Haemophilus Meningitis in an African Neonate: Time for Active Surveillance and Institution of
Appropriate Control Measure
ABSTRACT
Background: Childhood routine immunization in Nigeria, like most developing nations, did not
include vaccination against Haemophilus influenzae type b (Hib) infection. This is probably
because infection with Hib is uncommon in children younger than 2 months due to passive
acquisition of maternal antibodies which protects newborn till about 4-6month of life.
Objective: To illustrate a case of neonatal meningitis caused by Haemophilus influenzae and
highlights
its
other
peculiarities.
Case report: A 22 day old baby presented with excessive crying, refusal of feed, progressive
abdominal distension, fever and vomiting. The baby was also having tachypnoea (90bpm),
tachycardia (182bpm), tympanitic and hypoactive abdomen. However, the musculoskeletal and
central nervous systems appeared clinically normal. Based on the assessment of late onset sepsis,
the patient’s blood, urine, stool and cerebrospinal fluid (CSF) specimens were taken for
bacteriological examination along with other investigations. Haemophilus influenzae was
isolated by culture from the CSF. The isolate could not be typed due to sub-optimal laboratory
condition. The baby responded well to ceftriaxone and gentamycin while neurologic examination
remained normal after discharge for up to three months at follow-up visit.
Conclusion: There is the need for government to provide serological and molecular facilities for
typing Nigerian Haemophilus infulenzae strain(s) to enhance the development of appropriate
vaccine that will be most suitable for prevention of infection due to this organism in Nigeria.
However, presently available Haemophilus influenzae vaccine needs to be listed in the National
Programme for Immunization (NPI) for the control of infections associated with this organism
especially in childhood.
Keywords: Neonate, Haemophilus influenzae, Meningitis, Africa
INTRODUCTION
Throughout the modern era of bacteriology, Haemophilus influenzae type b (Hib) has been
identified as one of the three most common causes of bacterial meningitis. The others are
Neisseria meningitidis and Streptococcus pneumoniae.1 Hib is an infrequent cause of meningitis
in the neonatal population,1-5 the most common bacterial pathogens being Escherichia coli,
Group B Streptococci and Klebsiella pneumoniae.6-9Hib accounts for < 0.3% of meningitis
occurring in children < 3months, and is almost nonexistent in neonates. It has an overall 17.3%
case
fatality
rate
in
children
aged
<
5yrs.10
Haemophilus influenzae exists as two strains, encapsulated and unencapsulated. Encapsulated
strains (also known as typeable) are surrounded by a polysaccharide capsule that plays an
important role in the determination of virulence of the organism. The outer membrane lipooligosaccharides also contribute to the degree of virulence. The capsular antigens are employed
to subdivide encapsulated strains into six serotypes designated A through F. Un-encapsulated
strains lack the polysaccharide capsule and are designated untypeable strains.6-7 Most invasive
infections are caused by encapsulated strains of Haemophilus influenza and in particular the B
serotype. The polysaccharide capsule of these organisms not only confers virulence and
invasiveness, but it also provides resistance to opsonization and complement-mediated
bactericidal activities and inhibits neutrophil phagocytosis. It is also the source of the antigen
used
in
vaccine
formulation.
Neonates are generally at greater risk of sepsis and meningitis than other age groups largely due
to deficiency in humoral and cellular immunity. This may be in form of defective phagocytic
function, reduced maternal antibody transfer in babies less 32 weeks gestation, defective
alternative complement pathway which compromises their defence against encapsulated bacteria.
T-cell defence and mediation of B-cell activity also are compromised along with deficient
migration and phagocytosis by neutrophils in the neonatal period.
7-8
Diagnosis of meningitis in neonates could be difficult due to its non-specificity of signs and
symptoms.8 However, diagnosis of meningitis is established when at least two out of four
laboratory criteria are fulfilled. 9 The criteria include: isolation of the cause by CSF culture,
elevation of CSF leukocyte count more than 20cell/ mm3 with predominance of
polymorphonuclear leukocytes in the CSF, hypoglycorrhachia and identification of bacteria by
the Gram stain of CSF. Other important parameters useful in diagnosis and monitoring of
response to treatment in meningitis include CSF/ blood sugar and CSF protein.
The purpose of this communication is to sensitize medical practitioners about the occurrence of
Haemophilus influenzae meningitis in the neonatal period and alert policy markers on the need to
institute
preventive
measures.
Case
Report
Baby OD, a 22 day old term female who presented at the neonatal intensive care unit of the
University of Ilorin Teaching Hospital, Ilorin with history of excessive crying, irritability and
refusal of feeds for 3 days, progressive abdominal distension for 2 days and fever for one day
with an episode of vomiting just before presentation. Stools were of normal consistency but
frequency had reduced from the usual three to four times to once daily. Her feeds had consisted
of breast milk and water since birth. There were no adverse perinatal events. Her parents
belonged to the high socioeconomic class. The family of four lived in a well-ventilated three
bedroom
apartment.
On examination, she was acutely ill-looking but not irritable, pale, anicteric, febrile with an
axillary temperature of 39.80C. She was appropriately sized with a weight of 3.4kg,
occipitofrontal (OFC) of 38cm, and length of 51 cm. Gaseous abdominal distension without
palpable organomegaly was observed. She was tachypnoeic with a respiratory rate of 90cycles
per minute but there was no chest wall retraction and breath sounds were vesicular bilaterally.
There was a tachycardia of 182 beats per minute but the heart sounds were normal. The anterior
fontanelle was patent and normotensive. There was mild head lag but muscle tone and primitive
reflexes were normal. The working diagnosis was late onset neonatal sepsis with the possibility
of
meningitis
and
partial
intestinal
obstruction.
Lumbar puncture yielded turbid cerebrospinal fluid with relative hypoglycorrhacchia
(1.0mmol/L compared to blood sugar of 4.4mmol/L), modestly elevated protein content
(91mg/dl) and pleocytosis (280cells/mm3 mostly polymorphonuclear cells). Gram negative
coccobacilli were seen and the culture yielded Haemophilus influenzae. The isolate was sensitive
to
Ciprofloxacin,
Cefuroxime,
Ceftriaxone,
Ceftazidime
and
Augmentin.
Other investigations revealed anaemia (PCV = 26%), normal peripheral blood leucocyte count
(4.0 X 109/L) but with mostly neutrophils (84%), normal platelet count (463 X 109/L). Serum
electrolytes and creatinine were within reference range. Abdominal ultrasound scan and plain
abdominal radiography revealed normal findings. The blood culture was sterile.
She was placed on supplemental oxygen by face mask, intravenous 10% dextrose in 0.18saline,
intramuscular Ceftriaxone 100mg/kg/day, Gentamycin 5mg/kg 12 hourly, and Dexamethasone
0.5mg/kg
stat,
then
0.2mg/kg/dose
8
hourly
for
48hours.
A repeat CSF examination at about 48 hours of initiating treatment gave almost similar CSF
biochemistry and cell count results but no organism was cultured though few gram negative
coccobacili were seen on gram stain. The baby had first episode of subtle seizure at 24hours on
admission, then had several episodes characterised by lip smacking and staring gaze.
Intramuscular Phenobarbitone was prescribed at a dose of 15mg/kg stat and 2.5 mg/kg/dose 12
hourly. Phenobarbitone was discontinued and feeding commenced on fourth day of admission
after baby had been seizure free for >48hrs. The fever abated on the sixth day. Gentamycin was
discontinued on day 7 and baby had become stable enough to be discharged home. Her occipitofrontal circumference (OFC) remained constant and within normal range throughout admission.
She continued to receive Ceftriaxone on out-patient basis for the next 7 days, totalling 14 days
on
medication.
Transfontanelle ultrasound scan was normal on completion of antibiotics. She remained
clinically normal on neurologic examination at the outpatient clinic during the first three months
after discharge. Unfortunately, her parents defaulted on subsequent follow up visits.
DISCUSSION
Haemophilus influenzae was first identified in culture by Pfeiffer in 1892.1 The designation
influenza bacillus was applied because he mistakenly thought that it was the cause of the
influenza pandemic of 1890. The genus designation Haemophilus, indicating the hemophilic or
blood-loving characteristic of Haemophilus influenzae was applied because growth of the
organism in culture requires the presence of whole blood factors V and X.1,11- 12
Transmissibility of Haemophilus influenzae infection and the capacity of this organism to cause
purulent meningitis were first demonstrated by Wollstein in 1911. 1 She first drew attention to
the marked tendency for Haemophilus influenzae meningitis to occur in infants and young
children.
The child in focus presented with non-specific symptoms and signs as well as paucity of central
nervous system symptoms and sign such as tense and bulging anterior fontanelle. This underlines
the need for a high index of suspicion for the possible occurrence of meningitis in sick neonates.
Indeed, the appearance of neurologic signs is often an indication of late presentation and has
grave
consequences
for
long
term
prognosis.
Meningitis remains one of the leading causes of cerebral palsy and mental retardation in this
environment. Though we did not have the privilege to follow the child up till the end of the first
year of life, the short duration during which follow up occurred showed the possibility of a
normal
neurologic
outcome.
An unusual organism was responsible for the meningitis in this child with particular reference to
age. Infection with Hib is uncommon in children younger than 2 months, probably because of
passive acquisition of maternal antibodies which protects newborn till about 4-6month of life. 1,
12 Children that develop Hib disease most likely acquired the organism from other children
(contacts) in day care centres, schools, as less than one percent of adults have nasopharyngeal
colonization with Haemophilus influenzae.1 In the index case, the disease was probably
contracted from an adult contact since the baby was not yet mixing with other children. The
infrequency of Hib infection in young infants is related to the degree of protection conferred by
transplacentally acquired maternal antibodies. These antibodies decay with time, thus exposing
the older infant to the risk of infection. It is likely therefore that there was low level of maternal
antibody transfer or rapid decay of maternally transmitted antibodies in the index case.
The occurrence of this infection in a neonate may acquire greater significance if it does represent
a new trend. Policy changes may be needed to cope with the situation. It may for example be
necessary to incorporate routine typing of the organism into our laboratory techniques so as to
identify which strain is responsible for infection in these young infants. Secondly, routine
vaccination against Hib may have to be included in the national programme so as to prevent the
devastating
consequences
of
infection
due
to
this
organism.
In Nigeria like most African countries, vaccine for the control of Haemophilus influenzae
infections is not included in the national programme on immunization as against the practice in
the USA and other developed nations. This probably may be related to the unknown national and
continental prevalence, morbidity and mortality rates for infections due to Haemophilus
influenzae. Furthermore, Haemophilus influenzae isolates are not routinely typed in our
environment and the Haemophilus influenzae recovered from the baby in question was not typed.
There is therefore the need for active surveillance system for Haemophilus influenzae related
infections
in
Nigeria.
In conclusion, there is need for continuous high index of suspicion for meningitis in the
newborn. The reported case seems to be a relatively benign course of a highly invasive organism.
Are there environmental issues that have resulted in this reported case? Findings call for diligent
survey, provision of necessary laboratory needs and probably, inclusion of appropriate vaccine
among
childhood
immunization
in
Nigeria.
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