Scrub Typhus

Scrub typhus, caused by Orientia tsutsugamushi, is an important and neglected vector-borne zoonotic disease with an expanding known distribution. The ecology of the disease is complex and poorly understood, impairing discussion of public health interventions. To highlight what we know and the themes of our ignorance, we conducted a systematic review of all studies investigating the pathogen in vectors and non-human hosts. A total of 276 articles in 7 languages were included, with 793 study sites across 30 countries. There was no time restriction for article inclusion, with the oldest published in 1924. Seventy-six potential vector species and 234 vertebrate host species were tested, accounting for over one million trombiculid mites ('chiggers') and 83,000 vertebrates. The proportion of O. tsutsugamushi positivity was recorded for different categories of laboratory test and host species. Vector and host collection sites were geocoded and mapped. Ecological data associated with these sites were summarised. A further 145 articles encompassing general themes of scrub typhus ecology were reviewed. These topics range from the life-cycle to transmission, habitats, seasonality and human risks. Important gaps in our understanding are highlighted together with possible tools to begin to unravel these. Many of the data reported are highly variable and inconsistent and minimum data reporting standards are proposed. With more recent reports of human Orientia sp. infection in the Middle East and South America and enormous advances in research technology over recent decades, this comprehensive review provides a detailed summary of work investigating this pathogen in vectors and non-human hosts and updates current understanding of the complex ecology of scrub typhus. A better understanding of scrub typhus ecology has important relevance to ongoing research into improving diagnostics, developing vaccines and identifying useful public health interventions to reduce the burden of the disease.

BackgroundScrub typhus, a vector-borne zoonotic infection caused by the bacteria Orientia tsutsugamushi, is one of the most common and clinically important rickettsial infections worldwide. An estimated one million cases occur annually with a high case fatality rate. Although scrub typhus is a major public health threat in India, the burden and distribution remains unclear. We aimed to estimate the burden of scrub typhus in India.MethodologyWe performed a systematic review of published literature on scrub typhus from India to extract information on epidemiology, morbidity, and mortality. Important databases were searched using keywords and appropriate combinations. We identified observational, interventional, and population-based studies and extracted the data to evaluate the number of cases diagnosed using serology or PCR and the number of deaths due to scrub typhus. We conducted a systematic narrative synthesis to summarize included studies.Principal findingsIn the last decade, there were 18,781 confirmed scrub typhus cases reported in 138 hospital-based studies and two community-based studies. IgM ELISA was used in 122 studies to confirm the cases in majority (89%). The proportion of scrub typhus among acute undifferentiated febrile illness (AUFI) studies was 25.3%, and community seroprevalence was 34.2%. Ninety studies had data published on multiple organ involvement out of which 17.4% of cases had multiple organ dysfunction syndromes, 20.4% patients required ICU admission, and 19.1% needed ventilation. The overall case-fatality rate was 6.3%, and the mortality among those with multi-organ dysfunction syndrome was as high as 38.9%.Conclusion/significanceScrub typhus, a common acute febrile illness in India causing severe morbidity, accounts for a large number of deaths. The burden of the disease has been underappreciated. Early diagnosis and prompt treatment can significantly reduce complications and mortality. Establishing good surveillance and instituting appropriate control measures are urgently needed.

Scrub typhus is a potentially fatal rickettsiosis caused by Orientia species intracellular bacteria of the genus Orientia. Although considered to be restricted to the Asia Pacific region, scrub typhus has recently been discovered in southern Chile. We analyzed Orientia gene sequences of 16S rRNA (rrs) and 47-kDa (htrA) from 18 scrub typhus patients from Chile. Sequences were ≥99.7% identical among the samples for both amplified genes. Their diversity was 3.1%-3.5% for rrs and 11.2%-11.8% for htrA compared with O. tsusugamushi and 3.0% for rrs and 14.8% for htrA compared with Candidatus Orientia chuto. Phylogenetic analyses of both genes grouped the specimens from Chile in a different clade from other Orientia species. Our results indicate that Orientia isolates from Chile constitute a novel species, which, until they are cultivated and fully characterized, we propose to designate as Candidatus Orientia chiloensis, after the Chiloé Archipelago where the pathogen was identified.

Orientia tsutsugamushi (Ot), the causative agent of tsutsugamushi disease (TD), has been detected in Muridae, Soricidae, Cricetidae, Canidae, Artiodactyla, and birds, as well as in its trombiculid mite vectors. However, to date, scarce reports have documented Ot infection in bats. TD is an ancient zoonotic disease transmitted through the bite of infected trombiculid mites. The global disease burden of TD, particularly in impoverished regions, warrants renewed attention and a reevaluation of public health strategies. In this study, we analyzed bat samples for Ot using nested PCR (nPCR) and real-time quantitative PCR (qPCR) for both qualitative and quantitative detection. Genetic evolution and divergence time of the detected Ot sequences were assessed using bioinformatics tools, including BioAider, Clustal X2, MEGA-X, and BEAST. Ot was detected in 7.32% (44/601) of bat samples by qPCR. At least three genotypes, including Karp, Gilliam, and Kato, were identified in both insectivorous bats (Hipposideros larvatus and Hipposideros armiger) and frugivorous bats (Rousettus amplexicaudatus and Cynopterus sphinx). Ot DNA was detected in multiple tissues, including heart, kidney, spleen, lung, rectum, liver, and brain, with median copy numbers ranging from 28.60 to 1069.76 copies/μL. Notably, divergence analysis suggests that Ot isolated from bats emerged around 126 AD, later than its appearance in rodents, humans, and chiggers (approximately 4140 BC), indicating that Ot infection in bats may originate from other animals or vectors. Our findings recommend ongoing monitoring of Ot in bats and their ectoparasites, which will provide a basis for risk assessment and guide strategies for the prevention and control of scrub typhus.