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.

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.

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.

Fatal murine typhus with hemophagocytic lymphohistiocytosis in a child.

Hemophagocytic lymphohistiocytosis is a rare complication in Rickettsia typhi infections. We report the case of a 2-year-old boy with sudden night-onset fever, pallor, neck adenopathy and erythematous macular rash on the thorax, thighs and buttocks. During admission, he developed hyponatremia, hypoalbuminemia, anemia, thrombocytopenia, leukopenia, neutropenia, liver damage, hemorrhages and persistent fever. No hematological improvement was observed after the initial management, neoplastic diseases were discarded by bone marrow aspiration and lymph node biopsy; hemophagocytic lymphohistiocytosis was diagnosed. By immunohistochemistry and indirect immunofluorescence, murine typhus was also diagnosed and doxycycline was started with transitory recovery. Later, the child developed kidney failure and distributive shock that evolved to cardiac arrest and death. This is the first case report in Mexico on a fatal murine typhus associated with hemophagocytic lymphohistiocytosis in which the etiology was evidenced by histopathology.

Case Report: Renal Failure due to Focal Segmental Glomerulosclerosis in a Patient with Murine Typhus.

Murine typhus is a flea-borne rickettsiosis caused by Rickettsia typhi. When severe, endothelial dysfunction can lead to acute kidney injury secondary to prerenal azotemia or acute tubular necrosis. Here, we describe an unusual cause of kidney injury during the course of murine typhus-focal segmental glomerulosclerosis.

The epidemiology, characteristics and outbreaks of human leptospirosis and the association with animals in Taiwan, 2007-2014: A nationwide database study.

BACKGROUND: Leptospirosis (LS) is a neglected tropical zoonosis of global importance. A nationwide investigation of characteristics, epidemiology, risk factors and outbreak is crucial for awareness of this disease. METHODS: A nationwide database of reported LS cases from October 2007 to December 2014 obtained from the Centers for Disease Control, Taiwan, was analysed. Geographic information system software was used to map the distribution of confirmed LS cases and pigs. Cross-matching with the databases of Q fever, scrub typhus and murine typhus was conducted to identify possible coinfections. RESULTS: A total of 10,917 reported cases of LS were recorded in the database, which included 665 (6.1%) confirmed LS and 10,252 (93.9%) non-confirmed LS cases. The major residences of confirmed LS were the Kaohsiung-Pingtung (248, 37.3%) and Taipei (174, 26.2%) regions. The average annual incidence was 0.4/100,000 people. Compared with non-confirmed LS cases, confirmed LS cases had significantly higher percentages of male gender (83.6% vs. 67.9%, p < .001), high-risk occupations (farmer, animal husbandry or veterinarian) (24.8% vs. 13.7%, p < .001), residence in the Kaohsiung-Pingtung region (37.3% vs. 19.6%, p < .001) and exposure to rats (8.6% vs. 4.9%, p = .001) or pigs (9.4% vs. 1.9%, p < .001) but a lower mean age (47.8 ± 15.1 vs. 51.±18.5 years old). Rat and pig exposure trends were found in the northern and southern regions, respectively. Distribution of LS was consistent with pigs, and one outbreak associated with flooding and pigs occurred in the Pingtung region in 2009. Twenty-three and four patients with LS were coinfected with scrub typhus and Q fever, respectively. CONCLUSIONS: LS is an endemic disease in Taiwan, particularly in the Kaohsiung-Pingtung and Taipei regions. High-risk occupations and animal exposure history are important for the clinical presumptive diagnosis of LS, particularly for rats in northern Taiwan and pigs in southern Taiwan. Although uncommon, clinicians should be aware of coinfection of LS with endemic rickettsial diseases.

Murine typhus presenting with status epilepticus.

Patients with rickettsial infection usually present with a febrile illness, headache, arthromyalgia and various biochemical abnormalities. Neurologic involvement is rare in murine typhus. Here, we report a case of a patient who presented with status epilepticus secondary to Rickettsia typhi infection.

Seroprevalence of Dengue Virus and Rickettsial Infections in Cambodian Children.

Scrub typhus (ST, Orientia tsutsugamushi), murine typhus (MT, Rickettsia typhi), and dengue virus (DENV) are important causes of childhood morbidity in Cambodia. This prospective, cross-sectional seroprevalence study determined the proportion of Cambodian children infected by these pathogens and the ages at which initial infection is likely to occur. A total of 993 patient serum samples were tested for MT- and ST-specific IgG, and 837 samples tested for DENV-specific IgG. Overall, ST, MT, and DENV seroprevalence was high, estimated at 4.2%, 5.3%, and 50.7%, respectively. Scrub typhus and MT seropositivity peaked in children aged 8-11 and 12-15 years, respectively, suggesting initial infection occurs in these ages. Dengue virus seroprevalence steadily increased with age, indicating constant DENV exposure. The results of this study suggest that in Cambodian children presenting with undifferentiated febrile illness, dengue should be considered high in the list of differential diagnoses, and empirical anti-rickettsial antimicrobial therapy may be more indicated in 8- to 15-year-olds.

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.

Case Report: Fulminant Murine Typhus Presenting with Status Epilepticus and Multi-Organ Failure: an Autopsy Case and a Review of the Neurologic Presentations of Murine Typhus.

Murine typhus (MT) is an important cause of febrile illness in endemic areas, and there is an epidemiologic resurgence of this infection currently transpiring in Texas and California. Fatal cases and severe neurological complications are rare. A fatal case of MT in a middle-aged man is reported with a course culminating in multi-organ failure and refractory status epilepticus. An autopsy revealed hemorrhagic pneumonia, acute tubular necrosis, and ischemic necrosis in the liver, adrenals, and brain. We have also reviewed the neurologic complications of MT.

Murine Typhus with Marked Thrombocytopenia in a Child in Northern Greece and Literature Review.

We report a case of murine typhus in a 4-year-old boy living in northern Greece. Although the illness started with mild symptoms, a maculopapular rash appeared by the end of the first week of illness followed by marked thrombocytopenia. The detection of IgM antibodies against Rickettsia typhi in the patient's blood and a positive polymerase chain reaction result combined with sequencing confirmed the diagnosis of infection by Rickettsia typhi. Clinicians in northern Greece should be aware of the disease, even in cases presenting with no specific initial symptoms.

An Unusual Presentation of Murine Typhus and Mononucleosis.

A 20-year-old female presented to the emergency department complaining of fever, cough, and dyspnea after a recent camping trip. The patient remained ill appearing, persistently tachycardic and dyspneic despite nebulizer treatments, and fluids in the emergency department. She was admitted for observation and gradually improved over the next 4 d. Inpatient laboratory studies indicated acute Epstein-Barr virus infection and she was discharged with a presumptive diagnosis of infectious mononucleosis. However, further testing showed a simultaneous rickettsial infection producing murine typhus. The patient ultimately recovered uneventfully once proper treatment was initiated. This patient's presentation represents a unique description of simultaneous infectious mononucleosis and murine typhus which underscores the importance of maintaining a broad differential diagnosis in the approach to febrile illnesses.

Persistent febrile illnesses in Nepal: A systematic review.

BACKGROUND & OBJECTIVES: Although febrile illnesses are a frequent cause of consultation and hospitalization in low- and middle-income countries (LMICs), research has mainly focused on acute febrile illnesses (AFIs). In contrast, there are limited data on the causes of persistent febrile illnesses (PFIs) in LMIC. Lack of clarity on the differential diagnosis of PFIs in the rural tropics leads to the absence of diagnostic guidance tools. METHODS: In this study, a review of the potential causes of persistent fever defined as fever of more than seven days was done in Nepal, with a focus on nine pathogen-specific conditions. The current knowledge on their burden, distribution and diagnosis was summarized. RESULTS: Limited data were found on the incidence and public health burden of leptospirosis, murine typhus and brucellosis due to the absence of diagnostic tools outside reference laboratories and the overlap of signs and symptoms with other febrile conditions. The incidence of malaria and visceral leishmaniasis (VL) was found to be decreasing in Nepal, with some changes of the geographical areas at risk. INTERPRETATION & CONCLUSIONS: This review indicates a need for more research on the causes of PFIs in Nepal and in the region and for the development of clinical guidance tailored to current local epidemiology. Guidance tools should include specific clinical features (e.g. eschar), results of rapid diagnostic tests (e.g. malaria, VL), appropriate indications for more sophisticated tests (e.g. abdominal ultrasound, polymerase chain reaction) and recommendations for adequate use of empirical treatment.

A Severe Case of Murine Typhus Presenting With Anemia and Severe Thrombocytopenia.

We discuss a child with severe thrombocytopenia and mild anemia admitted to the Hematology service who quickly deteriorated to a life-threatening state. However, once rickettsial disease was considered in the differential diagnosis and empiric doxycycline begun, she quickly and fully recovered. A diagnostic panel, including Rickettsia typhi serology, confirmed the diagnosis of murine typhus but this occurred weeks after she had recovered. Given the potential severity of rickettsial diseases and the ease of modern travel across geographic borders, hematology-oncology providers everywhere must consider rickettsial diseases in their differential diagnosis of critically ill children and begin empiric therapy with doxycycline promptly.