National snakebite project on capacity building of health system on prevention and management of snakebite envenoming including its complications in selected districts of Maharashtra and Odisha in India: A study protocol.

BACKGROUND: Snakebite envenoming (SBE) is an acute, life-threatening emergency in tropical and subtropical countries. It is an occupational hazard and a major socioeconomic determinant. Limited awareness, superstitions, lack of trained health providers, poor utilization of anti-venom results in high mortality and morbidity. India is the snakebite capital of the world. Yet, information on awareness, knowledge, and perceptions about snakebite is limited. Data on capacity building of health systems and its potential impact is lacking. Recommended by the National Task Force on snakebite research in India, this protocol describes the National Snakebite Project aiming for capacity building of health systems on prevention and management of snakebite envenomation in Maharashtra and Odisha states. METHODS: A cross-sectional, multi-centric study will be carried out in Shahapur, Aheri blocks of Maharashtra, and Khordha, Kasipur blocks of Odisha. The study has five phases: Phase I involves the collection of retrospective baseline data of snakebites, facility surveys, and community focus group discussions (FGDs). Phase II involves developing and implementing educational intervention programs for the community. Phase III will assess the knowledge and practices of the healthcare providers on snakebite management followed by their training in Phase IV. Phase V will evaluate the impact of the interventions on the community and healthcare system through FGDs and comparison of prospective and baseline data. DISCUSSION: The National Snakebite Project will use a multi-sectoral approach to reduce the burden of SBE. It intends to contribute to community empowerment and capacity building of the public healthcare system on the prevention and management of SBE. The results could be useful for upscaling to other Indian states, South Asia and other tropical countries. The findings of the study will provide critical regional inputs for the revision of the National Snakebite Treatment protocol. TRIAL REGISTRATION: Registered under the Clinical Trials Registry India no. CTRI/2021/11/038137.

Clinical characteristics, outcomes, & mortality in pregnant women with COVID-19 in Maharashtra, India: Results from PregCovid registry.

Background & objectives: The PregCovid registry was established to document the clinical presentations, pregnancy outcomes and mortality of pregnant and post-partum women with COVID-19. Methods: The PregCovid registry prospectively collects information in near-real time on pregnant and post-partum women with a laboratory-confirmed diagnosis of SARS-CoV-2 from 19 medical colleges across the State of Maharashtra, India. Data of 4203 pregnant women collected during the first wave of the COVID-19 pandemic (March 2020-January 2021) was analyzed. Results: There were 3213 live births, 77 miscarriages and 834 undelivered pregnancies. The proportion of pregnancy/foetal loss including stillbirths was six per cent. Five hundred and thirty-four women (13%) were symptomatic, of which 382 (72%) had mild, 112 (21%) had moderate, and 40 (7.5%) had severe disease. The most common complication was preterm delivery (528, 16.3%) and hypertensive disorders in pregnancy (328, 10.1%). A total of 158 (3.8%) pregnant and post-partum women required intensive care, of which 152 (96%) were due to COVID-19 related complications. The overall case fatality rate (CFR) in pregnant and post-partum women with COVID-19 was 0.8 per cent (34/4203). Higher CFR was observed in Pune (9/853, 1.1%), Marathwada (4/351, 1.1%) regions as compared to Vidarbha (9/1155, 0.8%), Mumbai Metropolitan (11/1684, 0.7%), and Khandesh (1/160, 0.6%) regions. Comorbidities of anaemia, tuberculosis and diabetes mellitus were associated with maternal deaths. Interpretation & conclusions: The study demonstrates the adverse outcomes including severe COVID-19 disease, pregnancy loss and maternal death in women with COVID-19 in Maharashtra, India.

Perceptions, awareness on snakebite envenoming among the tribal community and health care providers of Dahanu block, Palghar District in Maharashtra, India.

INTRODUCTION: India has remarkably the highest number of snakebite cases contributing to nearly 50% of the global snakebite deaths. Despite this fact, there is limited knowledge and awareness regarding the management practices for snakebite in the Indian population. The study aimed to explore the knowledge, awareness, and perception of snakes and snakebites, first aid, and treatment amongst the community and the frontline health workers in a tribal block of Dahanu, Maharashtra, India. METHODS: A cross-sectional study was carried out from June 2016 to October 2018 in the Dahanu Block, Maharashtra. Perceptions, knowledge, awareness, and first-aid practices on the snakebites among the community were studied through focus group discussions (FGDs). Semi-structured questionnaires were used to assess the knowledge, awareness, and experience of the traditional faith healers, snake rescuers, frontline health workers on the snakebites and their management. A facility check survey was conducted using pre-tested questionnaires for different levels of the government health care facilities. RESULTS: Most of the tribal community was aware of the commonly found snakes and their hiding places. However, there was inadequate knowledge on the identification and classification of venomous snakes. Belief in a snake god, the perception that snakes will not come out during thunderstorms, change in taste sensation, the ability of tamarind seeds or magnet to reduce the venom effect were some of the superstitions reported by the tribal community. The application of a harmful method (Tourniquet) as the first aid for snakebite was practiced by the tribal community. They preferred herbal medicines and visiting the traditional faith healers before shifting the patient to the government health facility. The knowledge on the ability to identify venomous snakebites and anti-venom was significantly higher amongst nurses and accredited social health activists (ASHAs) than auxiliary nurse midwives (ANMs) and multi-purpose workers (MPWs) (p < 0.05). None of the traditional faith healers; but nearly 60% of snake rescuers were aware of anti-venom. Fifty percent of the medical officers in Dahanu block did not have correct knowledge about the Krait bite symptoms, and renal complications due to the Russell viper bite. CONCLUSIONS: Inappropriate perception, inadequate awareness, and knowledge about snakes and snakebites may predispose the tribal community to increased risks of venomous snakebites. Unproven and harmful methods for snakebite treatment practiced by the community and traditional faith healers could be dangerous leading to high mortality. Therefore, a multi-sectoral approach of community awareness, mapping of vulnerable populations, capacity building of health care facility, empowerment of health care workers (HCWs) could be useful for reducing the mortality and morbidity due to snakebite envenoming in India.

Rapid and Long-Term Immunity Elicited by DNA-Encoded Antibody Prophylaxis and DNA Vaccination Against Chikungunya Virus.

BACKGROUND: Vaccination and passive antibody therapies are critical for controlling infectious diseases. Passive antibody administration has limitations, including the necessity for purification and multiple injections for efficacy. Vaccination is associated with a lag phase before generation of immunity. Novel approaches reported here utilize the benefits of both methods for the rapid generation of effective immunity. METHODS: A novel antibody-based prophylaxis/therapy entailing the electroporation-mediated delivery of synthetic DNA plasmids encoding biologically active anti-chikungunya virus (CHIKV) envelope monoclonal antibody (dMAb) was designed and evaluated for antiviral efficacy, as well as for the ability to overcome shortcomings inherent with conventional active vaccination and passive immunotherapy. RESULTS: One intramuscular injection of dMAb produced antibodies in vivo more rapidly than active vaccination with an anti-CHIKV DNA vaccine. This dMAb neutralized diverse CHIKV clinical isolates and protected mice from viral challenge. Combination of dMAb and the CHIKV DNA vaccine afforded rapid and long-lived protection. CONCLUSIONS: A DNA-based dMAb strategy induced rapid protection against an emerging viral infection. This method can be combined with DNA vaccination as a novel strategy to provide both short- and long-term protection against this emerging infectious disease. These studies have implications for pathogen treatment and control strategies.

Association of Oligoadenylate Synthetase Gene Cluster and DC-SIGN (CD209) Gene Polymorphisms with Clinical Symptoms in Chikungunya Virus Infection.

Biology and pathogenesis of chikungunya virus (CHIKV) are not clearly established. Host factors play an important role in determining the progression and severity of the disease. Polymorphisms in the promoter region of CD209 gene (rs735239, rs4804803, rs2287886) and OAS1 (rs1131454 and rs10774671), OAS2 (rs15895 and rs1732778), and OAS3 (rs2285932 and rs2072136) genes were investigated in 100 patients with CHIKV infection and 101 healthy controls to find out the association of these polymorphisms with CHIKV infection. To evaluate the association of OAS and CD209 gene polymorphisms with the presence or absence of disease symptoms in CHIKV-infected patients. DNA was extracted and typed using polymerase chain reaction followed by restriction fragment length polymorphism methods. Results revealed that the allele and genotype frequencies of OAS1, OAS3, and OAS2 gene polymorphisms were not different between healthy controls and CHIKV patients. The frequency of CD209 gene G/G genotype of rs4804803 was significantly higher in CHIKV patients compared to healthy controls (p = 0.046). The present study suggests that rs4804803 GG genotype of CD209 gene is associated with susceptibility to CHIKV infection. To conclude, the present preliminary study suggests that OAS gene cluster and CD209 gene polymorphisms influence the risk of developing clinical symptoms in CHIKV-infected patients. Further follow-up studies with a large number of samples are needed to assess the role of these genes in association with post-sequela symptoms observed in CHIKV patients. A detailed research is required in these directions to understand the biology behind CHIKV infection and disease severity.

HLA class II allele polymorphism in an outbreak of chikungunya fever in Middle Andaman, India.

A sudden upsurge of fever cases with joint pain was observed in the outpatient department, Community Health Centre, Rangat during July-August 2010 in Rangat Middle Andaman, India. The aetiological agent responsible for the outbreak was identified as chikungunya virus (CHIKV), by using RT-PCR and IgM ELISA. The study investigated the association of polymorphisms in the human leucocyte antigen class II genes with susceptibility or protection against CHIKV. One hundred and one patients with clinical features suggestive of CHIKV infection and 104 healthy subjects were included in the study. DNA was extracted and typed for HLA-DRB1 and DQB1 alleles. Based on the amino acid sequences of HLA-DQB1 retrieved from the IMGT/HLA database, critical amino acid differences in the specific peptide-binding pockets of HLA-DQB1 molecules were investigated. The frequencies of HLA-DRB1 alleles were not significantly different, whereas lower frequency of HLA-DQB1*03:03 was observed in CHIKV patients compared with the control population [P = 0·001, corrected P = 0·024; odds ratio (OR)  = 0, 95% confidence interval (95% CI) 0·0-0·331; Peto's OR = 0·1317, 95% CI 0·0428-0·405). Significantly lower frequency of glutamic acid at position 86 of peptide-binding pocket 1 coding HLA-DQB1 genotypes was observed in CHIKV patients compared with healthy controls (P = 0·004, OR = 0·307, 95% CI 0·125-0·707). Computational binding predictions of CD4 epitopes of CHIKV by NetMHCII revealed that HLA-DQ molecules are known to bind more CHIKV peptides than HLA-DRB1 molecules. The results suggest that HLA-DQB1 alleles and critical amino acid differences in the peptide-binding pockets of HLA-DQB1 alleles might have role in influencing infection and pathogenesis of CHIKV.