Determinants of vaccine uptake in HIV-affected families from West Bengal.

Children living with Human Immunodeficiency virus (HIV; CLH) have special vaccine needs. Determinants of household-level uptake of vaccines need to be examined in high-risk families with CLH. We previously conducted a study on the impact of Haemophilus influenzae type b conjugate vaccine and pneumococcal conjugate vaccine (PCV-13) in 125 HIV-affected families and 47 HIV-unaffected families in West Bengal. We then interviewed 99 of these 172 families who had participated in the study to understand the household-level factors that determine vaccine uptake. Sixty-four of the 99 families had one or more CLH. Within these 64 families, 30% of CLH had missed vaccines under the universal immunization program (UIP), compared to only 6% of HIV-uninfected children (HUC) (p = .001). Maternal HIV positivity in a family increased risk of missing UIP vaccines nearly five times (4.82, p = .001). Almost all families accessed UIP vaccines at local primary vaccination centers, but 14% of families experienced stigma due to HIV and avoided getting one or more vaccine doses. In contrast, in our study, 100% of HIV-affected families actively sought PCV-13 and HibCV, despite having to travel. Factors that influenced uptake included awareness generation and activation by an outreach worker and availability of vaccines on pick-up days for anti-retroviral therapy. Eighty-six percent of families strongly recommended PCV-13 to other families. To conclude, while we found that CLH have barriers to getting vaccinations, a program designed to take into consideration the obstacles that HIV-affected families face showed a high rate of vaccine uptake.

Impact of pneumococcal conjugate vaccine on the carriage density of Streptococcus pneumoniae and Staphylococcus aureus in children living with HIV: a nested case-control study.

Nasopharyngeal colonization density of Streptococcus pneumoniae (pneumococcus) is associated with disease severity and transmission. Little is known about the density of pneumococcal carriage in children with HIV (CLH). Pneumococcal vaccines may impact the density of pneumococcus and competing microbes within the nasopharynx. We examined the impact of one dose of PCV13 on carriage density of pneumococcus and Staphylococcus aureus, in CLH, HIV-uninfected children (HUC), and their unvaccinated parents. We conducted a pilot-nested case-control study, within a larger prospective cohort study, on the impact of PCV13, in families in West Bengal India. Quantitative real-time PCR was run on 147 nasopharyngeal swabs from 27 CLH and 23 HUC, and their parents, before and after PCV13 immunization. CLH had higher median pneumococcal carriage density, compared to HUC: 6.28 × 108 copies/mL vs. 2.11 × 105 copies/mL (p = .005). Following one dose of PCV13, pneumococcal densities dropped in both groups, with an increase in S. aureus carriage to 80% from 48% in CLH, and to 60% in HUC from 25%. While limited in sample size, this pilot study shows that CLH carried higher densities of pneumococcus. PCV13 was associated with a decrease in pneumococcal density and a temporal increase in S. aureus carriage regardless of HIV status.

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.

Immediate access to antiretroviral therapy is important in children living with HIV.

This article reviews a case of a child with perinatal HIV followed for 30 months during a prospective cohort study on pneumonia prevention in HIV-infected children. The point of this case report is to illustrate how delayed access to antiretroviral therapy (ART) in HIV-infected children impacts immunization response and growth. Given the WHO's early release guideline changes on ART recommendations and the expected full revised guidelines coming out this year, this article is a timely discussion on the need for access to ART for HIV infected Indian children regardless of CD4 count.

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.

Oocyte quality reflected by follicular fluid analysis in poly cystic ovary syndrome (PCOS): a hypothesis based on intermediates of energy metabolism.

There is no clear acceptance of specific follicular fluid biomarker and its correlation with oocyte quality or related embryo variable till now. Most of the studies analyze correlation between certain biomolecules and the oocyte quality using single variable, instead of multivariate analysis algorithms. Our hypothesis is not based on single biomarker discovery, but attempts to explain oocyte quality in terms of energy metabolic pathways by considering its various intermediates. Reduced availability of glucose in the oocytes and follicular cells caused by defective transportation of glucose is expected in polycystic ovary syndrome (PCOS). This initiates alternative pathways to utilize fatty acid, amino acids etc. for energy as a compensatory mechanism to deal with the energy requirement. These compensations can be reflected by altered levels of various biomolecules in follicular fluid (e.g. ketone bodies, lipids, amino acids, lactate, pyruvate etc.). The amount of compensation, in order to meet the energy requirement can be directly correlated to quality of oocytes and better outcome after in vitro fertilization (IVF) in PCOS cases. This can be predicted with fair accuracy by doing a multivariate analysis of altered levels of various biomolecules in follicular fluid. Various supervised and unsupervised classification techniques based on spectroscopic data, obtained from follicular fluid samples may certainly prove to be an important tool to predict oocytes quality and IVF outcome with better accuracy in women with PCOS.

Surface EMG analysis and changes in gait following electrical stimulation of quadriceps femoris and tibialis anterior in children with spastic cerebral palsy.

PURPOSE: To evaluate the clinical feasibility and effect of neuromuscular electrical stimulation (NMES) therapy of quadriceps femoris (QF) and tibialis anterior (TA) muscles on improving gait and functional outcomes in children with spastic cerebral palsy (CP). METHOD: Ten children with spastic diplegic/hemiplegic CP who were in the age group of 7 to 14 years recruited from a rehabilitation institute were randomly assigned either to a control group or a NMES group. Both groups obtained conventional physiotherapy and muscle strengthening exercises. The NMES group in addition received surface electrical stimulation to QF and TA muscles for four weeks duration. RESULTS: The NMES group showed significant improvements as compared to the control group in walking speed (mean difference: 7.83 meters per min, 95% confidence interval: 3.13 to 12.53, p<0.01) and cadence (mean difference: 23.33 steps per min, 95% confidence interval: 5.90 to 40.77, p<0.01). The NMES group also showed significant reduction in physiological cost index of walking or PCI (mean difference: -1.32 beats per meter, 95% confidence interval: -1.83 to -0.80, p<0.001) indicating greater energy-efficiency of walking. No significant changes were seen in EMG parameters. CONCLUSIONS: The findings of this study suggests that NMES therapy together with conventional physiotherapy more efficiently improves walking ability and functional outcomes as compared to conventional physiotherapy alone in children with spastic CP.

Isoniazid preventive therapy programmes for healthcare workers in India: translating evidence into policy.

BACKGROUND: Occupational tuberculosis (TB) among healthcare workers (HCWs) is an important public health issue, especially in India where HCWs are exposed to a high burden of TB and infrastructural infection control procedures are inadequate. We examined the need for implementing isoniazid preventive therapy (IPT) programmes to protect Indian HCWs from occupational TB. METHODS: Bardach's 8-fold path was followed to analyse and formulate the policy for introducing IPT programmes for HCWs in India. The results of surveillance with tuberculin skin testing (TST) and treatment of latent TB infection with isoniazid (INH) for HCWs belonging to two different age groups (< or = 30 years and > 30 years) were compared with each other and with the alternative of maintaining status quo, i.e. no surveillance and no therapy, under various parameters such as the lifetime risks of active TB, deaths due to TB, benefit-risk ratios, cost-savings to the health system and relative risk reductions. RESULTS; The lifetime risk of TB was found to be higher among HCWs in the age group of < or = 30 years. IPT for HCWs reduced the lifetime risks of TB and death due to TB in both age groups, with better results in the age group of < or = 30 years. The relative lifetime risk reduction of active TB was 24.04% for the age group of < or = 30 years and 19.92% for the age group of > 30 years. The relative lifetime risk reduction of death due to TB by administration of IPT was from 13.96% to 19.62% in the two age groups. The benefit-risk ratio of IPT was 11.24 for the age group of < or = 30 years and 2.88 for the age group of > 30 years. IPT was associated with an approximate savings of rupee 4000-8000 for each case prevented. CONCLUSION: TB is a major occupational hazard for Indian HCWs. The inclusion of IPT programmes in the national policy to combat TB, along with infrastructural infection control measures, can contribute to reduction in workplace TB. IPT programmes for HCWs in the younger age group have better results in terms of prevention of active TB, TB-related mortality and INH-induced hepatitis as compared to the older age group. There is an urgent need for a mechanism of targeted testing and treatment of latent TB infection to minimize the risk of occupational exposure for TB among HCWs in all age groups.