Intussusception after Rotavirus Vaccine Introduction in India.

BACKGROUND: A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries. METHODS: We conducted a multicenter, hospital-based, active surveillance study at 27 hospitals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was ascertained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case-control analysis was performed, with matching for age, sex, and location. RESULTS: From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence, 0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case-control analysis. CONCLUSIONS: The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Foundation and others.).

Metabolic syndrome in people living with antiretroviral therapy: A cross-sectional investigation from Pune, India.

Background: Improved longevity of people living with HIV on highly active antiretroviral therapy and accelerated aging processes are considered contributory to Metabolic Syndrome. Objectives: The current study investigated metabolic syndrome (MetS) in people living with HIV (PLH) who were receiving antiretroviral therapy (ART) under the ongoing National AIDS Control Program. Methods: Clinic attendees (n = 3088) who were on ART for more than 6 months constituted the sampling frame, from which 378 study participants were randomly drawn and included in the analysis following the eligibility check. One hundred and fifty-nine clinic attendees, initiated on ART in ≤6 months, provided an opportunity to estimate the prevalence of MetS in them. Sixty-two PLH from this smaller group were enrolled. Results: MetS was found among 19% (73/378; 95% confidence interval [CI] 15.5%-23.7%) PLH who were on ART >6 months compared with 24% (15/62; 95% CI 14.2%-36.7%) in those who were on ART for ≤6 months based on harmonization criteria for the Asian population; the confidence intervals overlapped and apparently observed difference was not statistically significant. Adjusted for age, body mass index (BMI), protease inhibitor (PI)-based ART regimen, duration of ART, insulin resistance (IR), reported family history of hypertension and residential setting, factors independently associated with MetS were PI containing ART regimen, IR, duration of ART intake and BMI. In the adjusted model, the odds of MetS were three times higher among PLH on PI containing ART regimen (95% CI of adjusted odds ratio; aOR 1.27-8.51) and those having IR (95% CI of aOR 1.48-5.07). The odds of MetS among PLH with BMI ≥23 kg/m2 was 4 (95% CI of aOR 2.08-6.81) times higher than those with lower BMI. Conclusions: MetS in PLH requires the attention of health-care workers in India. Appropriate screening would help initiate early management.

Investigations of seasonal outbreaks of acute encephalitis syndrome due to Orientia tsutsugamushi in Gorakhpur region, India: A One Health case study.

Gorakhpur division consisting of Gorakhpur and neighboring districts Deoria, Kushinagar and Maharajganj in Uttar Pradesh, India, have been witnessing seasonal outbreaks of acute encephalitis syndrome (AES) among children for the last three decades. Investigations conducted during 2005 identified Japanese encephalitis (JE) virus as an aetiology of AES. With the introduction of JE vaccination and other control strategies, the incidence of JE in the region declined, however, outbreaks of acute febrile illness with neurological manifestations continued to occur. Subsequent investigations identified Orientia tsutsugamushi, as the major aetiology of AES outbreaks in the region. This review details clinical, epidemiological, animal and entomological investigations conducted for AES due to O. tsutsugamushi during 2015 and 2017 in Gorakhpur region. Surveillance of acute febrile illness among children attending peripheral health facilities identified scrub typhus as an important aetiology of febrile illness during monsoon and post-monsoon months. Population-based serosurveys indicated high endemicity of scrub typhus. Entomological studies demonstrated natural infection of O. tsutsugamushi in small animal hosts and vector mites. Children acquired this infection through recent exposure to outdoor environment, while playing, or visiting fields or defecating in open fields. A few of the children with scrub typhus progress to develop CNS manifestations. Hence, early administration of appropriate antibiotics is crucial in preventing progression of AFI due to scrub typhus to AES. The investigations conducted by the multi-disciplinary team helped understand the transmission dynamics of scrub typhus in Gorakhpur division and recommend strategies for its control.

Diversity of rotavirus genotypes circulating in children < 5 years of age hospitalized for acute gastroenteritis in India from 2005 to 2016: analysis of temporal and regional genotype variation.

BACKGROUND: From 2016, the Government of India introduced the oral rotavirus vaccine into the national immunization schedule. Currently, two indigenously developed vaccines (ROTAVAC, Bharat Biotech; ROTASIIL, Serum Institute of India) are included in the Indian immunization program. We report the rotavirus disease burden and the diversity of rotavirus genotypes from 2005 to 2016 in a multi-centric surveillance study before the introduction of vaccines. METHODS: A total of 29,561 stool samples collected from 2005 to 2016 (7 sites during 2005-2009, 3 sites from 2009 to 2012, and 28 sites during 2012-2016) were included in the analysis. Stools were tested for rotavirus antigen using enzyme immunoassay (EIA). Genotyping was performed on 65.8% of the EIA positive samples using reverse transcription- polymerase chain reaction (RT-PCR) to identify the G (VP7) and P (VP4) types. Multinomial logistic regression was used to quantify the odds of detecting genotypes across the surveillance period and in particular age groups. RESULTS: Of the 29,561 samples tested, 10,959 (37.1%) were positive for rotavirus. There was a peak in rotavirus positivity during December to February across all sites. Of the 7215 genotyped samples, G1P[8] (38.7%) was the most common, followed by G2P[4] (12.3%), G9P[4] (5.8%), G12P[6] (4.2%), G9P[8] (4%), and G12P[8] (2.4%). Globally, G9P[4] and G12P[6] are less common genotypes, although these genotypes have been reported from India and few other countries. There was a variation in the geographic and temporal distribution of genotypes, and the emergence or re-emergence of new genotypes such as G3P[8] was seen. Over the surveillance period, there was a decline in the proportion of G2P[4], and an increase in the proportion of G9P[4]. A higher proportion of mixed and partially typed/untyped samples was also seen more in the age group 0-11 months. CONCLUSIONS: This 11 years surveillance highlights the high burden of severe rotavirus gastroenteritis in Indian children < 5 years of age before inclusion of rotavirus vaccines in the national programme. Regional variations in rotavirus epidemiology were seen, including the emergence of G3P[8] in the latter part of the surveillance. Having pre-introduction data is important to track changing epidemiology of rotaviruses, particularly following vaccine introduction.

Seroprevalence & seroincidence of Orientia tsutsugamushi infection in Gorakhpur, Uttar Pradesh, India: A community-based serosurvey during lean (April-May) & epidemic (October-November) periods for acute encephalitis syndrome.

Background & objectives: In India, acute encephalitis syndrome (AES) cases are frequently reported from Gorakhpur district in Uttar Pradesh. Scrub typhus is one of the predominant aetiological agents for these cases. In order to delineate the extent of the background of scrub typhus seroprevalence and the associated risk factors at community level, serosurveys during both lean and epidemic periods (phase 1 and phase 2, respectively) of AES outbreaks were conducted in this region. Methods: Two community-based serosurveys were conducted during lean (April-May 2016) and epidemic AES (October-November 2016) periods. A total of 1085 and 906 individuals were enrolled during lean and epidemic AES periods, respectively, from different villages reporting recent AES cases. Scrub typhus-seronegative individuals (n=254) during the lean period were tested again during the epidemic period to estimate the incidence of scrub typhus. Results: The seroprevalence of Orientia tsutsugamushi during AES epidemic period [immunoglobulin (Ig) IgG: 70.8%, IgM: 4.4%] was high as compared to that of lean AES period (IgG: 50.6%, P <0.001; IgM: 3.4%). The factors independently associated with O. tsutsugamushi positivity during lean AES period were female gender, illiteracy, not wearing footwear, not taking bath after work whereas increasing age, close contact with animals, source of drinking water and open-air defecation emerged as additional risk factors during the epidemic AES season. IgM positivity was significantly higher among febrile individuals compared to those without fever (7.7 vs. 3.5%, P=0.006). The seroincidence for O. tsutsugamushi was 19.7 per cent, and the subclinical infection rate was 54 per cent. Interpretation & conclusions: The community-based surveys identified endemicity of O. tsutsugamushi and the associated risk factors in Gorakhpur region. The findings will be helpful for planning appropriate interventional strategies to control scrub typhus.

Rotavirus gastroenteritis in Indian children < 5 years hospitalized for diarrhoea, 2012 to 2016.

BACKGROUND: In 2016, the Government of India introduced the oral rotavirus vaccine (ROTAVAC, Bharat Biotech, India) in 4 states of India as part of the Universal Immunization Programme, and expanded to 5 more states in 2017. We report four years of data on rotavirus gastroenteritis in hospitalized children < 5 years of age prior to vaccine introduction. METHODS: Children from 7 sites in southern and northern India hospitalized for diarrhoea were recruited between July 2012 and June 2016. Stool samples were screened for rotavirus using enzyme immunoassay (EIA). The EIA positive samples were genotyped by reverse-transcription polymerase chain reaction. RESULTS: Of the 5834 samples from the 7 sites, 2069 (35.5%) were positive for rotavirus by EIA. Genotyping was performed for 2010 (97.1%) samples. G1P[8](56.3%), G2P[4](9.1%), G9P[4](7.6%), G9P[8](4.2%), and G12P[6](3.7%) were the common genotypes in southern India and G1P[8](36%), G9P[4](11.4%), G2P[4](11.2%), G12P[6](8.4%), and G3P[8](5.9%) in northern India. CONCLUSIONS: The study highlights the high prevalence of rotavirus gastroenteritis in India and the diversity of rotavirus genotypes across different geographical regions. Pre- vaccine surveillance data is necessary to evaluate the potential change in admission rates for gastroenteritis and circulating rotavirus genotypes after vaccine introduction, thus assessing impact.

Safety monitoring of ROTAVAC vaccine and etiological investigation of intussusception in India: study protocol.

BACKGROUND: ROTAVAC, an indigenous rotavirus vaccine, was introduced in the universal immunization program of India in four states in 2016 and expanded to five more states in 2017. The clinical trial on efficacy of ROTAVAC did not detect an increased risk of intussusception, but the trial was not large enough to detect a small risk. This protocol paper describes the establishment and implementation of a surveillance system to monitor the safety of rotavirus vaccine and investigate the potential infectious etiologies of intussusception. METHODS: This is a multi-centric hospital-based active surveillance being conducted at 28 hospitals in nine states of India. Data gathered from surveillance will be used to assess the risk of intussusception after ROTAVAC administration and to determine the infectious etiologies of intussusception. For safety assessment of ROTAVAC vaccine, children aged less than two years with intussusception admitted at the sentinel hospitals are enrolled into surveillance, a case report form completed, and a copy of the vaccination card obtained. The risk of intussusception following rotavirus vaccination will be assessed using a self-controlled case-series design. The investigation for potential infectious etiologies of intussusception is through a matched case-control design. Children enrolled for the safety assessment serve as cases and for each case, an age, gender and location matched control is enrolled within 30 days of case enrollment. Stool specimens are obtained from cases and controls. All forms and specimens are sent to the referral laboratory for data entry, analysis, multiplexed molecular testing, and storage. DISCUSSION: Anticipated public health benefits of this surveillance include the generation of information useful to national government on safety of vaccine and to make future decisions on vaccine use through risk-benefit analysis. Investigating infectious agents may help to determine the potential infectious etiologies of intussusception.

Immunogenicity & safety of a single dose of live-attenuated Japanese encephalitis vaccine SA 14-14-2 in adults.

BACKGROUND & OBJECTIVES: Japanese encephalitis (JE) caused by mosquito-borne Flavivirus is one of the leading causes of viral encephalitis in Asia. Control strategies include vector control and human vaccination. Due to lack of immunization programmes in endemic regions, there are still high mortality and morbidity. A live-attenuated SA 14-14-2 JE vaccine (LAJEV) has been licensed and used in Asian countries, including India. We report the assessment of immunogenicity and safety of the vaccine in adults during the first mass adult vaccination campaign carried out in Assam, India. METHODS: One thousand and seventy five adults (aged ≥15 yr) who received LAJEV were monitored for adverse events following immunization for one year. The safety assessment of vaccinated population was evaluated till 28 days and at 6 and 12 months. Blood samples collected from the enrolled participants were tested by plaque reduction neutralization test (PRNT 50 ) to assess the neutralizing antibody titres (NATs) before vaccination and 28 days, six and 12 months post-vaccination (PV). RESULTS: Among the 1075 vaccinated individuals, four reported minor adverse effects from 30 min to 28 days PV. Based on the pre-vaccination NAT, the study participants were categorized as seronegative, moderately seropositive and strongly seropositive. Nearly 85.5 per cent of JE seronegative participants seroconverted by 28 days PV. The geometric mean titre (GMT) in all the three groups increased by 28 days and decreased by six and 12 months PV. Nearly 60 per cent of the moderately positive individuals exhibited four-fold rise in GMT, 28 days PV. Almost 95.5 per cent of the participants in the study population remained seroprotected at the end of 12 months PV. INTERPRETATION & CONCLUSIONS: This study on immunogenicity and safety of LAJEV in adults showed that a single dose of the live-attenuated vaccine was safe and induced protective immunity to both JE seronegative and naturally seropositive adults. Further study is required to find out long term protective efficacy of this vaccine.

International open trial of uniform multidrug therapy regimen for leprosy patients: Findings & implications for national leprosy programmes.

BACKGROUND & OBJECTIVES: Uniform therapy for all leprosy patients will simplify leprosy treatment. In this context, we evaluated six-month multidrug therapy (MDT) currently recommended for multibacillary (MB) patients as uniform MDT (U-MDT) in a single-arm open trial under programme conditions. Primary objective was to determine efficacy to prevent five-year cumulative five per cent relapse. Secondary objectives were to assess acceptability, safety and compliance. METHODS: Newly detected, treatment-naive leprosy patients were enrolled in India (six sites) and P. R. China (two sites). Primary outcome was clinically confirmed relapse of occurrence of one or more new skin patches consistent with leprosy, without evidence of reactions post-treatment. Event rates per 100 person years as well as five-year cumulative risk of relapse, were calculated. RESULTS: A total of 2091 paucibacillary (PB) and 1298 MB leprosy patients were recruited from the 3437 patients screened. Among PB, two relapsed (rate=0.023; risk=0.11%), eight had suspected adverse drug reactions (ADRs) (rate=0.79) and rate of new lesions due toreactions was 0.24 (n=23). Rates of neuritis, type 1 and type 2 reactions were 0.39 (n=37), 0.54 (n=51) and 0.03 (n=3), respectively. Among MB, four relapsed (rate=0.07; risk=0.37%) and 16 had suspected ADR (rate=2.64). Rate of new lesions due to reactions among MB was 1.34 (n=76) and rates of neuritis, type 1 and type 2 reactions were 1.37 (n=78), 2.01 (n=114) and 0.49 (n=28), respectively. Compliance to U-MDT was 99 per cent. Skin pigmentation due to clofazimine was of short duration and acceptable. INTERPRETATION & CONCLUSIONS: We observed low relapse, minimal ADR and other adverse clinical events. Clofazimine-related pigmentation was acceptable. Evidence supports introduction of U-MDT in national leprosy programmes. [CTRI No: 2012/ 05/ 002696].

Cost-effective analysis of hepatitis A vaccination in Kerala state, India.

Several hepatitis A outbreaks have recently been reported in Kerala state, India. To inform coverage decision of hepatitis A vaccine in Kerala, this study aimed to examine the cost-effectiveness of 1) hepatitis A vaccination among children aged 1 year and individuals aged 15 years, and 2) serological screening of individuals aged 15 years and vaccination of susceptible as compared to no vaccination or vaccination without serological screening. Both live attenuated hepatitis A vaccine and inactivated hepatitis A vaccine were considered in the analysis. A combination of decision tree and Markov models with a cycle length of one year was employed to estimate costs and benefits of different vaccination strategies. Analysis were based on both societal and payer perspectives. The lifetime costs and outcomes were discounted by 3%. Our findings indicated that all strategies were cost-saving for both societal and payer perspectives. Moreover, budget impact analysis revealed that vaccination without screening among individuals aged 15 years could save the government's budget by reducing treatment cost of hepatitis A. Our cost-effectiveness evidence supports the inclusion of hepatitis A vaccination into the vaccination program for children aged 1 year and individuals aged 15 years in Kerala state, India.

Seven years of the field epidemiology training programme (FETP) at Chennai, Tamil Nadu, India: an internal evaluation.

BACKGROUND: During 2001-2007, the National Institute of Epidemiology (NIE), Chennai, Tamil Nadu, India admitted 80 trainees in its two-year Field Epidemiology Training Programme (FETP). We evaluated the first seven years of the programme to identify strengths and weaknesses. METHODS: We identified core components of the programme and broke them down into input, process, output and outcome. We developed critical indicators to reflect the logic model. We reviewed documents including fieldwork reports, abstracts listed in proceedings and papers published in Medline-indexed journals. We conducted an anonymous online survey of the graduates to collect information on self-perceived competencies, learning activities, field assignments, supervision, curriculum, relevance to career goals, strengths and weaknesses. RESULTS: Of the 80 students recruited during 2001-2007, 69 (86%) acquired seven core competencies (epidemiology, surveillance, outbreaks, research, human subjects protection, communication and management) and graduated through completion of at least six field assignments. The faculty-to-student ratio ranged between 0.4 and 0.12 (expected: 0.25). The curriculum was continuously adapted with all resources available on-line. Fieldwork led to the production of 158 scientific communications presented at international meetings and to 29 manuscripts accepted in indexed, peer-reviewed journals. The online survey showed that while most graduates acquired competencies, unmet needs persisted in laboratory sciences, data analysis tools and faculty-to-student ratio. CONCLUSIONS: NIE adapted the international FETP model to India. However, further efforts are required to scale up the programme and to develop career tracks for field epidemiologists in the country.

The heterogeneity of measles epidemiology in India: implications for improving control measures.

BACKGROUND: Measles vaccination coverage varies in India. Trainees of the Field Epidemiology Training Programme (FETP) investigated 8 outbreaks from 2004 through 2006 in Himachal Pradesh, Uttaranchal, Tamil Nadu, and West Bengal. We reviewed these outbreaks to contribute to the description of the epidemiology of measles and propose recommendations for control. METHODS: FETP trainees searched for measles cases through stimulated passive surveillance or door-to-door case search; estimated attack rates, case fatality, and the median age of case patients; interviewed mothers about vaccination status of their children; and collected serum samples for immunoglobulin M serological testing whenever possible. For 3 outbreaks, the trainees estimated the vaccine efficacy for children >12 months of age through cohort studies. RESULTS: Six of the 8 outbreaks were serologically confirmed. Compared with outbreaks in other states, outbreaks in states with vaccination coverage of >90% had a higher median age among case patients and a lower median attack rate. Six deaths (case fatality rate, 1.5%) occurred during the 5 outbreaks for which vitamin A was not used. The vaccine efficacy was 84% (95% confidence interval [CI], 74%-91%) in Himachal Pradesh. In West Bengal, it was 66% (95% CI, 44%-80%) in 2005 and 81% (95% CI, 67%-89%) in 2006. CONCLUSIONS: In states with higher coverage, attack rates were lower and case patients were older. Although states with coverage of <90% should increase 1-dose coverage and address coverage in pockets that are poorly reached, a second opportunity for measles vaccination could be considered in states such as Himachal Pradesh and Tamil Nadu. Use of vitamin A for case management needs to be generalized.

Maternal Vitamin B12 Status During Pregnancy and Its Association With Outcomes of Pregnancy and Health of the Offspring: A Systematic Review and Implications for Policy in India.

Background: Vitamins B12 and folate participate in the one-carbon metabolism cycle and hence regulate fetal growth. Though vitamin B12 deficiency is widely prevalent, the current public health policy in India is to supplement only iron and folic acid for the prevention of anaemia. Prompted by our research findings of the importance of maternal vitamin B12 status for a healthy pregnancy, birth and offspring health outcomes, we evaluated available literature evidence using a systematic review approach, to inform policy. Methods: A systematic search was performed for relevant Indian studies in the MEDLINE/PubMed and IndMed databases. We selected studies reporting maternal vitamin B12 status (dietary intake or blood concentrations), and/or metabolic markers of vitamin B12 deficiency (homocysteine, methylmalonic acid) or haematological indices during pregnancy and their associations with outcomes of pregnancy, infancy or in later life. Intervention trials of vitamin B12 during pregnancy were also included. Quality of evidence was assessed on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Of the 635 articles identified, 46 studies met the inclusion criteria (cohort studies-26, case-control studies-13, RCT's -7). There is a high prevalence of vitamin B12 deficiency in Indian women during pregnancy (40-70%) (3 studies). Observational studies support associations (adjusted for potential sociodemographic confounders, maternal body size, postnatal factors) of lower maternal B12, higher homocysteine or an imbalance between vitamin B12-folate status with a higher risk of NTDs (6 studies), pregnancy complications (recurrent pregnancy losses, gestational diabetes, pre-eclampsia) (9 studies), lower birth weight (10 studies) and adverse longer-term health outcomes in the offspring (cognitive functions, adiposity, insulin resistance) (11 studies). Vitamin B12 supplementation (7 RCT's) in pregnancy showed a beneficial effect on offspring neurocognitive development and an effect on birth weight was inconclusive. There is a high quality evidence to support the role of low maternal vitamin B12 in higher risk for NTD and low birth weight and moderate-quality evidence for higher risk of gestational diabetes and later life adverse health outcomes (cognitive functions, risk for diabetes) in offspring. Conclusion: In the Indian population low maternal vitaminB12 status, is associated with adverse maternal and child health outcomes. The level of evidence supports adding vitamin B12 to existing nutritional programs in India for extended benefits on outcomes in pregnancy and offspring health besides control of anaemia. Systematic Review Registration: [website], identifier [registration number].

The metabolic syndrome and associated risk factors in an urban industrial male population in South India.

BACKGROUND: The metabolic syndrome is characterized by clustering of risk factors, which predisposes subjects to increased risk of diabetes and cardiovascular disease. Objectives of this study were to estimate prevalence of the metabolic syndrome and determine the association of risk factors with the metabolic syndrome in an urban industrial male population in Chennai, India. METHODS: We conducted a cross-sectional survey for male employees working in an industrial unit. The survey included questionnaire for risk factors, anthropometric and blood pressure measurements. Blood samples were collected for the fasting plasma glucose, serum cholesterol, high-density lipoprotein cholesterol and triglycerides. The metabolic syndrome was defined using International Diabetes Federation (IDF) and American Heart Association (AHA)/National Heart Lung and Blood Institute (NHLBI) criteria. RESULTS: The total numbers of male subjects included in the study were 1077. The prevalence of the metabolic syndrome was 41.3% and 51.4% using IDF and AHA/NHLBI criteria respectively. Risk factors were age above 35 years, family history of diabetes and body mass index (BMI) above 23.9 kg/m2. The consumption of more than three servings of fruits and vegetables was protective. CONCLUSION: The prevalence of the metabolic syndrome was very high in select industrial population in south India. Higher BMI and low intake of fruits and vegetables are modifiable by life style modification. Work site screening for the metabolic syndrome would facilitate the early detection and treatment.

Detection of Immunoglobulin M and Immunoglobulin G Antibodies Against Orientia tsutsugamushi for Scrub Typhus Diagnosis and Serosurvey in Endemic Regions.

OBJECTIVE: To estimate the regional cutoff of optical density (OD) values for immuno-globulin M (IgM) antibodies against Orientia tsutsugamushi in serum and cerebrospinal fluid (CSF) for clinical diagnosis of scrub typhus and immunoglobulin G (IgG) antibodies in serum for sero-epidemiology in Gorakhpur, Uttar Pradesh, India. METHODS: We used data from a serological investigation of acute encephalitis syndrome patients (n=407) during the 2016 outbreak in Gorakhpur, India to determine the cutoff for OD values for IgM antibodies, and from community-based serosurveys (n=1991) to estimate the cutoff for OD values for IgG antibodies. RESULTS: We determined regionally relevant cutoff for OD values of 0.76 for IgM antibodies in serum and 0.22 in cerebrospinal fluid for scrub typhus diagnosis. For serosurveys, IgG antibody cutoff was 1.5. CONCLUSION: We have proposed locally relevant cutoffs for scrub typhus endemic regions, which may be useful for correctly classifying infected population.

A malaria outbreak in Naxalbari, Darjeeling district, West Bengal, India, 2005: weaknesses in disease control, important risk factors.

An outbreak of malaria in Naxalbari, West Bengal, India, in 2005 was investigated to understand determinants and propose control measures. Malaria cases were slide-confirmed. Methods included calculation of annual blood examination rates (ABER, number of slides examined/population), collection of water specimens from potential vector-breeding sites, sorting of villages in categories depending on the number of abandoned wells within two kilometers radius and review of the DDT spray coverage. Cases were compared with matched neighbourhood controls in terms of personal protection using matched odds ratios (MOR). 7,303 cases and 17 deaths were reported between April 2005 and March 2006 with a peak during October rains (Attack rate: 50 per 1,000, case fatality: 0.2%). The attack rate increased according to the number of abandoned wells within 2 kilometres radius (P < 0.0001, Chi-square for trend). Abandoned wells were Anopheles breeding sites. Compared with controls, cases were more likely to sleep outdoors (MOR: 3.8) and less likely to use of mosquito nets and repellents (MOR: 0.3 and 0.1, respectively). DDT spray coverage and ABER were 39% and 3.5%, below the recommended 85% and 10%, respectively. Overall, this outbreak resulted from weaknesses in malaria control measures and a combination of factors, including vector breeding, low implementation of personal protection and weak case detection.

Risk factors for cardiovascular disease in rural South India: cohort study.

BACKGROUND AND OBJECTIVES: Cardiovascular diseases (CVD) accounted for one-third of the deaths in India. We conducted a cohort study to estimate the incidence of CVD and the association of established risk factors with the incident CVD in a rural population in South India. DESIGN, SETTING AND PARTICIPANTS: We conducted a community-based cohort study among 6026 adults aged 25-64 years in five villages in Tiruvallur, Tamil Nadu. We did baseline (2005-2007) and two follow-up surveys in 2008-2009 and 2013-2015. Risk factors studied were tobacco, alcohol, hypertension, self-reported diabetes and central obesity. OUTCOME MEASURES: Outcome measures were fatal or non-fatal ischaemic heart disease or cerebrovascular event. We estimated HRs for the risk factors and population attributable fraction (PAF). RESULTS: We followed up 5641 (94.4%) subjects, and follow-up duration was 33 371 person years. The overall incidence of cardiovascular event or death was 4.6 per 1000 person years. Current smoking (HR 1.6, 95% CI 1.1 to 2.6) and hypertension (HR 2.2, 95% CI 1.5 to 3.4) were the risk factors among men and accounted for 47% of the PAF. Among women, hypertension (HR 1.8, 95% CI 1.0 to 3.4), self-reported diabetes (HR 4.3, 95% CI 2.2 to 8.1) and central obesity (HR 2.2, 95% CI 1.2 to 4.0) were associated with CVD and accounted for more than half of the PAF. CONCLUSIONS: We described the high burden of fatal CVD and identified the role of CVD risk factors such as hypertension, self-reported diabetes, smoking and central obesity. There is an urgent need to implement low-cost interventions such as smoking cessation and treat hypertension and diabetes in primary care settings.