Ischemic Hepatitis and Septic Shock Secondary to Murine Typhus Infection in Pregnancy.

Infection with murine typhus may be associated with significant morbidity. With nonspecific symptoms and laboratory abnormalities, diagnosis may be challenging. In this case, a pregnant patient presented with complaints of fevers and myalgias. Her laboratory results included severe transaminitis as well as thrombocytopenia and hyponatremia. She ultimately required vasopressor support and intensive care unit admission despite fluid resuscitation and broad-spectrum antibiotics. Empiric doxycycline was initiated due to suspicion for murine typhus, which laboratory testing later confirmed. Her clinical status improved with these interventions. This was a severe case of murine typhus resulting in septic shock and ischemic hepatitis. It is important to know the typical findings of murine typhus and consider it in a differential diagnosis, especially when practicing in endemic areas.

Identification of Bacteria and Viruses Associated with Patients with Acute Febrile Illness in Khon Kaen Province, Thailand.

The majority of cases of undifferentiated acute febrile illness (AFI) in the tropics have an undefined etiology. In Thailand, AFI accounts for two-thirds of illnesses reported to the Ministry of Public Health. To characterize the bacterial and viral causes of these AFIs, we conducted molecular pathogen screening and serological analyses in patients who sought treatment in Chum Phae Hospital, Khon Kaen province, during the period from 2015 to 2016. Through integrated approaches, we successfully identified the etiology in 25.5% of cases, with dengue virus infection being the most common cause, noted in 17% of the study population, followed by scrub typhus in 3.8% and rickettsioses in 6.8%. Further investigations targeting viruses in patients revealed the presence of Guadeloupe mosquito virus (GMV) in four patients without other pathogen co-infections. The characterization of four complete genome sequences of GMV amplified from AFI patients showed a 93-97% nucleotide sequence identity with GMV previously reported in mosquitoes. Nucleotide substitutions resulted in amino acid differences between GMV amplified from AFI patients and mosquitoes, observed in 37 positions. However, these changes had undergone purifying selection pressure and potentially had a minimal impact on protein function. Our study suggests that the GMV strains identified in the AFI patients are relatively similar to those previously reported in mosquitoes, highlighting their potential role associated with febrile illness.

Severe murine typhus complicated by multiple organ dysfunctions: A case report.

Background: Rickettsioses are infectious diseases which are caused by intracellular bacteria which belong to the family Rickettsiaceae. This zoonosis endemically prefers tropical and subtropical regions of which the Mediterranean is included. Murine typhus is a type of rickettsial disease that commonly presents with undulating fever, headache rash, chills, malaise, and myalgias. It can lead to complications such as multi-organ failure and has a lethality rate of <5% in such cases. Case Presentation: A 70-year-old male was hospitalized at the Unit of Infectious Diseases, Mother Teresa Hospital, Tirana, Albania in a comatose condition. He had a seven-day history of fever up to 39-40°C, headache, fatigue, anorexia, vomiting, cough, and myalgia. He was a farmer and had contact with animals. Upon admission, he had scleral hemorrhages, hepatosplenomegaly, jaundice, maculopapular rash over the trunk, abdomen, and palms of his hands as well as severe acidosis, depressed bicarbonate levels, alteration in liver, kidney, and pancreas function tests. He was urgently transferred to the Intensive care unit of the Infectious Diseases Department. He was hemodynamically unstable and was put immediately on vasoactive agents and mechanical ventilation. ELISA Rickettsia typhi IgM resulted positive. Supportive treatment along with antibiotics Levofloxacin and Ceftriaxone was initiated. However, the patient died on the 4th day of hospitalization and the 11th of the disease onset. Conclusion: Murine typhus should be included in the investigation of possible causes when dealing with patients presenting with fever and maculopapular rash complicated by multi-organ failure and coming from a typhus-endemic area, especially in the summer season.

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.

Knowledge and practices related to louse- and flea-borne diseases among staff providing services to people experiencing homelessness in the United States.

BACKGROUND AND AIMS: Louse-borne Bartonella quintana infection and flea-borne murine typhus are two potentially serious vector-borne diseases that have led to periodic outbreaks among people experiencing homelessness in the United States. Little is known about louse- and flea-borne disease awareness and prevention among staff who provide services to the population. We surveyed staff in seven US states to identify gaps in knowledge and prevention practices for these diseases. METHODS AND RESULTS: Surveys were administered to 333 staff at 89 homeless shelters and outreach teams in California, Colorado, Georgia, Maryland, Minnesota, New York and Washington from August 2022 to April 2023. Most participants (>68%) agreed that body lice and fleas are a problem for people experiencing homelessness. About half were aware that diseases could be transmitted by these vectors; however, most could not accurately identify which diseases. Less than a quarter of staff could describe an appropriate protocol for managing body lice or fleas. Misconceptions included that clients must isolate or be denied services until they are medically cleared. CONCLUSIONS: Our findings reveal significant knowledge gaps among staff who provide services to people experiencing homelessness in the prevention and control of louse- and flea-borne diseases. This demonstrates an urgent need for staff training to both reduce disease and prevent unnecessary restrictions on services and housing.

Murine Typhus: A Review of a Reemerging Flea-Borne Rickettsiosis with Potential for Neurologic Manifestations and Sequalae.

Murine typhus is an acute febrile illness caused by Rickettsia typhi, an obligately intracellular Gram-negative coccobacillus. Rats (Rattus species) and their fleas (Xenopsylla cheopis) serve as the reservoir and vector of R. typhi, respectively. Humans become infected when R. typhi-infected flea feces are rubbed into flea bite wounds or onto mucous membranes. The disease is endemic throughout much of the world, especially in tropical and subtropical seaboard regions where rats are common. Murine typhus is reemerging as an important cause of febrile illness in Texas and Southern California, where an alternate transmission cycle likely involves opossums (Didelphis virginiana) and cat fleas (Ctenocephalides felis). Although primarily an undifferentiated febrile illness, a range of neurologic manifestations may occur, especially when treatment is delayed. Serology is the mainstay of diagnostic testing, but confirmation usually requires demonstrating seroconversion or a fourfold increase in antibody titer from acute- and convalescent-phase sera (antibodies are seldom detectable in the first week of illness). Thus, early empiric treatment with doxycycline, the drug of choice, is imperative. The purpose of this review is to highlight murine typhus as an important emerging and reemerging infectious disease, review its neurologic manifestations, and discuss areas in need of further study.

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.

Longitudinal comparison of bacterial pathogen seropositivity among wet market vendors in the Lao People's Democratic Republic.

Wild animal trade for human consumption is a global issue, involving complex interactions between economics, culture, food security and conservation. Whilst being a biodiversity issue, it is also a major public health concern, with recent epidemics and pandemics of zoonotic pathogens linked to interactions with wildlife. At three time points, between March 2017 and June 2018, a longitudinal sero-survey of 150 market vendors from three wet markets in Laos (selling vegetables, domestic animal meat and/or wildlife meat) was conducted to determine if vendors had been differentially exposed to three endemic bacterial pathogens - Orientia tsutsugamushi, Rickettsia typhi, and Leptospira spp. A total of 367 serum samples were tested by IgG enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA, for scrub typhus group (STG) and typhus group (TG) only). Among vendors, 32.7% were IgG-positive for at least one pathogen, 13.3% sero-converted during the study. Multi-season occupancy modelling for STG indicated a significantly higher prevalence of STG IgG in vegetable vendors (27.3%) and wildlife vendors (28.4%) than in domestic animal meat vendors (6.9 %, p=0.05), and higher in Phonsavanh market (OR=9.6, p=0.03) compared to Lak Sao and Salavan markets. Estimated mean incidence was 57 cases per 10,000 per 7.5-month period. For TG, vendor age had a significant effect on prevalence (OR=1.04, p=0.006), estimated mean incidence was 64 cases per 10,000 per season (7.5-month period). Despite individuals selling domestic meat having a higher prevalence of Leptospira infections than those that did not (11.6% versus 4.5%), the difference was not significant. Whilst this study has a number of limitations, including vendors changing what food types they sold and no investigation of exposure outside of markets, the finding that the risk of exposure of vendors to zoonotic pathogens may be associated with types of food sold for human consumption warrants further investigation.

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.

Imported rickettsial infections to the United Kingdom, 2015-2020.

OBJECTIVE: The burden of imported rickettsial infection in the UK is not previously described. This retrospective review identifies rickettsial cases diagnosed at the national reference laboratory between 2015 and 2022. METHODS: Samples testing positive for spotted fever group, typhus group, and scrub typhus IgG/IgM on acute and convalescent blood samples, and/or PCR on tissue/blood were categorized as suspected, confirmed or past infection. RESULTS: 220 patients had rickettsioses, and the commonest import was acute spotted fever group infection (61%, 125/205), 54% (62/114) from South Africa. In acute typhus group cases, 60% (40/67) were from Southeast Asia. One patient with Rickettsia typhi bacteremia died. Scrub typhus group infections (5%, 10/205) were exclusively from Asia and the Western Pacific regions. Overall, 43% of confirmed cases (39/91) had not received doxycycline prior to results. CONCLUSIONS: Rickettsial infections are important and under-recognized causes of imported fever in the UK. Thorough history, examination, and timely treatment with doxycycline should be considered if there is suspicion of Rickettsia infection before testing.

Rickettsioses in Colombia during the 20th century: A historical review.

Rickettsioses are vector-borne zoonotic diseases whose etiological agents are bacteria of the genera Rickettsia and Orientia. In Colombia, literature published on rickettsioses during the 20th century is limited and disperse; to date, there are no detailed publications that compile the affected regions or the involved Rickettsia species in each outbreak. Since early works of Luis Patiño-Camargo, the study of rickettsioses gained major importance with the subsequent description of significant outbreaks in some departments of the country. During the 1940s, many articles were published reporting outbreaks probably caused by Rickettsia rickettsii, Rickettsia typhi, and Rickettsia prowazekii, as well as studies on their diagnosis, vaccination, and prophylaxis. One of the most notorious works was published by Patiño-Camargo where he named the R. rickettsii rickettsiosis as "Tobia fever". However, in the subsequent decades, these entities entered a prolonged period of neglected research and surveillance, and just gained importance until the 21st century, when new fatal cases began to be reported in the country; thus, many questions remained unanswered during this overlooked period. The present work reviewed online databases, repositories, and libraries to compile literature related to rickettsioses in Colombia published during the 20th century. Gathered data show that typhus group rickettsioses (including infections by R. typhi and R. prowazekii) were broadly distributed in departments from the Andean and Caribbean regions, and that spotted fever group rickettsioses cases (including infections by R. rickettsii) were registered in other locations different from Tobia (Cundinamarca), like Atlántico, Bolivar, and Santander departments. These findings contribute to the knowledge of these diseases, their historical distribution, public health burden, and set new horizons for rickettsioses research in different Colombian locations.

Increased Seroprevalence of Typhus Group Rickettsiosis, Galveston County, Texas, USA.

Whether increases in typhus group rickettsiosis in Galveston County, Texas, USA, are caused by increased recognition or true reemergence is unclear. We conducted a serosurvey that demonstrated Rickettsia typhi antibodies increased from 1.2% in 2013 to 7.8% in 2021 (p<0.001). These findings support pathogen reemergence rather than enhanced recognition alone.

Rickettsia typhi infection in a clinically-ill dog from Houston, Texas.

In 2020, Rickettsia typhi was diagnosed in a dog from Houston, Texas, USA based upon R. typhi IFA seroreactivity in both acute and convalescent sera, and PCR with DNA sequencing of 4 different gene regions, all of which were 100% identical to R. typhi. The dog was clinically ill with intermittent fever, lethargy, inappetence, and lymphadenopathy. Clinicopathological abnormalities included a mild nonregenerative anemia, neutrophilia, lymphopenia, thrombocytopenia, hypoalbuminemia, and elevated ALP. The dog rapidly recovered with doxycycline administration.

Murine typhus.

Murine typhus is a rare condition caused by the gram-negative bacterium Rickettsia typhi which classically presents with the triad of fever, rash, and headache. Herein we report a rare presentation of murine typhus in an adult who presented predominantly with fever and gastrointestinal symptoms. Initial imaging showed cardiomegaly and hepatosplenomegaly, which led to further workup revealing rickettsial disease. Although this illness is considered a rare diagnosis in the emergency department, every person with a pet that might have fleas is susceptible to it.

Murine typhus complicated by sHLH mimicking adult-onset Still's disease.

INTRODUCTION: Adult-onset Still's disease (AOSD) is a rare multisystemic disorder and a diagnostic challenge for physicians because of the wide range of differential diagnoses. Common features of AOSD and secondary hemophagocytic lymphohistiocytosis (sHLH) could favour diagnostic uncertainty, in particular in case of infection-related sHLH. OBSERVATION: A 61-year-old man was admitted to our internal medicine department for suspected AOSD. He reported a 2-week history of sudden onset fever, headaches, myalgia, sore throat, diarrhoea, and an erythematous macular rash of the trunk as well as petechial purpuric lesions on both legs on return from Reunion Island. Laboratory tests found cytopenia, hepatic cytolysis, hypertriglyceridaemia, and hyperferritinaemia. Hemophagocytosis was diagnosed on bone marrow aspiration in favour of the diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH). Subcutaneous anakinra (100mg) was initiated to treat sHLH with favourable course. Oral doxycycline was added 3days later because of atypical features for AOSD diagnosis such as diarrhoea, hypergammaglobulinaemia, and doubtful serologies for Rickettsia and Coxiella. Three weeks later, Rickettsia typhi serology was checked again and revealed an increase in IgG titer>4 times that confirmed the diagnosis of murine typhus. A diagnosis of murine typhus complicated by sHLH was retained, successfully treated by anakinra and doxycycline. CONCLUSION: Our observation shows that AOSD diagnosis has to be stringent due to the many differential diagnoses, particularly infection complicated by sHLH, which may be rare. It is important to consider murine typhus in patients returning from endemic areas, such as La Reunion or other tropical areas, when they present fever of unknown origin with non-specific clinical features. Moreover, this case illustrates the effectiveness of IL-1 blockers as a treatment for symptomatic sHLH without severity criteria, regardless of the aetiology.