Margaret Mokomane

Impact of Rotavirus Vaccination on Hospitalizations and Deaths From Childhood Gastroenteritis in Botswana.

BACKGROUND A monovalent human rotavirus vaccine (RV1) was introduced in Botswana in July 2012. We assessed the impact of RV1 vaccination on childhood gastroenteritis-related hospitalizations and deaths in 2013 and 2014. METHODS We obtained data from registers of 4 hospitals in Botswana on hospitalizations and deaths from gastroenteritis, regardless of cause, among children <5 years of age. Gastroenteritis hospitalizations and deaths during the prevaccine period (January 2009-December 2012) were compared to the postvaccine period (January 2013-December 2014). Vaccine coverage was estimated from data collected through a concurrent vaccine effectiveness study at the same hospitals. RESULTS By December 2014, coverage with ≥1 dose of RV1 was an estimated 90% among infants <1 year of age and 76% among children 12-23 months of age. In the prevaccine period, the annual median number of gastroenteritis-related hospitalizations in children <5 years of age was 1212, and of gastroenteritis-related deaths in children <2 years of age was 77. In the postvaccine period, gastroenteritis-related hospitalizations decreased by 23% (95% confidence interval [CI], 16%-29%) to 937, and gastroenteritis-related deaths decreased by 22% (95% CI, -9% to 44%) to 60. Declines were most prominent during the rotavirus season (May-October) and among infants <1 year of age, with reductions of 43% (95% CI, 34%-51%) in gastroenteritis hospitalizations and 48% (95% CI, 11%-69%) in gastroenteritis deaths. CONCLUSIONS Following introduction of RV1 into the national immunization program, significant declines in hospitalizations and deaths from gastroenteritis were observed among children in Botswana, suggestive of the beneficial public health impact of rotavirus vaccination.

Evaluation of Anatomically Designed Flocked Rectal Swabs for Molecular Detection of Enteric Pathogens in Children Admitted to Hospital with Severe Gastroenteritis in Botswana

ABSTRACT 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.

Microbiology of Urinary Tract Infections in Gaborone, Botswana

Objective The microbiology and epidemiology of UTI pathogens are largely unknown in Botswana, a high prevalence HIV setting. Using laboratory data from the largest referral hospital and a private hospital, we describe the major pathogens causing UTI and their antimicrobial resistance patterns. Methods This retrospective study examined antimicrobial susceptibility data for urine samples collected at Princess Marina Hospital (PMH), Bokamoso Private Hospital (BPH), or one of their affiliated outpatient clinics. A urine sample was included in our dataset if it demonstrated pure growth of a single organism and accompanying antimicrobial susceptibility and subject demographic data were available. Results A total of 744 samples were included. Greater than 10% resistance was observed for amoxicillin, co-trimoxazole, amoxicillin-clavulanate, and ciprofloxacin. Resistance of E. coli isolates to ampicillin and co-trimoxazole was greater than 60% in all settings. HIV status did not significantly impact the microbiology of UTIs, but did impact antimicrobial resistance to co-trimoxazole. Conclusions Data suggests that antimicrobial resistance has already emerged to most oral antibiotics, making empiric management of outpatient UTIs challenging. Ampicillin, co-trimoxazole, and ciprofloxacin should not be used as empiric treatment for UTI in this context. Nitrofurantoin could be used for simple cystitis; aminoglycosides for uncomplicated UTI in inpatients.

Advanced Human Immunodeficiency Virus Disease in Botswana Following Successful Antiretroviral Therapy Rollout: Incidence of and Temporal Trends in Cryptococcal Meningitis

Background Botswana has a well-developed antiretroviral therapy (ART) program that serves as a regional model. With wide ART availability, the burden of advanced human immunodeficiency virus (HIV) and associated opportunistic infections would be expected to decline. We performed a nationwide surveillance study to determine the national incidence of cryptococcal meningitis (CM), and describe characteristics of cases during 2000-2014 and temporal trends at 2 national referral hospitals. Methods Cerebrospinal fluid data from all 37 laboratories performing meningitis diagnostics in Botswana were collected from the period 2000-2014 to identify cases of CM. Basic demographic and laboratory data were recorded. Complete national data from 2013-2014 were used to calculate national incidence using UNAIDS population estimates. Temporal trends in cases were derived from national referral centers in the period 2004-2014. Results A total of 5296 episodes of CM were observed in 4702 individuals; 60.6% were male, and median age was 36 years. Overall 2013-2014 incidence was 17.8 (95% confidence interval [CI], 16.6-19.2) cases per 100000 person-years. In the HIV-infected population, incidence was 96.8 (95% CI, 90.0-104.0) cases per 100000 person-years; male predominance was seen across CD4 strata. At national referral hospitals, cases decreased during 2007-2009 but stabilized during 2010-2014. Conclusions Despite excellent ART coverage in Botswana, there is still a substantial burden of advanced HIV, with 2013-2014 incidence of CM comparable to pre-ART era rates in South Africa. Our findings suggest that a key population of individuals, often men, is developing advanced disease and associated opportunistic infections due to a failure to effectively engage in care, highlighting the need for differentiated care models.

Hospital-based surveillance for rotavirus gastroenteritis using molecular testing and immunoassay during the 2011 season in Botswana.

We describe rotavirus testing and clinical characteristics for children admitted with acute gastroenteritis during Botswanas 2011 rotavirus season. The rotavirus season extended from June to October with rotavirus-specific case fatality being 2.8%. Using molecular testing as reference, the immunochromatographic test had a sensitivity of 76.5% and specificity of 68.0%. Rotavirus vaccine may significantly reduce childhood morbidity and mortality in Botswana.

The global problem of childhood diarrhoeal diseases: emerging strategies in prevention and management:

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 Escherichia coli and Shigella 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.

A comparison of flocked swabs and traditional swabs, using multiplex real-time PCR for detection of common gastroenteritis pathogens in Botswana

We compared the performance of flocked and matched traditional rectal swabs collected from 236 children admitted with gastroenteritis in Botswana. All samples were tested using real time multiplex-PCR assays for nine enteric pathogens. There was a 20% higher detection of Shigella from flocked swabs, but most other pathogens had similar detection rates.

Rapid enteric testing to permit targeted antimicrobial therapy, with and without Lactobacillus reuteri probiotics, for paediatric acute diarrhoeal disease in Botswana: A pilot, randomized, factorial, controlled trial

Introduction Diarrhoeal disease is the second-leading cause of death in young children. Current guidelines recommend treating children with acute non-bloody diarrhea with oral rehydration solutions and zinc, but not antimicrobials. However, in many resource-limited settings, infections with treatable enteric bacterial and protozoan pathogens are common. Probiotics have shown promise as an adjunct treatment for diarrhoea but have not been studied in sub-Saharan Africa. Methods We conducted a pilot, factorial, randomized, placebo-controlled trial of children aged 2–60 months hospitalized in Botswana for acute non-bloody diarrhoea. A rapid test-and-treat intervention, consisting of multiplex PCR testing of rectal swabs taken at enrolment, accompanied by targeted antimicrobial therapy if treatable pathogens were detected, was compared to the reference standard of no stool testing. Additionally, Lactobacillus reuteri DSM 17938 x 60 days was compared to placebo treatment. The main objective of this pilot study was to assess feasibility. The primary clinical outcome was the increase in age-standardized height (HAZ) at 60 days adjusted for baseline HAZ. Results Seventy-six patients were enrolled over a seven-month study period. We judged that the recruitment rate, lab processing times, communication protocols, provision of specific antimicrobials, and follow-up rates were acceptable. Compared to the reference arm (no stool testing and placebo treatment), the combination of the rapid test-and-treat strategy plus L. reuteri DSM 17938 was associated with an increase of 0.61 HAZ (95% CI 0.09–1.13) and 93% lower odds of recurrent diarrhoea (OR 0.07, 95%CI 0.01–0.61) at 60 days. Discussion We demonstrated that it was feasible to evaluate the study interventions in Botswana. Despite the small sample size, we observed a statistically significant increase in HAZ at 60 days and significantly lower odds of recurrent diarrhoea in children receiving both rapid test-and-treat and L. reuteri. There is sufficient evidence to warrant proceeding with a larger follow-up trial in a similar setting.

High mortality in HIV-associated cryptococcal meningitis treated with amphotericin B-based therapy under routine care conditions in Africa

Abstract Background Cryptococcal 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. Methods Electronic 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. Results There 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. Conclusions Mortality 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.