Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in four malaria endemic states of India.

BACKGROUND: Malaria is a major public health problem in India and accounts for about 88% of malaria burden in South-East Asia. India alone accounted for 2% of total malaria cases globally. Anti-malarial drug resistance is one of the major problems for malaria control and elimination programme. Artemether-lumefantrine (AL) is the first-line treatment of uncomplicated Plasmodium falciparum in north eastern states of India since 2013 after confirming the resistance against sulfadoxine-pyrimethamine. In the present study, therapeutic efficacy of artemether-lumefantrine and k13 polymorphism was assessed in uncomplicated P. falciparum malaria. METHODS: This study was conducted at four community health centres located in Koraput district of Odisha, Bastar district of Chhattisgarh, Balaghat district of Madhya Pradesh and Gondia district of Maharashtra state. Patients with uncomplicated P. falciparum malaria were administered with fixed dose combination (6 doses) of artemether-lumefantrine for 3 days and clinical and parasitological response was recorded up to 28 days as per World Health Organization protocol. Nucleotide sequencing of msp1 and msp2 gene was performed to differentiate between recrudescence and reinfection. Amplification and sequencing of k13 propeller gene region covering codon 450-680 was also carried out to identify the polymorphism. RESULTS: A total 376 malaria patients who fulfilled the enrolment criteria as well as consented for the study were enrolled. Total 356 patients were followed up successfully up to 28 days. Overall, the adequate clinical and parasitological response was 98.9% and 99.4% with and without PCR correction respectively. No case of early treatment failure was observed. However, four cases (1.1%) of late parasitological failure were found from the Bastar district of Chhattisgarh. Genotyping of msp1 and msp2 confirmed 2 cases each of recrudescence and reinfection, respectively. Mutation analysis of k13 propeller gene showed one non-synonymous mutation Q613H in one isolate from Bastar. CONCLUSIONS: The study results showed that artemether-lumefantrine is highly effective in the treatment of uncomplicated P. falciparum malaria among all age groups. No functional mutation in k13 was found in the study area. The data from this study will be helpful in implementation of artemether-lumefantrine in case of treatment failure by artesunate plus sulfadoxine-pyrimethamine.

HIV prevalence trend from HIV sentinel surveillance over a decade in India: An overview.

We aim to describe trends in antenatal HIV prevalence in India, at a national and regional level from consistent sentinel surveillance sites (2003-2015) among Antenatal Clinic (ANC) attendees. Data were analyzed from a total of 1,885,207 ANC attendees recruited at ANC sites. The consistent sites were grouped by years of initiation (Group 1: 2003-2005 and Group 2: 2006-2008) and according to six regions. Chi-square test for linear trend was applied to test the statistical significance of the trend. Nationally, at Group 1 sites, HIV prevalence was 0.93% in 2003, which declined to 0.36% in 2015 (P < 0.001). Similarly, at Group 2 sites, prevalence ranged from 0.25% to 0.23% during 2006-2015 (P > 0.05). The findings suggest that HIV is conclusively declining at old sites, nationally as well as in most of the other regions but increasing in the northern region. At newer sites, the conclusive declining trend is evident only in the southern region. National AIDS response must consider these variations to allow locally appropriate responses to the epidemic.

Sustained progress, but no room for complacency: Results of 2015 HIV estimations in India.

BACKGROUND & OBJECTIVES: Evidence-based planning has been the cornerstone of India's response to HIV/AIDS. Here we describe the process, method and tools used for generating the 2015 HIV estimates and provide a summary of the main results. METHODS: Spectrum software supported by the UNAIDS was used to produce HIV estimates for India as a whole and its States/Union Territories. This tool takes into consideration the size and HIV prevalence of defined population groups and programme data to estimate HIV prevalence, incidence and mortality over time as well as treatment needs. RESULTS: India's national adult prevalence of HIV was 0.26 per cent in 2015. Of the 2.1 million people living with HIV/AIDS, the largest numbers were in Andhra Pradesh, Maharashtra and Karnataka. New HIV infections were an estimated 86,000 in 2015, reflecting a decline by around 32 per cent from 2007. The declining trend in incidence was mirrored in most States, though an increasing trend was detected in Assam, Chandigarh, Chhattisgarh, Gujarat, Sikkim, Tripura and Uttar Pradesh. AIDS-related deaths were estimated to be 67,600 in 2015, reflecting a 54 per cent decline from 2007. There were variations in the rate and trend of decline across India for this indicator also. INTERPRETATION & CONCLUSIONS: While key indicators measured through Spectrum modelling confirm success of the National AIDS Control Programme, there is no room for complacency as rising incidence trends in some geographical areas and population pockets remain the cause of concern. Progress achieved so far in responding to HIV/AIDS needs to be sustained to end the HIV epidemic.

HIV care continuum among men who have sex with men and persons who inject drugs in India: barriers to successful engagement.

BACKGROUND: We characterize the human immunodeficiency virus (HIV) care continuum for men who have sex with men (MSM) and persons who inject drugs (PWID) across India. METHODS: We recruited 12 022 MSM and 14 481 PWID across 26 Indian cities, using respondent-driven sampling (September 2012 to December 2013). Participants were aged ≥18 years and either self-identified as male and reported sex with a man in the prior year (MSM) or reported injection drug use in the prior 2 years (PWID). Correlates of awareness of HIV-positive status were characterized using multilevel logistic regression. RESULTS: A total of 1146 MSM were HIV infected, of whom a median of 30% were aware of their HIV-positive status, 23% were linked to care, 22% were retained before antiretroviral therapy (ART), 16% had started ART, 16% were currently receiving ART, and 10% had suppressed viral loads. There was site variability (awareness range, 0%-90%; suppressed viral load range, 0%-58%). A total of 2906 PWID were HIV infected, of whom a median of 41% were aware, 36% were linked to care, 31% were retained before ART, 20% had started ART, 18% were currently receiving ART, and 15% had suppressed viral loads. Similar site variability was observed (awareness range: 2%-93%; suppressed viral load range: 0%-47%). Factors significantly associated with awareness were region, older age, being married (MSM) or female (PWID), use of other services (PWID), more lifetime sexual partners (MSM), and needle sharing (PWID). Ongoing injection drug use (PWID) and alcohol use (MSM) were associated with lower awareness. CONCLUSIONS: In this large sample, the major barrier to HIV care engagement was awareness of HIV-positive status. Efforts should focus on linking HIV testing to other essential services. CLINICAL TRIALS REGISTRATION: NCT01686750.

Effect of peer-led outreach activities on injecting risk behavior among male drug users in Haryana, India.

BACKGROUND: For the past two decades, there has been an enduring HIV epidemic among injecting drug users (IDUs) in India, and the Indian national AIDS control program (NACP) led by the National AIDS Control Organization (NACO) has kept IDUs at the forefront along with other key populations, in its efforts to prevent HIV. Given this, the objective of this study is to examine the association between IDUs' degree of exposure to peer-led education sessions (under NACP) and their needle sharing practices in Haryana, India. METHODS: The data for this study were drawn from a program monitoring system for the years 2009-2010 and 2010-2011. The relationship between IDUs' background characteristics/injecting practices and degree of exposure to the program was assessed using chi-square and Student's t tests. Generalized estimating equations (GEE) were used to examine changes in needle sharing practices over time by degree of exposure to peer-led education sessions. Further, the analysis was stratified by frequency of injecting drug use. All statistical analyses were conducted using STATA version 11. RESULTS: The proportion of IDUs who shared needles substantially decreased from 2009 to 2011, particularly among those who attended three or more peer-led education sessions (49% vs 11%, p < 0.001) in a month. Further, subgroup analysis by frequency of injecting drugs demonstrates that this decline was significant among IDUs who injected frequently (adjusted odds ratio = 0.6, 95% confidence interval = 0.3-0.9, p = 0.043). CONCLUSION: The study results indicate that repeated peer-led outreach sessions are more effective than exposure to a single education session. Hence, HIV prevention programs must promote repeated peer contacts with IDUs every month (at least two meetings) in order to promote safe injecting practices and behavior change.

Introduction of Triple-Drug Therapy for Accelerating Lymphatic Filariasis Elimination in India: Lessons Learned.

There are 670 million people at risk of contracting lymphatic filariasis (LF) in India, which bears 40% of the global burden of the disease. The National Program to Eliminate LF was launched in 2004 first with a single-drug therapy-diethylcarbamazine (DEC), followed by a two-drug therapy-DEC + albendazole (DA). In 2017, following successful drug trials, World Health Organization endorsed a new triple-drug therapy to fight LF using ivermectin with DEC and albendazole (IDA). 1 In June 2018, India made new commitments to accelerate their program to eliminate LF and initiated the new IDA protocol in five districts in the country. This article looks at the experience of India in the roll out of the new drug protocol and shares their preparations, successes, challenges, and lessons learned.

Adult and child malaria mortality in India: a nationally representative mortality survey.

BACKGROUND: National malaria death rates are difficult to assess because reliably diagnosed malaria is likely to be cured, and deaths in the community from undiagnosed malaria could be misattributed in retrospective enquiries to other febrile causes of death, or vice-versa. We aimed to estimate plausible ranges of malaria mortality in India, the most populous country where the disease remains common. METHODS: Full-time non-medical field workers interviewed families or other respondents about each of 122,000 deaths during 2001-03 in 6671 randomly selected areas of India, obtaining a half-page narrative plus answers to specific questions about the severity and course of any fevers. Each field report was sent to two of 130 trained physicians, who independently coded underlying causes, with discrepancies resolved either via anonymous reconciliation or adjudication. FINDINGS: Of all coded deaths at ages 1 month to 70 years, 2681 (3·6%) of 75,342 were attributed to malaria. Of these, 2419 (90%) were in rural areas and 2311 (86%) were not in any health-care facility. Death rates attributed to malaria correlated geographically with local malaria transmission ratesderived independently from the Indian malaria control programme. The adjudicated results show 205,000 malaria deaths per year in India before age 70 years (55,000 in early childhood, 30,000 at ages 5-14 years, 120,000 at ages 15-69 years); 1·8% cumulative probability of death from malaria before age 70 years. Plausible lower and upper bounds (on the basis of only the initial coding) were 125,000-277,000. Malaria accounted for a substantial minority of about 1·3 million unattended rural fever deaths attributed to infectious diseases in people younger than 70 years. INTERPRETATION: Despite uncertainty as to which unattended febrile deaths are from malaria, even the lower bound greatly exceeds the WHO estimate of only 15,000 malaria deaths per year in India (5000 early childhood, 10 000 thereafter). This low estimate should be reconsidered, as should the low WHO estimate of adult malaria deaths worldwide. FUNDING: US National Institutes of Health, Canadian Institute of Health Research, Li Ka Shing Knowledge Institute.

A nationally representative case-control study of smoking and death in India.

BACKGROUND: The nationwide effects of smoking on mortality in India have not been assessed reliably. METHODS: In a nationally representative sample of 1.1 million homes, we compared the prevalence of smoking among 33,000 deceased women and 41,000 deceased men (case subjects) with the prevalence of smoking among 35,000 living women and 43,000 living men (unmatched control subjects). Mortality risk ratios comparing smokers with nonsmokers were adjusted for age, educational level, and use of alcohol. RESULTS: About 5% of female control subjects and 37% of male control subjects between the ages of 30 and 69 years were smokers. In this age group, smoking was associated with an increased risk of death from any medical cause among both women (risk ratio, 2.0; 99% confidence interval [CI], 1.8 to 2.3) and men (risk ratio, 1.7; 99% CI, 1.6 to 1.8). Daily smoking of even a small amount of tobacco was associated with increased mortality. Excess deaths among smokers, as compared with nonsmokers, were chiefly from tuberculosis among both women (risk ratio, 3.0; 99% CI, 2.4 to 3.9) and men (risk ratio, 2.3; 99% CI, 2.1 to 2.6) and from respiratory, vascular, or neoplastic disease. Smoking was associated with a reduction in median survival of 8 years for women (99% CI, 5 to 11) and 6 years for men (99% CI, 5 to 7). If these associations are mainly causal, smoking in persons between the ages of 30 and 69 years is responsible for about 1 in 20 deaths of women and 1 in 5 deaths of men. In 2010, smoking will cause about 930,000 adult deaths in India; of the dead, about 70% (90,000 women and 580,000 men) will be between the ages of 30 and 69 years. Because of population growth, the absolute number of deaths in this age group is rising by about 3% per year. CONCLUSIONS: Smoking causes a large and growing number of premature deaths in India.

HIV, HSV-2 and syphilis among married couples in India: patterns of discordance and concordance.

OBJECTIVES: Differences in sexual networks probably explain the disparity in the scale of HIV epidemics in sub-Saharan Africa and India. HIV and sexually transmitted infection (STI) discordant couple studies provide insights into important aspects of these sexual networks. The authors quantify the role of male sexual behaviour in HIV transmission in married couples in India. METHODS: The authors analysed patterns of HIV and STI discordance in married couples from two community surveys in India: the National Family Health Study-3 for HIV-1 and the Centre for Global Health Research health check-up for HSV-2 and syphilis. A statistical model was used to estimate the fraction of infections introduced by each of the two partners. RESULTS: Only 0.8%, 16.0% and 3.5% of couples were infected (either partner or both) with HIV-1, HSV-2 and syphilis, respectively. A large proportion of infected couples were discordant (73.0%, 56.3% and 84.2% for HIV-1, HSV-2 and syphilis, respectively). This model estimated that, among couples with any STI, the male partner introduced the infection the majority of the time (HIV-1: 85.4%, HSV-2: 64.1%, syphilis: 75.0%). CONCLUSIONS: Male sexual activity outside of marriage appears to be a driving force for the Indian HIV/STI epidemic. Male client and female sex worker contacts should remain a primary target of the National AIDS Control Program in India.

Mental illnesses and related vulnerabilities in the Hijra community: A cross-sectional study from India.

PURPOSE: The Hijra community is a cultural and gender grouping in South Asia broadly similar to western transgender communities, but with literature suggesting some differences in gender experience and patterns of psychosocial adversity. The present study aims to describe patterns of mental illness and psychoactive substance use in Hijra subjects and study their association with gender experience and psychosocial adversity. METHODS: Fifty self-identified Hijras availing HIV-prevention services in New Delhi, India, were interviewed. Data on mental disorders, psychoactive substance use, quality of life, discrimination, empowerment, violence and gender identity were assessed using structured instruments. RESULTS: Subjects were mostly in their mid-twenties, and had joined the Hijra community in their mid-teens. More subjects (46%) were involved in begging than in traditional Hijra roles (38%). Sex work was reported by 28% subjects. The rates of lifetime mental illness was 38%, most commonly alcohol abuse (26%); others had anxiety or depressive disorders (8% each), somatoform disorders (6%) and bulimia nervosa (n = 1). Disempowerment was mostly experienced in domains of autonomy and community participation; 52% had experienced sexual or psychological violence. Discrimination was attributed to gender (100%), appearance (28%) or sexual orientation (28%). There were negative correlations between the physical domain of WHO-QOL and physical violence and depression scores; and between discrimination and WHO-QOL environmental, physical and psychological domains. CONCLUSIONS: This Hijra group showed high rates of mental disorder and substance involvement, related to QOL domains and experiences of discrimination and disempowerment.

Optimizing Village-Level Targeting of Active Case Detection to Support Visceral Leishmaniasis Elimination in India.

Background: India has made major progress in improving control of visceral leishmaniasis (VL) in recent years, in part through shortening the time infectious patients remain untreated. Active case detection decreases the time from VL onset to diagnosis and treatment, but requires substantial human resources. Targeting approaches are therefore essential to feasibility. Methods: We analyzed data from the Kala-azar Management Information System (KAMIS), using village-level VL cases over specific time intervals to predict risk in subsequent years. We also graphed the time between cases in villages and examined how these patterns track with village-level risk of additional cases across the range of cumulative village case-loads. Finally, we assessed the trade-off between ACD effort and yield. Results: In 2013, only 9.3% of all villages reported VL cases; this proportion shrank to 3.9% in 2019. Newly affected villages as a percentage of all affected villages decreased from 54.3% in 2014 to 23.5% in 2019, as more surveillance data accumulated and overall VL incidence declined. The risk of additional cases in a village increased with increasing cumulative incidence, reaching approximately 90% in villages with 12 cases and 100% in villages with 45 cases, but the vast majority of villages had small cumulative case numbers. The time-to-next-case decreased with increasing case-load. Using a 3-year window (2016-2018), a threshold of seven VL cases at the village level selects 329 villages and yields 23% of cases reported in 2019, while a threshold of three cases selects 1,241 villages and yields 46% of cases reported in 2019. Using a 6-year window increases both effort and yield. Conclusion: Decisions on targeting must consider the trade-off between number of villages targeted and yield and will depend upon the operational efficiencies of existing programs and the feasibility of specific ACD approaches. The maintenance of a sensitive, comprehensive VL surveillance system will be crucial to preventing future VL resurgence.

Learnings from two independent malaria elimination demonstration projects in India.

PROBLEM: India and sub-Saharan Africa contributes about 85% of the global malaria burden, and India is committed to eliminating malaria by 2030. APPROACH: Two novel initiatives-the Malaria Elimination Demonstration Project (MEDP) in Madhya Pradesh and Durgama Anchalare Malaria Nirakaran (DAMaN) in Odisha-were initiated independently to demonstrate that indigenous malaria can be eliminated in a short period of time. LOCAL SETTING: These initiatives focused on rural, tribal areas where there is a high malaria burden and complex epidemiology. RELEVANT CHANGES: The case management and vector control strategies used in these programmes were based on the national guidelines, with context-specific changes and introduction of accountability at management, operational, technical and financial levels. The MEDP achieved a 91% reduction in malaria cases and recorded zero transmission for 6 consecutive and a total of 9 mo. The DAMaN project brought about an 88% reduction in malaria cases. LESSONS LEARNED: Malaria elimination will require robust surveillance and case management, monitoring of vector control interventions, community-centric information education communication and behaviour change communication initiatives and management controls, as well as regular internal and external reviews.

Development and Evaluation of Active Case Detection Methods to Support Visceral Leishmaniasis Elimination in India.

As India moves toward the elimination of visceral leishmaniasis (VL) as a public health problem, comprehensive timely case detection has become increasingly important, in order to reduce the period of infectivity and control outbreaks. During the 2000s, localized research studies suggested that a large percentage of VL cases were never reported in government data. However, assessments conducted from 2013 to 2015 indicated that 85% or more of confirmed cases were eventually captured and reported in surveillance data, albeit with significant delays before diagnosis. Based on methods developed during these assessments, the CARE India team evolved new strategies for active case detection (ACD), applicable at large scale while being sufficiently effective in reducing time to diagnosis. Active case searches are triggered by the report of a confirmed VL case, and comprise two major search mechanisms: 1) case identification based on the index case's knowledge of other known VL cases and searches in nearby houses (snowballing); and 2) sustained contact over time with a range of private providers, both formal and informal. Simultaneously, house-to-house searches were conducted in 142 villages of 47 blocks during this period. We analyzed data from 5030 VL patients reported in Bihar from January 2018 through July 2019. Of these 3033 were detected passively and 1997 via ACD (15 (0.8%) via house-to-house and 1982 (99.2%) by light touch ACD methods). We constructed multinomial logistic regression models comparing time intervals to diagnosis (30-59, 60-89 and ≥90 days with <30 days as the referent). ACD and younger age were associated with shorter time to diagnosis, while male sex and HIV infection were associated with longer illness durations. The advantage of ACD over PCD was more marked for longer illness durations: the adjusted odds ratios for having illness durations of 30-59, 60-89 and >=90 days compared to the referent of <30 days for ACD vs PCD were 0.88, 0.56 and 0.42 respectively. These ACD strategies not only reduce time to diagnosis, and thus risk of transmission, but also ensure that there is a double check on the proportion of cases actually getting captured. Such a process can supplement passive case detection efforts that must go on, possibly perpetually, even after elimination as a public health problem is achieved.

The Summary Index of Malaria Surveillance (SIMS): a stable index of malaria within India.

BACKGROUND: Malaria in India has been difficult to measure. Mortality and morbidity are not comprehensively reported, impeding efforts to track changes in disease burden. However, a set of blood measures has been collected regularly by the National Malaria Control Program in most districts since 1958. METHODS: Here, we use principal components analysis to combine these measures into a single index, the Summary Index of Malaria Surveillance (SIMS), and then test its temporal and geographic stability using subsets of the data. RESULTS: The SIMS correlates positively with all its individual components and with external measures of mortality and morbidity. It is highly consistent and stable over time (1995-2005) and regions of India. It includes measures of both vivax and falciparum malaria, with vivax dominant at lower transmission levels and falciparum dominant at higher transmission levels, perhaps due to ecological specialization of the species. CONCLUSIONS: This measure should provide a useful tool for researchers looking to summarize geographic or temporal trends in malaria in India, and can be readily applied by administrators with no mathematical or scientific background. We include a spreadsheet that allows simple calculation of the index for researchers and local administrators. Similar principles are likely applicable worldwide, though further validation is needed before using the SIMS outside India.

Child mortality from solid-fuel use in India: a nationally-representative case-control study.

BACKGROUND: Most households in low and middle income countries, including in India, use solid fuels (coal/coke/lignite, firewood, dung, and crop residue) for cooking and heating. Such fuels increase child mortality, chiefly from acute respiratory infection. There are, however, few direct estimates of the impact of solid fuel on child mortality in India. METHODS: We compared household solid fuel use in 1998 between 6790 child deaths, from all causes, in the previous year and 609 601 living children living in 1.1 million nationally-representative homes in India. Analyses were stratified by child's gender, age (neonatal, post-neonatal, 1-4 years) and colder versus warmer states. We also examined the association of solid fuel to non-fatal pneumonias. RESULTS: Solid fuel use was very common (87% in households with child deaths and 77% in households with living children). After adjustment for demographic factors and living conditions, solid-fuel use significantly increase child deaths at ages 1-4 (prevalence ratio (PR) boys: 1.30, 95%CI 1.08-1.56; girls: 1.33, 95%CI 1.12-1.58). More girls than boys died from exposure to solid fuels. Solid fuel use was also associated with non-fatal pneumonia (boys: PR 1.54 95%CI 1.01-2.35; girls: PR 1.94 95%CI 1.13-3.33). CONCLUSIONS: Child mortality risks, from all causes, due to solid fuel exposure were lower than previously, but as exposure was common solid, fuel caused 6% of all deaths at ages 0-4, 20% of deaths at ages 1-4 or 128 000 child deaths in India in 2004. Solid fuel use has declined only modestly in the last decade. Aside from reducing exposure, complementary strategies such as immunization and treatment could also reduce child mortality from acute respiratory infections.

Rates, knowledge and risk factors of non-fatal opioid overdose among people who inject drugs in India: A community-based study.

INTRODUCTION AND AIMS: Non-fatal opioid overdose (NFOO) predicts future fatal opioid overdose and is associated with significant morbidity. There is limited literature on the rates and risk factors for NFOO in people who inject drugs (PWID) from India. We aimed to study the rates of NFOO and documented risk factors for NFOO, as well as knowledge-level of NFOO among PWID from India. DESIGN AND METHODS: Community-based, cross-sectional and observational study. We interviewed 104 adult male participants receiving HIV prevention services. Drug use patterns, rates of NFOO and opioid overdose risk factors, knowledge about opioid overdose and its management were assessed. RESULTS: The mean age of the participants was 27.9 years. The most common opioid used for injecting was heroin followed by buprenorphine. About 45% (n = 47) participants had experienced an opioid overdose at least once in their lifetime. Around 25% (n = 26) participants had overdosed in the past year, while 21% (n = 22) participants had overdosed within the past 3 months. The majority had risk factors that could predispose them to NFOO. No participant was aware of the use of naloxone for opioid overdose. DISCUSSION AND CONCLUSION: The rates of NFOO as well as risk factors for overdose among PWID from India are high, with poor knowledge on overdose management. There is urgent need for a program to prevent and manage opioid overdose among PWID in India.

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.

Survival of Children Living with Human Immunodeficiency Virus on Antiretroviral Therapy in Andhra Pradesh, India.

OBJECTIVE: To assess the survival probability and associated factors among children living with human immunodeficiency virus (CLHIV) receiving antiretroviral therapy (ART) in India. METHODS: The data on 5874 children (55% boys) from one of the high HIV burden states of India from the cohort were analyzed. Data were extracted from the computerized management information system of the National AIDS Control Organization (NACO). Children were eligible for inclusion if they had started ART during 2007-2013, and had at least one potential follow-up. Kaplan Meier survival and Cox proportional hazards models were used to measure survival probability. RESULTS: The baseline median (IQR) CD4 count at the start of antiretroviral therapy was 244 (153, 398). Overall, the mortality was 30 per 1000 child years; 39 in the <5 year age group and 25 in 5-9 year age group. Mortality was highest among infants (86 per 1000 child years). Those with CD4 count ≤ 200 were six times more likely to die (adjusted HR: 6.3, 95% CI 3.5, 11.4) as compared to those with a CD4 count of ≥350/mm3. CONCLUSION: Mortality rates among CLHIV is significantly higher among children less than five years when the CD4 count at the start of ART is above 200. Additionally, lower CD4 count, HIV clinical staging IV, and lack of functional status seems to be associated with high mortality in children who are on ART.

Low female[corrected]-to-male [corrected] sex ratio of children born in India: national survey of 1.1 million households.

BACKGROUND: Fewer girls than boys are born in India. Various hypotheses have been proposed to explain this low sex ratio. Our aim was to ascertain the contribution of prenatal sex determination and selective abortion as measured by previous birth sex. METHODS: We analysed data obtained for the Special Fertility and Mortality Survey undertaken in 1998. Ever-married women living in 1.1 million households in 6671 nationally-representative units were asked questions about their fertility history and children born in 1997. FINDINGS: For the 133 738 births studied for 1997, the adjusted sex ratio for the second birth when the preceding child was a girl was 759 per 1000 males (99% CI 731-787). The adjusted sex ratio for the third child was 719 (675-762) if the previous two children were girls. By contrast, adjusted sex ratios for second or third births if the previous children were boys were about equal (1102 and 1176, respectively). Mothers with grade 10 or higher education had a significantly lower adjusted sex ratio (683, 610-756) than did illiterate mothers (869, 820-917). Stillbirths and neonatal deaths were more commonly male, and the numbers of stillbirths were fewer than the numbers of missing births, suggesting that female infanticide does not account for the difference. INTERPRETATION: Prenatal sex determination followed by selective abortion of female fetuses is the most plausible explanation for the low sex ratio at birth in India. Women most clearly at risk are those who already have one or two female children. Based on conservative assumptions, the practice accounts for about 0.5 million missing female births yearly, translating over the past 2 decades into the abortion of some 10 million female fetuses.