Search Results (88)

Background: Scrub typhus (ST) is caused by Orientia tsutsugamushi (OT) infection, which is transmitted to humans through the bites of infected chiggers. The clinical presentations range from mild to life-threatening multi-organ dysfunction. This report describes a cluster of ST cases involving five oil palm estate workers in Pekan district, Pahang, Malaysia. Methods: The clinical history, laboratory, and entomological investigation were conducted on the patients, including the index case and four suspected cases in the cluster. Polymerase chain reaction (PCR) tests for OT and genotyping were performed on the patients’ blood and urine samples. Serological testing by indirect immunoperoxidase (IIP) test against Rickettsial diseases was also conducted. Principal Findings: Patients presented with fever, myalgia, headache, rash, cough, and eschar. The index case developed severe ST complicated by acute kidney injury (AKI) and respiratory distress, requiring intubation and ventilation at the intensive care unit of a tertiary hospital. ST was confirmed through PCR analysis of a urine sample, showcasing a novel diagnostic approach. The other four cases were confirmed by a four-fold rise in immunoglobulin G (IgG) antibody titers. Conclusions: oil palm estate workers are at high risk for chigger exposure in Malaysia. Awareness among clinicians and the public of ST is crucial for effective prevention, accurate diagnosis, and optimal management. Full article

Background: Rickettsioses are diseases caused by obligate intracellular non-motile coccobacilli transmitted via arthropods. The most common rickettsioses are scrub typhus (ST), typhus group rickettsioses (TGR), and spotted fever group rickettsioses (SFGR). This study aims to provide information and insight into rickettsioses seropositivity among suspected patients in East and Peninsular Malaysia over a six-year period from 2016 to 2021. Methodology/Principal Findings: Data obtained from four state hospitals and one national research institute providing rickettsial serological testing were analyzed using the IBM SPSS (Statistical Package for the Social Sciences) software program. The six-year analysis revealed that ST had the highest number of seropositivity cases, followed by TGR, and SFGR, for both immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. Of the 3228 samples, 21.6%, 16.1%, and 13.9% of suspected patients were IgM seropositive for ST, TGR, and SFGR, respectively. IgG seropositivity for ST was 21.9%, followed by TGR at 21.4%, and SFGR at 17.2% among suspected rickettsioses cases. All regions in Malaysia were significantly associated with IgM seropositivity for ST, TGR, and SFGR. IgM seropositivity for SFGR was significantly higher in females. Age group 41–65 years was highly associated with IgG seropositivity for ST, TGR, and SFGR. Conclusions/Significance: Analysis of six-year data on ST, TGR, and SFGR seropositivity in Malaysia revealed variations across regions, age groups, and genders. This seropositivity study underscores ST, TGR, and SFGR as possible causes of acute febrile illness among patients suspected of rickettsial disease in Malaysia. The findings contributed to the awareness of reemerging rickettsioses and warrant public health interventions that may reduce the incidence of rickettsioses in Malaysia. Abstract summary: Scrub typhus (ST), typhus group rickettsioses (TGR), and spotted fever group rickettsioses (SFGR) are significant global public health concerns. Our results showed that the highest number of IgM and IgG seropositivity cases was observed for ST, followed by TGR and SFGR. All regions in Malaysia were significantly associated with IgM seropositivity for ST, TGR, and SFGR. East Malaysia exhibited significantly higher seropositivity for ST, TGR, and SFGR than other regions in Malaysia. IgM seropositivity for SFGR was significantly higher in females. The age group 41–65 years was highly associated with IgG seropositivity for ST, TGR, and SFGR. This study highlights the value of serological data in uncovering the hidden burden of disease in Malaysia. In addition, the findings contributed to bridging knowledge gaps on the limited data from Malaysia spanning extended periods, despite being one of the countries in the endemic Tsutsugamushi Triangle. The findings from this study may direct future research on rickettsioses and warrant public health interventions in Malaysia. Full article

Scrub typhus is an acute febrile vector-borne infectious disease caused by Orientia tsutsugamushi (O. tsutsugamushi) and transmitted through the bite of infected chigger mite larvae. Transmission involves complex ecological interactions among vectors, hosts, and environmental factors. Accumulating evidence indicates complex interactions between the scrub typhus incidence and multilevel environmental determinants, encompassing meteorological factors (e.g., temperature, humidity, precipitation, wind speed, sunshine duration, and atmospheric pressure), geographical conditions (e.g., topography, elevation, and landcover), and socioeconomic factors (e.g., economic level, cultural practices, residential conditions, and human behaviors). However, significant discrepancies persist among studies regarding the effect sizes and temporal associations, and the precise mechanisms remain incompletely elucidated. This review synthesizes the evidence on environment–disease relationships, clarifies the methodological inconsistencies, analyzes the potential sources of heterogeneity, and highlights the critical knowledge gaps to inform targeted prevention and control strategies and guide future research priorities. Full article

Scrub typhus is an emerging chigger-borne disease caused by the obligate intracellular bacterium Orientia tsutsugamushi. Necroptosis is a form of programmed cell death (PCD) mediated by RIPK3 (serine/threonine kinase receptor interacting protein 3) and its downstream effector MLKL (mixed-lineage kinase domain-like). While O. tsutsugamushi modulates apoptosis, another form of PCD, its interplay with necroptosis is unknown. Much of Orientia pathobiology is linked to its ankyrin repeat (AR)-containing effectors (Anks). Two of these, Ank1 and Ank6, share similarities with the cowpox AR protein, vIRD (viral inducer of RIPK3 degradation) that prevents necroptosis. Here, we show that Ank1 and Ank6 reduce RIPK3 cellular levels although not as robustly as and mechanistically distinct from vIRD. Orientia infection lowers RIPK3 amounts and does not elicit necroptosis in endothelial cells. In HeLa cells ectopically expressing RIPK3, Orientia fails to inhibit RIPK3 and MLKL phosphorylation as well as cell death. MLKL colocalization with Orientia or Listeria monocytogenes, another intracytoplasmic pathogen, was not observed. Thus, O. tsutsugamushi reduces cellular levels of RIPK3 and does not elicit necroptosis but cannot inhibit this PCD pathway once it is induced. This study is a first step toward understanding how the relationship between Orientia and necroptosis contributes to scrub typhus pathogenesis. Full article

Chiggers (chigger mites) and gamasid mites are two groups of ectoparasites on rodents, and they can be the vectors or potential vectors of scrub typhus and hemorrhagic fever with renal syndrome (HFRS), while Bower’s white-toothed rat (Berylmys bowersi) can serve as the reservoir host of the diseases. Based on field investigations at 117 survey sites of southwest China, a total of 2512 mites were collected from 55 B. bowersi rats. Under a microscope, these mites were taxonomically identified as 56 distinct species, comprising 37 chigger mite species and 19 gamasid mite species. The mite infestation burdens on B. bowersi were heavy, with a high prevalence (P_M = 85.45%), mean abundance (MA = 45.67), and intensity (MI = 53.45). Of 56 mite species identified, 7 are vectors of scrub typhus and HFRS. Of the seven vector mite species, Leptotrombidium scutellare was one of dominant chigger species, with a higher infestation index on rats (P_M = 21.82%, MA = 7.76) than the other six vector mite species. The sex ratio of female gamasid mites was higher than that of males. The number and infestation of adult gamasid mites were higher than those of immature mites. The infestation indexes of mites on B. bowersi hosts varied with the host’s sex and age and fluctuated along different environmental gradients. The association coefficient (V) showed a slight positive association between chiggers and gamasid mites, suggesting that these two groups of mites may coexist on B. bowersi rats. Spearman correlation coefficients showed positive correlations among some dominant and vector mite species, indicating that some mite species tend to select the same hosts. A total of 69 mite species (47 chigger mite species and 22 gamasid mite species) on B. bowersi were estimated by species rarefaction and extrapolation curves. In conclusion, Berylmys bowersi has a high susceptibility to mite infestation, and it has the potential to harbor abundant mites, with heavy mite burdens. The occurrence of vector mite species, especially L. scutellare (the dominant species), increases the potential risk of transmission and the focus persistence of scrub typhus and HFRS in southwest China. Full article

Background/Objectives: Before the Coronavirus disease 2019 (COVID-19) era, the global prevalence of pulmonary arterial hypertension (PAH) was between 0.4 and 1.4 per 100,000 people. The long-term effects of protracted COVID-19 associated with pulmonary vascular disease (PVD) risk factors may increase this prevalence. According to preliminary data, the exact prevalence of early estimates places the prevalence of PVD in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 22%, although its predictive value remains unknown. PVD caused by COVID-19 co-infections is understudied and underreported, and its future impact is unclear. However, due to COVID-19/co-infection pathophysiological effects on pulmonary vascularization, PVD mortality and morbidity may impose a genuine concern—both now and in the near future. Based on reported studies, this literature review focused on the potential link between COVID-19, parasitic co-infection, and PVD. This review article also highlights hypothetical pathophysiological mechanisms between COVID-19 and parasitic co-infection that could trigger PVD. Methods: We conducted a systematic literature review (SLR) searching peer-reviewed articles, including link between COVID-19, parasitic co-infection, and PVD. Results: This review hypothesized that multiple pathways associated with pathogens such as underlying schistosomiasis, human immunodeficiency virus (HIV), pulmonary tuberculosis (PTB), pulmonary aspergillosis, Wuchereria bancrofti, Clonorchis sinensis, paracoccidioidomycosis, human herpesvirus 8, and scrub typhus coupled with acute or long COVID-19, may increase the burden of PVD and worsen its mortality in the future. Conclusions: Further experimental studies are also needed to determine pathophysiological pathways between PVD and a history of COVID-19/co-infections. Full article

Scrub typhus is a mite-borne, re-emerging public health problem in India, particularly in Tamil Nadu, South India. More than 40 serotypes of Orientia tsutsugamushi have been documented worldwide. However, the information on the circulation of its molecular sub-types in India is scanty. A retrospective study was conducted among serologically confirmed cases of scrub typhus. DNA isolated from blood was screened by a nested polymerase chain reaction (nPCR) targeting the GroEL and the 56 kDa type-specific antigen (TSA) genes. Out of 59 samples, 14 partial fragments of GroEL and the twelve 56 kDa genes were PCR-amplified and DNA-sequenced. The neighbor-joining (NJ) analysis indicated three distinct phylogenetic clades, including a novel genotype designated as Ot-Thanjavur-Tamil Nadu (Ot-TJTN, 9 nos. 64.3%); Karp-like (4 nos. 28.6%); and Kuroki-Gilliam type (1 no. 7.1%). Also, phylogenetic analysis of twelve 56 kDa variable domains (VDΙ-ΙΙΙ) of TSA gene sequences revealed a distinctive new genotypic cluster of eight samples (66.6%), and the remaining four (33.4%) were Karp-like genotypes. The Simplot analysis for the similarity and event of recombination testing elucidated the existence of the new genotype of the Ot-TJTN cluster, which was undescribed so far, in the Kato and TA716 lineages. The significant findings recommend further studies to understand the ongoing transmission dynamics of different O. tsutsugamushi strains in vector mites, rodent hosts, and humans in this region. Full article

Scrub typhus, caused by Orientia tsutsugamushi, is a neglected and reemerging disease that causes considerable morbidity and mortality. It now extends beyond the Tsutsugamushi Triangle, the region wherein it has traditionally been endemic. Influenza has also resurged since the infection control measures against COVID-19 were relaxed. A few cases of scrub typhus and influenza co-infection have been reported. Herein, we report the case of a 74-year-old woman with fever and upper respiratory symptoms diagnosed with influenza A and treated with oseltamivir; however, her fever persisted, and she developed respiratory failure, liver dysfunction, headache, diarrhea, and an erythematous skin rash. She lived in a forested area where scrub typhus was endemic and worked on a farm. Physical examination revealed an eschar on her posterior neck, and she was diagnosed with scrub typhus and influenza A co-infection. After minocycline treatment, her symptoms improved within a few days. This is the first reported case of scrub typhus and influenza A co-infection in Japan. This case illustrates that co-infection should be suspected in patients with fever persisting after their initial infection has been treated and that in patients living in endemic areas, scrub typhus can occur concurrently with influenza. The symptoms of scrub typhus are flu-like and nonspecific, which may delay diagnosis and treatment. Full article

Scrub typhus is caused by intracellular bacteria belonging to the genus Orientia. Until 2010, the endemic region was thought to be restricted to the Asia–Pacific region. Orientia species have recently been discovered in South America, Africa, Europe, and North America. In accordance with these circumstances, we tried to find new or novel bacterial strains in the Republic of Korea (ROK). We found that a new strain of O. tsutsugamushi formed a unique clade based on a 56-kDa type-specific antigen gene and showed 63.2–77.8% similarity to other strains of the same species. Additionally, we identified another sequence with 99.8% similarity to the O3 strain, which has not been recorded in the ROK and whose pathogenicity remains unknown. These findings confirm the diversity of O. tsutsugamushi strains in the ROK, and highlight the need for continued surveillance and further studies to characterize the pathogenicity of this novel bacterial strain. Full article

Background/Objectives: This study explores the potential of using elevated levels of blood double-stranded RNA (dsRNA) as a diagnostic tool for severe fever with thrombocytopenia syndrome (SFTS) infection. Methods: Blood samples from SFTS patients were collected, dsRNA was purified, and total dsRNA expression was quantitatively analyzed using a spiropyran-based method. Comparative analysis was performed using blood samples from healthy individuals and scrub typhus patients with similar symptoms. Results: The results revealed that individuals infected with SFTS had significantly higher total blood dsRNA levels compared to healthy or scrub typhus controls. The dsRNA-based method also has potential for assessing infection severity based on dsRNA levels. Conclusions: These findings suggest that total dsRNA expression can serve as a quick and convenient method to differentiate SFTS from other non-viral conditions with similar clinical presentations. This method shows promise as a novel diagnostic tool. Full article

While urbanization leads to habitat loss for medium and large mammals, small mammals can survive in fragmented habitats. As they are known to be the primary hosts of chigger mites (Acari: Trombiculidae) that transmit scrub typhus, their habitat can be considered the primary distribution area for chigger mites. This study aims to examine the distribution of small mammals and chigger mites in four habitat types and analyzed species richness, mean intensity (MI), dominance, and infestation rate (IR). A total of six small mammal species were captured, 76.8% of which were identified as Apodemus agrarius. Species richness of small mammals was highest in forests, followed by ecotones, grasslands, and agricultural lands. Apodemus agrarius accounted for 61% of the captures in forests, 80% in ecotones, 84% in grasslands, and 50% in agricultural lands, highlighting its varying dominance across habitat types. The MI of chigger mites was higher in grasslands (215.41 ± 20.70) and ecotones (171.67 ± 30.33) and lower in forests (76.67 ± 32.11). The MI of chigger mites was higher in the fall than that in the spring, and according to the MaxEnt model, they had a narrow, dense distribution in the fall and a wide distribution in the spring. These results suggest that inducing increased species richness of small mammalian hosts by habitat management and vegetation diversification may contribute to a reduction in the MI of chigger mites. Full article

Chiggers are the exclusive vector of Orientia tsutsugamushi, which is the causative agent of scrub typhus. Based on the field surveys in southwest China between 2001 and 2022, this paper retrospectively reported the chigger infestation and distribution on the large-eared field mouse (Apodemus latronum), an endemic rodent species in the region, for the first time. A total of 933 chiggers were collected from 501 mice, and these chiggers were identified as 2 families, 8 genera, and 61 species. The overall infestation prevalence (P_M) and mean abundance (MA) of A. latronum with chiggers reached 19.76% and 1.86 mites/per mouse, respectively. The chigger infestation indices on adult A. latronum (P_M = 38.28%, MA = 5.11) were higher than those on juvenile mice (P_M = 12.63%, MA = 0.97) with p < 0.01, showing an age bias of infestation. The relative fatness (K) was used to reflect the nutrition status of the mouse host. The mouse hosts with good nutrition (K = 3.4 ± 0.89 g/cm³) harbored fewer chiggers than the hosts with poor nutrition (K = 2.2 ± 0.90 g/cm³) (p < 0.01). The infestation indices of chiggers on A. latronum obviously fluctuated along different altitude gradients (p < 0.01). With the increase in altitudes, the β diversity of the chigger community showed a gradually increasing tendency. The spillover chord diagram, which was based on indices of PAC (potential for apparent competition), revealed high spillover potentials of dominant chigger species dispersing from high altitude gradients to the lowest one. The chigger abundance was positively correlated with the mean monthly temperature (tmp), mean monthly humidity (hum), the mean monthly precipitation (pre), and the human footprint (hfp), and it was negatively correlated with the altitude (ele) (p < 0.05). The temperature and humidity are the most important factors which influence the chigger infestation. Full article

Chiggers (chigger mites) are a group of tiny arthropods, and they are the exclusive vector of Orientia tsutsugamushi (Ot), the causative agent of scrub typhus (tsutsugamushi disease). Dehong Prefecture in Yunnan Province of southwest China is located on the China–Myanmar border and is an important focus of scrub typhus. Based on the field surveys in Dehong between 2008 and 2022, the present paper reports the infestation and ecological distribution of chiggers on the body surface of rodents and other sympatric small mammals (shrews, tree shrews, etc.) in the region for the first time. The constituent ratio (C_r), prevalence (P_M), mean abundance (MA), and mean intensity (MI) were routinely calculated to reflect the infestation of small-mammal hosts with chiggers. Additionally, the species richness (S), Shannon–Wiener diversity index (H), Simpson dominance index (D), and Pielou’s evenness index (E) were calculated to illustrate the chigger community structure. Preston’s log-normal model was used to fit the theoretical curve of species abundance distribution, and the Chao 1 formula was used to roughly estimate the expected total species. The “corrplot” package in R software (Version 4.3.1) was used to analyze interspecific relationships, and the online drawing software was used to create a chord diagram to visualize the host–chigger associations. From 1760 small-mammal hosts, a total of 9309 chiggers were identified as belonging to 1 family, 16 genera, and 117 species, with high species diversity. The dominant chigger species were Leptotrombidium deliense, Walchia ewingi, and Gahrliepia longipedalis, with a total C_r = 47.65% (4436/9309), among which L. deliense is the most important vector of Ot in China. The overall infestation indexes (P_M, MA, and MI) and community parameters (S, H, and E) of chiggers in the mountainous areas and outdoors were higher than those in the flatland areas and indoors, with an obvious environmental heterogeneity. Leptotrombidium deliense was the dominant species in the flatland and indoors, while G. longipedalis was the prevalent species in the mountainous and outdoor areas. The species abundance distribution of the chigger community conformed to log-normal distribution with the theoretical curve equation: ${S\left(R\right)}^{\prime }=28e^{{-[0.23(R-0)]}^2}$, indicating the existence of many rare species and only a few dominant species in the community. The expected total number of chigger species was roughly estimated to be 147 species, 30 more than the 117 species actually collected, suggesting that some uncommon species may have been missed in the sampling survey. The host–parasite association analysis revealed that one host species can harbor different chigger species, and one chigger species can parasitize different host species with low host specificity. A positive or negative correlation existed among different chigger species, indicating a cooperative or competitive interspecific relationship. The species diversity of chiggers is high in Dehong on the China–Myanmar border, and a large host sample is recommended to find more uncommon species. There is an obvious environmental heterogeneity of the chigger community, with different species diversity and dominant species in different environments. The low host specificity of chiggers and the occurrence of a large number of L. deliense in Dehong, especially in flatland areas and indoors, would increase the risk of persistent transmission of scrub typhus in the region. Full article

Scrub typhus is caused by the Gram-negative obligate intracellular bacterium Orientia tsutsugamushi, and this tick-borne disease is difficult to distinguish from other acute febrile illnesses as it typically presents with symptoms such as rash, crusting at the bite site, headache, myalgia, lymphadenopathy, and elevated liver transaminases. It can often be diagnosed clinically, but not all patients present with characteristic symptoms, so serological diagnosis and molecular techniques may be required. However, existing diagnostic tests often have low sensitivity and specificity, making early detection difficult. This study presents a nucleic acid extraction method using large volumes of plasma and buffy coat to increase sensitivity, as well as an improved detection method using two target genes. Using the I-PULL device, nucleic acids can be extracted from up to 4 mL of sample in 30 min, avoiding contamination. The extracted DNA detects two genes of O. tsutsugamushi, increasing sensitivity compared to single-gene detection. Clinical validation in 38 patient samples showed 100% specificity and 95.24% sensitivity for the single target gene, with specificity and sensitivity rising to 100% when both genes are analyzed. This molecular diagnostic platform can be useful for distinguishing scrub typhus from similar diseases. Full article

Prior to the devastating earthquake in Nepal in 2015, scrub typhus was not recognized as a highly endemic disease in the country. This contrasted with neighboring India, where scrub typhus is endemic and there have been sporadic outbreaks of severe forms. This discrepancy underscores the limitations in our comprehensive understanding of the scrub typhus epidemiological patterns in Nepal, especially before 2015. To better understand the dynamic and current status of scrub typhus, this study investigated its prevalence among patients with acute febrile illness in two hospitals located in Pokhara city, Kaski district and Bharatpur city, Chitwan district during 2009–2010. Our findings revealed that 31.5% (239 of 759 patients) of the cases were positives for scrub typhus based on serological and pathogen detection assays. These results provide crucial insights into the pre-earthquake endemicity of scrub typhus in Nepal, implying its long-standing presence in the region prior to the significant environmental transformations caused by the 2015 earthquake. This study also emphasizes the need for heightened awareness and improved diagnostic capabilities to effectively manage and control scrub typhus, which remains a significant public health concern in Nepal. Full article