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 ~  Abstract
 ~ Introduction
 ~ Case Report
 ~ Discussion
 ~ Conclusion
 ~  References

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  Table of Contents  
Year : 2015  |  Volume : 33  |  Issue : 1  |  Page : 158-160

Hemophilus influenzae meningitis and septicaemia in a 14-month-old child after primary immunisation

1 Department of Microbiology, Max Super Speciality Hospital, Saket, New Delhi, India
2 Department of Pediatrics, Max Super Speciality Hospital, Saket, New Delhi, India
3 Department of Laboratory Medicine, Max Super Speciality Hospital, Saket, New Delhi, India

Date of Submission15-Mar-2014
Date of Acceptance23-May-2014
Date of Web Publication5-Jan-2015

Correspondence Address:
B Tarai
Department of Microbiology, Max Super Speciality Hospital, Saket, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0255-0857.148431

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 ~ Abstract 

We report a 14-month-male child, who developed Hemophilus influenzae meningitis after three primary doses of the vaccine. The child presented with fever and seizures. H. influenzae was isolated from both cerebrospinal fluid (CSF) and blood. The child also had features of septicaemia. Procalcitonin (104 ng/ml) and C-reactive protein (CRP - 42.6 mg/dl) were high. Appropriate antibiotics were given. The child made an uneventful recovery. This case highlights vaccine failure, especially after primary immunisation alone.

Keywords: Hemophilus influenzae, meningitis, vaccine failure

How to cite this article:
Tarai B, Ravishankar N, Vohra P, Das P. Hemophilus influenzae meningitis and septicaemia in a 14-month-old child after primary immunisation. Indian J Med Microbiol 2015;33:158-60

How to cite this URL:
Tarai B, Ravishankar N, Vohra P, Das P. Hemophilus influenzae meningitis and septicaemia in a 14-month-old child after primary immunisation. Indian J Med Microbiol [serial online] 2015 [cited 2021 Jan 25];33:158-60. Available from:

 ~ Introduction Top

Haemophilus influenzae type b (Hib) meningitis was recognised as a common cause of childhood meningitis before the use of Hib vaccine in routine infant immunisation. [1] In Indian infants 0-11 months of age, the incidence of Hib meningitis was 32 per 100,000 and in the 0-23 month group it was 19 per 100,000. [2],[3] In the UK, since the incorporation of Hib vaccine into routine immunization, the attack rate has decreased from 20-40 to 1 per 100,000 children under the age of 5 years. [4] Vaccine failure after regular Hib vaccination is rare. We report a 14-month-male child who developed H. influenzae meningitis and septicaemia after primary immunisation with three doses of the conjugate vaccine.

 ~ Case Report Top

A 14-month-male child weighing 10.2 kg was admitted to the paediatric intensive care unit (ICU) with fever (101°F) for two days. He was lethargic, had stopped interacting with his mother and had poor oral intake for one day. He also had one generalised tonic clonic seizure that lasted for 30-40 seconds. On examination, the child was febrile, with full fontanelle and neck rigidity, abdomen was soft with no organomegaly; chest was clear and throat normal. There was no vomiting, diarrhoea, cough, cold or ear discharge. There was no past history of seizures or contact with tuberculosis. He had been immunised with three doses of pentavalent conjugate vaccine (DTaP + Hib + hepatitis B) and oral polio vaccine. Lumbar puncture was performed suspecting meningitis. Cerebrospinal fluid (CSF) findings were: Glucose 3 mg/dl (blood glucose 95 mg/dl), protein 316 mg/dl, and leucocyte count 1300/ml with predominance of neutrophils (70%). Procalcitonin (104 ng/ml) and C-reactive protein (42.6 mg/dl) were elevated. The blood counts showed leucocyte count of 8.5 × 109/L with neutrophils 63% and anaemia (Hb = 7.9 g/dl). HIV was non-reactive.

The CSF Gram stain showed Gram negative pleomorphic coccobacilli suggestive of H. influenzae. The H. influenzae type b antigen was detected in CSF using latex agglutination test (Wellcogen TM bacterial antigen kit, Remel). CSF was cultured using sheep blood and chocolate agar plates that were provided commercially (BioMerieux). Blood culture sample was collected in BactAlert aerobic bottle and processed in BactAlert 3D automated blood system (BioMerieux). Both CSF and blood culture yielded H. influenzae. The positive growth from CSF and blood were further processed for identification on VITEK 2 Compact (BioMerieux) and the serotype b was demonstrated on culture isolates by latex agglutination test. Throat swab culture did not grow H. influenzae. The antibiotic susceptibility test was carried out on chocolate agar by a disc diffusion method (Kirby-Baur method) as per the Clinical and Laboratory Standards Institute (CLSI) guidelines 2012. The strain was sensitive to beta-lactam antibiotics, chloramphenicol, and was resistant to co-trimoxazole.

Magnetic resonance imaging (MRI) brain after 6 days showed sulcal and cisternal enhancement with exudates in bilateral frontal subdural region. A repeat CSF examination after 5 days of admission showed glucose 57 mg/dl and protein 123 mg/dl with 75 cells (90% lymphocytes); CSF and blood culture were sterile. Serum complement levels were normal: C3 = 154 mg/dl (range: 79-152 mg/dl) and C4 = 44 mg/dl (range: 16-38 mg/dl).

Intravenous antibiotics ceftriaxone and vancomycin were started empirically at the time of admission. Dexamethasone was administered concurrently. Seizures were controlled with phenytoin. Vitamin D3 deficiency was detected for which oral supplements were started. The child also required packed red blood cells (RBC) to maintain hemodynamic stability. Antibiotic vancomycin was replaced with ampicillin after H. influenzae was cultured.

The child was discharged after 2 weeks of admission. At discharge he was afebrile, his head circumference was 44 cm and had no neurologic deficits. Hearing assessment was done after 6 weeks follow-up and was normal.

 ~ Discussion Top

Haemophilus influenzae serotype b (Hib) disease was previously thought to be not widely prevalent in Asia, either because of true biologic or geographic variation in the incidence of invasive Hib disease [5] or, perhaps, because of failure to determine invasive disease. [6] Early microbiological diagnosis is essential for the management of invasive Hib infection. Most laboratories cannot culture or identify H. influenzae reliably. [3] This factor was not a constraint for us as we used an experienced reference laboratory having automated BactALERT 3D system (BioMerieux) for blood culture and VITEK 2 Compact (BioMerieux) for identification and sensitivity. In our patient, we are able to recover the isolates both in blood and CSF and identified the strain with antibiotic sensitivity within 48 hours.

Vaccine failure after primary immunisation with Hib vaccine has been reported worldwide. Booy et al., investigated invasive Hib infection that occurred over a 3-year period in children in the UK after they received at least one dose of the Hib-conjugated vaccine. They identified two types of vaccine failure: Apparent (early) and true failure. True failure was defined as Hib invasive disease occurring either more than 1 week after a child up to the age of 1 year had received at least two doses of the vaccine, or more than 2 weeks after a single dose was received by a child >1 year of age. [7] Our patient had received three primary doses of Hib vaccine at 6, 10, and 14 weeks of age. Hence this qualifies as a true vaccine failure.

There are various risk factors associated with vaccine failure - immunogenicity of the vaccine, cold chain maintenance, and immune status of the child. In young children, host factors play a key role: Age (immaturity of the immune system) and "non-responders", despite the improved effectiveness of conjugate vaccines. It also appears that the age of Hib infection is lower for preterm infants than in children born at term; this observation being consistent with the hypothesis of a weaker response to vaccination and thus a shorter protection for the first group. [8],[9]

Other risk factors described in the literature include concomitant illness, immunodeficiency, or deficits in humoral immunity such as hypogammaglobulinaemia, especially a deficiency of IgG2 subtype, particularly important in protecting against encapsulated bacteria. [10] Our patient was born at term and was human immunodeficiency (HIV) negative. He had no past history of any significant illness or hospitalisation. He was exclusively breastfed for the initial 6 months and was not malnourished. Screening for complement deficiency was negative.

Antibody is the central component of protective immunity against encapsulated bacteria like H. influenzae. The level of antibody wanes rapidly after primary immunisation in infants; and therefore, infants immunised in the first 6 months of life would rely on immunologic memory (rapid rise in high concentration of antibody after re-exposure or re-immunisation) to provide sustained protection after infection. [11] Further, the impact of Hib vaccine is also largely due to its effectiveness against asymptomatic carriage of H. influenzae. This reduces transmission, resulting in herd immunity, and population based studies of the effects of the introduction of the Hib vaccine have consistently demonstrated an immediate and sharp decline in the incidence of invasive Hib infection even among those who are not immunised. [12] But the relative contribution of the level of antibodies, immunologic memory, and herd immunity to individual protection are difficult to estimate.

It has been observed that vaccine failures still occur in individuals with demonstrable immunologic memory and adequate herd immunity as documented in the UK after introduction of a combination vaccine with acellular pertussis that was known to interact with the Hib component and reduce the initial antibody response. It is now thought that protection against Hib may be dependent on the absolute level of anti-Hib serum antibody at the time of acquisition of the organism in the nasopharynx. This is because the levels of antibody on re-exposure may not always rise fast enough to prevent invasive diseases. Hence, it is now recognised that the key to sustain protection in the population is by maintenance of serum antibody levels above the protective threshold by booster immunisation.

India's National Technical Advisory Group on Immunisation (NTAGI) has recommended that Hib vaccine be introduced in India through national immunization programme as a pentavalent vaccine combined with DPT (diphtheria, pertussis, and tetanus) and hepatitis B as this child received. A Cochrane meta-analysis has, however, shown that the combination is less effective than the vaccines given separately. [13] The clinical significance is unclear. It is not used for primary immunisation in many countries and the experience with this particular vaccine is therefore limited. Further, the expanded programme of immunisation (EPI) recommends only three doses for the primary immunisation. In view of the above findings, a booster dose in the second year of life is strongly recommended to sustain levels of antibody in the protective range.

 ~ Conclusion Top

conclusion, although there is widespread Hib vaccination awareness and coverage by primary immunisation, but this does not always translate into eradication of invasive disease associated with Hib. This is contributed by various factors and, in particular, to the persistent circulation of the organism by nasopharyngeal carriage, presence of unvaccinated children, and the existence of "poor responders" to vaccination. We made an effort to determine the cause of vaccination failure leading to meningitis and septicaemia in the case reported but was not successful in pinpointing the same. Also despite excellent coverage in the population and the absence of proven risk factors, clinicians have to remain alert to the risk of meningitis and septicaemia caused by H. influenzae b in vaccinated children as well.

 ~ References Top

Peltola H. Worldwide Haemophilus influenzae type b disease at the beginning of the 21 st century: Global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates. Clin Microbiol Rev 2000;13:302-17.  Back to cited text no. 1
Minz S, Balraj VM, Lalitha K, Murali N, Cherian T, Manoharan G, et al. Incidence of Haemophilus influenzae type b meningitis in India. Indian J Med Res 2008;128:57-64.  Back to cited text no. 2
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Levine OS, Wenger JD. Defining the burden of Hib disease in India. Indian Pediatr 2002;39:5-11.  Back to cited text no. 3
Heath PT, McVernon J. The UK Hib vaccine experience. Arch Dis Child 2002;86:396-9.  Back to cited text no. 4
Rosenthal J, Dagan R, Press J, Sofer S. Differences in the epidemiology of childhood community-acquired bacterial meningitis between two ethnic populations cohabiting in one geographic area. Pediatr Infect Dis J 1988;7:630-3.  Back to cited text no. 5
Gellert GA, Wenger JD, Brilla A. Haemophilus influenzae type b disease in Latvia. Lancet 1994;344:959.  Back to cited text no. 6
Booy R, Heath PT, Slack MP, Begg N, Moxon ER. Vaccine failures after primary immunization with Haemophilus influenzae type-b conjugate vaccine without booster. Lancet 1997;349:1197-202.  Back to cited text no. 7
Heath PT, Booy R, McVernon J, Bowen-Morris J, Griffiths H, Slack MP, et al. Hib vaccination in infants born prematurely. Arch Dis Child 2003;88:206-10.  Back to cited text no. 8
Metreau Z, Le Bars H, Desgranges-Federico M, Monnier M, Ryckewaert A, Chasle V, et al. Hemophilus meningitis in properly vaccinated children: Report of three cases. Arch Pediatr 2013;20:492-5.  Back to cited text no. 9
McVernon J, Andrews N, Slack MP, Ramsay ME. Risk of vaccine failure after Haemophilus influenzae type b (Hib) combination vaccines with acellular pertussis. Lancet 2003;361:1521-3.  Back to cited text no. 10
Blanchard-Rohner G, Pollard AJ. Sustaining immunity after immunization against encapsulated bacteria. Hum Vaccin 2008;44:309-12.  Back to cited text no. 11
MacIntyre PB, O'Brien KL, Greenwood B, van de Beek D. Effect of vaccines on bacterial meningitis worldwide. Lancet 2012;380:1703-11.  Back to cited text no. 12
Bar-On ES, Goldberg E, Fraser A, Vidal L, Hellmann S, Leibovici L. Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (HIB). Cochrane Database Syst Rev 2009;CD005530.  Back to cited text no. 13

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