Seropositivity of Chlamydia trachomatis & Toxoplasma gondii among male partners of infertile couples in Odisha, India: A facility-based exploratory study.

Chlamydia trachomatis (CT) is the most common curable sexually transmitted non-viral infection, which can cause urethritis, prostatitis, orchitis and epididymitis among males. Toxoplasma gondii, a protozoan causes toxoplasmosis among humans. These infections may lead to decreased fertility. Hence, this study was aimed to estimate the seropositivity of CT and T. gondii infection among the male partners of infertile couples in Odisha, India. In this facility-based cross-sectional study, first void urine, seminal fluid and blood sample were collected from 153 males attending infertility clinics including 74 healthy controls. Urine and seminal fluid were tested through polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay was used to detect immunoglobulin (Ig) G, IgA and IgM anti-Chlamydia and IgM anti-Toxoplasma antibodies through serum. The prevalence of CT was 1.26 per cent (95% CI: 0.03-6.85) as estimated from semen samples using PCR. We detected anti-Chlamydia antibodies IgM-four per cent [95% confidence interval (CI): 0.83-11.24]; IgA-28.16 per cent (95% CI: 18.13-40.09) and IgG-12.5 per cent (95% CI: 5.87-22.4) among participants. Anti-Toxoplasma antibodies IgM were observed in 27.63 per cent (95% CI: 17.98-39.08) of participants. None of the control samples were found positive. Overall seropositivity of CT and Toxoplasma infections is comparable, which suggests that greater attention is required for screening these infections at clinics, especially among infertile couples.

Mapping the distribution and trends of co-circulating dengue virus serotypes in Odisha, India: A retrospective facility-based analysis.

Background Dengue, caused by mosquito bite, is an emerging disease of international concern. Evidence regarding the prevalent dengue serotypes is scarce, but essential for its management during the outbreaks. Hence, we mapped the distribution and trends of currently prevalent dengue virus (DENV) serotypes in Odisha. Methods We conducted a facility-based retrospective study from referral samples sent for the diagnosis/confirmation of dengue in 2018. The samples were serologically tested for enzyme-linked immunosorbent assay (ELISA) IgM antibody and NS1. Only NS1-positive samples were chosen for sero-typing. A pool of 8-10 NS1-positive samples were analysed for district-wise serotypes. Ribonucleic acid extraction and nested polymerase chain reaction (PCR) was done from NS1-positive samples. The PCR products were then subjected to gel electrophoresis. Results A total of 2892 samples were screened for dengue virus across various districts of Odisha where 763 samples were found to be NS1-positive. Thirteen of 18 districts covering all topographies of Odisha predominantly had DENV2 serotype. Only few districts such as Balangir, Kalahandi and Rayagada had mixed serotypes. Conclusion Although DENV2 is predominantly prevalent, mixed serotypes too exist in Odisha. Evidence based on variations of dengue serotypes across topographies, seasons, gender and age groups may support public health efforts in preventing the disease.

Self-reactive IgG4 antibodies are associated with blocking of pathology in human lymphatic filariasis.

Lymphatic filariasis, a chronic disfiguring disease exhibits complex pathology. Based on different clinical manifestations, infected individuals are categorized into asymptomatic-carriers and chronic-patients. The mechanism behind differential clinical outcomes remains unclear. Roles of filaria-specific B cell responses in filariasis have been documented, whereas the contribution of B1 cell response and poly-specific IgG and IgA in the context of clinical filariasis is not deciphered. In this study, we measured the poly-specific IgG and IgA levels in different clinical categories of filariasis. Asymptomatic-carriers exhibited increased IgG4 antibodies against both filarial-antigens as well as auto-antigens compared to other clinical categories, although IgG against these auto-antigens remained lower. IgA levels against both filarial and auto-antigens were decreased in asymptomatic-carriers. A positive correlation between anti-filarial IgG4 and IgG4 against auto-antigens were observed, suggesting the synergistic role of poly-specific natural IgG4 with anti-filarial IgG4 in blocking the pathogenesis in asymptomatic microfilarial cases.

Species-specific and cross-reactive antigen of filarial worm: Brugia malayi and Setaria digitata.

BACKGROUND & OBJECTIVES: Generally filarial antigens have been found to be cross-reactive in nature. Identification of genus and species-specific antigens has not been successful so far. Due to lack of human adult filarial parasite, researchers have been using other adult worms like Setaria digitata, a cattle parasite or Brugia malayi, a rodent model for their research work. In this situation, specificity of the prepared antigen (S. digitata or B. malayi) to detect the antibodies to Wuchereria bancrofti is questionable. METHODS: In the present investigation, we have tested a panel of human sera (collected from the areas, endemic for bancroftian filariasis) to correlate the immune reactivity against somatic antigens of adult stages and microfilarial stages of S. digitata and B. malayi. Further, using intact microfilariae (mf) from the above two parasites along with W. bancrofti, we have analyzed the antibody response to the sheath antigens. A panel of infected human and cattle sera was tested by immunoperoxidase assay using intact mf of three different parasites, viz. W. bancrofti, B. malayi, and S. digitata. RESULTS: A very significant positive correlation in filarial Igs (polyvalent), IgG, IgM, IgE and IgG4 levels were found between the two adult somatic antigens of B. malayi and S. digitata when tested against human filarial sera. However, such a correlation was not found when mf antigens of B. malayi and S. digitata were tested against a panel of W. bancrofti sera indicating that antigens present in mf could be far less cross-reactive in comparison to those in adult stage parasites. INTERPRETATION & CONCLUSION: The results indicated the differential cross-reactivity of antisheath antibodies to the mf sheath of three different filarial parasites. Soluble antigens of S. digitata could inhibit antisheath antibody reactivity to only S. digitata mf sheath and not to mf sheath of W. bancrofti further confirming the specificity of sheath antigen.

Factors influencing implementation of mass drug administration for lymphatic filariasis elimination: a mixed-method study in Odisha, India.

Background: Lymphatic filariasis (LF) persists as a public health problem in India. Despite more than ten rounds of mass drug administration (MDA), LF continues to be endemic in the Dhenkanal district of Odisha. Hence, we assessed the coverage and compliance of the MDA program and explored the factors affecting it in the Dhenkanal district. Methods: An explanatory mixed-method study was conducted, wherein for the quantitative survey, 552 participants aged 2 years and above were recruited following a multistage cluster random sampling during February 2022. In-depth interviews were conducted among purposively selected key stakeholders and program implementers. Descriptive statistics were used to report coverage and compliance, along with a 95% confidence interval. Qualitative data were analyzed using a thematic approach. Results: We observed coverage of 99.28% and compliance of 85.87% for MDA drugs. Supervised drug administration proved to be a major pillar in increasing compliance. There was difficulty in administering drugs in urban areas due to gated societies, the absence of individuals during the day, and the perspective toward healthcare providers. Participants reported a lack of confidence in drug distributors and a fear of side effects as major causes for non-compliance. Conclusion: There is a need to strengthen MDA, especially in urban areas. An urban-specific strategy, along with surveillance, behavioral change communication, and the involvement of multi-disciplinary teams, is required.

Motivation-opportunity-ability-behaviour of community members and program implementers towards mass drug administration for lymphatic filariasis elimination in India: a systematic review and implementation priority.

Lymphatic filariasis (LF) is a significant public health issue in India. Despite 10-15 rounds of mass drug administration (MDA) in India, the global LF elimination target of 2030 appears challenging. To strengthen the program, community and provider perspectives on ways to bridge a gap in MDA are needed. Through the motivation-opportunity-ability-behaviour (MOAB) lens, we systematically reviewed the facilitators and barriers encountered in LF elimination in India. We followed Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We searched PubMed, Embase, ProQuest and Google Scholar databases to explore factors related to MDA program implementation in India through 30 June 2021. We analysed the data using a thematic framework. We identified 576 studies; of these, 20 studies were included. This review revealed that the public health system for distributing MDA drugs in India created a better enabling environment, including zero out-of-pocket expenditure, door-step distribution of medicines and ample capacity-building training and follow-up. However, community members were unaware of the rationale for drug consumption, leading to a gap in drug distribution and consumption. Motivation is required among community members, which suggests capacity-building training for service providers to counsel the community.

Palmitate induces integrated stress response and lipoapoptosis in trophoblasts.

Maternal obesity increases the risk of childhood obesity and programs the offspring to develop metabolic syndrome later in their life. Palmitate is the predominant saturated free fatty acid (FFA) that is transported across the placenta to the fetus. We have recently shown that saturated FFA in the maternal circulation as a result of increased adipose tissue lipolysis in third trimester of pregnancy induces trophoblast lipoapoptosis. Here, we hypothesized that palmitate induces integrated stress response by activating mitogen-activated protein kinases (MAPKs), endoplasmic reticulum (ER) stress and granular stress and lipoapoptosis in trophoblasts. Choriocarcinoma-derived third-trimester placental trophoblast-like cells (JEG-3 and JAR) referred as trophoblasts were exposed to various concentrations of palmitate (PA). Apoptosis was assessed by nuclear morphological changes and caspase 3/7 activity. Immunoblot and immunofluorescence analysis was performed to measure the activation of MAPKs, ER stress and granular stress response pathways. Trophoblasts exposed to pathophysiological concentrations of PA showed a concentration-dependent increase in trophoblast lipoapoptosis. PA induces a caspase-dependent trophoblast lipoapoptosis. Further, PA induces MAPK activation (JNK and ERK) via phosphorylation, and activation of ER stress as evidenced by an increased phosphorylation eIF2α & IRE1α. PA also induces the activation of stress granules formation. Two pro-apoptotic transcriptional mediators of PA-induced trophoblast lipoapoptosis, CHOP and FoxO3 have increased nuclear translocation. Mechanistically, PA-induced JNK is critical for trophoblast lipoapoptosis. However, PA-induced activation of ERK and stress granule formation were shown to be cell survival signals to combat subcellular stress due to PA exposure. In conclusion, PA induces the activation of integrated stress responses, among which small molecule inhibition of JNK demonstrated that activation of JNK is critical for PA-induced trophoblast lipoapoptosis and small molecule activation of stress granule formation significantly prevents PA-induced trophoblast lipoapoptosis.

Human lymphatic filariasis: genetic polymorphism of endothelin-1 and tumor necrosis factor receptor II correlates with development of chronic disease.

BACKGROUND: Hydrocele and elephantiasis are 2 clinically very diverse and often mutually exclusive chronic manifestations of human bancroftian filariasis. Plasma levels of endothelin-1 (ET-1), a major angiogenic factor, and tumor necrosis factor receptors (TNFRs) that regulate host inflammation have been associated with development of chronic filariasis, although their genetic basis are not known. METHODS: We studied polymorphisms of ET-1 (Ala288Ser) and TNFR-II (Met196Arg) genes by means of the polymerase chain reaction confronting 2 pairs primers method and restriction fragment length polymorphism, respectively. Plasma ET-1 level was measured by enzyme-linked immunosorbent assay. RESULTS: Met196Arg genotype frequency of TNFR-II polymorphism was significantly greater in hydrocele patients, compared with elephantiasis patients (OR, 4.34 [95% CI, 2.04-9.20]). Conversely, a significantly high prevalence of the Ala288Ser mutation of ET-1 was observed in elephantiasis patients, compared with hydrocele cases (OR, 2.15 [95% CI, 1.13-4.10]). Decreased plasma ET-1 levels associated significantly with Ala288Ser mutation in the study population. A combined analysis indicated a 23-fold higher risk for developing elephantiasis in individuals with TNFR-II (Met196Met) and ET-1 mutants (Ala288Ser + Ser288Ser). CONCLUSIONS: ET-1 (Ala288Ser) and TNFR-II (Met196Arg) polymorphisms are associated with development of one or the other form of chronic disease in bancroftian filariasis.

Facilitators and barriers in implementation of mass drug administration for lymphatic filariasis elimination in India: A protocol for systematic review and qualitative meta-synthesis.

Introduction: Lymphatic filariasis (LF) is a debilitating and disabling parasitic disease of immense public health concern in India with more than 650 million people at risk. Mass drug administration (MDA) is the recommended preventive chemotherapy strategy to eliminate LF. But, its coverage and compliance has been a mixed success. There is an urgent need of evidence to strengthen the program further, which can be done by exploring and understanding implementer as well as beneficiary perspectives. Objective: To systematically review the facilitators and barriers experienced during the coverage and compliance of MDA for LF elimination in India from both beneficiary and provider's (health system) perspective. Methods and Analysis: We will search at Medline database through PubMed and Embase, along with ProQuest and Google Scholar to retrieve literature. Original qualitative observational studies exploring challenges and enablers in MDA program will be screened by two independent reviewers systematically based on title and abstract followed by full text. The risk of bias will be assessed through critical appraisal skills program checklist for each included article. Data will be extracted in a pre-designed proforma with study characteristics, demographic features, and texts and quotes of qualitative data. Data will be analyzed through thematic analysis and motivation-opportunity-ability-behavior framework using MAXQDA software. Ethics and Dissemination: This is a literature-based review with minimal privacy concerns. The findings of this study will be published in a peer-reviewed journal and disseminated through policy brief to program implementers.

Mass drug administration for lymphatic filariasis elimination amidst COVID-19 pandemic in Odisha, India: A step towards achieving SDG-3.

Sustainable Development Goal-3 (SDG) aims to eliminate lymphatic filariasis by 2030 through >65% coverage and compliance of mass drug administration (MDA), the preventive chemotherapy strategy of delivering anthelminthic drugs. However, the ongoing COVID-19 pandemic has disrupted such programmes, yet MDA was administered during February 2021 in Odisha, India. We aimed to assess the coverage and compliance of the present round of MDA amidst the pandemic and explore factors for non-compliance in Cuttack district of Odisha, a filariasis endemic area. Community-based participants enrolled through multistage stratified sampling were administered a semi-structured questionnaire following COVID-19 protocols. The coverage of MDA was 93.2% whereas consumption was 73.7%. Participants reported that healthcare workers were motivated and satisfactorily explained the benefits of MDA but still fear of side-effects was the major cause of non-compliance. Nonetheless, this recent round of MDA was effective, despite challenges posed by the ongoing pandemic.

Transition metal-free approach for late-stage benzylic C(sp3)-H etherifications and esterifications.

We report a transition metal-free approach for the regioselective functionalization of benzylic C(sp3)-H bonds using alcohols and carboxylic acids as the nucleophiles. This straightforward and general route has provided various benzylic ethers and esters, including twelve pharmaceutically relevant compounds.

Investigating immunological interaction between lymphatic filariasis and COVID-19 infection: a preliminary evidence.

The foremost concerns of COVID-19 vaccines are safety and efficacy, which becomes grave in countries with a high burden of Neglected Tropical Diseases. Studies proposed helminthic infections might alleviate the efficacy of COVID-19 vaccines. We share preliminary evidence on the association between filariasis and COVID-19 infection. We collated 2 ml of blood from 174 participants residing in filariasis endemic area. To determine filarial antigen, the Og4C3 test and for COVID-19 antibodies, tests through ELISA was performed. COVID-19 antibodies were present among 74/174 (42.5%), whereas filarial antigens were detected in 24/174 (13.8%) participants. An insignificant association [OR = 0.855 (0.36-2.034)] between two was observed. Hence, people in filarial endemic regions can continue taking vaccines without worrying about their efficacy due to the helminthic load in community.

Association of leptospirosis and scrub typhus in acute encephalitis syndrome in a tertiary care hospital in Odisha, India.

BACKGROUND: Acute encephalitis syndrome (AES) is a major public health concern in India, causing febrile illness principally associated with viral infection. Bacteria-like scrub typhus and leptospirosis also cause acute febrile illness. Therefore, this study was conceived to address the possible etiological agents contributing to sporadic AES in a tertiary care center in Odisha, India. METHOD: This was a prospective hospital-based study that enrolled 92 consecutive patients with clinically diagnosed AES whose blood/cerebrospinal fluid samples were tested for IgM antibodies to dengue, Japanese encephalitis (JE), herpes simplex virus (HSV), Epstein-Barr virus (EBV), leptospirosis and scrub typhus. RESULTS: Viral antibodies to dengue were detected in three (3.26%) cases, HSV1 in four (4.34%) and HSV2 in three (3.26%) cases. Significantly, antibodies to EBV in 22 (23.591%) and to JE in 27 (29.34%) cases were detected. Notably, 30 (32.60%) and 11(12.0%) of patients had IgM antibodies to leptospirosis and scrub typhus, respectively. CONCLUSION: This observation indicates an association of leptospirosis and scrub typhus infection in sporadic cases of AES, besides other viruses.

Burden of Rubella virus infection among females attending tertiary care hospitals of Odisha, India: a need for adult women vaccination.

Rubella is a contagious disease caused by rubella virus leading to adverse outcomes among pregnant women including abortions, low birth weight, stillbirths and congenital rubella syndrome (CRS) in the baby. If not pregnant, the clinical manifestations are mild and self-limiting. In this hospital based cross-sectional study, 1985 blood samples were collected from females attending outpatient services of various hospitals to serologically detect Rubella infection. Rubella antibodies namely Immunoglobulin M (IgM)/Immunoglobulin G (IgG) were detected through enzyme linked immunosorbent assay (ELISA) or by identifying virus through polymerase chain reaction (PCR). From the total enrolled participants, 1951 samples were tested with age ranging from 16 to 38 years. Among the positive samples, about 60% patients had IgG antibodies as compared to less than 1% IgM and 0.40% by PCR. Out of 1951 samples, 7/849 (0.82%) and 651/1070 (60.8%) had IgM & IgG rubella antibodies respectively. The odds of having abortion was [OR-13.14 (4.94-34.97)] among anti-rubella positive and primi-gravida [OR-43.6 (5.9-322)] women. Therefore, vaccination of women against rubella before planning of pregnancy or at adolescence seems to be the need of hour to avoid the ill consequences during pregnancy as well as for the new born baby.

Immunity against diphtheria among children aged 5-17 years in India, 2017-18: a cross-sectional, population-based serosurvey.

BACKGROUND: Diphtheria is re-emerging as a public health problem in several Indian states. Most diphtheria cases are among children older than 5 years. In this study, we aimed to estimate age-specific immunity against diphtheria in children aged 5-17 years in India. METHODS: We used residual serum samples from a cross-sectional, population-based serosurvey for dengue infection done between June 19, 2017, and April 12, 2018, to estimate the age-group-specific seroprevalence of antibodies to diphtheria in children aged 5-17 years in India. 8309 serum samples collected from 240 clusters (122 urban and 118 rural) in 60 selected districts of 15 Indian states spread across all five geographical regions (north, northeast, east, west, and south) of India were tested for the presence of IgG antibodies against diphtheria toxoid using an ELISA. We considered children with antibody concentrations of 0·1 IU/mL or greater as immune, those with levels less than 0·01 IU/mL as non-immune (and hence susceptible to diphtheria), and those with levels in the range of 0·01 to less than 0·1 IU/mL as partially immune. We calculated the weighted proportion of children who were immune, partially immune, and non-immune, with 95% CIs, for each geographical region by age group, sex, and area of residence (urban vs rural). FINDINGS: 29·7% (95% CI 26·3-33·4) of 8309 children aged 5-17 years were immune to diphtheria, 10·5% (8·6-12·8) were non-immune, and 59·8% (56·3-63·1) were partially immune. The proportion of children aged 5-17 years who were non-immune to diphtheria ranged from 6·0% (4·2-8·3) in the south to 16·8% (11·2-24·4) in the northeast. Overall, 9·9% (7·7-12·5) of children residing in rural areas and 13·1% (10·2-16·6) residing in urban areas were non-immune to diphtheria. A higher proportion of girls than boys were non-immune to diphtheria in the northern (17·7% [12·6-24·2] vs 7·1% [4·1-11·9]; p=0·0007) and northeastern regions (20·0% [12·9-29·8] vs 12·9% [8·6-19·0]; p=0·0035). INTERPRETATION: The findings of our serosurvey indicate that a substantial proportion of children aged 5-17 years were non-immune or partially immune to diphtheria. Transmission of diphtheria is likely to continue in India until the immunity gap is bridged through adequate coverage of primary and booster doses of diphtheria vaccine. FUNDING: Indian Council of Medical Research.

Seroprevalence of chikungunya virus infection in India, 2017: a cross-sectional population-based serosurvey.

BACKGROUND: Since its re-emergence in 2005, chikungunya virus (CHIKV) transmission has been documented in most Indian states. Information is scarce regarding the seroprevalence of CHIKV in India. We aimed to estimate the age-specific seroprevalence, force of infection (FOI), and proportion of the population susceptible to CHIKV infection. METHODS: We did a nationally representative, cross-sectional serosurvey, in which we randomly selected individuals in three age groups (5-8, 9-17, and 18-45 years), covering 240 clusters from 60 selected districts of 15 Indian states spread across all five geographical regions of India (north, northeast, east, south, and west). Age was the only inclusion criterion. We tested serum samples for IgG antibodies against CHIKV. We estimated the weighted age-group-specific seroprevalence of CHIKV infection for each region using the design weight (ie, the inverse of the overall probability of selection of state, district, village or ward, census enumeration block, and individual), adjusting for non-response. We constructed catalytic models to estimate the FOI and the proportion of the population susceptible to CHIKV in each region. FINDINGS: From June 19, 2017, to April 12, 2018, we enumerated 117 675 individuals, of whom 77 640 were in the age group of 5-45 years. Of 17 930 randomly selected individuals, 12 300 individuals participated and their samples were used for estimation of CHIKV seroprevalence. The overall prevalence of IgG antibodies against CHIKV in the study population was 18·1% (95% CI 14·2-22·6). The overall seroprevalence was 9·2% (5·4-15·1) among individuals aged 5-8 years, 14·0% (8·8-21·4) among individuals aged 9-17 years, and 21·6% (15·9-28·5) among individuals aged 18-45 years. The seroprevalence was lowest in the northeast region (0·3% [95% CI 0·1-0·8]) and highest in the southern region (43·1% [34·3-52·3]). There was a significant difference in seroprevalence between rural (11·5% [8·8-15·0]) and urban (40·2% [31·7-49·3]) areas (p<0·0001). The seroprevalence did not differ by sex (male 18·8% [95% CI 15·2-23·0] vs female 17·6% [13·2-23·1]; p=0·50). Heterogeneous FOI models suggested that the FOI was higher during 2003-07 in the southern and western region and 2013-17 in the northern region. FOI was lowest in the eastern and northeastern regions. The estimated proportion of the population susceptible to CHIKV in 2017 was lowest in the southern region (56·3%) and highest in the northeastern region (98·0%). INTERPRETATION: CHIKV transmission was higher in the southern, western, and northern regions of India than in the eastern and northeastern regions. However, a higher proportion of the population susceptible to CHIKV in the eastern and northeastern regions suggests a susceptibility of these regions to outbreaks in the future. Our survey findings will be useful in identifying appropriate target age groups and sites for setting up surveillance and for future CHIKV vaccine trials. FUNDING: Indian Council of Medical Research.

Hepatitis-B virus infection in India: Findings from a nationally representative serosurvey, 2017-18.

INTRODUCTION: India introduced a hepatitis-B (HB) vaccine in the Universal Immunization Program in 2002-2003 on a pilot basis, expanded to ten states in 2007-2008 (phase-1), and the entire country in 2011-2012 (phase-2). We tested sera from a nationally representative serosurvey conducted duing 2017, to estimate the seroprevalence of different markers of HB infection among children aged 5-17 years in India and to assess the impact of vaccination. METHODS: We tested sera from 8273 children for different markers of HB infection and estimated weighted age-group specific seroprevalence of children who were chronically infected (HBsAg and anti-HBc positive), and immune due to past infection (anti-HBc positive and HBsAg negative), and having serological evidence of HB vaccination (only anti-HBs positive). We compared the prevalence of serological markers among children born before (aged 11-17 years) and after (aged 5-10 years) introduction of HB-vaccine from phase-1 states. RESULTS: Among children aged 5-8 years, 1.1% were chronic carriers, 5.3% immune due to past infection, and 23.2% vaccinated. The corresponding proportions among children aged 9-17 years were 1.1%, 8.0%, and 12.0%, respectively. In phase-1 states, children aged 5-10 years had a significantly lower prevalence of anti-HBc (4.9% vs. 7.6%, p<0.001) and higher prevalence of anti-HBs (37.7% vs. 14.7%, p<0.001) compared to children aged 11-17 years. HBsAg positivity, however, was not different in the two age groups. CONCLUSIONS: Children born after the introduction of HB vaccination had a lower prevalence of past HBV infection and a higher prevalence of anti-HBs. The findings of our study could be considered as an interim assessment of the impact of the hepatitis B vaccine introduction in India.

Burden of dengue infection in India, 2017: a cross-sectional population based serosurvey.

BACKGROUND: The burden of dengue virus (DENV) infection across geographical regions of India is poorly quantified. We estimated the age-specific seroprevalence, force of infection, and number of infections in India. METHODS: We did a community-based survey in 240 clusters (118 rural, 122 urban), selected from 60 districts of 15 Indian states from five geographical regions. We enumerated each cluster, randomly selected (with an Andriod application developed specifically for the survey) 25 individuals from age groups of 5-8 years, 9-17 years, and 18-45 years, and sampled a minimum of 11 individuals from each age group (all the 25 randomly selected individuals in each age group were visited in their houses and individuals who consented for the survey were included in the study). Age was the only inclusion criterion; for the purpose of enumeration, individuals residing in the household for more than 6 months were included. Sera were tested centrally by a laboratory team of scientific and technical staff for IgG antibodies against the DENV with the use of indirect ELISA. We calculated age group specific seroprevalence and constructed catalytic models to estimate force of infection. FINDINGS: From June 19, 2017, to April 12, 2018, we randomly selected 17 930 individuals from three age groups. Of these, blood samples were collected and tested for 12 300 individuals (5-8 years, n=4059; 9-17 years, n=4265; 18-45 years, n=3976). The overall seroprevalence of DENV infection in India was 48·7% (95% CI 43·5-54·0), increasing from 28·3% (21·5-36·2) among children aged 5-8 years to 41·0% (32·4-50·1) among children aged 9-17 years and 56·2% (49·0-63·1) among individuals aged between 18-45 years. The seroprevalence was high in the southern (76·9% [69·1-83·2]), western (62·3% [55·3-68·8]), and northern (60·3% [49·3-70·5]) regions. The estimated number of primary DENV infections with the constant force of infection model was 12 991 357 (12 825 128-13 130 258) and for the age-dependent force of infection model was 8 655 425 (7 243 630-9 545 052) among individuals aged 5-45 years from 30 Indian states in 2017. INTERPRETATION: The burden of dengue infection in India was heterogeneous, with evidence of high transmission in northern, western, and southern regions. The survey findings will be useful in making informed decisions about introduction of upcoming dengue vaccines in India. FUNDING: Indian Council of Medical Research.

Iron-Catalyzed Selective Etherification and Transetherification Reactions Using Alcohols.

Simple and readily available iron(III) triflate turned out to be a cheap, environmentally benign, and efficient catalyst for the direct etherification of alcohols. The use of ammonium chloride as an additive (5 mol %, 1 equiv relative to catalyst) suppressed the side reactions completely and ensured the selective ether formation even on challenging substrates containing electron-donating substituents. This method allows the selective synthesis of symmetrical ethers from benzylic secondary alcohols and unsymmetrical ethers directly from secondary and primary alcohols. Moreover, transetherification of symmetrical ethers using primary alcohols is attained. The reaction progress of symmetrical ether and unsymmetrical ether formation followed zero-order and first-order kinetics, respectively. Electron paramagnetic resonance (EPR) measurements of the reaction mixture and simple iron(III) triflate clearly indicated that oxidation state of the metal center remains same throughout the catalysis. Mechanistic studies confirmed that the unsymmetrical ether formation occurs via the in situ formed symmetrical ethers.

Anti-filarial immunity blocks parasite development and plays a protective role.

Lymphatic filariasis is a complex parasitic disease having a spectrum of clinical parameters which are critical in deciding the severity of the pathogenesis. Individuals residing in the endemic areas are categorized into different clinical groups such as: EC (endemic controls-free of disease and infection), AS (asymptomatic carriers- free of disease but carries both antigens and microfilaria (Mf) in circulation), CR (cryptic-free of disease and Mf but having circulatory antigen) and CH (chronic-having manifestations of elephantiasis and hydrocele). The immune response to the parasitic infection is well studied, whereas the protective mechanism explaining the fate of antigenemia and filaremia between AS and CR group remains unexplained. Increased anti-Mf antibodies have been implicated for Mf clearance in experimental infection models whereas its role in clinical filariasis is not known. Here, we followed up two groups of 24 and 33 CR cases for 18 and 36 months respectively and analyzed both the clinical parameters and the anti-filarial antibody response. The humoral response to both whole filarial antigen and Mf antigens as well as recombinant active parasitic antigens was significantly higher in CR cases than AS individuals, whereas the clinical parameters remain unchanged. This study made insights into the protective immune mechanism responsible for the clearance of Mf from circulation in CR individuals.