Introduction of the pneumococcal conjugate vaccine in humanitarian and fragile contexts: Perspectives from stakeholders in four African countries.

Childhood pneumonia causes a significant burden of preventable child morbidity and mortality in Chad, Guinea, Somalia/Somaliland, and South Sudan. Leaders from these countries have committed to reducing this burden and are preparing to introduce the pneumococcal conjugate vaccine (PCV) into their immunization programs. To support long-term sustainability for expected PCV introductions in settings afflicted by prolonged humanitarian crises this research explores national stakeholders' perspectives on contextual factors that may influence optimal vaccine implementation. This qualitative study used purposive sampling to identify and interview stakeholders involved in vaccine decision-making. Interview transcripts were analyzed through the framework method, an approach involving charting data into pre-populated matrices. Findings from interviews with 16 key informants from government, partner organizations, and international health agencies fit within the following four overarching themes: (1) population-level vulnerabilities to pneumonia, exacerbated by climatic risks and low levels of maternal education; (2) disease burden and the interest in enhancing surveillance to monitor vaccine impact and integrate disease control efforts; (3) policy processes, including formalizing vaccine decision-making; and (4) vaccine implementation preparation, including the conduct of robust communication campaigns, training, and cold chain upgrades. This research explores perspectives from leaders in these countries which are at pivotal moments in their journeys toward introducing PCV. Widespread commitment among leaders, in addition to financial support, will facilitate vaccine introduction. Further, fostering a shared understanding among partners about context-specific determinants of program success will help build tailored implementation strategies for each country.

Understanding household-level risk factors for zero dose immunization in 82 low- and middle-income countries.

INTRODUCTION: In 2021, an estimated 18 million children did not receive a single dose of routine vaccinations and constitute the population known as zero dose children. There is growing momentum and investment in reaching zero dose children and addressing the gross inequity in the reach of immunization services. To effectively do so, there is an urgent need to characterize more deeply the population of zero dose children and the barriers they face in accessing routine immunization services. METHODS: We utilized the most recent DHS and MICS data spanning 2011 to 2020 from low, lower-middle, and upper-middle income countries. Zero dose status was defined as children aged 12-23 months who had not received any doses of BCG, DTP-containing, polio, and measles-containing vaccines. We estimated the prevalence of zero-dose children in the entire study sample, by country income level, and by region, and characterized the zero dose population by household-level factors. Multivariate logistic regressions were used to determine the household-level sociodemographic and health care access factors associated with zero dose immunization status. To pool multicountry data, we adjusted the original survey weights according to the country's population of children 12-23 months of age. To contextualize our findings, we utilized United Nations Population Division birth cohort data to estimate the study population as a proportion of the global and country income group populations. RESULTS: We included a total of 82 countries in our univariate analyses and 68 countries in our multivariate model. Overall, 7.5% of the study population were zero dose children. More than half (51.9%) of this population was concentrated in African countries. Zero dose children were predominantly situated in rural areas (75.8%) and in households in the lowest two wealth quintiles (62.7%) and were born to mothers who completed fewer than four antenatal care (ANC) visits (66.5%) and had home births (58.5%). Yet, surprisingly, a considerable proportion of zero dose children's mothers did receive appropriate care during pregnancy (33.5% of zero dose children have mothers who received at least 4 ANC visits). When controlled for other factors, children had three times the odds (OR = 3.00, 95% CI: 2.72, 3.30) of being zero dose if their mother had not received any tetanus injections, 2.46 times the odds (95% CI: 2.21, 2.74) of being zero dose if their mother had not received any ANC visits, and had nearly twice the odds (OR = 1.87, 95% CI: 1.70, 2.05) of being zero dose if their mother had a home delivery, compared to children of mothers who received at least 2 tetanus injections, received at least 4 ANC visits, and had a facility delivery, respectively. DISCUSSION: A lack of access to maternal health care was a strong risk factor of zero dose status and highlights important opportunities to improve the quality and integration of maternal and child health programs. Additionally, because a substantial proportion of zero dose children and their mothers do receive appropriate care, approaches to reach zero dose children should incorporate mitigating missed opportunities for vaccination.

Leveling the Research Playing Field: Decolonizing Global Health Research Through Web-Based Platforms.

Global health research has traditionally been rooted in colonialism, with some investigators in high-income countries leading and managing research and investigators in low- and middle-income countries serving as implementing partners. The Community Health Worker-Led Intervention for Vaccine Information and Confidence (CIVIC) Project, conducted in India and led jointly by India- and US-based investigators, leveraged web-based platforms to facilitate a more horizontal, inclusive, and balanced approach to partnerships between researchers and the community. Using web-based platforms to conduct research was found to be an effective strategy to engage researchers at all levels and combat systemic barriers associated with in-person activities such as power, economic, social, and gender dynamics. Connecting online for research meetings created a more equitable environment for community members to engage meaningfully with research. Further, by conducting research through web-based platforms, we found that we were able to strengthen the diversity of participants, provide a space for more marginalized groups to speak up, and minimize logistical barriers to attendance. Harnessing web-based approaches in research provides a pathway toward opportunities to promote equity and contribute to the decolonization of global health spaces.

Country ownership as a guiding principle for IA2030: A case study of the measles and rubella elimination programs in Nepal and Nigeria.

Country-owned, as opposed to donor-driven, is a principle within the development sector that recognizes the centrality of countries' leadership, systems, and resources in executing programs and achieving sustainable development. In alignment with this notion, the Immunization Agenda 2030 was developed with country ownership as one of four core principles of the ambitious ten-year plan. This means that the success of immunization programs, including those with eradication and elimination goals such as polio, measles, and rubella, and those with broader equity goals to "leave no one behind" on immunization, would be largely driven by country systems. In this paper we deconstruct country ownership into five operational principles: commitment, coordination, capacity, community participation, and accountability. Through this lens, we illustrate how two countries, Nepal and Nigeria, have exemplified country ownership in their measles and rubella elimination programs and we infer the ways in which country ownership drives system performance and sustains program efforts.

Why vaccines matter: understanding the broader health, economic, and child development benefits of routine vaccination.

The direct benefits of childhood vaccination in reducing the burden of disease morbidity and mortality in a cost-effective manner are well-established. By preventing episodes of vaccine-preventable diseases, vaccination can also help avert associated out-of-pocket medical expenses, healthcare provider costs, and losses in wages of patients and caregivers. Studies have associated vaccines positively with cognition and school attainment, suggesting benefits of long-term improved economic productivity. New evidence suggests that the measles vaccine may improve immunological memory and prevent co-infections, thereby forming a protective shield against other infections, and consequently improving health, cognition, schooling and productivity outcomes well into the adolescence and adulthood in low-income settings. Systematically documenting these broader health, economic, and child development benefits of vaccines is important from a policy perspective, not only in low and middle-income countries where the burden of vaccine-preventable diseases is high and public resources are constrained, but also in high-income settings where the emergence of vaccine hesitancy poses a threat to benefits gained from reducing vaccine-preventable diseases. In this paper, we provide a brief summary of the recent evidence on the benefits of vaccines, and discuss the policy implications of these findings.

National, regional, and state-level all-cause and cause-specific under-5 mortality in India in 2000-15: a systematic analysis with implications for the Sustainable Development Goals.

BACKGROUND: India had the largest number of under-5 deaths of all countries in 2015, with substantial subnational disparities. We estimated national and subnational all-cause and cause-specific mortality among children younger than 5 years annually in 2000-15 in India to understand progress made and to consider implications for achieving the Sustainable Development Goal (SDG) child survival targets. METHODS: We used a multicause model to estimate cause-specific mortality proportions in neonates and children aged 1-59 months at the state level, with causes of death grouped into pneumonia, diarrhoea, meningitis, injury, measles, congenital abnormalities, preterm birth complications, intrapartum-related events, and other causes. AIDS and malaria were estimated separately. The model was based on verbal autopsy studies representing more than 100 000 neonatal deaths globally and 16 962 deaths among children aged 1-59 months at the subnational level in India. By applying these proportions to all-cause deaths by state, we estimated cause-specific numbers of deaths and mortality rates at the state, regional, and national levels. FINDINGS: In 2015, there were 25·121 million livebirths in India and 1·201 million under-5 deaths (under-5 mortality rate 47·81 per 1000 livebirths). 0·696 million (57·9%) of these deaths occurred in neonates. There were disparities in child mortality across states (from 9·7 deaths [Goa] to 73·1 deaths [Assam] per 1000 livebirths) and regions (from 29·7 deaths [the south] to 63·8 deaths [the northeast] per 1000 livebirths). Overall, the leading causes of under-5 deaths were preterm birth complications (0·330 million [95% uncertainty range 0·279-0·367]; 27·5% of under-5 deaths), pneumonia (0·191 million [0·168-0·219]; 15·9%), and intrapartum-related events (0·139 million [0·116-0·165]; 11·6%), with cause-of-death distributions varying across states and regions. In states with very high under-5 mortality, infectious-disease-related causes (pneumonia and diarrhoea) were among the three leading causes, whereas the three leading causes were all non-communicable in states with very low mortality. Most states had a slower decline in neonatal mortality than in mortality among children aged 1-59 months. Ten major states must accelerate progress to achieve the SDG under-5 mortality target, while 17 are not on track to meet the neonatal mortality target. INTERPRETATION: Efforts to reduce vaccine-preventable deaths and to reduce geographical disparities should continue to maintain progress achieved in 2000-15. Enhanced policies and programmes are needed to accelerate mortality reduction in high-burden states and among neonates to achieve the SDG child survival targets in India by 2030. FUNDING: Bill & Melinda Gates Foundation.

National, regional, and state-level burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in India: modelled estimates for 2000-15.

BACKGROUND: India accounts for a disproportionate burden of global childhood illnesses. To inform policies and measure progress towards achieving child health targets, we estimated the annual national and state-specific childhood mortality and morbidity attributable to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) between 2000 and 2015. METHODS: In this modelling study, we used vaccine clinical trial data to estimate the proportion of pneumonia deaths attributable to pneumococcus and Hib. The proportion of meningitis deaths attributable to each pathogen was derived from pathogen-specific meningitis case fatality and bacterial meningitis case data from surveillance studies. We applied these proportions to modelled state-specific pneumonia and meningitis deaths from 2000 to 2015 prepared by the WHO Maternal and Child Epidemiology Estimation collaboration (WHO/MCEE) on the basis of verbal autopsy studies from India. The burden of clinical and severe pneumonia cases attributable to pneumococcus and Hib was ascertained with vaccine clinical trial data and state-specific all-cause pneumonia case estimates prepared by WHO/MCEE by use of risk factor prevalence data from India. Pathogen-specific meningitis cases were derived from state-level modelled pathogen-specific meningitis deaths and state-level meningitis case fatality estimates. Pneumococcal and Hib morbidity due to non-pneumonia, non-meningitis (NPNM) invasive syndromes were derived by applying the ratio of pathogen-specific NPNM cases to pathogen-specific meningitis cases to the state-level pathogen-specific meningitis cases. Mortality due to pathogen-specific NPNM was calculated with the ratio of pneumococcal and Hib meningitis case fatality to pneumococcal and Hib meningitis NPNM case fatality. Census data from India provided the population at risk. FINDINGS: Between 2000 and 2015, estimates of pneumococcal deaths in Indian children aged 1-59 months fell from 166 000 (uncertainty range [UR] 110 000-198 000) to 68 700 (44 600-86 000), while Hib deaths fell from 82 600 (52 300-112 000) to 15 600 (9800-21 500), representing a 58% (UR 22-78) decline in pneumococcal deaths and an 81% (59-91) decline in Hib deaths. In 2015, national mortality rates in children aged 1-59 months were 56 (UR 37-71) per 100 000 for pneumococcal infection and 13 (UR 8-18) per 100 000 for Hib. Uttar Pradesh (18 900 [UR 12 300-23 600]) and Bihar (8600 [5600-10 700]) had the highest numbers of pneumococcal deaths in 2015. Uttar Pradesh (9300 [UR 5900-12 700]) and Odisha (1100 [700-1500]) had the highest numbers of Hib deaths in 2015. Less conservative assumptions related to the proportion of pneumonia deaths attributable to pneumococcus indicate that as many as 118 000 (UR 69 000-140 000) total pneumococcal deaths could have occurred in 2015 in India. INTERPRETATION: Pneumococcal and Hib mortality have declined in children aged 1-59 months in India since 2000, even before nationwide implementation of conjugate vaccines. Introduction of the Hib vaccine in several states corresponded with a more rapid reduction in morbidity and mortality associated with Hib infection. Rapid scale-up and widespread use of the pneumococcal conjugate vaccine and sustained use of the Hib vaccine could help accelerate achievement of child survival targets in India. FUNDING: Bill & Melinda Gates Foundation.

Metabolic syndrome and cardiovascular disease risk assessment among human immunodeficiency virus-infected individuals on antiretroviral therapy.

BACKGROUND: The association of cardiovascular risk with first-line antiretroviral therapy (ART) in Indians has been a matter of concern with the background of a high risk in South Asians. AIMS: This study aimed to compare metabolic syndrome and its components, dyslipidemia, insulin resistance, and cardiovascular risk among patients on first-line ART (Group 1) with age-matched, ART-naïve human immunodeficiency virus (HIV)-infected patients (Group 2) and normal controls (Group 3). METHODS: Patients attending a tertiary care center in Mysore were enrolled in the study after obtaining informed consent and controls were chosen from relatives of patients. RESULTS: The total number of patients enrolled in the study was 217 (males 111; females 106), and the mean age of these patients was 34.1 ± 7.4 years. The number of patients in Group 1 (HIV+, ART experienced) was 76; in Group 2 (HIV+, ART naïve) was 71, and in Group 3 (HIV-) was 70. There was no statistically significant difference in the prevalence of metabolic syndrome between the three groups. On comparing the components of metabolic syndrome, serum triglycerides (mg/dl) were significantly higher in the ART group (Group 1: 149.5 [interquartile range (IQR): 84-187], Group 2: 108 [IQR: 74-152], and Group 3: 141.5 [IQR: 89-192]; P = 0.014) and serum high-density lipoprotein cholesterol was higher in HIV-uninfected individuals (Group 1: 37.5 ± 11.83, Group 2: 31.5 ± 12.23, and Group 3: 40.1 ± 12.09; P = 0.0002). There was no association between metabolic syndrome, duration of HIV, and type of first-line ART. Total and low-density lipoprotein (LDL) cholesterol were significantly higher in the ART group. Homeostatic model assessment and Framingham scores did not reveal any significant difference across the three groups. CONCLUSION: HIV-infected individuals on ART had higher levels of triglycerides, LDL, and total cholesterol, but no increased cardiovascular risk compared to other groups.

Can HIV reverse transcriptase activity assay be a low-cost alternative for viral load monitoring in resource-limited settings?

OBJECTIVE: To evaluate the performance and cost of an HIV reverse transcriptase-enzyme activity (HIV-RT) assay in comparison to an HIV-1 RNA assay for routine viral load monitoring in resource limited settings. DESIGN: A cohort-based longitudinal study. SETTING: Two antiretroviral therapy (ART) centres in Karnataka state, South India, providing treatment under the Indian AIDS control programme. PARTICIPANTS: A cohort of 327 HIV-1-infected Indian adult patients initiating first-line ART. OUTCOME MEASURES: Performance and cost of an HIV-RT assay (ExaVir Load V3) in comparison to a gold standard HIV-1 RNA assay (Abbott m2000rt) in a cohort of 327 Indian patients before (WK00) and 4 weeks (WK04) after initiation of first-line therapy. RESULTS: Plasma viral load was determined by an HIV-1 RNA assay and an HIV-RT assay in 629 samples (302 paired samples and 25 single time point samples at WK00) obtained from 327 patients. Overall, a strong correlation of r=0.96 was observed, with good correlation at WK00 (r=0.84) and at WK04 (r=0.77). Bland-Altman analysis of all samples showed a good level of agreement with a mean difference (bias) of 0.22 log10copies/mL. The performance of ExaVir Load V3 was not negatively affected by a nevirapine/efavirenz based antiretroviral regimen. The per test cost of measuring plasma viral load by the Abbott m2000rt and ExaVir Load V3 assays in a basic lab setting was $36.4 and $16.8, respectively. CONCLUSIONS: The strong correlation between the HIV-RT and HIV-1 RNA assays suggests that the HIV-RT assay can be an affordable alternative option for monitoring patients on antiretroviral therapy in resource-limited settings. TRIAL REGISTRATION NUMBER: ISRCTN79261738.

Pharmacy-based dispensing of antimicrobial agents without prescription in India: appropriateness and cost burden in the private sector.

BACKGROUND: Inappropriate antibiotic use for treatment of common self-limiting infections is a major problem worldwide. We conducted this study to determine prevalence of non-prescription sale of antimicrobial drugs by pharmacies in Bangalore, India, and to assess their associated avoidable cost within the Indian private healthcare sector. METHODS: Between 2013 and 2014, two researchers visited 261 pharmacies with simulated clinical scenarios; upper respiratory tract infection in an adult and acute gastroenteritis in a child. Using a pre-defined algorithm, the researchers recorded questions asked by the pharmacist, details of medicines dispensed, and instructions regarding drug allergies, dose and side effects. RESULTS: Antimicrobial drugs were obtained without prescription from 174 of 261 (66.7 %) pharmacies visited. Instructions regarding dose of these drugs were given by only 58.0 % pharmacies. Only 18.4 % (16/87) of non-antimicrobial-dispensing pharmacies cited the need for a prescription by a medical practitioner. None gave advice on potential side effects or possible drug allergies. In the upper respiratory infection simulation, 82 (71.3 %) of the 115 pharmacies approached dispensed antimicrobials without a prescription. The most common antimicrobial drug prescribed was amoxicillin (51.2 %), followed by azithromycin and ciprofloxacin (12.2 % each). Among 146 pharmacies where acute gastroenteritis was simulated, 92 (63.0 %) dispensed antimicrobials. Common ones were fluoroquinolones (66.3 %), particularly norfloxacin in combination with metronidazole. Standard treatment for diarrhea such as oral rehydration solution and zinc was prescribed by only 18 of 146 (12.3 %) pharmacies. Assuming the average cost of a 5-day course of common antimicrobials in India is $1.93, with 2.5 and 2.1 annual episodes of adult upper respiratory and childhood gastrointestinal infections respectively, and with 30-45 % of the population of 1.3 billion visiting pharmacies, the estimated cost of unnecessary antimicrobial drugs dispensed by pharmacies in India would range from $1.1 to 1.7 billion. CONCLUSIONS: The study shows that dispensing of antimicrobial drugs without prescription by pharmacies in the private sector in India within an urban setting was unacceptably high, thus placing a high burden on healthcare expenditure. There is an urgent need to institute measures to curb unnecessary antimicrobial usage in India, address market incentives and involve pharmacists as partners for creating awareness among communities.

Mobile phones to support adherence to antiretroviral therapy: what would it cost the Indian National AIDS Control Programme?

INTRODUCTION: Adherence to antiretroviral treatment (ART) is critical to maintaining health and good clinical outcomes in people living with HIV/AIDS. To address poor treatment adherence, low-cost interventions using mobile communication technology are being studied. While there are some studies that show an effect of mobile phone reminders on adherence to ART, none has reported on the costs of such reminders for national AIDS programmes. This paper aims to study the costs of mobile phone reminder strategies (mHealth interventions) to support adherence in the context of India's National AIDS Control Program (NACP). METHODS: The study was undertaken at two tertiary level teaching hospitals that implement the NACP in Karnataka state, South India. Costs for a mobile phone reminder application to support adherence, implemented at these sites (i.e. weekly calls, messages or both) were studied. Costs were collected based on the concept of avoidable costs specific to the application. The costs that were assessed were one-time costs and recurrent costs that included fixed and variable costs. A sequential procedure for costing was used. Costs were calculated at national-programme level, individual ART-centre level and individual patient level from the NACP's perspective. The assessed costs were pooled to obtain an annual cost per patient. The type of application, number of ART centres and number of patients on ART were varied in a sensitivity analysis of costs. RESULTS: The Indian NACP would incur a cost of between 79 and 110 INR (USD 1.27-1.77) per patient per year, based on the type of reminder, the number of patients on ART and the number of functioning ART centres. The total programme costs for a scale-up of the mHealth intervention to reach the one million patients expected to be on treatment by 2017 is estimated to be 0.36% of the total five-year national-programme budget. CONCLUSIONS: The cost of the mHealth intervention for ART-adherence support in the context of the Indian NACP is low and is facilitated by the low cost of mobile communication in the country. Extending the use of mobile communication applications beyond adherence support under the national programme could be done relatively inexpensively.

Dried blood spot HIV-1 RNA quantification: a useful tool for viral load monitoring among HIV-infected individuals in India.

BACKGROUND & OBJECTIVES: Monitoring of HIV-infected individuals on antiretroviral treatment (ART) ideally requires periodic viral load measurements to ascertain adequate response to treatment. While plasma viral load monitoring is widely available in high-income settings, it is rarely used in resource-limited regions because of high cost and need for sophisticated sample transport. Dried blood spot (DBS) as source specimens for viral load measurement has shown promise as an alternative to plasma specimens and is likely to be a useful tool for Indian settings. The present study was undertaken to investigate the performance of DBS in HIV-1 RNA quantification against the standard plasma viral load assay. METHODS: Between April-June 2011, 130 samples were collected from HIV-1-infected (n=125) and non-infected (n=5) individuals in two district clinics in southern India. HIV-1 RNA quantification was performed from DBS and plasma using Abbott m2000rt system after manual RNA extraction. Statistical analysis included correlation, regression and Bland-Altman analysis. RESULTS: The sensitivity of DBS viral load was 97 per cent with viral loads >3.0 log 10 copies/ml. Measurable viral load (>3.0 log 10 copies/ml) results obtained for the 74 paired plasma-DBS samples showed positive correlation between both the assays (r=0.96). For clinically acceptable viral load threshold values of >5,000 copies/ml, Bland-Altman plots showed acceptable limits of agreement (-0.21 to +0.8 log 10 copies/ml). The mean difference was 0.29 log 10 copies/ml. The cost of DBS was $2.67 lower compared to conventional plasma viral load measurement in the setting. INTERPRETATION & CONCLUSIONS: The significant positive correlation with standard plasma-based assay and lower cost of DBS viral load monitoring suggest that DBS sampling can be a feasible and economical means of viral load monitoring in HIV-infected individual in India and in other resource-limited settings globally.

Determinants of anemia among young children in rural India.

OBJECTIVE: More than 75% of Indian toddlers are anemic. Data on factors associated with anemia in India are limited. The objective of this study was to determine biological, nutritional, and socioeconomic risk factors for anemia in this vulnerable age group. METHODS: We conducted a cross-sectional study of children aged 12 to 23 months in 2 rural districts of Karnataka, India. Children were excluded if they were unwell or had received a blood transfusion. Hemoglobin, ferritin, folate, vitamin B(12), retinol-binding protein, and C-reactive protein (CRP) levels were determined. Children were also tested for hemoglobinopathy, malaria infection, and hookworm infestation. Anthropometric measurements, nutritional intake, family wealth, and food security were recorded. In addition, maternal hemoglobin level was measured. RESULTS: Anemia (hemoglobin level < 11.0 g/dL) was detected in 75.3% of the 401 children sampled. Anemia was associated with iron deficiency (low ferritin level), maternal anemia, and food insecurity. Children's ferritin levels were directly associated with their iron intake and CRP levels and with maternal hemoglobin level and inversely associated with continued breastfeeding and the child's energy intake. A multivariate model for the child's hemoglobin level revealed associations with log(ferritin level) (coefficient: 1.20; P < .001), folate level (0.05; P < .01), maternal hemoglobin level (0.16; P < .001), family wealth index (0.02; P < .05), child's age (0.05 per month; P < .005), hemoglobinopathy (-1.51; P < .001), CRP level (-0.18; P < .001), and male gender (-0.38; P < .05). Wealth index and food insecurity could be interchanged in this model. CONCLUSIONS: Hemoglobin level was primarily associated with iron status in these Indian toddlers; however, maternal hemoglobin level, family wealth, and food insecurity were also important factors. Strategies for minimizing childhood anemia must include optimized iron intake but should simultaneously address maternal anemia, poverty, and food insecurity.