Comparison of prevention of parent-to-child HIV transmission programme & national biennial HIV sentinel surveillance data for tracking HIV epidemic in India

Background & objectives: HIV sentinel surveillance (HSS) among antenatal women in India has been used to track the epidemic for many years. However, reliable tracking at the local level is not possible as ANC sentinel sites are limited in number and cover a smaller sample size at each site. Prevention of parent-to-child-transmission (PPTCT) programme data has a potential advantage due to better geographical coverage, which could provide more precise HIV case estimates; therefore, we compared HSS ANC data with PPTCT programme data for HIV tracking. Methods: Out of the 499 surveillance sites, where HSS and PPTCT programme was being conducted in 2015, 210 sites (140 urban and 70 rural) were selected using a stratified random sampling method. HSS (n=72,981) and PPTCT (n=112,832) data records were linked confidentially. The sociodemographic characteristics of HSS and PPTCT attendees were compared. HIV prevalence from HSS ANC was compared with the PPTCT programme data using Chi-square test. State- and site-level correlation of HIV prevalence was also done. Concordance between HSS and PPTCT HIV positivity was estimated using kappa statistics. Results: The age distribution of HSS and PPTCT attendees was similar (range: 23 to 27 yr); however, HSS ANC participants were better educated, whereas PPTCT recorded a higher proportion of homemakers. The correlation of HIV prevalence between HSS and PPTCT was high (r=0.9) at the State level and moderate at the site level (r=0.7). The HIV positivity agreement between HSS ANC and PPTCT was good (kappa=0.633). A similar prevalence was reported across 26 States, whereas PPTCT had a significantly lower prevalence than HSS in three States where PPTCT coverage was low. Overall HIV prevalence was 0.31 per cent in HSS and 0.22 per cent in PPTCT (P<0.001). Interpretation & conclusions: High-quality PPTCT programme data can provide reliable HIV trends in India. An operational framework for PPTCT-based surveillance should be pilot-tested in a phased manner before replacing HSS with PPTCT.

Preparedness of primary & secondary care health facilities for the management of non-communicable diseases in tribal population across 12 districts in India

Background and objectives: Non-communicable diseases (NCDs) are highly prevalent in the tribal populations; however, there are limited data regarding health system preparedness to tackle NCDs among these populations. We estimated the availability of human resources, equipment, drugs, services and knowledge of doctors for NCD management in the selected tribal districts in India. Methods: A cross-sectional survey was conducted in 12 districts (one from each State) with at least 50 per cent tribal population in Andaman and Nicobar Islands, Himachal Pradesh, Madhya Pradesh, Odisha and eight northeastern States. Primary health centres (PHCs), community health centres (CHCs) and district/sub-district hospitals (DHs) were surveyed and data on screening and treatment services, human resources, equipment, drugs and information systems indicators were collected and analysed. The data were presented as proportions.Results: In the present study 177 facilities were surveyed, including 156 PHCs/CHCs and 21 DHs. DHs and the majority (82-96%) of the PHCs/CHCs provided outpatient treatment for diabetes and hypertension. Overall, 97 per cent of PHCs/CHCs had doctors, and 78 per cent had staff nurses. The availability of digital blood pressure monitors ranged from 35 to 43 per cent, and drugs were either not available or inadequate. Among 213 doctors, three-fourths knew the correct criteria for hypertension diagnosis, and a few correctly reported diabetes diagnosis criteria. Interpretation & conclusions: The results of this study suggest that the health system of the studied tribal districts was not adequately prepared to manage NCDs. The key challenges included inadequately trained workforce and a lack of equipment and drugs. It is suggested that capacity building and, procurement and distribution of equipment, drugs and information systems to track NCD patients should be the key focus areas of national programmes

Non-communicable diseases as a major contributor to deaths in 12 tribal districts in India

Background & objectives: Non-communicable diseases (NCDs) are the leading cause of death in India. Although studies have reported a high prevalence of NCD in tribal populations, there are limited data pertaining mortality due to NCDs. Therefore, in this study we estimated the proportion of deaths due to NCDs among 15 yr and older age group in tribal districts in India. Methods: We conducted a community-based survey in 12 districts (one per State) with more than 50 per cent tribal population. Data were collected using a verbal autopsy tool from the family member of the deceased. The estimated sample size was 452 deaths per district. We obtained the list of deaths for the reference period of one year and updated it during the survey. The cause of death was assigned using the International Classification of Diseases-10 classification and analyzed the proportions of causes of death. The age-standardized death rate (ASRD) was also estimated. Results: We surveyed 5292 deaths among those above 15 years of age. Overall, NCDs accounted for 66 per cent of the deaths, followed by infectious diseases (15%) and injuries (11%). Cardiovascular diseases were the leading cause of death in 10 of the 12 sites. In East Garo Hills (18%) and Lunglei (26%), neoplasms were the leading cause of death. ASRD due to NCD ranged from 426 in Kinnaur to 756 per 100,000 in East Garo Hills. Interpretation & conclusions: The findings of this community-based survey suggested that NCDs were the leading cause of death among the tribal populations in India. It is hence suggested that control of NCDs should be one of the public health priorities for tribal districts in India.

Injecting drug use & HIV prevalence among female sex workers: Evidence from the National Integrated Biological & Behavioural Surveillance, India

Background & objectives: Female sex workers (FSWs) who inject drugs (FSW-IDs) have a higher risk of HIV infection and transmission. Understanding the socio-demographic characteristics and other risk behaviours among FSW-IDs will help in strengthening targeted interventions for HIV prevention and management. In the present study, the HIV prevalence, associated socio-demographic characteristics and risk behaviours among FSWs who injected drugs (FSW-IDs) and those who did not ID (FSW-NIDs) was determined in India. Methods: The national cross-sectional, community-based, integrated biological and behavioural surveillance was conducted in 2014-2015 at 73 randomly selected FSW domains across 28 States and Union Territories in India. The sample size was fixed at 400 for each domain, and a probability-based sampling method was followed. The data were analyzed by logistic regression methods. Results: Data from 27,007 FSWs were included in the analysis, of which 802 (3%) were FSW-IDs. HIV prevalence among FSW-IDs was significantly higher than that in FSW-NIDs (4.5 vs. 1.9%). Univariate analysis showed that factors significantly associated with higher HIV prevalence among FSW-IDs were older age, sex work as the only source of income, dissolved marriage, living with a sex worker, urban locality of sex work and consumption of alcohol or oral drugs. In multivariable analysis, factors such as older age of FSW-IDs (35 yr and above), having a dissolved marriage and sex work being the only source of income were observed to be independently and significantly associated with higher HIV prevalence. Interpretation & conclusions: Scaling up the HIV preventive interventions for FSW-IDs, such as facilitating awareness and improved access to needle and syringe exchange programme (NSEP) and opioid substitution therapy (OST), encouraging safe sex and injecting practices, educating on the harmful effects of alcohol and drugs and providing alternative vocation options to secure their financial needs are several strategies that may reduce HIV transmission among FSWs.

Interpretation of Rotavirus-positivity Patterns Across India.

bjective: To analyze variation in rotavirus-positivity using simple alternative statistical measures. Methods: Hospital-based rotavirus surveillance among children admitted with acute gastroenteritis between 2005 and 2009. Prevalence, adjusted proportions and symmetrized index were calculated. Results: Rotavirus prevalence was 40% (range 37% - 44%). Adjusted proportion analysis revealed higher level of deviation from annual prevalence in seasons (December – February and September – November); age groups (<12 months and 12-23 months) and regions (East and South). Analysis of symmetrized index revealed higher estimates of variation in all years, except in 2006. Conclusion: Proposed statistical measures are useful as refined measures to study extent of disease spread in surveillance programmes, aiding evaluation of the load and pattern of disease burden in different regions over time.

Profile and Trends of Rotavirus Gastroenteritis in Under-five Children in India (2012-2014): Preliminary Report of the Indian National Rotavirus Surveillance Network.

Objective: To estimate the burden of rotavirus-associated gastroenteritis in India. Methods: Hospital-based surveillance network was established, with clinical evaluation and laboratory testing for rotavirus among children aged below 5 years hospitalized with acute gastroenteritis. Results: Between September 2012 and December 2014, stool samples from 10207 children were tested and rotavirus was detected in 39.6% of cases. Infections were more commonly seen among younger children (<2 years). Detection rates were higher during cooler months of September – February. Among rotavirus infected-children, 64.0% had severe or very severe disease. G1P[8] was the predominant rotavirus genotype (62.7%) observed during the surveillance period. Conclusions: Surveillance data highlights the high rotavirus disease burden and emphasizes the need for close monitoring to reduce morbidity and mortality associated with rotavirus gastroenteritis in India.

Rotavirus Infections in Children Vaccinated Against Rotavirus in Pune, Western India.

Objective: To characterize rotavirus infections detected in rotavirus vaccinated children hospitalized for acute gastroenteritis. Design: Observational, hospital-based study. Setting: Three hospitals in Pune, Western India. Participants: Children aged <5 years hospitalized for acute gastroenteritis during 2013-14. Methods: Rotavirus capture ELISA was performed on all stool samples that were collected from patients following informed consent from parents. VP7 and VP4 genes of rotavirus strains were genotyped by multiplex RT-PCR. Stool samples from vaccinated children were tested for other enteric viruses. Results: Among the 529 children, 53 were vaccinated with at least one dose of the rotavirus vaccine. There was no difference in the mean (SD) (months) age of vaccinated [14.8 (10.6)] and unvaccinated [14.4 (10.5)] children. Rotavirus positivity was significantly higher (47%) in unvaccinated than in vaccinated (28.3%) children (P=0.01). Mean Vesikari score and severe cases were significantly more in rotavirus positive than in negative children within unvaccinated group (P<0.001), while these did not differ within the vaccinated group. Rotavirus strain G1P[8] was identified as the most prevalent strain in both, vaccinated (60%) and unvaccinated (72.8%) groups. No association was found between mean Vesikari score and viral coinfections. Conclusions: This study suggests decline in rotavirus positivity in rotavirus-vaccinated children hospitalized for acute gastroenteritis and high prevalence of G1P[8] and non-rotaviral co-infections in Pune, Western India.

Expanded Indian National Rotavirus Surveillance Network in the Context of Rotavirus Vaccine Introduction.

Objective: To extend a nation-wide rotavirus surveillance network in India, and to generate geographically representative data on rotaviral disease burden and prevalent strains. Design: Hospital-based surveillance. Setting: A comprehensive multicenter, multi-state hospital based surveillance network was established in a phased manner involving 28 hospital sites across 17 states and two union territories in India. Patients: Cases of acute diarrhea among children below 5 years of age admitted in the participating hospitals. Results: During the 28-month study period between September 2012 and December 2014, 11898 children were enrolled and stool samples from 10207 children admitted with acute diarrhea were tested; 39.6% were positive for rotavirus. Highest positivity was seen in Tanda (60.4%) and Bhubaneswar (60.4%) followed by Midnapore (59.5%). Rotavirus infection was seen more among children aged below 2 years with highest (46.7%) positivity in the age group of 12-23 months. Cooler months of September – February accounted for most of the rotavirus-associated gastroenteritis, with highest prevalence seen during December – February (56.4%). 64% of rotavirus-infected children had severe to very severe disease. G1 P[8] was the predominant rotavirus strain (62.7%) during the surveillance period. Conclusions: The surveillance data highlights the high rotaviral disease burden in India. The network will continue to be a platform for monitoring the impact of the vaccine.

A surveillance model for sexually transmitted infections in India.

The strategy for prevention and control of sexually transmitted infections (STIs) in India is based on syndromic case management delivered through designated STI/reproductive tract infection (RTI) centers (DSRCs) situated in medical colleges, district hospitals, and STI-clinics of targeted interventions programs. Laboratory tests for enhanced syndromic management are available at some sites. To ensure country-level planning and effective local implementation of STI services, reliable and consistent epidemiologic information is required on the distribution of STI cases, rate and trends of newly acquired infections, and STI prevalence in specific population groups. The present STI management information system is inadequate to meet these requirements because it is based on syndromic data and limited laboratory investigations on STIs reported passively by DSRCs and laboratories. Geographically representative information on the etiology of STI syndromes and antimicrobial susceptibility of STI pathogens although essential for optimizing available treatment options, is deficient. Surveillance must provide high quality information on: (a) prevalence of STIs such as syphilis, trichomoniasis, gonorrhea, and chlamydia among high-risk groups; syphilis in the general population and pregnant antenatal women; (b) demographic characteristics such as age, sex, new/recurrent episode, and type of syndromically diagnosed STI cases; (c) proportion of acute infections such as urethral discharge (UD) in men and nonherpetic genital ulcer disease (GUD) in men and women; (d) etiology of STI syndromes; and (e) gonococcal antimicrobial susceptibility. We describe here a framework for an STI sentinel surveillance system in India, building on the existing STI reporting systems and infrastructure, an overview of the components of the proposed surveillance system, and operational challenges in its implementation.

Perceptions of State Government stakeholders & researchers regarding public health research priorities in India: An exploratory survey.

Public health research has several stakeholders that should be involved in identifying public health research agenda. A survey was conducted prior to a national consultation organized by the Department of Health Research with the objective to identify the key public health research priorities as perceived by the State health officials and public health researchers. A cross-sectional survey was done for the State health officials involved in public health programmes and public health researchers in various States of India. A self-administered semi-structured questionnaire was used for data collection. Overall, 35 State officials from 15 States and 17 public health researchers participated in the study. Five leading public health research priorities identified in the open ended query were maternal and child health (24%), non-communicable diseases (22%), vector borne diseases (6%), tuberculosis (6%) and HIV/AIDS/STI (5%). Maternal and child health research was the leading priority; however, researchers also gave emphasis on the need for research in the emerging public health challenges such as non-communicable diseases. Structured initiatives are needed to promote interactions between policymakers and researchers at all stages of research starting from defining problems to the use of research to achieve the health goals as envisaged in the 12th Plan over next five years.

Mortality in HIV infected individuals in Pune, India.

Background & objectives: With the presence of HIV epidemic for more than two decades in India, rise in the number of HIV related deaths is expected. Data on mortality in HIV infected individuals from prospective studies are scanty in India. We report here data on mortality in a systematically followed cohort of HIV infected individuals at Pune, Maharashtra, India Methods: A total of 457 HIV infected individuals were enrolled in a prospective study in Pune between September 2002 and November 2004. They were evaluated clinically and monitored for CD4 counts at every quarterly visit. Mortality data were collected from the records of hospital facilities provided by the study. If the death occurred outside such hospitals; relatives of the participants were requested to inform about the death. Results: Median CD4 count in study participants was 218 cells/µl (95% CI: 107-373) at baseline. The median duration of follow up was 15 months (IQR: 12, 22). Mortality was higher in antiretroviral therapy (ART) naive patients compared to those who received treatment (16.59 vs. 7.25 per 100 person years). Participants above 35 yr of age, CD4 count less than or equal to 100 cells/µl at baseline, tuberculosis at any study time point and ART status were independently associated with high mortality [(RR=1.97; 95% CI: (1.23, 3.14), P=0.005, (RR=33.20, 95%CI (7.59, 145.29), P<0.001, (RR=2.38, 95% CI (1.38, 4.09), P= 0.002 and RR=5.60, 95% CI (3.18, 9.86), P<0.001, respectively]. Interpretation & conclusions: High mortality at advanced immunosuppression highlights the importance of early detection of HIV infection. Emphasis needs to be given at timely diagnosis and management of tuberculosis and ART initiation. It is important to create awareness about availability of free antiretroviral drugs in the government ART roll out programme.

Safety & immunogenicity of tgAAC09, a recombinant adeno-associated virus type 2 HIV-1 subtype C vaccine in India.

Background & objective: A phase 1 trial of adeno-associated virus based HIV-1 subtype C vaccine (tgAAC09) was conducted at two sites in Germany and Belgium and one site in India. This paper reports the safety and immunogenicity of tgAAC09 in healthy adult Indian volunteers. Methods: Between January 2005 and December 2006, 30 consenting volunteers were enrolled in the placebo controlled double-blind dose-escalation trial [3x109, 3x1010 and 3x1011 DNase resistant particles (DRPs)/ml]. Single injection of the candidate vaccine was administered to ten volunteers randomized in 8:2 ratio in vaccine and placebo arms at each dosage level. Results: The mean age of study volunteers (16 men and 14 women) was 34 yr. Six local reactogenicity events and 14 systemic reactogenicity events like malaise, fever, headache and myalgia were reported, both were dose-dependent. The difference between the adverse events reported by vaccine and placebo recipients (79 and 67%) was not significant. A modest IFN-γ ELISPOT response [248 spot forming units (SFU)/million cells] was detected in one volunteer from high dose group and low response (56 and 75 SFU/million cells) in two volunteers in low and mid-dose groups. A post-vaccination dose-dependent increase was observed in anti AAV2 neutralizing titres. None of the volunteers showed a positive antibody response to HIV-1. Interpretation & conclusions: The trial was a benchmark in phase I clinical evaluation of HIV candidate vaccines in India. The vaccine was generally well tolerated and raised no safety concerns. The vaccine was found to be weakly immunogenic. It is essential to understand the role of pre-existing immunity against vectors and significance of evaluation in a prime-boost strategy.

Drug resistance pattern of Mycobacterium tuberculosis in seropositive and seronegative HIV-TB patients in Pune, India.

BACKGROUND & OBJECTIVE: Tuberculosis is the commonest opportunistic disease in persons infected with human immunodeficiency virus (HIV). Emergence of drug resistant isolates of M. tuberculosis highlights the need for continuous monitoring of drug resistance to antituberculosis drugs. Considering the reported high prevalence of drug resistance in HIV infected tuberculosis patients, we studied the anti-tuberculosis drug resistance pattern of M. tuberculosis in HIV seropositive and seronegative tuberculosis patients in Pune, Maharashtra, India. METHODS: A total of 70 M. tuberculosis isolates, 30 from HIV seropositive and 40 from HIV seronegative tuberculosis patients with no previous history of anti-tuberculosis treatment, were isolated from sputum samples on Lowenstein-Jensen (LJ) medium, confirmed by conventional biochemical tests and stored at -70 degrees C. They were revived by subculturing on LJ medium and tested for drug resistance against four first-line antitubercular drugs by BACTEC Mycobacterial growth indicator tube 960 (MGIT 960) system. RESULTS: Of the 30 isolates from HIV infected patients, 10 per cent were resistant to isoniazid (H), 6.6 per cent to streptomycin (S), 6.6 per cent to ethambutol (E) and 10 per cent were multi drug resistant (MDR). Of the 40 M. tuberculosis isolates from HIV uninfected individuals, 10 per cent were resistant to H, 2.5 per cent to S, 2.5 per cent to E, and 2.5 per cent isolates were MDR. INTERPRETATION & CONCLUSION: The prevalence of drug resistant M. tuberculosis isolates among HIV seropositive tuberculosis patients was similar to that of HIV seronegative TB patients, indicating HIV infection may not be associated with drug resistant tuberculosis. However, considering the results from other studies and a high prevalence of HIV-TB infection in the country, monitoring of drug resistance in M. tuberculosis isolates needs prioritization to ensure success in national tuberculosis control programme.

HIV/AIDS epidemic in India: risk factors, risk behaviour & strategies for prevention & control.

Since the first report of HIV infection in India in 1986, the virus has spread all over the country although there is geographic variation. There are estimated 5.1 million people infected with HIV with an overall estimated adult prevalence below 1 per cent. Surveys carried out in different sub-populations have yielded prevalence estimates, but data on HIV incidence are limited. Both HIV serotypes 1 and 2 exist in India and HIV-1 C is the commonest subtype reported. Sexual transmission of HIV is most predominant. Spread of HIV in intravenous drug use settings is localized mostly in the north eastern region and metropolitan cities and parent to child transmission is on the rise. Dual epidemics of HIV and tuberculosis, increase in the number of infected women, stigma and discrimination are the main concerns in the Indian HIV/AIDS scenario. There is an increasing political will and commitment for HIV prevention and control efforts in India. A multi-disciplinary approach combining targeted interventions like early identification and treatment of STDs, condom promotion, blood safety, drug de-addiction programs and expanding and strengthening VCTCs and long-term strategies like awareness oriented to behavioural change especially among vulnerable populations, young people and women, steps towards improvement of literacy, status of women and overall development, reduction in poverty and development of primary prevention interventions like vaccines and microbicides will have to be considered for effective prevention and control of AIDS in India.

Preparing for efficacy trials of vaginal microbicides in Indian women.

Vaginal microbicides are topical compounds that are expected to protect women against vaginal transmission of HIV and other sexually transmitted pathogens. A large number of compounds are being evaluated as possible microbicides. Considering the spread of the HIV epidemic among women in India, clinical trials on microbicides starting from the Phase I safety and acceptability studies to Phase III efficacy trials are important. Conducting efficacy trials is a major endeavour and this review discusses challenges and issues and the preparatory steps to make such efficacy trials possible in India.

Incident HIV infection among men attending STD clinics in Pune, India: pathways to disparity and interventions to enhance equity.

Systematic disparities in rates of HIV incidence by socioeconomic status were assessed among men attending three sexually transmitted disease (STD) clinics in Pune, India, to identify key policy-intervention points to increase health equity. Measures of socioeconomic status included level of education, family income, and occupation. From 1993 to 2000, 2,260 HIV-uninfected men who consented to participate in the study were followed on a quarterly basis. Proportional hazards regression analysis of incident HIV infection identified a statistically significant interaction between level of education and genital ulcer disease. Compared to the lowest-risk men without genital ulcer disease who completed high school, the relative risk (RR) for acquisition of HIV was 7.02 (p < 0.001) for illiterate men with genital ulcer disease, 3.62 (p < 0.001) for men with some education and genital ulcer disease, and 3.02 (p < 0.001) for men who completed high school and had genital ulcer disease. For men with no genital ulcer disease and those with no education RR was 1.09 (p = 0.84), and for men with primary/middle school it was 1.70 (p = 0.03). The study provides evidence that by enhancing access to treatment and interventions that include counselling, education, and provision of condoms for prevention of STDs, especially genital ulcer disease, among disadvantaged men, the disparity in rates of HIV incidence could be lessened considerably. Nevertheless, given the same level of knowledge on AIDS, the same level of risk behaviour, and the same level of biological co-factors, the most disadvantaged men still have higher rates of HIV incidence.