Insight of Zoonotic Viruses at Human-Animal Interfaces in Cambodia

*Presenting author Emerging infectious diseases have been causing outbreaks in humans for centuries and most infectious diseases originate in animals. Re-emerging zoonotic pathogens are rapidly increasing in prevalence or geographic range and causing a significant and growing threat to global health. The present work provides an insight of zoonotic viruses risk at human-bat/rodent interfaces in Cambodia. We conducted studies to investigate the circulation of zoonotic viruses and the risk of exposure in human living at the interfaces with bats and rodents. Rodent's samples were collected in rural and urban areas of Cambodia. Organs were tested for Hantavirus, Orthohepevirus species C and Arenavirus. Bat's samples were collected in Steung Treng for Sarbecovirus and in Battambang and Kandal for Nipah virus detection. People working/living at the human-animal interfaces were screened for IgG antibodies. In rodents (750), hantavirus was detected in 3.3% rodents from urban areas only. Seoul orthohantavirus was the most predominant virus followed by Thottapalayam virus. HEV-C was detected only in rodents from urban settings (1.8%). Arenavirus was detected in both rural (6.8%) and urban (2.5%) areas. In humans (788), the seroprevalence of IgG antibodies against hantavirus, HEV-A and Arenavirus was 10.0%, 24% and 23.4% respectively. NiV was detected in flying fox's urines collected between 2013-2016 in Kandal (0.63%) and in Battambang (1.03%). Blood samples collected in both provinces were negative for NiV antibodies. SARS-CoV-2 related virus was detected in Rhinolphus shameli in Steung Treng in 2010, 2020 and 2021. Blood samples from people living at the vicinity of positive bats were positive for antibodies against CoV (7.7%), but no specific neutralizing SARS-CoV2 antibodies were detected. Our studies provided insight of the risk of zoonoses in Cambodia and highlighted the importance of zoonotic surveillance and further One Health effort to prevent, detect, and respond to future cross-species transmission.Copyright © 2023

Metagenomic Next-Generation Sequencing of Nasopharyngeal Swabs in Acute Febrile Illness in Cambodia

Background. There is growing recognition of metagenomic next-generation sequencing (mNGS) as a valuable diagnostic tool capable of providing unbiased pathogen detection, but data on performance in low-resource settings remains scant. Here, we use mNGS of nasopharyngeal (NP) swabs taken from subjects in Cambodia to identify potential pathogens causing acute febrile illness. Methods. Febrile subjects aged 2 months to 65 years were enrolled in a crosssectional study conducted across 4 tertiary hospitals in Cambodia. NP swabs were collected at hospital presentation. Depending on reported symptom constellations, sera was also taken in a subset of subjects for comparison of mNGS results. RNA was isolated from biosamples, converted to cDNA libraries, and sequenced on a NextSeq2000 (Illumina). Raw sequence reads were stripped for host reads and aligned to NCBI nucleotide and protein databases using a cloud-based bioinformatics platform (CZID). Results. NP swabs were collected from 97 subjects between April 2020 and June 2021. Subjects were predominantly male (53.6%) and young (median age 3 years [IQR 1-25]). Pathogens were identified in 42 (43.2%) NP swabs;of these, 26 (61.9%) were respiratory viruses including 9 rhinovirus, 7 coronavirus (1 SARS-CoV-2), and 5 respirovirus cases. Co-infection was identified in 3 subjects with coronavirus and respirovirus (N=2) and coronavirus and rhinovirus (N=1). Of subjects with paired sera and NP samples (N=61), 18 (29.5%) had positive NP swabs but negative sera, 7 (11.5%) had negative NP swabs but positive sera, 12 (19.7%) had positive NP swabs and sera, and 24 (39.3%) had negative NP swabs and sera. Pathogen hits correlated in NP swabs and sera in 10 of 12 subjects, including six subjects with chikungunya. Conclusion. mNGS can be successfully implemented in low-resource settings to identify emerging pathogens and common respiratory pathogens, including coinfecting pathogens, from NP swabs of febrile patients. mNGS may also be able to detect chikungunya from NP swab alone, raising the possibility of non-invasive diagnostics for infections associated with high viremic states.

Stochastic Reaction Network Modeling and Optimal Control for Covid-19

In this paper, we aim to build and study a stochastic SEIRS model with vaccination in which we consider two types of infected: undetected and confirmed. The latter are hospitalized and receive treatment. We also derive the Hamilton Jacobi Bellman (HJB) equation by using dynamic programming tools, and we study it from theoretical and numerical points of view. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.