Correlation of Clinical Outcomes With Multiplex Molecular Testing of Stool From Children Admitted to Hospital With Gastroenteritis in Botswana

Pernica, Jeffrey M.; Steenhoff, Andrew P.; Welch, Henry; Mokomane, Margaret; Quaye, Isaac; Arscott-Mills, Tonya; Mazhani, Loeto; Lechiile, Kwana; Mahony, James B.; Śmieja, Marek; Goldfarb, David M.

doi:10.1093/jpids/piv028

Cited by 29 publications

(31 citation statements)

References 12 publications

(17 reference statements)

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“…The provision of antimicrobials is recommended only if blood is observed in the stools; this recommendation is probably linked to the assumption that the majority of children presenting with acute non-bloody diarrhoea are infected with viral pathogens, for whom no specific treatment is available. However, we have previously found that up to one-third of children in Botswana admitted to hospital without dysentery harboured a potentially treatable pathogen in their stool [7], and other investigators have observed similar findings in other low- and middle-income countries [8, 9]. Although it is not possible to reliably distinguish treatable bacterial or protozoal gastroenteritis from non-treatable gastroenteritis on clinical grounds in the absence of bloody stools, the use of rapid enteric diagnostics at the time of patient presentation could permit the use of targeted antimicrobial treatment.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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IntroductionDiarrhoeal 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.MethodsWe 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.ResultsSeventy-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.DiscussionWe 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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…In our large (n=617) prospective study of community onset GE 15 where we also used a sensitive multiplex PCR assay, we detected at least one pathogen target in 83% of all children, which is a higher pathogen detection rate than we have found in these hospital associated cases described in this study. However, some of the leading pathogens detected in the community onset study were bacteria (e.g.…”

Section: Hospital-acquired Infection In Botswanacontrasting

confidence: 44%

Hospital-acquired gastroenteritis at a referral hospital in Gaborone, Botswana

Welch¹,

Goldfarb²,

Moorad³

et al. 2017

Int. j. infect. control

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Hospital-acquired infections, including hospital-acquired gastroenteritis (HAGE), are well documented in Western countries but little is known about these infections in sub-Saharan Africa. The aim of this study was to determine the incidence of and explore modifiable risk factors for HAGE.A prospective cohort study of children <13 years with HAGE admitted to Princess Marina Hospital in Gaborone, Botswana was performed. HAGE was defined as new-onset gastroenteritis (GE) >72 hours after admission or upon admission after recent discharge for a non-GE illness. Children were followed until discharge to ascertain therapies used and adverse outcomes. Enteric pathogens were identified by multiplex polymerase chain reaction.Virtually all of the 32 children with HAGE were < 2 years (n=30, 94%) and most were male (n=19, 59%). Few had human immunodeficiency virus infection (n=6, 19%), severe malnutrition (n=8, 25%), or a history of vitamin A use in the past 6 months (n=2, 6%). The mean monthly incidence of HAGE was 2.3 per 1000 patient days, and was associated with the monthly number of community-acquired gastroenteritis (CAGE) admissions (IRR 1.02, 95% CI 1.00, 1.04, p=0.025). A stool pathogen was detected in 15/27 (56%) children, including norovirus (n=7, 26%) and rotavirus (n=5, 18%). Most children received oral rehydration solution (n=26, 81%), or intravenous fluids (n=9, 28%). Antibiotics were administered to 5 (16%) children. Two (6%) children with HAGE were admitted to the intensive care unit and 4 (12%) died.In conclusion, we found HAGE was relatively common and associated with severe outcomes. The monthly incidence of HAGE was associated with CAGE admissions. Common pathogens included norovirus and rotavirus.

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“…Diarrheal illnesses, including rotavirus gastroenteritis, cause relatively high morbidity and mortality in Botswana in comparison with other African countries [20,21]. In July 2012, the Botswana Ministry of Health introduced a monovalent rotavirus vaccine (RV1; Rotarix) into its routine immunization program, recommending a 2-dose series at 2 and 3 months of age.…”

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

et al. 2016

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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.

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Correlation of Clinical Outcomes With Multiplex Molecular Testing of Stool From Children Admitted to Hospital With Gastroenteritis in Botswana

Cited by 29 publications

References 12 publications

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

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

Hospital-acquired gastroenteritis at a referral hospital in Gaborone, Botswana

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

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