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.

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.

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.

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.

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.

Diabetes and tuberculosis syndemic in India: A narrative review of facts, gaps in care and challenges.

Both diabetes mellitus (DM) and tuberculosis (TB) are prevalent all across in India. TB-DM comorbidity has emerged as a syndemic and needs more attention in India considering gaps in screening, clinical care, and research. This paper is intended to review published literature on TB and DM in India to understand the burden of the dual epidemic and its trajectory and to obtain perspectives on the gaps, constraints, and challenges in care and treatment of this dual epidemic. A literature search was carried out on PubMed, Scopus, and Google Scholar, using the key words 'Tuberculosis' OR 'TB' AND 'Diabetes' OR 'Diabetes Mellitus' AND 'India', focusing on the research published between the year 2000 to 2022. The prevalence of DM is high in patients with TB. Quantitative data on the epidemiological situation of TB/DM in India such as incidence, prevalence, mortality, and management are lacking. During the last 2 years convergence of TB-DM syndemic with the COVID-19 pandemic has increased cases with uncontrolled DM but also made coordinated control of TB-DM operationally difficult and of low effectiveness. Research regarding TB-DM comorbidity is required in the context of epidemiology and management. Detection and bidirectional screening are aggressively warranted. Management of DM in those with TB-DM comorbidity needs more efforts, including training and supervision of frontline workers.

Lahaul-Zanskar-Sham Valley Corridor in Indian Trans Himalayan Region Facilitates Dispersal and Gene Flow in Himalayan Ibex.

Wildlife corridors that connect mosaic habitats in heterogeneous mountainous landscapes can be of high significance as they facilitate the genetic and demographic stability of free-ranging populations. Peripheral populations of widespread species are usually ignored in conservation planning. However, these populations retain locally common alleles and are genetic reservoir under the changing climatic conditions. Capra sibirica has widespread distribution, and its southern peripheral population is distributed in the Indian trans-Himalayan region (ITR). In the present study, we studied the spatial distribution and genetic make-up of Himalayan ibex from the ITR following the landscape genetics approach. We obtained 16 haplotypes at the mitochondrial d-loop region and found a stable demography in the past with a recent decline. With 10 nuclear microsatellites, we ascertained 111 unique individuals assigned into two clusters following Bayesian and non-Bayesian clustering analysis with several admixed individuals. We also recorded 25 first-generation migrants that reflected relatively high dispersal and gene-flow across the range. We identified a 19,835 sq.km suitable area with 13,311 sq.km in Ladakh and 6524 sq.km in Lahaul-Spiti. We identified a novel movement corridor for Himalayan ibex across the Lahaul-Zanskar-Sham valley (L-Z-SV) that displayed a fairly good conductance with low genetic divergence among the samples collected on the L-Z-SV corridor. We propose declaring a protected area in the Lahaul and Kargil districts to prioritize dedicated conservation efforts for the Himalayan ibex and other sympatric ungulates that impart a major role in the diet of large carnivore and balancing ecosystem services in the trans-Himalayan region.

Landscape genetics identified conservation priority areas for blue sheep (Pseudois nayaur) in the Indian Trans-Himalayan Region.

The trans-Himalayan region of India, although have xeric features, still supports a unique assemblage of biodiversity, including some of the charismatic and endemic species. In the present study, we studied blue sheep (Pseudois nayaur) across the distribution range in the Western trans Himalayas of India and found about 18,775 km2 area suitable for blue sheep. The explicit Bayesian based spatial and non-spatial population structure analysis assigned blue sheep into two genetic populations, i.e., Ladakh and Lahaul-Spiti. We found relatively high genetic divergence in blue sheep which is also supported by the low current flow in Circuitscape model. With the multiple evidences, we explain landscape resistance facilitated by the landscape heterogeneity, and large patches of unsuitable habitats forced population divergence and poor functional connectivity. We found that blue sheep population has been demographically stable in the past, but showed a slight decline within the last few decades. This study is the first range-wide attempt to exhibit landscape features in shaping the spatial distribution, genetic structure and demography patterns of blue sheep in Western Himalayas, and will be of use in the conservation and management planning of blue sheep.

Health Emergency Risk Management in World Health Organization - South-East Asia Region during 2014-2023: synthesis of experiences.

Health Emergency Risk Management (ERM) has become increasingly critical on the global stage, prompted by the escalating frequency and severity of natural disasters and disease outbreaks. This paper offers a comprehensive synthesis of the World Health Organization's (WHO) experiences in the South-East Asia Region during the period 2014-2023, shedding light on its efforts to manage health emergencies and enhance resilience. The South-East Asia Region's unique environmental and economic diversity exposes it to significant health risks, including emerging infectious diseases and their implications for development, particularly in low-income countries. Here we document the transition from reactive emergency responses to proactive preparedness, catalyzed by prioritizing ERM as one of the regional flagship priorities in 2014. Key components of this initiative included capacity-building, the establishment of the South-East Asia Regional Health Emergency Fund (SEARHEF), and the implementation of the International Health Regulations (IHR 2005). This synthesis highlights the region's achievements in event reporting, development of national actions plan, successful Early Warning, Alert, and Response System (EWARS) implementation, and improvements in core capacities under IHR (2005). It also underscores the challenges associated with cross-border data sharing and regional collaboration that could strengthen ERM and enhance readiness for effective synergistic response.

Review deciphering potent therapeutic approaches targeting Notch signaling pathway in breast cancer.

In the current period of drug development, natural products have provided an unrivaled supply of anticancer medications. By modifying the cancer microenvironment and various signaling pathways, natural products and their derivatives and analogs play a significant role in cancer treatment. These substances are effective against several signaling pathways, particularly the cell death pathways (apoptosis and autophagy) and embryonic developmental pathways (Notch, Wnt, and Hedgehog pathways). Natural products have a long history, but more research is needed to understand their current function in the research and development of cancer treatments and the potential for natural products to serve as a significant source of therapeutic agents in the future. Several target-specific anticancer medications failed to treat cancer, necessitating research into natural compounds with multiple target properties. To help develop a better treatment plan for managing breast cancer, this review has outlined the anticancerous potential of several therapeutic approaches targeting the notch signaling system in breast tumors.

Litchi consumption and missed meals continue to be associated with acute encephalopathy syndrome among children: an investigation of the 2019 outbreak in Muzaffarpur district, Bihar, India.

BACKGROUND: Muzaffarpur district in Bihar State of India recorded a resurgence of acute encephalopathy syndrome (AES) cases in the summer of 2019 after no reported outbreak in 3 y. Earlier studies generated evidence that litchi consumption and missing the previous evening's meal were associated with AES. We investigated the recent outbreak to understand the risk factors associated with AES. METHODS: We conducted a matched case-control study by comparing AES cases with healthy controls from case-households and the neighborhood community for risk factors like missing evening meal and litchi consumption before onset of AES. RESULTS: We recruited 61 cases and 239 controls. Compared with the community controls, case-patients were five times more likely to have reported eating litchi in the 7 d preceding the onset of illness (adjusted OR [AOR]=5.1; 95% CI 1.3 to 19) and skipping the previous evening's meal (AOR=5.2; 95% CI 1.4 to 20). Compared with household controls, case-patients were five times more likely to be children aged <5 y (AOR=5.3; 95% CI 1.3 to 22) and seven times more likely to have skipped the previous evening's meal (AOR=7.4; 95% CI 1.7 to 34). CONCLUSIONS: Skipping the previous evening's meal and litchi consumption were significantly associated with AES among children in Muzaffarpur and adjoining districts of Bihar.