One Health activities to reinforce intersectoral coordination at local levels in India.

India's dense human and animal populations, agricultural economy, changing environment, and social dynamics support conditions for emergence/re-emergence of zoonotic diseases that necessitate a One Health (OH) approach for control. In addition to OH national level frameworks, effective OH driven strategies that promote local intersectoral coordination and collaboration are needed to truly address zoonotic diseases in India. We conducted a literature review to assess the landscape of OH activities at local levels in India that featured intersectoral coordination and collaboration and supplemented it with our own experience conducting OH related activities with local partners. We identified key themes and examples in local OH activities. Our landscape assessment demonstrated that intersectoral collaboration primarily occurs through specific research activities and during outbreaks, however, there is limited formal coordination among veterinary, medical, and environmental professionals on the day-to-day prevention and detection of zoonotic diseases at district/sub-district levels in India. Examples of local OH driven intersectoral coordination include the essential role of veterinarians in COVID-19 diagnostics, testing of human samples in veterinary labs for Brucella and leptospirosis in Punjab and Tamil Nadu, respectively, and implementation of OH education targeted to school children and farmers in rural communities. There is an opportunity to strengthen local intersectoral coordination between animal, human and environmental health sectors by building on these activities and formalizing the existing collaborative networks. As India moves forward with broad OH initiatives, OH networks and experience at the local level from previous or ongoing activities can support implementation from the ground up.

Brucellosis in India: Comparing exposure amongst veterinarians, para-veterinarians and animal handlers.

The exposure to Brucella species is an occupational hazard for veterinary personnel in India. In our previous study, paraveterinarians and animal handlers were found to be at higher risk of being seropositive. In the present study, we further investigate comparative exposure risk to brucellosis amongst the veterinary professionals, identify risk factors, and evaluate the perceptions and practices towards using adequate personal protective equipment (PPE) while attending high risk veterinary interventions. A cross-sectional study was conducted amongst veterinary personnel in the Punjab state of India. Logistic and negative binomial regression models were constructed to interpret the influence of categorical and numerical variables on prevalence of brucellosis and the adequacy of PPE use, respectively. Compared to veterinarians, animal handlers were less likely to consider veterinary practice in sheep and goats (odds ratio [OR] 0.3; 95% confidence interval [CI]: 0.2-0.7) or assisting in obstetric interventions (OR 0.3, 95% CI 0.1-0.8) as potential exposures. They were less aware of the signs and symptoms of the disease in humans (OR 0.05, 95% CI 0.02-0.14) and of the availability of vaccines for cattle (OR 0.07, 95% CI 0.01-0.3) than the veterinarians, and were least likely of the three groups to recommend vaccination of cattle against brucellosis to animal owners (OR 0.1, 95% CI 0.02-0.3). Compared to veterinarians, they were also less likely to consider zoonotic risk (OR 0.4, 95% CI 0.2-0.8) or better efficiency (OR 0.1, 95% CI 0.05-0.4) as enablers of PPE use during veterinary procedures. Of the three occupational groups, animal handlers were also less likely to use adequate PPE during high-risk veterinary exposures, although they were found to have handled the highest number of cases of abortion. The average use of adequate PPE during high-risk interventions in one month preceding this study was lowest for animal handlers. Veterinary personnel with a higher rate of PPE use during high-risk veterinary interventions were likely to obtain information on brucellosis from government sources (p = 0.06) and felt that PPE use enhanced their professional efficiency (Incidence rate ratio [IRR] 3.3, 95% CI 1.5-8.1) compared to those who were less likely to use adequate PPE. We recommend concerted efforts to increase awareness amongst veterinary personnel, particularly amongst animal handlers, regarding brucellosis and the importance of biosecurity measures in veterinary practice. Designing training courses on the importance of PPE use along with formulation of biosecurity guidelines at local levels could help reduce the prevalence of the disease in veterinary personnel.

Meta-analysis and adjusted estimation of COVID-19 case fatality risk in India and its association with the underlying comorbidities.

Management of coronavirus disease 2019 (COVID-19) in India is a top government priority. However, there is a lack of COVID-19 adjusted case fatality risk (aCFR) estimates and information on states with high aCFR. Data on COVID-19 cases and deaths in the first pandemic wave and 17 state-specific geodemographic, socio-economic, health and comorbidity-related factors were collected. State-specific aCFRs were estimated, using a 13-day lag for fatality. To estimate country-level aCFR in the first wave, state estimates were meta-analysed based on inverse-variance weighting and aCFR as either a fixed- or random-effect. Multiple correspondence analyses, followed by univariable logistic regression, were conducted to understand the association between aCFR and geodemographic, health and social indicators. Based on health indicators, states likely to report a higher aCFR were identified. Using random- and fixed-effects models, cumulative aCFRs in the first pandemic wave on 27 July 2020 in India were 1.42% (95% CI 1.19%-1.70%) and 2.97% (95% CI 2.94%-3.00%), respectively. At the end of the first wave, as of 15 February 2021, a cumulative aCFR of 1.18% (95% CI 0.99%-1.41%) using random and 1.64% (95% CI 1.64%-1.65%) using fixed-effects models was estimated. Based on high heterogeneity among states, we inferred that the random-effects model likely provided more accurate estimates of the aCFR for India. The aCFR was grouped with the incidence of diabetes, hypertension, cardiovascular diseases and acute respiratory infections in the first and second dimensions of multiple correspondence analyses. Univariable logistic regression confirmed associations between the aCFR and the proportion of urban population, and between aCFR and the number of persons diagnosed with diabetes, hypertension, cardiovascular diseases and stroke per 10,000 population that had visited NCD (Non-communicable disease) clinics. Incidence of pneumonia was also associated with COVID-19 aCFR. Based on predictor variables, we categorised 10, 17 and one Indian state(s) expected to have a high, medium and low aCFR risk, respectively. The current study demonstrated the value of using meta-analysis to estimate aCFR. To decrease COVID-19 associated fatalities, states estimated to have a high aCFR must take steps to reduce co-morbidities.

The feasibility and acceptability of various bovine brucellosis control strategies in India.

Bovine brucellosis is a neglected zoonotic disease prevalent in several developing countries including India. It has been successfully controlled in many developed countries by using vaccination in conjunction with extensive surveillance and test-and-cull approaches, but some of these approaches do not suit Indian culture and norms. This study was conducted to investigate the feasibility and social acceptability of various bovine brucellosis control strategies in India. Focus group discussions and key-informant interviews were conducted with veterinarians, para-veterinarians, veterinary academics, farmers and other stakeholders. Vaccination with the Brucella strain 19 vaccine was considered feasible, but the participants were concerned about the risk of self-inoculation, the inability to vaccinate pregnant and male animals, the difficulty to differentiate vaccinated from diseased animals and the challenges of maintaining the vaccine cold chain in India. As expected, the test-and-cull approach was not considered feasible as cattle are considered sacred by Hindus and their slaughter is banned in most states. Although the test-and-segregation approach appears reasonable in theory, it would have low acceptability, if implemented without providing any compensation to farmers. Negligible biosecurity was implemented by farmers: almost no biosecurity procedures were performed for visitors entering a farm, and testing of animals was rarely undertaken before introducing them to a farm. However, the participants considered that improving biosecurity would be more acceptable and feasible than both the test-and-cull and the test-and-segregation approaches. Similarly, inadequate personal protection was used by veterinary personnel for handling parturition, retention of placenta and abortion cases; this was considered as another area of possible improvement. Farmers and veterinarians expressed serious concerns about stray cattle as many of them could potentially be infected with brucellosis, and thus could spread the infection between farms. This study recommends using vaccination and biosecurity along with some ancillary strategies to control brucellosis in India. Information from the study could be used to develop an evidence-based disease control program for the disease in the country.

Public health interventions slowed but did not halt the spread of COVID-19 in India.

The government of India implemented social distancing interventions to contain the COVID-19 epidemic. However, effects of these interventions on epidemic dynamics are yet to be understood. Rates of laboratory-confirmed COVID-19 infections per day and effective reproduction number (Rt ) were estimated for 7 periods (Pre-lockdown, Lockdown Phases 1 to 4 and Unlock 1-2) according to nationally implemented interventions with phased relaxation. Adoption of these interventions was estimated using Google mobility data. Estimates at the national level and for 12 Indian states most affected by COVID-19 are presented. Daily case rates ranged from 0.03 to 285.60/10 million people across 7 discrete periods in India. From 18 May to 31 July 2020, the NCT of Delhi had the highest case rate (999/10 million people/day), whereas Madhya Pradesh had the lowest (49/10 million/day). Average Rt was 1.99 (95% CI 1.93-2.06) and 1.39 (95% CI 1.38-1.40) for the entirety of India during the period from 22 March 2020 to 17 May 2020 and from 18 May 2020 to 31 July 2020, respectively. Median mobility in India decreased in all contact domains during the period from 22 March 2020 to 17 May 2020, with the lowest being 21% in retail/recreation, except home which increased to 129% compared to the 100% baseline value. Median mobility in the 'Grocery and Pharmacy' returned to levels observed before 22 March 2020 in Unlock 1 and 2, and the enhanced mobility in the Pharmacy sector needs to be investigated. The Indian government imposed strict contact mitigation, followed by a phased relaxation, which slowed the spread of COVID-19 epidemic progression in India. The identified daily COVID-19 case rates and Rt will aid national and state governments in formulating ongoing COVID-19 containment plans. Furthermore, these findings may inform COVID-19 public health policy in developing countries with similar settings to India.

Cost-benefit analysis of intervention policies for prevention and control of brucellosis in India.

BACKGROUND: Brucellosis is endemic in the bovine population in India and causes a loss of US$ 3·4 billion to the livestock industry besides having a significant human health impact. METHODS: We developed a stochastic simulation model to estimate the impact of three alternative vaccination strategies on the prevalence of Brucella infection in the bovine populations in India for the next two decades: (a) annual mass vaccination only for the replacement calves and (b) vaccination of both the adult and young population at the beginning of the program followed by an annual vaccination of the replacement calves and, (c) annual mass vaccination of replacements for a decade followed by a decade of a test and slaughter strategy. FINDINGS: For all interventions, our results indicate that the prevalence of Brucella infection will drop below 2% in cattle and, below 3% in buffalo after 20 years of the implementation of a disease control program. For cattle, the Net Present Value (NPV) was found to be US $ 4·16 billion for intervention (a), US $ 8·31 billion for intervention (b) and, US $ 4·26 for intervention (c). For buffalo, the corresponding NPVs were US $ 8·77 billion, US $ 13·42 and, US $ 7·66, respectively. The benefit cost ratio (BCR) for the first, second and the third intervention for cattle were 7·98, 10·62 and, 3·16, respectively. Corresponding BCR estimates for buffalo were 17·81, 21·27 and, 3·79, respectively. CONCLUSION: These results suggest that all interventions will be cost-effective with the intervention (b), i.e. the vaccination of replacements with mass vaccination at the beginning of the program, being the most cost-effective choice. Further, sensitivity analysis revealed that all interventions will be cost-effective even at the 50% of the current prevalence estimates. The results advocate for the implementation of a disease control program for brucellosis in India.

Quantitative polymerase chain reaction based quantification of Brucella DNA in serum of pre- and post-therapeutic occupationally exposed infected human population.

BACKGROUND: Brucellosis is one of the neglected zoonotic diseases in humans. The serological methods based on antibody detections are unable to detect the effectiveness of treatment in humans as antibodies persist for long time in humans even after therapy. Therefore, we developed qPCR technique to overcome such discrepancy and device a rapid and efficient test for both diagnosis and follow up of the brucellosis affected individuals. METHODS: High risk suspected individuals with positive serology (RBPT, STAT and iELISA) and PCR were mainly analyzed for DNA quantification by qPCR assay. The bcsp-31 gene, a shared gene of Brucella species was amplified by genus specific primers and cloned to pGEMT™ easy vector and the cloned plasmid were used to construct a standard curve (R2=0.99, efficiency=1.98) over 7 orders of magnitude with sensitivity of ≈10 copy number. The assay was found 100% specific. RESULTS: Overall 85 individuals were found positive out of 188. Out of them, 23 serological, PCR and qPCR positive individuals were recommended for 45days therapy according to WHO regimen (Doxycycline and Rifampin) and each case was further followed by qPCR. The mean threshold cycle (Cq) before treatment was 26.05±0.347 (3940.5copies/µl), which increased significantly to 32.7±0.66 (259.13copies/µl) on 4th week during treatment, 35.12±3.12 (38.52copies/µl) at 6th week on day of treatment completion, 35.6±0.66 (34.21copies/µl) on 21st day after treatment depicting a significant reduction in DNA load over the course of treatment. Serological follow up showed that only 3 individuals had decreased STAT titre but no change in RBPT results. Out of 17 symptomatic individuals under therapy, 10 improved clinically, 5 improved clinically with persistent weakness and 2 had no effect of therapy. CONCLUSION: The study suggests that qPCR is more useful and rapid test to follow treated individuals than serology.

Fipronil induces lung inflammation in vivo and cell death in vitro.

BACKGROUND: Fipronil is an insecticide that acts at the gamma-aminobutyric acid receptor and glutamate-gated chloride channels in the central nervous systems of target organisms. The use of fipronil is increasing across the globe. Presently, very little data exist on the potential impact of exposure to fipronil on the lungs. METHODS: We studied effects of intranasal (N = 8) and oral (N = 8) treatment with fipronil (10 mg/kg) on lungs of mice. Control mice were given groundnut oil orally (N = 7) or ethanol intranasally (N = 7) as these were the vehicles for respective treatments. RESULTS: Hematoxylin-eosin stained lung sections showed normal histology in the control lungs compared to the thickened alveolar septa, disruption of the airways epithelium and damage to vascular endothelium in the intranasal and the oral groups. Mice exposed to fipronil either orally or intranasally showed increased von Willebrand factor staining in the endothelium and septal capillaries. Compared to the control mice, TLR4 expression in airway epithelium was increased in mice treated intranasally but not orally with fipronil. Oral fipronil reduced TLR9 staining in the airway epithelium but intranasal exposure caused intense staining in the alveolar septa and airway epithelium. There were higher numbers of TLR4 positive cells in alveolar septa in lungs of mice treated intranasally (P = 0.010) compared to the respective control and orally treated mice but no significant differences between treatments for TLR9 positive stained cells (P = 0.226). The U937 macrophage cells exposed to fipronil at concentrations of 0.29 µm to 5.72 µm/ml over 3- or 24-hour showed significant increase in cell death at higher concentrations of fipronil (P < 0.0001). Western blots revealed no effect of fipronil on TLR4 (P = 0.49) or TLR9 (P = 0.94) expression on macrophage cell line. CONCLUSION: While both oral or intranasal fipronil treatments induced signs of lung inflammation, the number TLR4-positive septal cells was increased only following intranasal treatment. Fipronil causes macrophage cell death without altering TLR4 and TLR9 expression in vitro.

Economic losses due to cystic echinococcosis in India: Need for urgent action to control the disease.

Cystic ehinococcosis (CE) caused by Echinococcus granulosus remains a neglected zoonotic disease despite its considerable human and animal health concerns. This is the first systematic analysis of the livestock and human related economic losses due to cystic echinococcosis in India. Data about human cases were obtained from a tertiary hospital. Human hydatidosis cases with and without surgical interventions were extrapolated to be 5647 and 17075 per year assuming a total human population of 1210193422 in India. Data about prevalence of hydatid cysts in important food producing animals were obtained from previously published abattoir based epidemiological surveys that reported a prevalence of 5.39% in cattle, 4.36% in buffaloes, 3.09% in pigs, 2.23% in sheep and 0.41% in goats. Animal population data were sourced from the latest census conducted by the Department of Animal Husbandry, Dairying and Fisheries, India. Other input parameters were obtained from published scientific literature. Probability distributions were included for many input values to account for variability and uncertainty. Sensitivity analyses were conducted to evaluate the effect of important parameters on the estimated economic losses. The analysis revealed a total annual median loss of Rs. 11.47 billion (approx. US $ 212.35 million). Cattle and buffalo industry accounted for most of the losses: 93.05% and 88.88% of the animal and total losses, respectively. Human hydatidosis related losses were estimated to be Rs. 472.72 million (approx. US $ 8.75 million) but are likely to be an under-estimate due to under-reporting of the disease in the country. The human losses more than quadrupled to Rs. 1953 million i.e. approx. US $ 36.17 million, when the prevalence of human undiagnosed cases was increased to 0.2% in the sensitivity analyses. The social loss and psychological distress were not taken into account for calculating human loss. The results highlight an urgent need for a science based policy to control and manage the disease in the country.