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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.

Summary 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.

The persistence of residual infection is one of the major factors in failure of the Global Programme to Eliminate Lymphatic Filariasis (GPELF). The present study aims to explore the status of sheath antibody and regulatory T cells (Tregs) known to play key roles in clearance of parasite and patent filarial infection, in individuals with residual infection after MDA. A total of 61 microfilaremic (Mf) individuals were followed up after at least 6 rounds of MDA. Infection status of subjects was assessed through the detection of Mf and circulating filarial antigen (CFA). Antibodies to Mf sheath were determined by immuno-peroxidase assay (IPA). The expression of Tregs was measured by a flow cytometer. IL-10 and IFN-γ were evaluated using the commercially available ELISA kit. The sheath antibody was present in subjects who have cleared both Mf and CFA and absent in individuals who were found to be Mf /CFA positive. Further individuals carrying infection have significantly high levels of Tregs and IL-10. A positive correlation was observed between Tregs, IL-10, and CFA in infected individuals. In contrast, a negative correlation was observed between IFN-γ and IL-10 in both infected and uninfected subjects. Our study reveals that the absence of a sheath antibody and a high level of Tregs and IL-10 are the hallmarks of the persistence of residual filarial infection.

BACKGROUND Rotavirus is an important cause of severe diarrhea requiring hospitalization, accounting for approximately 78,000 deaths annually in Indian children below 5 years of age. We present epidemiological data on severe rotavirus disease collected during hospital-based surveillance in India before the introduction of the oral rotavirus vaccine into the national immunization schedule. METHODS The National Rotavirus Surveillance Network was created involving 28 hospital sites and 11 laboratories across the four geographical regions of India. From September 2012 to August 2016 children less than 5 years of age hospitalized for diarrhea for at least 6 h, were enrolled. After recording clinical details, a stool sample was collected from each enrolled child, which was tested for rotavirus antigen using enzyme immunoassay (EIA). Nearly 2/3rd of EIA positive samples were genotyped using reverse transcription polymerase chain reaction to identify the G and P types. RESULTS Of the 21,421 children enrolled during the 4 years surveillance, 36.3% were positive for rotavirus. The eastern region had the highest proportion of rotavirus associated diarrhea (39.8%), while the southern region had the lowest (33.8%). Rotavirus detection rates were the highest in children aged 6-23 months (41.8%), and 24.7% in children aged

Background India has set a goal to eliminate measles and rubella/Congenital Rubella Syndrome (CRS) by 2023. Towards this goal, India conducted nationwide supplementary immunization activity (SIA) with measles-rubella containing vaccine (MRCV) targeting children aged between 9 months to, Author summary Rubella infection during the first trimester of pregnancy can affect fetus, resulting in spontaneous abortion, stillbirth or birth of a baby with a combination of birth defects known as congenital rubella syndrome (CRS). Vaccination with rubella containing vaccine (RCV) is recommended as one of the strategies for eliminating rubella/CRS. The Southeast Asia region has set a target to eliminate rubella/CRS by 2023. Towards this goal, India completed nationwide immunization campaigns using measles-rubella vaccine during 2017–19, targeting children aged 9 months to

Purpose: The primitive tribal groups (PTGs) need special attention because of their low population growth: declining population size with high mortality rates. Scanty reports are available on the prevalence of hepatitis C virus (HCV) infection in primitive tribes of the country emphasizing their cultural and social practices associated with transmission of the disease. Methods: The study was conducted on 1765 tribal individuals covering 5 PTGs, namely Lodha, Saora, Khadia, Juanga, and Mankidia, from 6 districts of Odisha. Serum samples were tested for the anti-HCV antibody using commercially available enzyme immunoassays. HCV RNA was detected based on the 5′ NCR region and genotyping was done by direct sequencing of the core region. Potential risk factors for HCV transmission were collected using a questionnaire and subjected to regression analysis through SPSS, version 17.0. Results: Antibody to HCV was detected in 0%, 3.3%, 5.7%, 8.5%, and 13.4% in Saora, Lodha, Khadia, Juanga, and Mankidia tribes, respectively. HCV RNA was detected in 8.6% (11/127) of the samples tested. Genotyping of HCV isolates in all HCV RNA-positive samples revealed genotype 1b. Sharing of razors and shaving by the village barber were found to be significantly (p

Dengue has emerged as a major public health challenge in terms of both changing clinical pattern and epidemiological features. The state of Odisha reported first dengue epidemic in the year 2010 and this continued each year in epidemic form during post monsoon period gradually becoming an endemic phenomenon. Present study depicts the changing epidemiological and clinical pattern of dengue with reference to its serotypes and genotypes. The study included 5320 suspected dengue cases from different health facilities of the state during 2010–2017. Dengue NS1 antigen and IgM antibody was done through ELISA. Serotyping was done through RTPCR by amplifying a part of core-pre-membrane gene (CprM) followed by sequencing and phylogenetic analysis. Dengue IgM antibody in 17.7% cases and NS1 antigen in 53.20% cases was detected. Dengue serotype 2 (DEN-2) was the only serotype detected in 2010 and 2011 where as all four serotypes 1, 2, 3, 4 were detected in 2012–2017, DEN-2 being dominant but in 2017 DEN-3 was found to be dominant. Phylogenetic analysis revealed genotype IV of DEN-2 and genotype III of DEN-1 and DEN-3 circulating in this region. In 6 cases involvement of DEN-2 in clinically evident encephalitis cases is an important observation in this region and needs public health attention. High prevalence of dengue was observed without any previous reported outbreaks in the state with increased number of cases from 2010 to 2012 affecting both urban and rural areas. High incidence in 2012 was due to co-circulation of more than one serotype which continued in the following years. Severity in some cases was associated with mixed infection but in most cases it was mild indicating the endemic nature of the virus in most parts of Odisha.

We conducted a nationally representative population-based survey in 60 districts from 15 Indian states covering all five geographic regions during 2017–2018 to estimate the age specific seroprevalence of dengue. Of the 12,300 sera collected, 4,955 were positive for IgG antibodies against dengue virus using IgG Indirect ELISA indicating past dengue infection. We tested 4,948 sera (seven had inadequate volume) positive for IgG antibodies on indirect ELISA using anti-dengue IgG capture ELISA to estimate the proportion of dengue infections with high antibody titers, suggestive of acute or recent secondary infection. Of the 4,948 sera tested, 529 (10.7%; 95% CI: 9.4–12.1) were seropositive on IgG capture ELISA. The proportions of dengue infections with high titers were 1.1% in the northeastern, 1.5% in the eastern, 6.2% in the western, 12.2% in the southern, and 16.7% in the northern region. The distribution of dengue infections varied across geographic regions, with a higher proportion of infections with high antibody titer in the northern and southern regions of India. The study findings could be useful for planning facilities for clinical management of dengue infections.

Introduction A hospital-based sentinel surveillance network for bacterial meningitis was established in India to estimate the burden of bacterial meningitis, and the proportion of major vaccine-preventable causative organisms. This report summarises the findings of the surveillance conducted between March 2012, and September 2016 in eleven hospitals. Methods We enrolled eligible children with bacterial meningitis in the age group of one to 59 months. CSF samples were collected and processed for biochemistry, culture, latex agglutination, and real-time PCR. Pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. Results Among 12 941 enrolled suspected meningitis cases, 586 (4.5%) were laboratory confirmed. S. pneumoniae (74.2%) was the most commonly detected pathogen, followed by H. influenzae (22.2%), and N. meningitidis (3.6%). Overall 58.1% of confirmed bacterial meningitis cases were children aged between one, and 11 months. H. influenzae meningitis cases had a high (12.3%) case fatality rate. The serotypes covered in PCV13 caused 72% pneumococcal infections, and the most common serotypes were 14 (18.3%), 6B (12.7%) and 19F (9.9%). Non-susceptibility to penicillin was 57%. Forty-five (43.7%) isolates exhibited multidrug resistance, of which 37 were PCV13 serotype isolates. Conclusions The results are representative of the burden of bacterial meningitis among under-five children in India. The findings were useful in rolling out PCV in the National Immunization Program. The non-susceptibility to penicillin and multidrug resistance was an important observation. Timely expansion of PCV across India will significantly reduce the burden of antimicrobial resistance. Continued surveillance is needed to understand the trend after PCV expansion in India.

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

Newly emerging or re-emerging infections are posing continuous threat to both public health system and clinical care globally. The emergence of infections especially caused by arboviruses can be linked to several mechanisms which include geographical expansion linked to human development and transportation, global warming, enhanced transmission in peridomestic area and close proximity of human habitations to domestic as well as wild animals. The co-circulation of Dengue, Chikungunya and Zika is a matter of public health priority due to the fact that they are transmitted by the same vector as well as increase in the number of reported cases of severe dengue, post-chikungunya chronic joint disease and microcephaly related to Zika virus disease. The study was designed to estimate the prevalence of these arboviral infections in Odisha. About 5198 cases presenting with common clinical symptoms of fever, arthralgia, headache, myalgia and malaise were screened during 2016–2019. A total of 42.2% patients tested positive for dengue NS1 antigen (n = 4154), 30.2% for dengue IgM (n = 2161) and 14.3% for chikungunya IgM (n = 1816). A total of 1684 samples were subjected to Zika RT-PCR and none was tested positive. Peak in the numbers of dengue/ chikungunya cases was evident in the post-monsoon months of July – October. Circulation of all four serotypes of dengue i.e. DEN 1, 2, 3, and 4 was noticed in the state. Molecular investigation of suspected Chik cases in early phases showed circulation of Eastern Central Southern African genotype (E1:226A). There is dearth of knowledge about disease severity during arbovirus co-infections and importance of adequate management of patients at an early stage residing in risk areas. It is the first study in Odisha to study the pattern and status of these three arboviral diseases Dengue, Chikungunya and Zika. The outcome of this study will help in focusing and improvement of existing surveillance systems and vector control tools, as well as on the development of suitable antiviral agents and formulating candidate vaccine.

Background: The nonzoonotic (nonsevere acute respiratory syndrome (SARS)/Middle East respiratory syndrome) human coronaviruses (HCoVs) are usually considered as the causative agent for acute respiratory infection. We studied the characteristics and outcome of children with non-SARS HCoV acute lower respiratory infection (ALRI). Methods: This was a cross-sectional study from a tertiary care teaching hospital in eastern India. Results: Of 137 samples tested positive for respiratory viruses, 13 were due to HCoV (7 boys, median age: 2 years). Cough was the most common symptom, followed by breathing difficulty and fever. An underlying comorbid condition present in 38.4%. Co-infection with other viruses was seen in 69% of cases. Chest radiograph was abnormal in 69.3% of children. Antibiotics were administered in 53.8%. The median length of hospitalization was 5 d, irrespective of underlying disease. There was no mortality. Conclusions: HCoV is an uncommon but increasingly recognized cause of ALRI in hospitalized children. No severe illness was found in children with underlying comorbidities. This study underscores the importance of HCoV in causation of childhood ALRI, necessitating a surveillance system in India.

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

Despite consistent public health efforts, the burden of viral disease in India remains high. The present study was undertaken to understand the aetiology, frequency and distribution of viral disease outbreaks in the state of Odisha between 2010 and 2019. This was a prospective study conducted at the Virology Research and Diagnostic Laboratory located at ICMR-Regional Medical Research Centre, Bhubaneswar, Odisha, wherein all the outbreaks of viral aetiologies were investigated and analysed to provide a comprehensive picture of the state of viral disease outbreaks in the region. A total of 191 suspected viral outbreaks were investigated by the team from VRDL during September 2010 and September 2019 reported from all the 30 districts of Odisha. Annual number of suspected cases ranged from 185 to 1002. The most commonly suspected outbreaks were of viral hepatitis (55 outbreaks; 1223 cases) followed by dengue (45 outbreaks; 1185 cases), chickenpox (30 outbreaks; 421 cases), viral encephalitis (27 outbreaks; 930 cases), measles (23 outbreaks; 464 cases), chikungunya (10 outbreaks; 593 cases) and rubella (1 outbreak; 60). The outbreaks peaked in frequency and intensity during the months of July and September. The epidemiology of viral disease outbreaks in the region is presented in the study. Health system preparedness based on evidence is essential for early detection and adequate response to such viral outbreaks.

Background: Despite consistent public health efforts, the burden of viral disease in India remains high. The present study was undertaken to understand the etiology, frequency and distribution of viral disease outbreaks in the state of Odisha between 2010 and 2019. Methods: This was a prospective study conducted at the Virology Research and Diagnostic Laboratory located at ICMR-Regional Medical Research Centre, Bhubaneswar, Odisha wherein all the outbreaks of viral etiologies were investigated and analyzed to provide a comprehensive picture of the state of viral disease outbreaks in the region. Findings: A total of 191 suspected viral outbreaks were investigated by the team from VRDL during September 2010 and September 2019 reported from all the 30 districts of Odisha.Annual number of suspected cases ranged from 185 to 1002. The most commonly suspected outbreaks were of Viral hepatitis (55 outbreaks; 1223 cases) followed by Dengue (45 outbreaks; 1185 cases), Chickenpox (30 outbreaks; 421 cases), Viral encephalitis (27 outbreaks; 930 cases), Measles (23 outbreaks; 464 cases), Chikungunya (10 outbreaks; 593 cases) and Rubella (1 outbreak; 60). The outbreaks peaked in frequency and intensity during the months of July and September. Interpretation : The epidemiology of viral disease outbreaks in the region is presented in the study. Health system preparedness based on evidence is essential for early detection and adequate response to such viral outbreaks. Funding Statement: The study uses data collected from the outbreaks investigated by the study team at VRDL, which is supported by the Department of Health Research, Ministry of health and family welfare, Government of India. Declaration of Interests: None. Ethics Approval Statement: Approval was obtained from the Institutional human ethical committee of ICMR RMRC Bhubaneswar for the study. Data confidentiality was ensured and only aggregated patient data is being presented in the analyses. Informed consent was obtained from the participants, following the ICMR National ethical guidelines for biomedical research involving human subjects.

The study was undertaken to find out the cause and etiology of an outbreak presumed to be due to water contamination that caused high morbidity in the western part of the state of Odisha during May, 2014. In this investigation 56 blood samples were collected and tested for HEV IgM through ELISA. Blood sample of 22 patients collected within 1 weeks post onset of symptoms and were subjected to RT-PCR and sequencing followed by phylogenetic analysis. Water samples were also analyzed for viral and bacterial contamination. A total of 290 individuals were examined for suspected jaundice. Out of 56 blood samples in 41 (73.2%) IgM for HEV was found. 12 samples out of 22 early phase samples were positive for RT-PCR and through phylogenetic analysis all were found to be of Genotype 1 and subtype A. This large outbreak was confirmed due to Hepatitis E virus and transmission was fast due to contamination of drinking water sources and lack of hygienic practices. The outcome of this investigation has created alertness among state health and municipal authorities to be prepared for the similar kind of situation for other part of the state.

The aim of this study was to determine the causative agent of acute respiratory infections (ARIs) in hospitalized children, as well as investigate the characteristics of ARIs with single and multiple pathogens detection from July 2015 to June 2016. The objective of the present study was to examine the role of viruses, bacteria and mix infection of both in hospitalized children with ARI and their correlation with two divergent geographical settings of Odisha. Hospitalized children with ARI aged 1bacteria, 40(15%) with > 1virus, 22(8.2%) with > 2 bacteria and 20(7-4%) with both bacteria and virus. Most frequently detected pathogens were Klebsiella pneumonae, Setrptococcus pneumonae, Parainfluenza A and Influenza A virus. Incidences of pathogens were detected more among children

Acute encephalitis syndrome (AES) is a clinical condition that occurs due to infectious and noninfectious agents- however, viruses are considered to be the dominant pathogen. agents- however, viruses are considered to be the dominant pathogen. In this study, suspected AES cases were enrolled and tested for viral etiology through serology and polymerase chain reaction (PCR)/reverse transcriptase PCR from August 2012-July 2013. During this period, 820 cases were investigated and 96 cases were diagnosed to have a viral etiology whereas 20 patients had IgM antibodies for measles in serum and HSV-1 DNA in cerebrospinal fluid. All 20 of the patients were children below 14 years of age. The median hospital stay was 15 days (IQR: 14.2-17 days) and median GCS score was 7(IQR: 6-8) and were significantly different with patients with co-infections when comapred with patients having HSV-1 infection only. It may be suspected that the measles infection may have a role in the pathogenesis and thus an impact on the prognosis of the AES when present with HSV-1.

Summary 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.

Objective To investigate the distribution and clinical profile of scrub typhus infection among children with acute febrile illness in Odisha. Methods Children ( 5 days) in 4 agro-climatic zones from June to November 2017 were evaluated. Patients were screened for malaria, leptospira, dengue, typhoid and scrub typhus. Scrub typhus was confirmed by IgM ELISA and PCR. Results Out of 413 cases examined, 48.7% were positive for scrub typhus, and 5.5% of them developed systemic complications. Eschar was found in 17.9% of cases. Five days treatment of Doxycycline and/or Azithromycin was clinically effective against scrub typhus. Conclusions Our study highlights that scrub typhus is one of the causes of high morbidity in children during rainy months in Odisha.

Epidemic of flu is highly contagious and it spreads through air. In 2009 H1N1 influenza virus emerged after reassortment of North American TRIG and Eurasia Avian like virus of swine and started epidemic in Mexico. The first cases were reported from Hyderabad city on 16th May 2009 in India that spread rapidly within a short span of time. During this period large population of Odisha situated at the eastern side of India was also affected and incidences of H1N1 cases were recorded through state Government surveillance system. In this study real time RT-PCR based diagnosis was conducted for the throat swabs collected from suspected H1N1 cases in Odisha during 2009–2017. A total of 2872 throat swabs were received from 23 different Government and private hospitals and 21.1% positivity was confirmed. The disease affected mostly 46–60 years age group, males (50.6%) being more affected. The clinical features had shown that fever with cough (89.6%) was the most common symptom followed by shortness of breath (72.7%). Post monsoon was the peak season in which most of the cases were reported. Neurological signs, pregnancy, diabetes and hypertension were found to be risk factors for H1N1. The case fatality rate (CFR) was 15%., Epidemiology; Infectious disease; Odisha; Real time RTPCR; H1N1; India

Background. Acute respiratory infections (ARIs) are important cause of mortality and morbidity in children under five in developing country.Methods. This observational study was conducted over two-year period in a tertiary care teaching hospital of Eastern India. Nasal and throat swabs were collected, transported to the laboratory at 2–8°C in viral transport media, and then processed for detection of viruses using mono/multiplex real-time polymerase chain reaction.Results. A total of 300 children aged 2–60 months with ARIs were included. The most common age group affected with LRI was 2–12 mo and with URI was >12–60 mo. Viruses were detected in 248 cases. In URI, 77 were positive for single virus and 19 were positive for more than one virus; in LRI, 113 were positive for single virus and 12 were positive for more than one virus. The most common viruses isolated from URI cases were rhinovirus and adenovirus. The most common viruses isolated from LRI cases were respiratory syncytial virus and influenza virus. Most cases occurred in the months of January, December, and August.Conclusion. Viruses constitute a significant cause of ARI in children under five. RSV, ADV, RV, and IFV were the most prevalent viruses isolated.

Up to 25% of hepatitis E virus (HEV)-infected pregnant women in their third trimester die. Despite HEV being an important cause of viral hepatitis, no robust surveillance exists in India. We reviewed jaundice outbreaks records and hospital records from jaundiced individuals seeking treatment and linked those records to laboratory results (HEV immunoglobulin M enzyme-linked immunosorbent assay) for January 2012 to September 2013 in Odisha state. A total of 14 HEV confirmed outbreaks were identified, of which 33% of 139 jaundiced cases were HEV positive. There were two deaths. An additional 495 jaundiced cases were identified through hospital records, of which 18% were HEV positive. Among HEV-positive women (n = 35), 34% were of childbearing age. While one may not be able to generalize our results, this finding suggests HE is widespread in Odisha and may represent hidden disease burden in this region. The policymakers should monitor HEV infections in similar geographical areas, especially among population of childbearing age women to initiate evidence-based control measures.

Rotavirus infection of young children particularly below five years of age resulting in severe diarhoea, is the cause of a large number of infant deaths all over the world, more so in developing countries like India. Vaccines developed against this infection in the last two decades have shown mixed results with some of them leading to complications. Oral vaccines have not been very effective in India. Significant diversity has been found in circulating virus strains in India. Development of a vaccine against diverse genetic variants of the different strains would go a long way in reducing the incidence of infection in developing countries. Success of such a vaccine would depend to a large extent on the antigenic peptide to be used in antibody production. The non-glycosylated protein VP4 on the surface capsid of the virus is important in rota viral immunogenicity and the major antigenic site(s) responsible for neutralization of the virus via VP4 is in the VP8* subunit of VP4. It is necessary that the peptide should be very specific and a peptide sequence which would stimulate both the T and B immunogenic cells would provide maximum protection against the virus. Advanced computational techniques and existing databases of sequences of the VP4 protein of rotavirus help in identification of such specific sequences. Using an in silico approach we have identified a highly conserved VP8* subunit of the VP4 surface protein of rotavirus which shows both T and B cell processivity and is also non-allergenic. This sub-unit could be used in in vivo models for induction of antibodies.

Essential hypertension which accounts 90–95% of the total hypertension cases is affected by both genetic and environmental factors. This study was undertaken to investigate the association of aldosterone synthase C-344T, angiotensin II type I receptor A1166C and 11- β hydroxysteroid dehydrogenase type 2 G534A polymorphisms with essential hypertension in the population of Odisha, India. A total of 246 hypertensive subjects (males, 159; females, 87) and 274 normal healthy individuals (males, 158; females, 116) were enrolled in this study based on the inclusion and exclusion criteria. Analysis of genetic and biochemical data revealed that in this population the CT and TT genotypes of aldosterone synthase C-344T polymorphism, frequency of alcohol consumption and aldosterone levels were significantly high among the total as well as male hypertensives, while the AC and CC genotypes of angiotensin II type I receptor A1166C polymorphism were significantly high among the total as well as female hypertensives. High density lipoprotein levels were higher in male hypertensives.

Introduction: Antimicrobial susceptibility testing of Mycobacterium tuberculosis is required for successful treatment of patients, mainly in retreatment cases which necessitate isolation of mycobacteria from sputum samples within 24-48 hours. In situations where transportation of sputum is required, the use of cetylpyridinium chloride (CPC) effectively sustains the viability of mycobacteria up to two weeks. Methodology: Sputum samples were collected from pulmonary TB patients attending designated microscopy centres (DMC), stored in CPC solution and transported to a culture drug susceptibility testing laboratory using overnight bus transport facilities. For culture, the sputum specimens were processed and inoculated in Lowenstein- Jensen (LJ) medium. Growth on LJ was identified by colony morphology, growth rate and biochemical tests, and transit time was calculated as the time taken from the date of sample collection to the inoculation date. Results: Out of the 816 sputum samples collected in CPC, 691 (84.7%) yielded M. tuberculosis, 97 (11.9%) yielded no growth, 21(2.6%) grew contaminants and 7 (0.8%) were nontuberculous mycobacteria. CPC containing sputum samples processed within two weeks showed 88.6% culture positivity, while positivity was significantly affected beyond two weeks. Conclusions: CPC is cheap, easy to use, inhibits the growth of other organisms and can effectively be used to transport sputum specimens within two weeks from hard to reach areas to central locations without compromising culture positivity. Bus transport services can also help in reducing delay and the cost of transportation from remote areas.

To determine the prevalence of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection in multitransfused thalassemic patients, with an aim to further highlight the need for donor screening strategy with supplementary molecular diagnostic tools for high risk population.The study was conducted in 174 thalassemic subjects from Thalassemia unit of Central Red Cross Blood Bank, Cuttack, Odisha, India. Sero molecular diagnosis was followed to detect antigen, antibody and DNA in the study subjects.Prevalence of antibody to Hepatitis C, HBsAg, Anti HBs and Anti HBc were found to be 3.4 %, 0.5 %, 30.4 % and 21.8 % respectively. HBV seropositivity increased with increase in number of transfusions. Anti HBc was 12 %, 26.8 % and 71.4 % in subjects who received40, 40-80 and80 units of transfusions respectively. HBV DNA was detected in 50 % (3/6) of subjects having anti HBc as the only marker (Occult HBV infection). More so, it was detected in 16.12 % (5/31) of cases who were sero positive for both Anti HBs and Anti HBc.These results indicate that thalassemic subjects need detailed screening of transfusion products. Fifty percent of occult HBV infection is a major concern suggesting inclusion of viral DNA amplification test along with antigen/antibody detection.

SUMMARYThis study reports clinico-epidemiological features and viral agents causing acute encephalitis syndrome (AES) in the eastern Indian region through hospital-based case enrolment during April 2011 to July 2012. Blood and CSF samples of 526 AES cases were investigated by serology and/or PCR. Viral aetiology was identified in 91 (17·2%) cases. Herpes simplex virus (HSV; types I or II) was most common (16·1%), followed by measles (2·6%), Japanese encephalitis virus (1·5%), dengue virus (0·57%), varicella zoster virus (0·38%) and enteroviruses (0·19%). Rash, paresis and cranial nerve palsies were significantly higher (P

Background Chickenpox or varicella is caused by Varicella zoster virus. In India chickenpox outbreak is not uncommon as the vaccination against varicella is not included in the program. We report, chickenpox outbreak in a tribal district Rayagada, Odisha state of India a South Asian country. The outbreak investigation was undertaken to assess the characteristics and determinants of the outbreak and make appropriate recommendations for control and prevention of further transmission. Methods A door to door survey was made for case finding and line listing with detailed travel, exposure and vaccination history. Qualitative research tools including key informant’s interview and focus group discussion were undertaken to understand community behavior and practice. Intravenous blood samples were collected for serological test to detect antibody to varicella-zoster virus. Results A total of 59 individuals out of 767 residents were affected with chickenpox in this outbreak with an attack rate of 8.73 per 100 populations. Age distribution indicated 69.5% belonged to the age group less than 14 years. No severe complication was reported. Blood sample of 33 case-patients was tested for Varicella zoster virus IgM antibodies and 24 (72.7%) found seropositive. The primary case was an 11-year-old girl who contracted infection in her residential school. None of the community members had received vaccination against chickenpox. Qualitative research indicated traditional beliefs and remedies prevailing in the communities that prevented case isolation and the modern treatment. Conclusion The study highlights the need for regular training of peripheral health workers for an effective awareness campaign to change beliefs and traditional practice and vaccination against Varicella zoster virus for prevention of such outbreaks. Disclosures All authors: No reported disclosures.

Background & objectives: Dengue virus infection is endemic in India with all the four serotypes of dengue virus in circulation. This study was aimed to determine the geographic distribution of the primary and secondary dengue cases in India. Methods: A multicentre cross-sectional study was conducted at Department of Health Research / Indian Council of Medical Research (DHR)/(ICMR) viral research and diagnostic laboratories (VRDLs) and selected ICMR institutes located in India. Only laboratory-confirmed dengue cases with date of onset of illness less than or equal to seven days were included between September and October 2017. Dengue NS1 antigen ELISA and anti-dengue IgM capture ELISA were used to diagnose dengue cases while anti-dengue IgG capture ELISA was used for identifying the secondary dengue cases. Results: Of the 1372 dengue cases, 897 (65%) were classified as primary dengue and 475 (35%) as secondary dengue cases. However, the proportion varied widely geographically, with Theni, Tamil Nadu; Tirupati, Andhra Pradesh and Udupi-Manipal, Karnataka reporting more than 65 per cent secondary dengue cases while Srinagar, Jammu and Kashmir reporting as low as 10 per cent of the same. The median age of primary dengue cases was 25 yr [interquartile range (IQR 17-35] while that of secondary dengue cases was 23 yr (IQR 13.5-34). Secondary dengue was around 50 per cent among the children belonging to the age group 6-10 yr while it ranged between 20-43 per cent among other age groups. Interpretation & conclusions: Our findings showed a wide geographical variation in the distribution of primary and secondary dengue cases in India. It would prove beneficial to include primary and secondary dengue differentiation protocol in the national dengue surveillance programme.

Objectives: The objective is to study the clinico-epidemiological features of viral acute encephalitis syndrome (AES) cases and compare them with nonviral AES cases in children from Eastern India. Methods: This prospective observational study was conducted in the department of pediatrics of a tertiary care teaching hospital in Eastern India over 18-month period. Children (6 months to 15 years) with acute onset of fever (≥37.5°C) and a change in mental status (including symptoms such as confusion, disorientation, coma, or inability to talk) and/or new onset of seizures (excluding simple febrile seizures) were included in the study. The main outcome measures were the etiology and proportion attributed to viruses causing AES with clinical correlation. Results: Of 834 of clinically suspected AES cases, viral etiology could be confirmed in 136 (16.3%) cases (herpes simplex virus-1 [HSV-I] was most common). The 5–15 years' age group was most commonly affected (boys > girls). More cases occurred from July to November. The presence of rash and Glasgow Coma Scale

Hypertension is a serious health issue worldwide and essential hypertension, which includes 90-95% of the cases, is influenced by both genetic and environmental factors. Identification of these factors may help in control of this disease. The Insertion/Deletion (I/D) polymorphism in Angiotensin-Converting Enzyme (ACE) gene and rs2106809 (C T) polymorphism in Angiotensin-Converting Enzyme 2 (ACE2) gene have been reported to be associated with essential hypertension in different populations.To investigate the association of ACE I/D and ACE2 rs2106809 polymorphisms with essential hypertension in the population of Odisha, an eastern Indian state.A total of 246 hypertensives (159 males and 87 females) and 274 normotensives (158 males and 116 females) were enrolled in the study. Detailed anthropometric data, tobacco, alcohol and food habits were recorded and 2 ml of venous blood was collected for biochemical and genetic analysis.The DD genotype of ACE and TT genotype of ACE2 were significantly high among female hypertensives, while T allele of ACE2 was linked to male hypertensives. In the male population, alcohol was also identified as a potential risk factor.Among females, ACE I/D and ACE2 rs2106809 polymorphisms, while among males, ACE2 rs2106809 polymorphism and alcohol consumption are associated with essential hypertension in the study population.

To describe the epidemiology and clinical features of cases in an outbreak of Hand, Foot and Mouth Disease (HFMD).Descriptive epidemiological study.Hospitals and community in urban areas of Bhubaneswar city, Odisha.Upon clinical suspicion of the first case as HFMD, local pediatricians and dermatologists were sensitized for case referral to Dermatology department of Institute of Medical Science and SUM hospital (IMS and SH) for evaluation and follow up. Community survey was undertaken by household visit by the team from Regional Medical Research Centre, Bhubaneswar in an outbreak area through hospital case tracing. Blood samples were tested for hematological counts and RT PCR assay done in a subset of samples for confirmation.Seventy eight cases of HFMD were detected between September 7 and November 6, 2009. Mean age (SD) was 5.13 (4.94) years (range 4 mo-31 yrs) and both sexes were equally affected. Fever and rash were the most common presenting symptoms with the rash distributed mostly over buttocks (83.3%), knees (77.5%), both surfaces of hands and oral mucosa (78.2%). Lesions healed in Mean (SD) 8.6 (1.5) days (range 7-15 d). Recovery was complete with minimal supportive treatment but, nail shedding was noted in three children within 4-5 weeks. CA16 was confirmed as the viral agent.Children (5-14 yrs) were majorly affected and complete recovery without neurological complications were noted. The characteristic clinical features described will be useful for early clinical diagnosis where laboratory confirmation is not feasible.

We have studied the clinical characteristics, severity and seasonality of rotavirus infection and prevalent genotypes in 652 non-rota vaccinated children in Odisha in eastern India. P genotypes were analysed for their association with host blood group antigens. P type of the virus is determined by the VP8* gene, and specific recognition of A - type of Histo - blood group antigen by P[14]VP8* has been reported. VP4, VP7 and VP6 genes of commonly identified G1P[8] strain were compared with genes of the same strain isolated from other parts of India, elsewhere and strains used for Rotarix and Rotateq vaccines. In 54.75% of children with gastroenteritis, rota virus was found. 9.65% of children had moderate, 78.07% severe, and 12.28% very severe disease as assessed using the Vesikari scoring system. The incidence of infection was highest during winter months. There was no association between any blood group and specific P genotypes. G1P[8] was the commonest cause of gastroenteritis, followed by G1P[11], G3P[8], G9P[8], G2P[4], G2P[6], G9P[4], G9P[11] and G1P[6]. Predominant G genotypes identified were G1 (72.9%), G9 (10.81%), G2 (8.10%) and G3 (8.10%). Sequence analysis of the VP7 gene, placed the G1P[8] strain in lineage 1 and of VP6 gene placed nine G1P[8] strains in subgroup II and one in subgroup I. The VP7 gene segment of two Odisha G1P[8] strains were found to cluster relatively close to the VP7 sequences of Rotarix vaccine. Antigenic differences were found with vaccine strains. Ten G1P[8] strains sequenced for the VP4 gene had 91-93% nucleotide and 92-96% amino acid identity with Rotateq vaccine P[8]). Rotarix vaccine VP4 had 89-91% nucleotide and 90-92% amino acid identity. Our findings indicate genetic variability of rotavirus strains circulating in the region and are significant, given the introduction of rota vaccination in the State.

Background India accounts for more than one-fifth of the world’s tuberculosis (TB) burden. In spite of efforts taken by the Revised National Tuberculosis Control Programme, tribal areas of the state of Odisha report a high TB incidence over the years. One of the reasons could be delay in reporting to health facilities by the symptomatic patients. During such delays an active case may infect numerous susceptible people thereby contributing to the perpetuation of the infection. The delay in diagnosis may be as long as 2–3 months and even more in hard-to-reach areas. Objective The present study aims to find out the extent of delay in diagnosis among pulmonary TB patients of a tribal dominated district that may help in planning effective control strategies for similar situations. Methods The information on delay in diagnosis is part of a cross-sectional drug resistance study carried out from June 2011 to May, 2013 in 20 Designated Microscopy Centres (DMCs) of Rayagada district of Odisha, India. Out of 634 smear positive pulmonary TB patients enrolled in this study, information on health seeking by the patients were available for 580 patients. The patients included had clinical signs and symptoms suggestive of pulmonary TB (cough, chest pain, and hemoptysis), with/without radiological evidence. Patients found smear positive by Ziehl–Neelsen microscopy were requested to take part in the study and accordingly a written questionnaire including history of: TB treatment; symptoms experienced by the patient and duration of suffering; and radiological examination was completed. The delay in diagnosis at the DMCs due to delay in health seeking by the symptomatic TB patients was evident as only 5.2% patients reported within 2 weeks and 62.6% up to 1 month of onset of symptoms. Results The delay in health seeking by the patients was not differentiated by sex or resistance profile, although more men attended the DMC for diagnosis. The present study is the first of its kind to report diagnostic delay of TB among smear-positive TB patients of Rayagada, a tribal-dominated district of Odisha, India and it reveals an extremely long diagnostic delay of TB in this area. We found that 12.9% of patients had a delay exceeding 2 months, and 50% of them had high sputum grade. This is a serious concern due to the fact that each of these patients dispenses up to 3500 bacilli in each cough, and may infect 10–15 people each year, eventually creating a public health problem. Conclusion Poor awareness of patients about the disease and limited access to health care are the bottom-line in apparent diagnostic delay of TB patients. This substantial patient delay to diagnosis is a major contributing factor for increasing transmission of TB in tribal districts of Odisha. Increased awareness of the disease is crucial in improving health-seeking behavior in these areas.

Sudden deaths in children due to acute encephalitis syndrome (AES) from a tribal dominated district of Malkangiri in Odisha, India, was reported during September-November, 2012. The investigation was carried out to search for the possible viral aetiology that caused this outbreak. Clinico-epidemiological survey and seromolecular investigation were carried out to confirm the viral aetiology. Two hundred seventy two suspected cases with 24 deaths were observed. The patients presented with low to moderate grade fever (87%), headache (43%), vomiting (27%), cold (18%), cough (17%), body ache (15%), joint pain (15%), rash (15%), abdomen pain (9%), lethargy (5%), altered sensorium (8%), convulsion (2%), diarrhoea (3%), and haematemesis (3%). Laboratory investigation showed Japanese encephalitis virus (JEV) IgM in 13.8 per cent (13/94) in blood samples and JEV RNA in one of two cerebrospinal fluid (CSF) samples. Paddy fields close to the houses, high pig to cattle ratio, high density (33 per man hour density) of Culex vishnui mosquitoes, low socio-economic status and low health awareness in the tribal population were observed. This report confirmed the outbreak of JEV infection in Odisha after two decades.

Acute Encephalitis Syndrome (AES) is one of the important health problems in childhood that leads to severe morbidity, mortality and sequelae. Herpes Simplex Virus (HSV) attributing towards such viral encephalitis carries importance with respect to its global prevalence challenging pathogenesis and morbidity outcomes. This report provides a review on several studies on epidemiology, pathogenesis (molecular and immune mechanism), clinical presentation, diagnosis and treatment related to Herpes simplex encephalitis (HSE) in children. It highlights wide spread distribution of HSE in children throughout the globe with mortality upto 70% in spite of availability of effective antiviral agent. In this context early diagnosis is a challenge as early CSF studies and imaging may not provide confirmatory diagnosis so an empirical treatment of Acyclovir will be of value. The review pointed that LATs play an important role in molecular modulation but it is still challenging to explain the exact cellular mechanism. The current antivirals available have shown to be potentially useful in curing symptomatic illness but eliminating neuronal carrier stage is still an issue of research for drug development. Better understanding of biochemical and immune response if available can open the scope for use of immunomodulators that can prevent reactivation. This review also focuses upon challenges in immunopathogenesis and treatment and vaccine development.

From September through October 2006, an unknown disease characterized by acute onset of fever, joint pain with or without swelling, and maculopapular rash along with fatigue was reported from three villages of Cuttack and one village of Kendrapara district of Orissa, India, by the State Health Department. Upon learning this, a team from Regional Medical Research Centre (Indian Council of Medical Research), Bhubaneswar, Orissa, conducted an epidemiological investigation in the area. Household survey was carried out and clinical examination of the symptomatic individuals (n = 1289: Kendrapara, 752; Cuttack, 537) undertaken. Based on the recorded chikungunya (CHIK) fever symptoms, a vector-borne viral disease was considered for provisional diagnosis. Blood samples were collected from 217 symptomatic individuals; to confirm the diagnosis, sera were tested for anti-CHIK antibody (immunoglobulin M), which revealed 63% (64/101) and 40% (47/116) seropositivity in the samples from Kendrapara and Cuttack district, respectively. The illness was managed with analgesics like paracetamol. No death was recorded due to the illness. Entomological survey in the areas revealed the presence of Aedes mosquitoes: aegypti, albopictus, and vittatus. The per-man-hour density of Aedes vectors ranged from 0.8 to 7.6. High larval indices, house index17% and Breteau index70%, also indicated Aedes breeding in the area. The investigation documented circulation of CHIK in Orissa, India, and helped to take preventive steps in the outbreak area, with the suggested vector control measures.

Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and ‘hot spots’ of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of “nests”, all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start., Author Summary In order to achieve global elimination of lymphatic filariasis, it may be necessary to consider alternative approaches to mass treatment using higher or more frequent dosing with the existing drugs used in the programmes. Outside Africa, the drugs used are albendazole and diethylcarbamazine given annually. The current study is the first to examine the use of higher or more frequent dosing in a bancroftian filariasis endemic area outside Africa. Four groups of infected subjects were followed for two years using standard techniques for monitoring drug efficacy in Odisha, India. We showed that higher doses of albendazole, or 6-monthly treatment, were more effective than the standard regimen in producing clearance of microfilaria and reductions in antigenemia. Additionally we found that these regimens were more effective in killing the adult filarial worms in the lymphatics. Importantly, the higher doses used did not increase the risk of side effects. These alternative approaches could accelerate lymphatic filariasis elimination either at the end of existing programmes or to permit new programmes to achieve their goals faster.

HPV is the major causative agent for cervical cancer. Study on the risk of cervical cancer associated with different hr-HPV genotypes would be useful for disease management and new vaccine strategy. With limited reports available, the present study aimed to investigate the pattern of HPV genotypes coinfections and risk of cervical carcinoma associated with them in Indian population. 15 HPV genotypes were detected by E6/E7 multiplex nested type-specific PCR in the HPV-positive cervical samples of 172 cervical cancer cases and 174 subjects with normal cytology. Association between the genotypes and cervical cancer was estimated by calculating the Odds ratio and 95% confidence interval. Risk of cervical carcinoma was associated with multiple genotypes excluding HPV16 (OR:5.87; 95% CI-1.28-26-29; p = .02), multiple genotypes excluding HPV18 (OR = 2.5; 95% CI = 1.09-6.05; p = .03), multiple genotypes of α9 species(OR = 5.3 95% CI = 1.14-24.03; p = .007), and multiple genotypes of α7 species (OR = 2.5; 95% CI = .49-13.45; p = .2). Genotypes not targeted by quadrivalent vaccine types (OR = 2.94 95% CI = 1.48-5.80; p = .001) conferred 2.94 fold higher risk of cervical carcinoma. Cases those coinfected with phylogenetically related genotypes (OR = 2.29; 95% CI(.69-7.59) p = .17) were at 2.9 fold higher risk of invasive cervical carcinoma than those infected with other genotypes although it is not statistically significant. Whereas phylogenetically unrelated genotypes coinfection is negatively associated with cervical carcinoma (OR = .44 95% CI (.244-.8) p = .007) and it is statistically significant.Genotypes not targeted by 9-valent vaccines (OR = .40; 95% CI = .19-.85; p = .017) associated with lesser risk of cervical carcinoma as compared to other genotypes. Subjects infected with any HPV genotype/genotypes excluding HPV16 in association with HPV 18 (OR = 4.1; 95% CI = 1.81-9.25 P = < .001) were at 4.1 fold higher risk of developing invasive cervical carcinoma.In conclusion, the risk of development of cervical cancer is genotype specific and might be associated with type-specific interactions between the genotypes in multiple infections.

Background Once interruption of transmission of lymphatic filariasis is achieved, morbidity prevention and management becomes more important. A study in Brugia malayi filariasis from India has shown sub-clinical lymphatic pathology with potential reversibility. We studied a Wuchereria bancrofti infected population, the major contributor to LF globally. Methods Children aged 5–18 years from Odisha, India were screened for W. bancrofti infection and disease. 102 infected children, 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then randomized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually. The lymphatic pathology was evaluated six monthly for two years. Findings Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80% of symptomatic (40/50) and 63·5% (33/52) of asymptomatic children. Progressive improvement in baseline pathology was seen in 70·8, 87·3, 98·6, and 98·6% of cases at 6, 12, 18, and 24 months follow up, while in 4·2, 22·5, 47·9 and 64·8%, pathology reverted to normal. This was independent of age (p = 0·27), symptomatic status (p = 0·57) and semi-annual/bi-annual dosing (p = 0·46). Six of eleven cases showed clinical reduction in lymphedema of legs. Interpretation A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole. This provides evidence for morbidity prevention & treatment of early lymphedema. It can also be used as a tool to improve community compliance during mass drug administration. Trial registration ClinicalTrials.gov No CTRI/2013/10/004121, Author summary Infection with lymphatic filarial parasites usually occurs early in childhood in endemic areas, but clinical signs appear much later. Reversal of lymphatic pathology has been shown with the much less common Brugia malayi infection using DEC and albendazole and there is scarce evidence whether the same occurs with bancroftian filariasis using the above drugs. We designed this study to look for prevalence of lymphatic pathology in children with and without clinical signs of infection and to observe the effect on the pre-treatment pathology using DEC and albendazole given once or twice a year. We have shown, using lymphoscintigraphy, that lymphatic vessel changes occur very early in infection, and treatment can reverse these changes, even when clinical symptoms are already apparent. This has important implications for lymphedema prevention, case management and for advocacy in the Lymphatic Filariasis Elimination Program. It also strengthens the previous evidence of benefit of treatment on early lymphedema management.

Cervical cancer is the fourth most common cancer in women worldwide. It is well known that high-risk HPV is the main etiological agent for this infectious viral carcinoma. Human papillomaviruses are small (50 nm) double-stranded DNA viruses composed of a genome of 8 kilobase pair, enclosed inside a non-enveloped capsid protein. The genome includes three portions: (a) early genes (E1, E2, E4, E5, E6, E7) those regulate the vegetative and productive phase of viral life cycle; (b) late genes (L1, L2) which encode the capsid protein and (c) a noncoding regulatory region called long control region (LCR) involved in the regulation of viral replication and transcription. The HPV oncoproteins E6 and E7 recognize numerous host proteins, in large part by hijacking cellular domain-motif interaction networks. E6 and E7 oncoproteins disrupt cell cycle checkpoint control by inhibiting CDKs inhibitors (P21, P27) and degrading P53. In the process of E6 mediated degradation, E6 binds to a short leucine (L)-rich LxxLL consensus sequence within the cellular ubiquitin ligase E6AP3. Subsequently, the E6/E6AP heterodimer recruits and degrades p53. The LxxLL peptide of E6AP is sufficient to render E6 liable to interact with p53 ‘core’ (DNA binding) domain of p53 required for the interaction with E6/E6AP9–11. In the present study, we explored specific novel inhibitors targeting three different druggable pocket i.e., E6-binding cleft, LxxLL pocket of AP and the p53-binding cleft of E6/E6AP/p53 ternary complex using AutoDock tool. A total of five novel compounds with higher binding energy were identified as potential competitive inhibitors against HPV16 E6/AP/P53 ternary complex. The combinatorial strategies targeting these druggable pockets are expected to open up better avenues for the development of therapeutic strategies against HPV-mediated oncogenesis in near future.

The paper an attempt has been made to analysis the status of acute respiratory tract infection among children in India. In the present study we aimed to present first time the detection of viruses, bacteria and mix infection of viruses and bacteria in hospitalized children with ARI and also to analyze the influence of socioeconomic status of parent in two divergent geographical settings of Odisha. Hospitalized children with ARI aged

Encephalitis is defined as inflammation of the brain parenchyma associated with neurologic dysfunction. AES occurs in explosive epidemics or in a non-epidemic (sporadic) form. Epidemic in India have been attributed to Japanese encephalitis virus (JEV) infection. Herpes simplex virus (HSV) is responsible for most sporadic cases of AES. This study was undertaken to detect JEV and HSV from CSF samples. Method: Two to three ml of CSF was collected in a dry sterile container. Samples were divided into 2 vials and kept at -20oC. One vial was used for ELISA test in while the other vial was used for PCR. Result: Of 90 cases, 61 were males (68%), 29 were females (32%). Majority belonged to 1 month-5years in 34 (38%) cases followed by 6-10 years in 23 (26%) cases. The commonest symptom was fever in 90 (100%) cases followed by change in mental status in 86 (95.6%).Of 90 samples 2 (2.2%) was positive for JEV in PCR while only 1 (1.1%) was positive in ELISA. A total of 9 (10%) samples were positive for HSV 1 & 2, of which 8 (8.9%) samples were positive in ELISA assay and 8 (8.9%) were positive in PCR assay. In our study only 2 (2.2%) samples were positive for JEV in PCR while one was negative in ELISA. 9 (10%) samples were tested positive for HSV which signifies the sporadic nature of the virus in this region. Conclusion: PCR was found to be more sensitive in detection of JEV, while in HSV detection both ELISA and PCR were equally sensitive. Key words: Japanese B encephalitis virus; Herpes simplex virus; Acute encephalitis syndrome; Polymerase chain reaction; Enzyme linked immunosorbent assay.

This letter to the editor discusses Chlamydia infections and goes on to state that India still needs to adopt the practice of screening women under the age of 24 years once per year for early diagnosis and treatment of Chlamydia. It includes pilot study results from Orissa that generate evidence on this infection in this region using highly sensitive and polymerase chain reaction (PCR) tests followed by southern hybridization.