Shifting research priorities in maternal and child health in the COVID-19 pandemic era in India: A renewed focus on systems strengthening.

BACKGROUND: The remarkable progress seen in maternal and child health (MCH) in India over the past two decades has been impacted by the COVID-19 pandemic. We aimed to undertake a rapid assessment to identify key priorities for public health research in MCH in India within the context and aftermath of the COVID-19 pandemic. METHODS: A web-based survey was developed to identify top research priorities in MCH. It consisted of 26 questions on six broad domains: vaccine preventable diseases, outbreak preparedness, primary healthcare integration, maternal health, neonatal health, and infectious diseases. Key stakeholders were invited to participate between September and November 2020. Participants assigned importance on a 5-point Likert scale, and assigned overall ranks to each sub-domain research priority. Descriptive statistics were used to examine Likert scale responses, and a ranking analysis was done to obtain an "average ranking score" and identify the top research priority under each domain. RESULTS: Amongst the 84 respondents from across 15 Indian states, 37% were public-health researchers, 25% healthcare providers, 20% academic faculty and 13% were policy makers. Most respondents considered conducting systems strengthening research as extremely important. The highest ranked research priorities were strengthening the public sector workforce (vaccine preventable diseases), enhancing public-health surveillance networks (outbreak preparedness), nutrition support through community workers (primary care integration), encouraging at least 4-8 antenatal visits (maternal health), neonatal resuscitation to reduce birth asphyxia (neonatal health) and screening and treatment of tuberculosis (infectious diseases). Common themes identified through open-ended questions primarily included systems strengthening priorities across domains. CONCLUSIONS: The overall focus for research priorities in MCH in India during the COVID-19 pandemic is on strengthening existing services and service delivery, rather than novel research. Our results highlight pivotal steps within the roadmap for advancing and sustaining maternal and child health gains during the ongoing COVID-19 pandemic and beyond.

Association of nasopharyngeal viruses and pathogenic bacteria in children and their parents with and without HIV.

BACKGROUND: Bacteria and respiratory viruses co-occur in the nasopharynx, and their interactions may impact pathogenesis of invasive disease. Associations of viruses and bacteria in the nasopharynx may be affected by HIV. METHODS: We conducted a nested case-control study from a larger cohort study of banked nasopharyngeal swabs from families with and without HIV in West Bengal India, to look at the association of viruses and bacteria in the nasopharynx of parents and children when they are asymptomatic. Quantitative polymerase chain reaction for 4 bacteria and 21 respiratory viruses was run on 92 random nasopharyngeal swabs from children--49 from children living with HIV (CLH) and 43 from HIV uninfected children (HUC)-- and 77 swabs from their parents (44 parents of CLH and 33 parents of HUC). RESULTS: Bacteria was found in 67% of children, viruses in 45%, and both in 27% of child samples. Staphylococcus aureus (53%) was the most common bacteria, followed by Streptococcus pneumoniae (pneumococcus) (37%) in children and parents (53, 20%). Regardless of HIV status, viruses were detected in higher numbers (44%) in children than their parents (30%) (p = 0.049), particularly rhinovirus (p = 0.02). Human rhinovirus was the most frequently found virus in both CLH and HUC. Children with adenovirus were at six times increased risk of also having pneumococcus (Odds ratio OR 6, 95% CI 1.12-31.9) regardless of HIV status. In addition, the presence of rhinovirus in children was associated with increased pneumococcal density (Regression coeff 4.5, 1.14-7.9). In CLH the presence of rhinovirus increased the risk of pneumococcal colonization by nearly sixteen times (OR 15.6, 1.66-146.4), and, pneumococcus and S. aureus dual colonization by nearly nine times (OR 8.7). CONCLUSIONS: Children more frequently carried viruses regardless of HIV status. In CLH the presence of rhinovirus, the most frequently detected virus, significantly increased co-colonization with pneumococcus and S. aureus.

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.

Addressing Hand Hygiene Compliance in a Low-Resource Neonatal Intensive Care Unit: a Quality Improvement Project.

OBJECTIVE: Our goal for this study was to quantify healthcare provider compliance with hand hygiene protocols and develop a conceptual framework for increasing hand hygiene compliance in a low-resource neonatal intensive care unit. MATERIALS AND METHODS: We developed a 3-phase intervention that involved departmental discussion, audit, and follow-up action. A 4-month unobtrusive audit during night and day shifts was performed. The audit results were presented, and a conceptual framework of barriers to and solutions for increasing hand hygiene compliance was developed collectively. RESULTS: A total of 1308 hand hygiene opportunities were observed. Among 1227 planned patient contacts, hand-washing events (707 [58.6%]), hand rub events (442 [36%]), and missed hand hygiene (78 [6.4%]) events were observed. The missed hand hygiene rate was 20% during resuscitation. Missed hand hygiene opportunities occurred 3.2 times (95% confidence interval, 1.9-5.3 times) more often during resuscitation procedures than during planned contact and 6.14 times (95% confidence interval, 2.36-16.01 times) more often when providers moved between patients. Structural and process determinants of hand hygiene noncompliance were identified through a root-cause analysis in which all members of the neonatal intensive care unit team participated. The mean hand-washing duration was 40 seconds. In 83% of cases, drying hands after washing was neglected. Hand recontamination after hand-washing was seen in 77% of the cases. Washing up to elbow level was observed in 27% of hand-wash events. After departmental review of the study results, hand rubs were placed at each bassinet to address these missed opportunities. CONCLUSIONS: Hand hygiene was suboptimal during resuscitation procedures and between patient contacts. We developed a conceptual framework for improving hand hygiene through a root-cause analysis.

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.

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.

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.

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.

Isolation and sequencing of a novel tropomyosin isoform preferentially associated with colon cancer.

BACKGROUND & AIMS: Nonmuscle human tropomyosin (hTM) isoforms have distinct functions and may play important roles in various disease processes. METHODS: In an attempt to identify colon epithelial tropomyosin isoform, a complementary DNA library prepared from a human colon cancer cell line T84 was screened by an oligonucleotide probe complementary to messages of all known hTM isoforms. A novel clone called TC22 was obtained. The amino acid sequence of TC22 isoform is identical to isoform 5 (hTM5) apart from the C terminal domain, amino acids 222-247 coding the exon 9. RESULTS: Northern blot analysis showed that TC22 message is expressed in transformed epithelial cell lines and tumor tissues but not in normal epithelial cells. We developed a monoclonal antibody specific to TC22 isoform (TC22-4). By Western blot and immunoperoxidase assays, we analyzed 105 colonic specimens (fresh frozen and formalin fixed) from 96 patients with colon polyps (hyperplastic) or adenomas with or without dysplasia and cancer. Twenty-one of 22 (95%) of colon cancer specimens showed the presence of TC22, compared with only 1 of the 17 normal colon specimens and none of the 13 hyperplastic polyps (P < 0.0001). As assayed by immunoperoxidase staining, TC22 expression progressively increased in benign adenomatous polyps (35%) and polyps with mild and severe dysplasia (57% and 100%, respectively). CONCLUSIONS: We cloned and sequenced a novel hTM isoform, TC22, which is strongly associated with colonic neoplasia and carcinoma. TC22 may provide a useful biomarker for surveillance of colon cancer.