Srinivas Venkatesh

Impact of targeted interventions on heterosexual transmission of HIV in India

BackgroundTargeted interventions (TIs) have been a major strategy for HIV prevention in India. We evaluated the impact of TIs on HIV prevalence in high HIV prevalence southern states (Tamil Nadu, Karnataka, Andhra Pradesh and Maharashtra).MethodsA quasi-experimental approach was used to retrospectively compare changes in HIV prevalence according to the intensity of targeted intervention implementation. Condom gap (number of condoms required minus condoms supplied by TIs) was used as an indicator of TI intensity. Annual average number of commercial sex acts per female sex worker (FSW) reported in Behavioral Surveillance Survey was multiplied by the estimated number of FSWs in each district to calculate annual requirement of condoms in the district. Data of condoms supplied by TIs from 1995 to 2008 was obtained from program records. Districts in each state were ranked into quartiles based on the TI intensity. Primary data of HIV Sentinel Surveillance was analyzed to calculate HIV prevalence reductions in each successive year taking 2001 as reference year according to the quartiles of TI intensity districts using generalized linear model with logit link and binomial distribution after adjusting for age, education, and place of residence (urban or rural).ResultsIn the high HIV prevalence southern states, the number of TI projects for FSWs increased from 5 to 310 between 1995 and 2008. In high TI intensity quartile districts (n = 30), 186 condoms per FSW/year were distributed through TIs as compared to 45 condoms/FSW/year in the low TI intensity districts (n = 29). Behavioral surveillance indicated significant rise in condom use from 2001 to 2009. Among FSWs consistent condom use with last paying clients increased from 58.6% to 83.7% (p < 0.001), and among men of reproductive age, the condom use during sex with non-regular partner increased from 51.7% to 68.6% (p < 0.001). A significant decline in HIV and syphilis prevalence has occurred in high prevalence southern states among FSWs and young antenatal women. Among young (15-24 years) antenatal clinic attendees significant decline was observed in HIV prevalence from 2001 to 2008 (OR = 0.42, 95% CI 0.28-0.62) in high TI intensity districts whereas in low TI intensity districts the change was not significant (OR = 1.01, 95% CI 0.67-1.5).ConclusionTargeted interventions are associated with HIV prevalence decline.

Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study.

BACKGROUNDnOutbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the countrys largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness.nnnMETHODSnIn this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses).nnnFINDINGSnBetween May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 - 24]) and absence of an evening meal (2·2 [1·2-4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3-18·8], without evening meal; OR 3·6 [1·1-11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged from 44·9 μg/g to 220·0 μg/g.nnnINTERPRETATIONnOur investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks.nnnFUNDINGnUS Centers for Disease Control and Prevention.

Survival probability and predictors of mortality and retention in care among patients enrolled for first-line antiretroviral therapy, Andhra Pradesh, India, 2008–2011

BACKGROUNDnThe national antiretroviral therapy (ART) initiative in India began in 2004. In order to better inform the national program, we estimated the mean cumulative survival probability and loss to follow-up (LFU) rate among patients initiated on ART.nnnMETHODSnWe identified a cohort of people living with HIV (PLHIV) aged ≥15 years initiated on ART in two ART centres in Hyderabad city, Andhra Pradesh state, India between January 2008 and December 2008. The cohort was followed-up until 31 December 2011 and death and/or LFU were the primary endpoints. Death from any cause during the study period was considered to be the result of HIV infection. We used the Kaplan-Meier estimation method for survival probability and Cox proportional hazard model to identify the predictors.nnnRESULTSnOf the 1690 patients initiated on ART, 259 (15.3%) were transferred out during the study period. Mortality rate was 7.6/100 person-years. Male gender, low CD4 count, history of tuberculosis before initiation of ART, and weight <48 kg were the predictors of mortality. Patients who were LFU were more likely to be males, unemployed, widowed, and had weight below 48 kg.nnnCONCLUSIONnSurvival rates on ART were higher compared to other resource-limited settings. Delayed diagnosis and initiation of ART and co-infection with TB were important predictors for both mortality and retention in care.

Modelling and estimation of HIV prevalence and number of people living with HIV in India, 2010–2011

This paper provides HIV estimation methodology used in India and key HIV estimates for 2010–2011. We used a modified version of the Spectrum tool that included an Estimation and Projection Package as part of its AIDS Impact Module. Inputs related to population size, age-specific pattern of fertility, gender-ratio at birth, age and gender-specific pattern of mortality, and volume and age–gender distribution of net migration were derived from census records, the Sample Registration System and large-scale demographic health surveys. Epidemiological and programmatic data were derived from HIV sentinel surveillance, large-scale epidemiological surveys and the programme management information system. Estimated adult HIV prevalence retained a declining trend in India, following its peak in 2002 at a level of 0.41% (within bounds 0.35–0.47%). By 2010 and 2011, it levelled at estimates of 0.28% (0.24–0.34%) and 0.27% (0.22–0.33%), respectively. The estimated number of people living with HIV (PLHIV) reduced by 8% between 2007 and 2011. While children accounted for approximately 6.3% of total HIV infections in 2007, this proportion increased to about 7% in 2011. With changing priorities and epidemic patterns, the programme has to customise its strategies to effectively address the emerging vulnerabilities and adapt them to suit the requirements of different geographical regions.

Comparative genetic variability in HIV‐1 subtype C nef gene in early age groups of infants

Targeting properties of vertically transmitted viruses in early infancy is important to understand disease progression. To investigate genotypic characteristics of transmitted viruses, blood samples were obtained from infants aged 6 weeks‐18 months, categorized in two age groups, acute (<6 months) and early (>6‐18 months). Nef having an important role in pathogenesis was selected to explore the viral characteristics. A total of 57 PCR positive samples, amplified by nef gene were sequenced. Analysis showed that 50 sequences belonged to subtype C. In one sequence of acute age group, a long insertion of 10 residues (AAERMRRAEP) in variable region and a 13 residues deletion (ATNNADCAWLEAQ) around proteolytic cleavage region of gene in another sequence was observed. Insertions were also observed in sequences of early age group, however, they ranged from two to eight residues only. In one sequence of early age group, 3/4 arginines at positions 19, 21, 22 of arginine cluster were mutated to glutamine, alanine, and glutamine, respectively. Entropy analysis of two age groups revealed presence of several residues with statistically significant differences in their variability. Among these, 15 (R18,R23,R24; A66,L68,Q71; E74,E77,E78; V87,M92; R119, P144, E167, and C176) belonged to functional motifs, out of which, 12 were in acute age group, suggesting that variability was greater in this group. Prediction of HLA binding peptide motif revealed that epitope LTFGWCFKL was present in >80% study sequences. This epitope was also present in maximum number of HLA types circulating in India and vaccine candidate sequences, suggesting that it may be helpful in designing an epitope‐based vaccine.

Molecular epidemiological analysis of three hepatitis C virus outbreaks in Jammu and Kashmir State, India

Outbreaks of hepatitis C virus (HCV) infection are associated with unsafe injection practices, intravenous drug abuse and other exposure to blood and body fluids. We report here three outbreaks of HCV infection from Jammu and Kashmir (J&K) State, India, which occurred over a period of 3 years and in which molecular epidemiological investigations identified a presumptive common source of infection, most likely a single healthcare venue. Representative blood samples collected from cases of hepatitis C were sent to the National Centre for Disease Control (NCDC) for molecular characterization. These samples were positive by HCV ELISA. Subsequently, specimens were also tested for the presence of HCV RNA by RT-PCR. Sequencing was carried out for all positive samples. A total of 812 cases were laboratory confirmed by HCV ELISA; a total of 115 samples were sent to the NCDC for RT-PCR, and 77 were positive. Subtype 3a of HCV was found in all samples from Anantnag (February 2013); and for subtype 3b, in all samples from Srinagar (May 2015). Subtypes 3a and 3g were identified from two samples from the Kulgam outbreak (July 2014). A detailed epidemiological investigation should be conducted whenever a cluster of HCV cases is revealed, as this potentially allows for the identification of larger outbreaks. Epidemiological investigations of outbreaks should be further supported by inclusion of molecular tests. Efforts to limit therapeutic injections to only those cases having strong medical/surgical indications and to restrict the use of non-sterile needles are essential to prevent transmission of HCV.

Comparative genetic variability in HIV-1 subtype C p24 Gene in early age groups of infants

It is important to study the molecular properties of vertically transmitted viruses in early infancy to understand disease progression. P24 having an important role in virus assembly and maturation was selected to explore the genotypic characteristics. Blood samples, obtained from 82 HIV-1 positive infants, were categorized into acute (≤u20096xa0months) and early (>u20096–18xa0months) age groups. Of the 82 samples, 79 gave amplification results for p24, which were then sequenced and analysed. Amino acid heterogeneity analysis showed that substitutions were more frequent. Several substitution mutations were present in some of the sequences of both the age groups in the functional motifs of the gene namely Beta hairpin, CyPA binding loop, residues L136 and L190, linker region and major homology region. In the acute age group, an insertion of Asparagine residue (N5NL6) was observed in the β hairpin region in one of the sequences. This insertion was accompanied with analogous substitutions of N5Q, Q7L and G8R. In the early age group, a deletion of two residues; VK181−182, was observed at the C-terminal end in one of the sequences. These mutations may impair the structure of the protein leading to defective virus assembly. Protein variation effect analyzer software showed that deleterious mutations were more in the acute than the early age group. Variability analysis revealed that the amino acid heterogeneity was comparatively higher in the acute than the early age group. Variability in the virus was decreasing with the increasing age of the infants indicating that the virus is gradually evolving under positive selection pressure. HLA class 1 binding peptide analysis showed that the epitopes TPQDLNTML and RMYSPVSIL may be helpful in designing epitope based vaccine.

Differing HIV vulnerability among female sex workers in a high HIV burden Indian state

Introduction The HIV sentinel surveillance [HSS] conducted in 2010–11 among female sex workers [FSW] in the state of Maharashtra, India provided an opportunity to assess characteristics of different types of FSWs and their HIV risk. It is important for India’s National AIDS Control Program, to understand the differences in vulnerability among these FSW, in order to define more specific and effective risk reduction intervention strategies. Therefore, we analyzed data from HSS with the objective of understanding the HIV vulnerability among different types of FSW in Maharashtra. Material and methods Cross sectional data collected as a part of HSS among FSWs in year 2010–11 from 21 sentinel sites in the state of Maharashtra were analyzed to understand the vulnerability and characteristics of different types of female sex workers based on their place of solicitation using multinomial logistic regression. Results While the HIV prevalence was 6.6% among all FSWs, it was 9.9% among brothel based [BB], 9% among street based [SB] and 3.1% and 3.7% among home based [HB], and bar based [Bar-B] sex workers respectively. SB FSWs were least likely to be located in HIV low burden districts [ANC] [ARRR: 0.61[95% CI: 0.49, 0.77]], but were 6 times more likely to be recently [<1 year] involved in sex work [ARRR: 6.15 [95% CI: 3.15, 12.0]]. The number of clients of SB FSWs in the preceding week were lower than 11% [ARRR: 0.89 [95%CI: 0.87, 0.90]] as compared to the BB FSWs denoting lesser client load. The duration since last paid sex was shorter [ARRR: 0.94[95%CI: 0.91, 0.96]] as compared to the BB FSWs. Conclusion Street based FSWs have emerged as one of the most vulnerable types of FSW with a high HIV prevalence similar to BB FSWs. Our study reveals that they have more frequent sex acts despite lower client loads, and are more likely to be located in districts highly affected by HIV (ANC prevalence >1%). We identify them as a group to be focused on for prevention interventions and it is likely that they would be easily amenable to novel interventions due to their higher literacy rate as compared to other typologies.

Mumps Outbreak Investigation in Jaisalmer, Rajasthan, India, June-September 2016: MOGHE et al.

Mumps, a vaccine‐preventable disease, cause inflammation of salivary glands and may cause severe complications, such as encephalitis, meningitis, deafness, and orchitis/oophoritis. In India, mumps vaccine is not included in the universal immunization program and during 2009 to 2014, 72 outbreaks with greater than 1500 cases were reported. In August 2016, a suspected mumps outbreak was reported in Jaisalmer block, Rajasthan. We investigated to confirm the etiology, describe the epidemiology, and recommend prevention and control measures. We defined a case as swelling in the parotid region in a Jaisalmer block resident between 23 June 2016 and 10 September 2016. We searched for cases in health facilities and house‐to‐house in affected villages and hamlets. We tested blood samples of cases for mumps immunoglobulin M (IgM) enzyme‐linked immunosorbent assay (ELISA). We found 162 cases (60% males) with a median age of 9.4 years (range: 7 month‐38 years) and 65 (40%) were females. Symptoms included fever (70%) and bilateral swelling in neck (65%). None of them were vaccinated against mumps. Most (84%) cases were school‐going children (3‐16 years old). The overall attack rate was 2%. Village A, with two hamlets, had the highest attack rate (hamlet 1u2009=u200913% and hamlet 2u2009=u200912%). School A of village A, hamlet 1, which accommodated 200 children in two classrooms, had an attack rate of 55%. Of 18 blood samples from cases, 11 tested positive for mumps IgM ELISA. This was a confirmed mumps outbreak in Jaisalmer block that disproportionately affected school‐going children. We recommended continued surveillance, 5‐day absence from school, and vaccination.

Lychee-associated acute hypoglycaemic encephalopathy outbreaks in Muzaffarpur, India – Author's reply

www.thelancet.com/lancetgh Vol 5 September 2017 e861 to hypoglycin A and MCPG toxicity in cases but not controls, provided the conclusive data to confirm the lychee– hypoglycin A–MCPG hypothesis. During prospective surveillance, we used a highly sensitive case definition to ensure that all potential cases were captured. This is not unusual in investigations of unexplained, severe illnesses, and also helped to ensure patients received appropriate and prompt clinical management. If there had been misclassification between cases and controls, as Das and John suggest, the significant associations identified between lychee consumption, absence of evening meal, and illness would have, at worst, been biased toward the null. Both case-patients and controls were residents of villages in the Muzaffarpur district—ie, the same community. Controls were identified among children who were admitted to the same hospitals where case-patients were admitted. The presence of lychee orchards and agricultural fields, and the availability of lychees were ubiquitous in the Muzaffarpur villages where both case-patients and controls lived. It was with these data, and after a multisectoral meeting of stakeholders from district-level, state-level, and national-level agencies in February, 2015, that the Director General of Health Services, Government of India, issued official recommendations to the Government of Bihar to encourage parents and carers in the affected Muzaffarpur area to minimise children’s lychee consumption and ensure they eat an evening meal, and to re-emphasise the need for clinicians to rapidly test for, and correct, hypoglycaemia among children with suspected illness. After this, the NCDC and, more broadly, the Ministry of Health and Family Welfare, and the Ministry of Women and Child Development have continued to support the Government of Bihar’s response to the Muzaffarpur outbreaks in 2015 and 2016, and Lychee-associated acute hypoglycaemic encephalopathy outbreaks in Muzaffarpur, India