Murine typhus mistaken for COVID-19 in a young man.

Fever is a widely recognised presenting symptom of COVID-19. Consequently, other febrile illnesses may be difficult to distinguish from COVID-19-leading to delays in diagnosis and treatment. One such illness is murine typhus, a fleaborne illness with worldwide distribution caused by Rickettsia typhi It often presents with fever, headache and myalgia, all of which have been commonly reported with COVID-19. Although the disease is usually mild with a good prognosis, there have been reports of severe illness and death. I present a case of murine typhus in a young male who had 2 weeks of headaches and daily fevers during the COVID-19 pandemic. He was ultimately tested for murine typhus when his occupation as a dog trainer was queried, and he experienced resolution of symptoms after treatment with doxycycline. During this pandemic, clinicians must be vigilant of other febrile illnesses whose symptoms overlap with COVID-19.

A systematic review of the untreated mortality of murine typhus.

Murine typhus is an acute febrile, flea-borne disease caused by the bacteria Rickettsia typhi. The disease occurs worldwide but is likely underrecognized due to its non-specific symptoms, causing significant morbidity. A systematic review found disease complications in one-fourth of all patients and a long fever duration in those untreated. Although mortality in treated cases is estimated to be very low, some case series have shown a notably higher mortality in untreated patients. This study aimed to describe the outcomes and estimate the mortality of untreated murine typhus through a comprehensive systematic literature review. We systematically searched the literature for articles describing untreated murine typhus patients, excluding cases with no laboratory assay confirmed diagnosis, those who received efficacious treatment, had incomplete information on primary outcome and articles describing less than 10 patients and performed a narrative synthesis of the study findings. The study protocol followed the PRISMA guidelines and was part of a more extensive protocol registered at PROSPERO (CRD42018101991). Twelve studies including a total of 239 untreated patients matched the eligibility criteria. Only a single study reported one death in 28 patients, giving a patient series mortality of 3.6% and an overall mortality of 0.4% in 239 untreated patients. Complications were reported in 10 of the 12 studies and included involvement of the central nervous system, kidney and lung, with a hospitalisation rate of 70% and ICU admission rate of 27% in one study. The mean duration of fever in untreated patients was 15 days in two and 12.7 days in one study. Although the untreated mortality in this study was low, the sample size was small. Murine typhus caused significant morbidity when untreated, leading to high hospitalisation rates and highlighting the importance of early diagnosis and treatment of this neglected disease to reduce disease burden and health-care related costs.

Clinical Manifestations and Molecular Diagnosis of Scrub Typhus and Murine Typhus, Vietnam, 2015-2017.

Rickettsioses are endemic to Vietnam; however, only a limited number of clinical studies have been performed on these vectorborne bacteria. We conducted a prospective hospital-based study at 2 national referral hospitals in Hanoi to describe the clinical characteristics of scrub typhus and murine typhus in northern Vietnam and to assess the diagnostic applicability of quantitative real-time PCR assays to diagnose rickettsial diseases. We enrolled 302 patients with acute undifferentiated fever and clinically suspected rickettsiosis during March 2015-March 2017. We used a standardized case report form to collect clinical information and laboratory results at the time of admission and during treatment. We confirmed scrub typhus in 103 (34.1%) patients and murine typhus in 12 (3.3%) patients. These results highlight the need for increased emphasis on training for healthcare providers for earlier recognition, prevention, and treatment of rickettsial diseases in Vietnam.

Characteristics of scrub typhus, murine typhus, and Q fever among elderly patients: Prolonged prothrombin time as a predictor for severity.

BACKGROUND/PURPOSE: The clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear. METHODS: We conducted a retrospective study to identify the characteristics of the elderly aged ≥65 years with a comparison group aged 18-64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002-2011. RESULTS: Among 441 cases, including 187 cases of scrub typhus, 166 acute Q fever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly (p = 0.022), dyspnea (p = 0.006), less relative bradycardia (p = 0.004), less febrile illness (p = 0.004), prolonged prothrombin time (PT) (p = 0.002), higher levels of initial C-reactive protein (p = 0.039), blood leukocyte counts (p = 0.01), and lower platelet counts (p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis (p = 0.018, CI 95% 0.01-0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly (p = 0.012, 95% confidence interval [CI]: 1.33-9.99). CONCLUSION: The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications.

Concomitant Plasmodium vivax malaria and murine typhus infection with pulmonary involvement.

We report a case of Plasmodium vivax and murine typhus coinfection in a 30-year-old woman who presented with intermittent, high-grade fever. Her peripheral blood smear showed ring-form trophozoites of P. vivax, with an initial murine typhus serological test being negative. Although the P. vivax infection was successfully treated, she still had intermittent, high-grade fever, developed dyspnoea and bilateral interstitial pneumonitis shown in the chest X-ray. Thus, coinfection was suspected, and empirical antibiotics were given. The second serological test confirmed the concomitant murine typhus infection, and antibiotics treatment were successful with the complete recovery. This case emphasises that an initial negative murine typhus serological test does not necessarily rule out the presence of the disease. A follow-up murine typhus serological or molecular test within 1-2 weeks is therefore recommended.

Pregnancy outcome in relation to treatment of murine typhus and scrub typhus infection: a fever cohort and a case series analysis.

BACKGROUND: There is a paucity of published reports on pregnancy outcome following scrub and murine typhus despite these infections being leading causes of undifferentiated fever in Asia. This study aimed to relate pregnancy outcome with treatment of typhus. METHODOLOGY/PRINCIPAL FINDINGS: Data were analyzed from: i) pregnant women with a diagnosis of scrub and/or murine typhus from a fever cohort studies; ii) case series of published studies in PubMed using the search terms "scrub typhus" (ST), "murine typhus" (MT), "Orientia tsutsugamushi", "Rickettsia tsutsugamushi", "Rickettsia typhi", "rickettsiae", "typhus", or "rickettsiosis"; and "pregnancy", until February 2014 and iii) an unpublished case series. Fever clearance time (FCT) and pregnancy outcome (miscarriage and delivery) were compared to treatment. Poor neonatal outcome was a composite measure for pregnancies sustained to 28 weeks or more of gestation ending in stillbirth, preterm birth, or delivery of a growth restricted or low birth weight newborn. RESULTS: There were 26 women in the fever cohort. MT and ST were clinically indistinguishable apart from two ST patients with eschars. FCTs (median [range] hours) were 25 [16-42] for azithromycin (n=5), 34 [20-53] for antimalarials (n=5) and 92 [6-260] for other antibiotics/supportive therapy (n=16). There were 36.4% (8/22) with a poor neonatal outcome. In 18 years, 97 pregnancies were collated, 82 with known outcomes, including two maternal deaths. Proportions of miscarriage 17.3% (14/81) and poor neonatal outcomes 41.8% (28/67) were high, increasing with longer FCTs (p=0.050, linear trend). Use of azithromycin was not significantly associated with improved neonatal outcomes (p=0.610). CONCLUSION: The published ST and MT world literature amounts to less than 100 pregnancies due to under recognition and under diagnosis. Evidence supporting the most commonly used treatment, azithromycin, is weak. Collaborative, prospective clinical trials in pregnant women are urgently required to reduce the burden of adverse maternal and newborn outcomes and to determine the safety and efficacy of antimicrobial treatment.

Murine typhus in elderly patients: a prospective study of 49 patients.

BACKGROUND: The characteristics of Rickettsia typhi infection in elderly patients have not been extensively described in the literature. METHODS: We conducted a prospective study on murine typhus in patients > 65 years old in two endemic areas of Greece. RESULTS: Forty-nine elderly patients were analyzed, including 30 (61.2%) males. The clinical triad of fever (100% of patients), headache (83.7%), and rash (73.5%), occurred in 63% of patients, whereas malaise (85.7%), anorexia (65.3%), and myalgia (59.2%) were also common. Frequent laboratory findings were transaminasemia (89.8%), lactate dehydrogenase elevation (65.3%), hematuria (55.1%), thrombocytopenia (53.1%), anemia (51%), leucopenia (40.8%), and mild hyponatremia (23.5%). Complications developed in 16 patients (32.7%); no deaths were recorded. CONCLUSIONS: The main clinical and laboratory characteristics of murine typhus are similar in elderly and younger adults. However, elderly patients have a more severe clinical picture, evidenced by a higher complication rate and longer duration of fever, even with appropriate treatment. To our knowledge, this is the first study to focus on murine typhus in a geriatric population.

Murine typhus as a cause of cognitive impairment: case report and a review of the literature.

BACKGROUND: Murine typhus is a systemic febrile illness caused by Rickettsia typhi, a gram-negative, obligate intracellular bacterium. It is found worldwide, including in the United States, where cases are concentrated in suburban areas of Texas and California. The disease manifests with fever, headache, and rash. Central nervous system involvement is rare in both adults and children. Aseptic meningitis and meningoencephalitis are the most common neurological presentations, occurring in 2% to 5% of cases. Neurological dysfunction, including memory impairment and behavioral alterations, can occur and usually are reversible. Long-term deficits are considered rare even in untreated cases and have not been described in the pediatric population. METHODS: Single case report. RESULTS: We describe a previously healthy 17-year-old girl infected with R. typhi who developed meningoencephalitis that resulted in chronic cognitive impairment despite treatment. CONCLUSION: Murine typhus should be considered in the differential diagnosis of aseptic meningitis and meningoencephalitis. Early diagnosis and treatment can prevent death and long-term morbidity.

Severe murine typhus with shock and acute respiratory failure in a Japanese traveler after returning from Thailand.

We treated a case of severe murine typhus in a Japanese traveler after returning from Thailand. Although the disease is typically self-limited or mild, the patient showed shock and multiple organ failure including acute respiratory distress syndrome. Then the patient fully recovered following intensive care and administration of antirickettsial medicines.

Murine typhus returns to New South Wales: a case of isolated meningoencephalitis with raised intracranial pressure.

Murine typhus (MT) occurs worldwide, but, in Australia, is only regularly diagnosed in south-west Western Australia. Meningoencephalitis is an uncommon complication of MT, often accompanied by rash or systemic involvement. We report a case of MT presenting exclusively with meningoencephalitis, raised intracranial pressure, papilloedema and bilateral 6th cranial nerve palsies. MT should be considered in patients with "aseptic" meningitis or meningoencephalitis, even in the absence of other typical features of a typhus-like illness.

Endemic typhus (murine typhus) in an 18 year old Libyan adult.

We present a case of an 18 year old Libyan with a history of fever, frontal headache, bodyache, malaise, abdominal pain, nausea and vomiting, followed by macular to maculopapular rash. A diagnosis of endemic typhus (murine typhus) was made based on the typical clinical findings and epidemiological history given by the patient. Routine blood investigations were inconclusive and a chest x-ray was normal. The patient was treated by oral doxycycline. The patient responded favorably to treatment.

Epidemiology and clinical aspects of rickettsioses in Thailand.

Scrub typhus and murine typhus are widespread in Thailand. Clinical manifestations of both diseases are nonspecific and vary widely. Acute undifferentiated fever (AUF), with or without organ dysfunction, is a major clinical presentation of these two diseases. The epidemiology and clinical manifestations including severe complications of scrub typhus and murine typhus in Thailand are summarized. Sixteen hundred and sixty-three patients with AUF were studied in six hospitals in Thailand between 2000 and 2003. Scrub typhus and murine typhus were diagnosed in 16.1% and 1.7% of them, respectively. Clinical spectrum of murine typhus was similar to scrub typhus. Hepatic dysfunction and pulmonary involvement were common complications. Multi-organ dysfunction mimicking sepsis syndrome occurred in 11.9% of patients with scrub typhus. The mortality of severe scrub typhus varied from 2.6% to 16.7%. Awareness that scrub typhus and murine typhus are prominent causes of AUF in adults in Thailand improves the probability of an accurate clinical diagnosis. Early recognition and appropriate treatment reduces morbidity and mortality. Results from recent clinical studies from Thailand indicated that rational antimicrobial therapy would be doxycycline in mild cases and a combination of either cefotaxime or ceftriaxone and doxycycline in severe cases. Azithromycin could be considered as an alternative treatment when doxycycline allergy is suspected. This would be either curative, or have no ill effect, in the majority of instances. Failure to improve or defervesce within 48 hours would indicate the need to perform a thorough re-evaluation of clinical findings and initial laboratory investigation results, as well as a need to change antibiotic.

Epidemiological features of Mediterranean spotted fever, murine typhus, and Q fever in Split-Dalmatia County (Croatia), 1982-2002.

We determined the epidemiological features of three zoonoses in hospitalized patients in southern Croatia. Patients were diagnosed by serological testing. Clinical and epidemiological data were also collected. Between 1982 and 2002, Mediterranean spotted fever (MSF) was diagnosed in 126 (incidence rate 1.27/100,000 per year), murine typhus (MT), in 57 (incidence rate 0.57/100,000 per year), and Q fever in 170 (incidence rate 1.7/100,000 per year) patients. MSF and Q fever were characterized by a marked seasonality. Incidences of Q fever and of MSF were higher for males than for females (P<0.0001 and P=0.0024, respectively). The most frequent of the three zoonoses in children was MSF. Q fever and MT cases were mostly seen in the 21-50 years age group. We found no statistically significant differences between season- and gender-specific incidence rates of MT. Whereas infections due to rickettsiae decreased, the incidence of Q fever increased over the last 12 years of the study.

Clinical and laboratory features of murine typhus in central Tunisia: a report of seven cases.

INTRODUCTION: Murine or endemic typhus, caused by Rickettsia typhi, has been reported in all continents. In the 1970s, no cases of murine typhus were diagnosed in Tunisia. METHODS: The clinico-epidemiological characteristics of seven cases of murine typhus diagnosed at our hospitals since 1993 are reported. Diagnosis was confirmed by indirect fluorescence assay detecting specific R. typhi antibodies. RESULTS: Murine typhus occurred in all ages from 18-80 years during the hot season in rural areas. Clinical features were: sudden onset of fever and absence of eschar in all cases, with maculo-papular rash (five cases), prostration (four cases), meningism (three cases) and pneumonia (four cases). Frequent laboratory findings were moderate thrombopenia (four cases) and elevated transaminases (four cases). Before the results of serology, clinical diagnoses were Mediterranean Spotted Fever (four cases), Q fever (one case), pneumonia (one case), and lymphocytic meningitis (one case). Serology confirmed all diagnoses with cross-reactivity with Rickettsia conorii. CONCLUSION: Murine typhus exists in Tunisia and its prevalence is underestimated. Further, more specific studies are needed to evaluate the true prevalence.

[Fever and calf tenderness after travel in Thailand: murine typhus and deep vein thrombosis]. / Fieber und Wadenschmerz nach Thailandaufenthalt: Murines Fleckfieber und tiefe Beinvenenthrombose.

HISTORY AND CLINICAL FINDINGS: A 37-year-old German fell ill with fever and diffuse headaches 3 weeks after flying to Thailand for a holiday. Because of increasing sickness he began his return (13 h by train then 11 h by plane). Besides a temperature of 39.3 degrees C he presented with a unproductive cough and pain in his left calf. On examination there were no other pathological findings than a borderline tachycardia, mild hypotension and signs of dehydration. INVESTIGATIONS: Laboratory tests showed elevated inflammatory parameters (CRP 77.8 mg/l, ESR 36 mm), normal range of leucocytes with obvious shift to the left, mild thrombocytopenia and elevated liver enzymes. The Weil-Felix-reaction revealed a high antibody titre against OX 19, the IFT for Rickettsia typhi a significant increase of IgM with seroconversion for IgG. Duplex ultrasonography and phlebography confirmed a phlebothrombosis of the left upper thigh. DIAGNOSIS: Murine typhus and deep vein thrombosis of the left upper leg. TREATMENT AND COURSE: Suspecting typhoid fever with ciprofloxacin was started. In less then 2 days the patient became afebrile and recovered. The deep vein thrombosis was treated with low-molecular-weight heparin (Tinzaparin) overlapping with phenprocoumon. CONCLUSION: In patients with fever after travel to tropical or subtropical areas (including southern Europe) the diagnosis of murine typhus should be considered, especially if concomitant with thromboembolic events. The Weil-Felix-reaction is a helpful screening test supplemented by Rickettsia specific serologic tests. Overall a higher risk of thrombosis should be taken into account after long sedentary travel.

Clinical, laboratory, and epidemiologic features of murine typhus in 97 Texas children.

OBJECTIVE: To document the clinical, laboratory, and epidemiologic characteristics of pediatric patients with murine typhus. DESIGN: Pediatric patients were diagnosed using serologic testing, and clinical, laboratory, and epidemiologic data were retrospectively reviewed. SETTING: Of 97 patients, 77 (79%) were identified and treated as inpatients and 20 (21%) were treated as outpatients; most resided in south Texas. PATIENTS: Between 1979 and 1996, medical records and patient-physician interviews were available for 97 patients aged 16 years and younger with murine typhus. MAIN OUTCOME MEASURES: The frequency of clinical symptoms and signs, abnormal laboratory findings, epidemiologic findings, and measures of disease severity were determined. RESULTS: The clinical triad of fever, headache, and rash occurred in only 43 (49%) of 87 pediatric patients throughout the illness. Musculoskeletal symptoms were experienced by 43% of patients, whereas gastrointestinal tract symptoms (nausea, vomiting, anorexia, and diarrhea) occurred in 77%. Systemic involvement was evident by the frequent occurrence of abnormal laboratory findings referable to multiple organ systems, including the liver, kidney, blood, and central nervous system. CONCLUSIONS: Pediatric infection by Rickettsia typhi usually causes mild to moderate systemic illness. In children, the median duration of illness was 12 days (range, 5-29 days), but severe complications were rare. Length of illness was significantly related to the initial diagnosis, whereas the interval to defervescence was related to therapy with a tetracycline or chloramphenicol. Early recognition and treatment is important to prevent prolonged morbidity.

Murine typhus in travelers returning from Indonesia.

We report the first three documented cases of murine typhus imported into Europe from Indonesia, discuss clues for the diagnosis of the disease, and urge that murine fever be considered in the diagnosis of febrile disease in travelers.