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.

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 in 5 Children Hospitalized for Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) is an emerging disease described in children in association with infection or epidemiological link to severe acute respiratory syndrome coronavirus 2. Signs and symptoms include fever, rash, and cardiac dysfunction; US Centers for Disease Control and Prevention have put forth broad criteria for diagnosis. The illness is serious and can progress rapidly to heart failure and death. However, findings in MIS-C are nonspecific, and there is significant overlap with other systemic illnesses, including Kawasaki disease and several viral and bacterial infections. We present 5 children admitted to a teaching hospital within an 11-day period in May 2020 for MIS-C evaluation who were later diagnosed with murine typhus. Typhus is a rickettsial infection that presents with fever and rash, and, although usually self-limited, responds well to treatment with doxycycline to shorten the course of illness. Clinical and laboratory characteristics of these children are presented to illustrate similarities to MIS-C, which can also be shared with viral, bacterial, or other regional endemic infections, as well as noninfectious inflammatory diseases. This case series serves to remind pediatric hospitalists to be vigilant to avoid premature closure on MIS-C for children admitted with fever and systemic inflammation. Maintaining a wide differential diagnosis in approaching such patients is of utmost importance as community exposure to severe acute respiratory syndrome coronavirus 2 is likely and evidence of past infection becomes commonplace.

Murine Typhus Presenting With Mucosal Involvement.

Lipschutz ulcers (LU) present as painful genital ulcers in nonsexually active females. Associated infections include Epstein Barr virus, Mycoplasma pneumoniae, Cytomegalovirus, and influenza. To our knowledge, this is the first report of LU occurring with murine typhus. Murine typhus is caused by Rickettsia typhi, a Gram-negative, obligate intracellular organism. Rat fleas (Xenopsylla cheopis) are the classic vector, although cat fleas (Ctenocephalides felis) found on cats, dogs, and opossums have been implicated in maintaining the life cycle of R. typhi in suburban areas. Murine typhus can have a nonspecific presentation making a strong index of suspicion crucial to its diagnosis. The most common presenting signs include fever, poor appetite, malaise, and headache. Laboratory abnormalities may include elevated C-reactive protein, elevated erythrocyte sedimentation rate, hypoalbuminemia, elevated transaminases, elevated neutrophil band count, and thrombocytopenia. The treatment of choice for R. typhi is doxycycline.

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.

Typhus Group Rickettsiosis, Brazilian Amazon.

Rickettsia rickettsii infection is the only rickettsiosis included in the list of reportable diseases in Brazil, where typhus group rickettsioses, mainly murine typhus, have been underreported. We report a case of typhus group rickettsiosis with unique ecologic particularities in a patient from the Brazilian Amazon, where, to our knowledge, rickettsioses have not been reported.

Serum C-reactive protein and procalcitonin values in acute Q fever, scrub typhus, and murine typhus.

BACKGROUND: Although C-reactive protein (CRP) and procalcitonin (PCT) are widely used inflammatory markers for infectious diseases, their role and potential application for rickettsioses were rarely studied. METHODS: A retrospective chart review and serological study were conducted in patients with rickettsioses. The clinical presentations, characteristics, laboratory data, and treatment responses were recorded and their associations with CRP and PCT values were analyzed. RESULTS: A total of 189 cases of rickettsioses, including 115 cases of acute Q fever (60.8%), 55 cases of scrub typhus (29.1%), and 19 cases of murine typhus (10.1%) were investigated. Both CRP and PCT values increased in the acute phase and declined in the convalescent phase. In the acute phase, mean CRP and PCT values were 78.2 ± 63.7 mg/L and 1.05 ± 1.40 ng/mL, respectively. Percentages of patients falling under different cut-off values of CRP and PCT were calculated systematically. Only 10.8% of CRP was > 150 mg/L and 14.2% of PCT was > 2.0 ng/mL. Patients with delayed responses to doxycycline treatment (> 3 days from treatment to defervescence) had significantly higher CRP values (102.7 ± 77.1 vs. 72.2 ± 58.2 mg/L, p = 0.041) and more PCT > 1.0 ng/ml (48.4% vs. 26.0%, p = 0.019) in the acute phase; higher CRP values (19.1 ± 37.4 vs. 3.6 ± 13.1 mg/L, p = 0.049) and more PCT > 0.5 ng/ml (19.2% vs. 1.4%, p = 0.005) in the convalescent phase. Correlation analysis was conducted for patients with acute Q fever. CRP and PCT values were positively correlated to each other, and both markers also had a positive correlation with serum aspartate transaminase values. Both CRP and PCT values and white blood cell counts were positively correlated to the days needed from doxycycline treatment to defervescence. CONCLUSION: CRP and PCT values might be useful in clinical investigations for patients with suspected rickettsioses and in predicting the response to doxycycline treatment for rickettsioses.

The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients.

OBJECTIVES: This study examined individuals with Rickettsia typhi infection in the Lao People's Democratic Republic (Lao PDR) to (a) investigate humoral immune dynamics; (b) determine the differences in reference diagnostic results and recommend appropriate cut-offs; (c) determine differences in immune response after different antibiotic treatments; and (d) determine appropriate diagnostic cut-off parameters for indirect immunofluorescence assay (IFA). METHODS: Sequential serum samples from 90 non-pregnant, adults were collected at seven time-points (days 0, 7, 14, 28, 90, 180 and 365) as part of a clinical antibiotic treatment trial. Samples were tested using IFA to determine IgM and IgG antibody reciprocal end-point titres against R. typhi and PCR. RESULTS: For all 90 individuals, reciprocal R. typhi IgM and IgG antibody titres ranged from <400 to ≥3200. The median half-life of R. typhi IgM was 126 days (interquartile range 36-204 days) and IgG was 177 days (interquartile range 134-355 days). Overall median patient titres for R. typhi IgM and IgG were significantly different (p < 0.0001) and at each temporal sample collection point (range p < 0.0001 to p 0.0411). Using Bayesian latent class model analysis, the optimal diagnostic cut-off reciprocal IFA titer on patient admission for IgM was 800 (78.6%, 95% CI 71.6%-85.2% sensitivity; 89.9%, 95% CI 62.5%-100% specificity), and for IFA IgG 1600 (77.3%; 95% CI 68.2%-87.6% sensitivity; 99%, 95% CI 95%-100% specificity). CONCLUSIONS: This study suggests suitable diagnostic cut-offs for local diagnostic laboratories and other endemic settings and highlights antibody persistence following acute infection. Further studies are required to validate and define cut-offs in other geographically diverse locations.

Case Report: Early Doxycycline Therapy for Potential Rickettsiosis in Critically Ill Patients in Flea-Borne Typhus-Endemic Areas.

Flea-borne typhus (FBT), although usually perceived as a self-resolving febrile illness, actually encompasses a wide spectrum of disease severity, including fulminant sepsis with multi-organ failure. In endemic Texas and California, the incidence of FBT has more than doubled over the last decade. Clinicians remain unfamiliar with severe septic presentations of FBT when considering the etiologies of acute undifferentiated febrile syndromes. The diagnostic challenges of FBT include the nonspecific and variable nature of both history and physical examination and the lack of diagnostic testing that can provide clinically relevant information early in the course of infection. These barriers perpetuate misdiagnoses in critically ill patients and lead to delay in initiating appropriate antibiotics, which may contribute to preventable morbidity and mortality. This case series describes the clinical and diagnostic trajectories of three patients who developed FBT-associated multi-organ dysfunction. These patients achieved resolution of infection after receiving doxycycline in the context of a high clinical suspicion. Patients residing in FBT-endemic areas presenting with a febrile illness of unknown etiology with a suggestive constellation of hyponatremia, elevated transaminase levels, and thrombocytopenia should be suspected of having FBT. Clinicians should proceed to serologic testing with early doxycycline therapy for potential rickettsiosis. Familiarizing clinicians with the presentation of rickettsiosis-associated septic syndromes and its early and appropriate antibiotic treatment can provide lifesaving care and reduce health-care costs through prevention of the morbidity associated with FBT.

First description of a clinical case of murine typhus in Campeche, Mexico.

Murine typhus is a flea-borne disease caused by Rickettsia typhi, which was first detected in Mexico in 1927. It was not until 1996 that the first systematized study involving this pathogen was conducted in two coastal states of Mexico. We now report the first confirmed case of murine typhus in the state of Campeche, which occurred in a male patient who exhibited fever, thrombocytopenia, hyperbilirubinemia, and a rash. Furthermore, the patient reported having had previous contact with Rickettsia reservoirs.

Murine typhus in Mexico City: report of an imported case.

Murine typhus is endemic in several countries. We herein report an imported case of murine typhus caused by Rickettsia typhi in Mexico City. This is the first report of a case after almost 20 years since the last report. The species was confirmed by DNA sequencing and phylogenetic reconstruction.

A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus.

BACKGROUND: Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy. METHODS: A prospective, open, randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse. RESULTS: Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)-confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P < .001). Among R. typhi PCR-positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P = .005) and D7 (1.5- and 1.6-fold higher; P = .02). No patients returned with PCR-confirmed R. typhi relapse. CONCLUSION: In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed. CLINICAL TRIAL REGISTRATION: ISRCTN47812566.

First description of a clinical case of murine typhus in Campeche, Mexico

Abstract Murine typhus is a flea-borne disease caused by Rickettsia typhi, which was first detected in Mexico in 1927. It was not until 1996 that the first systematized study involving this pathogen was conducted in two coastal states of Mexico. We now report the first confirmed case of murine typhus in the state of Campeche, which occurred in a male patient who exhibited fever, thrombocytopenia, hyperbilirubinemia, and a rash. Furthermore, the patient reported having had previous contact with Rickettsia reservoirs.

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.

Murine Typhus Mimicking Kawasaki Disease in a Preadolescent Girl.

We report the case of an 11-year-old preadolescent girl presenting with prolonged fever, lymphadenitis, nonpurulent conjunctivitis, a generalized maculopapular rash, erythematous lips and edema of hands/feet. Although major diagnostic criteria for Kawasaki disease were met, local epidemiologic data suggested a possible vector-borne etiology. Treatment with doxycycline was initiated, and defervescence occurred. Laboratory investigation confirmed the diagnosis of Rickettsia typhi infection.