Abstract
Two and a half million children globally, live with the Human Immunodeficiency virus (HIV) and 105,000 live in India. Each year, 21,000 Indian children are newly infected. HIV infection significantly increases risk for severe disease and death from vaccine preventable pathogens in infected children. Pneumonia is the leading cause of death in HIV infected children and the three leading pathogens are Streptococcus pneumoniae (Pneumococcus), Haemophilus influenzae b (Hib) and Staphylococcus aureus, the first two being vaccine preventable. HIV infected children are at twenty times increased risk of bacteremic pneumonia from Hib and forty times increased risk of bacteremic pneumonia from pneumococcus. HIV infected children are at particular risk for coinfection with Hepatitis B. India qualifies as intermediate-high endemicity in Hepatitis B.
Given the increased burden of disease in HIV infected children, global and national bodies have made additional specific recommendations for immunizations in HIV infected children many of which have yet to be incorporated into the Indian national program for HIV infected children. There are no studies on the incidence or impact of invasive Hib, pneumococcal disease or hepatitis B, or any information on immunization access and history in HIV infected children in India.
We carried out a cross-sectional nasopharyngeal swab study from March 2008 to April 2009 in a cohort of ambulatory HIV infected children presenting for routine care at a tertiary center in Kolkata with a limited budget. The aim of the study was to determine (i) immunization rates and factors associated with incomplete immunization, (ii)
nasopharyngeal colonization rates of Hib and Pneumococcus, (iii) antibiotic susceptibility of the isolates from the nasopharynx of HIV infected children, (iv) bacterial associations of S. pneumoniae, Staphylococcus aureus, and H.influenzae in the nasopharynx, and (v) effectiveness of the current government immunization program in preventing bacterial pneumonia and Hepatitis B in HIV infected children in India.
A standardized instrument was developed and translated into Bengali, capturing information on demographics, and immunization. Written informed consent was
obtained from caregivers and assent from all children over five. The study was approved by the Institutional Review Boards of three institutions Indian Institute of Technology Kharagpur, the Medical College Kolkata, and the National Institute of Cholera and Enteric Diseases (NICED). 206 HIV affected children were enrolled. The median age of children in this cohort was 6 years. 197/206 was HIV infected 9 were HIV exposed, but indeterminate. 200 missed opportunities for immunizations were documented. Data was entered and edited in Epi info 3.5 and analyzed with STATA 9. Children were classified into immunologic categories based on CD4 count or CD4% by the 1994 CDC Revised Classification Guidelines.
Copyright
IIT Kharagpur
The major findings corresponding to the five objectives were as follows:
(i) HIV infected children in India are at risk for incomplete immunization coverage though they regularly access medical care. Including routine immunizations, particularly catch-up immunizations in programs for HIV infected children maybe an effective way of protecting these children from vaccine preventable disease.
(ii) 65% had moderate to severe malnutrition, 53% were moderately to severely immunosuppressed, 17% were on antiretroviral therapy (ART), 90% were on cotrimoxazole prophylaxis (TMP/SMX). None had received the pneumococcal or Hib conjugate vaccines. Hib prevalence was 13% and pneumococcal prevalence was 28%. Children with normal or moderate immune suppression had high rates of colonization compared to those with severe immunosuppression (71% Hib, 61% pneumococcus). Neither ART nor TMP/SMX prevented colonization with either organism.
(iii) Hib and pneumococcal isolates had high rates of resistance to tested antibiotics including TMP/SMX and third generation cephalosporins. Children colonized with multidrug resistant isolates had high rates of exposure to TMP/SMX. High rates of colonization with multidrug resistant Hib and pneumococcus were documented in HIV infected children with normal or moderate immune status who were not yet on ART.
(iv) The negative association between S. pneumoniae and S. aureus colonization in the nasopharynx described in healthy populations was not present. We found a strong positive association between carriage with H. influenzae and S. pneumoniae.
These findings provide insight into the increased risk of invasive disease from these organisms in HIV infected children.
(v) We found the overwhelming majority of children with HIV infection are dependent on government programs for immunizations (93%) and that the current program for routine immunizations in children is not doing enough to protect the HIV infected child in India from vaccine preventable infections.
Children with mothers having low formal education had a significantly higher risk of being incompletely immunized. None of the children who participated in the nasopharyngeal swab study had obtained Hib or pneumococcal conjugate vaccines. No child on ART with immune reconstitution was revaccinated with any routine immunization.
