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.

Tropical infectious diseases diagnosis and surveillance are often hampered by difficulties of sample collection and transportation. Filter paper potentially provides a useful medium to help overcome such problems. We reviewed the literature on the use of filter paper, focusing on the evaluation of nucleic acid and serological assays for diagnosis of infectious diseases using dried blood spots (DBS) compared with recognized gold standards. We reviewed 296 eligible studies and included 101 studies evaluating DBS and 192 studies on other aspects of filter paper use. We also discuss the use of filter paper with other body fluids and for tropical veterinary medicine. In general, DBS perform with sensitivities and specificities similar or only slightly inferior to gold standard sample types. However, important problems were revealed with the uncritical use of DBS, inappropriate statistical analysis, and lack of standardized methodology. DBS have great potential to empower healthcare workers by making laboratory-based diagnostic tests more readily accessible, but additional and more rigorous research is needed.

ObjectivesIntestinal carriage constitutes an important reservoir of antimicrobial-resistant bacteria, with some of the highest rates reported from Asia. Antibiotic resistance has been little studied in Laos, where some antibiotics are available without restriction, but others such as carbapenems are not available.Patients and methodsWe collected stools from 397 healthy children in 12 randomly selected pre-school childcare facilities in and around Vientiane. Colonization with ESBL-producing Enterobacteriaceae (ESBLE) and carbapenemase-producing Enterobacteriaceae (CPE) was detected using a disc diffusion screening test and ESBLE were characterized using WGS. Risk factor data were collected by questionnaire.ResultsNinety-two children (23%) were colonized with ESBLE, mainly Escherichia coli carrying blaCTX-M and Klebsiella pneumoniae carrying blaSHV or blaCTX-M, which were frequently resistant to multiple antibiotic classes. Although residence in Vientiane Capital, foreign travel, higher maternal level of education, antibiotic use in the preceding 3 months and attending a childcare facility with a ‘good’ level of hygiene were all associated with ESBLE colonization on univariable analysis, a significant association remained only for antibiotic use when a stepwise approach was used with a multivariate random-effects model. WGS analysis suggested transmission in both childcare facilities and community settings.ConclusionsThe high prevalence of paediatric colonization with ESBLE in Laos, one of the highest reported in Asia, is probably the result of inappropriate antibiotic use. Paediatric colonization with CPE was not identified in this study, but it is important to continue to monitor the spread of antibiotic-resistant Enterobacteriaceae in Laos.

ObjectiveTablet splitting is frequently performed to facilitate correct dosing, but the practice and implications in low-income settings have rarely been discussed.MethodsWe selected eight drugs, with narrow therapeutic indices or critical dosages, frequently divided in the Lao PDR (Laos). These were split, by common techniques used in Laos, by four nurses and four laypersons. The mean percentage deviation from the theoretical expected weight and weight loss of divided tablets/capsules were recorded.ResultsFive of eight study drugs failed, on splitting, to meet European Pharmacopoeia recommendations for tablet weight deviation from the expected weight of tablet/capsule halves with 10% deviating by more than 25%. There was a significant difference in splitting accuracy between nurses and laypersons (P = 0.027). Coated and unscored tablets were less accurately split than uncoated (P = 0.03 and 0.0019 for each half) and scored (0.0001 for both halves) tablets.ConclusionThese findings have potential clinical implications on treatment outcome and the development of antimicrobial resistance. Investment by drug companies in a wider range of dosage units, particularly for narrow therapeutic index and critical dosage medicines, is strongly recommended.

Melioidosis, a severe infection with the environmental bacterium Burkholderia pseudomallei, is being recognised increasingly frequently. What determines its uneven distribution within endemic areas is poorly understood. We cultured soil from a rice field in Laos for B. pseudomallei at different depths on 4 occasions over a 13-month period. We also measured physical and chemical parameters in order to identify associated characteristics. Overall, 195 of 653 samples (29.7%) yielded B. pseudomallei. A higher prevalence of B. pseudomallei was found at soil depths greater than the 30 cm currently recommended for B. pseudomallei environmental sampling. B. pseudomallei was associated with a high soil water content and low total nitrogen, carbon and organic matter content. Our results suggested that a sampling grid of 25 five metre square quadrats (i.e. 25 × 25 m) should be sufficient to detect B. pseudomallei at a given location if samples are taken at a soil depth of at least 60 cm. However, culture of B. pseudomallei in environmental samples is difficult and liable to variation. Future studies should both rely on molecular approaches and address the micro-heterogeneity of soil when investigating physico-chemical associations with the presence of B. pseudomallei.

BackgroundScrub typhus is a major cause of acute febrile illness in the tropics and is endemic over large areas of the Asia Pacific region. The national and global burden of scrub typhus remains unclear due to limited data and difficulties surrounding diagnosis. Methodology/Principal findingsScrub typhus reporting data from 2003-2018 were collected from the Thai national disease surveillance system. Additional information including the district, sub-district and village of residence, population, geographical, meteorological and satellite imagery data were also collected for Chiangrai, the province with the highest number of reported cases from 2003 . From 2003,345 cases of scrub typhus were reported with the number of reported cases increasing substantially over the observed period. There were more men than women, with agricultural workers the main occupational group affected. The majority of cases occurred in the 15-64 year old age group (72,144/99,543, 72%). Disease burden was greatest in the northern region, accounting for 53% of the total reported cases per year (mean). In the northern region, five provinces-Chiangrai, Chiangmai, Tak, Nan and Mae Hong Son-accounted for 84% (46,927/55,872) of the total cases from the northern region or 45% (46,927/103,345) of cases nationally. The majority of cases occurred from June to November but seasonality was less marked in the southern region. In Chiangrai province, elevation, rainfall, temperature, population size, habitat complexity and diversity of land cover contributed to scrub typhus incidence. PLOS NEGLECTED TROPICAL DISEASESPLOS Neglected Tropical Diseases | https://doi.

Background Scrub typhus is an important neglected vector-borne zoonotic disease across the Asia–Pacific region, with an expanding known distribution. The disease ecology is poorly understood, despite the large global burden of disease. The key determinants of high-risk areas of transmission to humans are unknown. Methods Small mammals and chiggers were collected over an 18-month period at three sites of differing ecological profiles with high scrub typhus transmission in Chiang Rai Province, northern Thailand. Field samples were identified and tested for Orientia tsutsugamushi by real-time PCR. The rates and dynamics of infection were recorded, and positive and negative individuals were mapped over time at the scale of single villages. Ecological analyses were performed to describe the species richness, community structure and interactions between infected and uninfected species and habitats. Generalised linear modelling (GLM) was applied to examine these interactions. Results The site with the highest rates of human infection was associated with the highest number of infected chigger pools (41%), individual chiggers (16%), proportion of the known vector species Leptotrombidium deliense (71%) and chigger index (151). Chigger species diversity was lowest (Shannon diversity index H′: 1.77) and rodent density appeared to be high. There were no consistent discrete foci of infection identified at any of the study sites. The small mammals Rattus tanezumi and Bandicota indica and the chiggers L. deliense and Walchia kritochaeta emerged as central nodes in the network analysis. In the GLM, the end of the dry season, and to a lesser extent the end of the wet season, was associated with O. tsutsugamushi-infected small mammals and chiggers. A clear positive association was seen between O. tsutsugamushi-positive chigger pools and the combination of O. tsutsugamushi-positive chigger pools and O. tsutsugamushi-positive small mammals with lowland habitats. Conclusions These findings begin to reveal some of the factors that may determine high-risk foci of scrub typhus at a fine local scale. Understanding these factors may allow practical public health interventions to reduce disease risk. Further studies are needed in areas with diverse ecology. Graphical abstract

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