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

We assessed the impact of pre-exposure prophylaxis (PrEP) in the context of a community-based HIV program among female sex workers (FSWs) in Kolkata, India. This was an open-label, uncontrolled demonstration trial. HIV seronegative FSWs over 18 years were eligible. Participants were administered daily tenofovir/emtricitabine (TDF-FTC) with follow-up visits at months 1, 3, 6, 9, 12, and 15. Drug adherence was monitored by self-report, and a random subset of participants underwent plasma TDF testing. 843 women were screened and 678 enrolled and started on PrEP. Seventy-nine women (11%) did not complete all scheduled visits: four women died of reasons unrelated to PrEP and 75 withdrew, for a 15-month retention rate of 89%. Self-reported daily adherence was over 70%. Among those tested for TDF, the percentage of women whose level reached ≥40 ng/mL was 65% by their final visit. There were no HIV seroconversions, and no evidence of significant changes in sexual behavior. This study demonstrated the feasibility and effectiveness of PrEP for FSWs in Kolkata, with very high levels of adherence to PrEP and no HIV seroconversions. The integration of PrEP into an existing community-based HIV prevention program ensured community support and facilitated adherence.

Background: The Revised National Tuberculosis Control Programme (RNTCP) in Andhra Pradesh, India, introduced TrueNat™ MTB/Rif, a rapid molecular test for detecting Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance at 193 TB units (TUs) in October 2018. We evaluated its impact on TB diagnosis and assessed the operational feasibility of its deployment at point-of-care (POC) settings.Methods: We compared the number of presumptive TB cases tested and the number (proportion) of microbiologically positive before (January–August 2018) and after (January–August 2019) the deployment of TrueNat. We interviewed laboratory technicians and Senior TB Laboratory Supervisor from 25 randomly selected TUs to assess operational feasibility.Results: In 2018, 10.5% (range 8.9–13.1) of 245,989 presumptive cases tested were positive. In 2019, of the 185,435 presumptive cases tested, 13.7% (range 9.6–18.9) were positive. The proportion of presumptive TB cases in whom MTB was detected using TrueNat was 14.4% (range 10.0–21.2). TrueNat significantly increased case detection (incidence rate ratio [IRR] 1.30; 95%CI 1.15–1.46), yielding an additional 18 TB cases per 100 000 population. Laboratory technicians became comfortable in performing TrueNat after a median of 10 tests (interquartile range 5–17.5). Invalid reports declined from 6.8% to 3.6%.Conclusion: The deployment of TrueNat as POC diagnostic test improved case detection and was operationally feasible under RNTCP.

We evaluated the prevalence and determinants of bacterial vaginosis (BV) in HIV-infected women from Maharashtra, India. Among 912 HIV-infected women enrolled, BV was diagnosed in 191 (20.9%) and intermediate BV was diagnosed in 258 (28.3%) women. Women with more than two pregnancies had 1.6 times increased risk of BV (95% CI 1.0, 2.5, p-value 0.038), women who were menopausal had 6.2 times increased risk of BV (95% CI 2.4, 15.6, p-value

Transgenders (TGs) are highly affected by HIV with high prevalence of 3.14% in India. Since 2017, targeted preventive efforts have been initiated by the government and HIV-infected TGs are being provided the antiretroviral (ART) treatment. Information on the primary HIV drug resistance is crucial for appropriate treatment selection to curb further spread of HIV in this population. In this study, we analyzed HIV-1 pol gene sequences from 36 TGs for presence of drug resistance mutations. To our knowledge, this first study from India reports high-level primary drug resistance (13.8%) among the TG population. Mutations M184V, A98G, K103N, G190A, and Y318F associated with resistance to nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitors were observed. All pol gene sequences revealed HIV-1 subtype C in all study TG. High-level HIV-1 drug resistance warrant nationwide larger studies on TGs to understand the level of primary ART drug resistance among this population.

Background India plans elimination of HIV-Mother-to-Child-Transmission in 2020. Targets include >95% coverage of Antenatal-care (ANC) and HIV-testing. In 2015-16, while 43% of the estimated Indian pregnant-women (PW) received HIV-tests, one state reported >95% testing. Indian public-health-care is a three-tiered system from primary-level sub-centres (population-5000) to tertiary-level hospitals. ANC involves multiple-visits per pregnancy at different care-levels and data are aggregated in the Health-Management-Information-System (HMIS) at all levels. We validated (public and private-sector data from this state, for duplication in ANC registration and HIV-testing using mixed methods. Methods In the absence of guidelines for assessing aggregate-data duplication, we used mixed-methods, including surveys among 9845 PW and providers from 240 facilities in 10/36 representative districts; in-depth-interviews; case-studies and analysis of HMIS and HIV-program data (April 2015-Mar 2017). Interviews and case-studies highlighted inadvertent duplicate data-capture. Surveys quantified levels of duplication and adjustment factors (public and private-sector) were developed. Results Twenty-four% PW, visited multiple facilities for ANC, while 81% providers reported all the PW coming to their facilities as new ANC registrations (irrespective of lower-tier registration); identifying a minimum duplication of 19% (24%*81%) in ANC coverage. Twenty-nine% and 28% PW from public and private-facilities reported >1 HIV-test; while 75% and 36% reported visiting another public-facility where HIV test was likely to be reported again. Minimum duplication of 22% and 10% in HIV testing was noted in public and private-sectors respectively. Conclusions We report methods to quantify repeat HIV-testing and duplicate-reporting, due to inherent processes in ANC in public-healthcare in India. Modification of data-capture was recommended and adopted across India. Key messages Assessing duplication in aggregate health data is key to developing robust datasets for disease elimination

Youth and adolescents are the priority population to target the interventions as risky behaviors persist and they contribute to almost half of the new Human immunodeficiency virus (HIV) infections. The youth in India have a unique and diverse need of sex health education. The present study was conducted with the objective to understand their sexual behavior and requirements of sexual health. Focus group discussions were conducted among 74 college students, separately for boys and girls. The participant students were from different streams of education. The domains of enquiry were related to the relationships, risk behaviors, sources of information and use of technology for sex health education. The qualitative data was analyzed based on the themes and subthemes derived from these discussions. A majority of the youth favoured active involvement of parents, school teachers in sex health education. They suggested that better-informed parents lead to better-informed adolescents. Open discussion with experts was also desired by the students. The use of mobile/web based application for sex health education and awareness about HIV and sexually transmitted infections (STIs) was preferred, however, they suggested that based on personal requirements, individual need based counseling and guidance is important. Active parental involvement and open discussions on sexuality were the preferred options by the student to seek the knowledge and guidance. Innovative mobile application for sex health education will be useful for the young adults for information and communication. The study highlighted a need to develop a holistic approach to generate a culturally-sensitive sex health education and life skills model.

Background & objectives: Early case detection is essential to interrupt transmission and to prevent further spread of tuberculosis (TB) in high endemic settings. Nucleic acid amplification tests (NAATs) with visual read-outs are ideal as point-of-care tests. Truenat™ MTB is an indigenous chip-based NAAT for detection of Mycobacterium tuberculosis, which involves extraction of DNA and real-time polymerase chain reaction (PCR) using portable, automated, battery-operated instruments. The current multicentric study was aimed to evaluate Truenat for detection of MTB in sputum samples obtained from patients with presumptive pulmonary TB with reference to culture as gold standard and Xpert as a comparator. Methods: The study was conducted at four sites, namely ICMR-National Institute for Research in Tuberculosis, Chennai; All India Institute of Medical Sciences, New Delhi; ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra; and National Institute of TB and Respiratory Diseases, New Delhi. Patients suspected to have TB were screened for eligibility. Two sputum samples were collected from each patient. Tests included smear, Xpert and Truenat directly from the sputum sample and culture by Lowenstein-Jensen (L-J) medium and MGIT960 from decontaminated pellets. Sample used for Truenat assay was coded. Resolution of Truenat false positives was done using an in-house PCR with TRC4 primers. Results: The study enrolled 2419 presumptive TB patients after screening 2465 patients, and 3541 sputum samples were collected from the enrolled patients. Results of 2623 samples were available for analysis. Truenat showed a positivity rate of 48.5 per cent as compared to 37.0 per cent by Xpert. The sensitivities of Truenat and Xpert were was 88.3 and 79.7 per cent, respectively in comparison with culture. Interpretation & conclusions: Truenat MTB identified more positives among culture-confirmed samples than Xpert and had higher sensitivity. In addition, other advantageous operational features of Truenat MTB were identified which would be useful in field settings.

BACKGROUND & OBJECTIVES: An outbreak of respiratory illness of unknown aetiology was reported from Hubei province of Wuhan, People's Republic of China, in December 2019. The outbreak was attributed to a novel coronavirus (CoV), named as severe acute respiratory syndrome (SARS)-CoV-2 and the disease as COVID-19. Within one month, cases were reported from 25 countries. In view of the novel viral strain with reported high morbidity, establishing early countrywide diagnosis to detect imported cases became critical. Here we describe the role of a countrywide network of VRDLs in early diagnosis of COVID-19. METHODS: The Indian Council of Medical Research (ICMR)-National Institute of Virology (NIV), Pune, established screening as well as confirmatory assays for SARS-CoV-2. A total of 13 VRDLs were provided with the E gene screening real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay. VRDLs were selected on the basis of their presence near an international airport/seaport and their past performance. The case definition for testing included all individuals with travel history to Wuhan and symptomatic individuals with travel history to other parts of China. This was later expanded to include symptomatic individuals returning from Singapore, Japan, Hong Kong, Thailand and South Korea. RESULTS: Within a week of standardization of the test at NIV, all VRDLs could initiate testing for SARS-CoV-2. Till February 29, 2020, a total of 2,913 samples were tested. This included both 654 individuals quarantined in the two camps and others fitting within the case definition. The quarantined individuals were tested twice - at days 0 and 14. All tested negative on both occasions. Only three individuals belonging to different districts in Kerala were found to be positive. INTERPRETATION & CONCLUSIONS: Sudden emergence of SARS-CoV-2 and its potential to cause a pandemic posed an unsurmountable challenge to the public health system of India. However, concerted efforts of various arms of the Government of India resulted in a well-coordinated action at each level. India has successfully demonstrated its ability to establish quick diagnosis of SARS-CoV-2 at NIV, Pune, and the testing VRDLs.

Background & objectives: There is a need for an affordable, easy, high-sensitivity test usable at the peripheral health facility for diagnosis of drug-resistant (DR) tuberculosis (TB) to interrupt disease transmission. Nucleic acid amplification tests (NAATs) for early detection of DR-TB are ideal to bring testing near to the patient. TruenatTM MTB (Mycobacterium tuberculosis) and TruenatTM MTB-RIF (rifampicin) is an indigenous chip-based real-time polymerase chain reaction (PCR) based test for detection of multidrug-resistant (MDR) TB. The test involves extraction of DNA using automated, battery operated Trueprep instrument and real-time PCR performed on the Truelab analyzer. We report here multicentric validation of Truenat MTB-RIF for detection of DR-TB in suspected DR-TB patients. Methods: Consecutive patients aged 18-65 yr, with symptoms suggestive of TB and with a history of previous treatment, reporting to the National TB Elimination Programme (NTEP) clinics under four national institutes, namely AIIMS (All India Institute of Medical Sciences, New Delhi), NITRD (National Institute of Tuberculosis and Respiratory Diseases, New Delhi), NIRT (National Institute for Research in Tuberculosis, Chennai) and ICMR-National JALMA Institute for Leprosy and other Mycobacterial Diseases, Agra, were included in the study. Two sputum samples (one spot and one morning) were collected from each patient, after obtaining informed written consent. The samples were subjected to smear, GeneXpert and MGIT 960 culture (and drug susceptibility testing to RIF) (surrogate for MDR-TB) to serve as reference tests. The samples were coded to ensure blinding and subjected to Truenat MTB-RIF. Truenat MTB-RIF Version 1.5 was used for testing 1084 samples for RIF resistance, while Version 2.0 was used to test another 1201 samples. Results: Truenat MTB-RIF Version 1.5 in comparison with comprehensive laboratory reference standards yielded sensitivity and specificity of 76.2 and 94.7 per cent, respectively for the detection of RIF resistance in 1084 samples, collected across four sites. Based on the analysis of discordant samples, Version 2.0 of Truenat was developed by the manufacturer and this was further tested on additional 1201 samples, yielding a sensitivity of 87.5 per cent and specificity of 99.5 per cent. Interpretation & conclusions: Multicentric trial of TruenatTM MTB-RIF demonstrated a great potential of this point of care NAAT for detection of MDR-TB. The test would be useful in limited resource settings and inaccessible areas without need for any additional infrastructure.

Background & objectives: Healthcare workers (HCWs) are at an elevated risk of contracting COVID-19. While intense occupational exposure associated with aerosol-generating procedures underlines the necessity of using personal protective equipment (PPE) by HCWs, high-transmission efficiency of the causative agent [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] could also lead to infections beyond such settings. Hydroxychloroquine (HCQ), a repurposed antimalarial drug, was empirically recommended as prophylaxis by the National COVID-19 Task Force in India to cover such added risk. Against this background, the current investigation was carried out to identify the factors associated with SARS-CoV-2 infection among HCWs in the country. Methods: A case-control design was adopted and participants were randomly drawn from the countrywide COVID-19 testing data portal maintained by the ICMR. The test results and contact details of HCWs, diagnosed as positive (cases) or negative (controls) for SARS-CoV-2 using real-time reverse transcription-polymerase chain reaction (qRT-PCR), were available from this database. A 20-item brief-questionnaire elicited information on place of work, procedures conducted and use of PPE. Results: Compared to controls, cases were slightly older (34.7 vs. 33.5 yr) and had more males (58 vs. 50%). In multivariate analyses, HCWs performing endotracheal intubation had higher odds of being SARS-CoV-2 infected [adjusted odds ratio (AOR): 4.33, 95% confidence interval (CI): 1.16-16.07]. Consumption of four or more maintenance doses of HCQ was associated with a significant decline in the odds of getting infected (AOR: 0.44; 95% CI: 0.22-0.88); a dose-response relationship existed between frequency of exposure to HCQ and such reductions (χ[2] for trend=48.88; P

Background & objectives: In India, acute encephalitis syndrome (AES) cases are frequently reported from Gorakhpur district in Uttar Pradesh. Scrub typhus is one of the predominant aetiological agents for these cases. In order to delineate the extent of the background of scrub typhus seroprevalence and the associated risk factors at community level, serosurveys during both lean and epidemic periods (phase 1 and phase 2, respectively) of AES outbreaks were conducted in this region. Methods: Two community-based serosurveys were conducted during lean (April-May 2016) and epidemic AES (October-November 2016) periods. A total of 1085 and 906 individuals were enrolled during lean and epidemic AES periods, respectively, from different villages reporting recent AES cases. Scrub typhus-seronegative individuals (n=254) during the lean period were tested again during the epidemic period to estimate the incidence of scrub typhus. Results: The seroprevalence of Orientia tsutsugamushi during AES epidemic period [immunoglobulin (Ig) IgG: 70.8%, IgM: 4.4%] was high as compared to that of lean AES period (IgG: 50.6%, P

The medicinal plants are important source for pharmaceutical manufacturing. Medicinal plants & herbal medicines account for a significant percentage of the pharmaceutical market. There is increasing awareness and general acceptability of the use of herbal drugs in today’s medical practice although most of these applications are not scientific. Herbal medicines are not a simple task since many factors influence the biological efficacy and Reproducible therapeutic effect. So it is necessary to improve safety of herbal drugs by developing certain quality control parameters & by following the WHO guidelines for herbal medicines. This review seeks to enlighten the need to establish quality parameters for collection, handling, processing and production of herbal medicine as well as employ such parameters in ensuring the safety of the global herbal market. It is necessary to introduce measures on the regulation of herbal medicines to ensure quality, safety, efficacy of herbal medicines by using modern suitable standards & GMP. The processes of good quality assurance and standardization of herbal medicines and products using various spectroscopic, chromatographic and electrophoretic methods were also discussed. In fact, the research field of quality control of herbal medicines is really an interdisciplinary research. It needs crossover of chemistry, pharmacology, medicine and even statistics to provide a platform for the quality control of traditional herbal medicines and further to discover the novel therapeutics composed of multiple chemical compounds. Keywords: Herbal drugs, Adulteration, Standardization, Chromatography, Electrophoresis, HP-LC and GC-MS.

Background:IL-2 cytokine is involved in HIV replication and is also known to cause hepatic injury. Polymorphisms in the IL-2 gene are associated with altered interleukin-2 production.Methods:Hence, we assessed the prevalence of IL-2-303G/T polymorphism in 165 HIV patients (34 with and 131without hepatotoxicity) and 155 healthy controls using the PCR-RFLP method.Results:In patients with hepatotoxicity, IL-2-303GT, -303GT+TT genotypes were less prevalent as compared to without hepatotoxicity and healthy controls (29.4% vs. 42.7%, 58.8% vs. 69.5%; 29.4% vs. 40.6%, 58.8% vs. 66.5%, respectively). In patients with hepatotoxicity using tobacco and alcohol, IL-2-303GT,-303TT genotypes were distributed higher as compared to non-users (42.9% vs. 25.9%, OR=8.52, 42.9% vs. 25.9%, OR=9.09, and 28.6% vs. 29.6%, OR=1.63, 42.9% vs. 25.9%, OR=2.93), while IL-2-303TT genotype occurred more often in HIV patients consuming alcohol (34.1% vs. 23.0%). Nevirapine users with hepatotoxicity overrepresented the IL-2-303GT,-303TT genotypes as compared to efavirenz (34.8% vs. 18.2%, OR=4.64, 34.8% vs. 18.2%, OR=3.88). Among nevirapine users, IL-2-303GT genotype was associated with susceptibility to the acquisition of hepatotoxicity with borderline significance (OR=4.24, P=0.06). HIV patients using nevirapine majorly represented the IL-2-303TT genotype (26.9% vs. 25.0%, OR=2.35) while HIV patients with nevirapine + alcohol usage presented the IL-2 -330TT genotype at a higher frequency (34.2% vs. 23.5%, OR=1.51). In patients with hepatotoxicity using nevirapine + alcohol, the genotype IL-2 - 330TT was predominant (60.0% vs. 27.8%, OR=3.16).Conclusion:Thus, IL-2-303G/T polymorphism did not confer the susceptibility to ARV associated hepatotoxicity. However, IL-2-303G/T polymorphism with nevirapine usage may facilitate the risk for acquisition of ARV associated hepatotoxicity.

Background: Immunological non-responders (INR) represent a unique category of HIV-infected patients on antiretroviral therapy. These patients have suppressed viremia but a suboptimal increase in CD4 cell count, which might have opposing effects on functional immune reconstitution. Hence, the extent of immune reconstitution in INR patients was investigated in order to determine their susceptibility to opportunistic infections. Methods: Twenty-three INR patients (CD4 increase 100 cells/mm3, viral load

Background High Risk Human Papilloma Viruses (HR-HPV) recurrently infect women having Human Immunodeficiency Virus − 1 (HIV-1)infection. Transforming HPV E6 and E7 genes promote invasive cancers and interact with Notch-1receptor. Concomitantly, HIV-1 Tat binds to EGF motifs within the Notch-1extracellular domain. HR-HPV infection activates Notch-1 signalling. Permissive HIV-1entry into the cervix is allowed. Notch-1 inhibitors may offer solace to the aggressive cancer phenotype in HIV-1 positive women. Still, the molecular cross talk between different oncogenes within the Notch-1pathway during HIV-1/HPV-16 + co-infections has not been elucidated. Methods Adherent cervical tumor derived cell lines-CaSki cell line (with inherent HPV16+ sequence and endogenous Notch-1 activity) and C33A cell line (cervical cancer phenotype, HPV -ve for HPV DNA and RNA) were used. Plasmids (pLEGFPN1 encoding HIV-1 Tat and pNL 4 − 3 encoding HIV-1(full HIV-1 genome), were transfected at 600 ng/mL into the above mentioned cell lines, in order to examine independent effects of HIV-1 Tat and HIV-1 transfection in HPV-16+ cervical cancer cells. We performed western blotting, cell cycle analysis and RT-qPCR post transfection. Three sets of independent experiments were analyzed by Graph Pad Prism 5. Statistical significance was calculated using Student t -test. Data expressed as mean ± standard deviation (SD). p values ≤ 0.05* were considered statistically significant. Results HIV-1 Tat and HIV-1 inhibited Notch-1expression, with differential effects on EGFR when comparing C33A and CaSki cell lines. CDK2 induction in Tat transfected CaSki cells, showed concomitant G0/G1 phase accumulation favouring cancer progression. Notch-1 inhibition shut off significant Cyclin D expression with a significant p21 induction and increased G2-M cell population in CaSki cells. On the contrary, HIV-1 infection utilized Hes-1-EGFR-CyclinD-p21axis, G2-M arrest, DDR response and cancer progression. Conclusion Our study highlights for the first time that HIV-1 Tat and/or HIV-1 driven cancers in HPV-16+ CaSki cells, show Notch-1 suppression and CDK2 dependent activity. HIV-1 Tat activates Hes-1 amplifying the EGFR gene which improves the aggressive state possibly through irreversible oxidative-stress induced senescence. HIV-1, favours cancer progression through its CXCR4 receptor, responsible for unbridled mitosis, G2-M arrest and damaged DNA response (DDR). Treatment of CaSki cells with a Notch-1 inhibitor, DAPT showed marginal recovery in p21expression with Go/G1 and S phase recovery.

The COVID-19 pandemic is a global health crisis that poses a great challenge to the public health system of affected countries. Safe and effective vaccines are needed to overcome this crisis. Here, we develop and assess the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine in rhesus macaques. Twenty macaques were divided into four groups of five animals each. One group was administered a placebo, while three groups were immunized with three different vaccine candidates of BBV152 at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which exhibited interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. This vaccine candidate BBV152 has completed Phase I/II (NCT04471519) clinical trials in India and is presently in phase III, data of this study substantiates the immunogenicity and protective efficacy of the vaccine candidates., SARS-CoV-2 vaccines are needed to fight the pandemic. Here, authors show protective efficacy and immunogenicity of the inactivated SARS-CoV-2 vaccine BBV152 in rhesus macaques. This vaccine is currently in clinical development.

Background Thirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load, antibody kinetics, cytokine profile and phylogenetic analysis between fatal and non- fatal cases. Methods Thirty four cases were included in this study. Blood and urine samples were collected from all the cases on the day of admission to hospital. Non-fatal cases were followed weekly for understanding the profile of viral kinetics, anti-CCHFV IgM and IgG antibodies. We also quantified the cytokines in both fatal and non-fatal cases. For epidemiological correlation, livestock were screened for anti-CCHF IgG antibodies and the tick pool specimens were tested by real time RT-PCR. Virus isolation was attempted on tick pools and human specimens and phylogenetic analysis performed on human and ticks complete genome sequences. Results CCHF cases were detected throughout year in 2019 with the peak in August. Out of 34 cases, eight secondary CCHF cases were reported. Cases were predominantly detected in males and in 19–45 years age group (55.88%). The persistence of viremia was observed till 76th POD (post onset date) in one case whereas anti-CCHFV IgM and IgG was detected amongst these cases from the 2nd and 20th POD respectively. Positivity observed amongst livestock and tick pools were was 21.57% and 7.4% respectively. The cytokine analysis revealed a significant increase in the level of serum IL-6, IL-10 and IFN-γ during the acute phase of the infection, but interestingly IL-10 lowered to normal upon clearance of the virus in the clinically recovered case. Fatal cases had high viral RNA copy numbers. Bleeding from one or two mucosal sites was significantly associated with fatality (OR-16.47;p-0.0034 at 95% CI). We could do CCHF virus isolation from two cases. Phylogenetic analysis revealed circulation of re-assortment of Asian-West African genotypes in humans and ticks. Conclusions The persistence of CCHF viral RNA was detected till 76th POD in one of the survivors. The circulation of a re-assortment Asian-West African genotype in a CCHF case is also reported first time from India., Author summary Crimean Congo hemorrhagic fever is a zoonotic tick-borne viral hemorrhagic disease. This disease is reported from Europe, Mediterranean, north-western China, central Asia, Africa, and the Middle East. Several outbreaks of CCHF were reported from Gujarat and Rajasthan states, India from 2011 to 2019. In this study, we discuss the clinical, molecular, serological, and the cytokine data of 34 CCHF cases (17 fatal and 17 survived) which were detected from Gujarat state in the year 2019. A sequential weekly follow up of the CCHF survivors was performed to understand the viral kinetics and the antibody profile. Interestingly, the presence of persistence CCHF viral RNA was observed till 76th POD in one of the survivors. To our knowledge, we are reporting this long term persistence of viremia for the first time. We also observed that the anti-CCHFV IgM detection in the serum samples starts as soon as 2nd POD but anti-CCHFV IgG antibody could be detected in the majority of the cases only after the 28th POD. The cytokine analysis revealed a significant increase in the level of serum IL-6, IL-10 and IFN-γ during the acute phase of the infection, but interestingly IL-10 lowered to normal upon clearance of the virus in the clinically recovered case. We did the phylogenetic analysis and concluded the circulation of the Asian-West African re-assortment genotype in humans, which has not been reported from India prior to this study.

We report a child with Proboscis Lateralis with nasal aplasia and complete agenesis of maxillary and ethmoidal sinuses. This is a rare congenital malformation. Embryological basis has not been proven, and it is often associated with facial malformation. However, no such abnormality was noted in our patient. This condition is diagnosed clinically and confirmed radiologically of which CT scan plays a pivotal role. Reconstructive surgery is planned at the age of fifteen years.

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

The COVID-19 pandemic is a global health crisis that has severely affected mankind and posed a great challenge to the public health system of affected countries. The availability of a safe and effective vaccine is the need of the hour to overcome this crisis. Here, we have developed and assessed the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152) in rhesus macaques (Macaca mulata). Twenty macaques were divided into four groups of five animals each. One group was administered a placebo while three groups were immunized with three different vaccine candidates at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab, and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which showed features of interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. Data from this study substantiate the immunogenicity of the vaccine candidates and BBV152 is being evaluated in Phase I clinical trials in India (NCT04471519).

Background Early detection of viremia in HIV infected patients on anti-retroviral therapy (ART) is important to prevent disease progression as well as accumulation of drug resistance mutations. This makes HIV viral load (VL) monitoring indispensable in HIV infected patients on ART. However VL, being an expensive test, results in heavy financial burden on health services. Hence, cheaper surrogate markers of viremia are desired to reduce overall cost of management of HIV infected patients. Methods We enrolled aviremic (n = 63, M:F = 31:32) and viremic (n = 43, M:F = 21:22) HIV infected patients at 1 year after ART initiation. Viremic individuals were identified as those having a plasma VL of more than 1000 copies/µl and aviremic individuals as less than 40 copies/µl. The study participants also included immuno-virologically discordant patients as they demonstrate differential degrees of immune-reconstitution and are likely to harbour concomitant infections influencing levels of immune-activation markers screened as the surrogate markers. Immune activation markers viz. plasma hs-CRP, soluble-CD14 and Galectin-9 levels were estimated by ELISA, IL-6 by luminex assay and percentages of CD38+ CD8+ cells were determined by flow cytometry. The levels were compared between viremic and aviremic patients and correlated with plasma viral load. Receiver operated curve (ROC) analysis was done for plasma Galectin-9 levels. Results Viremic patients had significantly higher levels of Galectin-9 and %CD38+ CD8+ cells (p values Conclusions Plasma Galectin-9 levels could identify viremic individuals with sensitivity and specificity of more than 90%. Thus, they showed a potential to serve as a surrogate marker of viremia in HIV infected patients on ART and would have cost implications on HIV management especially in resource-limited settings. However, the findings need to be confirmed in the patients on ART for different durations of time.

Galectin-9 (Gal-9) and osteopontin (OPN) play immunomodulatory roles in tuberculosis and HIV infections. Evaluation of their levels as well as their interplay with different pro-inflammatory cytokines is critical to understand their role in immunopathogenesis of HIV/tuberculosis co-infection considering the complexity of the disease. Plasma levels of these proteins were measured by ELISAs in HIV-negative individuals with pulmonary (n = 21), extrapulmonary (n = 33), and latent tuberculosis (n = 22) and in HIV infected patients with pulmonary (n = 14), latent tuberculosis (n = 17), and without tuberculosis (n = 41). Levels of pro-inflammatory cytokines were estimated by Luminex assay. Receiver operated characteristic curve analysis was performed to evaluate discriminatory roles of these proteins. Spearman’s correlation analysis was performed with the markers of HIV and tuberculosis disease progression to evaluate their immunopathogenic roles. Gal-9 and OPN levels were higher in HIV uninfected patients with active tuberculosis than with latent tuberculosis. Gal-9 but not OPN levels were higher in HIV infected patients with active tuberculosis than with latent tuberculosis. Area under curve for Galectin-9 was >0.9 in HIV/tuberculosis co-infection and extrapulmonary tuberculosis. OPN and IL-6 levels were higher in patients with severe chest X-ray grade indicating its association with severity of the disease and positively correlated with each other. Stronger positive and negative correlations of Gal-9 levels, respectively, with viral loads and CD4 cell counts in HIV infected patients were observed than OPN levels indicating their association with HIV disease progression. Thus, significantly elevated Gal-9 levels were reported for the first time in HIV/tuberculosis co-infection and extrapulmonary tuberculosis in our study than single infections with HIV and tuberculosis. The study indicated a need for further evaluation of monitoring role of Gal-9 for detection of developing tuberculosis in HIV infected individuals. The findings also indicated differential roles of Gal-9 and OPN in the pathogenesis of tuberculosis and HIV infections.

Background & objectives: A cluster of SARS-CoV-2 infection occurred among Italian tourists visiting India. We report here the epidemiological, clinical, radiological and laboratory findings of the first cluster of SARS-CoV-2 infection among the tourists. Methods: Information was collected on demographic details, travel and exposure history, comorbidities, timelines of events, date of symptom onset and duration of hospitalization from the 16 Italian tourists and an Indian with laboratory-confirmed SARS-CoV-2 infection. The clinical, laboratory, radiologic and treatment data was abstracted from their medical records and all tourists were followed up till their recovery or discharge or death. Throat and deep nasal swab specimens were collected on days 3, 8, 15, 18, 23 and 25 to evaluate viral clearance. Results: A group of 23 Italian tourists reached New Delhi, India, on February 21, 2020 and along with three Indians visited several tourist places in Rajasthan. By March 3, 2020, 17 of the 26 (attack rate: 65.4%) had become positive for SARS-CoV-2 infection. Of these 17 patients, nine were symptomatic, while eight did not show any symptoms. Of the nine who developed symptoms, six were mild, one was severe and two were critically ill. The median duration between the day of confirmation for COVID-19 and RT-PCR negativity was 18 days (range: 12-23 days). Two patients died with a case fatality of 11.8 per cent. Interpretation & conclusions: This study reconfirms higher rates of transmission among close contacts and therefore, public health measures such as physical distancing, personal hygiene and infection control measures are necessary to prevent transmission.

Nipah virus (NiV) outbreak occurred in Kozhikode district, Kerala, India in 2018 with a case fatality rate of 91% (21/23). In 2019, a single case with full recovery occurred in Ernakulam district. We described the response and control measures by the Indian Council of Medical Research and Kerala State Government for the 2019 NiV outbreak. The establishment of Point of Care assays and monoclonal antibodies administration facility for early diagnosis, response and treatment, intensified contact tracing activities, bio-risk management and hospital infection control training of healthcare workers contributed to effective control and containment of NiV outbreak in Ernakulam.

Background: High-quality data are of prime importance in any health survey because survey data are considered as a gold standard for nationally representative data. The quality of data collection largely depends on the design of the questionnaire, training, and skills of the interviewer. Objectives: In the present study, we tried to evaluate three key components, such as questionnaire design, human resource and training of the field staff for Integrated Biological and Behavioural Surveillance carried out among the HIV high-risk subpopulation. Methods: A mixed-methods approach was used. Qualitative and quantitative data collection was carried out in the year 2015 with cross-sectional survey design in western states of India. The in-depth interviews of 10 stakeholders, structured interviews of the survey respondents (n = 560), and field investigators (n = 71) were conducted. Data triangulation was used to find out the concurrence of the qualitative and quantitative data. Results: Comprehensive and standardized survey questionnaire, structured training agenda, and strategic preparation for recruiting human resources were the overall strengths of the survey. However, during the implementation of the survey, there were some difficulties reported in data collection process. Overall, the respondents and investigators felt that the questionnaire was long and exhaustive. Difficulties were faced while collecting data on sexual history. The field staffs were not adequately experienced to work with sensitive population. Conclusions: In order to have accurate, reliable data, especially on sexual behavior; emphasis should be given on simple questionnaire with the use of community-friendly language, skilled and experienced interviewers for data collection, and extensive field training.

Hepatic CYP2D6 enzyme metabolizes antiretroviral drugs (ARVs) including nevirapine. Polymorphism in CYP2D6 gene affects drug metabolism and displays distinctive phenotypes in the population. Hence, we investigated the prevalence of CYP2D6*4 1934G/A polymorphism in a total of 165 HIV patients that include 34 with and 131 without hepatotoxicity and 160 unrelated healthy controls by the PCR-RFLP method. The prevalence of CYP2D6*4 1934AA genotype was higher in total HIV patients as compared to healthy controls (1.81% vs 0.6%, OR = 2.86). Similarly, CYP2D6*4 1934AA genotype was much more prevalent in HIV patients without hepatotoxicity as compared to healthy controls (2.3% vs 0.6%, OR = 2.87). Likewise, CYP2D6*4 1934AA genotype was predominant in advanced HIV disease stage as compared to healthy controls (3.8% vs 0.6%, OR = 6.15). CYP2D6*4 1934GA genotype was distributed higher in HIV patients taking tobacco and nevirapine as compared to non-users (23.3% vs 19.3%, OR = 1.21, 21.0% vs 16.7%, OR = 1.2). Likewise, CYP2D6*4 1934GA genotype was overrepresented in patients with hepatotoxicity taking alcohol + nevirapine as compared to alcohol non-users + nevirapine users (20.00% vs 16.67%, OR = 1.25). Thus, there was no significant difference in genotype or allele frequencies of CYP2D6*4 1934G/A polymorphism between the patients with hepatotoxicity and those without or healthy controls.

The genetic variations in APOBEC3G gene are correlated with HIV disease progression. These variations differ in different ethnic groups. The prevalence of APOBEC3G (-90C/G, −571G/C) variations have not been studied in Indian population. Hence, we assessed the occurrence of APOBEC3G polymorphisms in HIV patients and its association with acquisition of HIV and disease progression. Polymorphisms in APOBEC3G were genotyped in a total of 153 HIV patients, naive to ARV and 156 healthy controls by PCR-RFLP method. In single locus model, the frequency of distribution of APOBEC3G −90CG, −571 GC genotypes were higher in HIV patients as compared to healthy controls (57.5% vs. 50.0%, OR = 1.22; 17.0% vs. 12.8%, OR = 1.39). In double locus model, the dominant −571 GC + CC genotype was distributed at a much higher frequency in HIV patients as compared to healthy controls (18.3% vs. 14.1%, OR = 1.50). The frequency of APOBEC3G −571CC and CC + GC genotypes were higher in early HIV disease stage as compared to healthy controls (23.9% vs. 12.8%, OR = 2.23, P = 0.08; 28.3% vs. 14.1%, OR = 2.40, P = 0.04). APOBEC3G-571 GC and GC + CC genotypes were more prevalent in HIV patients consuming tobacco and alcohol as compared to non-users (22.7% vs. 15.3%, OR = 1.71, P = 0.56; 27.3% vs. 16.5%, OR = 1.90, P = 0.39 and 31.6% vs. 13.6%, OR = 2.31, P = 0.08; 36.8% vs14.8%, OR = 2.49, P = 0.04, respectively). In conclusion, APOBEC3G-571G/C polymorphism was associated with the early stage of HIV infection and could potentially influence HIV disease progression in alcohol users. The distribution of APOBEC3G polymorphisms and its haplotypes were not significantly different between HIV patients and healthy controls.

Background: Dermatoglyphic features have been associated with numerous medical disorders.. This study is an effort to determine the association between dermatoglyphics and chronic kidney disease. Objectives: To record and compare the dermatoglyphic pattern in patients of chronic kidney disease and in control group Methods: A case control descriptive study was conducted over six months period on 100 patients with chronic kidney disease and 100 individuals with no evidence of kidney disease in Hemodialysis Department of National Dialysis Centre situated in Kantipur General Hospital, Basundhara, Kathmandu.Patient’s hands were cleaned with soap and water. Once dried, black duplicating ink was applied on fingers and palm. Finger tips followed by palm were recorded on white A4 size paper. Frequency of each ridge pattern analysis was done and paired t-test was performed using SPSS version 16. Results: The distribution of frequency and percentage of ulnar loop pattern in right hand of patients with chronic kidney disease was 350(70%) whereas the distribution of ulnar loop pattern in left hand was 282(56.4%). Conclusion: The predominant fingerprint pattern in patients with chronic kidney disease was found as ulnar loop but the increased frequency of ulnar loop was recorded in right hand of chronic kidney disease patients as compared to the right hand of control group.

Purpose. Emergence of multidrug resistance in Neisseria gonorrhoeae, an STI of public health significance is the biggest challenge to gonorrhoea control. Monitoring for antimicrobial resistance is essential for the early detection of emergent drug resistance patterns. Methodology. One hundred and twenty four N. gonorrhoeae strains were isolated between September 2013-August 2016 [82-New Delhi, 3-Pune, 3-Mumbai, 20-Secunderabad and 16-Hyderabad] to determine antimicrobial susceptibility and to compare the CLSI disc diffusion method with Etest for these strains. The results of the two methods were compared by using kappa statistics. Results. Ninety eight percent [CI: 96.2–100] of isolates were resistant to ciprofloxacin, 52 % [CI: 43.2–60.8] to penicillin, 56 % [CI: 47.2–64.7] to tetracycline and 5 % [CI: 1.2–8.8] to azithromycin. All the strains were susceptible to spectinomycin, ceftriaxone and cefixime except for two strains which showed decreased susceptibility to ceftriaxone and cefixime. Kappa scores for penicillin, azithromycin, ciprofloxacin, ceftriaxone and cefixime showed that the CLSI method had high agreement with Etest while tetracycline had substantial agreement. Conclusion. Our data suggest that the disc diffusion method which is both cost effective and more feasible, can effectively be used routinely for monitoring antibiotic susceptibility in N. gonorrhoeae, in limited resource countries like India. We demonstrate the emergence of decreased susceptibility to ceftriaxone and cefixime and threshold levels of resistance to azithromycin in India. This underscores the importance of maintaining continued surveillance for antibiotic resistance in N. gonorrhoeae and a potential requirement for strategic change in guidelines in the not so distant future.

The World Health Organization recommends point-of-care testing (POCT) to detect human immunodeficiency virus (HIV) infected individuals in the community. This will help improve treatment coverage through detection of HIV infection among those who are unaware of their status.This study was planned with an objective to investigate the feasibility and acceptability of POCT for HIV in the community.A community-based cross-sectional study was conducted in rural and peri-urban areas of Pune, India. These sites were selected based on the distance from the nearest HIV testing center. Testing locations were identified in consultation with the local stakeholders and grass-root health workers to identify and capture the priority population. The POCT was performed on blood samples collected by the finger-prick method.The proportion of participants seeking HIV tests for the first time was 79.6% that signifies the feasibility of POCT. The acceptability in the peri-urban and rural areas was 70.2% and 69.7%, respectively. POCT was performed at construction sites (24.9%), nearby industries (16.1%) and parking areas of long-distance trucks (8.1%) in the peri-urban area. Three newly diagnosed HIV-infected participants (0.1%) were detected from the peri-urban areas but none from the rural areas. Two of the newly diagnosed participants and their spouses were linked to care.There was a high acceptability of POCT and wider coverage of priority population with a strategy of testing at places preferable to the study population. Therefore, we believe that community-based POCT is a promising tool for improving HIV testing coverage even in low prevalence settings with the concentrated HIV epidemic.

A good point-of-care diagnostic test holds a promise to reduce inappropriate use of antibiotics by enabling early detection of the pathogen and facilitating rapid testing of antimicrobial susceptibility. India has taken many initiatives in the recent past to augment the development and deployment of diagnostics in Indian health care system. Funding opportunities to promote innovation in diagnostics development were started in early 2000s through various ministries and departments. India released National Essential Diagnostics List which enlists essential tests and there is now Free Diagnostics Service Initiative of Government of India under National Health Mission that mandates to provide all essential tests free of cost. We wanted to understand how these initiatives have impacted the diagnostics that could be of use in containment of antimicrobial resistance (AMR) and whether there is a smooth process for bringing indigenously developed products relevant to AMR into the healthcare system. We conducted a longitudinal survey (January 2019 and January 2021) to understand the availability of market ready indigenous rapid diagnostics for AMR in the country and their progress towards introduction in the private market or uptake in healthcare system. We found that many innovators and developers are working towards development of rapid tests that can be useful in the containment of AMR in India. While there are many promising diagnostics on the horizon, the pathway for uptake of indigenously developed diagnostics in healthcare system remains disjointed and needs to be harmonised for the investments made towards development to translate as tangible gains. Since most of these efforts are government funded, it is incumbent upon the government to also provide a seamless pathway to make these diagnostics available in health care system. In absence of this guidance, most of these diagnostics will sit with the innovators/developers and will never be used for the purpose they were intended to serve.

Non-nucleoside reverse transcriptase inhibitors are metabolized in the liver by cytochrome P450 (CYP) isoenzymes. Variations in the genes encoding these enzymes may influence the activity of corresponding metabolizing enzymes. This study aimed at assessing association of CYP2C9*2 430C/T, CYP2C9*31075A/C, and CYP1A1m1 3801T/C polymorphism with risk to develop ARV Antiretroviral-associated hepatotoxicity and its severity. In this case-control study, genotyping of CYP2C9*2, CYP2C9*3, and CYP1A1m1 genes was done in 34 HIV-infected individuals with hepatotoxicity and 131 without hepatotoxicity, and 153 unrelated healthy individuals using PCR-RFLP. CYP1A1m13801CC genotype was likely to be associated with severe ARV-associated hepatotoxicity (OR = 1.78, p = 0.70). CYP1A1m13801CC genotype and combined genotype TC + CC were likely to be associated with development of ARV-associated hepatotoxicity (OR = 2.57, p = 0.08; OR = 1.42, p = 0.17). CYP1A1m1 3801CC genotype among advanced and intermediate HIV disease stage was likely to be associated with advancement of disease (OR = 2.56, p = 0.77; OR = 2.37, p = 0.45). CYP2C9*31075AC genotype among alcohol users was likely to be associated with development of ARV-associated hepatotoxicity (OR = 1.67, p = 0.38). CYP1A1m1 3801TC genotype and combined genotype TC + CC among nevirapine users were likely to be associated with severe ARV-associated hepatotoxicity (OR = 3.68, p = 0.27; OR = 4.91, p = 0.13). Among those who received nevirapine, presence of CYP1A1m1 3801TC genotype was likely to be associated with increased risk of development of ARV-associated hepatotoxicity (OR = 1.50, p = 0.78). CYP1A1m1 3801TC, 3801CC, and CYP2C9*3 1075AC genotypes among combined alcohol + nevirapine users increased the risk of development of ARV-associated hepatotoxicity (OR = 1.41, p = 0.53; OR = 1.49, p = 0.83; OR = 1.78, p = 0.35). In conclusion, individuals with CYP1A1m13801CC and 3801TC genotypes independently and in the presence of alcohol and nevirapine usage is likely to be associated with increased risk of development of ARV-associated hepatotoxicity, its severity, and advancement of disease. CYP2C9*31075AC genotype with combined alcohol and nevirapine usage indicated a risk for development of ARV-associated hepatotoxicity.

Background: Bringing reliable and accurate tuberculosis (TB) diagnosis closer to patients is a key priority for global TB control. Molbio Diagnostics have developed the Truenat point-of-care molecular assays for detection of TB and rifampicin (RIF) resistance. Methods: We conducted a prospective multicentre study at 19 microscopy centres and seven reference laboratories in Peru, India, Ethiopia and Papua New Guinea to determine the diagnostic accuracy of the Truenat MTB, MTB Plus and MTB-RIF Dx assays in comparison with Xpert MTB/RIF (‘Xpert’) and Xpert MTB/RIF Ultra (‘Ultra’) using culture as the reference standard (NCT03712709). Findings: Of 1,807 enrolled participants with TB signs/symptoms, 24% were culture positive for Mycobacterium tuberculosis , of which 15% were RIF-resistant by phenotypic drug sensitivity testing. In microscopy centres, the pooled sensitivity of Truenat MTB and Truenat MTB Plus was 73% [95% CI: 67, 78] and 80% [95% CI: 75, 84], respectively. Among smear-negative specimens, sensitivities were 36% [95% CI: 27, 47] and 47% [95% CI: 37, 58], respectively. Specificity of Truenat MTB and MTB Plus was 98% [95% CI: 97, 99] and 96% [95% CI: 95, 97], respectively. Sensitivity of Truenat MTB-RIF was 84% [95% CI: 62, 95], and specificity was 95% [95% CI: 90, 97]. Interpretation: Truenat assays have comparable accuracy with Xpert and can be performed in microscopy centres and primary health centres. Funding Statement: Bill & Melinda Gates Foundation (OPP1208706), India TB Research Consortium, Indian Council for Medical Research, Australian Department of Foreign Affairs and Trade via the PNGAus Partnership, and German KfW. Declaration of Interests: APN, AMa, CMd, MR, PN and SGS are employed by the Foundation for Innovative New Diagnostics (FIND). FIND is a not-for-profit foundation that supports the evaluation of publicly prioritized tuberculosis assays and the implementation of WHO-approved (guidance and prequalification) assays using donor grants. FIND has product evaluation agreements with several private sector companies that design diagnostics for tuberculosis and other diseases. These agreements strictly define FIND's independence and neutrality with regard to these private sector companies. All other authors have nothing to declare. Ethics Approval Statement: The study was conducted in accordance with the 1964 Helsinki declaration and its subsequent amendments and approved by the relevant institutional review boards and independent ethics committees. All participants provided informed consent, either written, or if illiterate, as a thumbprint on the consent form signed and dated by an impartial witness.

BACKGROUND & OBJECTIVES: Coronavirus disease 2019 (COVID-19) has raised urgent questions about containment and mitigation, particularly in countries where the virus has not yet established human-to-human transmission. The objectives of this study were to find out if it was possible to prevent, or delay, the local outbreaks of COVID-19 through restrictions on travel from abroad and if the virus has already established in-country transmission, to what extent would its impact be mitigated through quarantine of symptomatic patients? METHODS: These questions were addressed in the context of India, using simple mathematical models of infectious disease transmission. While there remained important uncertainties in the natural history of COVID-19, using hypothetical epidemic curves, some key findings were illustrated that appeared insensitive to model assumptions, as well as highlighting critical data gaps. RESULTS: It was assumed that symptomatic quarantine would identify and quarantine 50 per cent of symptomatic individuals within three days of developing symptoms. In an optimistic scenario of the basic reproduction number (R0) being 1.5, and asymptomatic infections lacking any infectiousness, such measures would reduce the cumulative incidence by 62 per cent. In the pessimistic scenario of R0=4, and asymptomatic infections being half as infectious as symptomatic, this projected impact falls to two per cent. INTERPRETATION & CONCLUSIONS: Port-of-entry-based entry screening of travellers with suggestive clinical features and from COVID-19-affected countries, would achieve modest delays in the introduction of the virus into the community. Acting alone, however, such measures would be insufficient to delay the outbreak by weeks or longer. Once the virus establishes transmission within the community, quarantine of symptomatics may have a meaningful impact on disease burden. Model projections are subject to substantial uncertainty and can be further refined as more is understood about the natural history of infection of this novel virus. As a public health measure, health system and community preparedness would be critical to control any impending spread of COVID-19 in the country.

As of February 29, 2020, more than 85,000 cases of coronavirus disease 2019 (COVID-19) have been reported from China and 53 other countries with 2,924 deaths. On January 30, 2020, the first laboratory-confirmed case of COVID was reported from Kerala, India. In view of the earlier evidence about effectiveness of repurposed lopinavir/ritonavir against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus (CoV), as well as preliminary docking studies conducted by the ICMR-National Institute of Virology, Pune, the Central Drugs Standard Control Organization approved the restricted public health use of lopinavir/ritonavir combination amongst symptomatic COVID-19 patients detected in the country. Hospitalized adult patients with laboratory-confirmed SARS-CoV-2 infection with any one of the following criteria will be eligible to receive lopinavir/ritonavir for 14 days after obtaining written informed consent: (i) respiratory distress with respiratory rate ≥22/min or SpO2of 60 yr, diabetes mellitus, renal failure, chronic lung disease and immunocompromised persons. Patients will be monitored to document clinical (hospital length of stay and mortality at 14, 28 and 90 days), laboratory (presence of viral RNA in serial throat swab samples) and safety (adverse events and serious adverse events) outcomes. Treatment outcomes amongst initial cases would be useful in providing guidance about the clinical management of patients with COVID-19. If found useful in managing initial SARS-CoV-2-infected patients, further evaluation using a randomized control trial design is warranted to guide future therapeutic use of this combination.

Lack of viral monitoring in HIV infected patients on anti-retroviral therapy in low income countries may result in missing virologic non-responders (VNR) who show immunologic recovery in spite of unsuppressed viral replication. Biomarkers and drug resistance patterns in these discordant patients in comparison to the concordant treatment failure group need to be studied to understand possible risk factors associated with this condition. HIV infected patients on anti-retroviral therapy for one year were enrolled under three categories namely VNRs (n = 25), treatment failures (n = 18) and treatment responders (n = 40). They were assessed for HIV drug resistance by sequencing, plasma cytokines by luminex assay, T cell activation status by flow cytometry and total IgE levels by ELISA. VNR and failure patients had significantly lower median baseline CD4 counts than the responders. VNRs had significantly higher CD4 counts but lower viral load than treatment failures at one year of ART. VNRs had the highest eosinophil counts and the highest IL-5 levels among all the groups. IL-5 levels in them correlated with their viral load values. Frequency of Treg cells was also highest among the VNR group participants. More than 60% of the viremic patients irrespective of their groups harboured multiple HIV drug resistance mutations and mutation pattern did not differ between the groups. Low baseline CD4 counts and presence of multiple drug resistance mutations in the viremic groups highlighted the importance of early ART initiation and viral load monitoring irrespective of presence of immunologic failure. High IL-5 levels in VNR group indicated a need for investigating causal relationship between IL-5 and viral replication to devise therapeutic strategies to control viremia.

This multicenter, double-blind, randomized study compared the efficacy, pharmacokinetics (PKs)/pharmacodynamics (PDs), safety and immunogenicity profile of RTXM83 vs. reference rituximab (R-rituximab), both with CHOP, as first-line treatment of diffuse large B-cell lymphoma (DLBCL). A total of 272 patients

The flat-lining of HIV incidence in India has raised concerns about the presence of emerging risk groups. As HIV prevalence among pregnant women is reflective of the situation in general population, its closer scrutiny provides valuable insights about the evolving epidemic. The present study assesses temporal trends of sero-discordance (where woman is HIV infected and husband is uninfected), among pregnant women living with HIV (pWLHIV) from India. Data of program for prevention of parent to child transmission of HIV was analyzed. Statistical analysis was done using Cochrane-Armitage trend test and logistic regression. Of the 1209 currently married pWLHIV, 302 (25%) were sero-discordant. The proportion increased from 16% in 2007 to 36% in 2016-17 (p = 0.000). The likelihood of sero-discordance was higher for women aged 18-20 (OR: 2.68, CI: 1.30-5.83) and 21-23 (OR: 1.98, CI: 1.01-4.15) years compared to 36-40 years; and for primi-parous women (OR: 1.84, CI: 1.31-2.58) compared to women pregnant for second/third time. The findings are indicative of changing HIV transmission dynamics. Steeper rise in sero-discordance in younger women implies an increasing risk of HIV in unmarried women population. A better understanding of HIV specific vulnerabilities of young women, married and unmarried, is warranted.

Background Bringing reliable and accurate tuberculosis (TB) diagnosis closer to patients is a key priority for global TB control. Molbio Diagnostics have developed the Truenat point-of-care molecular assays for detection of TB and rifampicin (RIF) resistance. Methods We conducted a prospective multicentre diagnostic accuracy study at 19 primary healthcare centres and seven reference laboratories in Peru, India, Ethiopia and Papua New Guinea to estimate the diagnostic accuracy of the point-of-care Truenat MTB, MTB Plus and MTB-RIF Dx assays for pulmonary TB using culture and phenotypic drug susceptibility testing as the reference standard, compared with Xpert MTB/RIF or Ultra. Results Of 1807 enrolled participants with TB signs/symptoms, 24% were culture-positive for Mycobacterium tuberculosis, of which 15% were RIF-resistant. In microscopy centres, the pooled sensitivity of Truenat MTB and Truenat MTB Plus was 73% (95% CI 67–78%) and 80% (95% CI 75–84%), respectively. Among smear-negative specimens, sensitivities were 36% (95% CI 27–47%) and 47% (95% CI 37–58%), respectively. Sensitivity of Truenat MTB-RIF was 84% (95% CI 62–95%). Truenat assays showed high specificity. Head-to-head comparison in the central reference laboratories suggested that the Truenat assays have similar performance to Xpert MTB/RIF. Conclusion We found the performance of Molbio's Truenat MTB, MTB Plus and MTB-RIF Dx assays to be comparable to that of the Xpert MTB/RIF assay. Performing the Truenat tests in primary healthcare centres with very limited infrastructure was feasible. These data supported the development of a World Health Organization policy recommendation of the Molbio assays., Diagnostic performance of point-of-care Truenat assays in primary healthcare centres is comparable to that of Xpert MTB/RIF placed in reference laboratories. The WHO now recommends Truenat as an initial test for detection of TB and RIF resistance. https://bit.ly/31Wj3S6

Background Early detection of symptoms of loss of smell and taste lately added for Coronavirus disease 2019 (COVID-19) has the potential for improving pandemic response. In the Indian context, we compared proportion experiencing new loss of smell or taste among COVID-19 positive and negative individuals in Chennai city, Southern India. Methods We did an analytical cross-sectional study among individuals aged 18–80 years undergoing testing at COVID-19 sample collection centres. We ascertained loss of smell and taste using standardised self-reporting and clinical examination procedures. We administered Sino Nasal Outcome (SNOT 22) questionnaire for comprehensive understanding of these symptoms. We compared proportion having symptoms between COVID-19 positive and negative persons. We compared the two assessment methods to compute diagnostic validity indicators. Results Of the 277 participants, 169 (61%) were men and mean age of 40.7 years [SD = 13.3]. Fifty eight (21%) had COVID-19 and 12 (36%) of them were asymptomatic. Predominantly reported symptoms were fever (30%), headache (18%) and cough (18%). Self-reported or clinically identified new loss of smell or taste was higher among COVID-19 positive (n = 13; 22%) than negative persons (n = 23; 11%) [p = 0.02]. Sensitivity was higher for self-reported or clinically identified loss of smell (17.2%) than that of loss of taste (6.9%). Negative predictive value for loss of smell or taste, self-reported or clinically identified was 81%. Likelihood ratio of positive test was 2.13. Conclusion Loss of smell or taste are predominantly reported by COVID-19 confirmed individuals. Objective and subjective assessments of smell and taste may be required to identify those requiring COVID-19 testing.

Facebook has become the most important source of news and people’s feedback and opinion about almost every daily topic. Facebook represents one of the largest and most dynamic datasets of user generated content. Facebook posts can express opinions on different topics. With this massive amount of information in Facebook, there has to be an automatic tool that can categorize these information based on emotions. The proposed system is to develop a prototype that help to come to an inference about the emotions of the posts namely anger, surprise, happy, fear, sorrow, trust, anticipation and disgust with three sentic levels in each. This helps in better understanding of the posts when compared to the approaches which senses the polarity of the posts and gives just their sentiments i.e., positive, negative or neutral. The posts handling these emotions might be sarcastic too. When detecting sarcasm in social media posts, the various features that are especially inherent to Facebook must be considered with importance.

SETTING Little is known about outcomes of patients co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB) who are treated in the private sector in India. OBJECTIVE To describe the treatment outcomes of daily anti-tuberculosis treatment (ATT) and their determinants among HIV-TB co-infected patients treated at a private clinic in Pune, India. DESIGN Data on adult HIV-TB co-infected patients treated with daily ATT were analysed using logistic regression and Cox model to assess risk factors for default and death. RESULTS Of 769 cases, 78% were aged 2 months) and 3.9% died during ATT. The risk of default was higher among males (aOR 1.67, 95%CI 1.17-2.39), ART-naive patients (aOR 1.91, 95%CI 1.34-2.73) and those with a past history of TB (aOR 1.86, 95%CI 1.15-3.01). Survival probability at 365 days was 95% (95%CI 93-97). The risk of death was higher among patients with CD4 200 cells/mm3. CONCLUSIONS Low overall mortality was seen with daily ATT in HIV-TB co-infected patients. High default rates in private facilities warrant urgent attention.

Background: HIV is pandemic and remains as a public health concern for many decades. This infection though associated with many opportunistic infections and neoplasms, it is further complicated with marked hematological abnormalities. The aim of this study is to determine the magnitude & severity of hematological abnormalities in HIV infected individuals and also to analyze these abnormalities in correlation with the CD4 counts. We also compared these hematological abnormalities in patients on ART and those not on ART.Materials and Methods: The study was conducted for a period of one year, on 120 HIV positive cases including both patients on ART & not on ART. Controls with similar age and sex distribution was set up. The blood samples were collected and processed in an automated cell counter. The parameters were tabulated and analyzed with respect to CD4 count & ART status.Results: Among the total of 120 HIV cases, 77% had anemia, 21% had leucopenia and 5% had thrombocytopenia. The magnitude and severity of anemia, leucopenia, thrombocytopenia and other parameters was found to be more in patients not on ART, when compared to patients on ART. Similarly, the magnitude and severity of most of hematological abnormalities were inversely proportional to the CD4 count in non-ART cases but not with cases on ART.Conclusion: The basic hematological parameters can be used as a prospective screening test to assess the severity and progression of HIV infection when CD4 count is not available. These parameters can also be used to assess the response to anti-retroviral treatment. Therefore, these basic hematological investigations readily available at all medical centers are of great use while treating HIV infected patients.Asian Journal of Medical Sciences Vol.7(4) 2016 14-18

In India, the roll out of the free antiretroviral therapy (ART) program completed a decade of its initiation in 2014. The success of first-line ART is influenced by prevalence of HIV pretreatment drug resistance (PDR) in the population. In this cross-sectional study, we sought to determine the prevalence of PDR among adults attending the state-sponsored free ART clinic in Pune in western India. Fifty-two individuals eligible for ART as per national guidelines with median CD4 cell count of 253 cells/mm(3) (inter quartile range: 149-326) were recruited between January 2014 and April 2015. Population-based sequencing of partial pol gene sequences from plasma specimen revealed predominant HIV-1 subtype C infection (96.15%) and presence of single-drug resistance mutations against non-nucleoside reverse transcriptase inhibitor in two sequences. The study supports the need for periodic surveillance, when offering PDR testing at individual level is not feasible.