An appraisal of peer-reviewed published literature on Influenza, 2000-2021 from countries in South-East Asia Region.

Background: Influenza poses a major public health challenge in South-East Asia Region (SEAR). To address the challenge, there is a need to generate contextual evidence that could inform policy makers and program managers for response preparedness and impact mitigation. The World Health Organization has identified priority areas across five streams for research evidence generation at a global level (WHO Public Health Research Agenda). Stream 1 focuses on research for reducing the risk of emergence, Stream 2 on limiting the spread, Stream 3 on minimizing the impact, Stream 4 on optimizing the treatment and Stream 5 on promoting public health tools and technologies for Influenza. However, evidence generation from SEAR has been arguably low and needs a relook for alignment with priorities. This study aimed to undertake a bibliometric analysis of medical literature on Influenza over the past 21 years to identify gaps in research evidence and for identifying major areas for focusing with a view to provide recommendations to member states and SEAR office for prioritizing avenues for future research. Methods: We searched Scopus, PubMed, Embase, and Cochrane databases in August 2021. We identified studies on influenza published from the 11 countries in WHO SEAR in the date range of 1 January 2000-31 December 2021. Data was retrieved, tagged and analyzed based on the WHO priority streams for Influenza, member states, study design and type of research. Bibliometric analysis was done on Vosviewer. Findings: We included a total of 1,641 articles (Stream 1: n = 307; Stream 2: n = 516; Stream 3: n = 470; Stream 4: n = 309; Stream 5: n = 227). Maximum number of publications were seen in Stream 2, i.e., limiting the spread of pandemic, zoonotic, and seasonal epidemic influenza which majorly included transmission, spread of virus at global and local levels and public health measures to limit the transmission. The highest number of publications was from India (n = 524) followed by Thailand (n = 407), Indonesia (n = 214) and Bangladesh (n = 158). Bhutan (n = 10), Maldives (n = 1), Democratic People's Republic of Korea (n = 1), and Timor-Leste (n = 3) had the least contribution in Influenza research. The top-most journal was PloS One which had the maximum number of influenza articles (n = 94) published from SEAR countries. Research that generated actionable evidence, i.e., implementation and intervention related topics were less common. Similarly, research on pharmaceutical interventions and on innovations was low. SEAR member states had inconsistent output across the five priority research streams, and there was a much higher scope and need for collaborative research. Basic science research showed declining trends and needed reprioritization. Interpretation: While a priority research agenda has been set for influenza at the global level through the WHO Global Influenza Program since 2009, and subsequently revisited in 2011 and again in 2016-2017, a structured contextualized approach to guide actionable evidence generation activities in SEAR has been lacking. In the backset of the Global Influenza Strategy 2019-2030 and the COVID-19 pandemic, attuning research endeavors in SEAR could help in improved pandemic influenza preparedness planning. There is a need to prioritize contextually relevant research themes within priority streams. Member states must inculcate a culture of within and inter-country collaboration to produce evidence that has regional as well as global value.

Extended spectrum beta-lactamase-producing Escherichia coli surveillance in the human, food chain, and environment sectors: Tricycle project (pilot) in Indonesia.

The World Health Organization (WHO) has been implementing antimicrobial surveillance with a "One Health" approach, known as the Global Surveillance ESBL E. coli Tricycle Project. We describe the implementation of the Tricycle Project (pilot) in Indonesia, focusing on its results, challenges and recommendations. The samples were 116 patients with bloodstream infections caused by ESBL E. coli, 100 rectal swabs collected from pregnant women, 240 cecums of broiler, and 119 environmental samples, using the standardized method according to the guidelines. ESBL-producing E. coli was found in 40 (40%) of the 100 pregnant women, while the proportion of ESBL-producing E. coli was 57.7% among the total E. coli-induced bloodstream infections. ESBL-producing E. coli was isolated from 161 (67.1%) out of 240 broilers. On the other hand, the average concentration of E. coli in the water samples was 2.0 × 108 CFU/100 mL, and the ratio of ESBL-producing E. coli was 12.8% of total E. coli. Unfortunately, 56.7% of questionnaires for patients were incomplete. The Tricycle Project (pilot) identified that the proportion of ESBL-producing E. coli was very high in all types of samples, and several challenges and obstacles were encountered during the implementation of the study in Indonesia. The finding of this study have implication to health/the antimicrobial resistance (AMR) surveillance. We recommend continuing this project and extending this study to other provinces to determine the AMR burden as the baseline in planning AMR control strategies in Indonesia. We also recommend improving the protocol of this study to minimize obstacles in the field.

Research priorities for control of zoonoses in South Africa.

BACKGROUND: Zoonoses pose major threats to the health of humans, domestic animals and wildlife, as seen in the COVID-19 pandemic. Zoonoses are the commonest source of emerging human infections and inter-species transmission is facilitated by anthropogenic factors such as encroachment and destruction of wilderness areas, wildlife trafficking and climate change. South Africa was selected for a 'One Health' study to identify research priorities for control of zoonoses due to its complex disease burden and an overstretched health system. METHODS: A multidisciplinary group of 18 experts identified priority zoonotic diseases, knowledge gaps and proposed research priorities for the next 5 y. Each priority was scored using predefined criteria by another group of five experts and then weighted by a reference group (n=28) and the 18 experts. RESULTS: Seventeen diseases were mentioned with the top five being rabies (14/18), TB (13/18), brucellosis (11/18), Rift Valley fever (9/11) and cysticercosis (6/18). In total, 97 specific research priorities were listed, with the majority on basic epidemiological research (n=57), such as measuring the burden of various zoonoses (n=24), followed by 20 on development of new interventions. The highest research priority score was for improving existing interventions (0.77/1.0), followed by health policy and systems research (0.72/1.0). CONCLUSION: Future zoonotic research should improve understanding of zoonotic burden and risk factors and new interventions in public health. People with limited rural services, immunocompromised, in informal settlements and high-risk occupations, should be the highest research priority.

Comparative analysis of virulence determinants, phylogroups, and antibiotic susceptibility patterns of typical versus atypical Enteroaggregative E. coli in India.

Enteroaggregative Escherichia coli (EAEC) is an evolving enteric pathogen that causes acute and chronic diarrhea in developed and industrialized nations in children. EAEC epidemiology and the importance of atypical EAEC (aEAEC) isolation in childhood diarrhea are not well documented in the Indian setting. A comparative analysis was undertaken to evaluate virulence, phylogeny, and antibiotic sensitivity among typical tEAEC versus aEAEC. A total of 171 EAEC isolates were extracted from a broad surveillance sample of diarrheal (N = 1210) and healthy children (N = 550) across North India. Polymerase chain reaction (PCR) for the aggR gene (master regulator gene) was conducted to differentiate tEAEC and aEAEC. For 21 virulence genes, we used multiplex PCR to classify possible virulence factors among these strains. Phylogenetic classes were identified by a multiplex PCR for chuA, yjaA, and a cryptic DNA fragment, TspE4C2. Antibiotic susceptibility was conducted by the disc diffusion method as per CLSI guidelines. EAEC was associated with moderate to severe diarrhea in children. The prevalence of EAEC infection (11.4%) was higher than any other DEC group (p = 0.002). tEAEC occurrence in the diarrheal group was higher than in the control group (p = 0.0001). tEAEC strain harbored more virulence genes than aEAEC. astA, aap, and aggR genes were most frequently found in the EAEC from the diarrheal population. Within tEAEC, this gene combination was present in more than 50% of strains. Also, 75.8% of EAEC strains were multidrug-resistant (MDR). Phylogroup D (43.9%) and B1 (39.4%) were most prevalent in the diarrheal and control group, respectively. Genetic analysis revealed EAEC variability; the comparison of tEAEC and aEAEC allowed us to better understand the EAEC virulence repertoire. Further microbiological and epidemiological research is required to examine the pathogenicity of not only typical but also atypical EAEC.

Monitoring COVID-19 where capacity for testing is limited: use of a three-step analysis based on test positivity ratio.

In an effort to monitor coronavirus disease 2019 (COVID-19), many countries have been calculating the ratio of cases confirmed to tests performed (test positivity ratio - TPR). While inferior to sentinel surveillance, TPR has the benefit of being easily calculated using readily available data; however, interpreting TPR and its trends can be complex because both the numerator and the denominator are constantly changing. We describe a three-step process where the ratio of relative increase in cases to relative increase in tests is accounted for in an adjusted TPR. This adjusted value more appropriately reflects the case number and factors out the effect of changes in the number of tests done. Unadjusted and adjusted TPRs are then assessed step-wise with reference to the epidemic curve and the cumulative numbers of cases and tests. Use of this three-step analysis and its potential use in guiding public health interventions are demonstrated for selected countries and subnational areas of the World Health Organization South-East Asia Region, together with the Republic of Korea as a reference. To date, application of the three-step analysis to data from countries of the region has signalled potential inadequacies of testing strategies. Further work is needed on approaches to support countries where testing capacity is likely to remain constrained. One example would be enumeration of the average number of tests needed to detect one COVID-19 case, which could be stratified by factors such as location and population. Such data would allow evidence-informed strategies that best balance the highest detection rate with the prevailing testing capacity.

The Extent and Structure of Peri-urban Smallholder Dairy Farming in Five Cities in India.

Livestock keeping is common in many cities in India, driven by the demand for animal-source foods, particularly perishable milk. We selected five cities from different regions of the country and conducted a census in 34 randomly selected peri-urban villages to identify and describe all smallholder dairy farms. In total 1,690 smallholder dairy farms were identified, keeping on average 2.2 milking cows and 0.7 milking buffaloes. In Bhubaneswar, the proportion of cows milking was only 50%, but in other cities it was 63-73%. In two of the five cities, more than 90% of the farmers stated that dairy production was their main source of income, while <50% in the other cities reported this. In one of the cities, only 36% of the households kept milk for themselves. Market channels varied considerably; in one city about 90% of farms sold milk to traders, in another, 90% sold to the dairy cooperative, and in another around 90% sold directly to consumers. In conclusion, peri-urban dairy systems in India are important but also varying between different cities, with only one city, Bengaluru, having a well-developed cooperative system, and the northeastern poorer region being more dependent on traders. Further studies may be needed to elucidate the importance and to design appropriate developmental interventions.

Pesticide Residues in Peri-Urban Bovine Milk from India and Risk Assessment: A Multicenter Study.

Pesticides residue poses serious concerns to human health. The present study was carried out to determine the pesticide residues of peri-urban bovine milk (n = 1183) from five different sites (Bangalore, Bhubaneswar, Guwahati, Ludhiana and Udaipur) in India and dietary exposure risk assessment to adults and children. Pesticide residues were estimated using gas chromatography with flame thermionic and electron capture detectors followed by confirmation on gas chromatography-mass spectrometer. The results noticed the contamination of milk with hexachlorocyclohexane (HCH), dichloro-diphenyl trichloroethane (DDT), endosulfan, cypermethrin, cyhalothrin, permethrin, chlorpyrifos, ethion and profenophos pesticides. The residue levels in some of the milk samples were observed to be higher than the respective maximum residue limits (MRLs) for pesticide. Milk samples contamination was found highest in Bhubaneswar (11.2%) followed by Bangalore (9.3%), Ludhiana (6.9%), Udaipur (6.4%) and Guwahati (6.3%). The dietary risk assessment of pesticides under two scenarios i.e. lower-bound scenario (LB) and upper-bound (UB) revealed that daily intake of pesticides was substantially below the prescribed acceptable daily intake except for fipronil in children at UB. The non-cancer risk by estimation of hazard index (HI) was found to be below the target value of one in adults at all five sites in India. However, for children at the UB level, the HI for lindane, DDT and ethion exceeded the value of one in Ludhiana and Udaipur. Cancer risk for adults was found to be in the recommended range of United States environment protection agency (USEPA), while it exceeded the USEPA values for children.

Risk Factors for Brucella Seroprevalence in Peri-Urban Dairy Farms in Five Indian Cities.

Brucellosis is endemic among dairy animals in India, contributing to production losses and posing a health risk to people, especially farmers and others in close contact with dairy animals or their products. Growing urban populations demand increased milk supplies, resulting in intensifying dairy production at the peri-urban fringe. Peri-urban dairying is under-studied but has implications for disease transmission, both positive and negative. In this cross-sectional study, five Indian cities were selected to represent different geographies and urbanization extent. Around each, we randomly selected 34 peri-urban villages, and in each village three smallholder dairy farms (defined as having a maximum of 10 dairy animals) were randomly selected. The farmers were interviewed, and milk samples were taken from up to three animals. These were tested using a commercial ELISA for antibodies against Brucella abortus, and factors associated with herd seroprevalence were identified. In all, 164 out of 1163 cows (14.1%, 95% CI 12.2-16.2%) were seropositive for Brucella. In total, 91 out of 510 farms (17.8%, 95% CI 14.6-21.4%) had at least one positive animal, and out of these, just seven farmers stated that they had vaccinated against brucellosis. In four cities, the farm-level seroprevalence ranged between 1.4-5.2%, while the fifth city had a seroprevalence of 72.5%. This city had larger, zero-grazing herds, used artificial insemination to a much higher degree, replaced their animals by purchasing from their neighbors, were less likely to contact a veterinarian in case of sick animals, and were also judged to be less clean. Within the high-prevalence city, farms were at higher risk of being infected if they had a young owner and if they were judged less clean. In the low-prevalence cities, no risk factors could be identified. In conclusion, this study has identified that a city can have a high burden of infected animals in the peri-urban areas, but that seroprevalence is strongly influenced by the husbandry system. Increased intensification can be associated with increased risk, and thus the practices associated with this, such as artificial insemination, are also associated with increased risk. These results may be important to identify high-risk areas for prioritizing interventions and for policy decisions influencing the structure and development of the dairy industry.

Community, system and policy level drivers of bovine tuberculosis in smallholder periurban dairy farms in India: a qualitative enquiry.

BACKGROUND: Rapid urbanization has led to expansion of peri-urban fringes, where intensive, industry-style livestock rearing has led to emerging vulnerabilities at the human-animal-environment interface. This study was undertaken to understand the health system and farm-level factors that influenced the risk of transmission of bovine Tuberculosis (bTB) in animals and humans in peri-urban smallholder dairy farms of India. METHODS: Thematic guides were developing through literature review and expert consultation. In-depth interviews were conducted till attainment of saturation. Identification of core themes was followed by etiological enquiry and generation of a conceptual model. RESULTS: Veterinarians were consulted as a last resort after home-remedies and quacks had failed. Damage control measures, especially with respect to- selling or abandoning sick animals, added to the risk of disease transmission. Although civic authorities believed in the adequacy of a functioning laboratory network, end users were aggrieved at the lack of services. Despite the presence of extension services, knowledge and awareness was limited, promoting risky behaviour. The absence of cogent policies in dealing with bTB was a significant barrier. Stakeholders did not consider bTB to be a major concern. It is possible that they underestimate the problem. CONCLUSION: The current study helps to identify gaps which need to be addressed through collaborative research, and OneHealth interventions to build community awareness.

Antimicrobial resistance in South East Asia: time to ask the right questions.

Antimicrobial resistance (AMR) has emerged as a major public health concern, around which the international leadership has come together to form strategic partnerships and action plans. The main driving force behind the emergence of AMR is selection pressure created due to consumption of antibiotics. Consumption of antibiotics in human as well as animal sectors are driven by a complex interplay of determinants, many of which are typical to the local settings. Several sensitive and essential realities are tied with antibiotic consumption - food security, livelihoods, poverty alleviation, healthcare access and national economies, to name a few. That makes one-size-fits-all policies, framed with the developed country context in mind, inappropriate for developing countries. Many countries in the South East Asian Region have some policy structures in place to deal with AMR, but most of them lack detailed implementation plans or monitoring structures. In this current debates piece, the authors argue that the principles driving the AMR agenda in the South East Asian countries need to be dealt with using locally relevant policy structures. Strategies, which have successfully reduced the burden of AMR in the developed countries, should be evaluated in the developing country contexts instead of ad hoc implementation. The Global Action Plan on AMR encourages member states to develop locally relevant National Action Plans on AMR. This policy position should be leveraged to develop and deploy locally relevant strategies, which are based on a situation analysis of the local systems, and are likely to meet the needs of the individual member states.

The social biography of antibiotic use in smallholder dairy farms in India.

Background: Antimicrobial resistance (AMR) has been identified as one of the major threats to global health, food security and development today. While there has been considerable attention about the use and misuse of antibiotics amongst human populations in both research and policy environments, there is no definitive estimate of the extent of misuse of antibiotics in the veterinary sector and its contribution to AMR in humans. In this study, we explored the drivers ofirrational usage of verterinary antibiotics in the dairy farming sector in peri-urban India. Methods and materials: The study was conducted in the peri-urban belts of Ludhiana, Guwahati and Bangalore. A total of 54 interviews (formal and non-formal) were carried out across these three sites. Theme guides were developed to explore different drivers of veterinary antimicrobial use. Data was audio recorded and transcribed. Analysis of the coded data set was carried out using AtlasTi. Version 7. Themes emerged inductively from the set of codes. Results: Findings were presented based on concept of 'levels of analyses'. Emergent themes were categorised as individual, health systems, and policy level drivers. Low level of knowledge related to antibiotics among farmers, active informal service providers, direct marketing of drugs to the farmers and easily available antibiotics, dispensed without appropriate prescriptions contributed to easy access to antibiotics, and were identified to be the possible drivers contributing to the non-prescribed and self-administered use of antibiotics in the dairy farms. Conclusions: Smallholding dairy farmers operated within very small margins of profits. The paucity of formal veterinary services at the community level, coupled with easy availability of antibiotics and the need to ensure profits and minimise losses, promoted non-prescribed antibiotic consumption. It is essential that these local drivers of irrational antibiotic use are understood in order to develop interventions and policies that seek to reduce antibiotic misuse.

Protocol for developing a Database of Zoonotic disease Research in India (DoZooRI).

INTRODUCTION: Zoonotic and emerging infectious diseases (EIDs) represent a public health threat that has been acknowledged only recently although they have been on the rise for the past several decades. On an average, every year since the Second World War, one pathogen has emerged or re-emerged on a global scale. Low/middle-income countries such as India bear a significant burden of zoonotic and EIDs. We propose that the creation of a database of published, peer-reviewed research will open up avenues for evidence-based policymaking for targeted prevention and control of zoonoses. METHODS AND ANALYSIS: A large-scale systematic mapping of the published peer-reviewed research conducted in India will be undertaken. All published research will be included in the database, without any prejudice for quality screening, to broaden the scope of included studies. Structured search strategies will be developed for priority zoonotic diseases (leptospirosis, rabies, anthrax, brucellosis, cysticercosis, salmonellosis, bovine tuberculosis, Japanese encephalitis and rickettsial infections), and multiple databases will be searched for studies conducted in India. The database will be managed and hosted on a cloud-based platform called Rayyan. Individual studies will be tagged based on key preidentified parameters (disease, study design, study type, location, randomisation status and interventions, host involvement and others, as applicable). ETHICS AND DISSEMINATION: The database will incorporate already published studies, obviating the need for additional ethical clearances. The database will be made available online, and in collaboration with multisectoral teams, domains of enquiries will be identified and subsequent research questions will be raised. The database will be queried for these and resulting evidence will be analysed and published in peer-reviewed journals.

One Health/EcoHealth capacity building programs in South and South East Asia: a mixed method rapid systematic review.

BACKGROUND: Although One Health (OH) or EcoHealth (EH) have been acknowledged to provide comprehensive and holistic approaches to study complex problems, like zoonoses and emerging infectious diseases, there remains multiple challenges in implementing them in a problem-solving paradigm. One of the most commonly encountered barriers, especially in low- and middle-income countries, is limited capacity to undertake OH/EH inquiries. A rapid review was undertaken to conduct a situation analysis of the existing OH/EH capacity building programs, with a focused analysis of those programs with extensive OH engagement, to help map the current efforts in this area. METHODS: A listing of the OH/EH projects/initiatives implemented in South Asia (SA) and South East Asia (SEA) was done, followed by analysis of documents related to the projects, available from peer-reviewed or grey literature sources. Quantitative data was extracted using a data extraction format, and a free listing of qualitative themes was undertaken. RESULTS: In SEA, 13 unique OH/EH projects, with 37 capacity building programs, were identified. In contrast, in SA, the numbers were 8 and 11 respectively. In SA, programs were oriented to develop careers in program management, whereas, in SEA, the emphasis was on research. Two thirds of the programs in SEA had extensive OH engagement, whereas only one third of those in SA did. The target for the SEA programs was wider, including a population more representative of OH stakes. SEA program themes reveal utilization of multiple approaches, usually in shorter terms, and are growing towards integration with the traditional curricula. Such convergence of themes was lacking in SA programs. In both regions, the programs were driven by external donor agencies, with minimal local buy-in. CONCLUSIONS: There is limited investment in research capacity building in both SA and SEA. The situation appears to be more stark in SA, whilst SEA has been able to use the systematic investment and support to develop the OH/EH agenda and strategize capacity building in the core competencies. In order to effectively address the disease emergence hotspots in these regions, there needs to be strategic funding decisions targeting capacity building in the core OH/EH competencies especially related to transdisciplinarity, systems thinking, and adaptive management.

Perceptions, practices and health seeking behaviour constrain JE/AES interventions in high endemic district of North India.

BACKGROUND: Acute Encephalitis Syndrome (AES) and Japanese Encephalitis (JE) stay as poorly understood phenomena in India. Multiple linkages to determinants such as poverty, socio-economic status, gender, environment, and population distribution, make it a greater developmental issue than just a zoonotic disease. METHODS: A qualitative study was conducted to map knowledge, perceptions and practices of community and health systems level stakeholders. Seventeen interviews with utilizers of AES care, care givers from human and veterinary sectors, Non-governmental Organizations (NGOs), and pig owners and 4 Focused Group Discussions (FGDs) with farmers, community leaders, and students were conducted in an endemic north Indian district-Kushinagar. RESULTS: Core themes that emerged were: JE/AES been perceived as a deadly disease, but not a major health problem; filthy conditions, filthy water and mosquitoes seen to be associated with JE/AES; pigs not seen as a source of infection; minimal role of government health workers in the first-contact care of acute Illness; no social or cultural resistance to JE vaccination or mosquito control; no gender-based discrimination in the care of acute Illness; and non-utilization of funds available with local self govt. Serious challenges and systematic failures in delivery of care during acute illness, which can critically inform the health systems, were also identified. CONCLUSION: There is an urgent need for promotive interventions to address lack of awareness about the drivers of JE/AES. Delivery of care during acute illness suffers with formidable challenges and systematic failures. A large portion of mortality can be prevented by early institution of rational management at primary and secondary level, and by avoiding wastage of time and resources for investigations and medications that are not actually required.

Identifying sources, pathways and risk drivers in ecosystems of Japanese Encephalitis in an epidemic-prone north Indian district.

Japanese Encephalitis (JE) has caused repeated outbreaks in endemic pockets of India. This study was conducted in Kushinagar, a highly endemic district, to understand the human-animal-ecosystem interactions, and the drivers that influence disease transmission. Utilizing the ecosystems approach, a cross-sectional, descriptive study, employing mixed methods design was employed. Four villages (two with pig-rearing and two without) were randomly selected from a high, a medium and a low burden (based on case counts) block of Kushinagar. Children, pigs and vectors were sampled from these villages. A qualitative arm was incorporated to explain the findings from the quantitative surveys. All human serum samples were screened for JE-specific IgM using MAC ELISA and negative samples for JE RNA by rRT-PCR in peripheral blood mononuclear cells. In pigs, IgG ELISA and rRT-PCR for viral RNA were used. Of the 242 children tested, 24 tested positive by either rRT-PCR or MAC ELISA; in pigs, 38 out of the 51 pigs were positive. Of the known vectors, Culex vishnui was most commonly isolated across all biotopes. Analysis of 15 blood meals revealed human blood in 10 samples. Univariable analysis showed that gender, religion, lack of indoor residual spraying of insecticides in the past year, indoor vector density (all species), and not being vaccinated against JE in children were significantly associated with JE positivity. In multivariate analysis, only male gender remained as a significant risk factor. Based on previous estimates of symptomatic: asymptomatic cases of JE, we estimate that there should have been 618 cases from Kushinagar, although only 139 were reported. Vaccination of children and vector control measures emerged as major control activities; they had very poor coverage in the studied villages. In addition, lack of awareness about the cause of JE, lack of faith in the conventional medical healthcare system and multiple referral levels causing delay in diagnosis and treatment emerged as factors likely to result in adverse clinical outcomes.