar majorityctica and of rarely infections subspecies in humans philomiragia and animals and novicidaare caus.ed by the two species: F. tularensis subspecies tularensis (most virulent) and F. tularensis subspecies holarThe diseasectica and occurs rarely naturallysubspecies throughout philomiragia much and of novicida North America. and Eurasia. F. tularensis is found in widely diverse animal hosts and habitats and can be recovered fromThe disease contaminated occurs naturallywater, soil, throughout and vegetation. much of NorthA variety America of small and Eurasia.mammals, F. includingtularensis voles,is found mice, in widely water rats,diverse squirrels, animal rabbits,hosts and and habitats hares, andare naturalcan be recoveredreservoirs fromof infection. contaminated water, soil, and vegetation. A variety of small mammals, including voles, mice, water rats, squirrels, rabbits, and hares, are natural reservoirs Tulof inaremiafection. is almost entirely a rural disease, though exposure in urban or suburban settings does occur. Certain activities, such as hunting, trapping, butchering, and Tulfarming,aremia are is associated almost entirely with transmission a rural disease, risk. though exposure in urban or suburban settings does occur. Certain activities, such as hunting, trapping, butchering, and farming,The agent are for associated tularemia with is transmission not indigenous risk. in Singapore. Bioterrorism should be suspected should this disease be diagnosed in Singapore in persons without a Therelevant agent travel for history tularemia. is not indigenous in Singapore. Bioterrorism should be suspected should this disease be diagnosed in Singapore in persons without a relevant travel history.

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Clinical Features  Clinical forms vary in presentation and severity depending on virulence of the Clinicalinfecting Features organism , dose and site of inoculation.  Clinical forms vary in presentation and severity depending on virulence of the  Maininfecting forms organism of disease:, dose and site of inoculation. Pneumonia:  Main. formsPleuropneumonitis of disease: with hilar lymphadenitis (through airborne or Pneumoniaha:ematogenous routes). . OccursPleuropneumonitis more often inwith the hilar elderly lymphadenitis and has a higher (through mortality airborne rate. or . Radiographichaematogenous features routes). of tularemic pneumonia include patchy . unilateralOccurs more or bilateral often in infiltrates,the elderly lobarand has or segmentala higher mortality opacities, rate. hilar . adenopathy,Radiographic pleural features effusions, of tularemic cavitary pneumonia lesions andinclude occasionally patchy a miliaryunilateral pa orttern. bilateral infiltrates, lobar or segmental opacities, hilar Ulceroglandularadenopathy, (60-80%): pleural effusions, cavitary lesions and occasionally a . Patientsmiliary pa typicallyttern. present with fever and a single erythematous Ulceroglandularpapuloulcerative (60-80%): lesion with a central eschar accompanied by tender . rPatientsegional typicallylymphadenopathy present with. fever and a single erythematous . Patientspapuloulcerative usually report lesion recent with a handling central eschar of an animal,accompanied an animal by tender bite (especiallyregional lymphadenopathy cat bites), or exposure. to potential vectors, particularly . ticksPatients. usually report recent handling of an animal, an animal bite Oculoglandular(especially (1-2%): cat bites), or exposure to potential vectors, particularly . Chemosisticks. /conjunctivitis with regional lymphadenitis (through Oculoglandularinocula (1tion-2%): of conjunctiva). Oropharyngeal. Chemosis (1-4%): /conjunctivitis with regional lymphadenitis (through . Exudativeinoculation pharyngitis/tonsillitis of conjunctiva). with cervical adenitis (through Oropharyngealinoculation (1-4%): of oropharyngeal mucosa). . DiagnosisExudative shpharyngitis/tonsillitisould be considered inwith patients cervical with adenitis pharyngitis (through unrespoinoculationnsive of to oropharyngeal penicillin. mucosa). Glandular. Diagnosis (3-15%): sh ould be considered in patients with pharyngitis . unrespoEnlargementnsive toof penicillin.a single or multiple lymph nodes without an Glandularidentif (3-15%):iable skin lesion. Typhoidal. Enlargement: of a single or multiple lymph nodes without an . Typhoidalidentifiable tularemiaskin lesion. with or without pneumonia is an uncommon Typhoidalpre: sentation. . SystemicTyphoidal illness tularemia with non with-localizing or without fever. pneumonia is an uncommon presentation.  Onset. ofSystemic illness is illness usually with abrupt, non-localizing with fever fever. (38° - 40°C), headache, chills, coryza and sore throat. Pulse-temperature dissociation has been noted in as

 Onsetmany as of 42% illness of patients.is usually abrupt, with fever (38°- 40°C), headache, chills,

 coryzaA dry or and slightly sore throatproductive. Pulse cough-temperature and substernaldissociation pain or has tightness been noted frequently in as occurmany as with 42% or ofwithout patients. objective signs of pneumonia, such as purulent sputum,

 dyspnoea,A dry or slightly tachypn productiveoea, pleuritic cough pain, and or haemoptysis. substernal pain or tightness frequently occur with or without objective signs of pneumonia, such as purulent sputum, dyspnoea, tachypnoea, pleuritic pain, or haemoptysis.

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 Nausea, vomiting, and diarrhoea sometimes occur. Sweats, fever and chills, progressive weakness, malaise, anorexia, and weight loss characterize the  Nausea,continuing vomiting, illness. and diarrhoea sometimes occur. Sweats, fever and chills,  Anyprogressive form of weakness,tularemia maymalaise, be complicated anorexia, andby hematogenous weight loss characterizespread, resulting the coin nsecondarytinuing illness. pleuro -pneumonia, sepsis and rarely, meningitis.  Any form of tularemia may be complicated by hematogenous spread, resulting Investigatiin secondaryons pleuro-pneumonia, sepsis and rarely, meningitis. The laboratory needs to be notified for special diagnostic and safety procedures. Investigati Direct ons examination of secretions, exudates and biopsy specimens using Gram The stain,laboratory direct needs fluorescent to be notified antibody for or special immunochemical diagnostic and stains. safety procedures.  CultureDirect examination of F. tularensis of secretions, from clinical exudates specimens and biopsy(pharyngeal specimens washings, using sputum Gram orstain, fasting direct gastric fluorescent aspirates). antibody or immunochemical stains.  SerologyCulture of with F. tularensisa fourfold fromtitre changeclinical of specimens serum antibodies (pharyngeal against washings, F. tularensis. sputum or fasting gastric aspirates). Management Serology with a fourfold titre change of serum antibodies against F. tularensis. In contained casualty setting: DrugsManagement of choice: In contained. IM streptomycincasualty setting: 1gm 12 hourly for 10 days; or Drugs. of IV/IMchoice: gentamicin 5mg/kg once daily for 10 days Alternatives:. IM streptomycin 1gm 12 hourly for 10 days; or . IVIV/IM doxycycline gentamicin 100 5mg/kg mg 12 oncehourly daily for for14- 2110 days; or Alternatives:. IV ciprofloxacin 400 mg 12 hourly for 10 days . IV doxycycline 100 mg 12 hourly for 14-21 days; or In mass. casualtyIV ciprofloxacin setting: 400 mg 12 hourly for 10 days Drugs of choice: In mass. casualtyDoxycycline setting: 100 mg orally 12 hourly for 14-21 days; or Drugs. of Ciprofloxacinchoice: 500 mg orally 12 hourly for 10 days . Doxycycline 100 mg orally 12 hourly for 14-21 days; or Chemoprophylaxis. Ciprofloxacin 500 mg orally 12 hourly for 10 days Exposed persons can be prophylactically treated with 14 days of oral doxycycline or Chemoprophylaxisciprofloxacin. If unexplained fever or flu-like illness develops within 14 days of Exposedexposure ,persons then treat can as be for prophylactically infection. treated with 14 days of oral doxycycline or ciprofloxacin. If unexplained fever or flu-like illness develops within 14 days of Notificationexposure, then treat as for infection. Notify MOH immediately on suspicion. Call MOH Communicable Diseases SuNotificationrveillance team at: 98171463 Notify MOH immediately on suspicion. Call MOH Communicable Diseases SuVaccinerveillance team at: 98171463 Currently no vaccine is available locally. In the United States, a live attenuated vaVaccineccine has been used by laboratory staff working routinely with the bacterium. Currently no vaccine is available locally. In the United States, a live attenuated va ccine has been used by laboratory staff working routinely with the bacterium.

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Isolation Precautions Standard precautions are recommended. Respiratory isolation is not necessary given theIsolation lack of Precautions human-to-human transmission. Bodies of patients who die of tularemia shoulStandardd be precautions handled using are standardrecommended. precautions. Respiratory Autopsy isolation procedures is not likely necessary to produce given aerosolsthe lack ofor dropletshuman-to should-human be transmission. avoided. Bodies of patients who die of tularemia shoul d be handled using standard precautions. Autopsy procedures likely to produce aerosols or droplets should be avoided.

References 1. Dennis DT, Ingleshy TV, Henderson DA et al. Tularemia as a biological weapon: medical and Referencespublic health management. JAMA. 2001; 285:2763-73 1.2. DennisEllis J, OystonDT, Ingleshy PC, Green TV, HendersonM, et al. Tularemia. DA et al. ClinTularemia Microbiol as a Rebiologicalv. 2002;15 weapon::631-46 medical and 3. publicCDC (Atlanta) health management. informational JAMA. website: 2001 http://www.bt.cdc.gov/agent/tularemia; 285:2763-73 . Accessed Dec 2010. 2. Ellis J, Oyston PC, Green M, et al. Tularemia. Clin Microbiol Rev. 2002;15:631-46 3. CDC (Atlanta) informational website: http://www.bt.cdc.gov/agent/tularemia. Accessed Dec 2010.

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TYPHOID AND PARATYPHOID FEVER

Causative Agents TYPHOID AND PARATYPHOID FEVER Salmonella typhi (Typhoid fever) SalmonellaCausative Agents paratyphi A, B and C (Paratyphoid fever). Salmonella typhi (Typhoid fever) IncubationSalmonella paratyphiPeriod A, B and C (Paratyphoid fever). 1 - 3 weeks Incubation Period Infectious1 - 3 weeks Period During acute infection and until stool and urine clearance. Infectious Period TransmissionDuring acute infection and until stool and urine clearance. Faeco -oral route through contaminated food or water. Transmission through sexual contact,Transmission especially among men who have sex with men have been documented. ThereFaeco -oral is no route animal through reservoir contaminated so ultimately food theor water. disease Tran alwayssmission involves through human sexual-to- humancontact, spread. especially among men who have sex with men have been documented. There is no animal reservoir so ultimately the disease always involves human-to- Epidemiologyhuman spread. During the period 2005-2009, there were 349 reported cases of typhoid (94% iEpidemiologymported) and 139 reported cases of paratyphoid (88.5% imported). The disease is endemicDuring thein Southeast period 2005 Asia-2009, and the there Indian were subcontinent. 349 repor ted cases of typhoid (94% imported) and 139 reported cases of paratyphoid (88.5% imported). The disease is Clinicalendemic Featuresin Southeast Asia and the Indian subcontinent.  Typhoid fever Clinical. Features1st week of illness: Rising, “stepwise” fever, bacteraemia and diarrhoea  Typhoid(78% fever of children) or constipation (more frequent in adults). . 21ndst weekweek ofof illness:illness: Rising,Abdominal “stepwise” pain and fever, rash bacteraemia (rose spots) and diarrhoea . 3(78%rd week of children)of illness: or Hepatosplenomegaly, constipation (more frequent intestinal in adults).bleeding and . perfor2nd weekation of illness: Abdominal pain and rash (rose spots) . 3rd week of illness: Hepatosplenomegaly, intestinal bleeding and  Complicationsperforation (rare if diagnosed and treated early) . Intestinal haemorrhage or perforation  .Complications Toxic myocarditis (rare if diagnosed and treated early) . Confusion,Intestinal haemorrhage convulsions, or encephalitis perforation . HaemolyticToxic myocarditis anaemia (especially in G6PD deficiency) . RenalConfusion, failure convulsions, encephalitis . AbscessesHaemolytic in anaemia liver, spleen (especially, bone etc.in G6PD deficiency) . Renal failure  Paratyphoid. Abscesses fever in liver, spleen, bone etc. . Maybe clinically mild or asymptomatic  Paratyphoid fever . Maybe clinically mild or asymptomatic

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. Nausea, vomiting, fever, diarrhoea, and cramping—usually occur within 8 to 72 hours of ingesting contaminated food or water . . LessNausea, than vomiting, 5% of non fever,-typhoidal diarrh oea,salmonella and cramping gastroenteritis—usually develop occur within 8 bacteraemiato 72 hours of and ingesting may result contaminated in extra-intestinal food or manifestationswater including . endocaLess thanrditis, 5% mycoticof non-typhoidal aneurysm salmonella and osteomyelitis. gastroenteritis develop bacteraemia and may result in extra-intestinal manifestations including Investigationsendoca rditis, mycotic aneurysm and osteomyelitis.  Blood test frequently show anaemia, elevated hepatic transaminases and either Investigationsleucopoenia or leucocytosis.  IsolationBlood test of frequently organism showis the anaemia,gold standard elevated for diagnosis.hepatic transaminases and either  Bloodleucopoenia culture or usually leucocytosis. positive for 1st two weeks only.  StoolIsolation and of urine organism culture is positive the gold from standard 2nd to for 4th diagnosis. weeks.  Blood culture usually positive for 1st two weeks only. The yield from bone marrow culture isnd highth and is usually positive even after  Stoolantibiotics and urine have culturebeen initiated. positive from 2 to 4 weeks.  The Widalyield from test isbone unreliable marrow in cultureitself, but is highmay andprovide is usually additional positive support even for after the antibioticsdiagnosis when have thebeen clinical initiated. picture is suggestive.  The Widal test is unreliable in itself, but may provide additional support for the diagnosis when the clinical picture is suggestive. Notification A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 orNotification electronically via CD-LENS) not later than 24 hours from the time of diagnosis. A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 or electronically via CD-LENS) not later than 24 hours from the time of diagnosis. Management Typhoid Management Patients should be hospitalised during antibiotic treatment. Typhoid Rehydration and other supportive care.  CurrentPatients drugshoulds of be choice: hospitalised during antibiotic treatment.  Rehydration. PO Ciprofloxacin and other 500supportive mg bd care.x 7-10 days (if sensitive to ciprofloxacin and  Currentnalidixic drugs acid)of choice: . . IVPO CCiprofloxacineftriaxone 2- 3g500 once mg dailybd x 7x- 10 -days14 days (if sensitive to ciprofloxacin and nalidixic acid) . Alternative: PO Azithromycin 1g once then 500mg once daily x 5-7 days . IV Ceftriaxone 2-3g once daily x 10-14 days . N.B. 70-90 % of isolates in some parts of Nepal, India and Vietnam are . Alternativenalidixic acid: PO resistant Azithromycin strains. 1g once then 500mg once daily x 5-7 days  .Dexamethasone N.B. 70-90 % 3mg/kg of isolates then in 1mg/kg some parts 6 hourly of Nepal, x 8 India doses and for Vietnam severe typhoidare fevernalidixic (as suggested acid resistant by delirium, strains. shock and altered mental status) decreases  Dexamethasonemortality. 3mg/kg then 1mg/kg 6 hourly x 8 doses for severe typhoid  Relapsefever (as rate suggested 1-6% with by newer delirium, antibiotics shock (10 and-25% altered with mental chlora mphenicol) status) decreases  Onemortality. to four percent of adults become chronic carriers despite antibiotics.  FollowRelapse- uprate stool 1-6% evaluation with newer to documentantibiotics stool (10- 25%clearance with afterchlor treatment:amphenicol)  .One Threeto four consecutive percent of adults stool becomesamples chronictaken at carriers weekly despite intervals antibioti no soonercs. than  Followtwo-up weeks stool after evaluation completion to document of antibiotic stool treatment.clearance after treatment: . Three consecutive stool samples taken at weekly intervals no sooner than two weeks after completion of antibiotic treatment.

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. Chronic carriers (positive stool samples after 6 months): give prolonged course of ciprofloxacin (750 bd orally for 1 month) and perform abdominal . ultrasound;Chronic carriers cholecystectomy (positive stool may samplesbe necessary after if 6 gallstones months): giveare present prolonged and prolongedcourse of ciprofloxacin antibiotic treatment (750 bd fails. orally for 1 month) and perform abdominal ultrasound; cholecystectomy may be necessary if gallstones are present and Preventionprolonged and Control antibiotic treatment fails.  Public health measures: education on good personal and food hygiene. Prevention Vaccination and Controlfor travellers: (see section on travel vaccination in Appendix 3).  FollowPublic health up stool measures: examinations education recommended on good personal for all cases and food and mandatoryhygiene. for  foodVaccination handlers. for travellers: (see section on travel vaccination in Appendix 3).  FoodFollow handlers up stool require examinations further stoolrecommended examination for (threeall cases consecutive and mandatory daily stoolfor foodsamples) handlers. at three and six months post treatment.  CarriersFood handlers (convalescent, require further temporary stool and examina chronic)tion must (three not consecutive work as food daily handlers. stool samples) at three and six months post treatment.  Carriers (convalescent, temporary and chronic) must not work as food handlers. References 1. Teoh YL, Goh KT, Neo KS et al. A nationwide outbreak of coconut-associated paratyphoid A fever Referencesin Singapore. Ann Acad Med Singapore 1997; 26:544-8. 2.1. ParryTeoh YL,CM, Goh Hien KT, TT, Neo Dougan KS et G al et. Aal. nationwide Typhoid fever. outbreak N Engl of Jcoconut Med 2002;-associated 347: 1770 paratyphoid-82. A fever 3. Slingerin Singapore. R, Desjardins Ann Acad M, Med McCarthy Singapore AE 1997; et al. 26:544 Suboptimal-8. clinical response to ciprofloxacin in 2. pParryatients CM, with Hien enteric TT, Dougan fever due G et to al. Salmonella Typhoid fever. spp. N with Engl reduced J Med fluoroquinolone2002; 347: 1770 - susceptibility:82. a 3. caSlingerse series. R, DesjardinsBMC Infect M, Dis McCarthy 2004; 20 :4 AE-36. et al. Suboptimal clinical response to ciprofloxacin in 4. Effapatients EE, with Bukirwa enteric H. fever Azithromycin due to Salmonella for treating spp. uncomplicated with reduced fluoroquinolone typhoid and paratyphoid susceptibility: fever a (ecanseteric series. fever). BMC Cochrane Infect Dis Data 2004;base 20Syst:4- 36.Rev. 2008;(4):CD006083. 5.4. ConnorEffa EE, B, BukirwaSchwartz H.E. Typhoid Azithromycin and paratyphoid for treating fever uncomplicated in travellers. Lancet typhoid Infect and Dis paratyphoid 2005; 5:623 fever-8 6. Bhan(enteric M, fever). Bahl R, Cochrane Bhatnager Data S. baseTyphoid Syst and Rev. paratyphoid 2008;(4):CD006083. fever. Lancet 2005; 366: 749-62. 5.7. ConnorTy AU, B,Ang Schwartz GY, Ang E. LWTyphoid et al. and Changing paratyphoid epidemiology fever in travellers. of enteric Lancet fevers Infectin Singapore. Dis 2005; Ann 5:623 Acad-8 6. MedBhan 2010;39:889 M, Bahl R, Bhatnager-96. S. Typhoid and paratyphoid fever. Lancet 2005; 366: 749-62. 7. Ty AU, Ang GY, Ang LW et al. Changing epidemiology of enteric fevers in Singapore. Ann Acad Med 2010;39:889-96.

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