Haemophilus Influenzae B Disease

Nitin Shah
HIB - Clinical Spectrum
Hib leads to a spectrum of clinical manifestations starting from asymptomatic carrier state to various types of invasive diseases including meningitis, pneumonia, epiglottitis, bacteremia, skin infections, bone infection & others.

60-80 % of healthy people are carriers of all types of H. influenza in their upper respiratory tract. Of this Hib is a commensal in children <5 yrs. In west, 3-5% of children are carriers whereas in developing countries it rises to 15-30 % of children (9). It is rare before 6 months, peaks at 2-5 years & then falls >5 yrs of age. In west, carrier state remains for 5 - 6 weeks whereas in developing countries it can remain for months. Similarly age at 1st exposure is early in developing countries & later in western worlds.

Hib gets transmitted from a carrier to susceptible host via respiratory droplets let out on coughing or sneezing. When it invades the respiratory mucosa to enter into the blood stream it leads to invasive disease.

Pyogenic meningitis is a leading cause of death due to Hib in children < 5yr old. It can also lead to complications like ventriculitis, subdural effusion or long term sequelae in survivors.

Hib is a fastidious organism to grow on culture & hence one should use enriched media to increase the yield. Similarly use of antibiotics leads to decreased chances of growing causative organism. In preantibiotic era, 85% of cultures of CSF used to be positive in pyogenic meningitis, now it is positive in <50% of cases due to use of antibiotics prior to collections of CSF. CIE for Hib & pneumococcus can increase the yield to 89% in such cases. (4)

In west 50-60% of total Hib cases present as meningitis whereas it is 70-90% in developing countries due to early peak as discussed before. Annual incidence of Hib meningitis depends on age of exposure. In west where peak occurs late 50-60% of Hib present as meningitis like in Finland, UK or USA whereas 70-90% of total Hib presents as meningitis in countries like Alaska, Gambia etc (2,6). In India, IBIS study has shown that 68% of all Hib cases presented as meningitis & 30% of all cases of pyogenic meningitis were due to Hib (8). Other studies done in India has shown that 30% of total cases of pyogenic meningitis (45% of CSF culture +ve cases) were caused by Hib, 29% (43% of CSF culture positive cases) were due to pneumococcus & 4% (59% of CSF culture positive cases) were due to meningococcus & rest due to other organisms (4,7).

Studies from west have shown 3-5% mortality due to Hib meningitis in UK, USA or Finland. In developing countries the mortality is as high as 30-50% due to lack of proper health care system (2). With increasing resistance of Hib to antimicrobials, one has to use 3rd generation cephalosporins like Cefotaxime or Ceftriaxone as first line of drug. One study showed 100% mortality when Cefotaxime was delayed in MDR Hib meningitis (4,7). The IBIS study has shown 30% mortality due to Hib meningitis in < 1yr old & 10% in > 1yr old. The mortality in non meningitis Hib cases was also 10% (8).

10-16% of survivors of Hib meningitis have long term sequelae in west. This figure rises to 30-40% in developing countries.11% of survivors have deafness, 15 % have language problems, 11% have mental retardation & 25% have motor defects or visual defects. This adds to the cost of treatment (2,8).

Hib pneumonia is usually seen between 4 months to 4 years of age. 40% of them have associated bacteremia or meningitis. In west, it is rare & is seen in 2-4 % of total Hib cases whereas in developing countries 8-20% of total Hib cases present as pneumonia (2). In some south east Asian countries it can account for upto 40% of total Hib cases (2).
It is difficult to ascertain the causative organism in pneumonia as <10% of cases have positive blood cultures, <50% have positive lung tap culture. It is difficult to perform lung tap in all cases. Similarly 50% of cases have positive CIE when done on blood or lung tap or pleural fluid.

One study from Calcutta has shown that 46% of lung tap cultures grew Hib (4). Another study from Delhi has shown that of the cases of pneumonia 28% were caused by pneumococcus and 19% due to Hib. Of the Hib cases 9% had positive blood culture & 10% more had positive CIE (11). Study from Vellore has shown that 8% of pneumonia cases had Hib grown on blood cultures, 30% had pneumococcus, 28% grew staphylococcus aureus & 40% grew other organisms (4). 2 studies from Chandigarh have focused on respiratory diseases (3,10). In one study, Ayyagiri et al showed that of acute upper respiratory tract disease 7% were due to Hib & 21% due to nontypable H. influenza; of acute lower respiratory tract disease 6% were caused by Hib & 9% by nontypable H. influenza & none of the cases of chronic respiratory tract disease were caused by Hib. Similarly in another study they showed that of pneumonia cases 8% were due to Hib & 61.5% due to pneumococcus & 20% due to staphylococcus. Lastly IBIS study has shown that of total Hib cases, 16% presented as pneumonia as proved by positive blood culture or pus culture (8).

8-12 % of total Hib cases present as epiglottitis. It is usually seen in 2-4 yr old child & rarely in adults. Patient develops sudden onset of fever, drooling of saliva, anxious look, inflammation of larynx, upper respiratory tract & epiglottis which becomes enlarged & red. Patients can die of choking. It is commonly seen in developed countries but virtually not seen in developed countries. In such countries however epiglottitis is seen pushing the peak age of Hib to older age (2).

Similarly skin infections involving face is rarely seen in countries like India but was commonly seen in west before mass vaccination.

Age is the most important factor affecting both incidence and type of Hib disease as discussed before. Males are affected often than females in a ratio of 2:1 to 3:2. Poor socio-economic conditions, over crowded housing, day care centre setup adversely affect the incidence of Hib disease. Certain diseases like asplenia, sickle cell anemia, splenectomy, immunodeficiency, nephrotic syndrome, complement deficiency etc. also predispose to Hib disease. Chemical pollutants can increase chances of carriage & invasion by Hib. Lastly access to health care system & vaccination will decide both incidence & outcome of Hib disease.(2)

Haemophilus Influenzae B Disease Haemophilus Influenzae B Disease 04/09/2001
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