A prospective, open-label, randomized trial of doxycycline versus azithromycin for the treatment of uncomplicated murine typhus

Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy.; 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.; 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.; 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.; ISRCTN47812566

Rickettsial Infections and Fever, Vientiane, Laos

Rickettsia spp. are an underrecognized cause of undifferentiated febrile illness

Simultaneous multiple regression analyses.

<p>Simultaneous multiple regression analyses.</p

A comparison of Lao Loum anthropometric and clinical data collected 5 years apart.

<p>A comparison of Lao Loum anthropometric and clinical data collected 5 years apart.</p

<i>APOE</i> Genotype in the Ethnic Majority and Minority Groups of Laos and the Implications for Non-Communicable Diseases

<div><p>Background</p><p>Increasing age is associated with elevated risk of non-communicable diseases, including dementia and Alzheimer’s disease (AD). The apolipoprotein E (<i>APOE</i>) ε4 allele is a risk factor not only for AD, but also for cognitive decline, depressive symptoms, stroke, hypertension, coronary heart disease, cardiovascular disease, and diabetes. The Lao People’s Democratic Republic (Laos) is undergoing development; consequently, life expectancy has risen. To evaluate the future risk of non-communicable diseases, we investigated <i>APOE</i> genotypes and anthropometric characteristics in the Laotian population.</p><p>Methodology/Principal Findings</p><p>Subjects were 455 members of the Lao Loum majority and 354 members of ethnic minorities. <i>APOE</i> genotypes, anthropometric characteristics, blood pressure, and blood glucose were recorded. To compare individual changes, health examination data collected 5 years apart were obtained from a subset of Lao Loum subjects. <i>APOE</i> ε4 allele frequencies were higher among minorities (31.3%) than among Lao Loum (12.6%). In Lao Loum, but not in minorities, mean waist circumference and blood pressure increased significantly across age groups. Comparisons of health conditions between the beginning and end of the 5-year period revealed significant increases in obesity and blood glucose levels in Lao Loum. <i>APOE</i> ε4 carriers exhibited significant increases in resting heart rate in both ethnic groups.</p><p>Conclusions/Significance</p><p>A higher ε4 allele frequency was observed in Laotian minorities than in the Laotian majority. Furthermore, higher obesity, blood pressure and blood glucose were observed in the middle-aged ethnic majority. Therefore, given these genetic and non-communicable disease risk factors, it seems likely that as the Laotian population ages, elevated rates of non-communicable aging-related diseases, such as dementia, will also become more prevalent.</p></div

Breakdown of participants by age and gender category.

<p>Breakdown of participants by age and gender category.</p

Comparison of <i>APOE</i> ε4 Carriers with non-carriers.

<p>Statistical analysis was performed using the Mann–Whitney U test (#; <i>P</i> < 0.05, ##; <i>P</i> < 0.01, significant difference relative to non-carriers). Outliers are represented by open circles (values between 1.5 and 3 times greater than the interquartile range).</p

Anthropometric and clinical characteristics of age categories in Lao Loum and minorities.

<p>Anthropometric and clinical characteristics of age categories in Lao Loum and minorities.</p

Genotype distribution of the <i>APOE</i> polymorphism in Laos.

<p>Genotype distribution of the <i>APOE</i> polymorphism in Laos.</p