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.

Cluster of Angiostrongyliasis Cases Following Consumption of Raw Monitor Lizard in the Lao People's Democratic Republic and Review of the Literature.

Angiostrongyliasis in humans causes a range of symptoms from mild headache and myalgia to neurological complications, coma and death. Infection is caused by the consumption of raw or undercooked intermediate or paratenic hosts infected with Angiostrongylus cantonensis or via contaminated vegetables or water. We describe a cluster of cases involved in the shared meal of wild raw monitor lizard in the Lao PDR. Seven males, aged 22-36 years, reported headaches, abdominal pain, arthralgia, myalgia, nausea/vomiting, diarrhea, neurological effects and loss of appetite. Five were admitted to hospital. The final diagnosis was made by clinical presentation and case history, and positive A. cantonensis PCR for two cases. All hospitalized patients recovered fully following supportive treatment. The remaining two individuals sought local home remedies and made full recovery. Whilst most published reports concern infections via consumption of molluscs, few detailed reports exist on infections that result from the consumption of reptiles and there exists little awareness in Lao PDR. This case cluster, which originates from a single meal, highlights the potential public health risk of the consumption of raw and wild-caught meat in Lao PDR and the Southeast Asia region. Without specific diagnostics, clinical history and the consideration of recent food consumption are important when evaluating patients.

A randomized comparison of oral chloramphenicol versus ofloxacin in the treatment of uncomplicated typhoid fever in Laos.

We conducted a randomized open trial of oral chloramphenicol (50mg/kg/day in four divided doses for 14 days) versus ofloxacin (15 mg/kg/day in two divided doses for 3 days) in 50 adults with culture-confirmed uncomplicated typhoid fever in Vientiane, Laos. Patients had been ill for a median (range) of 8 (2-30) days. All Salmonella enterica serotype typhi isolates were nalidixic acid-sensitive, four (8%) were chloramphenicol-resistant and three (6%) were multidrug-resistant. Median (range) fever clearance times were 90 (24-224) hours in the chloramphenicol group and 54 (6-93) hours in the ofloxacin group (P<0.001). One patient in the chloramphenicol group developed an ileal perforation. Three days ofloxacin was more effective than 14 days chloramphenicol for the in-patient treatment of typhoid fever, irrespective of antibiotic susceptibility, and was of similar cost.

Rickettsial infections and fever, Vientiane, Laos.

Rickettsial diseases have not been described previously from Laos, but in a prospective study, acute rickettsial infection was identified as the cause of fever in 115 (27%) of 427 adults with negative blood cultures admitted to Mahosot Hospital in Vientiane, Laos. The organisms identified by serologic analysis were Orientia tsutsugamushi (14.8%), Rickettsia typhi (9.6%), and spotted fever group rickettsia (2.6% [8 R. helvetica, 1 R. felis, 1 R. conorii subsp. indica, and 1 Rickettsia "AT1"]). Patients with murine typhus had a lower frequency of peripheral lymphadenopathy than those with scrub typhus (3% vs. 46%, p<0.001). Rickettsioses are an underrecognized cause of undifferentiated febrile illnesses among adults in Laos. This finding has implications for the local empiric treatment of fever.