SummaryBackgroundWe aimed to investigate whether gatifloxacin, a new generation and affordable fluoroquinolone, is better than chloramphenicol for the treatment of uncomplicated enteric fever in children and adults.MethodsWe did an open-label randomised superiority trial at Patan Hospital, Kathmandu, Nepal, to investigate whether gatifloxacin is more effective than chloramphenicol for treating uncomplicated enteric fever. Children and adults clinically diagnosed with enteric fever received either gatifloxacin (10 mg/kg) once a day for 7 days, or chloramphenicol (75 mg/kg per day) in four divided doses for 14 days. Patients were randomly allocated treatment (1:1) in blocks of 50, without stratification. Allocations were placed in sealed envelopes opened by the study physician once a patient was enrolled into the trial. Masking was not possible because of the different formulations and ways of giving the two drugs. The primary outcome measure was treatment failure, which consisted of at least one of the following: persistent fever at day 10, need for rescue treatment, microbiological failure, relapse until day 31, and enteric-fever-related complications. The primary outcome was assessed in all patients randomly allocated treatment and reported separately for culture-positive patients and for all patients. Secondary outcome measures were fever clearance time, late relapse, and faecal carriage. The trial is registered on controlled-trials.com, number ISRCTN 53258327.Findings844 patients with a median age of 16 (IQR 9–22) years were enrolled in the trial and randomly allocated a treatment. 352 patients had blood-culture-confirmed enteric fever: 175 were treated with chloramphenicol and 177 with gatifloxacin. 14 patients had treatment failure in the chloramphenicol group, compared with 12 in the gatifloxacin group (hazard ratio [HR] of time to failure 0·86, 95% CI 0·40–1·86, p=0·70). The median time to fever clearance was 3·95 days (95% CI 3·68–4·68) in the chloramphenicol group and 3·90 days (3·58–4·27) in the gatifloxacin group (HR 1·06, 0·86–1·32, p=0·59). At 1 month only, three of 148 patients were stool-culture positive in the chloramphenicol group and none in the gatifloxacin group. At the end of 3 months only one person had a positive stool culture in the chloramphenicol group. There were no other positive stool cultures even at the end of 6 months. Late relapses were noted in three of 175 patients in the culture-confirmed chloramphenicol group and two of 177 in the gatifloxacin group. There were no culture-positive relapses after day 62. 99 patients (24%) experienced 168 adverse events in the chloramphenicol group and 59 (14%) experienced 73 events in the gatifloxacin group.InterpretationAlthough no more efficacious than chloramphenicol, gatifloxacin should be the preferred treatment for enteric fever in developing countries because of its shorter treatment duration and fewer adverse events.FundingWellcome Trust.

The data on the burden of invasive bacterial infections and pneumonia from this study suggest that vaccines in development against Salmonella Typhi and the pneumococcus have the potential to significantly improve the health of children in Nepal.

BackgroundThere are limited data on the etiology and characteristics of bloodstream infections in children presenting in hospital outpatient settings in South Asia. Previous studies in Nepal have highlighted the importance of murine typhus as a cause of febrile illness in adults and enteric fever as a leading bacterial cause of fever among children admitted to hospital.MethodsWe prospectively studied a total of 1084 febrile children aged between 2 months and 14 years presenting to a general hospital outpatient department in Kathmandu Valley, Nepal, over two study periods (summer and winter). Blood from all patients was tested by conventional culture and by real-time PCR for Rickettsia typhi.ResultsPutative etiological agents for fever were identified in 164 (15%) patients. Salmonella enterica serovar Typhi (S. Typhi) was identified in 107 (10%), S. enterica serovar Paratyphi A (S. Paratyphi) in 30 (3%), Streptococcus pneumoniae in 6 (0.6%), S. enterica serovar Typhimurium in 2 (0.2%), Haemophilus influenzae type b in 1 (0.1%), and Escherichia coli in 1 (0.1%) patient. S. Typhi was the most common organism isolated from blood during both summer and winter. Twenty-two (2%) patients were PCR positive for R. typhi. No significant demographic, clinical and laboratory features distinguished culture positive enteric fever and murine typhus.ConclusionsSalmonella infections are the leading cause of bloodstream infection among pediatric outpatients with fever in Kathmandu Valley. Extension of immunization programs against invasive bacterial disease to include the agents of enteric fever and pneumococcus could improve the health of children in Nepal.

BackgroundSnake bite is a neglected public health problem in tropical and subtropical region. The study was conducted with objectives to determine the knowledge of first aid methods in snake bite and the perception of snake bite among the medical students of Gandaki Medical College, Pokhara, Nepal.MethodsWe conducted a cross sectional survey among 302 (231 preclinical and 71 clinical) Bachelor of Medicine and Bachelor of Surgery (MBBS) students of Gandaki Medical College using a pretested questionnaire to assess the knowledge of first aid of snake bite based on WHO protocol and perception of snakebite. The study duration was from January to May 2018. The total score of the knowledge was obtained and compared among variables using Mann-Whitney U test. Chi square test was used for comparing the responses with the level of students. P value of < 0.05 was considered as significant.ResultsAmong 302 respondents, 193(63.9%) were from Mountain districts. The families of 25 (8.3%) respondents were bitten by snakes. The correct responses were significantly higher from the 71 (23.5%) clinical students for most of the questions and the knowledge score of clinical students was significantly higher than the 231 (76.5%) preclinical students. Twenty eight (9.27%) students believed that the snake should be killed after it bites the victim and 25 (8.28%) believed that the snake will capture the image of the offender who teases it and takes revenge later. School books were the commonest source of such knowledge among the preclinical students.ConclusionMost of the preclinical students had inadequate knowledge of first aid of snake bite. The common source of the knowledge was school books which often provide faulty knowledge. Only a few students had negative perception about snakes. Incorporation of proper first aid measures in the textbooks of various levels is essential.

Cardiac impalement injury is rare and one of the most severe penetrating chest injuries, often fatal. The management of penetrating cardiac injuries is a challenging one. The success in management of impaling cardiac trauma requires stabilization of the impaling object, expeditious transfer to a facility for open heart surgery, rapid imaging, access to blood and blood products and a ready surgical team. We report a case of impalement injury to the heart by a stick, transfixing the right ventricle and its successful treatment.