Streptococcus pneumoniae Acquisition and Carriage in Vaccine Naïve Indian Children with HIV and their Parents: A Longitudinal Household Study.

OBJECTIVES: To investigate the difference in pneumococcal carriage, acquisition, antibiotic resistance profiles and serotype distribution, in human immunodeficiency virus (HIV) affected and unaffected families. METHODS: A prospective cohort study was conducted in children with and without HIV in West Bengal from March 2012 through August 2014, prior to 13-valent pneumococcal conjugate vaccine (PCV-13) immunization. One thousand four hundred forty one nasopharyngeal swabs were collected and cultured at five-time points from children and their parents for pneumococcal culture, and serotyping by Quellung method. RESULTS: One hundred twenty five HIV infected children and their parents, and 47 HIV uninfected children and their parents participated. Two hundred forty pneumococcal isolates were found. In children under 6 y, the point prevalence of colonization was 31% in children living with HIV (CLH) and 32% in HIV uninfected children (HUC), p = 0.6. The most common vaccine type (VT) serotypes were 6A, 6B and 19A. All isolates from parents and 71% from children in the HIV uninfected cohort were PCV-13 representative, compared to 33% of isolates from CLH and their parents. Acquisition rate in children was 1.77 times that of parents (OR = 1.77, 95%CI: 1.18-2.65). The HIV status of child or parent did not affect acquisition. Isolates from CLH were more frequently resistant to multiple antibiotics (p = 0.02). CONCLUSIONS: While the rate of pneumococcal carriage and acquisition did not differ between CLH and HUC, HIV affected families had exposure to a wider range of serotypes including non-vaccine type serotypes and antibiotic resistant serotypes, than HIV unaffected families.

Nasopharyngeal Pneumococcal Colonization and Impact of a Single Dose of 13-Valent Pneumococcal Conjugate Vaccine in Indian Children With HIV and Their Unvaccinated Parents.

BACKGROUND: Human immunodeficiency virus (HIV) infection increases risk of invasive disease from Streptococcus pneumoniae. Pneumococcal conjugate vaccines (PCV) prevent invasive disease and acquisition of vaccine type (VT) pneumococcus in the nasopharynx. OBJECTIVE: To look at the safety and impact of one dose of PCV13 on acquisition of VT pneumococcal carriage in Indian children with HIV. METHOD: We conducted a cohort study in families of HIV-infected children (CLH) and families of HIV-uninfected children (HUC) in West Bengal. All children received one dose of PCV13. Nasopharyngeal swabs were collected from children and parents at baseline and 2 months after vaccination. RESULT: One hundred and fifteen CLH and 47 HUC received one dose of PCV13. Fifty-eight percent of CLH were on antiretroviral therapy (ART), and the median nadir CD4 count was 287. There were no significant adverse events in either group. HUC had more VT colonization than CLH-55% versus 23% of all pneumococcal isolates. HIV infection doubled the risk of nonvaccine serotype colonization (P = 0.03). There was no difference in acquisition of VT isolates in CLH (4.4%) and HUC (4.5%) post-PCV13; however, older CLH (>5 years) had decreased clearance of VT strains. ART made no difference in pneumococcal colonization at baseline or after PCV13; however, CLH with higher nadir CD4 counts before starting ART were less likely to have VT colonization post-PCV13 (prevalence ratio, 0.2; 95% confidence interval: 0.1-0.5). CONCLUSION: While there was no difference in acquisition of VT nasopharyngeal carriage of pneumococcus in CLH and HUC after one dose of PCV13, earlier access to ART may impact response to PCV13 in CLH.

Impact of Haemophilus influenzae Type B Conjugate Vaccines on Nasopharyngeal Carriage in HIV-infected Children and Their Parents From West Bengal, India.

BACKGROUND: In addition to reducing Haemophilus influenzae type b (Hib) disease in vaccinated individuals, the Hib conjugate vaccine (HibCV) has indirect effects; it reduces Hib disease in unvaccinated individuals by decreasing carriage. Human immunodeficiency virus (HIV)-infected children are at increased risk for Hib disease and live in families where multiple members may have HIV. The aim of this study is to look at the impact of 2 doses of the HibCV on nasopharyngeal carriage of Hib in HIV-infected Indian children (2-15 years) and the indirect impact on carriage in their parents. METHODS: This prospective cohort study was conducted in HIV-infected and HIV-uninfected families. Nasopharyngeal swabs were collected from children and parents before and after vaccination. HIV-infected children 2-15 years of age got two doses of HibCV and were followed up for 20 months. Uninfected children 2-5 years of age got 1 dose of HibCV as catch-up. RESULTS: 123 HIV-infected and 44 HIV-uninfected children participated. Baseline colonization in HIV-infected children was 13.8% and dropped to 1.8% (P = 0.002) at 20 months. Baseline carriage in HIV-uninfected children was 4.5% and dropped to 2.3% after vaccination (P = 0.3). HIV-infected parents had 12.3 times increased risk of Hib carriage if their child was colonized (P = 0.04) and had 9.3 times increased risk if their child had persistent colonization postvaccine (P = 0.05). No parent of HIV-uninfected children had Hib colonization at any point. Pneumococcal colonization was associated with increased Hib colonization. CONCLUSION: Making the HibCV available to HIV-infected children could interrupt Hib carriage in high-risk families.

Immunogenicity and safety of two doses of catch-up immunization with Haemophilus influenzae type b conjugate vaccine in Indian children living with HIV.

BACKGROUND: Children living with HIV are at increased risk of disease from Haemophilus influenzae type b (Hib). Data are limited on the immunogenicity of a two-dose, catch-up schedule for Hib conjugate vaccine (HibCV) among HIV-infected children accessing antiretroviral therapy (ART) late. OBJECTIVES: The objectives of the study were to: (1) evaluate baseline immunity to Hib and the immunogenicity and safety of two doses of HibCV among HIV-infected Indian children; and (2) document the threshold antibody level required to prevent Hib colonization among HIV-infected children following immunization. METHODS: We conducted a prospective cohort study among HIV-infected children 2-15 years of age and HIV-uninfected children 2-5 years of age. HIV-infected children received two doses of HibCV and uninfected children received one. Serum anti-Hib PRP IgG antibodies were measured at baseline and two months after immunization in the HIV-infected children. Nasopharyngeal (NP) swabs were collected at baseline and follow-up. RESULTS: 125 HIV-infected and 44 uninfected children participated. 40% of HIV-infected children were receiving ART and 26% had a viral load >100,000 copies/mL. The geometric mean concentration of serum anti-Hib PRP antibody increased from 0.25 µg/mL at baseline to 2.65 µg/mL after two doses of HibCV, representing a 10.6-fold increase (p<0.0001). 76% percent of HIV-infected children mounted an immune response. Moderate or severe immune suppression, trimethoprim/sulfamethoxazole prophylaxis, and lower baseline antibody levels were associated with lower post-vaccine serum anti-Hib PRP IgG antibodies. A serum anti-Hib PRP IgG antibody level ≥ 3.3 µg/mL was protective against Hib NP colonization. There were no differences in adverse events between HIV-infected and uninfected children. CONCLUSION: Including a catch-up immunization schedule for older HIV infected children in countries introducing Hib vaccines is important. Older HIV-infected children with delayed access to ART and without suppressed viral loads mounted an adequate immune response following two doses of HibCV.

Risk factors for incomplete immunization in children with HIV infection.

OBJECTIVE: To document the immunization rates, factors associated with incomplete immunization, and missed opportunities for immunizations in children affected by HIV presenting for routine outpatient follow-up. METHODS: A cross-sectional study of immunization status of children affected by HIV presenting for routine outpatient care was conducted. RESULTS: Two hundred and six HIV affected children were enrolled. The median age of children in this cohort was 6 y. One hundred ninety seven of 206 children were HIV infected, nine were HIV exposed, but indeterminate. Fifty (25 %) children had incomplete immunizations per the Universal Immunization Program (UIP) of India. Hundred percent of children had received OPV. Ninety three percent of children got their UIP vaccines from a government clinic. Children with incomplete immunization were older, median age of 8 compared to 5 (p = 0.003). Each year of maternal education increased the odds of having a child with complete UIP immunizations by 1.18 (p = 0.008)-children of mothers with 6 y of education compared to those with no education were seven times more likely to have complete UIP vaccine status. The average number of visits to the clinic by an individual child in a year was 4. This represents 200 missed opportunities for immunizations. CONCLUSIONS: HIV infected children 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.

Associations between potential bacterial pathogens in the nasopharynx of HIV infected children.

OBJECTIVE: To investigate bacterial associations of S. pneumoniae, S. aureus, and H. influenzae in the nasopharynx of ambulatory children with HIV infection. METHODS: A cross-sectional nasopharyngeal swab survey of 148 children with HIV infection from West Bengal presenting for routine outpatient care was conducted. RESULTS: Forty-one (28 %) children carried S. pneumoniae, 35 (24 %) carried S. aureus and 39 (26 %) carried H. influenzae. Seventeen (11 %) had dual colonization with S. pneumoniae and H. influenzae, 13(8.8 %) had dual colonization with S. pneumoniae and S. aureus, and 6(4 %) had dual colonization with S. aureus and H. influenzae. Three (2 %) had triple carriage with H. influenzae, S. aureus, and S. pneumoniae. Neither Cotrimoxazole prophylaxis nor ART (antiretroviral therapy) affected colonization with any organism. There was no association between HIV immune status, recent antibiotic use, exposure to other children, household tuberculosis exposure and colonization with any organism. There was a strong negative association between malnutrition and colonization with H. influenzae. CONCLUSIONS: The negative association between S. pneumoniae and S. aureus colonization in the nasopharynx described in healthy populations was not present. The authors 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.

Developing nomogram to estimate birth weight from head circumference and mid-upper arm circumference.

BACKGROUND: Despite the huge proportion of the babies in the developing world being born low birthweight, only about half of the newborns are weighed at birth as weighing scales often tend to be either non-available or defective. OBJECTIVE: Designing a nomogram for estimation of birthweight from head circumference (HC) and mid-upper arm circumference (MUAC). METHOD: Birthweight, HC and MUAC of 500 newborns who were admitted in the baby nursery of Medical College and Hospital, Kolkata between July 2010 to December 2010 were measured. RESULTS: Multiple linear regression equation for prediction of birth weight from MUAC and HC was derived and a nomogram was constructed from the same. CONCLUSION: The birthweight estimation nomogram is an inexpensive and convenient tool for use in the community setting where weighing machines may not be always available and may thus allow prompt and early referral.

Food supplementation as an incentive to improve pre-antiretroviral therapy clinic adherence in HIV-positive children--experience from eastern India.

OBJECTIVE: To evaluate the importance of food supplementation as incentive in improving preantiretroviral therapy (pre-ART) adherence, and second its impact on health of HIV-infected children by a clinic-based observational study. METHODS: HIV-seropositive children aged between 2 and 12 years were followed-up sequentially for 2 years without and with food supplementation, respectively, with monitoring of disease parameters. The outcome morbidity parameters were compared and correlated. RESULT: Study showed significant improvement in clinic adherence (r = 0.165, p = 0.027) along with increased mean clinic visit (6.65 ± 1.43 vs. 8.01 ± 1.52, p = 0.000) and mean CD4 count (p = 0.028) with incentive. Provision of incentive correlated well (Pearson's r = 0.345) with number of visits which in turn had strong correlation with weight gain (r = 0.548), episodes of AIDS-defining illnesses (r = -0.412), hospitalization (r = -0.279). CONCLUSION: Food incentive could enhance pre-ART phase clinic adherence that decreases disease-related morbidities, setting the stage for improved treatment and care of seropositive children in future.

Successful outcome in a HIV infected child presenting with Pre-B Acute Lymphoblastic Leukemia.

The present case is a 5 y old child with Pre-B Acute Lymphoblastic Leukemia (ALL), presenting with fever, pallor, purpuric spots, hepato-splenomegaly and lymphadenopathy of 20 d duration. During re-induction chemotherapy, he developed atypical skin lesions diagnosed as Varicella Zoster infection. He and his parents tested positive for anti HIV antibody. He entered complete remission and Anti-retroviral therapy (ART) along with maintenance chemotherapy has been initiated 3 mon ago. Acute leukemia is rare in HIV and probably this is the first case of Pre-B Acute Leukemia in association with perinatally transmitted HIV.

Giant condyloma acuminata in pediatric HIV.

We report a 2 year 6 months old girl suffering from HIV infection and presenting with two giant condyloma acuminata of perianal and perivulvar region along with oral candidiasis.

High rates of colonization with drug resistant hemophilus influenzae type B and Streptococccus Pneumoniae in unvaccinated HIV infected children from West Bengal.

OBJECTIVE: To determine nasopharyngeal colonization rates of two vaccine preventable bacterial pathogens Hemophilus influenzae type b (Hib), and Streptococcus pneumoniae (Pneumococcus), antibiotic susceptibility of isolates, factors associated with their colonization, and immunization history in a cohort of HIV infected children. METHODS: The authors conducted a cross-sectional nasopharyngeal swab survey of 151 children affected with HIV presenting for routine outpatient care in West Bengal, India. RESULTS: 151 HIV affected children were enrolled. The median age was 6, 148/151 children were HIV positive, 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). Hib and pneumococcal isolates had high rates of resistance to tested antibiotics including TMP/SMX and third generation cephalosporins. Neither ART nor TMP/SMX prevented colonization. Children colonized with multidrug resistant isolates had high rates of exposure to TMP/SMX. CONCLUSIONS: HIV infection, late access to ART, high rates of colonization to resistant organisms and lack of access to vaccines makes this population vulnerable to invasive disease from Hib and pneumococcus.

Clinicoepidemiological scoring system for early diagnosis of pediatric HIV.

This pilot study was aimed at testing the feasibility of using a standardized questionnaire as a screening tool for detection of pediatric HIV at first contact. A prospective study was carried out on a cohort of 400 new patients attending the pediatric outdoor patient department in Medical College, Kolkata. After examining, the attending physician noted his clinical impression, filled the standardized questionnaire and scored each patient. ELISA test was performed. The results of the diagnostic tests were correlated with the clinical impression and the score. Taking a score of 9 as the cut-off, the sensitivity and specificity of the scoring system was 95.7% and 98.6% respectively. We conclude that this clinicoepidemiological scoring system may be used to screen children for HIV in resource-limited settings.

Oncogenic human papilloma virus and cervical pre-cancerous lesions in brothel-based sex workers in India.

A community-based cross-sectional study was conducted in brothel-based sex workers of West Bengal, Eastern India, to determine their oncogenic human papillomavirus (HPV) status and the presence of pre-cancerous lesions. A total of 229 sex workers from three districts of West Bengal participated in the study. All the study participants were interviewed with the aid of a pre-tested questionnaire to determine their sociodemographics, risk behaviour and risk perceptions after obtaining informed verbal consent. The interview was followed by collection of cervical cells from all participants using a disposable vaginal speculum and cervical cytobrush. Oncogenic HPV DNA was detected by real-time polymerase chain reaction (PCR). A simultaneous Papanicolaou test ('Pap smear') was performed to detect cervical cytological abnormalities. Overall, the prevalence of oncogenic HPV was found to be 25% (58/229) among the studied population. A subset (n=112) of the sample was tested separately to determine the existence and magnitude of HPV genotypes 16 and 18. The results showed that genotype 16 was prevalent in 10% (11/112), genotype 18 in 7% (8/112) and both genotype 16 and 18 in 7% (8/112). The HPV prevalence rate showed a decreasing trend with age, being 71.4% in the 10-19 years age group, 32.3% in the 20-29 years age group, 18.3% in the 30-39 years age group and 2.5% in the >or=40 years age group (statistically significant differences, P1 year, respectively. This difference was found to be statistically significant both by univariate and multivariate analysis. In this study, it was observed that sex workers with an average number of daily clients of six or more had an HPV prevalence of 67% (n=6), those with four to five clients had a prevalence of 45% (n=9), those with two to three clients had a prevalence of 30% (n=34) and those with one or less clients had a prevalence of 10% (n=9) (statistically significant differences, P=0.00003). Multivariate analysis showed a statistical association only with a duration of sex work of or=101 (OR=2.5; 95% CI 1.3-5). Regarding pre-cancerous lesions, 2 of 229 sex workers showed the presence of a low-grade squamous intraepithelial lesion along with high-risk HPV. Thus, 1% of the studied population suffer from a pre-cancerous lesion caused by high-risk HPV. This study concludes that young sex workers are particularly vulnerable to high-risk HPV, similar to human immunodeficiency virus (HIV). The observation of older sex workers relatively free from HPV supports the view of acquired immunity against HPV, which needs to be studied in-depth further. There is a need for a suitable community-based intervention programme targeted towards sex workers, with special reference to younger sex workers, for control and prevention of HPV and cervical cancer. Vaccination against HPV for newly entrant sex workers may be an important component for a successful intervention programme.