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BACKGROUND: The first national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurvey in India, done in May-June, 2020, among adults aged 18 years or older from 21 states, found a SARS-CoV-2 IgG antibody seroprevalence of 0·73% (95% CI 0·34-1·13). We aimed to assess the more recent nationwide seroprevalence in the general population in India. METHODS: We did a second household serosurvey among individuals aged 10 years or older in the same 700 villages or wards within 70 districts in India that were included in the first serosurvey. Individuals aged younger than 10 years and households that did not respond at the time of survey were excluded. Participants were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. 3-5 mL of venous blood was collected from each participant and blood samples were tested using the Abbott SARS-CoV-2 IgG assay. Seroprevalence was estimated after applying the sampling weights and adjusting for clustering and assay characteristics. We randomly selected one adult serum sample from each household to compare the seroprevalence among adults between the two serosurveys. FINDINGS: Between Aug 18 and Sept 20, 2020, we enrolled and collected serum samples from 29 082 individuals from 15 613 households. The weighted and adjusted seroprevalence of SARS-CoV-2 IgG antibodies in individuals aged 10 years or older was 6·6% (95% CI 5·8-7·4). Among 15 084 randomly selected adults (one per household), the weighted and adjusted seroprevalence was 7·1% (6·2-8·2). Seroprevalence was similar across age groups, sexes, and occupations. Seroprevalence was highest in urban slum areas followed by urban non-slum and rural areas. We estimated a cumulative 74·3 million infections in the country by Aug 18, 2020, with 26-32 infections for every reported COVID-19 case. INTERPRETATION: Approximately one in 15 individuals aged 10 years or older in India had SARS-CoV-2 infection by Aug 18, 2020. The adult seroprevalence increased approximately tenfold between May and August, 2020. Lower infection-to-case ratio in August than in May reflects a substantial increase in testing across the country. FUNDING: Indian Council of Medical Research.

Background/Objectives: Globally, the COVID-19 pandemic and its prevention and control policies have impacted maternal and child health (MCH) services. This study documents the challenges faced by patients in accessing MCH services, and the experiences of health care providers in delivering those services during the COVID-19 outbreak, explicitly focusing on the lockdown period in India. Methods: A cross-sectional study (rapid survey) was conducted in 18 districts from 6 states of India during March to June, 2020. The sample size included 540 MCH patients, 18 gynaecologists, 18 paediatricians, 18 district immunisation officers and 108 frontline health workers. Bivariate analysis and multivariable analysis were used to assess the association between sociodemographic characteristics, and challenges faced by the patients. Results: More than one-third of patients (n = 212; 39%) reported that accessing MCH services was a challenge during the lockdown period, with major challenges being transportation-related difficulties (n = 99; 46%) unavailability of hospital-based services (n = 54; 23%) and interrupted outreach health services (n = 39; 18.4%). The supply-side challenges mainly included lack of infrastructural preparedness for outbreak situations, and a shortage of human resources. Conclusions/Recommendations: A holistic approach is required that focuses on both preparedness and response to the outbreak, as well reassignment and reinforcement of health care professionals to continue catering to and maintaining essential MCH services during the pandemic.

The aetiology of non-malaria vector-borne diseases in malaria-endemic, forested, rural, and tribal-dominated areas of Dhalai, Tripura, in north-east India, was studied for the first time in the samples collected from malaria Rapid Diagnostic Kit negative febrile patients by door-to-door visits in the villages and primary health centres. Two hundred and sixty serum samples were tested for the Dengue NS1 antigen and the IgM antibodies of Dengue, Chikungunya, Scrub Typhus (ST), and Japanese Encephalitis (JE) during April 2019–March 2020. Fifteen Dengue, six JE, twelve Chikungunya, nine ST and three Leptospirosis, and mixed infections of three JE + Chikungunya, four Dengue + Chikungunya, three Dengue + JE + Chikungunya, one Dengue + Chikungunya + ST, and one Dengue + ST were found positive by IgM ELISA tests, and four for the Dengue NS1 antigen, all without any travel history. True prevalence values estimated for infections detected by Dengue IgM were 0.134 (95% CI: 0.08–0.2), Chikungunya were 0.084 (95% CI: 0.05–0.13), Scrub were 0.043 (95% CI: 0.01–0.09), and Japanese Encephalitis were 0.045 (95% CI: 0.02–0.09). Dengue and Chikungunya were associated significantly more with a younger age. There was a lack of a defined set of symptoms for any of the Dengue, Chikungunya, JE or ST infections, as indicated by the k-modes cluster analysis. Interestingly, most of these symptoms have an overlapping set with malaria; thereby, it becomes imperative that malaria and these non-malaria vector-borne disease diagnoses are made in a coordinated manner. Findings from this study call for advances in routine diagnostic procedures and the development of a protocol that can accommodate, currently, in practicing the rapid diagnosis of malaria and other vector-borne diseases, which is doable even in the resource-poor settings of rural hospitals and during community fever surveillance.

Background Malaria continues to be a major public health problem in the Northeastern part of India despite the implementation of vector control measures and changes in drug policies. To develop successful vaccines against malaria, it is important to assess the diversity of vaccine candidate antigens in field isolates. This study was done to assess the diversity of Plasmodium falciparum AMA-1 vaccine candidate antigen in a malaria-endemic region of Tripura in Northeast India and compare it with previously reported global isolates with a view to assess the feasibility of developing a universal vaccine based on this antigen. Methods Patients with fever and malaria-like illness were screened for malaria and P. falciparum positive cases were recruited for the current study. The diversity of PfAMA-1 vaccine candidate antigen was evaluated by nested PCR and RFLP. A selected number of samples were sequenced using the Sanger technique. Results Among 56 P. falciparum positive isolates, Pfama-1 was successfully amplified in 75% (n = 42) isolates. Allele frequencies of PfAMA-1 antigen were 16.6% (n = 7) for 3D7 allele and 33.3% (n = 14) in both K1 and HB3 alleles. DNA sequencing revealed 13 haplotypes in the Pfama-1 gene including three unique haplotypes not reported earlier. No unique amino-acid substitutions were found. Global analysis with 2761 sequences revealed 435 haplotypes with a very complex network composition and few clusters. Nucleotide diversity for Tripura (0.02582 ± 0.00160) showed concordance with South-East Asian isolates while recombination parameter (Rm = 8) was lower than previous reports from India. Population genetic structure showed moderate differentiation. Conclusions Besides documenting all previously reported allelic forms of the vaccine candidate PfAMA-1 antigen of P. falciparum, new haplotypes not reported earlier, were found in Tripura. Neutrality tests indicate that the Pfama-1 population in Tripura is under balancing selection. This is consistent with global patterns. However, the high haplotype diversity observed in the global Pfama-1 network analysis indicates that designing a universal vaccine based on this antigen may be difficult. This information adds to the existing database of genetic diversity of field isolates of P. falciparum and may be helpful in the development of more effective vaccines against the parasite.

BACKGROUND While leukocyte telomere length has been linked with altered risk in adult cancer, limited information is available on its association with risk in pediatric solid tumors. We investigated the association of telomeric alterations with risk of pediatric solid tumors. We also investigated whether altered telomeres cooperated with the TP53 rs1042522, MDM2 rs2279744 and CDKN1A (p21cip1 ) rs1059234 single-nucleotide polymorphisms to modify cancer risk. METHODS A total of 101 tumor patients and 202 controls were recruited for this age- and gender-matched case-control study. Relative telomere length (RTL) was determined in peripheral blood leukocytes using quantitative real-time polymerase chain reaction (PCR), and the polymorphisms were genotyped using PCR-restriction fragment length polymorphism. RESULTS Using median RTL in the healthy controls as a cut-off, children with longer telomeres were at an increased risk of developing a solid tumor (OR, 2.70; P

Visceral leishmaniasis (VL) or Kala-azar is a vector borne protozoan infection caused by Leishmania donovani in the Indian subcontinent mainly India, Nepal and Bangladesh. It is a major public health problem in these countries mostly affecting the socio-economically poor population. Leishmaniasis ranks the third most important disease after malaria and filariasis but is still considered as one of the neglected tropical diseases of the world. For development of better therapeutic agents and effective vaccine against VL, there is a need to understand host immunological changes that play a vital role during course of infection. Therefore, we investigated the role of Th17 pathway in Balb/c mice during Leishmania donovani infection and treatment with amphotericin B. Mice were divided in four groups i.e. Control, Infected, Uninfected treated and Infected treated. The cytokine levels were estimated in the spleen of Balb/c mice on days 1, 3, 7, 14, 17, 21, 28, 35, 45 and 60 post infection and during course of treatment. The mRNA levels of the Th17 pathway during active Leishmania donovani infection and after treatment were determined by real time polymerase chain reaction (RT-PCR) and protein levels by flow cytometry and ELISA. Results of our study revealed that active infection was associated with low levels of Th17 cytokines IL-17, IL-22 and IL-23 and elevated levels of IL-6, IL-1β and TGF-β. Amphotericin B treatment restored production of pro-inflammatory cytokines IL-17 and IL-22. The levels of transcription factor RORγt were found to correlate with the levels of IL-17 during infection and also after chemotherapy whereas STAT3 levels were elevated during infection and vice versa after treatment. The findings of this study suggest that Th17 cytokines IL-17 and IL-22 are associated with protection against VL infection and development of any interventions or chemotherapeutic agents targeting Th17 pathway could be an important approach for VL treatment.

Neurocysticercosis is a significant cause of epilepsy in the tropics. The present cross-sectional survey was conducted in the socioeconomically backward tea garden community of Assam to gauge the prevalence of neurocysticercosis in patients with active epilepsy and to determine the associated risk factors. In a door to door survey, a total of 1028 individuals from every fifth household of the study Teagarden were enrolled to identify self-reported seizure cases, followed by a neurological examination to confirm the diagnosis of active epilepsy. Patients with active epilepsy underwent clinical, epidemiological, neuroimaging (contrast-enhanced computerized tomography) and immunological evaluations to establish the diagnosis of neurocysticercosis. Clinically confirmed 53 (5.16%) active epilepsy were identified; 45 agreed to further assessment for neurocysticercosis and 19 (42.2%) cases fulfilled either definitive or probable diagnostic criteria for neurocysticercosis. Patients with epilepsy due to neurocysticercosis were more likely to suffer from taeniasis (20.0% vs 0.0%), rear pigs (57.9% vs 15.4%) or have pigs in their neighbourhood (78.9% vs 53.8%) relative to epileptic patients without neurocysticercosis. Rearing pigs (aOR 14.35, 95% CI: 3.98–51.75) or having pigs in the neighbourhood (aOR 12.34, 95% CI: 2.53–60.31) were independent risk factors of neurocysticercosis. In this community, the prevalence of taeniasis (adult worm infection) was 6.6% based on microscopy. The study reports a high prevalence of active epilepsy in the tea garden community of Assam and neurocysticercosis as its primary cause. The high prevalence of taeniasis is also a significant concern.

BACKGROUND A surveillance system is the foundation for disease prevention and control. Malaria surveillance is crucial for tracking regional and temporal patterns in disease incidence, assisting in recorded details, timely reporting, and frequency of analysis. OBJECTIVE In this study, we aim to develop an integrated surveillance graphical app called FeverTracker, which has been designed to assist the community and health care workers in digital surveillance and thereby contribute toward malaria control and elimination. METHODS FeverTracker uses a geographic information system and is linked to a web app with automated data digitization, SMS text messaging, and advisory instructions, thereby allowing immediate notification of individual cases to district and state health authorities in real time. RESULTS The use of FeverTracker for malaria surveillance is evident, given the archaic paper-based surveillance tools used currently. The use of the app in 19 tribal villages of the Dhalai district in Tripura, India, assisted in the surveillance of 1880 suspected malaria patients and confirmed malaria infection in 93.4% (114/122; Plasmodium falciparum), 4.9% (6/122; P vivax), and 1.6% (2/122; P falciparum/P vivax mixed infection) of cases. Digital tools such as FeverTracker will be critical in integrating disease surveillance, and they offer instant data digitization for downstream processing. CONCLUSIONS The use of this technology in health care and research will strengthen the ongoing efforts to eliminate malaria. Moreover, FeverTracker provides a modifiable template for deployment in other disease systems.

Background: Repeated cross-sectional serosurveys in the same geographic area establish the trend of the evolving pandemic. We present the findings of the third round of a national serosurvey to estimate the seroprevalence of SARS-CoV-2 infection among the general population and health care workers of India. Methods: We conducted the third population-based serosurvey between Dec 18, 2020 and Jan 6, 2021 in the same 700 villages or wards from 70 districts in 21 states across India, which were selected for the first and second serosurveys. We enrolled from each district, at least 400 individuals aged ≥ 10 years from general population and 100 HCWs from sub-district level public health facilities. Serum samples from general population were tested for the presence of IgG antibodies against nucleocapsid (N) and spike protein (S1-RBD) of SARS-CoV-2 using the Abbott and Siemens assays respectively, whereas sera from HCWs were tested for anti-S1-RBD. For general population, sera positive for either of the antibodies were considered positive, while sera positive for anti-S1-RBD were considered as positive for HCW. Weighted seroprevalence estimates were adjusted for sensitivity and specificity of respective assays. Findings: Of the 28,598 sera from general population, 4585 (16%) had IgG antibodies against N, 6647 (23.2%) against S1-RBD and 7436 (26%) against either. The weighted and assay characteristic adjusted seroprevalence against either of the antibodies was 24.1 (95%CI: 23.0% to 25.3%). Seroprevalence was lower in rural areas (21.4%, 95% CI: 20.3% to 22.6%) compared to urban non-slum (29.4%, 95% CI: 26.9% - 32.1%) and slum areas (34.6%, 95% CI: 31.0% to 38.3%). Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI: 23.5% to 27.8%). Interpretation: Nearly one in four individuals aged 10 years or older from general population as well as HCWs were exposed to SARS-CoV-2 by December 2020 amounting to 271 million infections in India. Funding Statement: Indian Council of Medical Research Declaration of Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare no competing interests Ethics Approval Statement: The project was approved by Institutional Human Ethics Committee at ICMR-National Institute of Epidemiology.

Background: India witnessed a severe second wave of COVID-19 during March and June 2021. We did the fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged >=6 years and health care workers (HCWs). Methods: We did a cross-sectional study between 14 June and 6 July 2021 in 700 clusters in the same 70 districts across 21 states/Union Territory. From each district, a minimum of 400 individuals aged >=6 years from general population and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test adjusted seroprevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein along with 95% CI. Findings: Of the 28,975 sera tested, the weighted and test adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged >=6 years was 67.6% (95% CI: 66.4 – 68.7). The seroprevalence increased with age and was not different in rural and urban areas. Compared to unvaccinated adults (62.3%, 95% CI: 60.9 – 63.7), seroprevalence was significantly higher among individuals who received one (81.0%, 95% CI: 79.6 - 82.3) and two doses (89.8%, 95% CI: 88.4 - 91.1). The seroprevalence of IgG antibodies among 7,252 health care workers was 85.2% (95% CI: 83.5 - 86.7). Interpretation: Nearly one third of the population is still seronegative. It is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions. Funding: Indian Council of Medical Research. Declaration of Interest: None to declare. Ethical Approval: The Institutional Human Ethics Committee of the ICMR National Institute of Epidemiology, Chennai approved the study protocol.

Background & objectives: Population-based seroepidemiological studies measure the extent of SARS-CoV-2 infection in a country. We report the findings of the first round of a national serosurvey, conducted to estimate the seroprevalence of SARS-CoV-2 infection among adult population of India. Methods: From May 11 to June 4, 2020, a randomly sampled, community-based survey was conducted in 700 villages/wards, selected from the 70 districts of the 21 States of India, categorized into four strata based on the incidence of reported COVID-19 cases. Four hundred adults per district were enrolled from 10 clusters with one adult per household. Serum samples were tested for IgG antibodies using COVID Kavach ELISA kit. All positive serum samples were re-tested using Euroimmun SARS-CoV-2 ELISA. Adjusting for survey design and serial test performance, weighted seroprevalence, number of infections, infection to case ratio (ICR) and infection fatality ratio (IFR) were calculated. Logistic regression was used to determine the factors associated with IgG positivity. Results: Total of 30,283 households were visited and 28,000 individuals were enrolled. Population-weighted seroprevalence after adjusting for test performance was 0.73 per cent [95% confidence interval (CI): 0.34-1.13]. Males, living in urban slums and occupation with high risk of exposure to potentially infected persons were associated with seropositivity. A cumulative 6,468,388 adult infections (95% CI: 3,829,029-11,199,423) were estimated in India by the early May. The overall ICR was between 81.6 (95% CI: 48.3-141.4) and 130.1 (95% CI: 77.0-225.2) with May 11 and May 3, 2020 as plausible reference points for reported cases. The IFR in the surveyed districts from high stratum, where death reporting was more robust, was 11.72 (95% CI: 7.21-19.19) to 15.04 (9.26-24.62) per 10,000 adults, using May 24 and June 1, 2020 as plausible reference points for reported deaths. Interpretation & conclusions: Seroprevalence of SARS-CoV-2 was low among the adult population in India around the beginning of May 2020. Further national and local serosurveys are recommended to better inform the public health strategy for containment and mitigation of the epidemic in various parts of the country.

COVID-19 pandemic has triggered social stigma towards individuals affected and their families. This study describes the process undertaken for the development and validation of scales to assess stigmatizing attitudes and experiences among COVID-19 and non-COVID-19 participants from the community.COVID-19 Stigma Scale and Community COVID-19 Stigma Scale constituting 13 and six items, respectively, were developed based on review of literature and news reports, expert committee evaluation and participants' interviews through telephone for a multicentric study in India. For content validity, 61 (30 COVID-19-recovered and 31 non-COVID-19 participants from the community) were recruited. Test-retest reliability of the scales was assessed among 99 participants (41 COVID-19 recovered and 58 non-COVID-19). Participants were administered the scale at two-time points after a gap of 7-12 days. Cronbach's alpha, overall percentage agreement and kappa statistics were used to assess internal consistency and test-retest reliability.Items in the scales were relevant and comprehensible. Both the scales had Cronbach's α above 0.6 indicating moderate-to-good internal consistency. Test-retest reliability assessed using kappa statistics indicated that for the COVID-19 Stigma Scale, seven items had a moderate agreement (0.4-0.6). For the Community COVID-19 Stigma Scale, four items had a moderate agreement.Validity and reliability of the two stigma scales indicated that the scales were comprehensible and had moderate internal consistency. These scales could be used to assess COVID-19 stigma and help in the development of appropriate stigma reduction interventions for COVID-19 infected, and mitigation of stigmatizing attitudes in the community.

Neurocysticercosis (NCC) is a parasitic disease of the central nervous system, which is caused by the metacestode of the pork tapeworm,Over a period of 2 years, 152 active epilepsy patients were investigated based on clinical, epidemiological, neuroimaging (contrast-enhanced computerized tomography), and immunological techniques to establish the diagnosis of NCC. A precoded questionnaire was administered to patients and/or guardians to collect detailed medical history.Ninety-three cases (61.2%) fulfilled either definitive or probable diagnostic criteria for NCC. Anti-cysticercus immunoglobulin G antibodies were detected by ELISA and enzyme electro-immune transfer blot in 69 (45.4%) active epilepsy patients. Seroprevalence was higher in males, 46.6% (54/116); than in females, 41.7% (15/36), and increased significantly with age; peaking in the 20-39 years age group (36/76; χThis study indicates that NCC is a major cause of active epilepsy in Assam. A high prevalence of pediatric NCC is also a major concern.

Background Dietary factors, tobacco, and alcohol use have been identified as important factors of rising various cancer incidence in several northeastern states of India. However, little is known about the factors associated with hepatocellular carcinoma (HCC) in this region. The aim of the paper was to identify the factors associated with HCC in the northeast region. Methods A case-control study was conducted in Arunachal Pradesh and Sikkim, two northeastern states of India, including 104 histologically-confirmed cases of HCC and same number (104) of age and sex matched control enrolled. Logistic regression analysis was performed to identify the factors associated with HCC. Results A statistically significant association was demonstrated between HCC and alcohol consumption, consumption of ‘Sai-mod’ (OR 2.77, CI 1.57–4.87) a homemade alcohol beverage, and with HBV (OR 7.97, CI 3.36–18.94). Positive synergism index (S = 3.04) was observed between HBV and alcohol consumption to risk of HCC. Higher intake of processed meat (OR 2.56, CI 1.09–6.03) and processed fish (OR 2.24, CI 1.02–4.95) were found associated with increased risk of HCC; and decreased risk of HCC with fresh fish, fruits, and milk. Conclusions Strong relationship between different dietary factors, alcohol beverage with HCC suggests that control on dietary and drinking habit will be an important strategy to combat HCC in this region. Risk factors identified in this study will help to plan more effectively targeted risk reduction strategies and programs in this region.

Background A surveillance system is the foundation for disease prevention and control. Malaria surveillance is crucial for tracking regional and temporal patterns in disease incidence, assisting in recorded details, timely reporting, and frequency of analysis. Objective In this study, we aim to develop an integrated surveillance graphical app called FeverTracker, which has been designed to assist the community and health care workers in digital surveillance and thereby contribute toward malaria control and elimination. Methods FeverTracker uses a geographic information system and is linked to a web app with automated data digitization, SMS text messaging, and advisory instructions, thereby allowing immediate notification of individual cases to district and state health authorities in real time. Results The use of FeverTracker for malaria surveillance is evident, given the archaic paper-based surveillance tools used currently. The use of the app in 19 tribal villages of the Dhalai district in Tripura, India, assisted in the surveillance of 1880 suspected malaria patients and confirmed malaria infection in 93.4% (114/122; Plasmodium falciparum), 4.9% (6/122; P vivax), and 1.6% (2/122; P falciparum/P vivax mixed infection) of cases. Digital tools such as FeverTracker will be critical in integrating disease surveillance, and they offer instant data digitization for downstream processing. Conclusions The use of this technology in health care and research will strengthen the ongoing efforts to eliminate malaria. Moreover, FeverTracker provides a modifiable template for deployment in other disease systems.

With India aiming to achieve malaria elimination by 2030, several strategies have been put in place. With that aim, mass surveillance is now being conducted in some malaria-endemic pockets. As dry season mass surveillance has been shown to have its importance in targeting the reservoir, a study was undertaken to assess the parasite load by a sensitive molecular method during one of the mass surveys conducted in the dry winter period. It was executed in two malaria-endemic villages of Dhalai District, Tripura, in northeast India, also reported as P. falciparum predominated area. The present study found an enormous burden of Rapid Diagnostic Test negative malaria cases with P. vivax along with P. vivax and P. falciparum mixed infections during the mass surveillance from febrile and afebrile cases in dry winter months (February 2021–March 2021). Of the total 150 samples tested, 72 (48%) were positive and 78 (52%) negative for malaria by PCR. Out of the 72 positives, 6 (8.33%) were P. falciparum, 40 (55.55%) P. vivax, and 26 (36.11%) mixed infections. Out of 78 malaria negative samples, 6 (7.7%) were with symptoms, while among the total malaria positive, 72 cases 7 (9.8%) were with symptoms, and 65 (90.2%) were asymptomatic. Out of 114 samples tested by both microscopy and PCR, 42 samples turned out to be submicroscopic with 4 P. falciparum, 23 P. vivax, and 15 mixed infections. Although all P. vivax submicroscopic infections were asymptomatic, three P. falciparum cases were found to be febrile. Evidence of malaria transmission was also found in the vectors in the winter month. The study ascertained the use of molecular diagnostic techniques in detecting the actual burden of malaria, especially of P. vivax, in mass surveys. As Jhum cultivators in Tripura are at high risk, screening for the malarial reservoirs in pre-Jhum months can help with malaria control and elimination.

X-ray repair cross complementary group gene is one of the most studied candidate gene involved in different types of cancers. Studies have shown that X-ray repair cross complementary genes are significantly associated with increased risk of breast cancer in females. Moreover, studies have revealed that X-ray repair cross complementary gene polymorphism significantly varies between and within different ethnic groups globally. The present case-control study was aimed to investigate the association of X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross complementary 3 (Thr241Met) polymorphism with the risk of breast cancer in females from northeastern region of India. The present case-control study includes histopathologically confirmed and newly diagnosed 464 cases with breast cancer and 534 apparently healthy neighborhood community controls. Information on sociodemographic factors and putative risk factors were collected from each study participant by conducting face-to-face interviews. Genotyping of X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross complementary 3 (Thr241Met) was carried out by polymerase chain reaction-restriction fragment length polymorphism. For statistical analysis, both univariate and multivariate logistic regression analyses were performed. We also performed stratified analysis to find out the association of X-ray repair cross complementary genes with the risk of breast cancer stratified based on menstrual status. This study revealed that tryptophan allele (R/W-W/W genotype) in X-ray repair cross complementary 1A (Arg194Trp) gene significantly increased the risk of breast cancer (adjusted odds ratio = 1.44, 95% confidence interval = 1.06-1.97, P < .05 for R/W-W/W genotype). Moreover, it was found that tryptophan allele (W/W genotype) at codon 194 of X-ray repair cross complementary 1A (Arg194Trp) gene significantly increased the risk of breast cancer in premenopausal females (crude odds ratio = 1.66, 95% confidence interval = 1.11-2.46, P < .05 for R/W-W/W genotype). The present study did not reveal any significant association of X-ray repair cross complementary 3 (Thr241Met) polymorphism with the risk of breast cancer. The present study has explored that X-ray repair cross complementary 1A (Arg194Trp) gene polymorphism is significantly associated with the increased risk of breast cancer in premenopausal females from northeastern region of India which may be beneficial for prognostic purposes.

Background Anterior encephalocele (AE) is a rare congenital anomaly of the central nervous system which is thought to be associated with genetic defects in folate metabolism. Methods This case-control study investigated the interactions of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1)-1958G>A (rs2236225) and the methylenetetrahydrofolate reductase (MTHFR) - 677C>T (rs1801133) and 1298A>C (rs1801131) polymorphisms with the risk of AE in the Northeast Indian population. A total of 40 AE cases and 80 controls were investigated using polymerase chain reaction-restriction fragment length polymorphism technique. Results MTHFR 1298CC was significantly associated with AE risk (odds ratio [OR] 4.21; p = 0.01). The MTHFR haplotypes 677C-1298C/677T-1298A (OR, 2.50) and 677T-1298C (OR, 2.86) conferred risk in a progressive manner (χ2 = 9.82; p A was not associated with disease susceptibility. Children with the rs2236225 GA and the rs1801131 CC genotypes were at an increased risk as compared to the reference genotype of rs2236225 GG and rs1801131 AA (OR, 14.4; p = 0.02). Children with the rs2236225 GG and rs1801133 CT genotypes were also at an elevated risk (OR, 4.76; p = 0.01). The MTHFD1 polymorphism together with the MTHFR haplotypes elevated risk in a progressive manner (χ2 = 6.29; p = 0.01). Conclusion The data support our hypothesis of gene-gene interaction between MTHFD1 and MTHFR and the risk of AE. Together with the MTHFR haplotypes, MTHFD1 elevates risk in a progressive manner. The minor allelic frequencies of the MTHFD1 1958G>A and MTHFR 1298A>C in our populations were similar to those reported from Southeast Asian population, suggesting a possible explanation for the prevalence of this malformation in these regions. Birth Defects Research 109:432-444, 2017. © 2017 Wiley Periodicals, Inc.

Background Foodborne infections caused by lung flukes of the genus Paragonimus are a significant and widespread public health problem in tropical areas. Approximately 50 Paragonimus species have been reported to infect animals and humans, but Paragonimus westermani is responsible for the bulk of human disease. Despite their medical and economic importance, no genome sequence for any Paragonimus species is available. Results We sequenced and assembled the genome of P. westermani, which is among the largest of the known pathogen genomes with an estimated size of 1.1 Gb. A 922.8 Mb genome assembly was generated from Illumina and Pacific Biosciences (PacBio) sequence data, covering 84% of the estimated genome size. The genome has a high proportion (45%) of repeat-derived DNA, particularly of the long interspersed element and long terminal repeat subtypes, and the expansion of these elements may explain some of the large size. We predicted 12,852 protein coding genes, showing a high level of conservation with related trematode species. The majority of proteins (80%) had homologs in the human liver fluke Opisthorchis viverrini, with an average sequence identity of 64.1%. Assembly of the P. westermani mitochondrial genome from long PacBio reads resulted in a single high-quality circularized 20.6 kb contig. The contig harbored a 6.9 kb region of non-coding repetitive DNA comprised of three distinct repeat units. Our results suggest that the region is highly polymorphic in P. westermani, possibly even within single worm isolates. Conclusions The generated assembly represents the first Paragonimus genome sequence and will facilitate future molecular studies of this important, but neglected, parasite group.

a Prevalence of anaemia among adolescent girl students of Assam, a north-eastern state of India, was evaluated along with its associating determinants. The present study revealed that anaemia is a major public health problem among adolescent girl students of Assam. The overall prevalence of anaemia among adolescent girl students of Assam is as high as 71.5%. Non-nutritional factors such as infection due to helminths was substantially low (24.71%). Ascaris lumbricoides was the most frequent infection (10.6%), followed by Trichuris trichiura (6.2%), and hookworm infestations (3.9%). Polyparasitic infection (A. lumbricoides, T. trichiura and hookworm) was observed in 0.5% of the study subjects. While coinfection due to A. lumbricoides and T. trichiura was 2.3%, A. lumbricoides and hookworm was 1.1% and T. trichiura and hookworm was 0.9%. Serum ferritin level in a subgroup of samples was in the lower normal range. Malaria parasite was not detected in any of the slides. We have observed a gene frequency of 0.188 for β E -globin gene among the adolescent girl students of Assam. The gene frequency for β E -globin gene ranged from 0.071 to 0.266. Statistically significant difference (F=3.471; P=0.001) of mean haemoglobin level was observed in different types of haemoglobin variants. Multiple regression analysis, in a sub- set of samples having information on Hb levels (g/dl), helminthic infestation (A. lumbricoides, T. trichuria and hookworm), haemoglobin type, revealed haemoglobin type (Hb E) was the important determinant of anaemia among adolescent girl students in the present study.

Previous studies have not adequately captured the heterogeneous nature of the diabetes epidemic in India. The aim of the ongoing national Indian Council of Medical Research-INdia DIABetes study is to estimate the national prevalence of diabetes and prediabetes in India by estimating the prevalence by state.We used a stratified multistage design to obtain a community-based sample of 57 117 individuals aged 20 years or older. The sample population represented 14 of India's 28 states (eight from the mainland and six from the northeast of the country) and one union territory. States were sampled in a phased manner: phase I included Tamil Nadu, Chandigarh, Jharkhand, and Maharashtra, sampled between Nov 17, 2008, and April 16, 2010; phase II included Andhra Pradesh, Bihar, Gujarat, Karnataka, and Punjab, sampled between Sept 24, 2012, and July 26, 2013; and the northeastern phase included Assam, Mizoram, Arunachal Pradesh, Tripura, Manipur, and Meghalaya, with sampling done between Jan 5, 2012, and July 3, 2015. Capillary oral glucose tolerance tests were used to diagnose diabetes and prediabetes in accordance with WHO criteria. Our methods did not allow us to differentiate between type 1 and type 2 diabetes. The prevalence of diabetes in different states was assessed in relation to socioeconomic status (SES) of individuals and the per-capita gross domestic product (GDP) of each state. We used multiple logistic regression analysis to examine the association of various factors with the prevalence of diabetes and prediabetes.The overall prevalence of diabetes in all 15 states of India was 7·3% (95% CI 7·0-7·5). The prevalence of diabetes varied from 4·3% in Bihar (95% CI 3·7-5·0) to 10·0% (8·7-11·2) in Punjab and was higher in urban areas (11·2%, 10·6-11·8) than in rural areas (5·2%, 4·9-5·4; p0·0001) and higher in mainland states (8·3%, 7·9-8·7) than in the northeast (5·9%, 5·5-6·2; p0·0001). Overall, 1862 (47·3%) of 3938 individuals identified as having diabetes had not been diagnosed previously. States with higher per-capita GDP seemed to have a higher prevalence of diabetes (eg, Chandigarh, which had the highest GDP of US$ 3433, had the highest prevalence of 13·6%, 12.8-15·2). In rural areas of all states, diabetes was more prevalent in individuals of higher SES. However, in urban areas of some of the more affluent states (Chandigarh, Maharashtra, and Tamil Nadu), diabetes prevalence was higher in people with lower SES. The overall prevalence of prediabetes in all 15 states was 10·3% (10·0-10·6). The prevalence of prediabetes varied from 6·0% (5·1-6·8) in Mizoram to 14·7% (13·6-15·9) in Tripura, and the prevalence of impaired fasting glucose was generally higher than the prevalence of impaired glucose tolerance. Age, male sex, obesity, hypertension, and family history of diabetes were independent risk factors for diabetes in both urban and rural areas.There are large differences in diabetes prevalence between states in India. Our results show evidence of an epidemiological transition, with a higher prevalence of diabetes in low SES groups in the urban areas of the more economically developed states. The spread of diabetes to economically disadvantaged sections of society is a matter of great concern, warranting urgent preventive measures.Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare, Government of India.

Anterior encephalocele (AE) is a rare congenital anomaly of the central nervous system which is thought to be associated with genetic defects in folate metabolism.This case-control study investigated the interactions of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1)-1958GA (rs2236225) and the methylenetetrahydrofolate reductase (MTHFR) - 677CT (rs1801133) and 1298AC (rs1801131) polymorphisms with the risk of AE in the Northeast Indian population. A total of 40 AE cases and 80 controls were investigated using polymerase chain reaction-restriction fragment length polymorphism technique.MTHFR 1298CC was significantly associated with AE risk (odds ratio [OR] 4.21; p = 0.01). The MTHFR haplotypes 677C-1298C/677T-1298A (OR, 2.50) and 677T-1298C (OR, 2.86) conferred risk in a progressive manner (χThe data support our hypothesis of gene-gene interaction between MTHFD1 and MTHFR and the risk of AE. Together with the MTHFR haplotypes, MTHFD1 elevates risk in a progressive manner. The minor allelic frequencies of the MTHFD1 1958GA and MTHFR 1298AC in our populations were similar to those reported from Southeast Asian population, suggesting a possible explanation for the prevalence of this malformation in these regions. Birth Defects Research 109:432-444, 2017. © 2017 Wiley Periodicals, Inc.

Background : One of the infections that mimic tuberculosis (TB) is paragonimiasis (PRG), a foodborne parasitic disease caused by lung flukes of the genus Paragonimus . In the northeastern states of India, TB and PRG are endemic; however, PRG is rarely included in the differential diagnosis of TB. Objective : To address limited evidence on the dual burden of TB and PRG in northeastern India, we aimed to document the prevalence of PRG among TB patients using sputum smear, stool examination for children

BACKGROUND: A high number of pulmonary tuberculosis (PTB) cases have been reported from tea garden communities of Assam. Till date, no molecular epidemiological study was performed to investigate the association of candidate gene(s) with the risk PTB in this region. The present case‐control study was aimed to investigate the association of vitamin D receptor (VDR) gene polymorphisms and 22 bp deletion in the promoter region of toll‐like receptor 2 (TLR2) gene with the risk of PTB in tea garden communities of Assam. METHODS: Genotyping of VDR polymorphisms and TLR2Δ22 (‐196‐174) gene was carried out for 169 PTB cases and 227 apparently healthy community controls using blood samples by PCR‐RFLP followed by DNA sequencing. For association study, both univariate and multivariate logistic regression analyses were performed. RESULTS: This study has shown that BsmI and FokI polymorphisms of VDR gene significantly associated with an increased risk of PTB (AOR = 3.58, 95% CI = 1.64‐7.80, P

Toll-like receptors (TLRs) are evolutionary conserved cell surface receptors of the innate immune system. Smoking has significant immunological effects which are mediated via TLRs on various receptor-mediated innate response pathways. Polymorphisms of TLR genes are associated with susceptibility toward various malignancies. The present study was undertaken to examine the association between TLR2 ∆22 and gastric cancer. In this study, we also investigated the interaction between TLR2 ∆22 and smoking. A total of 133 histologically confirmed gastric cancer cases and 266 age-sex-matched controls were selected for this study. TLR2 ∆22 genotypes were determined by allele-specific polymerase chain reaction (PCR). Binary conditional logistic regression analysis was used to find the association of TLR2 ∆22 with risk of gastric cancer. Logistic regression using hierarchically well-formulated models was used for interaction analysis between smoking and TLR2 ∆22. Persons having TLR2 ∆22 heterozygous genotype had two times increased risk of gastric cancer in multivariate logistic regression model. The interaction analysis using hierarchical logistic regression models between smoking and TLR2 ∆22 by calculating separate X (2) for interaction model and only main effect model, the difference of X (2) 57.68-47.70 = 9.98 and degrees of freedom (df) 5-3 = 2, revealed significant (α = 0.05, df = 2) omnibus interaction. Our present study revealed TLR2 ∆22 to be significantly and independently associated with gastric cancer risk in Mizoram, and there is also evidence of significant interaction between smoking and TLR2 ∆22 with risk of gastric cancer.