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Haemophilus influenzae Last updated: September 5, 2018

Vaccine-Preventable Diseases 1 SurveillanceWHO -Preventable Standards Diseases Surveillance Standards

Haemophilus influenzae

DISEASE AND VACCINE CHARACTERISTICS

The Haemophilus influenzae type b (Hib) was Current Hib conjugate the Hib polysaccharide the leading cause of non-epidemic bacterial capsule to one of several carrier proteins that can worldwide in children prior to the introduction of be used effectively (2). Hib vaccines are available in . H. influenzae can be unencapsulated or monovalent formulations or combined with other capsulated (six capsular types or serotypes), although antigens: --pertussis (DTP) vaccine, 95% of severe disease is caused by capsular type b vaccine and inactivated (IPV). (Hib). H. influenzae can asymptomatically colonize Hib vaccines are given as a three- or four-dose schedule the human nasopharynx, particularly in children. in the primary series starting as early as six weeks The bacteria can spread contiguously to cause otitis of age; some countries give a booster dose at 12–18 media and or be aspirated to cause . months of age. Recommended schedules include three More rarely, it can cause invasive disease, predominantly primary doses without a booster (3p+0), two primary meningitis and pneumonia but also , septic doses plus a booster (2p+1) or three primary doses with arthritis and others. Over 90% of invasive H. influenzae a booster (3p+1). Countries that have high coverage of disease occurs in children < 5 years of age, the majority Hib vaccine with any of these schedules have observed in infants; children in less developed settings tend to a > 90% decline in invasive Hib disease. Some countries be infected earlier in infancy. Case fatality rates can be have identified an increase in Hib disease in countries high for H. influenzae meningitis, ranging from 5% without a booster dose, but this has been small and not with proper treatment to as high as 60% without. sustained (3). Among survivors, 20-40% suffer sequelae such as deafness and blindness. It is estimated that in 2008, 199 000 HIV-negative children < 5 years of age died from H. influenzae disease (1). HIV-infected infants are at a several-fold increased risk of invasive H. influenzae disease.

RATIONALE AND OBJECTIVES OF SURVEILLANCE

The objectives of surveillance H. influenzae are to: hh evaluate vaccine impact and monitor serotype distribution hh quantify disease burden and epidemiology to inform vaccine introduction decisions (such as dosing hh identify immunization programme implementation schedule and product choice) gaps and provide data to determine if changes in vaccine policy are needed (such as booster doses).

3 WHO Vaccine-Preventable Diseases Surveillance Standards TYPES OF SURVEILLANCE RECOMMENDED

MINIMAL SURVEILLANCE »» Population-based surveillance can be done The minimal surveillance standard for H. influenzae around one sentinel hospital or at a regional level disease is sentinel hospital surveillance for meningitis, with multiple hospitals. Previously, this had been previously referred to as Tier 1 Invasive Bacterial Vaccine called Tier 3 IB-VPD surveillance. Preventable Disease (IB-VPD) surveillance (4). »» If done in multiple hospitals in a defined hh Surveillance can be implemented in one or multiple region (district, province, etc.), most hospitals hospitals that admit children with meningitis and in the catchment area should collect sterile site other severe diseases. Surveillance should be active specimens on most suspected cases as part of in enrolling suspected cases and implementing routine clinical practice, and these specimens appropriate laboratory testing to confirm H. should be tested for H. influenzae. This approach influenzae. is often laboratory-based, where the entry point into the surveillance system is a laboratory hh Sentinel surveillance is case-based and prospective. It should be undertaken only in hospitals with detection of an invasive pneumococcal disease sufficient numbers of cases identified to make (IPD) case. These cases can then be followed the surveillance useful (100 cases per site per year up to gather more epidemiologic information. of suspected meningitis). Surveillance in smaller An example of this type of surveillance is the hospitals is not worth the resource investment and GERMS network in South Africa (3). can also lead to erroneous conclusions due to small »» Population-based surveillance achieves the same numbers of cases. objectives as sentinel site surveillance, with the addition of assessing incidence to monitor hh Sentinel site surveillance may not be sufficient to meet all objectives. Addition of other surveillance burden by age group andincreases in non-b H. or research methods, such as case-control studies to influenzae serotypes, because serotype-specific assess vaccine effectiveness, might be needed. incidence rates are preferable to case counts for following temporal trends.

ENHANCED SURVEILLANCE TARGET POPULATION Two types of enhanced surveillance for H. influenzae are possible. The target population is children aged 0–59 months for all types of surveillance. Primary disease affects infants, 1. Expanded sentinel hospital surveillance while vaccine failures tend to occur in children > 1 year Meningitis sentinel surveillance can be expanded of age (7). Hib disease is rare in older children and to include pneumonia and sepsis (previously adults. In practice, however, older children and adults referred to as Tier 2 IB-VPD surveillance). The may be included in enhanced surveillance systems characteristics of this surveillance are the same as for bacterial meningitis, since pneumococcus and meningitis sentinel surveillance: case-based, active meningococcus do occur in older age groups. and prospective. Pneumonia and sepsis surveillance should only be undertaken in hospitals of sufficient LINKAGES TO OTHER SURVEILLANCE size to have a meaningful number of cases (500 Where possible, surveillance for H. influenzae should cases per site per year for meningitis + pneumonia/ be integrated with that for other causes of bacterial sepsis). While it is difficult to identify the etiology meningitis and pneumonia, such as pneumococcus and of pneumonia, radiography can be used to identify meningococcus. When conducting sentinel surveillance WHO-defined endpoint pneumonia, which is more for meningitis, pneumonia or sepsis, all three specific for such as that caused should be routinely tested for. Laboratory testing by H. influenzae (6). for antimicrobial resistance can be integrated with surveillance for other bacteria (such as typhoid). 2. Population-based surveillance for invasive H. influenzae disease

»» A defined catchment population is required in order to calculate incidence. 4 Haemophilus influenzae Haemophilus influenzae

CASE DEFINITIONS AND FINAL CLASSIFICATION

SUSPECTED MENINGITIS FOR CASE FINDING SUSPECTED SEVERE PNEUMONIA FOR CASE FINDING hh Any child aged 0–59 months admitted to hospital with sudden onset fever (> 38.5°C rectal or 38°C Any child aged 0–59 months with a cough or difficulty axillary) and one of the following signs: neck breathing and displaying one or more of the following: stiffness, altered consciousness with no other hh inability to drink or breastfeed alternative diagnosis, or other meningeal signs. hh vomiting everything OR hh convulsions h Any patient aged 0–59 months hospitalized with a h h clinical diagnosis of meningitis. h prostration/lethargy hh chest in-drawing PROBABLE BACTERIAL MENINGITIS hh stridor when calm. A suspected meningitis case with cerebrospinal

fluid (CSF) examination showing at least one of the WHO-DEFINED ENDPOINT PNEUMONIA following: Pneumonia in a patient with a showing h h Turbid appearance an infiltrate consistent with pneumonia: dense, fluffy 3) hh Leucocytosis (> 100 cells/mm alveolar consolidation or pleural effusion (or both). h 3 h Leucocytosis (10–100 cells/mm ) AND either CONFIRMED H. INFLUENZAE PNEUMONIA an elevated protein (> 100 mg/dL) or decreased Any person meeting the definition of pneumonia glucose (< 40 mg/dL). Note: If protein and glucose or severe pneumonia who has a positive culture of results are not available, diagnose using the first H. influenzae from blood or pleural fluid. two conditions (turbid appearance or leucocytosis > 100 cells/mm3). SUSPECTED SEPSIS FOR CASE FINDING

CONFIRMED H. INFLUENZAE MENINGITIS Any child aged 0–59 months admitted to hospital with the presence of at least two of the following danger A suspected or probable meningitis case that is signs and without meningitis nor pneumonia clinical laboratory-confirmed by culture or identification syndrome: of H. influenzae (by antigen detection, h immunochromotography, polymerase chain reaction h inability to drink or breastfeed (PCR) or other methods) in the CSF or blood from hh vomiting everything a child with a clinical syndrome consistent with h meningitis. h convulsions (except in malaria endemic areas) hh prostration/lethargy SUSPECTED PNEUMONIA FOR CASE FINDING hh severe malnutrition Any child aged 0–59 months demonstrating cough or h difficulty breathing and displaying fast breathing when h hypothermia (≤ 36°C). calm, as defined by age: CONFIRMED H. INFLUENZAE SEPSIS hh Age 0 to < 2 months: 60 breaths/minute or more A person who meets the definition of sepsis and has h h Age 2 to < 12 months: 50 breaths/minute or more a positive culture of H. influenzaefrom a normally hh Age 12 to ≤ 59 months: 40 breaths/minute or more sterile site.

5 WHO Vaccine-Preventable Diseases Surveillance Standards CONFIRMED INVASIVE H. INFLUENZAE DISEASE Note that for blood, only culture confirms invasive hh H. influenzae identified via culture from any normally Hib disease, as these other detection methods sterile site (e.g., blood, CSF, pleural fluid, joint fluid) have not been shown to have enough specificity to in a symptomatic person diagnosis Hib, particularly in children. hh H. influenzae identified in the CSF or pleural fluid by antigen detection, immunochromotography or PCR.

CASE INVESTIGATION

In sentinel hospital surveillance, all children aged surveillance approaches, patients with suspected 0–59 months with suspected meningitis meeting pneumonia and sepsis should also have appropriate the suspected case definition should have a lumbar clinical specimens taken. Treatment of patients should puncture to collect CSF unless the procedure is clinically not be delayed while awaiting collection of specimens or contraindicated. CSF should be collected before results from the laboratory. In sentinel surveillance and antibiotic administration, otherwise the laboratory may population-based surveillance, case report forms should be unable to culture the and therefore unable be filled out on all suspected cases. In laboratory-based to provide information on antimicrobial susceptibility. IPD surveillance, cases will be reported retrospectively, However, a specimen should be obtained in all suspect and likely will already have been treated. Medical record cases as bacterial pathogens can still be detected even follow-up should be done to gather key data elements. after antimicrobial therapy has begun. For expanded

SPECIMEN COLLECTION

Care should be taken to minimize any risk of cross- »» The presence of blood in the CSF can affect contamination during manipulation or aliquotting. cultures, since antibiotics in blood can inhibit For example, use sterile dispensing technique with bacterial growth. If more than one tube is appropriate pipettes, tips and tubes. The types of being collected, the first tube may contain specimen that may be collected include CSF (meningitis contaminated blood from lumbar puncture and cases), blood samples (meningitis, pneumonia and sepsis) should not be the tube sent to the microbiology and pleural fluid (pneumonia cases). laboratory.

h Blood VOLUME OF SPECIMENS TO COLLECT h »» 1–3 mL is considered adequate for a child, and hh CSF 5–10 mL for an adult. »» 3 mL in total, 1 mL into each of three test tubes. »» Collected blood should be diluted in blood • Tube 1: Chemical analysis: protein and culture broth in order to obtain blood cultures. glucose tests It is important to use appropriate ratios of blood • Tube 2: Microbiological tests to culture broth for optimal bacterial growth. • Tube 3: Record overall appearance; perform The recommendations of the culture broth white blood cell count manufacturer should be closely followed. » » If only one tube of CSF is available, it should • Add 1–3 mL of blood from a child to 20 mL be given to the microbiological laboratory for of blood culture broth. culture/PCR/antigen testing. However, an • Add 5–10 mL of blood from an adult to aliquot of 50–100 µL should be spared from that 50 mL of blood culture broth. tube for molecular testing. 6 Haemophilus influenzae Haemophilus influenzae

» hh Pleural fluid » CSF should be processed in a microbiology laboratory within two hours of collection. If Approximately 20–40 mL of aspirated fluid should there is not access to a microbiology laboratory, be immediately placed into tubes coated with inoculated T-I media should be sent from appropriate anticoagulant (EDTA or heparin) for the health facility to the district or reference biochemistry (5 mL), microbiology (5–10 mL), laboratory as soon as possible. Districts should cytology (10–25 mL), and PCR testing (200 µL–1 send the inoculated T-I media to the reference mL). Use a heparin-coated syringe for the pH laboratory at least twice a week. measurement. hh Blood and pleural fluid TIMING OF COLLECTION »» Blood and pleural fluid should be immediately h h CSF inoculated (within one minute) into a blood »» Collect CSF as soon as possible after admission, culture bottle and transported to a microbiology preferably before antibiotic therapy is started. laboratory as soon as possible for overnight incubation and growth of bacteria. All inoculated »» Inform the laboratory that a lumbar puncture is blood culture media should be protected from to be performed so the technician can be ready to temperature extremes (< 18°C or > 37°C) with a process the sample as soon as possible. transport carrier and thermal insulator (such as hh Blood and pleural fluid extruded polystyrene foam). »» Collect prior to administration of antibiotics, »» Inoculated blood culture bottles should not be whenever possible. placed in the refrigerator.

»» Blood cannot be transported before being placed STORAGE AND TRANSPORT in a blood culture bottle because the syringes do h h CSF not contain any anticoagulant and the blood will »» Refer CSF to the laboratory immediately. coagulate within a few minutes. » » If specimen cannot be processed in one or two LONG-TERM STORAGE hours, inoculate 0.5–1.0 mL into trans-isolate h CSF, blood, and pleural fluid (T-I) medium and incubate vented at 35–37°C h » with 5% CO2 overnight, or until transport is » Store isolates frozen at -20°C to allow possible (up to four days). If transport is delayed further testing (serotyping and antimicrobial beyond four days, store at room temperature susceptibility testing) in the future, or if culture (unvented) until referral. capacity does not exist in local hospitals and processing needs to occur at reference laboratory. »» CSF specimen should not be refrigerated – keep at room temperature. »» If available, storing isolates in a -70°C freezer is preferable.

LABORATORY TESTING

CSF Many local hospitals will not have adequate capacity Meningitis syndrome may be caused by various for culture, and frozen samples will need to be sent to pathogens; therefore, clinical syndromic surveillance reference laboratories in the region. must be complemented by a strong laboratory CSF samples should be cultured on blood agar plates component. Laboratory confirmation of H. influenzae (BAP) and supplemented plates (CAP) meningitis is done by culture, PCR or antigen detection that are prepared with 5–10% sheep or horse blood. The (8). Bacterial culture is the first priority for confirmation optimal medium for growth for H. influenzae is CAP and isolation of the pathogen. Culture is considered as with X and V factors, whereas pneumococcus grows best a gold standard but has low sensitivity due to potential on BAP. antibiotic use by the patient before sample collection.

7 WHO Vaccine-Preventable Diseases Surveillance Standards PCR is recommended on all suspected cases because Report all RDT results to clinical staff within one to two bacterial culture might be inhibited if the case has hours of testing. Report CSF and blood culture results already received antibiotics. As PCR capacities are to the clinicians daily if cultures are done in hospital not always available at district or hospital level, the laboratory. remaining volume of original non-manipulated CSF can be frozen and sent to either a national or regional ANTIMICROBIAL RESISTANCE (AMR) TESTING reference laboratory for further testing. hh To the greatest extent possible, sites should perform Rapid diagnostic test kits (RDTs) can be used since they antimicrobial sensitivity testing for all H. influenzae increase yield and provide results quickly for clinical isolates and evaluate these data by the following: care and outbreak identification. In general, RDTs only antibiotic type and route, time of antibiotic identify the species and not the serotype or serogroup. administration before culture, volume of fluid There are two commonly used types of RDTs. Results cultured, geographic area and serotype (8). should be interpreted according to manufacturer’s hh Recommended methods are disk diffusion instructions. (modification of the Kirby-Bauer technique) and hh Immunochromatography: BinaxNOW® kit can antimicrobial gradient strip diffusion (9). be used on CSF and pleural fluid for detection and QUALITY ASSURANCE SYSTEMS lower-level characterization of pneumococcus. While it identifies only S. pneumoniae and not H. influenzae, All of the above laboratory standards should be it is recommended for use in cases of suspected complemented by good quality assurance and quality meningitis to identify bacterial etiology. control systems to ensure that laboratory data generated for surveillance are of good quality. WHO recommends h Latex agglutination testing (LAT): Commercial h that laboratories participate in external quality latex kits often have a short shelf life and can be assessment (EQA) programmes and send out a selection expensive. of specimens and isolates for confirmatory testing to should not be used to confirm cases, but it is another level of laboratory (national, regional or global) reliable and relatively inexpensive if staff are well trained for quality control (QC). and reagents are quality controlled. On Gram stain, H. Most sentinel site laboratories will not have the influenzae are small, pleomorphic gram-negative rods or necessary equipment to carry out higher level coccobacilli with random arrangements. characterization (serotyping, antimicrobial susceptibility Report all RDT results to clinical staff within one to two or PCR), and thus should refer isolates and specimens hours of testing. Report CSF and blood culture reports from suspected, probable and confirmed cases to to the clinicians daily if cultures are done in hospital national or regional reference laboratories that are able laboratory. to provide quality assurance and higher level testing of CSF specimens. Each laboratory should be enrolled in BLOOD an appropriate EQA/proficiency testing programme. Blood culture can be used to diagnosis H. influenzae While not an explicit objective of surveillance for meningitis, pneumonia and sepsis. The laboratory pneumococcus (or other IB-VPDs), such surveillance methods for blood culture are the same for all systems can be used to build laboratory capacity globally syndromes. However, the sensitivity of blood culture as well as identify gaps in laboratory capacity. for H. influenzae pneumonia is lower than for the other syndromes because only approximately 10–15% of H. LABORATORY NETWORKS influenzae pneumonia cases are bacteremic. The Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) Laboratory Network is a global hh For blood culture with maximum yield of isolates, network of > 100 laboratories that support invasive subculture all negative cultures after five days of bacterial disease surveillance (10). It is coordinated incubation before they are discarded. by WHO and Public Health England. IB-VPD has h h PCR and RDTs are not used routinely on blood to developed standardized laboratory procedures and diagnose H. influenzae due to low sensitivity and guidelines for data collection, and has implemented specificity. quality assurance and quality control systems.

8 Haemophilus influenzae Haemophilus influenzae

DATA COLLECTION, REPORTING AND USE

RECOMMENDED DATA ELEMENTS »» Laboratory methods and results hh Minimal data elements for sentinel hospital • CSF collected meningitis surveillance –– Unique ID for linkage to clinical data »» Sentinel site information – site name or code –– Local laboratory ID » » Demographics –– Date and time of collection • Name (if confidentiality is a concern the –– Specimen collected before antibiotic name can be omitted if a unique identifier provision? exists) –– Appearance of CSF • Unique case identifier –– Date specimens sent to laboratory • Date of birth (or age if date of birth not –– Date and time of CSF specimen received available) at laboratory • Sex –– Condition of specimen • Place of residence (city, district, and province) –– Upstream test results if referred from » » Clinical data a lower tiered laboratory (Gram stain, • Signs and symptoms of illness (including WBC, protein, glucose, culture, RDT) those in case definitions) • Results – • Date of symptom onset – CSF • Date of admission * Whole cell count • Treatment * Glucose level • Patient outcome (survived without sequelae, * Protein level survived with sequelae, died) * Culture done • Discharge diagnosis ~ Culture results » » Vaccination history * Gram stain done • Source of information [vaccination card, ~ Gram stain result Expanded Programme on Immunisation * BinaxNOW® done (EPI) registry, verbal report) ~ BinaxNOW® result • Hib vaccine received. If yes: * LAT done – – Number of doses received ~ LAT result – – Date(s) received * PCR done – – Type of Hib vaccine ~ PCR results • Pneumococcal vaccine received. If yes: * Serotyping/serogrouping – – Number of doses received ~ H. influenzae – – Date(s) received ~ S. pneumoniae – – Type and formulation of pneumococcal ~ N. meningitidis vaccine • Final case classification • received. If yes: –– Number of doses received –– Date(s) received –– Type of meningococcal vaccine

9 WHO Vaccine-Preventable Diseases Surveillance Standards REPORTING REQUIREMENTS AND hh Additional minimal data elements for pneumonia/ RECOMMENDATIONS sepsis and IPD surveillance Report confirmed Hib cases to the Ministry of Health »» Laboratory monthly. Zero reporting (no cases) should be done • Blood collection in sentinel surveillance sites. Aggregate reporting is –– Blood specimen ID sufficient for routine reporting, even if case-based surveillance is conducted. There are no global reporting –– Date and time of collection requirements for Hib. –– Specimen collected before antibiotic

treatment RECOMMENDED DATA ANALYSES – – Date specimens sent to laboratory Sentinel hospital meningitis surveillance * Date and time of blood specimen h Confirmed H. influenzae and Hib meningitis case received at laboratory h counts, stratified by onset date (week, month, year), * Culture done age group and sex. ~ Culture result hh Probable and suspected meningitis case counts, * Gram stain done stratified by the same groupings as confirmed cases. ~ Gram stain result hh Confirmed H. influenzae and Hib meningitis death • Pleural fluid (PF) collected counts and case-fatality ratios. –– Pleural fluid pecimen ID h Probable and suspected meningitis death counts and – h – Date and time of collection case-fatality ratios. –– Specimen collected before antibiotic h Median and range of duration of hospital stay for treatment h all suspected meningitis hospitalizations and for – – Date specimens sent to laboratory meningitis due to H. influenzae and Hib. –– Date and time of pleural fluid specimen h Note: If IB-VPD surveillance is ongoing for other received at laboratory h bacterial causes of meningitis (meningococcus and – – Culture done pneumococcus), then a similar reporting structure * Culture result should be used for laboratory-confirmed cases of –– Gram stain done those etiologies. * Gram stain result Sentinel hospital invasive H. influenzae disease –– BinaxNOW® done surveillance (meningitis, pneumonia and sepsis) * BinaxNOW® result hh Confirmed invasive H. influenzae and Hib disease –– PCR done case counts, stratified by onset date (week, month, * PCR results year), age group, sex and syndrome. h –– Biochemistry results h Suspected meningitis, pneumonia and sepsis case counts, stratified by the same groupings as confirmed hh Additional data elements for population-based invasive H. influenzae disease surveillance cases. h »» Catchment area population by age groups (0–5 h Confirmed invasive H. influenzaeand Hib disease months, 6–11 months, 12–23 months, and 24–59 death counts and case-fatality ratios. months) hh Suspected meningitis, pneumonia and sepsis death counts and case-fatality ratios

10 Haemophilus influenzae Haemophilus influenzae

Population-based invasive H. influenzae disease hh Prioritize H. influenzae disease among other diseases surveillance of public health importance. hh Incidence of confirmed invasive H. influenzae and hh Advocate for and implement proper control Hib disease, stratified by onset date (week, month, strategies such as immunization. year), age group, sex and syndrome. hh Evaluate the impact of immunization services and identify areas with weak performance. USING DATA FOR DECISION-MAKING h Evaluate vaccine impact and effectiveness. hh Determine the local disease burden (cases, deaths, h disability). hh Monitor trends in disease epidemiology.

SURVEILLANCE PERFORMANCE INDICATORS

TABLE 1 Surveillance performance indicators for H. influenzae

HOW TO CALCULATE SURVEILLANCE INDICATOR TARGET (NUMERATOR / COMMENTS ATTRIBUTE DENOMINATOR)

Consistent At least 10 months with Ideal is 12 months and COMPLETENESS Number months reporting reporting (including zero confirmed zero reporting OF REPORTING reporting per year throughout year reporting) if no cases

≥ 80 suspected meningitis Ideal is ≥ 100 suspected Minimum cases per year; ≥ 400 meningitis cases per year; CASE number of Number of cases suspected cases of ≥ 500 suspected cases of ASCERTAINMENT cases reported reported per year meningitis plus pneumonia meningitis plus pneumonia annually or sepsis, per year or sepsis, per year

# of suspected Specimen is CSF for meningitis Proportion of cases with specimen surveillance and CSF, blood SPECIMEN suspected cases ≥ 80% collected / # of or pleural fluid in pneumonia COLLECTION with specimens suspected cases and sepsis surveillance; ideal collected x 100 is ≥ 90%

# of laboratory- Proportion of LABORATORY confirmed cases laboratory- For sentinel hospitals that do CONFIRMATION classified as Hib confirmed cases > 60% serotyping or send isolates for WITH SEROTYPE vs. non-Hib / # of classified as Hib serotyping; ideal is ≥ 80% DETERMINATION laboratory-confirmed vs. non-Hib cases x 100

LABORATORY hh There is no minimum number of cases that should hh EQA and QC of the laboratory should be completed test positive for H. influenzae since it varies widely annually. among countries and depends on Hib use.

11 WHO Vaccine-Preventable Diseases Surveillance Standards CLINICAL CASE MANAGEMENT

All cases of invasive H. influenzae disease should be possibly mechanical ventilation might be necessary. Take hospitalized and promptly treated with intravenous CSF and blood samples before antibiotic treatment, (or intramuscular) antibiotics to which the bacteria are if possible. Treat patient with presumptive antibiotics susceptible. Supportive care including fluids, oxygen and without waiting for laboratory results.

CONTACT TRACING AND MANAGEMENT

Contact tracing is not routinely done for H. influenzae surveillance.

SURVEILLANCE, INVESTIGATION AND RESPONSE IN OUTBREAK SETTINGS

Although most Hib disease is sporadic, Hib can cause influenzae disease. If the serotype is the same among outbreaks in setting such as daycare centers. Sentinel H. influenzae cases, this strengthens the evidence for an site surveillance is not designed to identify all outbreaks epidemiologically linked cluster. since they will be geographically limited, so other types of surveillance with greater geographic coverage will be CHANGES TO SURVEILLANCE needed to identify outbreaks. DURING AN OUTBREAK No change to surveillance is generally needed during an DEFINITION OF AN OUTBREAK outbreak. There is no accepted definition of a H. influenzae or Hib cluster or outbreak. Some have considered a PUBLIC HEALTH RESPONSE cluster of serious pneumococcal disease to be two or Reactive vaccination is not an established strategy for H. more temporally linked cases that occurred in a closed influenzae outbreaks. Prompt recognition of cases and setting (11), and this could also be applied to H. timely treatment with antibiotics is important.

12 Haemophilus influenzae Haemophilus influenzae

SPECIAL CONSIDERATIONS FOR H. INFLUENZAE SURVEILLANCE

hh Some countries in the African meningitis belt, hh IB-VPD surveillance can be leveraged to monitor which have significant other VPDs and non-VPDs such as typhoid, burden and limited confirmation capacity, perform diphtheria and pertussis, and can help to build syndromic meningitis surveillance. Typically, this global bacteriology capacity, especially in a time is part of the Integrated Disease Surveillance and where antimicrobial resistance is a high public health Response (IDSR). Meningitis surveillance is not priority. pathogen-specific and covers the three vaccine hh Measuring the impact of Hib conjugate vaccine preventable disease pathogens associated with can be challenging. The impact of Hib conjugate bacterial meningitis: N. meningitidis, S. pneumoniae vaccines can be measured using surveillance data and and H. influenzae. These require laboratory capacity observational studies, such as case-control studies to identify and distinguish. This surveillance can be and time series analysis of secondary data sources nationwide or regional, and is typically aggregate (12). The most appropriate method for measuring passive surveillance. The objective of this surveillance vaccine impact should be chosen based on the is to detect outbreaks for a rapid public health setting, and multiple methods and outcomes may response. For meningococcus, the public health need to be used to accurately measure impact. response includes reactive vaccination; for H. influenzae and pneumococcal outbreaks, reactive vaccination is not an accepted strategy.

13 WHO Vaccine-Preventable Diseases Surveillance Standards REFERENCES

REFERENCES CITED 1. World Health Organization. Estimated Hib and pneumococcal deaths for children under 5 years of age, 2008. In: Immunization, vaccines and biologicals [website]. Geneva: World Health Organization; 2013 (http://www.who.int/ immunization/monitoring_surveillance/burden/estimates/Pneumo_hib/en/). 2. World Health Organization. Haemophilus influenzae type b (Hib) vaccination position paper – September 2013. Wkly Epidemiol Rec. 2013;88(39):413–28 (http://www.who.int/wer/2013/wer8839.pdf?ua=1). 3. von Gottberg A, Cohen C, Whitelaw A, Chhagan M, Flannery B, Cohen AL, et al. Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination, South Africa, 2003–2009. Vaccine. 2012;30(3):565- 71. doi: 10.1016/j.vaccine.2011.11.066. 4. World Health Organization. WHO-coordinated Sentinel Hospital VPD Surveillance Networks. In: Immunization, vaccines and biologicals [website]. Geneva: World Health Organization; 2018 (http://www.who.int/immunization/monitoring_ surveillance/burden/vpd/sentinel_surveillance/en/). 5. World Health Organization. Surveillance tools for meningitis sentinel hospital surveillance: field guide to rapidly estimate the hospital catchment population (denominator) and the annual rate of hospitalisations. Geneva: World Health Organization; 2015 (http://www.who.int/immunization/documents/monitoring/WHO_IVB_15.02/en/). 6. World Health Organization. Standardization of interpretation of chest radiographs for the diagnosis of pneumonia in children. Geneva: World Health Organization; 2001 (http://apps.who.int/iris/bitstream/10665/66956/1/ WHO_V_and_B_01.35.pdf). 7. Ladhani S, Heath PT, Slack MP, McIntyre PB, Diez-Domingo J, Campos J, et al. Haemophilus influenzae serotype b conjugate vaccine failure in twelve countries with established national childhood immunization programmes. Clin Microbiol Infect. 2010;16(7):948–54. doi: 10.1111/j.1469-0691.2009.02945.x. 8. European Society of Clinical Microbiology and Infectious Diseases. EUCAST guidance documents in susceptibility testing. In: European Committee on Antimicrobial Susceptibility Testing [website]. Basel, Switzerland: European Society of Clinical Microbiology and Infectious Diseases; 2016 (http://www.eucast.org/guidance_documents/). 9. Centers for Disease Control and Prevention & World Health Organization. Laboratory methods for the diagnosis of meningitis caused by , , and Haemophilus influenzae, nd2 edition. Geneva: World Health Organization; 2011 (http://www.who.int/immunization/research/development/WHO_IVB_11.09_eng.pdf?ua=1). 10. World Health Organization. Invasive Bacterial Vaccine Preventable Diseases Laboratory Network. In: Immunization, vaccines and biologicals [website]. Geneva: World Health Organization; 2017 (http://www.who.int/immunization/monitoring_ surveillance/burden/laboratory/IBVPD/en/). 11. Basarab M, Ihekweazu C, George R, Pebody R. Effective management in clusters of pneumococcal disease: a systematic review. Lancet Infect Dis. 2011;11(2):119–30. doi: 10.1016/S1473-3099(10)70281-4. 12. World Health Organization. Measuring impact of Streptococcus pneumoniae and Haemophilus influenzae type b conjugate vaccination. Geneva: World Health Organization; 2012 (http://apps.who.int/iris/bitstream/10665/75835/1/WHO_ IVB_12.08_eng.pdf).

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