44 HAND, FOOT and MOUTH DISEASE Causative Agent

HAND, FOOT AND MOUTH DISEASE

Causative Agent HAND, FOOT AND MOUTH DISEASE Numerous members of the Enteroviruses group of the family Picornaviridae e.g. coxsackievirus,Causative Agent echovirus, enterovirus (EV) 71. Numerous members of the Enteroviruses group of the family Picornaviridae e.g. Incubationcoxsackievirus, Period echovirus, enterovirus (EV) 71. 3 -5 days (range 2 days to 2 weeks) Incubation Period Infectious3-5 days (range Period 2 days to 2 weeks) Few days before onset of prodromal symptoms to about 1 week from the onset of illness.Infectious Period Few days before onset of prodromal symptoms to about 1 week from the onset of Maximumillness. duration of excretion: nasopharynx (3-4 weeks), faeces (6-12 weeks).

TransmissioMaximum durationn of excretion: nasopharynx (3-4 weeks), faeces (6-12 weeks). Faecal-oral route, direct contact with respiratory droplets, saliva, vesicular fluid or indirectlyTransmissio by narticles/ fomites contaminated by secretions. Faecal-oral route, direct contact with respiratory droplets, saliva, vesicular fluid or indirectlyEpidemiology by articles/ fomites contaminated by secretions. Infection leads to specific immunity against the particular virus but can be reinfected byEpidemiology a different virus from the enterovirus group. Infection leads to specific immunity against the particular virus but can be reinfected Afterby a different an epidemic virus offrom HFMD the enterovirus in Sarawak group. in 1997 and Taiwan in 1998, a system of surveillance for the disease, based on notifications from child-care centres was Afterimplemented an epidemic in April of HFMD 1998. in Singapore Sarawak in experienced 1997 and Taiwan an epidemic in 1998, of a HFMDsystem of in surveillanceSeptember–October for the 2000 disease, during based which on 3790 notifications cases were from reported. child- careThe predominant centres was virusimplemented was EV71. in AprilThere 1998.were four Singapore EV71- related experienced deaths an in epidemic2000 and three of HFMD in 2001. in ReportingSeptember – theOctober disease 2000 was during made which legally 3790 mandatory cases were onreported. October The 1, predominant 2000. The outbvirusreak was wasEV71. finally There interrupted were four by EV71 a swift- related coordinated deaths in inter 2000-agency and three response in 2001. that Reportingled to the closure the disease of all preschools was made from legally 1 Oct mandatory – 15 Oct. on October 1, 2000. The outb reak was finally interrupted by a swift coordinated inter-agency response that Duringled to the the closure period of 2005 all preschools-2009, there from were 1 betweenOct – 15 15,257Oct. and 29,686 reported cases per year, including one death in 2008. Coxsackievirus A 16 was the predominant circulatingDuring the virusperiod in 2005 2005,-2009, 2007 thereand 2009, were andbetween EV 71 15,257 in 2006 and and 29,686 2008. reported cases per year, including one death in 2008. Coxsackievirus A 16 was the predominant circulatingClinical Features virus in 2005, 2007 and 2009, and EV 71 in 2006 and 2008. Children younger than 10 yrs of age have the highest risk but infection also occurs Clinicalin adults. Features The majority of the infections occur at the preschool ages. Children younger than 10 yrs of age have the highest risk but infection also occurs in adults.50-80% The are majority asymptomatic of the infecti ons occur at the preschool ages.

 50-80% are asymptomatic

 Fever lasts 2-3 days ( up to 5 days) followed by a rash over the palms, soles, dorsum of the feet, shins and buttocks. Rash starts as papules and become  vesFevericles. lasts Resolves 2-3 days in 7( -up10 daysto 5 days) followed by a rash over the palms, soles,  Mouthdorsum ulcers of the over feet, the shins soft/ andhard palate, buttocks. uvula, Rash buccal starts mucosa as papules and tongue. and become  Mayvesicles. also Resolves have cough in 7or-10 rhinitis. days  MayMouth also ulcers have over no therash soft/ but hardonly palate, ulcers uvula,in which buccal case mucosa the patient and tongue.is labelled as  herpanginaMay also have which cough is due or rhinitis.to the same group of enteroviruses.  May also have no rash but only ulcers in which case the patient is labelled as Complications:herpangina which is due to the same group of enteroviruses. Rarely myocarditis, pulmonary oedema, acute respiratory distress syndrome, viral Complications:pneumonitis, aseptic meningitis, brainstem encephalitis, acute flaccid paralysis, seRarecondaryly myocarditis, bacterial infection pulmonary oedema, acute respiratory distress syndrome, viral pneumonitis, aseptic meningitis, brainstem encephalitis, acute flaccid paralysis, Differentialsecondary bacterial diagnosis: infection Herpes simplex stomatitis – ulcers more in the anterior mouth and visible externally Differential diagnosis: InvestigationsHerpes simplex stomatitis – ulcers more in the anterior mouth and visible externally  Rapid diagnosis can be performed by sending a nasopharyngeal throat swab or Investigationsstool sample for enterovirus PCR.  Stool/rectalRapid diagnosis swab, can swab be ofperformed vesicle fluid by sending or oral ulcersa nasopharyngeal can be sent forthroat enterovirus swab or isostoollation sample which for takes enterovirus 5-6 weeks. PCR. The yield of virus isolation is highest from the  stoolStool/rectal followed swab, by vesiclesswab of andvesicle throat fluid swabs. or oral ulcers can be sent for enterovirus isolation which takes 5-6 weeks. The yield of virus isolation is highest from the Notificationstool followed by vesicles and throat swabs. 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 Detailsor electronically of school/child via CD-care-LENS) centre not should later than be provided 24 hours for from cases the involving time of diagnosis. children.

ManagementDetails of school/child -care centre should be provided for cases involving children.  Patients with signs and symptoms of severe disease should be referred to Managementhospital for further management; e.g. prolonged hyperpyrexia, tachycardia,  tachyPatientspnoea, with poor signs feeding and or symptoms severe vomiting, of severe lethargy. disease should be referred to  Symptomatichospital for furthermeasures: management; anti-pyretics, e.g. tepid prolonged sponging, hyperpyrexia, IV drip for rehydration. tachycardia,  Hospitalisationtachypnoea, poor for feeding treatment or severe of complications. vomiting, lethargy.  AntibioticsSymptomatic (especially measures: versus anti-pyretics, Staphyl ococcustepid sponging,) are used IV whendrip for there rehydration. is evidence  ofHospitalisation secondary bacterial for treatment infection; of complications. e.g. raised total white counts.  Antibiotics (especially versus Staphylococcus) are used when there is evidence Preventionof secondary and Control bacterial infection; e.g. raised total white counts.  No vaccines against enteroviruses are available. Good personal hygiene such as Preventionhand washing and Control and isolation of infected cases are key to controlling an outbreak.  No sharingvaccines of against food and enteroviruses contaminated are items. available. Good personal hygiene such as hand washing and isolation of infected cases are key to controlling an outbreak. No sharing of food and contaminated items.

 HFMD cases should be given medical leave until 10 days (2 incubation periods) from the onset of illness in order to break the transmission in child-care centres  andHFMD schools. cases should be given medical leave until 10 days (2 incubation periods)  Parefromnts the should onset ofbe illness advised in thatorder children to break with the HFMDtransmission are to in avoid child -contactcare centres with otherand schools. children at home and to refrain from visiting crowded public places during  Parethe acutents should infection be advised and not that swim children until 6with weeks HFMD later; are and to toavoid disinfect contact articles with contaminatedother children at by home the droandplets, to refrain saliva, from vesicular visiting fluidcrowded and public excreta places of infected during cases.the acute infection and not swim until 6 weeks later; and to disinfect articles  MOHcontaminated monitors by the the regional droplets, EV saliva, 71-associated vesicular HFMD fluid andsituation excreta and of tracks infected the typescases. of enteroviruses circulating in the community through a sentinel  surveiMOH l monitorslance system. the regional EV 71-associated HFMD situation and tracks the  typesMOH, of together enteroviruses with MCYS circulating and M inOE, the closely community monitors through the local a sentinel disease incsurveiidencellance and system. trends and provides guidance to childcare centres and  kindergartensMOH, together to ensure with MCYS that these and institutions MOE, closely exercise monitors a high thelevel local of vigilance disease ininc theiridence ma n andagement trends of HFMD. and provides guidance to childcare centres and kindergartens to ensure that these institutions exercise a high level of vigilance in their management of HFMD. References 1. Chan KP, Goh KT, Chong CY et al. Epidemic hand, foot and mouth disease caused by human Referencesenterovirus 71, Singapore. Emerging Infect Dis 2003; 9:78-85. 1.2. ChanChong KP, CY, Goh Chan KT, KP, Chong VA Shah CY VA et et al. al. Epidemic Hand,, foot hand, and foot mouth and disease mouth in disease Singapore: caused a comparison by human eofn terovirusfatal and 71,non Singapore.-fatal cases. Emerging Acta Paediatrica Infect Dis 2003; 2003; 92: 9:78 1-8.- 85. 2.3. ChongOoi EE, CY, Phoon Chan MC, KP, IshakVA Shah B et VA al. etSeroepidemiology al. Hand,, foot and of mouthhuman disease enterovirus in Singapore: 71, Singapore. a comparison Emerg ofInfect fatal Dis and 2002;8:995 non-fatal cases.-7. Acta Paediatrica 2003; 92: 1-8. 4.3. AngOoi EE,LW, Phoon Koh BKW,Chan MC, Ishak BKP et et al. al. Seroepidemiology Epidemiology and of control human of enterovirus hand, foot 71,and Singapore. mouth disease Emerg in Singapore,Infect Dis 2002;8:995 2001-2007.-7. Ann Acad Med Singapore 2009;38:106-12. 4. Ang LW, Koh BKW,Chan KP et al. Epidemiology and control of hand, foot and mouth disease in Singapore, 2001-2007. Ann Acad Med Singapore 2009;38:106-12.

HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION

CausativeHUMAN Agent IMMUNODEFICIENCY VIRUS (HIV) INFECTION Human immunodeficiency virus I and II Causative Agent IncubationHuman immunodeficiency Period virus I and II Variable. The median incubation period is shorter in infants than in adults. Incubation Period TheVariable. time The from median infection incubation to development period is shorter of detectable in infants antibodies than in adults. is generally 1- 3months. The time from infection to development of detectable antibodies is generally 1- Between3months. 1 and 6 weeks (median 3 weeks) after exposure to HIV, one half to two thirds of recently infected individuals develop a mononucleosis-like illness referred toBetween as the acute1 and re 6troviral weeks syndrome.(median 3 weeks) after exposure to HIV, one half to two thirds of recently infected individuals develop a mononucleosis-like illness referred Withoutto as the treatment,acute retroviral about syndrome. half of infected adults will develop AIDS within 10 years after infection. Without treatment, about half of infected adults will develop AIDS within 10 years Transmissionafter infection. Via sexual route (most common), transfusion of infected blood (or blood products) andTransmission contaminated needles; from mother-to-child during in-utero, intrapartum and perinatalVia sexual period route and (most via common), breastfeeding. transfusion Transmission of infected after bloodcontact (or with blood saliva, products) tears, urine,and contaminated stool and bronchial needles; secretions from mother has not-to -beenchild reported. during in-utero, intrapartum and perinatal period and via breastfeeding. Transmission after contact with saliva, tears, Infectiousurine, stool Period and bronchial secretions has not been reported. Infectious for whole duration of infection; most infectious during the period of seroconversionInfectious Period and untreated late-stage disease when the viral load (measured as numberInfectious of HIV for wholecopies/ml duration plasma) of is infection; very high. mos t infectious during the period of seroconversion and untreated late-stage disease when the viral load (measured as number of HIV copies/ml plasma) is very high. Epidemiology By the end of 2009, there were a total of 4404 cases reported in Singapore (2009 notificationEpidemiology rate: 124 per million population). The majority (94%) were infected via Bythe the sexual end routeof 2009,: heterosexual there were sex a total (66%), of 4404 homosexual cases reported (21%) inand Singapore bisexual (2009 (7%). notificationMost cases rate:(90%) 124 are per males million with population). the highest Theproportion majority (32%) (94%) in wer thee 30infected-39 years via theage sexual group. route There: heterosexual have been sex 29 (66%), children homosexual infected (21 through%) and motherbisexual-to - (7%).child transmiMost casesssion (90%) locally. are males with the highest proportion (32%) in the 30-39 years age group. There have been 29 children infected through mother-to-child transmiClinicals sionFeatures locally. Progression through 4 stages; individuals with higher viral loads generally progress faster.Clinical Features Progression through 4 stages; individuals with higher viral loads generally progress faster.

1. Seroconversion illness/Acute retroviral syndrome Mononucleosis-like illness. Combination of more than one of the following 1. symptoms:Seroconversion fever, illness/Acute adenopathy, retroviral rash, sore syndrome throat, myalgia, diarrhoea, nausea, vomiting,Mononucleosis headache,-like illness. weight Combination loss or oral thrush. of more Some than have one of oral the and following genital usymptoms:lcerations and fever, neurological adenopathy, illnesse rash,s (e.g. sore aseptic throat, meningitis). myalgia, diarrhoea, Median duration nausea, ofvomiting, illness is headache, 20 days (range weight < loss1 week or oralto 3 thrush.months). Some Resolves have spontaneously oral and genital in mostulcerations patients. and Majority neurological of infected illnesse casess (e.g. experience aseptic meningitis). this but condition Median isduration under- diagnosed.of illness is 20 days (range < 1 week to 3 months). Resolves spontaneously in most patients. Majority of infected cases experience this but condition is under- 2. Asymptomaticdiagnosed. (“latent”) disease No specific symptoms or signs of infection, but active viral replication and 2. iAsymptomaticmmune destruction (“latent”) (declining disease CD4 counts) is occurring throughout this period. LymphadenopathyNo specific symptoms (often or not signs noticed of infection,by patient) but is usually active present. viral replication and immune destruction (declining CD4 counts) is occurring throughout this period. 3. SymptomaticLymphadenopathy disease (often not noticed by patient) is usually present. Fever, weight loss, persistent generalised lymphadenopathy, skin and oral 3. coSymptomaticnditions (oral disease thrush, hairy leukoplakia, herpes zoster, recurrent herpes simplex)Fever, weigh andt immunological loss, persistent conditions generalised (e.g. lymphadenopathy, idiopathic thrombocytopenic skin and oral purpura,conditions mu (oralltiple drug thrush, allergies). hairy leukoplakia, herpes zoster, recurrent herpes simplex) and immunological conditions (e.g. idiopathic thrombocytopenic 4. Acquirepurpura,d mu immuneltiple drug deficiency allergies). syndrome (AIDS) The development of a specific indicator disease including: 4. Acquire. Viral:d immune Persistent deficiency HSV syndrome ulceration (AIDS) (>1 month); CMV retinitis or disease The developmentother than liver,of a specific spleen, lymphindicator node disease involvement. including: . Bacterial:Viral: Persistent tuberculosis HSV ulceration (esp. extrapu (>1 lmonary); month); CMV atypical retinitis mycobacteria or disease iothernfections; than liver, recurrent spleen, bacterial lymph node pneumonia involvement. (2 or more episodes in one . year);Bacterial: recurrent tuberculosis non-typhoid (esp.-salmonella extrapulmonary); septicaemia. atypical mycobacteria . Fungi:infections; oesophageal recurrent candidiasis; bacterial pneumonia cryptococcal (2 meningitis; or more episodes histoplasmosis in one (extrayear);- recurrentpulmonary) non; Pneumocysti-typhoid-salmonellas jiroveci septicaemia. pneumonia. . Protozoa:Fungi: oesophageal cerebral toxoplasmosis; candidiasis; cryptococcal cryptosporidial meningitis; diarrhoea. histoplasmosis . Selected(extra-pulmonary) tumours ; Pneumocysti (e.g. non-Hodgkin’ss jiroveci pneumonia. lymphoma, CNS lymphoma, . KProtozoa:aposi’s sarcoma, cerebral toxoplasmosis;cervical cancer) cryptosporidial diarrhoea. . Others:Selected wasting; tumours dementia; (e.g. non progressive-Hodgkin’s multi lymphoma,-focal leucoencepholopathy) CNS lymphoma, Kaposi’s sarcoma, cervical cancer) Investigation. Others: wasting; dementia; progressive multi-focal leucoencepholopathy)  Serology: screening test (e.g. fourth generation antibody-P24 antigen Investigationcombination test, rapid test kits) followed by confirmatory test (e.g. Western  blot).Serology: screening test (e.g. fourth generation antibody-P24 antigen  Acombin signedation consent test, is rapid not needed test kits) for followed HIV testing. by confirmatoryWhen HIV testing test (e.g. is medically Western indicatedblot). and carried out as part of the overall medical management of the  pAa tient,signed extensive consent ispre not-HIV needed test counselling for HIV testing. is not When required. HIV However, testing is justmedically like in anyindicated diagnostic and carriedinvestigation, out as it part is prudent of the to overall inform medical patients management that you are ofdoing the thispatient, test extensive and offer pre to-HIV answ tester counselling any queries. is Younot required. may want However, to document just like that in any diagnostic investigation, it is prudent to inform patients that you are doing this test and offer to answer any queries. You may want to document that

patient is agreeable for HIV testing. Reasons for refusal should also be documented.  Ifpatient a patient is agreeable voluntarily for requests HIV testing. HIV testing, Reasons e.g. for because refusal he should has engaged also be in highdocu-mented.risk sexual behaviours, pre-HIV test counselling should be carried out for  theIf a patient patient. voluntarilyThe implications requests of HIV positive testing, and e.g. negative because test he results has engaged and the in phighatient’s-risk potentialsexual behaviours, risk factors pre should-HIV betest discussed, counselling and should the patient be carried educated out foron HIVthe patient infection. The and implicationssafer sex practices. of positive and negative test results and the  Directpatient’s viral potential testing risk (e.g. factors PCR) shouldis not recommendedbe discussed, andas a the diagnostic patient educatedtest (except on inHIV infants infection and childrenand safer < sex 18 practices.months of age) but utilized as a management tool to  guideDirect and viral monitor testing treatment. (e.g. PCR) is not recommended as a diagnostic test (except in infants and children < 18 months of age) but utilized as a management tool to Notificationguide and monitor treatment. Notify the National Public Health Unit, MOH using Form MD 131 (fax) or eleNotificationctronically via CD-LENS. Notification through CD-LENS is strongly Notifyencouraged. the National Public Health Unit, MOH using Form MD 131 (fax) or electronically via CD-LENS. Notification through CD-LENS is strongly HIV/AIDSencouraged. cases should be notified if they have:

HIV/AIDS A posicasestive should result be from notified a confirmatory if they have: HIV antibody test (e.g. Western blot);  A positive virological test for HIV or its components (HIV-RNA or HIV-  DNAA posi ortive HIV result p24 from antigen); a confirmatory HIV antibody test (e.g. Western blot);  ClinicallyA positive suspectedvirological or test probable for HIV HIV or itsinfection componen (e.g.ts presence (HIV-RNA of AIDS or HIV- - definingDNA or HIVcondition). p24 antigen);  Clinically suspected or probable HIV infection (e.g. presence of AIDS- Managementdefining condition).  Post-test counselling (see below). Management Referral to ID Physician for specialist care in HIV Medicine.  EffectivePost-test counsellingtherapy is available (see below). that can significantly prolong survival and reduce  morbidityReferral to and ID Physicianinfectivity for. specialist care in HIV Medicine.  ManagementEffective therapy includes: is available that can significantly prolong survival and reduce .morbidity antiretroviral and infectivity therapy. to prevent destruction of immune system  Management. prophylaxis includes: and treatment of opportunistic infections. . antiretroviral therapy to prevent destruction of immune system Special. Circumprophylaxisstances and treatment of opportunistic infections.  HIV in pregnant women Special. CircumAnte-natalstances screening is advised, so that anti-HIV medications can be  HIV instin pregnantituted. women . AnteEmploying-natal screeningcombination is interventions advised, so that during anti pregnancy,-HIV medications labour and can post be deliveryinstituted. (e.g. antiretroviral therapy, elective caesarean section and . avoEmployingidance of combination breastfeeding) interventions can markedly during reduce pregnancy, the transmission labour andto baby. post Now,delivery with (e.g. combination antiretroviral therapy therapy, and undetectable elective caesarean maternal viral section load, and the riskavoi disance minimal of breastfeeding) (from about 23%can markedlyto < 1-2 %). reduce the transmission to baby. Now, with combination therapy and undetectable maternal viral load, the risk is minimal (from about 23% to < 1-2 %).

 Post-exposure prophylaxis for needle-stick injuries in HCW  Post. -Postexposure-exposure prophylaxis antiretroviral for needle prophylaxis-stick injuries significantly in HCW reduces risk of . Posttransmission-exposure of HIV antiretroviral (up to 80% prophylaxis risk reduction significantly if started early). reduces risk of . Combinationtransmission of therapy HIV (up with to 80% at least risk reduction 2 – 3 drugs if started is recommended early). for all . Combinationsignificant exposures therapy (see with Appendix at least 1 2 for– 3details). drugs is recommended for all significant exposures (see Appendix 1 for details).  HIV in children: refer to ID physician, KK Women’s & Children’s Hospital.  HIV in children: refer to ID physician, KK Women’s & Children’s Hospital. Post-test counselling Post1. -Negativetest counselling test 1. .Negative Explain test results. . IfExplain risk activity results. within last 6 months, inform patient of window period and . adviseIf risk activityre-testing within 3 months last 6later. months, inform patient of window period and . Reinforceadvise re-testing advice 3on months risk reduction. later. . ReassureReinforce confidentiality. advice on risk reduction. . Reassure confidentiality. 2. Positive test 2. .Positive Reassure test confidentiality. . AssessReassure risk confidentiality. factors. . ExplainAssess risk results. factors. . ProvideExplain results.basic information about HIV, AIDS and transmission. . AssessProvide patient’s basic information support system about andHIV, coping AIDS mechanism. and transmission. . ExplainAssess patient’s that very support effective system therapies and coping are mechanism. now available for HIV/AIDS . treatment.Explain that very effective therapies are now available for HIV/AIDS . Advisetreatment. that treatment cost has declined and treatment can be affordable. . MedifundAdvise that assistance treatment for cost treatment has declined is available and treatment for needy can patients. be affordable. Other fundsMedifund are also assistance available for to treatmenthelp these ispatients available. for needy patients. Other . Explainfunds are also the available need for to helpfurther these medicalpatients . assessment and long-term . managExplaine ment the at needa specialist for referralfurther centre. medical assessment and long-term . managHelp toe mentdecide at whoa specialist else should referral be informedcentre. of the diagnosis. . AdviseHelp to decide on the who need else for should contact be tracing,informed partner of the diagnosis notification. and partner . screening.Advise on U thender need the forInfectious contact Diseases tracing, Act partner (IDA), notification a medical andpractitioner partner mayscreening. disclose Under information the Infectious relating Diseases to any Act person (IDA), whoma medical he practitioner reasonably bmayelieves disclose to be information infected with relating HIV/AIDS to any to theperson spouse, whom former he reasonably spouse or otherbelieves contact to be of infectedthe infected with person, HIV/AIDS if: to the spouse, former spouse or .other H contacte/she reason of theably infected believes person, that if: it is medically appropriate and that . Htheree/she is areason significantably believes risk of infection that it isto medicallythe partner; appropriate and that . Htheree/she is hasa significant counselled risk the of infected infection person to the regardingpartner; the need to notify . theHe/she partner has counselled and the medical the infected practitioner person reasonablyregarding the believes need to that notify the ithenfected partner person and will the not medical inform practitioner the partner; reasonably and believes that the . Hinefected/she has person informed will not the inform infected the partner; person ofand his intent to make such . diHesclosure/she has to informed the partner. the infected person of his intent to make such disclosure to the partner.

50 50

. Advise on the risk of infecting others through sexual activities, blood/organ donation, sharing injection needles etc and the need to take preventive . Advisemeasures on at the all risk times of toinfecting prevent others the transmission through sexual of HIV. activities, blood/organ . Informdonation, the sharing patient injectionthat it is needlean offences etc under and thethe needIDA for to takea HIV preventive-infected personmeasures to atcarry all timesout activities to prevent that the could transmission transmit ofHIV. HIV. It is also an offence . Informunder th thee IDA patient for athat person it is withan offence HIV/AIDS under to the engage IDA infor sex a HIVwith- infectedanother person to unless carry priorout activities to sex, hethat hascould informed transmit that HIV. person It is also of thean offence risk of undercontracting the IDA HIV/AIDS for a person from withhim HIV/AIDSand that person to engage has voluntarily in sex with agreed another to persontake that unless risk. prior to sex, he has informed that person of the risk of contracting HIV/AIDS from him and that person has voluntarily agreed to Preventiontake and that Control risk.  Being faithful to one uninfected partner. Prevention Practise and safer Control sex (correct and consistent condom use).  AvoidBeing faicasualthful and to one commercial uninfected sex. partner.  PractiseAvoid needle safer sexsharing. (correct and consistent condom use).  AtAvoid-risk casual people and should commercial not donate sex. blood.  DonorAvoid needleassessment sharing. and screening of donated blood.  AtScreening-risk people of STI should and TnotB patients.donate blood.  EnhancedDonor assessment screening and; e.g screening. opt-out of testing donated in blood pregnant. females and hospitalised  Spatients.creening of STI and TB patients.  EnhancedStandard universal screening precautions; e.g. opt-out for testingblood and in pregnantbody fluids. females and hospitalised  Nopatients. effective vaccination is available at present.  Standard universal precautions for blood and body fluids.  No effective vaccination is available at present. References 1. The Body. www.thebody.com (A patient informational website). Accessed Oct 2010. 2. AIDSinfo: http://aidsinfo.nih.gov. (A physician and patient informational website). Accessed Oct References2010. 1. The Body. www.thebody.com (A patient informational website). Accessed Oct 2010. 3. Huang XH, Chen MI, Ang LW et al. Seroprevalence of human immunodeficiency virus (HIV) 2. AIDSinfo: http://aidsinfo.nih.gov. (A physician and patient informational website). Accessed Oct among sentinel surveillance populations in Singapore, 1989-2008. Epidemiol News Bulletin 2010. 2009;35:63-8 3. Huang XH, Chen MI, Ang LW et al. Seroprevalence of human immunodeficiency virus (HIV) 4. Lee CC, Sun YJ, Barkham T et al. Primary drug resistance and transmission analysis of HIV-1 in among sentinel surveillance populations in Singapore, 1989-2008. Epidemiol News Bulletin acute and recent drug-naïve seroconverters in Singapore. HIV Med. 2009 ;10:370-7 2009;35:63-8 5. US Centers for Disease Control and Prevention. Guidelines for prevention and treatment of 4. Lee CC, Sun YJ, Barkham T et al. Primary drug resistance and transmission analysis of HIV-1 in opportunistic infections in HIV-infected adults and adolescents. MMWR 2009; 58(RR-4): 1-207. acute and recent drug-naïve seroconverters in Singapore. HIV Med. 2009 ;10:370-7

5. US Centers for Disease Control and Prevention. Guidelines for prevention and treatment of

opportunistic infections in HIV-infected adults and adolescents. MMWR 2009; 58(RR-4): 1-207.

HUMAN AND AVIAN INFLUENZA

HUMAN INFLUENZAHUMAN AND AVIAN INFLUENZA

CausativeHUMAN INFLUENZA Agent Influenza virus type A (subtypes H1N1, H2N2, H3N2), B and C. Influenza type C Causativeinfection causes Agent a febrile mild upper respiratory illness and does not occur in Influenzepidemics.a virus type A (subtypes H1N1, H2N2, H3N2), B and C. Influenza type C infection causes a febrile mild upper respiratory illness and does not occur in epIncubationidemics. Period 24 - 72 hours Incubation Period 24Infectious - 72 hours Period One day before symptoms develop and up to 5-7 days after symptom onset. Infectious Period TransmissionOne day before symptoms develop and up to 5-7 days after symptom onset. Mainly via respiratory droplets and direct contact with nasal or throat secretions. Transmission MainlyEpidemiology via respiratory droplets and direct contact with nasal or throat secretions. Influenza A and B virus infections occur all year round in Singapore with small Epidemiologypeaks in the middle and the end/beginning of the year. Influenza A and B virus infections occur all year round in Singapore with small peaksIn April in 2009,the middle an outbreak and the ofend/be influenzaginning caused of the by year. a novel influenza A virus (H1N1- 2009), was reported in Mexico. It subsequently spread to the rest of the world. InSi nAprilgapore 2009, reported an outbreak its first ofcase influenza in a returning caused bystudent a novel from influenza New York, A virus US, (H1N1 on 26- May2009), 2009. was On reported 11 June, in Mexico the World. It subsequently Health Organisation spread (WHO) to the rest declared of the the world. first inflSingaporeuenza pandemic reported itsof thefirst 21 casest century. in a returning By September student 2009, from itNew was York,estimated US, thaton 26at Mayleast 270,000 2009. On persons 11 June, had the been World infected Health in OrganisationSingapore. A (WHO)total of declared18 H1N1 the-related first st infldeauthsenza were pandemic reported of the during 21 thiscentury. period, By September representing 2009, slightly it was more estimated than 1%that ofat holeastspitalized 270,000 cases persons and had a casebeen fatalityinfected rate in Singapore. of 6.7 per A 100,000 total of cases.18 H1N1 The- related WHO declareddeaths were an end reported to the pandemic during this in August period, 2010. representing slightly more than 1% of hospitalized cases and a case fatality rate of 6.7 per 100,000 cases. The WHO Clinicaldeclared Featuresan end to the pandemic in August 2010.  Classic influenza includes symptoms of fever, chills, headache, malaise, Clinicalmyalgia, Features and anorexia. Respiratory symptoms include sore throat, dry cough  Classicand nasal influenza discharge. includes Elderly patients symptom mays of present fever, with chills, confusion. headache, malaise,  myalgia,Well recognised and anorexia. pulmonary Respiratory complications symptoms include include primary sore viral throat, pneumonia dry cough and andsecondary nasal discharge. bacterial Elderly pneumonia patients may (most present often with Staphylococcus confusion. aureus,  StreptocoWell recognisedccus pneumoniae pulmonary and complications Haemophilus include influenzae primary). viral pneumonia and  secondaryOther complications bacterial include pneumonia croup, exacerbation (most often of chronicStaphylococcus pulmonary disease, aureus, Streptocomyocarditis,ccus Guillain pneumoniae-Barré and syndrome Haemophilus and Reye’s influenzae syndrome.).  Other complications include croup, exacerbation of chronic pulmonary disease, myocarditis, Guillain-Barré syndrome and Reye’s syndrome.

Investigations Investigations Rapid diagnosis can be performed using antigen detection by  immunofluoreRapid diagnosisscence can (IF) on be nasopharyngeal performed using aspirates/swabs, antigen detection throat swabs, by immunofluorenasal or bronchialscence washings. (IF) on Rapid nasopharyngeal detection kits aspirates/swabs, using the membrane throat enzyme swabs, immunoassaynasal or bronchial (EIA) washings. method Rapid and detectionthe immunochromatographic kits using the membrane method enzyme are immunoassayavailable for point (EIA)-of -care method testing. and the immunochromatographic method are  Reverseavailable-transcriptase for point-of- carePCR testing.  ReverseFor epidemiological-transcriptase purposes, PCR serology by complement fixation test is carried  outFor onepidemiological paired sera taken purposes, 2 weeks serology apart. by complement fixation test is carried  Viralout on culture paired serausing taken the MDCK2 weeks (Madin apart. Darby canine kidney) cell line in shell  vialViral cultures. culture usingResults the are MDCK available (Madin after 5Darby days ofcanine incubation. kidney) cell line in shell vial cultures. Results are available after 5 days of incubation. NB: Diagnosis can be made on epidemiological grounds in the setting of an inflNB:u enza Diagnosis outbreak can. be made on epidemiological grounds in the setting of an influenza outbreak. Notification NotificationSeasonal influenza is not a notifiable disease in Singapore. Seasonal influenza is not a notifiable disease in Singapore. Management Management Symptomatic treatment with antipyretics and anti-histamines and adequate bed  Symptomaticrest and fluids treatment are usually with sufficient antipyretics in the and management anti-histamines of acute and adequatesymptoms bed of influenza.rest and fluids Avoid are salicylates usually sufficient in children in becausethe management of the risk of of acute Rey e’ssymptoms syndrome. of  Neuraminidaseinfluenza. Avoid inhibitors salicylates (zanamivir in children and because oseltamivir) of the ifrisk administered of Reye’s syndrome. within 48  hNeuraminidaseours of illness inhibitorsonset, reduce (zanamivir duration and of symptomsoseltamivir) for if bothadministered influenza within A and 48 B byhou oners of day. illness Recommended onset, reduce dose duration and duration: of symptoms for both influenza A and B by oneZanamivir day. Recommended 2 puffs (10 mg) dose bd and x 5duration: days (age 5 years and above)  OseltamivirZanamivir 2 75puffs mg (10 oral mg) bd bd x x 55 daysdays (a (agege 5 one years year and and above) above). Weight-  Oseltamivirbased dosing 75for mgthose oral less bd than x 540 days kg. (age one year and above). Weight-  Amantadinebased dosing can shorten for those the less duration than 40 and kg. severity of influenza A illness if used  withinAmantadine 48 hours can shorten of onset. the It duration is approved and severity for use of in influenza people age A illness one year if used and withinabove. 48 The hours dose of recommended onset. It is approved for adults for is u100se in mg people twice age daily one for year 3 days. and Weightabove. - Thebased dose dosing recommended for those aged for 1 adults-8 years is old. 100 mg twice daily for 3 days.  WeightRimatadine-based is approveddosing for to those treat aged influenza 1-8 years A infection old. in people age 13 years and  above.Rimatadine The drugis approved is not registered to treat influenza in Singapore. A infection in people age 13 years and  Antibioticsabove. The drugare used is not for registered proven bacterialin Singapore. superinfections. Other complications  Antibioticsare managed are by usedsupportive for proven treatment. bacterial superinfections. Other complications are managed by supportive treatment.

Prevention and Control Prevention Surveillance and Control of influenza activity is routinely carried out in Singapore. This is  basedSurveillance on weekly of influenza polyclinic activity attendances is routinely for influenza carried- likeout inillnesses Singapore. and clinicalThis is based on weekly polyclinic attendances for influenza-like illnesses and clinical

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specimens positive for influenza viruses reported to MOH by SGH and other selected laboratories.  specimensHealth education positive through for influenza the mass viruses media to reported prevent to rapid MOH spread by SGH of infection and other by indiscriminateselected laboratories. coughing and sneezing and instructions on proper hand-washing  isHealth carried education out during through an outbreak. the mass media to prevent rapid spread of infection by  Immunoprophylaxisindiscriminate coughing with and inactivated sneezing and vaccine instructions or chemoprophylaxis on proper hand -washing with an influenzais carried -outspecific during anti an- viraloutbreak. drug (oseltamivir or amantadine) can reduce the  iImmunoprophylaxismpact of influenza. with inactivated vaccine or chemoprophylaxis with an influenza-specific anti-viral drug (oseltamivir or amantadine) can reduce the Vaccinationimpact of influenza.  The trivalent inactivated influenza vaccine (TIV) is recommended annually. It is Vaccinationprepared from the prevailing strains of influenza A and B. The vaccine is  uThepdated trivalent every inactivated year based influenza on the predicted vaccine predominant(TIV) is recommende strain for dthe annually. season. It is prepared from the prevailing strains of influenza A and B. The vaccine is  Oneupdated dose every of inactivatedyear based on vaccine the predicted is used predominant if previously strain vaccinated for the orseason. age ≥ 9 years. In children ≤ 9 years not previously vaccinated, 2 doses at least 4 weeks  apartOne doseshould of be inactivated given. vaccine is used if previously vaccinated or age ≥ 9 years. In children ≤ 9 years not previously vaccinated, 2 doses at least 4 weeks  Inapart some should countries be given., a l ive, intranasal influenza vaccine (LAIV) is available for healthy people 2-49 years of age. LAIV is not presently registered in Singapore.  In some countries, a live, intranasal influenza vaccine (LAIV) is available for Routinehealthy influenza people vaccination 2-49 years ofis agenow. LAIVrecommended is not presently for all registeredpersons aged in Singapore. 6 months and older. It is especially important that certain people get vaccinated either because thRoutineey are influenza at high risk vaccination of having is seriousnow recommended influenza-related for all complications persons aged or 6 becausemonths theyand older. live withIt is especially or care forimportant people that at highcertain risk people for get developing vaccinated influenza either because-related complications.they are at high risk of having serious influenza-related complications or because they live with or care for people at high risk for developing influenza-related complications. Target groups for vaccination . Persons > 65 years old. Target. groupsResidents for ofvaccination nursing hom e or chronic care facilities. . AdultsPersons or> 65 children years old. with chronic pulmonary or cardiovascular disorders . Residentsincluding childrenof nursing with hom asthma.e or chronic care facilities. . Adults and or children with with chronic chronic metabolic pulmonary diseases. or cardiovascular disorders . Childrenincluding andchildren teenagers with asthma. (6 months - 18 years of age) receiving long-term . Adultsaspirin andtherapy children and thereforewith chronic at risk metabolic for developing diseases. Reye’s syndrome. . ChildrenHealthcare and workers teenagers and others (6 months providing - 18 care years to of persons age) receiving at high risk. long -term . Householdaspirin therapy members and therefore of persons at riskin high for -developingrisk groups. Reye’s syndrome. . WomenHealthcare who workers will be and in othersthe second providing or third care trimester to persons of at pregnancy high risk. during . Householdthe influenza members season. of persons in high-risk groups. . Women who will be in the second or third trimester of pregnancy during the influenza season.

Chemoprophylaxis . Oseltamivir 75 mg once daily for adults. Weight-based dosing for those less Chemoprophylaxisthan 40kg. . ZanamivirOseltamivir 1 75puff mg (5mg) once bd daily for those for adults.5 years Weightand above-based dosing for those less . Amantadinethan 40kg. 5mg/kg/day, up to 150mg /day in 2 divided doses (age 1-10 years); . 100Zanamivir mg bd 1 (age puff 10 (5mg) years bd and for above) those 5 years and above . Amantadine 5mg/kg/day, up to 150mg /day in 2 divided doses (age 1-10 years); Duration100 mg of bd chemoprophylaxis (age 10 years and depends above) on the period of influenza activity in the community. Duration of chemoprophylaxis depends on the period of influenza activity in the Preventioncommunity. of Nosocomial Influenza . Encourage vaccination and chemoprophylaxis for the hospital staff. .Prevention Instruct ofstaff Nosocomial members whoInfluenza develop illness to stay away from work. . RestrictEncourage visitors vaccination with any and illness. chemoprophylaxis for the hospital staff. . IsolateInstruct (in staff single members rooms) who or cohortdevelop patients illness withto stay acute away illness. from work. . RestrictObserve visitors standard with and any dropletillness. precautions against cross-infection: gowns, . Isolatemasks and(in singlehand- washing.rooms) or cohort patients with acute illness. . PoObservestpone standard all elective and surgery droplet because precautions anaesthesia against may cross add-infection: to the risk gowns, of pulmmaskso naryand handcomplications.-washing. . Postpone all elective surgery because anaesthesia may add to the risk of pulmonary complications. References 1. Nicholson KG, Wood JM, Zambon M. Influenza. Lancet. 2003; 362:1733-45. 2. US Centers for Disease Control and Prevention. Prevention and control of influenza with vaccines, ReferencesRecommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1. RNicholsonecomm Rep KG, 2010; Wood 59(RR JM, Zambon-8): 1-62. M. Influenza. Lancet. 2003; 362:1733-45. 2.3. USWorld Centers Health for Organization. Disease Control Statement and Prevention. by WHO DirectorPrevention-General and control Dr Margaret of influenza Chan 29with April vaccines, 2009. RecommendationsAvailable at http://www.who.int/mediacentre/news/statements/2009/h1n1_20090429/en/index.html of the Advisory Committee on Immunization Practices (ACIP). MMWR. RAeccessedcomm RepOctober 2010; 2009 59(RR. -8): 1-62. 3.4. WorldCutter HealthJL, Ang Organization. LW, Lai FYL Statement et al. Outbreak by WHO of Directorpandemic-General influenza Dr MargaretA (H1N1 -Chan2009) 29 in April Singapore, 2009. AvailableMay to September at http://www.who.int/mediacentre/news/statements/2009/h1n1_20090429/en/index.html 2009. Ann Acad Med Singapore 2010;39:273-82. . Accessed October 2009. 4. Cutter JL, Ang LW, Lai FYL et al. Outbreak of pandemic influenza A (H1N1-2009) in Singapore, May to September 2009. Ann Acad Med Singapore 2010;39:273-82.

AVIAN INFLUENZA (BIRD FLU)

CausativeAVIAN INFLUENZA Agent (BIRD FLU) Caused by type A strain of influenza. Two types of avian influenza are defined basedCausative on theirAgent virulence: a highly virulent type that causes fowl plague (highly pathogenicCaused by aviantype A influenza, strain of HPAI) influenza. and Twoan avirulent types of type avian that influenza causes only are milddefined or asymptomaticbased on their disease. virulence: All aHPAI highly are virulentof the H5 type and that H7 causessubtype fowl and responsible plague (highly for largepathogenic avian epidemics avian influenza, to date. HPAI) and an avirulent type that causes only mild or asymptomatic disease. All HPAI are of the H5 and H7 subtype and responsible for Incubationlarge avian epidemics Period to date. 2 -5days (range 1-9 days) Incubation Period Infectious2-5days (range Period 1-9 days) No sustained human-to-human transmission documented to date. Infectious Period TransmissionNo sustained human -to-human transmission documented to date. Avian influenza viruses spread among susceptible birds through contact with contaminatedTransmission excretions of other infected birds. They do not normally infect other spAvianecies influenzawith the exception viruses spreadof pigs amongand horses. susceptible Infection birds of other through mammals contact like withcats contaminatedhas also been reported.excretions of other infected birds. They do not normally infect other sp ecies with the exception of pigs and horses. Infection of other mammals like cats Humanhas also infectionbeen reported. results from close contact with infected poultry (secretions and excrement) or contaminated surfaces. Human infection results from close contact with infected poultry (secretions and Epidemiologyexcrement) or contaminated surfaces. The virus circulates among birds worldwide. Epidemiology The virus first documentedcirculates among human birds infection worldwide. with an avian influenza virus occurred in Hong Kong in 1997, when the H5N1 strain caused severe respiratory disease in 18 humans,The first of documented whom 6 died. human The infectioninfection withof humans an avian co incided influenza with virus an epidemic occurred of in HPAI,Hong Kong caused in by 1997, the samewhen strain, the H5N1 in Hong strain Kong’s caused poultry severe population. respiratory disease in 18 humans, of whom 6 died. The infection of humans coincided with an epidemic of TheHPAI, H7N7 caused subtype by the was same responsible strain, in Hongfor another Kong’s outbreak poultry inpopulation. the Netherlands in 2003 when 83 cases of conjunctivitis and one death from severe respiratory illness were reported.The H7N7 subtype was responsible for another outbreak in the Netherlands in 2003 when 83 cases of conjunctivitis and one death from severe respiratory illness were Inreported. the 2004 outbreaks involving H5N1 subtype in Thailand and Vietnam, human cases were associated with severe respiratory disease and high mortality. During the periodIn the 2004 2003 - outbreaks2010, a total involving of 512 H5N1 cases, subtype including in Thailand 304 deaths, and were Vietnam, reported human to WHO,cases were with associated most of the with cases severe from respiratory Indonesia disease(171 cases and withhigh 141mortality. deaths), During Vietnam the (119period cases 2003 with-2010, 59 deaths) a total and of Egypt 512 cases, (115 cases including with 38 304 deaths) deaths,. were reported to WHO, with most of the cases from Indonesia (171 cases with 141 deaths), Vietnam (119 cases with 59 deaths) and Egypt (115 cases with 38 deaths).

Clinical Features Human cases: The clinical presentations are variable and determined in part by the virusClinical cla Featuresde. A feature of H5N1 outbreaks is the predominance of infection in chiHumanldren cases:and young The clinicaladults. presentations are variable and determined in part by the virus clade. A feature of H5N1 outbreaks is the predominance of infection in chiAvianldren influenza and young H7N7 adults. and H7N3: Conjunctivitis is the most common presentation.

Avian influenza H5N1:H7N7 and H7N3: Conjunctivitis is the most common presentation.  Respiratory illness presenting with fever, cough and shortness of breath is the Avianmost influenza common H5N1: manifestation . Respiratory failure, ARDS and multi-organ failure  areRespiratory the major illness complication presentings of hospitalizedwith fever, cough patients. and shortness of breath is the  Gastrointestinalmost common manifestation symptoms such. Respiratory as watery failure, diarrhoea, ARDS vomiting and multi and-organ abdominal failure painare the may major be common complication earlys i ofn the hospitalized course of patients.the disease.  GastrointestinalCNS involvement symptoms has been described. such as watery diarrhoea, vomiting and abdominal  painCommon may be laboratory common findingsearly in the include course bilateral of the disease. pulmonary infiltrates on chest  CNSradiograph involvement (72%), ha lymphopenias been described. (73%), and increased serum transaminase  Commonlevels. Almost laboratory all human findings cases include had bilateral antecedent pulmonary avian exposureinfiltrates during on chest a radiographcoincident avian (72%), influenza lymphopenia outbreak (73%), among chickens. and increased serum transaminase levels. Almost all human cases had antecedent avian exposure during a Investigationscoincident avian influenza outbreak among chickens. Viral isolation, PCR assays or antigen detection from respiratory specimens. Investigations ViralTesting isolation, is indicated PCR in assays the following or antigen persons: detection from respiratory specimens. . Patients who have a travel history to a H5N1-affected country; and Testing. isHistory indicated of contactin the following with domestic persons: poultry or a known or suspected human . casePatients in a who H5N1 have-affected a travel country history within to a H5N1 10 days-affected of symptom country; onset; and and . RadiographicallyHistory of contact confirmed with domestic pneumonia, poultry ARDS,or a known or other or suspected severe respiratory human illnesscase in ofa H5N1uncertain-affected aetiology. country within 10 days of symptom onset; and . Radiographically confirmed pneumonia, ARDS, or other severe respiratory Notificationillness of uncertain aetiology. 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. ANotify legally MOH notifiable immediately disease in on Singapore. suspicion. Notify Call Ministry MOH of Communicable Health (Form DiseasesMD 131 orSurv electronicallyeillance 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 SurvManagementeillance team at: 98171463  Oseltamivir remains the primary recommended antiviral therapy. Management Modified regimens of oseltamivir treatment, including two-fold higher dosages,  longerOseltamivir duration remains and possiblythe primary combination recommended therapy antiviral with therapy.other antivirals may be  consideredModified regimens on a case of- byoseltamivir-case basis, treatment, especially including in patients two - withfold higher severe dosages, disease, longerdiarrhoea duration or late and presentation. possibly combination therapy with other antivirals may be considered on a case-by-case basis, especially in patients with severe disease, diarrhoea or late presentation.

 Corticosteroids should not be used routinely but may be considered for septic shock with suspected adrenal insufficiency requiring vasopressors.  CorticosteroidsOseltamivir resistance should cannot emergebe used duringroutinely therapy but mayfor avianbe considered H5N1 and for may septic be shockassociated with withsuspected clinical adrenal deterioration. insufficiency requiring vasopressors.  Oseltamivir resistance can emerge during therapy for avian H5N1 and may be Preventionassociated and with Control clinical deterioration.  Surveillance of affected flocks and culling (killing) of sick and exposed birds Preventionare the mostand Controleffective methods of controlling an epidemic.  SurveillancePatients suspected of affected or confirmed flocks and to haveculling avian (killing) influenza of sick must and be exposed isolated birds and aretreated. the most effective methods of controlling an epidemic.  Patients suspected or confirmed to have avian influenza must be isolated and Vaccinationtreated. Current seasonal influenza vaccine does not protect against H5N1 avian influenza butVaccination is recommended for selected populations at-risk to reduce opportunities for dual infections.Current seasonal influenza vaccine does not protect against H5N1 avian influenza but is recommended for selected populations at-risk to reduce opportunities for dual Chemoprophylaxisinfections. Recent H5N1 viruses are susceptible to oseltamivir but there are reports of resistance toChemoprophylaxis the M2 inhibitors (amantadine and rimantadine). Recent H5N1 viruses are susceptible to oseltamivir but there are reports of resistance to the M2 inhibitors (amantadine and rimantadine). References 1. Schünemann HJ, Hill SR, Kakad M, et al.WHO Rapid Advice Guidelines for pharmacological Referencesmanagement of sporadic human infection with avian influenza A (H5N1) virus. Lancet Infect Dis 1. Schünemann2007;7: 21–31. HJ, Hill SR, Kakad M, et al.WHO Rapid Advice Guidelines for pharmacological 2. maUyekinagement TM. Humanof sporadic infection human with infection highly with pathogenic avian influenza avian influenza A (H5N1) A (H5N1)virus. Lancet virus: Infect review Dis of 2007;7:clinical issues.21–31. Clin Infect Dis. 2009 Jul 15;49(2):279-90 3.2. LiemUyeki NT, TM. Tung Human CV, infection Hien ND with et al. highly Clinical pathogenic features avianof human influenza influenza A (H5N1) A (H5N1) virus: infection review ofin Vietnam:clinical issues. 2004 -Clin2006. Infect Clin Dis.Infect 2009 Dis. Jul 2009;48:1639 15;49(2):279-46.-90 3.4. LiemGambotto NT, ATung, Barratt CV,- BoyesHien NDSM ,et de al. Jong Clinical MD etfeatures al. Human of human infection influenza with highly A (H5N1) pathogenic infection H5N1 in influenzaVietnam: 2004virus -Lancet.2006. Clin 2008;371:1464 Infect Dis. 2009;48:1639-75. -46. 5.4. deGambotto Jong MD, A, BarrattBach VC,-Boyes Phan SM TQ, de et Jong al. Fatal MD avianet al. Humaninfluenza infection A (H5N1) with in highly a child pathogenic presenting H5N1 with influenzadiarrhea followed virus Lancet. by coma. 2008;371:1464 N Engl J Med.-75. 2005;352:686–91. 5.6. deWorld Jong Health MD, Organization.Bach VC, Phan Avian TQ Influenza.et al. Fatal Available avian influenza at: A (H5N1) in a child presenting with diarrheahttp://www.who.int/csr/disease/avian_influe followed by coma. N Engl J Med. 2005;352:686nza/en/index.html–91. . Accessed Dec 2010. 7.6. CutterWorld J.Health Preparing Organization. for an influenza Avian Influenza.pandemic Availablein Singapore. at: Ann Acad Med Singapore 2008;37:497- 503.http://www.who.int/csr/disease/avian_influe nza/en/index.html. Accessed Dec 2010. 8.7. OngCutter A, J. Kindhauser Preparing for M, an Smith influenza I et al. pandemic A global inperspective Singapore. on Ann avian Acad influenza. Med Singapore Ann Acad 2008;37:497 Med - 503.Singapore 2008;37:477-81. 8.9. OngLeong A, HK, Kindhauser Goh CS,Chew M, Smith ST Iet et al. al. Prevention A global perspective and control on of avianavian influenza.influenza inAnn Sing Acadapore. Med Ann SingaporeAcad Med 2008;37:477Singapore 2008;37:504-81. -9. 10.9. ChowLeong VTK,HK, Goh Tambyah CS,Chew PA, STGoh et KT.al. Prevention To kill a mocking and cont birdrol of flu? avian Ann influenza Acad Med in SingSingaporeapore. Ann 2008;37:451Acad Med Singapore-3. 2008;37:504-9. 10. Chow VTK, Tambyah PA, Goh KT. To kill a mocking bird flu? Ann Acad Med Singapore 2008;37:451 -3.

JAPANESE ENCEPHALITIS

Causative Agent JAPANESE ENCEPHALITIS Japanese encephalitis virus (Flaviviridae) Causati ve Agent IncubationJapanese en cephalitisPeriod virus (Flaviviridae) 5–15 days Incubation Period Infectious5–15 days Period No human-to-human transmission Infectious Period EpidemiologyNo human-to-human transmission Transmitted by Culex spp mosquitoes from animals (principally pigs and wild birds) toEpidemiology man. Disease occurs principally in summer months in temperate countries and yearTransmitted round inby tropical Culex spp countries. mosquitoes It is from primarily animals a disease (principally of rural pigs areas and wild where birds) pig farmingto man. and Disease rice cultivation occurs prin cocipally-exist. in summer months in temperate countries and year round in tropical countries. It is primarily a disease of rural areas where pig farmingOccurs mainly and rice in cultivation 3 areas (see co maps):-exist.  China Occurs Indian mainly subcontinent in 3 areas (see consisting maps): of India, parts of Bangladesh, southern Nepal,  SriChina Lanka.  SoutheastIndian subcontinent Asia including consisting Myanmar, of India, Thailand, parts of Bangladesh, Cambodia, Laos,southern Vietnam, Nepal, SriMa laysia,Lanka. Indonesia and the Philippines. It is uncommon in Japan, Korea,  SoutheastTaiwan and Asia Hong including Kong. Myanmar,Sporadic cases Thailand, have Cambodia, been reported Laos, in Vietnam,Northern MAustralia.alaysia, Indonesia and the Philippines. It is uncommon in Japan, Korea, Taiwan and Hong Kong. Sporadic cases have been reported in Northern The Australia.disease has virtually been eliminated from Singapore although seroprevalence surveys of feral pigs on Pulau Tekong, farm animals and birds in peripheral TheSing adiseasepore indicate has virtually continued been enzootic eliminated transmission. from Singapore During althoughthe period seroprevalence 2005-2009, a totalsurveys of 4 ofcases, feral comprising pigs on Pulau1 imported Tekong, and 3 farm local animalscases, were and reported. birds in peripheral Singapore indicate continued enzootic transmission. During the period 2005-2009, a totalClinical of 4 Features cases, comprising 1 imported and 3 local cases, were reported.  Most human infections are asymptomatic and mild; approximately 1 in 300 Clinicalinfections Features result in encephalitis.  MostIllness human begins infections with a non are-specific asymptomatic febrile andprodr mild;ome ofapproximately headache, abdominal 1 in 300 ipain,nfections nausea result and in vomitingencephalitis. for several days followed by altered mental state,  Illnessdrowsiness begins and withcoma. a Convulsions non-specific are febrile common prodr inome the paediatric of headache, population. abdominal  Neurologicalpain, nausea and signs vomiting include for cranial several nerve days palsies, followed tremors, by altered ataxia, mental rigidity, state, pdrowsinessarkinsonism and and coma. upper Convulsions motor neuron are paralysis.common in the paediatric population.  NeurologicalCase fatality signsis about include 20-30%. cranial Sequelae nerve palsies, include tremors, parkinsonism, ataxia, paralysis, rigidity, psearizures,kinsonism mental and upper retardation, motor neuron and psychiatric paralysis. complaints in up to 70% of  Casesurvivors. fatality is about 20-30%. Sequelae include parkinsonism, paralysis, seizures, mental retardation, and psychiatric complaints in up to 70% of survivors.

Investigations  CT/MRI may show abnormal areas in the thalamus and brainstem. Investigations CSF shows <1000 cells/mm3, mildly elevated protein, normal glucose.  Serology:CT/MRI may Complement show abnormal fixation areas titres in th toe thalamus flavivirus and group brainstem. in sera or CSF. A  presumptiveCSF shows <1000 diagnosis cells/mm may 3, be mildly made elevated if this isprotein, positive normal and glucose. is consistent with  clinSerology:ical and Complement epidemiologic fixation features. titres to flavivirus group in sera or CSF. A  JEpresumptive-specific PCR diagnosis should maybe done be madefor highly if this-suspect is positive cases andafter isconsultation consistent with theclin ilaboratorycal and epidemiologic director. Viral features. isolation and JE-specific PCR can be performed  fromJE-specific brain PCR tissue should and cerebrospinal be done for highly fluid - ofsuspect suspect cases patients after consultation within 1week with of thedeath. laboratory director. Viral isolation and JE-specific PCR can be performed from brain tissue and cerebrospinal fluid of suspect patients within 1week of It is death. important to exclude treatable cases such as herpes encephalitis, bacterial, fungal and mycobacterial infections of the CNS and metabolic encephalopathies. It is important to exclude treatable cases such as herpes encephalitis, bacterial, Notificationfungal and mycobacterial infections of the CNS and metabolic encephalopathies. Notify Ministry of Health (Form MD 131 or electronically via CD-LENS). Notification NotifyManagement Ministry of Health (Form MD 131 or electronically via CD-LENS).  There is no specific anti-viral treatment available. Management Treatment is supportive and anti-convulsants are used to control seizures.  There is no specific anti-viral treatment available. Prevention Treatment and is Control supportive and anti-convulsants are used to control seizures.  This is a vaccine-preventable disease. Prevention The vaccine and Control is recommended for persons who travel to endemic region for 1  monthThis is ora vaccine more and-preventable stay/work disease. in rural areas especially during the transmission  Theseason. vaccine is recommended for persons who travel to endemic region for 1  Travellersmonth or more who and are stay/work at risk need in rural to take areas mosquito especially precautions during the in transmission addition to vaseason.ccination.  AdultTravellers Culex who mosquitoes are at risk can need be destroyed to take mosquito by insecti precautionscide spraying in addition and larvae to eliminatedvaccination. by oiling potential breeding habitats.  Adult Culex mosquitoes can be destroyed by insecticide spraying and larvae eliminated by oiling potential breeding habitats.

References 1. Japanese Encephalitis vaccines. Recommendations of the Advisory Committee on Immunisation ReferencesPractices (ACIP). MMWR Recomm Rep 2010; 59(RR-1):1-32 2. See E,Tan HC,Wang D et al. Presence of hemagglutination inhibition and neutralization antibodies 1. Japanese Encephalitis vaccines. Recommendations of the Advisory Committee on Immunisation toPractices Japanese (ACIP). encephalitis MMWR virus Recomm in wild pigsRep on2010; an offshore59(RR-1):1 island-32 in Singapore. Acta Tropica 2002; 81:233-6 2. See E,Tan HC,Wang D et al. Presence of hemagglutination inhibition and neutralization antibodies 3. toTing Japanese SHL, Tan encephalitis HC, Wong virus WK in et wild al. Seroepidemiologypigs on an offshore of island neutralizing in Singapore. antibodies Acta to Tropica Japanese 2002; 81:233encephalitis-6 virus in Singapore: continued transmission despite abolishment of pig farming? Acta Tropica 2004;92:187-91 3. Ting SHL, Tan HC, Wong WK et al. Seroepidemiology of neutralizing antibodies to Japanese 4. encephalitisKoh YL,Tan virus BH, Lohin Singapore: JJP et al. continuedJapanese encephalitis, transmission Singapore. despite abolishment Emerg Infect of pig Dis farming? 2006;12:525 Acta- 6. Tropica 2004;92:187-91 4. Koh YL,Tan BH, Loh JJP et al. Japanese encephalitis, Singapore. Emerg Infect Dis 2006;12:525-6.

LEGIONELLOSIS

Causative Agent LEGIONELLOSIS Legionella pneumophila (serogroups 1, 4, 6 account for most human infections) Caus ative Agent LegionellaIncubation pneumophila Period (serogroups 1, 4, 6 account for most human infections) 2 - 10 days (range up to 16 days) Incubation Period Infectious2 - 10 days Period(range up to 16 days) No person-to-person transmission Infectious Period TransmissionNo person-to-person transmission Inhalation of aerosols and occasionally aspiration of water contaminated with TransmissionLegionella bacteria. Inhalation of aerosols and occasionally aspiration of water contaminated with EpidemiologyLegionella bacteria. Environmental organism found in man-made aquatic reservoirs including cooling towers,Epidemiology water storage tanks, hot water system, spas, evaporative condensers, Environmentaldecorative fountains organism and other found water in man-containing-made aquatic devices. reservoirs including cooling towers, water storage tanks, hot water system, spas, evaporative condensers, Seroprevalancedecorative fountains studies and suggest other water that -asymptomaticcontaining devices. or subclinical infection is more common than clinical or symptomatic cases. L. pneumophila serogroup 1 accounts Seroprevalancefor the majority ofstudies Legionnaires’ suggest that disease asymptomatic. or subclinical infection is more common than clinical or symptomatic cases. L. pneumophila serogroup 1 accounts Afor total the majorityof 103 cases of Legionnaires’ of legionellosis disease were. reported in Singapore from 2005-2009. Of these 22 were confirmed Legionnaires’ disease. Cases were sporadic with no cluA totalstering of 103by locality. cases of Overalllegionellosis case- fatalitywere reported rate was in 1.0% Singapore . from 2005-2009. Of these 22 were confirmed Legionnaires’ disease. Cases were sporadic with no clustering by locality. Overall case-fatality rate was 1.0% . Clinical Features There are 2 distinct clinical manifestations: Clinical Pontiac Features Fever : a self-limiting flu-like illness without pneumonia. Attack rate of Therethose are 2 exposed distinct clinical is >90%. manifestations Predominant: symptoms are malaise, myalgia, fever,  chillsPontiac and Fever headache.: a self -Chestlimiting X- rayflu- likeremains illness clear. without Only pneumonia. symptomatic Attack treatment rate ofis required.those exposed Recovery is >90%. occurs Predominant within one week. symptoms are malaise, myalgia, fever, chills and headache. Chest X-ray remains clear. Only symptomatic treatment is  Legionnaires’required. Recovery Disease occurs: Pneumonia within one isweek. the predominant clinical finding. The patient experiences a prodrome of symptoms which includes fever, myalgia,  headache,Legionnaires’ anorexia, Disease non: Pneumonia-bloody diarrhoea, is the predominant encephalopathy, clinical or finding. change The in sensorium.patient experiences The cough a prodromeis often dry. of Sputum, symptoms if any, which may includes be blood fever, stained myalgia, with aheadache,ccompanying anorexia, chest pain. non -bloody diarrhoea, encephalopathy, or change in sensorium. The cough is often dry. Sputum, if any, may be blood stained with accompanying chest pain.

 The following are helpful clues towards diagnosing/suspecting Legionnaires’ disease: Gram stain of respiratory secretions with large amounts of neutrophils  Theand followingfew, if any are organisms, helpful clues hyponatremia towards diagnosing/suspecting (Na+ < 130mEq/ml), Legionnaires’ failure to disease:respond toGram -lactam stain ofantibiotics respiratory or aminoglycoside,secretions with large and occurrenceamounts of in neutrophils a hospital orand environment few, if any where organisms, the potable hyponatremia and hot water (Na+ < system 130mEq/ml), or air-conditioning failure to coolingrespond towerto -lactam is known antibiotics to be contaminated or aminoglycoside, with Legionella and occurrence. Most patients in a hospital have abnormalor environment chest X where-ray findings. the potable and hot water system or air-conditioning cooling tower is known to be contaminated with Legionella. Most patients have Investigationsabnormal chest X-ray findings.  Definitive diagnosis is by isolation of the organism from respiratory secretions Investigationson special media which has to be specifically requested. Obtaining an adequate  Definitivesputum sampl diagnosise may is beby difficult.isolation of Based the organism on local from experience, respiratory the secretions yield of Lone gionellaspecial mediaculture which from expectoratedhas to be specifically sputum samplesrequested. is low.Obtaining an adequate  sputumAntigen sampl detectione may by immunofluorescencebe difficult. Based on (IF) local can beexperience, performed the on yield sputum of Landegionella other respiratoryculture from specimen. expectorated The sputum sensitivity samples is poor is low. (25 - 7 5%) and cross-  Antigenreactions detectionwith other by species immunofluorescence may occur unless (IF) a monoclonal can be performed antibody on reagent sputum is andused. other respiratory specimen. The sensitivity is poor (25-75%) and cross-  Serology:reactions withAn acuteother- phasespecies single may occurelevated unless titre a (≥1024)monoclonal is suggestive antibody reagentof recent is infection.used. A four-fold rise in acute and convalescent titres is more  confirmSerology:atory. An acute-phase single elevated titre (≥1024) is suggestive of recent  infection.Urinary antigen A four detection-fold riseis sensitive in acute (70 -100%) and convalescent and specific but titres only is detects more confirmL. pneumophilaatory. serogroup 1.  Urinary antigen detection is sensitive (70-100%) and specific but only detects NotificationL. pneumophila serogroup 1. 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 Managementor electronically via CD-LENS) not later than 24 hours from the time of diagnosis.  Depends upon the severity of illness, the underlying health of the patient and Managementdrug tolerance.  DependsHealthy patients upon the with severity mild of pneumonia illness, the not underlying requiring health hospitalization of the patient may and be treateddrug tolerance. with a wide variety of antimicrobial agents, including erythromycin,  teHealthytracycline, patients doxycycline, with mild azithromycin, pneumonia not clarithromy requiring cin, hospitalization levofloxacin may and be treatedmoxifloxacin with . a wide variety of antimicrobial agents, including erythromycin,  Azithromycintetracycline, doxycycline,or a fluoroquinolone azithromycin, (moxifloxacin clarithromy cin,or levofloxacin) levofloxacin and are recomoxifloxacinmmended. for severe disease.  AzithromycinA delay in therapy or isa associated fluoroquinolone with an increased (moxifloxacin mortality. or levofloxacin) are  recoThe mdurationmended of for treatment severe disease. should be 10-21 days.  A delay in therapy is associated with an increased mortality. Prevention The duration and Control of treatment should be 10-21 days.  Epidemiological investigations to identify the source of infection and the mode Preventionof transmission and Control includ e sampling of water and sludge from cooling towers of  airEpidemiological-conditioned premises investigations for the to isolation identify of the Legionella source of. infection and the mode of transmission include sampling of water and sludge from cooling towers of air-conditioned premises for the isolation of Legionella.

 Maintenance of good engineering practices which entail regular mechanical cleaning of the cooling towers and routine treatment with biocides to inhibit  oMaintenancerganic growth of within good engineering the air-conditioning practices system. which entail A corrosion regular inhibitor mechanical as wellcleaning as a scale of the inhibitor cooling should towers be and used. routine treatment with biocides to inhibit  Routineorganic growth environmental within the monitoring air-conditioning for Legionella system. should A corrosion be performed inhibitor asin howellspitals as a scale where inhibitor organ andshould bone be marrowused. transplants are performed, given the  Routinehigh risk environmentalfor Legionnaires’ monitoring disease in forthese Legionella patients. should be performed in hospitals where organ and bone marrow transplants are performed, given the high risk for Legionnaires’ disease in these patients.

References 1. Goh KT, Ng, DLK, Yap J et al. Surveillance, prevention, and control of legionellosis in a Referencestropical city -state. Am J Infect Control 2005;33:286-91 2. WHO. Legionellosis. Available at: 1. Goh KT, Ng, DLK, Yap J et al. Surveillance, prevention, and control of legionellosis in a http://www.who.int/mediacentre/factsheets/fs285/en/index.html. Accessed Aug 2010. tropical city-state. Am J Infect Control 2005;33:286-91 3. Murdoch DR. Diagnosis of Legionella infection. Clin Infect Dis 2003; 36:64-9 2. WHO. Legionellosis. Available at: 4. Plouffe JF, Breiman RF, Fields BS et al. Azithromycin in the treatment of Legionella http://www.who.int/mediacentre/factsheets/fs285/en/index.html. Accessed Aug 2010. pneumonia requiring hospitalization. Clin Infect Dis 2003; 37:1475-80 3. Murdoch DR. Diagnosis of Legionella infection. Clin Infect Dis 2003; 36:64-9 4. Plouffe JF, Breiman RF, Fields BS et al. Azithromycin in the treatment of Legionella pneumonia requiring hospitalization. Clin Infect Dis 2003; 37:1475-80

LEPROSY

Causative Agent LEPROSY Mycobacterium leprae Causative Agent IncubationMycobacterium Period leprae 5 to 15 years. Incubation Period Infectious5 to 15 years. Period Leprosy is not highly infectious. Although all patients with active disease are poteInfectiousntially Periodinfectious, only those with bacillus in the skin and nose lesion (i.e. slit skinLeprosy smear is showing not highly acid infectious.-fast bacilli) Although pose a allhigher patients risk. Oncewith active therapy disease is started, are patientspotentially are infectious,considered onlynon- infectiousthose with within bacillus 6 weeksin the ofskin treatment. and nose lesion (i.e. slit skin smear showing acid-fast bacilli) pose a higher risk. Once therapy is started, Transmissionpatients are considered non-infectious within 6 weeks of treatment. Exact mode of transmission not clearly established; household and prolonged close Transmissioncontact appears to be important. Transmission is believed to be airborne, and less effectively,Exact mode directof transmission skin-to-skin not contact. clearly Susceptibility established; household is genetically and determinedprolonged closewith morecontact than appears 90% of to population be important. naturally Transmission immune. is believed to be airborne, and less effectively, direct skin-to-skin contact. Susceptibility is genetically determined with Epidemiologymore than 90% of population naturally immune. Leprosy only infects human and armadillos naturally. Humans are the only reservoir ofEpidemiology infection. Leprosy only infects human and armadillos naturally. Humans are the only reservoir Betweenof infection. 10 and 12 cases are reported each year. Of these, one-third are ‘indig enous’ cases and the rest are amongst foreign workers .There have been no Betweenrelapse cases 10 in and the 12past casesten years. are reported each year. Of these, one-third are ‘indig enous’ cases and the rest are amongst foreign workers .There have been no Mostrelapse Singaporean cases in the patients past ten are years. elderly (>60 years old) and suffer from multibacillary leprosy. Foreign workers are usually young adults with paucibacillary leprosy. Most Singaporean patients are elderly (>60 years old) and suffer from multibacillary Clinicalleprosy. ForeignFeatures workers are usually young adults with paucibacillary leprosy. The disease mainly affects the skin, the peripheral nerves, mucosa of the upper reClinicalspiratory Features tract and also the eyes. The disease mainly affects the skin, the peripheral nerves, mucosa of the upper Mostrespiratory patients tract present and also with the asymptomaticeyes. skin lesions while some (<5%) present with nerve deficit without skin signs. The affected skin may be pale or red; it may beMost a plaque, patients nodule present or withtumour. asymptomatic Loss of pin skin prick lesions sensation while within some (<5%)skin lesions present is pathognomonicwith nerve deficit of without leprosy. skin Peripheral signs. The nerve affect ed involvement skin may be may pale causeor red; muscleit may weaknessbe a plaque, and nodule paralysis or tumour.of limbs. LossExamination of pin prick may sensationreveal enlarged within nskinerves lesions with oris witpathognomonichout functional of deficit. leprosy. Peripheral nerve involvement may cause muscle weakness and paralysis of limbs. Examination may reveal enlarged nerves with or without functional deficit.

Classification For the purpose of treatment, leprosy is divided into: Classification For thePaucibacillary purpose of treatment, leprosy (tuberculoidleprosy is divided leprosy, into: borderline-tuberculoid leprosy, single-lesion paucibacillary leprosy and pure neural leprosy) and  Paucibacillary leprosy (tuberculoid leprosy, borderline-tuberculoid leprosy,  Multibacillarysingle-lesion paucibacillary leprosy (borderline leprosy- andborderline pure neural leprosy, leprosy) borderline and -lepromatous leprosy and lepromatous leprosy).  Multibacillary leprosy (borderline-borderline leprosy, borderline-lepromatous Investigationsleprosy and lepromatous leprosy). Slit skin smear to detect acid-fast bacillus confirms diagnosis of multibacillary leprosy.Investigations However, paucibacillary leprosy does not show a positive skin smear. HistSlit o skinlogical smear confirmation to detect should acid-fast be bacillus done in confirms all cases. diagnosis The lepromin of multibacillary test is not usefulleprosy. for diagnosis However, as paucibacillary it only reflects leprosy the immune does status not show of the a subject. positive skin smear. Histological confirmation should be done in all cases. The lepromin test is not Notificationuseful for diagnosis as it only reflects the immune status of the subject. A legally notifiable disease in Singapore. Notify the National Skin Centre (Form NotificationMD 131 or electronically via CD-LENS) not later than 72 hours from the time of Adiagnosis. legally notifiable disease in Singapore. Notify the National Skin Centre (Form MD 131 or electronically via CD-LENS) not later than 72 hours from the time of diagnosis. Management  It is important to first check patient’s G6PD status; do not give dapsone if Managementdeficient.  It is important to first check patient’s G6PD status; do not give dapsone if  defWHOicient chemotherapy. regime for leprosy is as follows:

1. WHOPaucibacillary chemotherapy leprosy regime (tuberculoid for leprosy leprosy is as and follows: borderline -tuberculoid leprosy) . Rifampicin 600 mg once a month plus 1. .Paucibacillary Dapsone 100 leprosy mg daily (tuberculoid leprosy and borderline-tuberculoid leprosy) . Duration:Rifampicin 6 600months mg once a month plus . Dapsone 100 mg daily 2. .Multibacillary Duration: 6 leprosy months (borderline -borderline leprosy, borderline-lepromatous leprosy and lepromatous leprosy) 2. .Multibacillary Rifampicin leprosy600 mg (borderlinedaily for 7 -days,borderline then ONCE leprosy, A MONTH borderline plus-lepromatou s .leprosy Clofazamine and lepromatous 50 mg dailyleprosy) plus . DapsoneRifampicin 100 600 mg mg daily daily for 7 days, then ONCE A MONTH plus . Duration:Clofazamine The 50 presentmg daily WHO plus recommendation is to treat for 12 months. . DapsoneSome authorities 100 mg dailywould extend treatment for up to 24 months, or until the . slitDuration: skin smear The turns present negative, WHO whichever recommendation is longer, is toparticularly treat for 12for months.patients withSome very authorities high bacterial would loads.extend treatment for up to 24 months, or until the slit skin smear turns negative, whichever is longer, particularly for patients with very high bacterial loads.

3. Alternative regimen: (second line treatment in patients who are unable to use dapsone or who have developed secondary resistance to dapsone) . Rifampicin 600 mg monthly plus . Ofloxacin 400 mg daily plus . Minocycline 100 mg daily

Others Leprosy is the most important treatable cause of permanent physical disability. Early treatment prevents or even reverses nerve damage. Measures to avoid injury to anaesthetic limbs, and rehabilitation of disabled limbs are part of the management of all leprosy patients.

Prevention and Control Active cases with living organisms are the main source of infection. Once antibiotic therapy is started, the risk of transmission declines tremendously. Close contacts of cases can be offered skin examination. There is no reliable serological test for subclinical cases. There is no vaccine for leprosy.

References

1. WHO recommended MDT regimens. Available at: http://www.who.int/lep/mdt/regimens/en/index.html. Accessed Aug 2010. 2. Pardillo FE, Fajardo TT, Abalos RM et al. Methods for the classification of leprosy for treatment purposes. Clin Infect Dis. 2007; 44:1096-9. 3. Scollard DM, Adams LB, Gillis TP et al. The continuing challenges of leprosy. Clin Microbiol Rev. 2006;19:338-81

MALARIA

Causative Agents MALARIA Plasmodium falciparum, P. vivax, P. ovale and P. malariae. CausativeIn recent years, Agents P knowlesi, a parasite of Old World monkeys has been identified as thePlasmodium fifth major falciparum, human malaria P. vivax, parasite. P. ovale It is and an emergingP. malariae. infection in SE Asia and is capableIn recent of years, causing P knowlesi, serious life a parasite threatening of Old complications World monkeys and deathhas been in a iden minoritytified ofas cases.the fifth major human malaria parasite. It is an emerging infection in SE Asia and is capable of causing serious life threatening complications and death in a minority of Incubationcases. Period 1 to 4 weeks (months for non-falciparum Plasmodium) Incubation Period Infectious1 to 4 weeks Period (months for non-falciparum Plasmodium) Until parasites cleared from blood. Infectious Period TransmissionUntil parasites cleared from blood. Transmission via bite of infected female Anopheles mosquito. Vertical transmission Transmissionand by blood transfusion or organ transplant also possible. Transmission via bite of infected female Anopheles mosquito. Vertical transmission Epidemiologyand by blood transfusion or organ transplant also possible. Approximately 100-300 cases per annum in Singapore (80% vivax); almost all are imported.Epidemiology Approximately 100-300 cases per annum in Singapore (80% vivax); almost all are imported.One hundred and seventy laboratory-confirmed cases were reported in 2009, an i ncrease of 13.2% compared to the 152 cases reported in 2008. 16.8% of the cases Onewere hundred reportedly and acquired seventy locally, laboratory an - increaseconfirmed of cases16.1% were compared reported to the in 2009, previous an iyear.ncrease There of 13.2%were six compared cases of simianto the 152malaria cases involving reported fivein 2008. locals 16.8% and one of foreigner.the cases Threewere reportedly of the local acquired residents locally, acquired an increase their infection of 16.1% while compared trekking to in the Malaysia previous at separateyear. There occasions were six while cases two of weresimian infec malariated during involving jungle five trainings locals andat Brunei. one foreigner. Three of the local residents acquired their infection while trekking in Malaysia at Endemicseparate occasions in SE Asia, while particularly two were rural infec areas.ted during jungle trainings at Brunei.

ChloroquineEndemic in SE-resistant Asia, particularly falciparum rural malaria areas. is widespread in the region; occasional cases of chloroquine-resistant vivax have also been reported. Chloroquine-resistant falciparum malaria is widespread in the region; occasional cases of chloroquine-resistant vivax have also been reported. Clinical Features Symp toms Fever,Clinical chills, Features rigors Symptoms SignsFever, chills, rigors Hepatosplenomegaly sometimes present Signs Hepatosplenomegaly sometimes present

Severe falciparum malaria Defined by presence of any of the following features: Severe Clinical falciparum malaria Defined byimpaired presence consciousness of any of the or following unrousable features: coma  Clinical prostration, i.e. generalized weakness so that the patient is unable walk or  sitimpaired up without consciousness assistance or unrousable coma  failureprostration, to feed i.e. generalized weakness so that the patient is unable walk or  multiplesit up without convulsions assistance – more than two episodes in 24 h  deepfailure breathing, to feed respiratory distress (acidotic breathing)  circulatorymultiple convulsions collapse or – shock,more than systolic two bloodepisodes pressure in 24 h< 70 mm Hg in adults  anddeep < breathing, 50 mm Hg respiratory in children distress (acidotic breathing)  clinicalcirculatory jaundice collapse plus or evidence shock, systolic of other blood vital pressureorgan dysfunction < 70 mm Hg in adults  andhaemoglobinuria < 50 mm Hg in children  abnormalclinical jaundice spontaneous plus evidence bleeding of other vital organ dysfunction  pulmonaryhaemoglobinuria oedema (radiological)  abnormal spontaneous bleeding  Laboratory pulmonary oedema (radiological)  hypoglycaemia (blood glucose < 2.2 mmol/l or < 40 mg/dl)   Laboratory metabolic acidosis (plasma bicarbonate < 15 mmol/l)  severehypoglycaemia normocytic (blood anaemia glucose (Hb < < 2.2 5 g/dl, mmol/l packed or < cell40 mg/dl) volume < 15%)  haemoglobinuriametabolic acidosis (plasma bicarbonate < 15 mmol/l)  hyperparasitaemiasevere normocytic (>anaemia 2%/100 (Hb 000/μl < 5 g/dl, in low packed intensity cell transmissionvolume < 15%) areas or  >haemoglobinuria 5% or 250 000/μl in areas of high stable malaria transmission intensity)  hyperlactataemiahyperparasitaemia (lactate (> 2%/100 > 5 mmol/l) 000/μl in low intensity transmission areas or  renal> 5% impairmentor 250 000/μl (serum in areas creatinine of high >stable 265 μmol/l)malaria transmission intensity)  hyperlactataemia (lactate > 5 mmol/l) Investigations renal impairment (serum creatinine > 265 μmol/l)  Examination of thick and thin blood films (repeat 12 hourly for 48 hours if the Investigationsdiagnosis is considered likely and initial films are negative).  RExamapidination diagnostic of thick tests and (RDTs) thin blood offer films a useful(repeat alternative 12 hourly for to microscopy48 hours if the in situationsdiagnosis iswhere considered reliable likely microscopic and initial diag filmsnosis are is negative).not available  Anaemia,Rapid diagnostic thrombocytopenia tests (RDTs) and leucopenia offer a useful are common. alternative to microscopy in  FBC,situations electrolytes, where reliable glucose, microscopic LFTs, diag clottingnosis screenis not available and a CXR should be  peAnaemia,rformed thrombocytopenia in all patients with and acute leucopenia falciparum are common. malaria to assess severity (see  aboveFBC, criteria). electrolytes, glucose, LFTs, clotting screen and a CXR should be performed in all patients with acute falciparum malaria to assess severity (see Notificationabove criteria). 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 Management Cases should be treated in hospital until parasitaemia has cleared.  Cases should be treated in hospital until parasitaemia has cleared.  Non-falciparum malaria: chloroquine 600 mg stat, then 300 mg X 3 daily doses.  PrimaquineNon-falciparum 15mg malaria: daily forchloroquine 2 weeks 600 to eliminatemg stat, then hepatic 300 stagemg X (check3 daily G6PDdoses. levelsPrimaquine first). 15mg daily for 2 weeks to eliminate hepatic stage (check G6PD levels first).  Falciparum malaria, mild: Artemisinin-based combination therapies preferred.  AlternativeFalciparum malaria, choice is mild: oral Artemisinin quinine 600-based mg combination tds for 7 days, therapies together preferred. with Alternativedoxycycline choic100 mge isbd oralfor 7 quininedays. 600 mg tds for 7 days, together with doxycycline 100 mg bd for 7 days.  Falciparum malaria, severe (as defined above): a medical emergency. Treatment  isFalciparum urgent and malaria, experience severe with(as defined severe above): malaria a medical is essential. emergency. Intravenous Treatment (IV) artesunateis urgent and plus experienceclindamycin with or doxycycline severe malaria is treatment is essential. of choiceIntravenous for severe (IV) artesunatemalaria. Intravenous plus clindamycin quinine or plus doxycycline doxycycline is treatment is an alternative. of choice Meticulous for severe malfluida ria.management, Intravenous regular quinine monitoring plus doxycycline of blood sugar is an and alternative. supportive Meticuloustherapy for ofluidrgan management, dysfunction regular as required. monitoring Excha ofnge blood transfusion sugar and may supportive be considered therapy for highorgan parasitaemia dysfunction as with required. complications, Exchange but transfusion the indications may be considered and level for of parasitaemiahigh parasitaemia are controversial. with complications, but the indications and level of parasitaemia are controversial. Prevention and Control ThePrevention best community and Control-based control in malaria endemic countries is impregnated bed- Thenets. best community-based control in malaria endemic countries is impregnated bed- nets.  For personal protective measures for travellers to endemic areas:  Fo. r personalAvoid exposure protective between measures dusk for travellers and dawn to endemic as this areas: is when the female . anophelineAvoid exposure mosquito between is active. dusk and dawn as this is when the female . Wearanopheline long- sleevesmosquito light is -active.coloured clothing. . UseWear mosquito long-sleeves repellent light -containingcoloured clothing. 10% to 30% DEET. . Use mosquitomosquito repellentcoils. containing 10% to 30% DEET. . ConsiderUse mosquito treating coils. clothes with permethrin-based products. . SleepConsider under treating impregnated clothes withmosquito permethrin netting- basedand keep products. to well -screened or air- . conditionedSleep under rooms.impregnated mosquito netting and keep to well-screened or air- conditioned rooms.  Control: epidemic vector control measures will be implemented when local  transmissionControl: epidemic is detected. vector control measures will be implemented when local transmission is detected. Chemoprophylaxis (see maps). Chemoprophylaxis. Mefloquine: (see 250mg maps). (salt) per week, beginning 1 week before departure and . continuedMefloquine: for 250mg 4 weeks (salt) after per leaving week, beginningthe endemic 1 week area. before Advantage: departure weekly and dosing;continued reasonable for 4 weeks pricing. after Disadvantage: leaving the endemic neuropsychiatric area. Advantage: side effect weeklys. dosing; reasonable pricing. Disadvantage: neuropsychiatric side effects.

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. Doxycycline: 100mg daily beginning 1 to 2 days before entering the affected area and for 4 weeks after leaving the area. Advantage: cheap. . Doxycycline:Disadvantage: 100mg daily dosing. daily beginningSide effects: 1 tophotosensitivity, 2 days before vaginal entering thrush the affectedand oesophagitis. area and for 4 weeks after leaving the area. Advantage: cheap. . DiAtovaquone/proguanilsadvantage: daily dosing. (Malarone): Side effects:1 adult photosensitivity,tablet once daily beginning vaginal thrush 1 to 2and days oesophagitis. before entering affected area and for 7 days after leaving the area. . Advantage:Atovaquone/proguanil few side effects, (Malarone): short duration 1 adult oftablet intake once before daily and beginning after travel. 1 to 2Disadvantage: days before enteringexpensive, affected daily intake. area and for 7 days after leaving the area. . Advantage:Chloroquine/proguanil few side effects, is a less short optimal duration alternative. of intake before and after travel. Disadvantage: expensive, daily intake. . Chloroquine/proguanil is a less optimal alternative.

References 1. Lee YCA, Tang CS, Ang LW et al. Epidemiological characteristics of imported and locally- Referencesacquired malaria in Singapore. Ann Aca Med Singapore 2009;38:840-9. 2. Cox-Singh J, Davis TM, Lee KS, et al. Plasmodium knowlesi malaria in humans is widely 1. Lee YCA, Tang CS, Ang LW et al. Epidemiological characteristics of imported and locally- distributed and potentially life threatening. Clin Infect Dis 2008;46:165-71. acquired malaria in Singapore. Ann Aca Med Singapore 2009;38:840-9. 3. Ng OT, Ooi EE, Lee CC, et al. Naturally acquired human Plasmodium knowlesi infection, 2. Cox-Singh J, Davis TM, Lee KS, et al. Plasmodium knowlesi malaria in humans is widely Singapore. Emerg Infect Dis 2008;14:814-6. distributed and potentially life threatening. Clin Infect Dis 2008;46:165-71. 4. WHO. Guideline for the Treatment of Malaria - 2nd edition, 2010. World Health Organization. 3. Ng OT, Ooi EE, Lee CC, et al. Naturally acquired human Plasmodium knowlesi infection, 5. International Travel and Health 2010. World Health Organization. Singapore. Emerg Infect Dis 2008;14:814-6. 4. WHO. Guideline for the Treatment of Malaria - 2nd edition, 2010. World Health Organization. 5. International Travel and Health 2010. World Health Organization.

MEASLES

Causative Agent MEASLES Measles (Rubeola) virus Causative Agent IncubationMeasles (Rubeola) Period virus 8 - 14 days. Incubation Period Infectious8 - 14 days. Period Just before onset of prodromal symptoms to within 4 days after onset of the rash Infectious(usually 4 days Period before to 4 days after rash onset). Just before onset of prodromal symptoms to within 4 days after onset of the rash Transmission(usually 4 days before to 4 days after rash onset). Airborne transmission by respiratory droplets and by direct contact with nasal or Transmissionthroat secretions and less commonly by articles freshly soiled with nose and throat secretions.Airborne transmission by respiratory droplets and by direct contact with nasal or throat secretions and less commonly by articles freshly soiled with nose and throat Epidemiologysecretions. Measles vaccination was first introduced into the childhood vaccination programme inEpidemiology October 1976 and made compulsory in August 1985. The monovalent measles vaccineMeasles wasvaccination replaced was by firstthe trivalentintroduced measles, into the mumps, childhood rubella vaccination (MMR) programme vaccine in Januaryin October 1990. 1976 The and vaccination made compulsory coverage inwas August between 1985. 85% The and monovalent89% and the measles annual incidencevaccine was of replthe aceddisease by declinedthe trivalent to between measles, 123 mumps, and 218 rubella cases (MMR) during vaccinethe period in 1985January-1991. 1990. A The resurgence vaccination of measle coverages was was noted between in 199285% and- 1993 89% but and the the highestannual incincidenceidence of was the seendisease in declined 1997 when to between a total 123 of 1413and 218 cases cases were during notified. the period This resurgence1985-1991. was A resurgencenot due to vaccine of measle failures was but noted a build in- up 1992 of susceptible - 1993 buts among the highest older incchildren,idence youths was seenand adults in 1997 who when were a not total vaccinated. of 1413 A cases catch - wereup measles notified. (MMR) This vaccinationresurgence was campaign not due was to vaccine conducted failure in Julybut -aNovember build-up of 1997 susceptible for all sstudents among olderaged 12children,-18 years. youths In and January adults 1998, who were the two not -vaccinated.dose MMR Avaccination catch-up measles schedule (MMR) was introducedvaccination with campaign the second was doseconducted given into primaryJuly-November school leavers 1997 for (11+ all years students old). aged 12-18 years. In January 1998, the two-dose MMR vaccination schedule was introducedThere were with 13 laboratory the second confirmed dose given cases to primary of measles school reported leavers in(11+ 2009, years including old). 5 foreigners who sought medical treatment in Singapore. There were 13 laboratory confirmed cases of measles reported in 2009, including 5 foreignersClinical Features who sought medical treatment in Singapore.  Seldom seen in infants less than five months of age (due to passively transferred Clinicalprotective Features materna l antibodies).  HighSeldom fever seen and in toxicinfants looking. less than five months of age (due to passively transferred  Cough,protective Coryza materna andl Conjunctivitisantibodies). (the 3 C’s).  Koplik’sHigh fever spots and toxicappear looking. during the febrile phase. These are 1 - 2 mm diameter  whitishCough, -Coryzagrey spots and Conjunctivitis surrounded by (the erythematous 3 C’s). rings at the buccal mucosa  oKoplik’spposite thespots mo appearlar teeth. during the febrile phase. These are 1 - 2 mm diameter whitish-grey spots surrounded by erythematous rings at the buccal mucosa opposite the molar teeth.

 The rash appears on the fourth or fifth day - first behind the ears, or over the eyelids, then spreading to the rest of the face and upper neck and then the rest of  theThe body rash (centrifugal,appears on thetop fourthdown). or fifth day - first behind the ears, or over the  Wheneyelids, the then rash spreading appears, tothe the fever rest becomesof the face highe andr upperand the neck child and appears then the more rest ill.of Thethe body fever (centrifugal, lasts for another top down). 3 - 4 days. The Koplik’s spots disappear by the  seWhencond the day rash of appearance appears, the of fever the rash. becomes higher and the child appears more ill.  The rash fever fades lasts after for anotherabout five 3 -days 4 days. but there The is Koplik’s staining spotsof the disappear skin for days by the to weeks.second day of appearance of the rash.  DifferentialThe rash fades dia gnosesafter about of the five rash days can but include there : is staining of the skin for days to weeks.. Roseola infantum  .Differential Rubella dia gnoses of the rash can include : . OtherRoseola viral infantum exanthem (ECHO, coxsackievirus, parvovirus B19, etc) . KawasakiRubella disease . OtherDrug rash.viral exanthem (ECHO, coxsackievirus, parvovirus B19, etc) . Kawasaki disease Investigations. Drug rash.  Laboratory confirmation of measles MUST be attempted for all cases, Investigationspreferably by serologic tests. A fourfold or greater increase in measles antibody  titreLaboratory in acute confirmationand convalescent of serum measles specimens MUST is be diagnostic attempted of measles. for all cases,  Immunofluorescencepreferably by serolog ic (IF) tests. of A cells fourfold from or nasal greater exudates increase is in useful measles for antibody a rapid diatitreg nosisin acute (false and positive convalescent results serum have beenspecimens reported). is diagnostic of measles.  ImmunofluorescenceDetection of specific IgM (IF) antibody of cells fromis useful nasal for exudatesthe diagnosis is useful of acute for measles a rapid diaon gonenosis serum (false sample. positive results have been reported).  MeaslesDetection PCR of specific available IgM on antibodyresearch basis.is useful This for is therapid, diagnosis diagnostic, of acute specific measles (and sensitiveon one serum if done sample. within the 1st 4 days of rash onset) but costly.  MeaslesA chest PCR X-ray available should on be research done if basis. respiratory This is symptomsrapid, diagnostic, and signs specific indicate (and sensitivepneumonitis, if done or a within secondary the 1 bacterialst 4 days ofpneumonia. rash onset) but costly.  A chest X-ray should be done if respiratory symptoms and signs indicate Notificationpneumonitis, or a secondary bacterial pneumonia. 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  Symptomatic measures: anti-pyretics, tepid sponging, cough suppressants and Managementanti-histamines.  HospitalisationSymptomatic measures: for treatment anti -ofpyretics, complications. tepid sponging, cough suppressants and  Oxygenanti-histamines. should be provided for all individuals with measles who develop  Hospitalisationrespiratory distress. for treatment of complications.  AntibioticsOxygen should (especially be provided against Staphylococcus for all individuals) are withused when meas lesthere who is evidence develop ofresp secondaryiratory distress. bacterial infection e.g. raised total white counts.  Antibiotics (especially against Staphylococcus) are used when there is evidence of secondary bacterial infection e.g. raised total white counts.

 Intravenous immunoglobulin (polyclonal or measles-specific) and intravenous and/ or nebulised ribavirin have been used with success in some  immunocoIntravenousm promised immunoglobulin patients. (polyclonal or measles-specific) and intravenous  Twoand/ doses or nebulisedof 200,000 ribavirinIU (megadose) have vitamin been usedA given with over success2 days to in children some withimmunoco measlesmpromised (especially patients. hospitalised children) in areas with high case-fatality  ratesTwo dosescan reduce of 200,000 measles IU- related(megadose) overall vitamin and pneumoniaA given over-specific 2 days mortality to children by 64with-83%. measles This (especiallyis not routine hospitalised in Singapore. children) in areas with high case-fatality rates can reduce measles-related overall and pneumonia-specific mortality by Prevention64-83%. and This Control is not routine in Singapore.  All pre-school children should be immunised against measles. Combined PreventionMeasles/Mumps/Rubella and Control (MMR) vaccine is given to all children between 12  andAll 15pre - monthsschool ofchildren age as should part of be the immunised childhood immunisation against measles. programme Combined in SingaporeMeasles/Mumps/Rubella (see Appendix (MMR)2). Proof vaccine of vaccination is given is to required all children for admissions between 12to crèches,and 15 monthskindergartens of age and as primary part of schools. the childhood immunisation programme in  TheSingapore second (see dose Appendix of MMR 2 vaccine). Proof is of no vaccinationw given to isall required primary forI school admissions entrants to atcrèches, around kindergartens 6 years of age. and Infected primary children schools. should stay away from school for one  weekThe second after dose onset of ofMMR rash. vaccine All is unimmunised now given to children all primary at I theschool nursery entrants or kindergaat aroundr ten6 years where of age. the Infected infection children occurred should should stay be away immunised from school as soon for one as possible.week af ter onset of rash. All unimmunised children at the nursery or (Seekinderga sectionrten on where post -exposure the infection prophylaxis occurred for should management be immunised of measles as exposuresoon as inpossible. Appendix 1.)  All(See chilsectiondhood on vaccinationspost-exposure should prophylaxis be notified for management to the National of measles Immunisation exposure Registry,in Appendix Health 1.) Promotion Board, and post-vaccination adverse reactions to the  PharmacovigilanceAll childhood vaccinations Branch, Health should Sciences be notified Authority. to the National Immunisation Registry, Health Promotion Board, and post-vaccination adverse reactions to the Pharmacovigilance Branch, Health Sciences Authority.

References 1. Ong G, Heng BH, Ong A et al. A 24-year review on the epidemiology and control of measles in Singapore, 1981-2004. Southeast Asian J Trop Med Public Health 2006;37:96-101 2.References Perry RT, Halsey NA. The clinical significance of measles: a review. J Infect Dis 2004; 189:4-16 1. Ong G, Heng BH, Ong A et al. A 24-year review on the epidemiology and control of measles in 3. Duke T, Mgone CS. Measles: not just another viral exanthem. Lancet 2004; 361:763-73 Singapore, 1981-2004. Southeast Asian J Trop Med Public Health 2006;37:96-101 4. Huiming Y, Chaomin W, Meng M. Vitamin A for treating measles in children. Cochrane Database 2. SystPerry Rev RT, 2005; Halsey 4:CD001479. NA. The clinical significance of measles: a review. J Infect Dis 2004; 189:4-16 3. Duke T, Mgone CS. Measles: not just another viral exanthem. Lancet 2004; 361:763-73 4. Huiming Y, Chaomin W, Meng M. Vitamin A for treating measles in children. Cochrane Database Syst Rev 2005; 4:CD001479.

MELIOIDOSIS

Causative Agent MELIOIDOSIS Burkholderia pseudomallei Causative Agent Burkholderia pseudomallei Incubation Period Days to years Incubation Period InfectiousDays to years Period Person -to-person spread extremely rare. Infectious Period TransmissionPerson-to-person spread extremely rare. Direct inoculation through small cuts or abrasions, inhalation of contaminated dust, Transmissioningestion or aspiration of contaminated water. Direct inoculation through small cuts or abrasions, inhalation of contaminated dust, Epidemiologyingestion or aspiration of contaminated water. Endemic to Southeast Asia and Northern Australia where it is found in soil and suEpidemiologyrface water. Increasing reports from countries elsewhere in Asia, the Pacific, the AEndemicmericas, to the Southeast Caribbean Asia and andthe Middle Northern East. Australia where it is found in soil and su rface water. Increasing reports from countries elsewhere in Asia, the Pacific, the AOccupationalmericas, the (e.g.Caribbean farming, and construction), the Middle East. recreational (e.g. adventure travellers) or other contact with soil or stagnant water is a risk factor. Occupational (e.g. farming, construction), recreational (e.g. adventure travellers) or Diabetes,other contact chronic with soil renal or stagnant disease, water chronic is a risk lung factor. disease, cirrhosis, thalassemia, alcoholism and immunosupression are recognised clinical risk factors. Diabetes, chronic renal disease, chronic lung disease, cirrhosis, thalassemia, Aalc totaloholism of and 287 immunosupression local cases of melioidosis are recognised were clinical reported risk during factors. 2005 -2009. The majority were males and highest incidence rate was for adults >45 years of age. OveA totalrall c ofase 287-fatality local rate cases was of 17.4% melioidosis. were reported during 2005-2009. The majority were males and highest incidence rate was for adults >45 years of age. OveClinicalrall c Featuresase-fatality rate was 17.4%. Symptoms and Signs Clinical Variable Features according to site of infection. Symptoms Acute presentationand Signs as fulminant septicaemia.  SubacuteVariable accordingpresentation to sitewith of fever infection. and local infection (skin, lung, liver, spleen,  boneAcute abscesses). presentation as fulminant septicaemia.  MelioSubacuteidosis presentation should be withsuspected fever inand a localdiabetic infection patient (skin, with septicaemialung, liver, spleen,and/or multiplebone abscesses). abscesses.  MortalityMelioidosis is highshould in septicaemicbe suspected presentation. in a diabetic patient with septicaemia and/or  Relapsemultiple abscesses. (sometimes many years later) is common, even after appropriate  antMortalityibiotic therapy.is high in septicaemic presentation.  Relapse (sometimes many years later) is common, even after appropriate antibiotic therapy.

Investigations  Culture of blood, sputum and urine in addition to fluid obtained from any other Investigationsinfected site remains the gold standard for diagnosis.  SerologyCulture of blood, (e.g. indirectsputum and haemagglutination) urine in addition to has fluid limited obtained sensitivity from any other and infectedspecificity. site remains A strongly the gold positive standard titre for may diagnosis. lend support to a diagnosis of  melioidosisSerology (e.g. if the indirectclinical picture haemagglutination) is suggestive. has limited sensitivity and specificity. A strongly positive titre may lend support to a diagnosis of Notificationmelioidosis if the clinical picture is suggestive. 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 orManagemen electronicallyt via CD-LENS) not later than 24 hours from the time of diagnosis.  Ceftazidime 2g IV 8 hourly is the treatment of choice for acute infections. Managemen Imipenemt and meropenem may be suitable alternatives.  Duration:Ceftazidime at 2gleast IV 28 weekshourly ofis theintravenous treatment therapy, of choice even for acuteif clinical infections. response is  Imipenemrapid. and meropenem may be suitable alternatives.  AbscessesDuration: atshould least be2 weeksdrained of if intravenouspossible. therapy, even if clinical response is  Oralrapid. maintenance treatment to prevent relapse is important.  CombinationAbscesses should maintenance be drained if therapypossibl e. with co-trimoxazole, doxycycline,,  amoOralx maintenanceicillin/clavulanic treatment acid orto preventchloramphenicol relapse is (basedimportant. on susceptibility) for 6  Combinationmonths or more. maintenance These drugs reduce therapy the withrelapse co rate-trimoxazole, to 10%. doxycycline,,  Lifeamo xlongicillin/clavulanic follow-up recommended. acid or chloramphenicol (based on susceptibility) for 6 months or more. These drugs reduce the relapse rate to 10%. Prevention Life long and follow Control-up recommended. Patients with known risk factors should cover all cuts and minimise contact with Preventionsoil and stagnant and Controlwater. Patients with known risk factors should cover all cuts and minimise contact with soil and stagnant water.

References 1. White NJ. Melioidosis. Lancet 2003; 361:1715-22 2. Lo TJ, Ang LW, James L et al. Melioidosis in a tropical city state, Singapore. Emerg Infect Dis References2009; 15:1645 -6 3.1. CommitteeWhite NJ. Melioidosis. on Epidemic Lancet Diseases. 2003; 361:1715 Ministry- 22 of Health’s guidelines on the clinical diagnosis, 2. labLo o TJ,ratory Ang investigation, LW, James Ltreatment et al. Melioidosis and prevention in a tropicalof melioidosis. city state, Epidemiological Singapore. Emerg News Infect Bulletin Dis 2009;1998; 15:164524:21-3 -6 3.4. CommitteeSuputtamongkol on Epidemic Y, Rajchanuvong Diseases. A, Ministry Chaowagul of Health’s W et guidelinesal. Ceftazadime on the versus clinical amoxicillin/ diagnosis, labclavouratorylanate investigation, in the treatment treatment of severe and melioidosis. prevention Clinof melioidosis. Infect Dis 1994; Epidemiological 19:846-53 News Bulletin 1998; 24:21-3 4. Suputtamongkol Y, Rajchanuvong A, Chaowagul W et al. Ceftazadime versus amoxicillin/ clavulanate in the treatment of severe melioidosis. Clin Infect Dis 1994; 19:846-53

MENINGOCOCCAL DISEASE

MENINGOCOCCAL DISEASE Causative agent N eisseria meningitidis (serogroup A, B, C, W135, Y). Most infections are due to serogroupCausative B.agent Neisseria meningitidis (serogroup A, B, C, W135, Y). Most infections are due to Incubationserogroup B. period 4 days (range 2 to 10 days) Incubation period

Transmission4 days (range 2 to 10 days) Respiratory droplets and direct salivary contact with an infected person. Transmission EpidemiologyRespiratory droplets and direct salivary contact with an infected person. The human upper respiratory tract is the main reservoir of carriage and site of meEpidemiologyningococcal dissemination. There is no animal reservoir. The human upper respiratory tract is the main reservoir of carriage and site of Theremeningococcal were five dissemination. laboratory confirmed There is cases no animal of meningococcal reservoir. infection in 2009. Of these, four were due to N. meningitidis group B and the other was not grouped. There were five laboratory confirmed cases of meningococcal infection in 2009. Of Clinicalthese, four Features were due to N. meningitidis group B and the other was not grouped. Three main forms of the disease: Clinical Features  Meningeal syndrome - presents with stiff neck, high fever, sensitivity to light, Threeconfusion, main forms headaches of the disease: and vomiting.   SepticMeningeal form syndrome - is less - presents common with but stiff a moreneck, high severe fever, (often sensitivity fatal) formto light, of meningconfusion,ococcal headaches disease, and whichvomiting. is characterized by a haemorrhagic rash and  rapidSeptic circul formatory - iscollapse less common but a more severe (often fatal) form of  Pneumoniameningococcal disease, which is characterized by a haemorrhagic rash and rapid circulatory collapse The onsetPneumonia of symptoms is sudden and death can follow within hours. In as many as 10 -15% of survivors, there are persistent neurological defects, including hearing loss,The onsetspeech of disorders, symptoms mental is sudden retardation and death and can paralysis. follow within hours. In as many as 10-15% of survivors, there are persistent neurological defects, including hearing Investigationsloss, speech disorders, mental retardation and paralysis. Investigations Lumbar puncture shows a purulent spinal fluid   Gram stain and culture from CSF and blood.  Lumbar puncture shows a purulent spinal fluid  PCR assay helpful for culture-negative cases and identification of serogroup duringGram stain outbreaks. and culture from CSF and blood.   AcutePCR assayand convalescent helpful for culturephase serology-negative if cases highly and suspicious identificatio for nmeningococcal of serogroup diseaseduring outbreaks. but culture and PCR negative.  Acute and convalescent phase serology if highly suspicious for meningococcal disease but culture and PCR negative.

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 Managementor electronically via CD-LENS) not later than 24 hours from the time of diagnosis.  Medical emergency Management Admission to a hospital is necessary  EarlyMedical diagnosis emergency and institution of appropriate early intravenous antibiotics help  reduceAdmission mortality to a hospital to < 15%. is necessary  CeftriaxoEarly diagnosisne IV 2and – 4 institutiongm daily x of 10 appropriate-14 days; or early intravenous antibiotics help  Penicillinreduce mortality G 300,000 to < U/kg/day15%. IV (up to 24 million U/day)  Ceftriaxone IV 2 – 4 gm daily x 10-14 days; or Prevention Penicillin and G Control300,000 U/kg/day IV (up to 24 million U/day) There are two quadrivalent vaccines against serotype A, C, Y and W135 available in tPreventionhe U.S - meningococcaland Control polysaccharide vaccine and meningococcal conjugate vaThereccine are. O twonly thequadrivalent polysaccharide vaccines vaccine against is presentlyserotype A,licensed C, Y andin Singapore. W135 available in t he U.S - meningococcal polysaccharide vaccine and meningococcal conjugate Tvaheccine US. CDCOnly indicationsthe polysaccharide for meningococcal vaccine is presentlyvaccination licensed include in: Singapore. . Everyone aged 11 to 18 years; .T he AdolescentsUS CDC indications during their for meningococcal11- 12 year old vaccinationhealthcare visit; include : . AEveryonedolescents aged upon 11 to high 18 years school; entry (15 years of age), if they were not . previouAdolescentssly vaccinated during their; 11- 12 year old healthcare visit; . CAollegedolescents freshmen upon living high in school dormitories, entry if (15 not yearspreviously of age), vaccinated if they; were not . Ppreviouersonss withly vaccinated anatomic; or functional asplenia; . MCollegeilitary freshmenrecruits; living in dormitories, if not previously vaccinated; . CPersonsertain with international anatomic traveor functionalllers to asplenia regions ; with hyperendemic or epidemic . mMeilitaryningococcal recruits disease; ; . MCertainicrobiologists international routinely trave exposedllers to to regionsNeisseria with meningitidis hyperendemic isolates or; and epidemic . Pmatientseningococcal with terminal disease complement; deficiency. . Microbiologists routinely exposed to Neisseria meningitidis isolates; and Post. P-Exposureatients with C hemoprophylaxisterminal complement deficiency. (See also Appendix 1 Post-exposure prophylaxis) Post -Exposure Chemoprophylaxis Recommended(See also Appendix for close 1 Post contacts-exposure ( 4prophylaxis) hours contact the week before onset of illness) and healthcare workers at risk i.e. Recommended those who hadfor closedirect contacts contact with( 4 hourspatient’s contact secretions the week; or before onset of illness) and healthcarethose who workerswere involved at risk ini.e. mouth -mouth resuscitation or intubation; or  those whowho had came direct intocontact close with proximitypatient’s secretions of patient’s; or oropharynx during  examinthose whoation. were involved in mouth-mouth resuscitation or intubation; or  Chemoprophylaxisthose who came regimens: into close proximity of patient’s oropharynx during .examin Rifampicination. 600mg 12 hourly x two days (adults); children (> 1 month)  Chemoprophylaxis10mg/kg for 2 daysregimens:; or . Rifampicin 600mg 12 hourly x two days (adults); children (> 1 month) 10mg/kg for 2 days; or

. Ciprofloxacin 500mg oral single dose; or . IM ceftriaxone 250 mg single dose (adults); children <15years, 125mg . siCiprofloxacinngle IM dose. 500mg oral single dose; or . IM ceftriaxone 250 mg single dose (adults); children <15years, 125mg single IM dose.

References 1. Wilder-Smith A, Goh KT, Barkham TMS et al. Virulence of the Hajj-associated W135 outbreak Referencesstrain: estimates of attack rate in a defined population and the risk of developing invasive disease in 1. carriers.Wilder-Smith Clin Infect A, Goh Dis KT, 2003; Barkham 36:679 TMS-83 et al. Virulence of the Hajj-associated W135 outbreak 2. Recommendationstrain: estimates of from attack the rate Advisory in a defined Committee population on Immunization and the risk ofPractices developing (ACIP) invasive for u sedisease of in qcarriers.uadrivalent Clin mInfecteningococcal Dis 2003; c onjugate36:679-83 vaccine (MCV4) in children aged 2-10 years at increased risk 2. Recommendationfor invasive meningococcal from the Advisory disease. MMWR2007;Committee on 56:1265 Immunization-6 Practices (ACIP) for use of 3. qWilderuadriv-alentSmith m A,eningococcal Chow A, Goh conjugate KT. Emergence vaccine (MCV4) and disappearance in children of aged W135 2-10 meningococcal years at increased disease. risk Epidemiolfor invasive Infect meningococcal 2010;138:976 disease.-8. MMWR2007; 56:1265-6 3. Wilder-Smith A, Chow A, Goh KT. Emergence and disappearance of W135 meningococcal disease. Epidemiol Infect 2010;138:976-8.

MUMPS

Causative Agent MUMPS Mumps virus Causative Agent IncubationMumps virus Period 12 to 25 days (median 18 days). Incubation Period 12Infectious to 25 days Period (median 18 days). One week before and up to 9 days after the onset of parotitis. Infectious Period OneTransmission week before and up to 9 days after the onset of parotitis. Respiratory droplets and direct salivary contact with an infected person. Transmission EpidemiologyRespiratory droplets and direct salivary contact with an infected person. In January 1990, vaccination against mumps was introduced in the national chilEpidemiologydhood immunisation programme when the monovalent measles vaccine was replacedIn January by the1990, trivalent vaccination measles, against mumps, mumps rubella was (MMR) introdu vaccine.ced in Since the national January 1990,childhood 3 mumps immunisation-virus strains programme have been when used the in monovalent the MMR vaccine: measles Urabe vaccine strain, was Jerrylreplaced-Lynn by strain the trivalent and Rubini measles, strain. mumps, The Urabe rubella strain (MMR) was substituted vaccine. Sinceby the January Rubini strain1990, 3 during mumps 1993-virus-1995. strains Although have been the used incidence in the of MMR measles vaccine: and Urabe rubella strain, had declined,Jerryl-Lynn that strain of mumpsand Rubini increased strain. significantlyThe Urabe strain in 1999 was andsubstituted 2000 due by tothe primary Rubini vaccinestrain during failure 1993(lack- 1995.of protection Although by the the Rubini incidence strain of vaccine). measles In andview rubella of this, hadthe Ministrydeclined, of that Health of mumps deregistered increased the significantly MMR vaccine in 1999containing and 2000 the Rubini due to strain primary in Mayvaccine 1999. failure The (lack current of protectionvaccine contains by the theRubini Jerryl strain-Lynn vaccine). strain. In view of this, the Ministry of Health deregistered the MMR vaccine containing the Rubini strain in SinceMay 1999. 2000, Thethe incidencecurrent vaccine of mumps contains has thedecrea Jerrylsed- Lynndramatically strain. from 5981 cases in 2000 to 631 cases in 2009 (12.7 cases per 100,000 population). Since 2000, the incidence of mumps has decreased dramatically from 5981 cases in Clinical2000 to 631 Features cases in 2009 (12.7 cases per 100,000 population).  About 30% of cases may just have mild respiratory tract infection with no Clinicalapparent Features salivary gland swelling or have subclinical infection.  ProdromeAbout 30% with of casesmalaise, may headache, just have fevermild andrespiratory anorexia tract lasting infection 2-3 days. with no  Painapparent and salivaryswelling glandin one swelling or both parotidor have glandssubclinical (or other infection. salivary glands),  Prodromeincreasing with for 2 malaise,-3 days, headache,then resolving fever over and 1 anorexia week. lasting 2-3 days.  Complications:Pain and swelling in one or both parotid glands (or other salivary glands), increasing. Neurological: for 2- 3meningoencephalitis, days, then resolving facialover 1palsy, week. cerebellar ataxia,  Complications:transverse myelitis and sensorineural hearing loss . Neurological:Gonadal: epididymo meningoencephalitis,-orchitis occurs facialin approx. palsy, 20% cerebellar of post -ataxia,pubertal males; usuallytransverse unilateral myelitis so and sterility sensorineural is rare. Oophoritis hearing loss also occurs, causing pelvic . painGonadal: and tenderness. epididymo - orchitis occurs in approx. 20% of post-pubertal males; . usuallyPancreatitis: unilateral occurs so in sterility less than is rare. 10%. Oophoritis Usually presents also occurs, after causingparotitis. pelvic . painArthritis/ and tenderness. arthralgia: usually in adults . Pancreatitis: occurs in less than 10%. Usually presents after parotitis. . Arthritis/ arthralgia: usually in adults

Differential Diagnoses BDiaffcteerrenialt ipaal rDotitiaisgn osres e p ididymo-orchitis; parainfluenza/ influenza/ coxsackievirus Bpaarcotetitrialis, vpiaralro titlyism pohra deepniditiidsy; mpaor-ootricdh ictiaslc; upluasra oinr ftlumenozuar./ iBnilatefluenralza /p acrooxtisda cskwieevlliirnugs pcanro btite isse, evni rialn clyhmildprheand wenitithi sH; IpVa riontfiedc tciaolcn.u lus or tumour. Bilateral parotid swelling c an be seen in children with HIV infection.

Investigations In vestiSergoaltoigoicalns confirmation by detection of mumps IgM antibody or a significant Serisero liong icalmu mcopns fiIrgmGati aonnti byo ddyete titrctieosn boeft wmeuemn pas cIugteM aanndti bcodonvy alore sac esingtn isfeicarunmt rsiasme piles.n m umps IgG antibody titres between acute and convalescent serum Msamumples.ps v i rus culture from saliva, blood, urine and CSF. Mumps virus culture from saliva, blood, urine and CSF.

Notification NA olteigficalalyt ionontifi able disease in Singapore. Notify Ministry of Health (Form MD 131 Aor leleegalctlryo nnicalotifilya bvleia dCisDe-aLseE NinS Si) nnogta lpaoterer .t hNaontif 7y2 Mhoiunriss tfrryo mof tHehe atiltmhe ( Foof rdmia gMnDos i1s3. 1 o r electronically via CD-LENS) not later than 72 hours from the time of diagnosis. Management SMyamnpatgoemmaticent t reatment. S ymptomatic treatment.

Prevention and Control Pr evCenomtiobnin aend dm Ceoantslerso/lm umps/rubella (MMR) vaccination at age 15 months is Cgiovmenb ianse dp armt eoafs lethse/ mnatiumopnsal/r ubchellaildh o(odMM immR) uvnaicsciatnioanti opnr oagtr aamgme e1 i5n mSiongntahpso ries g(sievee n Aaps ppeanrdt ioxf t2h)e. nAati ocnoalm bcihniledh omodea simmles/munuimsaptiso/rnu bpellarogr/avmarmicele ilan S(iMngMapRoVre) v(saececi nAep ips ealsndoix a v2a)ila. bAle. combined measles/mumps/rubella/varicella (MMRV) vInafcecictened isc halsildro eanv asilahobule.ld stay away from school for 9 days from the onset of Ipnafreoctitedd s wchellildringen. should stay away from school for 9 days from the onset of Apalrl octihdil sdwhelloodin gv.a ccinations should be notified to the National Immunisation ARellg icshtrilyd, hoodHea ltvha cPcirnoamtiotinos ns hBouoladr db. e Anllo tipofiesdt -vtoa ctchine atiNaonti oandalv eIrmmse urenaictisatioonns Rsheoguisldtr yals, Heo balet hn oPtirfoiemdo titon thBe oaPrhda.r mAallc ovpoigsilt-avnaccec inBartianocnh ,a dHevearltseh rScieactienocnes sAhuotuhlodr italsy. o be notified to the Pharmacovigilance Branch, Health Sciences Authority.

References 1Re. feGroench KeTs. Resurgence of mumps in Singapore caused by the Rubini mumps virus vaccine strain. 1. GLaonhc KetT 1.99 Re9;s u3r5g4e:n1c3e5 o5f- 6m umps in Singapore caused by the Rubini mumps virus vaccine strain. 2. LOanngc Get, Go199h9; K 3T5, 4M:1a3 5S5 e-t6 a l. Comparative efficacy of Rubini, Jeryl-Lynn and Urabe mumps vaccine in an Asian population. J Infect 2005;51: 294-8. 2. Ong G,Goh KT, Ma S et al. Comparative efficacy of Rubini, Jeryl-Lynn and Urabe muthmps vaccine 3. inAm aner Aicasina nA pcoapduemlatiy oonf. P Je Idinfaetcritc 2s0. 0R5e;p5o1r:t 2o9f 4th-8e. Committee on Infectious Diseases (28 3. eAdmitieorinca).Rn eAdc Badooemk y20 o09f P:e 4di6a4t-r8ic s. Report of the Committee on Infectious Diseases (28th edition).Red Book 2009: 464-8

80 80

NIPAH VIRUS DISEASE

NIPAH VIRUS DISEASE Causative Agent Nipah virus, Paramyxoviridae family. Causative Agent IncubationNipah virus, Period Paramyxoviridae family. 4-45 days Incubation Period Infectious4-45 days Period Possible human-to-human transmission reported in Bangladesh. Infectious Period TransmissionPossible human -to-human transmission reported in Bangladesh. Via direct contact with secretions, tissues or respiratory droplets of sick pigs. IngeTransmissionstion of raw fruits contaminated with urine or saliva of infected fruit bats reportedVia direct in India contact and with Bangladesh secretions outbreaks., tissues Contact or respiratory with secretions droplets and of excretions sick pigs. ofInge patientsstion ofreported raw fruits as probable contaminated mode of withtransmission urine or in saliva Bangladesh of infected fruit bats reported in India and Bangladesh outbreaks. Contact with secretions and excretions Epidemiologyof patients reported as probable mode of transmission in Bangladesh A newly described human pathogen. The first human cases occurred in a zoonotic encephaliticEpidemiology outbreak between September 1998 and June 1999 in Malaysia and ASingapore. newly described Mortality human was up pathogen. to 40%. TheBats first of the human genus cases Pteropus occurred are reservoirsin a zoonotic for Nencephaliticipah virus in outbreak Malaysia. between The disease September caused 1998 a relatively and June mild 1999 disease in Malaysia in pigs. andNo newSingapore. cases reported Mortality in wasSingapore up to 40%.or Malaysia Bats of since the genusthen. Pteropus are reservoirs for Nipah virus in Malaysia. The disease caused a relatively mild disease in pigs. No newFurther cases outbreaks reported in of Singapore Nipah virus or Malaysia infection since have then occurred. elsewhere, mainly in wes tern Bangladesh and also West Bengal, India. Further outbreaks of Nipah virus infection have occurred elsewhere, mainly in wesClinicaltern BangladeshFeatures and also West Bengal, India.  Acute encephalitis picture with initial symptoms of fever, headache, myalgia, Clinicalvomiting Features and sore throat, followed by dizziness, drowsiness, altered  Acuteconsciou encephalitissness, seizures picture and withcoma. initial. symptoms of fever, headache, myalgia,  vomitingMay present and as an sore atypical throat, pneumonia followed, and byacute dizziness, respiratory drowsiness, distress. altered  Relaconscioupse s encephalitisness, seizures and and latecoma.-onset. encephalitis in those with initial non-  encephaliticMay present oras asymptomatican atypical pneumonia diseases ,reported. and acute respiratory distress.  Relapse encephalitis and late-onset encephalitis in those with initial non- encephalitic or asymptomatic diseases reported. Investigations  CSF abnormal in up to 75% of patients with lymphocytic pleocytosis and Investigationselevated protein .  CSF abnormal in up to 75% of patients with lymphocytic pleocytosis and elevated protein.

 Magnetic resonance imaging showed distinctive changes of multiple discrete and small high signal lesions, best seen with fluid-attenuated inversion recovery  Magnetic(FLAIR) sequences. resonance imaging showed distinctive changes of multiple discrete  andSerology small ishigh used signal for lesions, diagnosis. best Paired seen with samples fluid demonstrating-attenuated inversion seroconversion recovery (FLAIR)confirms sequences.the diagnosis. A single sample with a titre of >1:400 is suggestive of  Serologyacute infection. is used for diagnosis. Paired samples demonstrating seroconversion  confirmsReverse- transcriptasethe diagnosis. PCR A singlein CSF sa andmple tissue. with a titre of >1:400 is suggestive of acute infection. Notification Reverse- transcriptase PCR in CSF and tissue. 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. CAall legally MOH notifiable Communicable disease Diseasesin Singapore Surv. eillanceNotify Ministry team at: of 98171463 Health (Form as soo MDn as 131 the ordiagnosis electronically is suspected via CD -LENS) not later than 24 hours from the time of diagnosis. Call MOH Communicable Diseases Surveillance team at: 98171463 as soon as the diagnosisManagement is suspected  Supportive Management Role of ribavirin uncertain.  Supportive Prevention Role of andribavirin Control uncertain.  Prevention by avoiding animals that are known to be infected and using Preventionappropriate and Control personal protective equipment devices when in contact with  Preventionpotentially infected by avoiding animals. animals that are known to be infected and using  apprEarlyo priaterecognition personal of the protective disease in the equipment intermediate devices animal when host. in contact with  Quarantinepotentially infectedof affected animals. animal premises.  GlovesEarly recognition and protective of the equ diseaseipment in theshould intermediate be worn animal when caring host. for ill patients.  RegularQuarantine hand of washingaffected afteranimal caring premises. or visiting sick people.  Gloves and protective equipment should be worn when caring for ill patients. Regular hand washing after caring or visiting sick people.

References 1. Chua KB, Goh KJ, Wong KT, et al. Fatal encephalitis due to Nipah virus among pig-farmers in ReferencesMalaysia. Lancet 1999; 354:1257-9 2. Paton NI, Leo YS, Zaki SR, et al. Outbreak of Nipah-virus infection among abattoir workers in 1. Chua KB, Goh KJ, Wong KT, et al. Fatal encephalitis due to Nipah virus among pig-farmers in Singapore.Malaysia. Lancet Lancet 1999; 1999; 354:1257 354:1253-9-6 3. Lee KE, Umapathi T, Tan CB, et al. The neurological manifestations of Nipah virus encephalitis, a 2. Paton NI, Leo YS, Zaki SR, et al. Outbreak of Nipah-virus infection among abattoir workers in novel paramyxovirus. Ann Neurol 1999; 464:28-32 Singapore. Lancet 1999; 354:1253-6 4. WHO. Nipah virus. July 2009. Available at: http://www.who.int/mediacentre/factsheets/fs262/en. 3. Lee KE, Umapathi T, Tan CB, et al. The neurological manifestations of Nipah virus encephalitis, a Accessed August 2010 novel paramyxovirus. Ann Neurol 1999; 464:28-32 5. Luby SP, Gurley ES, Hossain MJ . Transmission of human infection with Nipah virus. Clin Infect 4. WHO. Nipah virus. July 2009. Available at: http://www.who.int/mediacentre/factsheets/fs262/en. AccessedDis. 2009; August 49:1743 2010-8 5. Luby SP, Gurley ES, Hossain MJ . Transmission of human infection with Nipah virus. Clin Infect Dis. 2009; 49:1743-8

PERTUSSIS

Causative Agent PERTUSSIS Bordetella pertussis. B.paratussis causes parapertussis. Causative Agent IncubationBordetella pertussis Period . B.paratussis causes parapertussis. 5 - 21 days (average 7 days) Incubation Period Infectious5 - 21 days Period(average 7 days) From catarrhal stage till 3 weeks after onset of typical paroxysm in patients not treatedInfectious with Period antibiotics. If antibiotic therapy initiated, period of infectiousness is usuallyFrom catarrhal 5 days or stage less tillafter 3 weeksonset of after therapy. onset A of h typicalighly contagious paroxysm diseasein patients with notan 80%treated attack with rate antibiotics. in non-immune If antibiotic persons therapy. initiated, period of infectiousness is usually 5 days or less after onset of therapy. A highly contagious disease with an Transmission80% attack rate in non-immune persons. Via respiratory droplets or direct contact with nasal or throat secretions of an iTransmissionnfected person. Adolescents and adults with unrecognized pertussis are a reservoir ofVia infection respiratory for infants droplets and or children direct . contact with nasal or throat secretions of an infected person. Adolescents and adults with unrecognized pertussis are a reservoir Epidemiologyof infection for infants and children.  The disease is far more severe in children and may be fatal in infants. The Epidemiologyhighest incidence continues to be in infants (<6 months) who are either  uniThem diseasemunised is or far incompletelymore severe in immunised children and with may the be fatal primary in infants course. The of vaccinationhighest incidence. continues to be in infants (<6 months) who are either  Increasingunimmunised incidence or incompletely in adolescents immunised and adults (with with occasional the primary community course and of schoolvaccination outbreaks). noted in many industrialised countries due to waning vaccine  immunity.Increasing incidence The true in disease adolescents burden and is adultshowever (with under occasional-estimated community due to lowand reschoolcognition, outbreaks) reporting noted and in limitationsmany industrialised in diagnostic coun testing.tries due to waning vaccine  Inimmunity. Singapore, The a true sharp disease increase burden in the is incidencehowever ofunder pertussis-estimated from due an to annual low arevcerageognition, of 4 reportinglaboratory and confirmed limitations cases in diagnostic to 38 cases testing. was reported in 2007. The  highestIn Singapore, incidence a sharprate was increase observed in thein children incidence under of pertussis6 months from of age. an Among annual theaverage three of major 4 labo ethnicratory groups, confirmed Malays cases had to 38the caseshighest was incidence reported ratein 2007 followed. The byhighest Chinese incidence and rate Indians. was observed Only nine in children cases had under at least6 months one of dose age. ofAmong DTP vaccinthe threeation major prior ethnic to onset groups, of illness Malays. had the highest incidence rate followed by Chinese and Indians. Only nine cases had at least one dose of DTP vaccination prior to onset of illness.

Clinical Features

 B. pertussis is the most common aetiological agent of whooping cough and Clinicalexclusively Features a human pathogen. B. parapertussis leads to less severe but similar  symptoms.B. pertussis is the most common aetiological agent of whooping cough and exclusively a human pathogen. B. parapertussis leads to less severe but similar symptoms.

 Typical pertussis infection lasts several weeks and consists of 3 stages. o Catarrhal stage: (1-2 weeks) rhinorrhea, mild fever (often absent), coryza and  Tymildpical coughpertussis; infants infection may lasts have several apnoea/respiratory weeks and consists distress of 3. stages. Other clinical o cluesCatarrhal to diagnosis stage: (1 -include2 weeks) exce rhinorrhea,ss lacrimation mild feverand conjunctival (often absent) injection, coryza andand haemorrhagemild cough; . infants may have apnoea/respiratory distress. Other clinical clues to diagnosis include excess lacrimation and conjunctival injection and o Paroxysmal stage: (2-6 weeks) increased cough with spells of repetitive usuallyhaemorrhage dry cough,. followed by sudden inspiratory effort (whoop) and post- o tussiveParoxysmal emesis. stage : (2-6 weeks) increased cough with spells of repetitive usually dry cough, followed by sudden inspiratory effort (whoop) and post- o Convalescent stage: (> 2weeks) decreasing frequency and severity of cougtussivehing emesis. episodes. Average duration of cough approximately 50 days. o Convalescent stage: (> 2weeks) decreasing frequency and severity of  Adolescentscoughing episodes. and adults Average may duration have of prominent cough approximately hacking cough 50 days. but lack characteristic whoop. Prior immunization can lead to atypical presentations.  Adolescents and adults may have prominent hacking cough but lack Potenticharactal complicationeristic whoop.s Prior immunization can lead to atypical presentations.  Complications: pneumonia, urinary incontinence, rib fractures, hearing loss, Potentidevelopmental complication of s hernias, sub-conjunctival haemorrhage, pneumothorax,  aspirComplications:ation, intracranial pneumonia, haemorrhage urinary (in incontinence, elderly), carotid rib fractures artery , dissection hearing loss,and deathdevelopment (rare in adults). of hernias, sub-conjunctival haemorrhage, pneumothorax,  Inaspir nonation,-immune intracranial infants: haemorrhagepneumonia, apnoea, (in elderly), failure carotid to thrive artery from dissection post-tussive and vomiting,death (rare seizures, in adults). encephalopathy and rectal prolapse.  In non-immune infants: pneumonia, apnoea, failure to thrive from post-tussive Investigationsvomiting, seizures, encephalopathy and rectal prolapse.  Nasopharyngeal swabs (use Dacron) for culture or PCR assay. Investigations Fastidious organism requiring special media for culture. Highest yield if  performedNasopharyngeal within swabs 3 weeks (use Dacron) of cough for onset culture or or 4 PCR weeks assay of. symptom onset.  SensitivFastidiousity and organism specificity requiring of culture special and mediaPCR negatively for culture. affected Highest by delayed yield if transportperformed to withinlaboratory, 3 weeks vaccinati of o coughn, recent onset antibiotic or 4 weeksuse and of pro symptomlonged illness. onset. CultureSensitiv remainsity and specificitythe gold standard of culture but andsuffers PCR from negatively low sensitivity. affected PCRby delayed-based assaystransport increasingly to laboratory, used vaccinati and mayo ben, recentmore sensitive. antibiotic use and prolonged illness.  SerologyCulture remains for p ertussisthe gold toxinstandard (PT) but IgGsuffers or from IgA low performed sensitivity. in PCR acute-based and convaleassays increasinglyscent specimens used mayand maysupport be more the dia sensitive.gnosis. A single high titer may be  indicativeSerology of for recent pertussis infection toxin (e.g. (PT) >100U/ml IgG oranti IgA-PT IgG). performed in acute and convalescent specimens may support the diagnosis. A single high titer may be Notificationindicative of recent infection (e.g. >100U/ml anti-PT IgG). 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.  Empiric treatment recommended if the diagnosis is strongly suspected. Management Respiratory isolation for known cases. Suspect cases should be removed from  theEmpiric presence treatment of young recommended children and if the non diagnosis-immunized is strongly infants suntiluspected. patients have  rRespiratoryeceived at least isolation 5 days for of knownantibiotics. cases. Suspect cases should be removed from the presence of young children and non-immunized infants until patients have received at least 5 days of antibiotics.

 Antibiotic treatment unlikely to shorten duration of illness if started more than one week after symptom onset, but is beneficial in shortening the infectious  Antibioticperiod and treatmentdecreasing unlikely transmission. to shorten duration of illness if started more than  oneIn vitro, week most after strai symptomns are sensitive onset, but to bothis beneficial macrolides in andshortening fluoroquinolones, the infectious but resistantperiod and to decreasingbeta-lactams. transmission. Limited clinical experience with fluoroquinolones.  MacrolidesIn vitro, most are strai thens arerecommended sensitive to bothfirst macrolides line of therapy.and fluoroquinolones, For adults andbut adoleresistantscents: to beta -lactams. Limited clinical experience with fluoroquinolones.  Macrolides are the recommended first line of therapy. For adults and adole. Aszithromycincents: : 500mg oral x 1 dose then 250mg daily for 4 days; or . Clarithromycin: 500mg bd x 7 days; . Erythromycin:Azithromycin: 500mg qidoral x x 14 1 dosdays;e then 250mg daily for 4 days; or . (Alternative)Clarithromycin Trimeth: 500mgoprim bd x-sulfamethoxazole 7 days; (Bactrim) oral bd x 14 days . Erythromycin: 500mg qid x 14 days;  .Infection (Alternative) in infants Trimeth underoprim age - 6sulfamethoxazole months may require (Bact rim) hospitalization oral bd x 14 due days to com plications of hypoxemia, apnoea or poor feeding.  Infection in infants under age 6 months may require hospitalization due to Managementcomplications of close of hypoxemia,contacts apnoea or poor feeding.  Administer antibiotic chemoprophylaxis if within 3 weeks of exposure. Management Use same of drugs close and contacts duration as for treatment (see Management above).  ReviewAdminister pertussis antibiotic vaccination chemoprophylaxis status of all if wicontactsthin 3 weeksespecially of exposure infants .or adults  Usecaring same for drugsinfants and to ensureduration currency. as for tr eatment (see Management above).  EvidenceReview pertussis for post -vaccinationexposure immunization status of all tocontacts prevent especially infection isinfants limited. or adults caring for infants to ensure currency.  Evidence for post-exposure immunization to prevent infection is limited. Prevention and Control  Routine childhood vaccination: primary immunisation at 3, 4 and 5 months Prevention(DPT); andfirst Controlbooster (D PT) before school entry at 18 months with a 2nd booster  Routine(either Td childhood or Tdap) at vaccination: 10-11 years primary (primary immunisation V). See Appendix at 3, 2 4. and 5 months  Notification(DPT); first booster of all (D childhoodPT) before immunisations school entry at to 18 the months National with Immunisationa 2nd booster Re(eithergistry Td, Healthor Tdap) Promotion at 10-11 years Board, (primary and post V)-.vaccination See Appendix adverse 2. reactions to  theNotification Pharmacovigilance of all childhood Branch, immunisations Health Sciences to the Authority. National I mmunityImmunisation after cRehilgdistryhood, Healthvaccina Promotiontion against Board, B. pertussis and post wanes-vaccination after 5 to adverse 10 years reactions and rarely to laststhe Pharmacovigilancemore than 12 years. Bra nch, Health Sciences Authority. Immunity after  Imchilmunizdhoodation vaccina of tionadolescents against B. and pertussis adults wanesaim to after decrease 5 to 10 the years reservoir and rarely and laststransmission more than of 12pertussis years. in these populations and to infants.  ImTdapmuniz vaccineation (tetanus of adolescents-reduced diphtheria and adults-acellular aim to pertussis)decrease theis licensed reservoir for anduse intransmission adults and of adolescents.pertussis in these Its usepopulations should and be consideredto infants. in the following  situTdapations: vaccine (tetanus-reduced diphtheria-acellular pertussis) is licensed for use in. adultsTo replace and adolescents.the next dose Itsof Td use for should adults beaged considered 19 to 64 years in the as part following of the situa10tions:-year Td boosting schedule. . ATodults replace who the have next close dose contactof Td for with adults infants aged less19 to than 64 years12 months as part ofof agethe 10(e.g.,-year parents, Td boosting grandparents schedule. and child-care providers). The optimal interval . Adults who have close contact with infants less than 12 months of age (e.g., parents, grandparents and child-care providers). The optimal interval

between Tdap and the last Td is 2 years or greater, but shorter intervals are acceptable. . betweenWomen ofTdap childbearing and the last age Td before is 2 years conception or greater, or immediatelybut shorter intervals postpartum are acceptable.prior to hospital discharge, if they have not previously received Tdap or . Womenwhose last of immunizationchildbearing age is more before than conception 2 yrs. or immediately postpartum . priorHealthcare to hospital personnel discharge, who have if theydirect have patient not contact. previously received Tdap or whose last immunization is more than 2 yrs. . Healthcare personnel who have direct patient contact.

References 1. Wood N, McIntyre P. Pertussis: review of epidemiology, diagnosis, management and prevention. Paediatr Respir Rev 2008; 9: 201-11 2.References Hoppe JE . Neonatal pertussis. Pediatr Infect Dis J 2000; 19: 244-7 1. Wood N, McIntyre P. Pertussis: review of epidemiology, diagnosis, management and prevention. 3. Mattoo S, Cherry JD. Molecular pathogenesis, epidemiology, and clinical manifestations of Paediatr Respir Rev 2008; 9: 201-11 respiratory infections due to Bordetella pertussis and other Bordetella subspecies. Clin Microbiol 2. Hoppe JE. Neonatal pertussis. Pediatr Infect Dis J 2000; 19: 244-7 Rev 2005;18:326-82 3. Mattoo S, Cherry JD. Molecular pathogenesis, epidemiology, and clinical manifestations of 4. Kretsinger K, Broder K R, Cortese M M et al. Preventing tetanus, diphtheria, and pertussis among respiratory infections due to Bordetella pertussis and other Bordetella subspecies. Clin Microbiol adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine. Rev 2005;18:326-82 Recommendations of the Advisory Committee on Immunization Practices (ACIP) and 4. Kretsinger K, Broder K R, Cortese M M et al. Preventing tetanus, diphtheria, and pertussis among recommendations of ACIP, supported by the Healthcare Infection Control Practices Advisory adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine. Committee (HICPAC), for use of Tdap among health-care personnel. MMWR Recommend. Rep. Recommendations of the Advisory Committee on Immunization Practices (ACIP) and 2006;55:1-37. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5517a1.htm. recommendations of ACIP, supported by the Healthcare Infection Control Practices Advisory Accessed Aug 2010. Committee (HICPAC), for use of Tdap among health-care personnel. MMWR Recommend. Rep. 5. Liew F,Ang LW,Cutter J et al.Evaluation on the effectiveness of the national childhood 2006;55:1-37. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5517a1.htm. immunisation programme in Singapore, 1982-2007. Ann Acad Med Singapore 2010;39:532-41 Accessed Aug 2010. 5. 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