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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.

Orientia tsutsugamushi, spotted fever group rickettsioses, and typhus group rickettsioses (TGR) are reemerging causes of acute febrile illness (AFI) in Southeast Asia. To further delineate extent, we enrolled patients >4 weeks of age with nonmalarial AFI in Sabah, Malaysia, during 2013-2015. We confirmed rickettsioses (past or acute, IgG titer >160) in 126/354 (36%) patients. We confirmed acute rickettsioses (paired 4-fold IgG titer rise to >160) in 38/145 (26%) patients: 23 O. tsutsugamushi, 9 spotted fever group, 4 TGR, 1 O. tsutsugamushi/spotted fever group, and 1 O. tsutsugamushi/TGR. PCR results were positive in 11/319 (3%) patients. Confirmed rickettsioses were more common in male adults; agricultural/plantation work and recent forest exposure were risk factors. Dizziness and acute hearing loss but not eschars were reported more often with acute rickettsioses. Only 2 patients were treated with doxycycline. Acute rickettsioses are common (>26%), underrecognized, and untreated etiologies of AFI in East Malaysia; empirical doxycycline treatment should be considered.

Rickettsial diseases (RD) are widely reported all over the world. Scrub typhus (ST) is a major tropical infection which is well documented all over India. Therefore, the index of suspicion of scrub typhus is high among physicians with regard to patients presenting with acute febrile illness (AFI) and acute undifferentiated febrile illness (AUFI) in India. Rickettsial diseases other than ST (non-ST RDs), which include spotted fever group (SFG) rickettsioses and typhus group (TG) rickettsioses are not uncommon in India, but the index of suspicion is not as high as ST unless there is a history of the presence of fever with rashes and/or recent arthropod bites. This review aims to look into the Indian scenario on the epidemiology of non-ST RDs, especially the SFG and TG rickettsioses based on various investigations, spectrum of clinical presentation, challenges and gaps in knowledge to suspect and diagnose these infections.

Rickettsioses are among the oldest known infectious diseases. In spite of this, and of the extensive research carried out, many aspects of the biology and epidemiology of tick-borne rickettsiae are far from being completely understood. Their association with arthropod vectors, the importance of vertebrates as reservoirs, the rarity of clinical signs in animals, or the interactions of pathogenic species with rickettsial endosymbionts and with the host intracellular environment, are only some examples. Moreover, new rickettsiae are continuously being discovered. In this review, we focus on the ‘neglected’ aspects of tick-borne rickettsioses and on the gaps in knowledge, which could help to explain why these infections are still emerging and re-emerging threats worldwide.

Testing for spotted fever group rickettsioses (SFGR) and the criteria for identifying suspected patients are not routinely used in Kazakhstan. In 2019, we performed a cross-sectional study in 6 sentinel hospitals in the Pavlodar region. We tested 105 hospitalized patients with SFGR-like symptoms by using PCR or indirect immunofluorescence antibody assay and identified 62 cases of SFGR. Most (78%) cases of disease were caused by Rickettsia sibirica and R. raoultii. Cutaneous signs (eschar or rash) were found in 87% of SFGR patients; 79% had a rash, 48% had an eschar, and 13% had neither. Testing of suspected rickettsia cases resulted in a 27% increase in laboratory-detected SFGR over the mean of the previous 3 years (62 vs. 49). Broadening the case definition by including fever, headache, or myalgia and expanding routine testing for suspected cases of SFGR could contribute to improved case detection and earlier treatment.

The complexity of rickettsial serodiagnostics during acute illness has limited clinical characterization in Africa. We used archived samples from sepsis (n = 259) and acute febrile illness (n = 70) cohorts in Uganda to identify spotted fever and typhus group rickettsiae by using immunofluorescence assay and clinically validated rRNA reverse transcription PCR (RT-PCR). Among 329 participants, 10.0% had rickettsial infections (n = 33; n = 20 identified with immunofluorescence assay and n = 13 by RT-PCR). Serum rRNA RT-PCR was 75.0% (95% CI 42.8-94.5%) sensitive and 91.2% (95% CI 85.8-95.1%) specific. Thrombocytopenia was more common among patients with rickettsial infections than with other nonmalarial infections (adjusted odds ratio 3.7; p = 0.003). No participants were on a tetracycline antimicrobial drug at admission. rRNA RT-PCR is a promising diagnostic strategy for identifying acute rickettsial infections. Doxycycline should be included in empiric antimicrobial drug regimens for nonmalarial febrile illness in this region.

During 2007-2020, we conducted a cross-sectional prevalence study among patients with acute undifferentiated febrile illness to describe the burden and long-term epidemiology of rickettsioses in Cambodia. Serum samples were collected from 10,243 participants, along with epidemiologic data, information on clinical symptoms, demographic characteristics, and risk factors. A total of 802 (7.8%) participants met the definition for acute rickettsial infection after ruling out malaria, influenza, dengue, and chikungunya; 557 (5.4%) cases were typhus, 154 (1.5%) spotted fever, and 136 (1.3%) scrub typhus. Overall seroprevalence was 18.1% (1,857/10,243). Increased age, residence in urban settings, and recent travel to forests were significantly associated with rickettsial infection. Symptoms significantly associated with infection included rash, vomiting, and skin lesions. Our results confirm the underlying burden of rickettsioses and associated risk factors in Cambodia and highlight the need for accessible diagnostics and clinical guidance that consider rickettsioses when treating persons with acute undifferentiated febrile illness.

Tick-borne rickettsioses are caused by obligate intracellular bacteria belonging to the spotted fever group of the genus Rickettsia. These infections are among the oldest known diseases transmitted by vectors. In the last three decades there has been a rapid increase in the recognition of this disease complex. This unusual expansion of information was mainly caused by the development of molecular diagnostic techniques that have facilitated the identification of new and previously recognized rickettsiae. A lot of currently known bacteria of the genus Rickettsia have been considered nonpathogenic for years, and moreover, many new species have been identified with unknown pathogenicity. The genus Rickettsia is distributed all over the world. Many Rickettsia species are present on several continents. The geographical distribution of rickettsiae is related to their vectors. New cases of rickettsioses and new locations, where the presence of these bacteria is recognized, are still being identified. The variety and rapid evolution of the distribution and density of ticks and diseases which they transmit shows us the scale of the problem. This review article presents a comparison of the current understanding of the geographic distribution of pathogenic Rickettsia species to that of the beginning of the century.

Background Historically, malaria has been the predominant cause of acute febrile illness (AFI) in sub-Saharan Africa. However, during the last two decades, malaria incidence has declined due to concerted public health control efforts, including the widespread use of rapid diagnostic tests leading to increased recognition of non-malarial AFI etiologies. Our understanding of non-malarial AFI is limited due to lack of laboratory diagnostic capacity. We aimed to determine the etiology of AFI in three distinct regions of Uganda. Methods A prospective clinic-based study that enrolled participants from April 2011 to January 2013 using standard diagnostic tests. Participant recruitment was from St. Paul’s Health Centre (HC) IV, Ndejje HC IV, and Adumi HC IV in the western, central and northern regions, which differ by climate, environment, and population density. A Pearson's chi-square test was used to evaluate categorical variables, while a two-sample t-test and Krukalis-Wallis test were used for continuous variables. Results Of the 1281 participants, 450 (35.1%), 382 (29.8%), and 449 (35.1%) were recruited from the western, central, and northern regions, respectively. The median age (range) was 18 (2–93) years; 717 (56%) of the participants were female. At least one AFI pathogen was identified in 1054 (82.3%) participants; one or more non-malarial AFI pathogens were identified in 894 (69.8%) participants. The non-malarial AFI pathogens identified were chikungunya virus, 716 (55.9%); Spotted Fever Group rickettsia (SFGR), 336 (26.2%) and Typhus Group rickettsia (TGR), 97 (7.6%); typhoid fever (TF), 74 (5.8%); West Nile virus, 7 (0.5%); dengue virus, 10 (0.8%) and leptospirosis, 2 (0.2%) cases. No cases of brucellosis were identified. Malaria was diagnosed either concurrently or alone in 404 (31.5%) and 160 (12.5%) participants, respectively. In 227 (17.7%) participants, no cause of infection was identified. There were statistically significant differences in the occurrence and distribution of TF, TGR and SFGR, with TF and TGR observed more frequently in the western region ( p  = 0.001; p  < 0.001) while SFGR in the northern region ( p  < 0.001). Conclusion Malaria, arboviral infections, and rickettsioses are major causes of AFI in Uganda. Development of a Multiplexed Point-of-Care test would help identify the etiology of non-malarial AFI in regions with high AFI rates.

In a multicenter, nationwide, retrospective study of patients hospitalized with spotted fever group rickettsiosis in Israel during 2010-2019, we identified 42 cases, of which 36 were autochthonous. The most prevalent species was the Rickettsia conorii Israeli tick typhus strain (n = 33, 79%); infection with this species necessitated intensive care for 52% of patients and was associated with a 30% fatality rate. A history of tick bite was rare, found for only 5% of patients; eschar was found in 12%; and leukocytosis was more common than leukopenia. Most (72%) patients resided along the Mediterranean shoreline. For 3 patients, a new Rickettsia variant was identified and had been acquired in eastern, mountainous parts of Israel. One patient had prolonged fever before admission and clinical signs resembling tickborne lymphadenopathy. Our findings suggest that a broad range of Rickettsia species cause spotted fever group rickettsiosis in Israel.