Leptospirosis with Indian Tick-borne Typhus Coinfection: A Rare Presentation of Tropical Febrile Illness.

INTRODUCTION: Leptospirosis and tick-borne typhus are zoonotic diseases, rarely reported as coinfection. More specific molecular tests are not easily accessible for diagnosis of these diseases, thus resulting in delayed diagnosis and eventually considerable morbidity and mortality. CASE DESCRIPTION: We report a case of leptospirosis with tick-borne typhus coinfection in an abattoir worker who presented with a short history of fever, myalgia, jaundice, nonoliguric renal failure, diffuse petechial rash, and altered sensorium. His lab investigations showed leukocytosis, raised C-reactive protein (CRP), elevated transaminases and creatinine, mild pleocytosis, and mildly raised proteins in cerebrospinal fluid (CSF). Serology for Leptospira IgM was positive by enzyme-linked immunosorbent assay (ELISA). A paired Weil-Felix test (WFT) showed a fourfold increase in OX19 and OX2 titers. The patient responded well to IV antibiotic therapy and was discharged. This is the first time that leptospirosis and Indian tick-borne typhus coinfection has been reported from western India. CONCLUSION: Leptospirosis and Indian tick-borne typhus coinfection is a rare but important cause of tropical fever. Arduous efforts to establish a definitive diagnosis help not only in surveillance for epidemiological data of the disease entities but also in avoiding severe complications resulting from considerable delay in appropriate therapy.

A case series of Mediterranean spotted fever and murine typhus with neurological manifestations.

BACKGROUND OBJECTIVES: Severe cases with neurological manifestations of rickettsiosis have been reported. We aimed to identify the epidemiological, clinical and laboratory features of central nervous system rickettsial infections and to describe the treatment. METHODS: We carried out a retrospective study that included all patients hospitalized with rickettsiosis in the infectious diseases department of Hedi Chaker University Hospital in Sfax, Tunisia between 1993 and 2018. RESULTS: We identified 47 patients with central nervous system rickettsial infections among 440 patients with rickettsial infections (10.7%). Skin rash (31.9% vs 87.8%; p<0.001) and eschar (4.2% vs 27.7%; p<0.001) were less frequent among patients with central nervous system rickettsial infections. Complications (6.4% vs 0.5%; p=0.01) and death (4.2% vs 0.3%; p=0.03) were more frequent among patients with central nervous system rickettsial infections. INTERPRETATION CONCLUSION: Cardinal clinical features and typical laboratory results including thrombocytopenia were less frequent, and prognosis was more severe in patients with central nervous system rickettsial infections.

Epidemiology of Murine Typhus in Taiwan from 2013 to 2020.

Murine typhus is a flea-borne disease caused by Rickettsia typhi infection. The disease is a notifiable infectious disease in Taiwan. Specimens from suspected cases are required to be sent to the Taiwan Centers for Disease Control and Prevention for laboratory diagnosis. In this study, 204 cases of murine typhus were identified by bacterial isolation, real-time polymerase chain reaction, or indirect immunofluorescence assay between 2013 and 2020. The average incidence rate was 0.11/100,000 person-years (95% CI: 0.08-0.13). Murine typhus occurred throughout the year, but it was most prevalent in summer (May to August). The majority of patients were males (75%), residents of Kaohsiung city (31%), and worked in agriculture, forestry, fishing, and animal husbandry (27%). Fever was the most common symptom, present in 95.6% of patients, followed by headache (41%), myalgia (33%), and liver dysfunction (33%). Only 13% of patients had a rash. Up to 80% of cases were among hospitalized patients, and 43% of patients developed severe manifestations. Serological assays also indicated coinfection events. Seven patients showed a 4-fold increase in antibody titers against Orientia tsutsugamushi (N = 2), Coxiella burnetii (n = 2), and Leptospira (N = 3). In conclusion, murine typhus is an endemic and important zoonotic rickettsial disease in Taiwan that cannot be ignored. Further epidemiological surveillance and clinical characteristics should be continuously investigated to prevent and control murine typhus.

Retinochoroiditis secondary to Rickettsia typhi infection: a case report.

BACKGROUND: To report a case of unusual presentation of retinochoroiditis caused by Rickettsia typhi in a patient without prior uveitis. CASE PRESENTATION: In this case, we describe a 24-year-old male soldier with no previous eye disease, who was referred to our ophthalmology department due to bilateral retinochoroiditis and vitritis. The patient initially presented with a paracentral scotoma in his right eye persisting for 7 days and scattered dark spots in his left eye for 2 days in June 2023. Preceding these ocular symptoms, he experienced a two-week episode of fever, headaches, night sweats, and rapid weight loss of 10 kg. A transient rash covered his body briefly. His mother had a history of recurrent eye inflammation. Physical examination revealed bilateral keratic precipitates on the lower corneal periphery, 1 + anterior vitreous cells, small retinal lesions and mild optic discs elevation. Fluorescein angiography indicated mild discs hyperfluorescence, and the clinically visible round punctate lesions on OCT showed inner retinal hyper-reflective lesion with a depth till outer plexiform layer possibly suggestive of a retinitis lesion. Laboratory tests were normal except thrombocytosis, elevated ESR, liver enzymes and ACE levels, with positive Rickettsia typhi serology tests. Rheumatology and infectious disease consultations ruled out autoimmune diseases, confirming Rickettsia typhi infection. Treatment included systemic doxycycline and prednisone, with improvement of visual acuity, ocular symptoms, OCT abnormalities and resolution of inflammation. Prednisone was discontinued, and after two months, additional improvement was seen clinically, with preserved retinal structures on OCT. CONCLUSION: This study explores retinochoroiditis as a rare ocular presentation of Rickettsia typhi, an unusual infection in the Middle East. Previously reported ocular manifestations include conjunctivitis, vitritis, post infectious optic neuropathy and a few cases of uveitis. Ocular symptoms followed systemic illness, highlighting the need for awareness among clinicians. Diagnosis relies on seroconversion, with fluorescein angiography and OCT aiding in assessment. Empiric doxycycline and systemic corticosteroid therapy is recommended. Ocular symptoms resolved in two months. Awareness of these ocular manifestations is essential for timely diagnosis and management. Further research is needed to fully understand this aspect of murine typhus.

Integrating core subtractive proteomics and reverse vaccinology for multi-epitope vaccine design against Rickettsia prowazekii endemic typhus.

Rickettsia prowazekii is an intracellular, obligate, gram-negative coccobacillus responsible for epidemic typhus. Usually, the infected body louse or its excrement when rubbed into the skin abrasions transmits the disease. The infection with R. prowazekii causes the highest death rate (> 20% without antibiotic treatment and now 1-7%), followed by epidemic typhus, which often manifests in unsanitary conditions (up to 15-30%). Conventionally, vaccine design has required pathogen growth and both assays (in vivo and in vitro), which are costly and time-consuming. However, advancements in bioinformatics and computational biology have accelerated the development of effective vaccine designs, reducing the need for traditional, time-consuming laboratory experiments. Subtractive genomics and reverse vaccinology have become prominent computational methods for vaccine model construction. Therefore, the RefSeq sequence of Rickettsia prowazekii (strain Madrid E) (Proteome ID: UP000002480) was subjected to subtractive genomic analysis, including factors such as non-similarity to host proteome, essentiality, subcellular localization, antigenicity, non-allergenicity, and stability. Based on these parameters, the vaccine design process selected specific proteins such as outer membrane protein R (O05971_RICPR PETR; OmpR). Eventually, the OmpR was subjected to a reverse vaccinology approach that included molecular docking, immunological simulation, and the discovery of B-cell epitopes and MHC-I and MHC-II epitopes. Consequently, a chimeric or multi-epitope-based vaccine was proposed by selecting the V11 vaccine and its 3D structure modeling along with molecular docking against TLR and HLA protein, in silico simulation, and vector designing. The obtained results from this investigation resulted in a new perception of inhibitory ways against Rickettsia prowazekii by instigating novel immunogenic targets. To further assess the efficacy and protective ability of the newly designed V11 vaccine against Rickettsia prowazekii infections, additional evaluation such as in vitro or in vivo immunoassays is recommended.

Case Report: Cardiovascular Manifestations due to Flea-Borne Typhus.

Flea-borne typhus is a vector-borne disease caused by Rickettsia typhi that occurs worldwide, except in Antarctica. In the United States, most cases are restricted to California, Hawaii, and Texas. The syndrome is characterized by nonspecific signs and symptoms: fever, headache, rash, arthralgia, cough, hepatosplenomegaly, diarrhea, and abdominal pain. Although flea-borne typhus can cause pulmonary, neurological, and renal complications, the cardiovascular system is rarely affected. We present a case of endocarditis resulting from flea-borne typhus diagnosed by blood microbial cell-free DNA testing that required valve replacement and antibiotic therapy for 6 months. In addition, we review 20 cases of presumed and confirmed cardiovascular manifestations resulting from flea-borne typhus in the literature.

Surveillance of Flea-Borne Typhus in California, 2011-2019.

Flea-borne typhus (FBT), also referred to as murine typhus, is an acute febrile disease in humans caused by the bacteria Rickettsia typhi. Currently, cases of FBT are reported for public health surveillance purposes (i.e., to detect incidence and outbreaks) in a few U.S. states. In California, healthcare providers and testing laboratories are mandated to report to their respective local public health jurisdictions whenever R. typhi or antibodies reactive to R. typhi are detected in a patient, who then report cases to state health department. In this study, we characterize the epidemiology of flea-borne typhus cases in California from 2011 to 2019. A total of 881 cases were reported during this period, with most cases reported among residents of Los Angeles and Orange Counties (97%). Demographics, animal exposures, and clinical courses for case patients were summarized. Additionally, spatiotemporal cluster analyses pointed to five areas in southern California with persistent FBT transmission.

Severe Rickettsia typhi Infections, Costa Rica.

Murine typhus is a febrile, fleaborne disease caused by infection with Rickettsia typhi bacteria. Cases can range from mild and nonspecific to fatal. We report 2 cases of murine typhus in Costa Rica, confirming the presence and circulation of R. typhi causing severe disease in the country.

Isothermal amplification technology (IAT) for rapid diagnosis of Rickettsioses: scope, overview, existing evidence, and the way forward.

Rickettsioses, a category of zoonosis primarily caused by Rickettsia and Orientia, is a huge cause of public health concern worldwide. Diseases like murine typhus, scrub typhus, Mediterranean spotted fever and rocky mountain spotted fever are major contributors of Rickettsioses globally, with peculiar distributions in south-east Asia, Africa, Arabia and the Americas. With the innovations in molecular diagnostics, Isothermal Amplification Technology is gaining popularity for its fidelity, rapidity and cost-effectiveness. Compared to commercial assays, they are easily adaptable for point-of-care (PoC) settings. Due to nonspecific presentation as an acute undifferentiated febrile illness, diagnosis of Rickettsioses poses a great challenge. Certain isothermal amplification assays have proven to be highly efficient in diagnosing vector borne diseases like dengue, malaria, and chikungunya. The purpose of this review is to provide readers the current advancements, scope, challenges, and future prospects of isothermal amplification technologies in the detection of zoonotic pathogens like Rickettsia and Orientia.

Fleaborne Typhus-Associated Deaths - Los Angeles County, California, 2022.

Fleaborne typhus (also known as murine typhus), a widely distributed vectorborne zoonosis caused by Rickettsia typhi, is a moderately severe, but infrequently fatal illness; among patients who receive doxycycline, the case-fatality rate is <1%. Fleaborne typhus is a mandated reportable condition in California. Reported fleaborne typhus cases in Los Angeles County have been increasing since 2010, with the highest number (171) reported during 2022. During June-October 2022, Los Angeles County Department of Public Health learned of three fleaborne typhus-associated deaths. This report describes the clinical presentation, illness course, and methods used to diagnose fleaborne typhus in these three cases. Severe fleaborne typhus manifestations among these cases included hemophagocytic lymphohistiocytosis, a rare immune hyperactivation syndrome that can occur in the infection setting; myocarditis; and septic shock with disseminated intravascular coagulation. Increased health care provider and public health awareness of the prevalence and severity of fleaborne typhus and of the importance of early doxycycline therapy is essential for prevention and treatment efforts.

Murine typhus is a common cause of acute febrile illness in Bandung, Indonesia.

Murine typhus (MT), an infection caused by the gram-negative bacteria Rickettsia typhi (R. typhi), is a significant cause of acute febrile illness (AFI) in Southeast Asia but is rarely reported in Indonesia. The current study aimed to describe the clinical characteristics of MT cases in Bandung, West Java. Non-confirmed AFI cases (n = 176) from a prospective cohort study of whom paired serum samples (acute (T1), midterm (T2), or convalescent (T3)) were available were screened using MT serology. IgG against R. typhi was detected in the T2 or T3 samples using an in-house ELISA. Positive IgG samples were further screened for the presence of IgM. If both IgM and IgG were positive, the endpoint titer of T1, T2, or T3 was determined. In cases with a fourfold increase in titer, real-time PCR of T1 samples was performed to detect R. typhi DNA. In total, 71/176 (40.3%) patients tested positive for IgG antibody, and 26 AFI cases were confirmed as MT (23 cases by PCR, 3 cases by fourfold titer increased IgG or IgM titer). The most common clinical symptoms in the confirmed cases were headache (80%), arthralgia (73%), malaise (69%), and myalgia (54%). In these cases, the presumptive clinical diagnoses were typhoid fever (43.2%), dengue (38.5%), and leptospirosis (19.2%). MT was not considered in any of the patients, and no patients received doxycycline. These findings confirmed that MT is an important cause of AFI in Indonesia. MT should be included in the differential diagnosis of AFI, and empirical treatment with doxycycline should be considered.

Nonnegligible Seroprevalence and Predictors of Murine Typhus, Japan.

To elucidate the epidemiology of murine typhus, which is infrequently reported in Japan, we conducted a cross-sectional study involving 2,382 residents of rickettsiosis-endemic areas in Honshu Island during August-November 2020. Rickettsia typhi seroprevalence rate was higher than that of Orientia tsutsugamushi, indicating that murine typhus is a neglected disease.

Detection of Severe Murine Typhus by Nanopore Targeted Sequencing, China.

We report a case of murine typhus in China caused by Rickettsia typhi and diagnosed by nanopore targeted sequencing of a bronchoalveolar lavage fluid sample. This case highlights that nanopore targeted sequencing can effectively detect clinically unexplained infections and be especially useful for detecting infections in patients without typical signs and symptoms.

Serological cross-reactivity between spotted fever and typhus groups of rickettsia infection in Japan.

OBJECTIVES: We examined the frequency of cross-reactions to Rickettsia typhi in patients with Japanese spotted fever (JSF) and evaluated the differences between two rickettsiae using antibody endpoint titers. METHODS: Patients' immunoglobulin (Ig)M and IgG titers against Rickettsia japonica and Rickettsia typhi in two phases were measured using an indirect immunoperoxidase assay at two reference centers for rickettsiosis in Japan. Cross-reaction was defined as a higher titer against R. typhi in convalescent sera than in acute sera among patients fulfilling the criteria for JSF diagnosis. The frequencies of IgM and IgG were also evaluated. RESULTS: Approximately 20% of cases showed positive cross-reactions. A comparison of antibody titers revealed the difficulty in identifying some positive cases. CONCLUSION: Cross-reactions of 20% in serodiagnosis may lead to the misclassification of rickettsial diseases. However, with the exception of some cases, we were able to successfully differentiate JSF from murine typhus using each endpoint titer.

Murine typhus and other potentially lethal rickettsial diseases in Chiapas, Mexico.

Not available.