Murine Typhus and Febrile Illness, Nepal

Abstract

Murine typhus was diagnosed by PCR in 50 (7%) of 756 adults with febrile illness seeking treatment at Patan Hospital in Kathmandu, Nepal. Of patients with murine typhus, 64% were women, 86% were residents of Kathmandu, and 90% were unwell during the winter. No characteristics clearly distinguished typhus patients from those with blood culture-positive enteric fever.I n 2001, we found Salmonella enterica serotype Typhi and S. enterica serotype Paratyphi A to be the most common causes of bloodstream infections among adults with febrile illness who sought treatment at Patan Hospital in Kathmandu, Nepal (1). Another important fi nding was the relatively high percentage of patients (11%) who had immunoglobulin (Ig) M antibodies against Rickettsia typhi in peripheral blood. Because most testing was performed on unpaired acute-phase sera, and a high percentage of seropositive results were found in a group of healthy study participants, we were uncertain whether these participants had acute murine typhus or more distant past infection.Recent studies have shown the value of PCR for diagnosing scrub typhus (2-4), and a real-time assay for R. typhi has recently been validated (5). In our study, we tested archived blood samples from our febrile adult cohort (1) with this R. typhi PCR to better characterize the incidence of murine typhus and to determine whether clinical features could help distinguish murine typhus from enteric (typhoid) fever. The StudyWe studied consecutive adult patients with fever (axillary temperature >38°C; >13 years of age) who sought treatment at Patan Hospital from January 15 through March 15, 2001 (winter) and July 2 through August 10, 2001 (summer), as detailed elsewhere (1). The study was approved by the Nepal Health Research Council and the Institutional Review Board of the Centers for Disease Control and Prevention. Blood from each patient was injected into blood culture bottles and serum samples were tested for R. typhi IgM antibodies (INDX Multi-Test Dip-S-Ticks SDLST; Integrated Diagnostics, Inc., Baltimore, MD, USA). In addition, whole blood samples (stored at −80ºC) were tested by real-time PCR for R. typhi at the Naval Medical Research Center, Silver Spring, MD (NMRC) and at Canterbury Health Laboratories, Christchurch, New Zealand (CHL). Details of the assay have been described elsewhere (5). We extracted DNA from 200 μL of whole blood and used primers and probes specifi c to a portion of the outer membrane protein B (ompB) unique to R. typhi to amplify and detect the target sequence in a SmartCycler (Cepheid, Sunnyvale, CA, USA) at NMRC and in a LightCycler (Roche Diagnostics, Mannheim, Germany) thermocycler at CHL. Thermocycling parameters included an initial denaturation step (2 min at 9°C) followed by 45 cycles of denaturation (94°C for 5 s) and annealing/ elongation (60°C for 30 s) steps. Positive samples were defi ned as those that demonstrated fl uorescence above background levels. Template-free controls assayed at the same time and under the same conditions as the experimental a...

Bloodstream Infection among Children Presenting to a General Hospital Outpatient Clinic in Urban Nepal

“…Recently, relatively high rate of murine typhus was reported among febrile adults in Nepal [7], and serological studies performed in various countries outside the region highlight the importance of this disease in children [8], [9], [10], [11].…”

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“…Another study done in Patan Hospital reported that no characteristics clearly distinguished typhus patients from those with blood culture-positive enteric fever 22 . A study done in Birendra hospital Kathmandu reported that Ofloxacin was most sensitive antibiotic in 95.23 % cases followed by third generation cephalosporins (Ceftriaxone and Cefixime) in 90.47 % cases.…”

An Unusual Cutaneous Manifestation in a Patient with Murine Typhus

“…In 10 large case series describing 841 patients with murine typhus, rash was found in 59%, but no localized inoculationtype lesions, similar to the one described here, were reported. [4][5][6][7][8][9][10][11][12][13] In a guinea pig model of R. typhi infection, intradermal inoculation of the organism resulted in cutaneous erythema, induration, and necrosis. 18 In another animal model, intended to predict eschar formation following infection with various rickettsial species, R. typhi failed to produce eschars in intradermally inoculated guinea pigs-a finding which the authors state is consistent with what is known clinically of typhus group rickettsioses in humans.…”

“…3 The disease presents as an undifferentiated febrile illness accompanied by a maculopapular rash in 59% of infected persons. [4][5][6][7][8][9][10][11][12][13] Unlike many spotted fever group rickettsioses (SFGR) and scrub typhus, infection caused by R. typhi is not associated with an inoculation lesion. We herein describe a patient with murine typhus and an unusual clinical feature at the site of rickettsial inoculation.…”