Murine typhus and febrile illness, Nepal.

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.

Emerging trends in enteric fever in Nepal: 9124 cases confirmed by blood culture 1993-2003.

This was a retrospective study in an urban hospital in Kathmandu, Nepal to determine the changing burden of salmonella septicaemia, the proportion of Salmonella paratyphi A, and the emergence of drug-resistant organisms. The participants were outpatients and inpatients over the period 1993-2003, and the main outcome measures were blood culture isolates and antibiotic sensitivity testing. The results showed that of 82467 blood cultures performed, a bacterium was isolated from 12252. Salmonella accounted for 9124 (74.5%) of the positive blood cultures: 6447 (70.7%) were Salmonella enterica serotype Typhi (S. typhi) and 2677 (29.3%) were Paratyphi A (S. paratyphi A). In comparing the period 1997-2000 to the period 2001-2003, we found that, as a proportion of total blood cultures taken, salmonella septicaemia more than doubled, from 6.2 to 13.6% (P<0.001). From the first half of the study (1993-1998) to the second half (1999-2003), S. paratyphi A as a proportion of all salmonella isolates rose from 23 to 34% (P<0.001), which paralleled its increased resistance to ciprofloxacin. Despite the introduction of new antibiotics, enteric fever continues to grow as a cause for hospital presentation in Nepal. Salmonella paratyphi A contributes an increasingly large proportion of cases, and ciprofloxacin resistance is also emerging more rapidly in S. paratyphi A.

Emergence of Salmonella enterica serotype Paratyphi A as a major cause of enteric fever in Kathmandu, Nepal.

We performed pulsed-field gel electrophoresis (XbaI) on 114 bloodstream isolates of Salmonella enterica serotype Paratyphi A and S. enterica serotype Typhi collected from febrile patients in Kathmandu, Nepal. Of the 56 S. Paratyphi A isolates, 51 (91%) were indistinguishable, which suggests the emergence of a single clone. In contrast, only 21 (36%) of the 58 S. Typhi isolates exhibited a common genotype, which is consistent with endemic disease from multiple sources.

Enteric (typhoid) fever in travelers.

The incidence of enteric (typhoid) fever in travelers is estimated to be approximately 3-30 cases per 100,000 travelers to developing countries. Recently, it is become clear that travelers who are visiting friends and relatives, especially travelers to the Indian subcontinent, seem to be the most vulnerable to enteric fever and require special attention for prevention. Recent concerns are the increasing incidence of paratyphoid fever in Asia, which is not covered by available typhoid vaccines, and the emergence of infections caused by antibiotic-resistant strains (including strains resistant to fluoroquinolones). Typhoid vaccination is recommended for most travelers to moderate- to high-risk countries. Because of the nonspecific clinical presentation of enteric fever, a high index of suspicion is important in febrile travelers who have traveled to areas of endemicity.

The etiology of febrile illness in adults presenting to Patan hospital in Kathmandu, Nepal.

In Nepal, many infections remain poorly characterized, partly due to limited diagnostic facilities. We studied consecutive febrile adults presenting to a general hospital in Kathmandu, Nepal. Of the 876 patients enrolled, enteric fever and pneumonia were the most common clinical diagnoses. Putative pathogens were identified in 323 (37%) patients, the most common being Salmonella enterica serotype Typhi and S. enterica serotype Paratyphi A (117), Rickettsia typhi (97), Streptococcus pneumoniae (53), Leptospira spp. (36), and Orientia tsutsugamushi (28). Approximately half of the Salmonella isolates were resistant to nalidixic acid. No clinical predictors were identified to reliably distinguish between the different infections. These findings confirm the heavy burden of enteric fever and pneumonia in Kathmandu, and highlight the importance of murine typhus, scrub typhus, and leptospirosis. Given the lack of reliable clinical predictors, the development of cheap and accurate diagnostic tests are likely to be of great clinical utility in this setting.

An open randomized comparison of gatifloxacin versus cefixime for the treatment of uncomplicated enteric fever.

OBJECTIVE: To assess the efficacy of gatifloxacin versus cefixime in the treatment of uncomplicated culture positive enteric fever. DESIGN: A randomized, open-label, active control trial with two parallel arms. SETTING: Emergency Room and Outpatient Clinics in Patan Hospital, Lagankhel, Lalitpur, Nepal. PARTICIPANTS: Patients with clinically diagnosed uncomplicated enteric fever meeting the inclusion criteria. INTERVENTIONS: Patients were allocated to receive one of two drugs, Gatifloxacin or Cefixime. The dosages used were Gatifloxacin 10 mg/kg, given once daily for 7 days, or Cefixime 20 mg/kg/day given in two divided doses for 7 days. OUTCOME MEASURES: The primary outcome measure was fever clearance time. The secondary outcome measure was overall treatment failure (acute treatment failure and relapse). RESULTS: Randomization was carried out in 390 patients before enrollment was suspended on the advice of the independent data safety monitoring board due to significant differences in both primary and secondary outcome measures in the two arms and the attainment of a priori defined endpoints. Median (95% confidence interval) fever clearance times were 92 hours (84-114 hours) for gatifloxacin recipients and 138 hours (105-164 hours) for cefixime-treated patients (Hazard Ratio[95%CI] = 2.171 [1.545-3.051], p<0.0001). 19 out of 70 (27%) patients who completed the 7 day trial had acute clinical failure in the cefixime group as compared to 1 out of 88 patients (1%) in gatifloxacin group(Odds Ratio [95%CI] = 0.031 [0.004 - 0.237], p<0.001). Overall treatment failure patients (relapsed patients plus acute treatment failure patients plus death) numbered 29. They were determined to be (95% confidence interval) 37.6 % (27.14%-50.2%) in the cefixime group and 3.5% (2.2%-11.5%) in the gatifloxacin group (HR[95%CI] = 0.084 [0.025-0.280], p<0.0001). There was one death in the cefixime group. CONCLUSIONS: Based on this study, gatifloxacin is a better treatment for uncomplicated enteric fever as compared to cefixime. TRIAL REGISTRATION: Current Controlled Trials ISRCTN75784880.

In vivo RF powering for advanced biological research.

An optimized remote powering architecture with a miniature and implantable RF power converter for an untethered small laboratory animal inside a cage is proposed. The proposed implantable device exhibits dimensions less than 6 mmx6 mmx1 mm, and a mass of 100 mg including a medical-grade silicon coating. The external system consists of a Class-E power amplifier driving a tuned 15 cmx25 cm external coil placed underneath the cage. The implant device is located in the animal's abdomen in a plane parallel to the external coil and utilizes inductive coupling to receive power from the external system. A half-wave rectifier rectifies the received AC voltage and passes the resulting DC current to a 2.5 kOmega resistor, which represents the loading of an implantable microsystem. An optimal operating point with respect to operating frequency and number of turns in each coil inductor was determined by analyzing the system efficiency. The determined optimal operating condition is based on a 4-turn external coil and a 20-turn internal coil operating at 4 MHz. With the Class-E amplifier consuming a constant power of 25 W, this operating condition is sufficient to supply a desired 3.2 V with 1.3 mA to the load over a cage size of 10 cmx20 cm with an animal tilting angle of up to 60 degrees, which is the worst case considered for the prototype design. A voltage regulator can be designed to regulate the received DC power to a stable supply for the bio-implant microsystem.