SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion.

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

India Field Epidemiology Training Program Response to COVID-19 Pandemic, 2020-2021.

The India Field Epidemiology Training Program (FETP) has played a critical role in India's response to the ongoing COVID-19 pandemic. During March 2020-June 2021, a total of 123 FETP officers from across 3 training hubs were deployed in support of India's efforts to combat COVID-19. FETP officers have successfully mitigated the effect of COVID-19 on persons in India by conducting cluster outbreak investigations, performing surveillance system evaluations, and developing infection prevention and control tools and guidelines. This report discusses the successes of select COVID-19 pandemic response activities undertaken by current India FETP officers and proposes a pathway to augmenting India's pandemic preparedness and response efforts through expansion of this network and a strengthened frontline public health workforce.

The Sela macaque (Macaca selai) is a distinct phylogenetic species that evolved from the Arunachal macaque following allopatric speciation.

Arunachal macaque (M. munzala) is an endangered and recently discovered cercopithecine primate from Western Arunachal Pradesh, India. On genetic analyses of Arunachal macaques, we observed spatially distributed substantial inter-species genetic divergence among the samples collected from Arunachal Pradesh. The results suggested that Arunachal macaque evolved into two phylogenetic species about 1.96 mya following allopatric speciation by means of Sela mountain pass in Arunachal Pradesh, India. We describe - Sela macaque (M. selai) as a new macaque species that interestingly exhibited high intra-specific genetic variation and also harbors at least two conservation units. Further, we report the past demographic trajectories and quantify genetic variation required for taxonomic clarification. The present study also identifies gap areas for undertaking surveys to document the relic and unknown trans-boundary populations of macaques through multinational, multi-lateral cross border collaboration.

DNA matchmaking in captive facilities: a case study with tigers.

BACKGROUND: Genetics driven interventions if adopted in conservation breeding projects may enhance the overall success by prioritizing breeding among genetically most competent individuals and delaying or completely diminishing the ill effects of inbreeding. METHODS AND RESULTS: In the present study, we investigated genetic make-up of 15 tigers housed at five different captive facilities of West Bengal in India and report the moderate level of genetic variation. We identified five tigers based on individual genetic attributes that may be prioritized for future breeding or animal exchange programmes. The occurrence of first and second order related individuals in captivity require management attention and they should be paired considering their immediate genetic background. CONCLUSION: Considering tiger as a case study, we highlight the use of genetic assessment and necessity to validate the studbook records in formulating adaptive management strategies for long-term conservation and management of species of interest.

Population genetics of Sambar (Rusa unicolor) from the Western Himalayas: preliminary findings.

BACKGROUND: The sambar (Rusa unicolor) is one of the largest deer distributed across diverse habitats of India and threatened due to habitat loss, changes in the land-use patterns, illegal poaching, and anthropogenic disturbances. Here, we report the first population genetics account of sambar deer from the Western Himalayas. METHODS AND RESULTS: We observed relatively compromised genetic diversity (π = 0.0008 ± 0.0006 at mtDNA and Ho = 0.499 ± 0.056 at nDNA). We identified 60 unique individuals using a select panel of seven loci (PID sib cum 1.60E-03). Bayesian skyline plot showed a stable demographic history since the past 8 kyr with a decline in recent years. The population lacked genetic structuring, likely due to the contiguous distribution and large dispersal patterns of sambar. CONCLUSION: The preliminary findings are valuable in exploring the utility of genetic diversity in monitoring the sambar population, estimating density following capture-recapture analysis, and aid to the conservation planning of sambar in large landscapes.

Population genetic attributes of common leopard (Panthera pardus fusca) from Uttarkashi, Western Himalayas.

BACKGROUND: The common leopard (Panthera pardus fusca), which persists in most of its historic range, is experiencing steady population decline due to habitat loss, anthrophonic disturbances, illegal poaching for their body parts, and retaliatory killings in response to the leopard-human conflicts. METHODS AND RESULTS: We analysed 143 scats samples and identified 32 unique leopards following a selected panel of seven loci with cumulative PID sibs 5.30E-04. We observed moderate genetic diversity at nuclear (Ho = 0.600 ± 0.06) and mitochondrial markers (Hd = 0.569 ± 0.009; π = 0.001 ± 0.0002) and found sub-structuring in the leopard population at Uttarkashi, Western Himalayas. CONCLUSIONS: The present study exhibits the utility of non-invasive genetics in monitoring the leopard population and paves the path to investigate population genetic parameters in further studies.

Elucidation of the inhibitory potential of flavonoids against PKP1 protein in non-small cell lung cancer.

PKP1 has been crucially involved in enhancing the MYC translation leading to lung carcinogenesis via evading numerous tumour-suppressing checkpoint systems. Plakophilin 1(PKP1) is the part of armadillo and plakophilin gene families and it is a necessary component of desmosomes. Several researches reported PKP1 protein as one of the most overexpressed proteins in human lung cancer. Therefore, we have designed our research towards elucidating better plant-based compounds as drug candidates for the management of lung cancer with minimal adverse effects over other chemotherapeutic drugs such as afatinib. This study comprises forty-six flavonoids for targeting PKP1 using in silico approaches that were not used earlier as an anti-cancerous agent targeting PKP1 in lung cancer treatment. Flavonoids are plant-derived natural compounds that exhibited enormous anti-cancerous potential against several human cancers. NPACT database was used to screen potent flavonoids that have not been used to target the PKP1 protein in lung cancer. Patch Dock and CB Dock were employed to elucidate the PKP1 (1XM9) inhibitory potential of selected flavonoids. Analysis with both the docking tools has revealed that calyxins I  showed maximum affinity in comparison to the standard drug, afatinib. Further PASS and BAS analyses were performed using SWISS ADME and molinspiration to investigate the pharmacokinetic profiling of potent flavonoids having significant binding energy. Visualization of complexes was done by using UCSF chimera. However, further detailed in vitro studies are needed to validate the candidature of calyxinsI for being developed as an anticancer drug for the management of lung cancer.

Characterizing the third wave of COVID-19: An analysis from the National Clinical Registry of COVID-19.

Background & objectives: Data from the National Clinical Registry for COVID-19 (NCRC) were analyzed with an aim to describe the clinical characteristics, course and outcomes of patients hospitalized with COVID-19 in the third wave of the pandemic and compare them with patients admitted earlier. Methods: The NCRC, launched in September 2020, is a multicentre observational initiative, which provided the platform for the current investigation. Demographic, clinical, treatment and outcome data of hospitalized COVID-19 patients were captured in an electronic data portal from 38 hospitals across India. Patients enrolled during December 16, 2021 to January 17, 2022 were considered representative of the third wave of COVID-19 and compared with those registered during November 15 to December 15, 2021, representative of the tail end of the second wave. Results: Between November 15, 2021 and January 17, 2022, 3230 patients were recruited in NCRC. Patients admitted in the third wave were significantly younger than those admitted earlier (46.7±20.5 vs. 54.6±18 yr). The patients admitted in the third wave had a lower requirement of drugs including steroids, interleukin (IL)-6 inhibitors and remdesivir as well as lower oxygen supplementation and mechanical ventilation. They had improved hospital outcomes with significantly lower in-hospital mortality (11.2 vs. 15.1%). The outcomes were better among the fully vaccinated when compared to the unvaccinated or partially vaccinated. Interpretation & conclusions: The pattern of illness and outcomes were observed to be different in the third wave compared to the last wave. Hospitalized patients were younger with fewer comorbidities, decreased symptoms and improved outcomes, with fully vaccinated patients faring better than the unvaccinated and partially vaccinated ones.

Addressing Reemergence of Diphtheria among Adolescents through Program Integration in India.

We report a diphtheria outbreak mostly among children (median 12 years; range 4-26 years) of a religious minority in urban India. Case-fatality rate (15%, 19/124) was higher among unimmunized patients (relative risk 4.1, 95% CI 1.5-11.7). We recommend mandating and integrating immunization into school health programs to prevent reemergence.

Genetic monitoring of Himalayan goral (Naemorhedus goral) from Western Himalayas, India.

BACKGROUND: Himalayan goral (Naemorhedus goral), solitary cliff-dwelling species and are distributed throughout the Indian Himalayan region. Its populations across the range are facing severe threats due to habitat loss, fragmentation and changes in the land-use patterns by various anthropogenic activities. METHODS AND RESULTS: We carried out genetic analyses of Himalayan goral using the mitochondrial control regions and microsatellite loci (n = 10) in the Uttarkashi district of Uttarakhand. We reported a moderate genetic diversity at nuclear (Ho 0.602 ± 0.057) and mitochondrial markers (Hd-0.6931 ± 0.053; π-0.0048 ± 001). Bayesian skyline plot indicates a sharp decline in the goral population in the last 100 years. CONCLUSIONS: Our results indicate the population of Himalayan goral in Uttarkashi is under panmictic condition, plausibly due to long-ranging behaviour. The present study laid the foundation for future non-invasive genetics monitoring and detailed population genetic assessment of goral from the entire range in the Western Himalayas.

Clinical profile of hospitalized COVID-19 patients in first & second wave of the pandemic: Insights from an Indian registry based observational study.

Background & objectives: India witnessed a massive second surge of COVID-19 cases since March 2021 after a period of decline from September 2020. Data collected under the National Clinical Registry for COVID-19 (NCRC) were analysed to describe the differences in demographic and clinical features of COVID-19 patients recruited during these two successive waves. Methods: The NCRC, launched in September 2020, is an ongoing multicentre observational initiative, which provided the platform for the current investigation. Demographic, clinical, treatment and outcome data of hospitalized, confirmed COVID-19 patients were captured in an electronic data portal from 41 hospitals across India. Patients enrolled during September 1, 2020 to January 31, 2021 and February 1 to May 11, 2021 constituted participants of the two successive waves, respectively. Results: As on May 11, 2021, 18961 individuals were recruited in the registry, 12059 and 6903 reflecting in-patients from the first and second waves, respectively. Mean age of the patients was significantly lower in the second wave [48.7 (18.1) yr vs. 50.7 (18.0) yr, P<0.001] with higher proportion of patients in the younger age group intervals of <20, and 20-39 yr. Approximately 70 per cent of the admitted patients were ≥ 40 yr of age in both waves of the pandemic. The proportion of males were slightly lower in second wave as compared to the first [4400 (63.7%) vs. 7886 (65.4%), P=0.02]. Commonest presenting symptom was fever in both waves. In the second wave, a significantly higher proportion [2625 (48.6%) vs. 4420 (42.8%), P<0.003] complained of shortness of breath, developed ARDS [422(13%) vs. 880 (7.9%), P<0.001], required supplemental oxygen [1637 (50.3%) vs. 4771 (42.7%), P<0.001], and mechanical ventilation [260 (15.9%) vs. 530 (11.1%), P<0.001]. Mortality also significantly increased in the second wave [OR: 1.35 (95% CI: 1.19, 1.52)] in all age groups except in <20 yr. Interpretation & conclusions: The second wave of COVID-19 in India was slightly different in presentation than the first wave, with a younger demography, lesser comorbidities, and presentation with breathlessness in greater frequency.

Pangolin Indexing System: implications in forensic surveillance of large seizures.

Demand for pangolin scales in East Asia has increased dramatically in the past two decades, raising concern to the pangolin survival and bringing them to the brink of local extinction. Enumerating the number of individuals from the seized pangolin scales primarily goes undocumented, mostly due to the unavailability of the appropriate methods. In this study, we developed a Pangolin Indexing System, a multi-locus STR panel of eight dinucleotide microsatellites that showed promising results in individualization and assignment of scales into Chinese and Indian pangolins. The combined power of exclusion was 0.83 and 0.99 for Chinese and Indian pangolin. The select panel of eight polymorphic STRs exhibited the cumulative probability of identity 3.7 × 10-9 for Indian pangolin and 3.6 × 10-7 for Chinese pangolin and identified 51 unique genotypes from the 74 scales selected from the four pangolin seizures. The study demonstrated the first report of cross-species validation of STRs developed from Malayan pangolin to Indian pangolin and showed the potential application of Pangolin Indexing System in screening of large seizures through DNA profiling from the scales of Indian and Chinese pangolin.

Severe acute respiratory illness surveillance for coronavirus disease 2019, India, 2020.

Background & objectives: Sentinel surveillance among severe acute respiratory illness (SARI) patients can help identify the spread and extent of transmission of coronavirus disease 2019 (COVID-19). SARI surveillance was initiated in the early phase of the COVID-19 outbreak in India. We describe here the positivity for COVID-19 among SARI patients and their characteristics. Methods: SARI patients admitted at 41 sentinel sites from February 15, 2020 onwards were tested for COVID-19 by real-time reverse transcription-polymerase chain reaction, targeting E and RdRp genes of SARS-CoV-2. Data were extracted from Virus Research and Diagnostic Laboratory Network for analysis. Results: A total of 104 (1.8%) of the 5,911 SARI patients tested were positive for COVID-19. These cases were reported from 52 districts in 20 States/Union Territories. The COVID-19 positivity was higher among males and patients aged above 50 years. In all, 40 (39.2%) COVID-19 cases did not report any history of contact with a known case or international travel. Interpretation & conclusions: COVID-19 containment activities need to be targeted in districts reporting COVID-19 cases among SARI patients. Intensifying sentinel surveillance for COVID-19 among SARI patients may be an efficient tool to effectively use resources towards containment and mitigation efforts.

National sero-surveillance to monitor the trend of SARS-CoV-2 infection transmission in India: Protocol for community-based surveillance.

Conducting population-based serosurveillance for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) will estimate and monitor the trend of infection in the adult general population, determine the socio-demographic risk factors and delineate the geographical spread of the infection. For this purpose, a serial cross-sectional survey would be conducted with a sample size of 24,000 distributed equally across four strata of districts categorized on the basis of the incidence of reported cases of COVID-19. Sixty districts will be included in the survey. Simultaneously, the survey will be done in 10 high-burden hotspot cities. ELISA-based antibody tests would be used. Data collection will be done using a mobile-based application. Prevalence from the group of districts in each of the four strata will be pooled to estimate the population prevalence of COVID-19 infection, and similarly for the hotspot cities, after adjusting for demographic characteristics and antibody test performance. The total number of reported cases in the districts and hotspot cities will be adjusted using this seroprevalence to estimate the expected number of infected individuals in the area. Such serosurveys repeated at regular intervals can also guide containment measures in respective areas. State-specific context of disease burden, priorities and resources should guide the use of multifarious surveillance options for the current COVID-19 epidemic.

A community-wide acute diarrheal disease outbreak associated with drinking contaminated water from shallow bore-wells in a tribal village, India, 2017.

BACKGROUND: In 2016, India reported 709 acute diarrheal disease (ADD) outbreaks (> 25% of all outbreaks). Tribal populations are at higher risk with 27% not having accessibility to safe drinking water and 75% households not having toilets. On June 26, 2017 Pedda-Gujjul-Thanda, a tribal village reported an acute diarrheal disease (ADD) outbreak. We investigated to describe the epidemiology, identify risk factors, and provide evidence-based recommendations. METHODS: We defined a case as ≥3 loose stools within 24 h in Pedda-Gujjul-Thanda residents from June 24-30, 2017. We identified cases by reviewing hospital records and house-to-house survey. We conducted a retrospective cohort study and collected stool samples for culture. We assessed drinking water supply and sanitation practices and tested water samples for faecal-contamination. RESULTS: We identified 191 cases (65% females) with median age 36 years (range 4-80 years) and no deaths. The attack-rate (AR) was 37% (191/512). Downhill colonies (located on slope of hilly terrains of the village) reported higher ARs (56%[136/243], p < 0.001) than others (20%[55/269]). Symptoms included diarrhea (100%), fever (17%), vomiting (16%) and abdominal pain (13%). Drinking water from five shallow bore-wells located in downhill colonies was significantly associated with illness (RR = 4.6, 95%CI = 3.4-6.1 and population attributable fraction 61%). In multi-variate analysis, drinking water from the shallow bore-wells located in downhill colonies (aOR = 7.9, [95% CI =4.7-13.2]), illiteracy (aOR =6, [95% CI = 3.6-10.1]), good hand-washing practice (aOR = 0.4, [95%CI = 0.2-0.7]) and household water treatment (aOR = 0.3, [95%CI = 0.2-0.5]) were significantly associated with illness. Two stool cultures were negative for Vibrio cholerae. Heavy rainfall was reported from June 22-24. Five of six water samples collected from shallow bore-wells located in downhill colonies were positive for faecal contamination. CONCLUSION: An ADD outbreak with high attack rate in a remote tribal village was associated with drinking water from shallow downhill bore-wells, likely contaminated via runoff from open defecation areas after heavy rains. Based on our recommendations, immediate public health actions including repair of leakages at contaminated water sources and alternative supply of purified canned drinking water to families, and as long-term public health measures construction of house-hold latrines and piped-water supply initiated.

Outbreak Investigation of Nipah Virus Disease in Kerala, India, 2018.

BACKGROUND: Nipah Virus (NiV) is a highly fatal emerging zoonotic virus and a potential threat to global health security. Here we describe the characteristics of the NiV outbreak that occurred in Kerala, India, during May-June 2018. METHODS: We used real-time reverse transcription polymerase chain reaction analysis of throat swab, blood, urine, and cerebrospinal fluid specimens to detect NiV. Further, the viral genome was sequenced and subjected to phylogenetic analysis. We conducted an epidemiologic investigation to describe the outbreak and elucidate the dynamics of NiV transmission. RESULTS: During 2-29 May 2018, 23 cases were identified, including the index case; 18 were laboratory confirmed. The lineage of the NiV responsible for this outbreak was closer to the Bangladesh lineage. The median age of cases was 45 years; the sex of 15 (65%) was male. The median incubation period was 9.5 days (range, 6-14 days). Of the 23 cases, 20 (87%) had respiratory symptoms. The case-fatality rate was 91%; 2 cases survived. Risk factors for infection included close proximity (ie, touching, feeding, or nursing a NiV-infected person), enabling exposure to droplet infection. The public health response included isolation of cases, contact tracing, and enforcement of hospital infection control practices. CONCLUSION: This is the first recorded NiV outbreak in South India. Early laboratory confirmation and an immediate public health response contained the outbreak.

The missing pieces in the jigsaw and need for cohesive research amidst coronavirus infectious disease 2019 global response.

Identifying the research needs and gaps amidst this COVID-19 travelling across the countries is absolutely important for finely improving on the way we think and act. The natural history of the disease as well as viral shedding in different stages of clinical illness needs to be known which helps in triaging the patients in hospital settings. Animal and environmental interface need to be studied for defining the high-risk situations. Transmission dynamics in community or hospital and defining the laboratory criteria for the case confirmation will be most crucial. Gene sequencing and validation and, suitable use of molecular based tests such as real-time polymerase chain reaction (qRT-PCR) should be clearly evaluated for diagnosis and/ or surveillance. The movement control strategy must be defined to prevent secondary transmission in healthcare as well as in community settings. Repurposing of drug molecules is an elegant strategy to develop therapeutics in the case of pandemics quickly. Unproven practices and treatment protocols should invite critical scrutiny on the basis of ethics. Socioeconomic status of the community is also an important determinant for the compliance and sustainable public health measures.

Emerging/re-emerging viral diseases & new viruses on the Indian horizon.

Infectious diseases remain as the major causes of human and animal morbidity and mortality leading to significant healthcare expenditure in India. The country has experienced the outbreaks and epidemics of many infectious diseases. However, enormous successes have been obtained against the control of major epidemic diseases, such as malaria, plague, leprosy and cholera, in the past. The country's vast terrains of extreme geo-climatic differences and uneven population distribution present unique patterns of distribution of viral diseases. Dynamic interplays of biological, socio-cultural and ecological factors, together with novel aspects of human-animal interphase, pose additional challenges with respect to the emergence of infectious diseases. The important challenges faced in the control and prevention of emerging and re-emerging infectious diseases range from understanding the impact of factors that are necessary for the emergence, to development of strengthened surveillance systems that can mitigate human suffering and death. In this article, the major emerging and re-emerging viral infections of public health importance have been reviewed that have already been included in the Integrated Disease Surveillance Programme.

Identifying the tick Amblyomma javanense (Acari: Ixodidae) from Chinese pangolin: generating species barcode, phylogenetic status and its implication in wildlife forensics.

Zoonotic diseases transmitted through ticks and other ectoparasites often travel across the globe with illegally traded wildlife parts and products. In this study, we analyzed a confiscated case of pangolin scales and observed a few dead ticks attached. On genetic analysis, the pangolin scales were identified to be originated from Chinese pangolin (Manis pentadactyla), an IUCN listed Critically Endangered species, and ticks were identified as Amblyomma javanense. Here, we provide the first authentic physical record of A. javanense from India as a parasite of Chinese pangolin and also generated its species DNA barcode that may be useful for biologists working on ticks in species validation and constructing phylogenies across the globe.