Acute diarrhoeal diseases remain a leading cause of global morbidity and mortality particularly among young children in resource-limited countries. Recent large studies utilizing case-control design, prospective sampling and more sensitive and broad diagnostic techniques have shed light on particular pathogens of importance and highlighted the previously under recognized impact of these infections on post-acute illness mortality and growth. Vaccination, particularly against rotavirus, has emerged as a key effective means of preventing significant morbidity and mortality from childhood diarrhoeal disease. Other candidate vaccines against leading diarrhoeal pathogens, such as enterotoxigenic and spp., also hold significant promise in further ameliorating the burden of enteric infections in children. Large studies are also currently underway evaluating novel and potential easy-to-implement water, sanitation and hygiene (WASH) preventive strategies. Given the ongoing global burden of this illness, the paucity of new advances in case management over the last several decades remains a challenge. The increasing recognition of post-acute illness mortality and growth impairment has highlighted the need for interventions that go beyond management of dehydration and electrolyte disturbances. The few trials of novel promising interventions such as probiotics have mainly been conducted in high-income settings. Trials of antimicrobials have also been primarily conducted in high-income settings or in travellers from high-income settings. Bloody diarrhoea has been shown to be a poor marker of potentially treatable bacterial enteritis, and rising antimicrobial resistance has also made empiric antimicrobial therapy more challenging in many settings. Novel effective and sustainable interventions and diagnostic strategies are clearly needed to help improve case management. Diarrhoeal disease and other enteric infections remain an unmet challenge in global child health. Most promising recent developments have been focused around preventive measures, in particular vaccination. Further advances in prevention and case management including the possible use of targeted antimicrobial treatment are also required to fully address this critical burden on child health and human potential.

f Two-hundred eighty matched bulk stool and anatomically designed flocked rectal swab samples were collected from children admitted to the hospital with acute diarrhea in Botswana. Their parents were asked about the acceptability of the swab collection method compared with bulk stool sampling. All samples underwent identical testing with a validated 15-target (9 bacterial, 3 viral, and 3 parasite) commercial multiplex PCR assay. The flocked swabs had a 12% higher yield for bacterial pathogen targets (241 versus 212; P ‫؍‬ 0.003) compared with that of stool samples, as well as similar yields for viral targets (110 versus 113; P ‫؍‬ 0.701) and parasite targets (59 versus 65; P ‫؍‬ 0.345). One hundred sixty-four of the flocked swab-stool pairs were also tested with separate laboratory-developed bacterial and viral multiplex assays, and the flocked rectal swabs had a performance that was similar to that seen with commercial assay testing. Almost all parents/guardians found the swabs acceptable. Flocked rectal swabs significantly facilitate the molecular diagnosis of diarrheal disease in children. Diarrheal disease remains a leading cause of global childhood morbidity and mortality, yet access to diagnostic laboratory testing is rarely available in much of the world. One of the barriers to diagnosing diarrheal disease, either for clinical or surveillance purposes, is the difficulty and time delays in obtaining and transporting a bulk stool specimen. Several investigators have sought to overcome this barrier through the use of rectal swab specimens for culture, molecular, and antigen testing, with variable results (1-5). Flocked swabs designed for respiratory and genitourinary sampling have been shown to acquire better samples than those acquired with more traditional spun fiber swabs (6, 7). We used a specially designed flocked rectal swab (FLOQSwabs; Copan Italia, Brescia, Italy) developed specifically for the diagnosis of diarrheal disease in children (Fig. 1) and then compared matched flocked rectal swabs to bulk stool samples in a clinical setting. The samples were collected from children admitted to the hospital in Botswana with severe acute gastroenteritis and tested using a U.S. FDAcleared commercial multiplex PCR assay in order to assess performance across a broad number of bacterial, viral, and parasitic pathogens.(These data were presented in part at the 29th Annual Clinical Virology Symposium, Daytona Beach, FL, 28 April to 1 May 2013, and at the Annual Pediatric Academic Society Meeting, Vancouver, Canada, 5 May 2014.) MATERIALS AND METHODSChildren Ͻ13 years of age who were admitted to the hospital with a diagnosis of acute gastroenteritis were enrolled prospectively at the Princess Marina Hospital in Gaborone, Botswana. Princess Marina Hospital is the largest referral hospital in Botswana.Clinical data were collected, and both the pediatric flocked rectal swab and bulk stool samples were obtained from each child as soon as possible after enrollment. The swab and stool samples were collected simultaneousl...

BackgroundCryptococcal meningitis (CM) causes 10%–20% of HIV-related deaths in Africa. Due to limited access to liposomal amphotericin and flucytosine, most African treatment guidelines recommend amphotericin B deoxycholate (AmB-d) plus high-dose fluconazole; outcomes with this treatment regimen in routine care settings have not been well described.MethodsElectronic national death registry data and computerized medical records were used to retrospectively collect demographic, laboratory, and 1-year outcome data from all patients with CM between 2012 and 2014 at Botswana’s main referral hospital, when recommended treatment for CM was AmB-d 1 mg/kg/d plus fluconazole 800 mg/d for 14 days. Cumulative survival was estimated at 2 weeks, 10 weeks, and 1 year.ResultsThere were 283 episodes of CM among 236 individuals; 69% (163/236) were male, and the median age was 36 years. All patients were HIV-infected, with a median CD4 count of 39 cells/mm3. Two hundred fifteen person-years of follow-up data were captured for the 236 CM patients. Complete outcome data were available for 233 patients (99%) at 2 weeks, 224 patients (95%) at 10 weeks, and 219 patients (93%) at 1 year. Cumulative mortality was 26% (95% confidence interval [CI], 20%–32%) at 2 weeks, 50% (95% CI, 43%–57%) at 10 weeks, and 65% (95% CI, 58%–71%) at 1 year.ConclusionsMortality rates following HIV-associated CM treated with AmB-d and fluconazole in a routine health care setting in Botswana were very high. The findings highlight the inadequacies of current antifungal treatments for HIV-associated CM and underscore the difficulties of administering and monitoring intravenous amphotericin B deoxycholate therapy in resource-poor settings.

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