Spatial clusters of human and livestock anthrax define high-risk areas requiring intervention in Lao Cai Province, Vietnam 1991-2022.

Anthrax, a widespread zoonosis in low and middle-income countries with low disease awareness and insufficient livestock vaccination coverage, has been known in Lao Cai Province in northern Vietnam for years before its apparent absence in 2009, which requires investigation as this infection is frequently reported from neighbouring provinces and countries. We aimed to describe the seasonal patterns of anthrax (1991-2008), compare livestock anthrax vaccine coverage to disease occurrence (1991- 2022), and delineate the high-risk areas to inform local disease surveillance in the province. We illustrated the seasonal pattern of anthrax and provided a comparison between livestock vaccine coverage and disease occurrence by purely spatial SaTScan (Poisson model, 25% population at risk) to detect spatial clusters of human and livestock anthrax using population derived from zonal statistics routines. The number of cases, crude cumulative incidence, and spatial clusters of human and livestock anthrax were mapped in QGIS. Results indicate peak anthrax incidence from May to October. Buffalo, domestic cattle, and horses accounted for 75% of total animal cases. Horse anthrax was more common in Lao Cai than in its neighbours and often occurred in years with human mortality. Vaccination covered less than 30% of the livestock population. We found an apparent pattern where anthrax was controlled from 1998-2003 with higher vaccine coverage (>20%) and identified spatial clusters of human and livestock anthrax in Muong Khuong, Bao Thang, and Bac Ha districts of Lao Cai. The local public health and veterinary agencies are recommended to revisit the high-risk areas and communicate with neighbouring provinces for a regional approach to anthrax surveillance and control.

Spatial epidemiology of human anthrax in Son La province, Vietnam, 2003-2022.

AIMS: Anthrax is reported with frequency but poorly understood in Southeast Asian countries including Vietnam. In Vietnam, anthrax surveillance is national. However, case detection, prevention, and control are implemented locally at the provincial level. Here, we describe the epidemiological characteristics, identify spatial clusters of human anthrax, and compare the variation in livestock anthrax vaccine coverage to disease incidence in humans and livestock using historical data in Son La province, Vietnam (2003-2020). METHODS AND RESULTS: Most human cases occurred between April and September. Most of the patients were male, aged 15-54 years old. The human cases were mainly reported by public district hospitals. There was a delay between disease onset and hospitalization of ~5 days. We identified spatial clusters of high-high incidence communes in the northern communes of the province using the local Moran's I statistic. The vaccine coverage sharply decreased across the study period. The province reported sporadic human anthrax outbreaks, while animal cases were only reported in 2005 and 2022. CONCLUSIONS: These results suggest underreporting for human and livestock anthrax in the province. Intersectoral information sharing is needed to aid livestock vaccination planning, which currently relies on reported livestock cases. The spatial clusters identify areas for targeted surveillance and livestock vaccination, while the seasonal case data suggest prioritizing vaccination campaigns for February or early March ahead of the April peak. A regional approach for studying the role of livestock trading between Son La and neighbouring provinces in anthrax occurrence is recommended.

Spatial analysis of human and livestock anthrax in Lai Chau province, Vietnam (2004-2021).

Anthrax is reported globally with varying disease intensity and seasonality among countries. In Vietnam, anthrax epidemiology and ecology remain understudied. We used historical data of human and livestock anthrax from 2004 to 2021 in Lai Chau province, to identify spatial clusters of human and livestock anthrax, describe epidemiological characteristics, and compare livestock anthrax vaccine coverage to human and livestock disease incidence. Local Moran's I (LISA) using spatial Bayes smoothed commune-level cumulative incidence (per 10,000) for the study period, epidemiological descriptive statistics, livestock vaccine coverage data, and annual incidence rates (per 10,000) at provincial level were used. LISA identified a human anthrax hotspot (high-high) in the southeast which did not overlap spatially with livestock anthrax hotspots in southeastern and northeastern communes. Most human cases were male, aged 15-59 years, handled sick animals, and/or consumed contaminated meat. Almost all cases were reported by grassroot health facilities with a delay of 6.3 days between exposure and case notification to the national surveillance system. 80 % of human cases were reported from June-October. The increase in disease incidence occurred shortly after livestock anthrax vaccine coverage decreased. This study informs vaccination strategy and targeted surveillance and control measures in newly identified high-risk areas and seasons of anthrax.

Spatial and phylogenetic patterns reveal hidden infection sources of Bacillus anthracis in an anthrax outbreak in Son La province, Vietnam.

Bacillus anthracis, the bacterial cause of anthrax, is a zoonosis affecting livestock and wildlife often spilling over into humans. In Vietnam, anthrax has been nationally reportable since 2015 with cases occurring annually, mostly in the northern provinces. In April 2022, an outbreak was reported in Son La province following the butchering of a water buffalo, Bubalus bubalis. A total of 137 humans from three villages were likely exposed to contaminated meat from the animal. Early epidemiological investigations suggested a single animal was involved in all exposures. Five B. anthracis isolates were recovered from human clinical cases along with one from the buffalo hide, another from associated maggots, and one from soil at the carcass site. The isolates were whole genome sequenced, allowing global, regional, and local molecular epidemiological analyses of the outbreak strains. All recovered B. anthracis belong to the A.Br.001/002 lineage based on canonical single nucleotide polymorphism analysis (canSNP). Although not previously identified in Vietnam, this lineage has been identified in the nearby countries of China, India, Indonesia, Thailand, as well as Australia. A twenty-five marker multi-locus variable number tandem repeat analysis (MLVA-25) was used to investigate the relationship between human, soil, and buffalo strains. Locally, four MLVA-25 genotypes were identified from the eight isolates. This level of genetic diversity is unusual for the limited geography and timing of cases and differs from past literature using MLVA-25. The coupled spatial and phylogenetic data suggest this outbreak originated from multiple, likely undetected, animal sources. These findings were further supported by local news reports that identified at least two additional buffalo deaths beyond the initial animal sampled in response to the human cases. Future outbreak response should include intensive surveillance for additional animal cases and additional molecular epidemiological traceback to identify pathogen sources.

Incidence and Spatial distribution of Human and Livestock Anthrax in Cao Bang Province, Vietnam (2004-2020).

Specific knowledge on the distribution of anthrax, a zoonosis caused by Bacillus anthracis, in Southeast Asia, including Vietnam, remains limited. In this study, we describe disease incidence and spatial distribution of human and livestock anthrax using spatially smoothed cumulative incidence from 2004 to 2020 in Cao Bang province, Vietnam. We employed the zonal statistics routine a geographic information system (GIS) using QGIS, and spatial rate smoothing using spatial Bayes smoothing in GeoDa. Results showed higher incidence of livestock anthrax compared with human anthrax. We also identified co-occurrence of anthrax in humans and livestock in northwestern districts and the province center. Livestock anthrax vaccine coverage was <6% and not equally distributed among the districts of Cao Bang province. We provide implications for future studies and recommend improving disease surveillance and response through data sharing between human and animal health sectors.

Informing One Health Anthrax Surveillance and Vaccination Strategy from Spatial Analysis of Anthrax in Humans and Livestock in Ha Giang Province, Vietnam (1999-2020).

Anthrax, caused by Bacillus anthracis, has a nearly global distribution but is understudied in Southeast Asia, including Vietnam. Here, we used historical data from 1999 to 2020 in Ha Giang, a province in northern Vietnam. The objectives were to describe the spatiotemporal patterns and epidemiology of human and livestock anthrax in the province and compare livestock vaccine coverage with human and livestock anthrax incidence. Annual incidence rates (per 10,000) for humans, buffalo/cattle, and goats were used to explore anthrax patterns and for comparison with livestock annual vaccine variations. A data subset describes anthrax epidemiology in humans by gender, age, source of infection, type of anthrax, admission site, and season. Zonal statistics and SaTScan were used to identify spatial and space-time clusters of human anthrax. SaTScan revealed space-time clusters in 1999, 2004, and 2007-2008 in the province, including in the northeastern, eastern, and western areas. Most human anthrax was reported between July and October. Most patients were male, aged 15-59 years, who had handled sick animals and/or consumed contaminated meat. High case-fatality rates were reported with gastrointestinal or respiratory cases. Our data suggest that vaccination in buffalo and cattle reduces the disease burden in humans and vaccinated animals but does not reduce the incidence in unvaccinated animals (goats). This study identified spatial areas of high risk for anthrax and can inform One Health surveillance and livestock vaccination planning in contextual settings similar to Ha Giang province.

Carriage of Plasmid-Mediated Colistin Resistance-1-Positive Escherichia coli in Humans, Animals, and Environment on Farms in Vietnam.

Plasmid-Mediated Colistin Resistance 1 (mcr-1) was first reported in 2015 and is a great concern to human health. In this study, we investigated the prevalence of mcr-1 and mcr-1-positive Escherichia coli (MCRPEC) and the association in infection status among various reservoirs connected to livestock. The study was conducted in 70 poultry and swine farms in a commune in Ha Nam province, northern Vietnam. Samples were collected from farmers, food animals, domestic animals, and farm environments (flies and wastewater) for polymerase chain reaction (PCR) screening for mcr-1 gene and species identification of PCR positive isolates. Among 379 obtained mcr-1 positives isolates, Escherichia coli was the major identified, varying from 50% (2/4) in dog feces to 100% (31/31) in humans feces isolates. The prevalence of MCRPEC was 14.4% (20/139), 49.7% (96/193), 31.3% (25/80), 36.7% (40/109), 26.9% (18/67), and 3.9% (2/51) in humans, chickens, pigs, flies, wastewater, and dogs, respectively. The study identified association between MCRPEC infection status in humans and flies (OR = 3.4), between flies and chickens (OR = 5.3), and between flies and pigs (OR = 9.0). Farmers' age and farm livestock unit were also associated factors of MCRPEC infection status in humans (OR = 5.1 and 1.05, respectively). These findings bring new knowledge on antibiotic resistance in livestock setting and important suggestions on potential role of flies in the transmission of mcr-1 resistance gene.

Inappropriate supply of antibiotics for common viral infections by community pharmacies in Vietnam: A standardised patient survey.

Background: This study aimed to evaluate the appropriateness of antibiotic dispensing of private pharmacies in Vietnam. Methods: Standardised patient surveys were conducted in randomly selected community pharmacies across 40 districts in Vietnam. Four clinical scenarios were represented by patient actors: (a) an adult requesting treatment for a sibling with a viral upper respiratory tract infection (URTI), (b) a parent requesting treatment for a child with acute diarrhoea, (c) an adult making a direct antibiotic request, and (d) an adult presenting with an antibiotic prescription. We calculated the proportion of interactions that resulted in inappropriate supply of antibiotics and patient advice. Predictors of inappropriate antibiotic supply were assessed. Findings: Patient actors attended 949 pharmacies, resulting in 1266 clinical interactions. Antibiotics were inappropriately supplied to 92% (291/316) of adults requesting treatment for URTI symptoms, 43% (135/316) for children with acute diarrhoea symptoms and to 84% (267/317) of direct request for antibiotics. Only 49% of pharmacies advised patients regarding their antibiotic use. Female actors were more likely to be given antibiotics than male actors for URTI (aOR 2·71, 1·12-6·60) but not for diarrhoeal disease. Pharmacies in northern Vietnam were more likely than those in southern Vietnam to supply antibiotics without a prescription: for adult URTI (aOR=5·8, 95% CI: 2·2-14·9) and childhood diarrhoea (aOR=3·5, 95% CI: 2·0-6·0) symptoms, but less likely to dispense for direct antibiotics request. Interpretation: Inappropriate antibiotic supply was common in Vietnamese private pharmacies. Multifaceted measures are urgently needed to achieve WHO's global action plan for the optimal use of antimicrobials. Funding: This study was funded by a grant from the Australian Department of Foreign Affairs and Trade.

Effect of Vitamin D supplementation to reduce respiratory infections in children and adolescents in Vietnam: A randomized controlled trial.

BACKGROUND: It is uncertain whether vitamin D can reduce respiratory infection. OBJECTIVE: To determine whether vitamin D supplementation reduces influenza and other upper viral respiratory tract infections. METHODS: A total of 1300 healthy children and adolescents between the ages of 3 and 17 years were randomized to vitamin D (14 000 U weekly) or placebo for 8 months in Vietnam. The primary outcome was reverse transcriptase (RT)-PCR-confirmed influenza infection, and the coprimary outcome was multiplex PCR-confirmed non-influenza respiratory viruses. Participants, caregivers, and those assessing outcomes were blinded to group assignment. RESULTS: A total of 650 children and adolescents were randomly assigned to vitamin D and 650 to placebo. The mean baseline serum 25-hydroxyvitamin D levels were 65.7 nmol/L and 65.2 nmol/L in the intervention and placebo groups, respectively, with an increase to 91.8 nmol/L in the vitamin D group and no increase, 64.5 nmol/L, in the placebo group. All 1300 participants randomized contributed to the analysis. We observed RT-PCR-confirmed influenza A or B occurred in 50 children (7.7%) in the vitamin D group and in 43 (6.6%) in the placebo group (hazard ratio [HR]: 1.18, 95% CI: 0.79-1.78). RT-PCR-confirmed non-influenza respiratory virus infection occurred in 146 (22.5%) in the vitamin D group and in 185 (28.5%) in the placebo group (hazard ratio [HR]: 0.76, 95% CI: 0.61-0.94). When considering all respiratory viruses, including influenza, the effect of vitamin D in reducing infection was significant, HR: 0.81, 95% CI: 0.66-0.99. CONCLUSION: Vitamin D supplementation did not reduce the incidence of influenza but moderately reduced non-influenza respiratory viral infection.

Chikungunya virus infection of corneal grafts.

BACKGROUND: Chikungunya virus (CHIKV) is an arbovirus with a high potential to spread globally. We investigated whether CHIKV is transmittable via corneal grafts. METHODS: Serum specimens from 69 potential corneal donors living in La Réunion during the 2005­2006 outbreak of CHIKV infection were screened for anti-CHIKV antibodies. Serum specimens and corneoscleral rims were subjected to quantitative reverse-transcription real-time polymerase chain reaction (qRT-PCR) for detection of CHIKV. CHIKV isolation and immunolabeling were performed on eye tissue specimens. Viral transmission via the ocular route was assessed in an animal model of human CHIKV infection. RESULTS: Twelve apparently uninfected donors were viremic and/or positive for immunoglobulin M (IgM) and/or immunoglobulin G. Eye tissue specimens from 12 donors who were or were not viremic and were or were not seropositive were investigated. qRT-PCR detected CHIKV RNA in corneoscleral rims from 4 patients: 1 patient was viremic, 2 were viremic and IgM positive, and 1 was IgM positive. Infectious CHIKV was isolated from all qRT-PCR­positive samples, and antigens were detected in corneal and scleral specimens, the iris, the ciliary body, and oculomotor muscles. CONCLUSIONS: One-third of eligible corneas (4 of 12) from donors apparently uninfected with CHIKV were infected with CHIKV during the study period. CHIKV infects the human cornea and can be transmitted via the ocular route. In the absence of systematic CHIKV screening in donors, cornea donation should be banned in areas where CHIKV circulates.