Continued...

Others :
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.

Factors affecting Hib disease:
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)

Hib-Mortality:
Meningitis & epiglottitis are 2 common cases of mortality. In west the mortality is low & is 3-5%. In developing countries it is as high as 30-50 % due to suboptimal health care system & access (2,4,7). It is estimated that world over 3,75,000 children die due to Hib every year. In India, the IBIS study has shown that the mortality due to meningitis is 30% in <1 yr old children & 10% in >1 yr old. Similarly mortality due to non-meningitis Hib cases is 10% (8). The mortality is likely to increase due to increasing drug resistance.

Hib drug resistance:Of late there is increase in the incidence of drug resistance in Hib. Ampicillin resistance was reported in 1974, chloramphenicol resistance in 1978. Both ampicillin and chloramphenicol resistant strains were reported in 1980 from UK, USA, Bangkok & Spain (12). Since then multidrug resistance mediated by R plasmid has spread all over world posing therapeutic challenges, threatening to increase mortality & increasing cost of treatment.

1^st multidrug resistant strain causing meningitis in India was reported from Chandigarh which proved fatal (12). This was followed by 2 more cases reported from Pondicherry & one more case from Chandigarh in 1990 (13). Use of cefotaxime saved this child. Large study from Vellore in 1992 reported that 42.5% of total Hib cases were MDR strains with 80% resistant to ampicillin, 90% to chloramphenicol & sulpha drugs & none to cefotaxime (4,7). This prompted them to use 3^rd generation cephalosporins as first line drug in cases of meningitis as mortality was 100% in MDR cases if cefotaxime was delayed. This is in contrast to UK where between 1985-90 only 12.5% strains were resistant to ampicillin & none to chloramphenicol. The increased incidence of MDR in India was be related to widespread misuse of antibiotics in general population. Similar report from Nagpur in 1996 showed that 80% of Hib infants were resistant to both ampicillin and chloramphenicol (14). In 1996 the second report from Vellore showed 30% resistance to ampicillin, 17% to chloramphenicol and 15% to both these drugs (4,7). Lastly IBIS study has shown 56% resistance to chloramphenicol, 40% to ampicillin & none to 3^rd generation cephalosporin (8). 

Hib Prevention:
As discussed above, the burden of Hib disease is tremendous. 3 million children suffer from invasive Hib disease annually world-over, of which 0.37 million succumb to it. Of the survivors of Hib meningitis, 20-30% have long term sequelae. Increasing microbial resistance has forced us to use 3^rd generation cephalosporins as 1^st line dung adding to the cost of therapy. Poor health infrastructure in developing countries leads to increased mortality. Chemoprophylaxis will only succeed in blocking 29% of transmission which occurs from index case & is not a long lasting solution.

Excellent conjugate Hib vaccines are available & used for mass vaccination since 1980. They have proved to be extremely potent, safe and efficacious. Mass vaccination has lead to elimination of Hib disease from countries like Finland, UK, USA etc. It is possible to eradicate Hib by universal immunisation world over.

Natural immunity:
Transplacental maternal antibodies protect a newborn till 6-8 weeks. Acquired immunity develops in baby only after 18-24 months following subclinical infection as before 18-24 months the immune system of baby is less developed. This leads to a susceptible period mainly during 3-18 months of life; the Hib disease peaks during this period. Hence Hib vaccine has to be effective during this period of 3-18 months for it to be meaningful (2).