Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 36 Records) |
Query Trace: Oundo J[original query] |
---|
Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition.
Pop M , Walker AW , Paulson J , Lindsay B , Antonio M , Hossain MA , Oundo J , Tamboura B , Mai V , Astrovskaya I , Corrada Bravo H , Rance R , Stares M , Levine MM , Panchalingam S , Kotloff K , Ikumapayi UN , Ebruke C , Adeyemi M , Ahmed D , Ahmed F , Alam MT , Amin R , Siddiqui S , Ochieng JB , Ouma E , Juma J , Mailu E , Omore R , Morris JG , Breiman RF , Saha D , Parkhill J , Nataro JP , Stine OC . Genome Biol 2014 15 (6) R76 BACKGROUND: Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease. RESULTS: We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age. CONCLUSIONS: Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques. |
Child deaths caused by Klebsiella pneumoniae in sub-Saharan Africa and south Asia: a secondary analysis of Child Health and Mortality Prevention Surveillance (CHAMPS) data
Verani JR , Blau DM , Gurley ES , Akelo V , Assefa N , Baillie V , Bassat Q , Berhane M , Bunn J , Cossa ACA , El Arifeen S , Gunturu R , Hale M , Igunza A , Keita AM , Kenneh S , Kotloff KL , Kowuor D , Mabunda R , Madewell ZJ , Madhi S , Madrid L , Mahtab S , Miguel J , Murila FV , Ogbuanu IU , Ojulong J , Onyango D , Oundo JO , Scott JAG , Sow S , Tapia M , Traore CB , Velaphi S , Whitney CG , Mandomando I , Breiman RF . Lancet Microbe 2024 BACKGROUND: Klebsiella pneumoniae is an important cause of nosocomial and community-acquired pneumonia and sepsis in children, and antibiotic-resistant K pneumoniae is a growing public health threat. We aimed to characterise child mortality associated with this pathogen in seven high-mortality settings. METHODS: We analysed Child Health and Mortality Prevention Surveillance (CHAMPS) data on the causes of deaths in children younger than 5 years and stillbirths in sites located in seven countries across sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and south Asia (Bangladesh) from Dec 9, 2016, to Dec 31, 2021. CHAMPS sites conduct active surveillance for deaths in catchment populations and following reporting of an eligible death or stillbirth seek consent for minimally invasive tissue sampling followed by extensive aetiological testing (microbiological, molecular, and pathological); cases are reviewed by expert panels to assign immediate, intermediate, and underlying causes of death. We reported on susceptibility to antibiotics for which at least 30 isolates had been tested, and excluded data on antibiotics for which susceptibility testing is not recommended for Klebsiella spp due to lack of clinical activity (eg, penicillin and ampicillin). FINDINGS: Among 2352 child deaths with cause of death assigned, 497 (21%, 95% CI 20-23) had K pneumoniae in the causal chain of death; 100 (20%, 17-24) had K pneumoniae as the underlying cause. The frequency of K pneumoniae in the causal chain was highest in children aged 1-11 months (30%, 95% CI 26-34; 144 of 485 deaths) and 12-23 months (28%, 22-34; 63 of 225 deaths); frequency by site ranged from 6% (95% CI 3-11; 11 of 184 deaths) in Bangladesh to 52% (44-61; 71 of 136 deaths) in Ethiopia. K pneumoniae was in the causal chain for 450 (22%, 95% CI 20-24) of 2023 deaths that occurred in health facilities and 47 (14%, 11-19) of 329 deaths in the community. The most common clinical syndromes among deaths with K pneumoniae in the causal chain were sepsis (44%, 95% CI 40-49; 221 of 2352 deaths), sepsis in conjunction with pneumonia (19%, 16-23; 94 of 2352 deaths), and pneumonia (16%, 13-20; 80 of 2352 deaths). Among K pneumoniae isolates tested, 121 (84%) of 144 were resistant to ceftriaxone and 80 (75%) of 106 to gentamicin. INTERPRETATION: K pneumoniae substantially contributed to deaths in the first 2 years of life across multiple high-mortality settings, and resistance to antibiotics used for sepsis treatment was common. Improved strategies are needed to rapidly identify and appropriately treat children who might be infected with this pathogen. These data suggest a potential impact of developing and using effective K pneumoniae vaccines in reducing neonatal, infant, and child deaths globally. FUNDING: Bill & Melinda Gates Foundation. |
Causes of stillbirth and death among children younger than 5 years in eastern Hararghe, Ethiopia: a population-based post-mortem study
Madrid L , Alemu A , Seale AC , Oundo J , Tesfaye T , Marami D , Yigzaw H , Ibrahim A , Degefa K , Dufera T , Teklemariam Z , Gure T , Leulseged H , Wittmann S , Abayneh M , Fentaw S , Temesgen F , Yeshi MM , Dubale M , Girma Z , Ackley C , Damisse B , Breines M , Orlien SMS , Blau DM , Breiman RF , Abate E , Dessie Y , Assefa N , Scott JAG . Lancet Glob Health 2023 11 (7) e1032-e1040 BACKGROUND: Child mortality is high in Ethiopia, but reliable data on the causes of death are scarce. We aimed to gather data for the contributory causes of stillbirth and child deaths in eastern Ethiopia. METHODS: In this population-based post-mortem study, we established a death-notification system in health facilities and in the community in Kersa (rural), Haramaya (rural) and Harar (urban) in eastern Ethiopia, at a new site of the Child Health and Mortality Prevention Surveillance (CHAMPS) network. We collected ante-mortem data, did verbal autopsies, and collected post-mortem samples via minimally invasive tissue sampling from stillbirths (weighing at least 1000 g or with an estimated gestational age of at least 28 weeks) and children who died younger than 5 years. Children-or their mothers, in the case of stillbirths and deaths in children younger than 6 months-had to have lived in the catchment area for the past 6 months to be included. Molecular, microbiological, and histopathological analyses were done in collected samples. Cause of death was established by an expert panel on the basis of these data and classified as underlying, comorbid, or immediate separately for stillbirths, neonatal deaths (deaths aged 0-27 days), and child deaths (aged 28 days to <5 years). FINDINGS: Between Feb 4, 2019, and Feb 3, 2021, 312 deaths were eligible for inclusion, and the families gave consent in 195 (63%) cases. Cause of death was established in 193 (99%) cases. Among 114 stillbirths, the underlying cause of death was perinatal asphyxia or hypoxia in 60 (53%) and birth defects in 24 (21%). Among 59 neonatal deaths, the most common underlying cause was perinatal asphyxia or hypoxia (17 [29%]) and the most common immediate cause of death was neonatal sepsis, which occurred in 27 (60%). Among 20 deaths in children aged 28 days to 59 months, malnutrition was the leading underlying cause (15 [75%]) and infections were common immediate and comorbid causes. Pathogens were identified in 19 (95%) child deaths, most commonly Klebsiella pneumoniae and Streptococcus pneumoniae. INTERPRETATION: Perinatal asphyxia or hypoxia, infections, and birth defects accounted for most stillbirths and child deaths. Most deaths could have been prevented with feasible interventions, such as improved maternity services, folate supplementation, and improved vaccine uptake. FUNDING: Bill & Melinda Gates Foundation. |
Pathogens associated with linear growth faltering in children with diarrhea and impact of antibiotic treatment: The global enteric multicenter study
Nasrin D , Blackwelder WC , Sommerfelt H , Wu Y , Farag TH , Panchalingam S , Biswas K , Saha D , Jahangir Hossain M , Sow SO , Reiman RFB , Sur D , Faruque ASG , Zaidi AKM , Sanogo D , Tamboura B , Onwuchekwa U , Manna B , Ramamurthy T , Kanungo S , Omore R , Ochieng JB , Oundo JO , Das SK , Ahmed S , Qureshi S , Quadri F , Adegbola RA , Antonio M , Mandomando I , Nhampossa T , Bassat Q , Roose A , O'Reilly CE , Mintz ED , Ramakrishnan U , Powell H , Liang Y , Nataro JP , Levine MM , Kotloff KL . J Infect Dis 2021 224 S848-s855 BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment. METHODS: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, approximately 60 days later, to calculate change in height-for-age z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested using linear mixed effects regression models. RESULTS: Among 8077 MSD cases analyzed, the proportion with stunting (HAZ below -1) increased from 59% at enrollment to 65% at follow-up (P < .0001). Pathogens significantly associated with linear growth decline included Cryptosporidium (P < .001), typical enteropathogenic Escherichia coli (P = .01), and untreated Shigella (P = .009) among infants (aged 0-11 months) and enterotoxigenic E. coli encoding heat-stable toxin (P < .001) and Cryptosporidium (P = .03) among toddlers (aged 12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (P = .02). CONCLUSIONS: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella. |
Deaths attributed to respiratory syncytial virus in young children in high-mortality rate settings: Report from Child Health and Mortality Prevention Surveillance (CHAMPS)
Blau DM , Baillie VL , Els T , Mahtab S , Mutevedzi P , Keita AM , Kotloff KL , Mehta A , Sow SO , Tapia MD , Tippett Barr BA , Oluoch BO , Onyango C , Revathi G , Verani JR , Abayneh M , Assefa N , Madrid L , Oundo JO , Scott JAG , Bassat Q , Mandomando I , Sitoe A , Valente M , Varo R , Bassey IA , Cain CJ , Jambai A , Ogbuanu I , Ojulong J , Alam M , El Arifeen S , Gurley ES , Rahman A , Rahman M , Waller JL , Dewey B , Breiman RF , Whitney CG , Madhi SA . Clin Infect Dis 2021 73 S218-s228 BACKGROUND: Lower respiratory tract infections are a leading cause of death in young children, but few studies have collected the specimens needed to define the role of specific causes. The Child Health and Mortality Prevention Surveillance (CHAMPS) platform aims to investigate causes of death in children aged <5 years in high-mortality rate settings, using postmortem minimally invasive tissue sampling and other advanced diagnostic techniques. We examined findings for deaths identified in CHAMPS sites in 7 countries in sub-Saharan Africa and south Asia to evaluate the role of respiratory syncytial virus (RSV). METHODS: We included deaths that occurred between December 2016 and December 2019. Panels determined causes of deaths by reviewing all available data including pathological results from minimally invasive tissue sampling, polymerase chain reaction screening for multiple infectious pathogens in lung tissue, nasopharyngeal swab, blood, and cerebrospinal fluid samples, clinical information from medical records, and verbal autopsies. RESULTS: We evaluated 1213 deaths, including 695 in neonates (aged <28 days), 283 in infants (28 days to <12 months), and 235 in children (12-59 months). RSV was detected in postmortem specimens in 67 of 1213 deaths (5.5%); in 24 deaths (2.0% of total), RSV was determined to be a cause of death, and it contributed to 5 other deaths. Younger infants (28 days to <6 months of age) accounted for half of all deaths attributed to RSV; 6.5% of all deaths in younger infants were attributed to RSV. RSV was the underlying and only cause in 4 deaths; the remainder (n = 20) had a median of 2 (range, 1-5) other conditions in the causal chain. Birth defects (n = 8) and infections with other pathogens (n = 17) were common comorbid conditions. CONCLUSIONS: RSV is an important cause of child deaths, particularly in young infants. These findings add to the substantial body of literature calling for better treatment and prevention options for RSV in high-mortality rate settings. |
Characteristics of Salmonella recovered from stools of children enrolled in the Global Enteric Multicenter Study.
Kasumba IN , Pulford CV , Perez-Sepulveda BM , Sen S , Sayed N , Permala-Booth J , Livio S , Heavens D , Low R , Hall N , Roose A , Powell H , Farag T , Panchalingham S , Berkeley L , Nasrin D , Blackwelder WC , Wu Y , Tamboura B , Sanogo D , Onwuchekwa U , Sow SO , Ochieng JB , Omore R , Oundo JO , Breiman RF , Mintz ED , O'Reilly CE , Antonio M , Saha D , Hossain MJ , Mandomando I , Bassat Q , Alonso PL , Ramamurthy T , Sur D , Qureshi S , Zaidi AKM , Hossain A , Faruque ASG , Nataro JP , Kotloff KL , Levine MM , Hinton JCD , Tennant SM . Clin Infect Dis 2021 73 (4) 631-641 BACKGROUND: The Global Enteric Multicenter Study (GEMS) determined the etiologic agents of moderate-to-severe diarrhea (MSD) in children under 5 years old in Africa and Asia. Here, we describe the prevalence and antimicrobial susceptibility of non-typhoidal Salmonella (NTS) serovars in GEMS and examine the phylogenetics of Salmonella Typhimurium ST313 isolates. METHODS: Salmonella isolated from children with MSD or diarrhea-free controls were identified by classical clinical microbiology and serotyped using antisera and/or whole genome sequence data. We evaluated antimicrobial susceptibility using the Kirby-Bauer disk diffusion method. Salmonella Typhimurium sequence types were determined using multi-locus sequence typing and whole genome sequencing was performed to assess the phylogeny of ST313. RESULTS: Out of 370 Salmonella-positive individuals, 190 (51.4%) were MSD cases and 180 (48.6%) were diarrhea-free controls. The most frequent Salmonella serovars identified were Salmonella Typhimurium, serogroup O:8 (C2-C3), serogroup O:6,7 (C1), Salmonella Paratyphi B Java and serogroup O:4 (B). The prevalence of NTS was low but similar across sites, regardless of age, and was similar amongst both cases and controls except in Kenya, where Salmonella Typhimurium was more commonly associated with cases than controls. Phylogenetic analysis showed that these Salmonella Typhimurium isolates, all ST313, were highly genetically related to isolates from controls. Generally, Salmonella isolates from Asia were resistant to ciprofloxacin and ceftriaxone but African isolates were susceptible to these antibiotics. CONCLUSION: Our data confirms that NTS is prevalent, albeit at low levels, in Africa and South Asia. Our findings provide further evidence that multi-drug resistant Salmonella Typhimurium ST313 can be carried asymptomatically by humans in sub-Saharan Africa. |
Factors associated with typical enteropathogenic Escherichia coli infection among children <5 years old with moderate-to-severe diarrhoea in rural western Kenya, 2008-2012.
Fagerli K , Omore R , Kim S , Ochieng JB , Ayers TL , Juma J , Farag TH , Nasrin D , Panchalingam S , Robins-Browne RM , Nataro JP , Kotloff KL , Levine MM , Oundo J , Parsons MB , Laserson KF , Mintz ED , Breiman RF , O'Reilly CE . Epidemiol Infect 2020 148 1-37 Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37-3.17), and convulsions (aOR 2.83, 95% CI 1.12-7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3-3.6) and wasted (OR 2.5, 95% CI 1.3-4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47-5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented. |
Diarrhoeal disease and subsequent risk of death in infants and children residing in low-income and middle-income countries: analysis of the GEMS case-control study and 12-month GEMS-1A follow-on study
Levine MM , Nasrin D , Acacio S , Bassat Q , Powell H , Tennant SM , Sow SO , Sur D , Zaidi AKM , Faruque ASG , Hossain MJ , Alonso PL , Breiman RF , O'Reilly CE , Mintz ED , Omore R , Ochieng JB , Oundo JO , Tamboura B , Sanogo D , Onwuchekwa U , Manna B , Ramamurthy T , Kanungo S , Ahmed S , Qureshi S , Quadri F , Hossain A , Das SK , Antonio M , Saha D , Mandomando I , Blackwelder WC , Farag T , Wu Y , Houpt ER , Verweiij JJ , Sommerfelt H , Nataro JP , Robins-Browne RM , Kotloff KL . Lancet Glob Health 2019 8 (2) e204-e214 BACKGROUND: The Global Enteric Multicenter Study (GEMS) was a 3-year case-control study that measured the burden, aetiology, and consequences of moderate-to-severe diarrhoea (MSD) in children aged 0-59 months. GEMS-1A, a 12-month follow-on study, comprised two parallel case-control studies, one assessing MSD and the other less-severe diarrhoea (LSD). In this report, we analyse the risk of death with each diarrhoea type and the specific pathogens associated with fatal outcomes. METHODS: GEMS was a prospective, age-stratified, matched case-control study done at seven sites in Africa and Asia. Children aged 0-59 months with MSD seeking care at sentinel health centres were recruited along with one to three randomly selected matched community control children without diarrhoea. In the 12-month GEMS-1A follow-on study, children with LSD and matched controls, in addition to children with MSD and matched controls, were recruited at six of the seven sites; only cases of MSD and controls were enrolled at the seventh site. We compared risk of death during the period between enrolment and one follow-up household visit done about 60 days later (range 50-90 days) in children with MSD and LSD and in their respective controls. Approximately 50 pathogens were detected using, as appropriate, classic bacteriology, immunoassays, gel-based PCR and reverse transcriptase PCR, and quantitative real-time PCR (qPCR). Specimens from a subset of GEMS cases and controls were also tested by a TaqMan Array Card that compartmentalised probe-based qPCR for 32 enteropathogens. FINDINGS: 223 (2.0%) of 11 108 children with MSD and 43 (0.3%) of 16 369 matched controls died between study enrolment and the follow-up visit at about 60 days (hazard ratio [HR] 8.16, 95% CI 5.69-11.68, p<0.0001). 12 (0.4%) of 2962 children with LSD and seven (0.2%) of 4074 matched controls died during the follow-up period (HR 2.78, 95% CI 0.95-8.11, p=0.061). Risk of death was lower in children with dysenteric MSD than in children with non-dysenteric MSD (HR 0.20, 95% CI 0.05-0.87, p=0.032), and lower in children with LSD than in those with non-dysenteric MSD (HR 0.29, 0.14-0.59, p=0.0006). In children younger than 24 months with MSD, infection with typical enteropathogenic Escherichia coli, enterotoxigenic E coli encoding heat-stable toxin, enteroaggregative E coli, Shigella spp (non-dysentery cases), Aeromonas spp, Cryptosporidium spp, and Entamoeba histolytica increased risk of death. Of 61 deaths in children aged 12-59 months with non-dysenteric MSD, 31 occurred among 942 children qPCR-positive for Shigella spp and 30 deaths occurred in 1384 qPCR-negative children (HR 2.2, 95% CI 1.2-3.9, p=0.0090), showing that Shigella was strongly associated with increased risk of death. INTERPRETATION: Risk of death is increased following MSD and, to a lesser extent, LSD. Considering there are approximately three times more cases of LSD than MSD in the population, more deaths are expected among children with LSD than in those with MSD. Because the major attributable LSD-associated and MSD-associated pathogens are the same, implementing vaccines and rapid diagnosis and treatment interventions against these major pathogens are rational investments. FUNDING: Bill & Melinda Gates Foundation. |
Colonization factors among enterotoxigenic Escherichia coli isolates from children with moderate-to-severe diarrhea and from matched controls in the Global Enteric Multicenter Study (GEMS).
Vidal RM , Muhsen K , Tennant SM , Svennerholm AM , Sow SO , Sur D , Zaidi AKM , Faruque ASG , Saha D , Adegbola R , Hossain MJ , Alonso PL , Breiman RF , Bassat Q , Tamboura B , Sanogo D , Onwuchekwa U , Manna B , Ramamurthy T , Kanungo S , Ahmed S , Qureshi S , Quadri F , Hossain A , Das SK , Antonio M , Mandomando I , Nhampossa T , Acacio S , Omore R , Ochieng JB , Oundo JO , Mintz ED , O'Reilly CE , Berkeley LY , Livio S , Panchalingam S , Nasrin D , Farag TH , Wu Y , Sommerfelt H , Robins-Browne RM , Del Canto F , Hazen TH , Rasko DA , Kotloff KL , Nataro JP , Levine MM . PLoS Negl Trop Dis 2019 13 (1) e0007037 BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) encoding heat-stable enterotoxin (ST) alone or with heat-labile enterotoxin (LT) cause moderate-to-severe diarrhea (MSD) in developing country children. The Global Enteric Multicenter Study (GEMS) identified ETEC encoding ST among the top four enteropathogens. Since the GEMS objective was to provide evidence to guide development and implementation of enteric vaccines and other interventions to diminish diarrheal disease morbidity and mortality, we examined colonization factor (CF) prevalence among ETEC isolates from children age <5 years with MSD and from matched controls in four African and three Asian sites. We also assessed strength of association of specific CFs with MSD. METHODOLOGY/PRINCIPAL FINDINGS: MSD cases enrolled at healthcare facilities over three years and matched controls were tested in a standardized manner for many enteropathogens. To identify ETEC, three E. coli colonies per child were tested by polymerase chain reaction (PCR) to detect genes encoding LT, ST; confirmed ETEC were examined by PCR for major CFs (Colonization Factor Antigen I [CFA/I] or Coli Surface [CS] antigens CS1-CS6) and minor CFs (CS7, CS12, CS13, CS14, CS17, CS18, CS19, CS20, CS21, CS30). ETEC from 806 cases had a single toxin/CF profile in three tested strains per child. Major CFs, components of multiple ETEC vaccine candidates, were detected in 66.0% of LT/ST and ST-only cases and were associated with MSD versus matched controls by conditional logistic regression (p</=0.006); major CFs detected in only 25.0% of LT-only cases weren't associated with MSD. ETEC encoding exclusively CS14, identified among 19.9% of 291 ST-only and 1.5% of 259 LT/ST strains, were associated with MSD (p = 0.0011). No other minor CF exhibited prevalence >/=5% and significant association with MSD. CONCLUSIONS/SIGNIFICANCE: Major CF-based efficacious ETEC vaccines could potentially prevent up to 66% of pediatric MSD cases due to ST-encoding ETEC in developing countries; adding CS14 extends coverage to ~77%. |
Diarrhoea, enteric pathogen detection and nutritional indicators among controls in the Global Enteric Multicenter Study, Kenya site: an opportunity to understand reference populations in case-control studies of diarrhoea
Berendes DM , O'Reilly CE , Kim S , Omore R , Ochieng JB , Ayers T , Fagerli K , Farag TH , Nasrin D , Panchalingam S , Nataro JP , Kotloff KL , Levine MM , Oundo J , Laserson K , Breiman RF , Mintz ED . Epidemiol Infect 2018 147 1-9 Given the challenges in accurately identifying unexposed controls in case-control studies of diarrhoea, we examined diarrhoea incidence, subclinical enteric infections and growth stunting within a reference population in the Global Enteric Multicenter Study, Kenya site. Within 'control' children (0-59 months old without diarrhoea in the 7 days before enrolment, n = 2384), we examined surveys at enrolment and 60-day follow-up, stool at enrolment and a 14-day post-enrolment memory aid for diarrhoea incidence. At enrolment, 19% of controls had 1 enteric pathogen associated with moderate-to-severe diarrhoea ('MSD pathogens') in stool; following enrolment, many reported diarrhoea (27% in 7 days, 39% in 14 days). Controls with and without reported diarrhoea had similar carriage of MSD pathogens at enrolment; however, controls reporting diarrhoea were more likely to report visiting a health facility for diarrhoea (27% vs. 7%) or fever (23% vs. 16%) at follow-up than controls without diarrhoea. Odds of stunting differed by both MSD and 'any' (including non-MSD pathogens) enteric pathogen carriage, but not diarrhoea, suggesting control classification may warrant modification when assessing long-term outcomes. High diarrhoea incidence following enrolment and prevalent carriage of enteric pathogens have implications for sequelae associated with subclinical enteric infections and for design and interpretation of case-control studies examining diarrhoea. |
Clinical, environmental, and behavioral characteristics associated with Cryptosporidium infection among children with moderate-to-severe diarrhea in rural western Kenya, 2008-2012: The Global Enteric Multicenter Study (GEMS)
Delahoy MJ , Omore R , Ayers TL , Schilling KA , Blackstock AJ , Ochieng JB , Moke F , Jaron P , Awuor A , Okonji C , Juma J , Farag TH , Nasrin D , Panchalingam S , Nataro JP , Kotloff KL , Levine MM , Oundo J , Roellig DM , Xiao L , Parsons MB , Laserson K , Mintz ED , Breiman RF , O'Reilly CE . PLoS Negl Trop Dis 2018 12 (7) e0006640 BACKGROUND: Cryptosporidium is a leading cause of moderate-to-severe diarrhea (MSD) in young children in Africa. We examined factors associated with Cryptosporidium infection in MSD cases enrolled at the rural western Kenya Global Enteric Multicenter Study (GEMS) site from 2008-2012. METHODOLOGY/PRINCIPAL FINDINGS: At health facility enrollment, stool samples were tested for enteric pathogens and data on clinical, environmental, and behavioral characteristics collected. Each child's health status was recorded at 60-day follow-up. Data were analyzed using logistic regression. Of the 1,778 children with MSD enrolled as cases in the GEMS-Kenya case-control study, 11% had Cryptosporidium detected in stool by enzyme immunoassay; in a genotyped subset, 81% were C. hominis. Among MSD cases, being an infant, having mucus in stool, and having prolonged/persistent duration diarrhea were associated with being Cryptosporidium-positive. Both boiling drinking water and using rainwater as the main drinking water source were protective factors for being Cryptosporidium-positive. At follow-up, Cryptosporidium-positive cases had increased odds of being stunted (adjusted odds ratio [aOR] = 1.65, 95% CI: 1.06-2.57), underweight (aOR = 2.08, 95% CI: 1.34-3.22), or wasted (aOR = 2.04, 95% CI: 1.21-3.43), and had significantly larger negative changes in height- and weight-for-age z-scores from enrollment. CONCLUSIONS/SIGNIFICANCE: Cryptosporidium contributes significantly to diarrheal illness in young children in western Kenya. Advances in point of care detection, prevention/control approaches, effective water treatment technologies, and clinical management options for children with cryptosporidiosis are needed. |
Do clients receiving Home based testing and counselling (HBTC) utilize the HIV prevention messages delivered? A study among residents in an urban informal settlement in Kenya who previously received HBTC
Oluoch P , Achia T , Mutinda D , Orwa J , Oundo J , Karama M , Ng'ang'a Z . Afr J Health Sci 2017 30 (2) 139-158 BACKGROUND: Home based HIV testing and counseling (HBTC) increases access to services and is associated with high testing uptake. Alongside testing, individuals are offered HIV prevention messages with an aim of helping them reduce HIV high risk sexual behaviors. This study explored the level of provision and subsequent utilization of HIV prevention messages and associated change in behavior among individuals who had received HBTC previously in an informal settlement. METHODS: In a mixed method cross sectional study, we interviewed 1257 individuals and conducted 6 focus group discussions (FGD). Multiple correspondence analysis (MCA) was used to construct provision of prevention messages and behavior change indices using STATA 3.0. Pearson's chi-square statistics was used to test for bivariate association between the outcomes and logistic regression analysis was carried out with the behavior change index as the outcome of interest and the predictors considered significant (p<0.1). Thematic content analysis for qualitative data was done using Atlas 3.0. RESULTS: Out of the 1257participants, 1078 (85.8%) had ever tested for HIV, with 74.2% having tested in the Kibera HBTC program. Nearly all (97.4%) rated HBTC experience as either excellent (62.4%) or good (37%) and would recommend it to a friend. Provision of prevention messages was high among HBTC clients compared to clients from other testing sites; partner reduction counselling (64% versus 52%) and faithfulness (78.3% versus 67%); p=0.001. Self-reported behavior change after HBTC was generally low with condom use at 10.7% and men more likely to practice safer sex (p = 0.002). Trust of the sexual partners and fear of suspicion were the main reasons given for not using condoms. Clients testing HIV positive after previous negative result were 3.4%. The focus group discussions reported multiple sexual partnerships among both HIV negative and positive residents alike. CONCLUSION: Although prevention messages delivered during HBTC are accepted and appreciated in this community, their utilization is low in both HIV negative and positive individuals. Innovative strategies for change of normative beliefs about sexual behavior are urgently needed. |
Application of psychosocial models to Home-Based Testing and Counseling (HBTC) for increased uptake and household coverage in a large informal urban settlement in Kenya
Oluoch P , Orwa J , Lugalia F , Mutinda D , Gichangi A , Oundo J , Karama M , Nganga Z , Galbraith J . Pan Afr Med J 2017 27 285 Introduction: Home Based Testing and Counselling (HBTC) aims at reaching individuals who have low HIV risk perception and experience barriers which prevent them from seeking HIV testing and counseling (HTC) services. Saturating the community with HTC is needed to achieve the ambitious 90-90-90 targets of knowledge of HIV status, ARV treatment and viral suppression. This paper describes the use of health belief model and community participation principles in HBTC to achieve increased household coverage and HTC uptake. Methods: This cross sectional survey was done between August 2009 and April 2011 in Kibera slums, Nairobi city. Using three community participation principles; defining and mobilizing the community, involving the community, overcoming barriers and respect to cultural differences and four constructs of the health belief model; risk perception, perceived severity, perceived benefits of changed behavior and perceived barriers; we offered HTC services to the participants. Descriptive statistics were used to describe socio-demographic characteristics, calculate uptake and HIV prevalence. Results: There were 72,577 individuals enumerated at the start of the program; 75,141 residents were found during service delivery. Of those, 71,925 (95.7%) consented to participate, out of which 71,720 (99.7%) took the HIV test. First time testers were (39%). The HIV prevalence was higher (6.4%) among repeat testers than first time testers (4.0%) with more women (7.4%) testing positive than men (3.6%) and an overall 5.5% slum prevalence. Conclusion: This methodology demonstrates that the use of community participation principles combined with a psychosocial model achieved high HTC uptake, coverage and diagnosed HIV in individuals who believed they are HIV free. This novel approach provides baseline for measuring HTC coverage in a community. |
Factors associated with the duration of moderate-to-severe diarrhea among children in rural western Kenya enrolled in the Global Enteric Multicenter Study, 2008-2012
Schilling KA , Omore R , Derado G , Ayers T , Ochieng JB , Farag TH , Nasrin D , Panchalingam S , Nataro JP , Kotloff KL , Levine MM , Oundo J , Parsons MB , Bopp C , Laserson K , Stauber CE , Rothenberg R , Breiman RF , O'Reilly CE , Mintz ED . Am J Trop Med Hyg 2017 97 (1) 248-258 Diarrheal disease is a leading cause of death among young children worldwide. As rates of acute diarrhea (AD; 1-6 days duration) have decreased, persistent diarrhea (PD; > 14 days duration) accounts for a greater proportion of the diarrheal disease burden. We describe factors associated with the duration of moderate-to-severe diarrhea in Kenyan children < 5 years old enrolled in the Global Enteric Multicenter Study. We found 587 (58%) children experienced AD, 360 (35%) had prolonged acute diarrhea (ProAD; 7-13 days duration), and 73 (7%) had PD. We constructed a Cox proportional hazards model to identify factors associated with diarrheal duration. Risk factors independently associated with longer diarrheal duration included infection with Cryptosporidium (hazard ratio [HR]: 0.868, P = 0.035), using an unimproved drinking water source (HR: 0.87, P = 0.035), and being stunted at enrollment (HR: 0.026, P < 0.0001). Diarrheal illness of extended duration appears to be multifactorial; given its association with adverse health and development outcomes, effective strategies should be implemented to reduce the duration and severity of diarrheal illness. Effective treatments for Cryptosporidium should be identified, interventions to improve drinking water are imperative, and nutrition should be improved through exclusive breastfeeding in infants ≤ 6 months and appropriate continued feeding practices for ill children. |
Evolution of atypical enteropathogenic E. coli by repeated acquisition of LEE pathogenicity island variants
Ingle DJ , Tauschek M , Edwards DJ , Hocking DM , Pickard DJ , Azzopardi KI , Amarasena T , Bennett-Wood V , Pearson JS , Tamboura B , Antonio M , Ochieng JB , Oundo J , Mandomando I , Qureshi S , Ramamurthy T , Hossain A , Kotloff KL , Nataro JP , Dougan G , Levine MM , Robins-Browne RM , Holt KE . Nat Microbiol 2016 1 15010 Atypical enteropathogenic Escherichia coli (aEPEC) is an umbrella term given to E. coli that possess a type III secretion system encoded in the locus of enterocyte effacement (LEE), but lack the virulence factors (stx, bfpA) that characterize enterohaemorrhagic E. coli and typical EPEC, respectively. The burden of disease caused by aEPEC has recently increased in industrialized and developing nations, yet the population structure and virulence profile of this emerging pathogen are poorly understood. Here, we generated whole-genome sequences of 185 aEPEC isolates collected during the Global Enteric Multicenter Study from seven study sites in Asia and Africa, and compared them with publicly available E. coli genomes. Phylogenomic analysis revealed ten distinct widely distributed aEPEC clones. Analysis of genetic variation in the LEE pathogenicity island identified 30 distinct LEE subtypes divided into three major lineages. Each LEE lineage demonstrated a preferred chromosomal insertion site and different complements of non-LEE encoded effector genes, indicating distinct patterns of evolution of these lineages. This study provides the first detailed genomic framework for aEPEC in the context of the EPEC pathotype and will facilitate further studies into the epidemiology and pathogenicity of EPEC by enabling the detection and tracking of specific clones and LEE variants. |
Epidemiology, seasonality and factors associated with rotavirus infection among children with moderate-to-severe diarrhea in rural western Kenya, 2008-2012: The Global Enteric Multicenter Study (GEMS)
Omore R , Tate JE , O'Reilly CE , Ayers T , Williamson J , Moke F , Schilling KA , Awuor AO , Jaron P , Ochieng JB , Oundo J , Parashar UD , Parsons MB , Bopp CC , Nasrin D , Farag TH , Kotloff KL , Nataro JP , Panchalingam S , Levine MM , Laserson KF , Nuorti JP , Mintz ED , Breiman RF . PLoS One 2016 11 (8) e0160060 OBJECTIVE: To evaluate factors associated with rotavirus diarrhea and to describe severity of illness among children <5 years old with non-dysenteric, moderate-to-severe diarrhea (MSD) in rural western Kenya. METHODS: We analyzed data from children <5 years old with non-dysenteric MSD enrolled as cases in the Global Enteric Multicenter Study (GEMS) in Kenya. A non-dysenteric MSD case was defined as a child with ≥3 loose stools in 24 hrs. and one or more of the following: sunken eyes, skin tenting, intravenous rehydration, or hospitalization, who sought care at a sentinel health center within 7 days of illness onset. Rotavirus antigens in stool samples were detected by ELISA. Demographic and clinical information was collected at enrollment and during a single follow-up home visit at approximately 60 days. We analyzed diarrhea severity using a GEMS 17 point numerical scoring system adapted from the Vesikari score. We used logistic regression to evaluate factors associated with rotavirus infection. RESULTS: From January 31, 2008 to September 30, 2012, among 1,637 (92%) non-dysenteric MSD cases, rotavirus was detected in stools of 245 (15.0%). Rotavirus-positive compared with negative cases were: younger (median age, 8 vs. 13 months; p<0.0001), had more severe illness (median severity score, 9 vs 8; p<0.0001) and had to be hospitalized more frequently (37/245 [15.1%] vs. 134/1,392 [9.6%]), p <0.013). Independent factors associated with rotavirus infection included age 0-11 months old (aOR = 5.29, 95% CI 3.14-8.89) and presenting with vomiting ≥3 times/24hrs (aOR = 2.58, 95% CI [1.91-3.48]). Rotavirus was detected more commonly in warm and dry months than in the cool and rainy months (142/691 [20%] vs 70/673 [10%]) p<0.0001). CONCLUSIONS: Diarrhea caused by rotavirus is associated with severe symptoms leading to hospitalization. Consistent with other settings, infants had the greatest burden of disease. |
The burden of cryptosporidium diarrheal disease among children < 24 months of age in moderate/high mortality regions of Sub-Saharan Africa and South Asia, utilizing data from the Global Enteric Multicenter Study (GEMS)
Sow SO , Muhsen K , Nasrin D , Blackwelder WC , Wu Y , Farag TH , Panchalingam S , Sur D , Zaidi AK , Faruque AS , Saha D , Adegbola R , Alonso PL , Breiman RF , Bassat Q , Tamboura B , Sanogo D , Onwuchekwa U , Manna B , Ramamurthy T , Kanungo S , Ahmed S , Qureshi S , Quadri F , Hossain A , Das SK , Antonio M , Hossain MJ , Mandomando I , Nhampossa T , Acacio S , Omore R , Oundo JO , Ochieng JB , Mintz ED , O'Reilly CE , Berkeley LY , Livio S , Tennant SM , Sommerfelt H , Nataro JP , Ziv-Baran T , Robins-Browne RM , Mishcherkin V , Zhang J , Liu J , Houpt ER , Kotloff KL , Levine MM . PLoS Negl Trop Dis 2016 10 (5) e0004729 BACKGROUND: The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized. METHODS: Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated. FINDINGS: Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27-4.67) and 3.18 (95% CI, 1.85-4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73-2.08) and 1.36 (95% CI, 0.66-2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33-5.01) and 4.88 (95% CI, 0.82-8.92) in infants and 4.04 (95% CI, 0.56-7.51) and 4.71 (95% CI, 0.24-9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative. CONCLUSIONS: The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies. |
Malaria parasitemia among febrile patients seeking clinical care at an outpatient health facility in an urban informal settlement area in Nairobi, Kenya
Njuguna HN , Montgomery JM , Cosmas L , Wamola N , Oundo JO , Desai M , Buff AM , Breiman RF . Am J Trop Med Hyg 2015 94 (1) 122-127 Nairobi is considered a low-risk area for malaria transmission, but travel can influence transmission of malaria. We investigated the demographic characteristics and travel history of patients with documented fever and malaria in a study clinic in a population-based surveillance system over a 5-year period, January 1, 2007 to December 31, 2011. During the study period, 11,480 (68%) febrile patients had a microscopy test performed for malaria, of which 2,553 (22%) were positive. Malaria was detected year-round with peaks in January, May, and September. Children aged 5-14 years had the highest proportion (28%) of positive results followed by children aged 1-4 years (23%). Almost two-thirds of patients with malaria reported traveling outside Nairobi; 79% of these traveled to three counties in western Kenya. History of recent travel (i.e., in past month) was associated with malaria parasitemia (odds ratio: 10.0, 95% confidence interval: 9.0-11.0). Malaria parasitemia was frequently observed among febrile patients at a health facility in the urban slum of Kibera, Nairobi. The majority of patients had traveled to western Kenya. However, 34% reported no travel history, which raises the possibility of local malaria transmission in this densely populated, urban setting. These findings have important implications for malaria control in large Nairobi settlements. |
A rapid assessment of drinking water quality in informal settlements after a cholera outbreak in Nairobi, Kenya
Blanton E , Wilhelm N , O'Reilly C , Muhonja E , Karoki S , Ope M , Langat D , Omolo J , Wamola N , Oundo J , Hoekstra R , Ayers T , De Cock K , Breiman R , Mintz E , Lantagne D . J Water Health 2015 13 (3) 714-25 Populations living in informal settlements with inadequate water and sanitation infrastructure are at risk of epidemic disease. In 2010, we conducted 398 household surveys in two informal settlements in Nairobi, Kenya with isolated cholera cases. We tested source and household water for free chlorine residual (FCR) and Escherichia coli in approximately 200 households. International guidelines are ≥0.5 mg/L FCR at source, ≥0.2 mg/L at household, and <1 E. coli/100 mL. In these two settlements, 82% and 38% of water sources met FCR guidelines; and 7% and 8% were contaminated with E. coli, respectively. In household stored water, 82% and 35% met FCR guidelines and 11% and 32% were contaminated with E. coli, respectively. Source water FCR ≥0.5 mg/L (p = 0.003) and reported purchase of a household water treatment product (p = 0.002) were associated with increases in likelihood that household stored water had ≥0.2 mg/L FCR, which was associated with a lower likelihood of E. coli contamination (p < 0.001). These results challenge the assumption that water quality in informal settlements is universally poor and the route of disease transmission, and highlight that providing centralized water with ≥0.5 mg/L FCR or (if not feasible) household water treatment technologies reduces the risk of waterborne cholera transmission in informal settlements. |
Association between Shigella infection and diarrhea varies based on location and age of children
Lindsay B , Saha D , Sanogo D , Das SK , Farag TH , Nasrin D , Li S , Panchalingam S , Levine MM , Kotloff K , Nataro JP , Magder L , Hungerford L , Oundo J , Hossain MA , Adeyemi M , Stine OC , Faruque AS . Am J Trop Med Hyg 2015 93 (5) 918-24 Molecular identification of the invasion plasmid antigen-H (ipaH) gene has been established as a useful detection mechanism for Shigella spp. The Global Enteric Multicenter Study (GEMS) identified the etiology and burden of moderate-to-severe diarrhea (MSD) in sub-Saharan Africa and south Asia using a case-control study and traditional culture techniques. Here, we used quantitative polymerase chain reaction (qPCR) to identify Shigella spp. in 2,611 stool specimens from GEMS and compared these results to those using culture. Demographic and nutritional characteristics were assessed as possible risk factors. The qPCR identified more cases of shigellosis than culture; however, the distribution of demographic characteristics was similar by both methods. In regression models adjusting for Shigella quantity, age, and site, children who were exclusively breast-fed had significantly lower odds of MSD compared with children who were not breast-fed (odds ratio [OR] = 0.47, 95% confidence interval (CI) = 0.28-0.81). The association between Shigella quantity and MSD increased with age, with a peak in children of 24-35 months of age (OR = 8.2, 95% CI = 4.3-15.7) and the relationship between Shigella quantity and disease was greatest in Bangladesh (OR = 13.2, 95% CI = 7.3-23.8). This study found that qPCR identified more cases of Shigella and age, site, and breast-feeding status were significant risk factors for MSD. |
Prevalence of classic, MLB-clade and VA-clade astroviruses in Kenya and the Gambia
Meyer CT , Bauer IK , Antonio M , Adeyemi M , Saha D , Oundo JO , Ochieng JB , Omore R , Stine OC , Wang D , Holtz LR . Virol J 2015 12 (1) 78 BACKGROUND: Infectious diarrhea leads to significant mortality in children, with 40 % of these deaths occurring in Africa. Classic human astroviruses are a well-established etiology of diarrhea. In recent years, seven novel astroviruses have been discovered (MLB1, MLB2, MLB3, VA1/HMO-C, VA2/HMO-B, VA3/HMO-A, VA4); however, there have been few studies on their prevalence or potential association with diarrhea. METHODS: To investigate the prevalence and diversity of these classic and recently described astroviruses in a pediatric population, a case-control study was performed. Nine hundred and forty nine stools were previously collected from cases of moderate-to-severe diarrhea and matched controls of patients less than 5 years of age in Kenya and The Gambia. RT-PCR screening was performed using pan-astrovirus primers. RESULTS: Astroviruses were present in 9.9 % of all stool samples. MLB3 was the most common astrovirus with a prevalence of 2.6 %. Two subtypes of MLB3 were detected that varied based on location in Africa. In this case-control study, Astrovirus MLB1 was associated with diarrhea in Kenya, whereas Astrovirus MLB3 was associated with the control state in The Gambia. Classic human astrovirus was not associated with diarrhea in this study. Unexpectedly, astroviruses with high similarity to Canine Astrovirus and Avian Nephritis Virus 1 and 2 were also found in one case of diarrhea and two control stools respectively. CONCLUSIONS: Astroviruses including novel MLB- and VA-clade members are commonly found in pediatric stools in Kenya and The Gambia. The most recently discovered astrovirus, MLB3, was the most prevalent and was found more commonly in control stools in The Gambia, while astrovirus MLB1 was associated with diarrhea in Kenya. Furthermore, a distinct subtype of MLB3 was noted, as well as 3 unanticipated avian or canine astroviruses in the human stool samples. As a result of a broadly reactive PCR screen for astroviruses, new insight was gained regarding the epidemiology of astroviruses in Africa, where a large proportion of diarrheal morbidity and mortality occur. |
Microbiota that affect risk for shigellosis in children in low-income countries.
Lindsay B , Oundo J , Hossain MA , Antonio M , Tamboura B , Walker AW , Paulson JN , Parkhill J , Omore R , Faruque AS , Das SK , Ikumapayi UN , Adeyemi M , Sanogo D , Saha D , Sow S , Farag TH , Nasrin D , Li S , Panchalingam S , Levine MM , Kotloff K , Magder LS , Hungerford L , Sommerfelt H , Pop M , Nataro JP , Stine OC . Emerg Infect Dis 2015 21 (2) 242-50 Pathogens in the gastrointestinal tract exist within a vast population of microbes. We examined associations between pathogens and composition of gut microbiota as they relate to Shigella spp./enteroinvasive Escherichia coli infection. We analyzed 3,035 stool specimens (1,735 nondiarrheal and 1,300 moderate-to-severe diarrheal) from the Global Enteric Multicenter Study for 9 enteropathogens. Diarrheal specimens had a higher number of enteropathogens (diarrheal mean 1.4, nondiarrheal mean 0.95; p<0.0001). Rotavirus showed a negative association with Shigella spp. in cases of diarrhea (odds ratio 0.31, 95% CI 0.17-0.55) and had a large combined effect on moderate-to-severe diarrhea (odds ratio 29, 95% CI 3.8-220). In 4 Lactobacillus taxa identified by 16S rRNA gene sequencing, the association between pathogen and disease was decreased, which is consistent with the possibility that Lactobacillus spp. are protective against Shigella spp.-induced diarrhea. Bacterial diversity of gut microbiota was associated with diarrhea status, not high levels of the Shigella spp. ipaH gene. |
Shigella isolates from the Global Enteric Multicenter Study (GEMS) inform vaccine development
Livio S , Strockbine N , Panchalingam S , Tennant SM , Barry EM , Marohn ME , Antonio M , Hossain A , Mandomando I , Ochieng JB , Oundo JO , Qureshi S , Ramamurthy T , Tamboura B , Adegbola RA , Hossain MJ , Saha D , Sen S , Faruque AS , Alonso PL , Breiman RF , Zaidi AK , Sur D , Sow SO , Berkeley LY , O'Reilly C , Mintz ED , Biswas K , Cohen D , Farag TH , Nasrin D , Wu Y , Blackwelder WC , Kotloff KL , Nataro JP , Levine MM . Clin Infect Dis 2014 59 (7) 933-41 BACKGROUND: Shigella, a major diarrheal disease pathogen worldwide, is the target of vaccine development. The Global Enteric Multicenter Study (GEMS) investigated burden and etiology of moderate-to-severe diarrheal disease in children age<60 months and matched controls without diarrhea during three years in four sites in Africa and three in Asia. Shigella was one of the four most common pathogens across sites and age strata. GEMS Shigella serotypes are reviewed to guide vaccine development. METHODS: Subjects' stool specimens/rectal swabs were transported to site laboratories in transport media and plated onto XLD and MacConkey's agar. Suspect Shigella colonies were identified by biochemical tests and agglutination with antisera. Shigella isolates were shipped to the GEMS Reference Laboratory (Baltimore) for confirmation and serotyping of S. flexneri; one-third of isolates were sent to Centers for Disease Control and Prevention for quality control. RESULTS: S. dysenteriae and S. boydii accounted for only 5.0% and 5.4%, respectively, of 1130 Shigella case isolates; S. flexneri comprised 65.9% and S. sonnei 23.7%. Five serotypes/subserotypes comprised 89.4% of S. flexneri, including S. flexneri 2a, S. flexneri 6, S. flexneri 3a, S. flexneri 2b and S. flexneri 1b. CONCLUSIONS: A broad spectrum Shigella vaccine must protect against S. sonnei and 15 serotypes/subserotypes of S. flexneri. A quadrivalent vaccine including O antigens from S. sonnei, S. flexneri 2a, S. flexneri 3a and S. flexneri 6 can provide broad direct coverage against these most common serotypes and indirect coverage against all but one (rare) remaining subserotype through shared S. flexneri group antigens. |
A national cholera epidemic with high case fatality rates--Kenya 2009
Loharikar A , Briere E , Ope M , Langat D , Njeru I , Gathigi L , Makayotto L , Ismail AM , Thuranira M , Abade A , Amwayi S , Omolo J , Oundo J , De Cock KM , Breiman RF , Ayers T , Mintz E , O'Reilly CE . J Infect Dis 2013 208 Suppl 1 S69-77 BACKGROUND: Cholera remains endemic in sub-Saharan Africa. We characterized the 2009 cholera outbreaks in Kenya and evaluated the response. METHODS: We analyzed surveillance data and estimated case fatality rates (CFRs). Households in 2 districts, East Pokot (224 cases; CFR = 11.7%) and Turkana South (1493 cases; CFR = 1.0%), were surveyed. We randomly selected 15 villages and 8 households per village in each district. Healthcare workers at 27 health facilities (HFs) were surveyed in both districts. RESULTS:. In 2009, cholera outbreaks caused a reported 11 425 cases and 264 deaths in Kenya. Data were available from 44 districts for 6893 (60%) cases. District CFRs ranged from 0% to 14.3%. Surveyed household respondents (n = 240) were aware of cholera (97.5%) and oral rehydration solution (ORS) (87.9%). Cholera deaths were reported more frequently from East Pokot (n = 120) than Turkana South (n = 120) households (20.7% vs. 12.3%). The average travel time to a HF was 31 hours in East Pokot compared with 2 hours in Turkana South. Fewer respondents in East Pokot (9.8%) than in Turkana South (33.9%) stated that ORS was available in their village. ORS or intravenous fluid shortages occurred in 20 (76.9%) surveyed HFs. CONCLUSIONS: High CFRs in Kenya are related to healthcare access disparities, including availability of rehydration supplies. |
Survey of culture, golden gate assay, universal biosensor assay, and 16S rRNA gene sequencing as alternative methods of bacterial pathogen detection
Lindsay B , Pop M , Antonio M , Walker AW , Mai V , Ahmed D , Oundo J , Tamboura B , Panchalingam S , Levine MM , Kotloff K , Li S , Magder LS , Paulson JN , Liu B , Ikumapayi U , Ebruke C , Dione M , Adeyemi M , Rance R , Stares MD , Ukhanova M , Barnes B , Lewis I , Ahmed F , Alam MT , Amin R , Siddiqui S , Ochieng JB , Ouma E , Juma J , Mailu E , Omore R , O'Reilly CE , Hannis J , Manalili S , Deleon J , Yasuda I , Blyn L , Ranken R , Li F , Housley R , Ecker DJ , Hossain MA , Breiman RF , Morris JG , McDaniel TK , Parkhill J , Saha D , Sampath R , Stine OC , Nataro JP . J Clin Microbiol 2013 51 (10) 3263-9 Cultivation-based assays combined with PCR or enzyme-linked immunosorbent assay (ELISA)-based methods for finding virulence factors are standard methods for detecting bacterial pathogens in stools; however, with emerging molecular technologies, new methods have become available. The aim of this study was to compare four distinct detection technologies for the identification of pathogens in stools from children under 5 years of age in The Gambia, Mali, Kenya, and Bangladesh. The children were identified, using currently accepted clinical protocols, as either controls or cases with moderate to severe diarrhea. A total of 3,610 stool samples were tested by established clinical culture techniques: 3,179 DNA samples by the Universal Biosensor assay (Ibis Biosciences, Inc.), 1,466 DNA samples by the GoldenGate assay (Illumina), and 1,006 DNA samples by sequencing of 16S rRNA genes. Each method detected different proportions of samples testing positive for each of seven enteric pathogens, enteroaggregative Escherichia coli (EAEC), enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), Shigella spp., Campylobacter jejuni, Salmonella enterica, and Aeromonas spp. The comparisons among detection methods included the frequency of positive stool samples and kappa values for making pairwise comparisons. Overall, the standard culture methods detected Shigella spp., EPEC, ETEC, and EAEC in smaller proportions of the samples than either of the methods based on detection of the virulence genes from DNA in whole stools. The GoldenGate method revealed the greatest agreement with the other methods. The agreement among methods was higher in cases than in controls. The new molecular technologies have a high potential for highly sensitive identification of bacterial diarrheal pathogens. |
Quantitative PCR for detection of Shigella improves ascertainment of Shigella burden in children with moderate-to-severe diarrhea in low-income countries
Lindsay B , Ochieng JB , Ikumapayi UN , Toure A , Ahmed D , Li S , Panchalingam S , Levine MM , Kotloff K , Rasko DA , Morris CR , Juma J , Fields BS , Dione M , Malle D , Becker SM , Houpt ER , Nataro JP , Sommerfelt H , Pop M , Oundo J , Antonio M , Hossain A , Tamboura B , Stine OC . J Clin Microbiol 2013 51 (6) 1740-6 Estimates of the prevalence of Shigella spp. are limited by the suboptimal sensitivity of current diagnostic and surveillance methods. We used a quantitative PCR (qPCR) assay to detect Shigella in the stool samples of 3,533 children aged <59 months from the Gambia, Mali, Kenya, and Bangladesh, with or without moderate-to-severe diarrhea (MSD). We compared the results from conventional culture to those from qPCR for the Shigella ipaH gene. Using MSD as the reference standard, we determined the optimal cutpoint to be 2.9 x 10(4) ipaH copies per 100 ng of stool DNA for set 1 (n = 877). One hundred fifty-eight (18%) specimens yielded >2.9 x 10(4) ipaH copies. Ninety (10%) specimens were positive by traditional culture for Shigella. Individuals with ≥ 2.9 x 10(4) ipaH copies have 5.6-times-higher odds of having diarrhea than those with <2.9 x 10(4) ipaH copies (95% confidence interval, 3.7 to 8.5; P < 0.0001). Nearly identical results were found using an independent set of samples. qPCR detected 155 additional MSD cases with high copy numbers of ipaH, a 90% increase from the 172 cases detected by culture in both samples. Among a subset (n = 2,874) comprising MSD cases and their age-, gender-, and location-matched controls, the fraction of MSD cases that were attributable to Shigella infection increased from 9.6% (n = 129) for culture to 17.6% (n = 262) for qPCR when employing our cutpoint. We suggest that qPCR with a cutpoint of approximately 1.4 x 10(4) ipaH copies be the new reference standard for the detection and diagnosis of shigellosis in children in low-income countries. The acceptance of this new standard would substantially increase the fraction of MSD cases that are attributable to Shigella. |
Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study
Kotloff KL , Nataro JP , Blackwelder WC , Nasrin D , Farag TH , Panchalingam S , Wu Y , Sow SO , Sur D , Breiman RF , Faruque AS , Zaidi AK , Saha D , Alonso PL , Tamboura B , Sanogo D , Onwuchekwa U , Manna B , Ramamurthy T , Kanungo S , Ochieng JB , Omore R , Oundo JO , Hossain A , Das SK , Ahmed S , Qureshi S , Quadri F , Adegbola RA , Antonio M , Hossain MJ , Akinsola A , Mandomando I , Nhampossa T , Acacio S , Biswas K , O'Reilly CE , Mintz ED , Berkeley LY , Muhsen K , Sommerfelt H , Robins-Browne RM , Levine MM . Lancet 2013 382 (9888) 209-22 BACKGROUND: Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multicenter Study (GEMS) to identify the aetiology and population-based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia. METHODS: The GEMS is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0-59 months residing in censused populations at four sites in Africa and three in Asia. We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea. From patients with moderate-to-severe diarrhoea and controls, we obtained clinical and epidemiological data, anthropometric measurements, and a faecal sample to identify enteropathogens at enrolment; one follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth. FINDINGS: We enrolled 9439 children with moderate-to-severe diarrhoea and 13,129 control children without diarrhoea. By analysing adjusted population attributable fractions, most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat-stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella. Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni). Odds of dying during follow-up were 8.5-fold higher in patients with moderate-to-severe diarrhoea than in controls (odd ratio 8.5, 95% CI 5.8-12.5, p<0.0001); most deaths (167 [87.9%]) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC (hazard ratio [HR] 1.9; 0.99-3.5) and typical enteropathogenic E coli (HR 2.6; 1.6-4.1) in infants aged 0-11 months, and Cryptosporidium (HR 2.3; 1.3-4.3) in toddlers aged 12-23 months. INTERPRETATION: Interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enteropathogenic E coli) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes. FUNDING: The Bill & Melinda Gates Foundation. |
Use of population-based surveillance to define the high incidence of shigellosis in an urban slum in Nairobi, Kenya
Njuguna HN , Cosmas L , Williamson J , Nyachieo D , Olack B , Ochieng JB , Wamola N , Oundo JO , Feikin DR , Mintz ED , Breiman RF . PLoS One 2013 8 (3) e58437 BACKGROUND: Worldwide, Shigella causes an estimated 160 million infections and >1 million deaths annually. However, limited incidence data are available from African urban slums. We investigated the epidemiology of shigellosis and drug susceptibility patterns within a densely populated urban settlement in Nairobi, Kenya through population-based surveillance. METHODS: Surveillance participants were interviewed in their homes every 2 weeks by community interviewers. Participants also had free access to a designated study clinic in the surveillance area where stool specimens were collected from patients with diarrhea (≥3 loose stools within 24 hours) or dysentery (≥1 stool with visible blood during previous 24 hours). We adjusted crude incidence rates for participants meeting stool collection criteria at household visits who reported visiting another clinic. RESULTS: RShigella species were isolated from 224 (23%) of 976 stool specimens. The overall adjusted incidence rate was 408/100,000 person years of observation (PYO) with highest rates among adults 34-49 years old (1,575/100,000 PYO). Isolates were: Shigella flexneri (64%), S. dysenteriae (11%), S. sonnei (9%), and S. boydii (5%). Over 90% of all Shigella isolates were resistant to trimethoprim-sulfamethoxazole and sulfisoxazole. Additional resistance included nalidixic acid (3%), ciprofloxacin (1%) and ceftriaxone (1%). CONCLUSION: More than 1 of every 200 persons experience shigellosis each year in this Kenyan urban slum, yielding rates similar to those in some Asian countries. Provision of safe drinking water, improved sanitation, and hygiene in urban slums are needed to reduce disease burden, in addition to development of effective Shigella vaccines. |
Diagnostic microbiologic methods in the GEMS-1 case/control study
Panchalingam S , Antonio M , Hossain A , Mandomando I , Ochieng B , Oundo J , Ramamurthy T , Tamboura B , Zaidi AK , Petri W , Houpt E , Murray P , Prado V , Vidal R , Steele D , Strockbine N , Sansonetti P , Glass RI , Robins-Browne RM , Tauschek M , Svennerholm AM , Kotloff K , Levine MM , Nataro JP . Clin Infect Dis 2012 55 Suppl 4 S294-302 To understand the etiology of moderate-to-severe diarrhea among children in high mortality areas of sub-Saharan Africa and South Asia, we performed a comprehensive case/control study of children aged <5 years at 7 sites. Each site employed an identical case/control study design and each utilized a uniform comprehensive set of microbiological assays to identify the likely bacterial, viral and protozoal etiologies. The selected assays effected a balanced consideration of cost, robustness and performance, and all assays were performed at the study sites. Identification of bacterial pathogens employed streamlined conventional bacteriologic biochemical and serological algorithms. Diarrheagenic Escherichia coli were identified by application of a multiplex polymerase chain reaction assay for enterotoxigenic, enteroaggregative, and enteropathogenic E. coli. Rotavirus, adenovirus, Entamoeba histolytica, Giardia enterica, and Cryptosporidium species were detected by commercially available enzyme immunoassays on stool samples. Samples positive for adenovirus were further evaluated for adenovirus serotypes 40 and 41. We developed a novel multiplex assay to detect norovirus (types 1 and 2), astrovirus, and sapovirus. The portfolio of diagnostic assays used in the GEMS study can be broadly applied in developing countries seeking robust cost-effective methods for enteric pathogen detection. |
Molecular epidemiology of geographically dispersed Vibrio cholerae, Kenya, January 2009-May 2010
Mohamed AA , Oundo J , Kariuki SM , Boga HI , Sharif SK , Akhwale W , Omolo J , Amwayi AS , Mutonga D , Kareko D , Njeru M , Li S , Breiman RF , Stine OC . Emerg Infect Dis 2012 18 (6) 925-31 Numerous outbreaks of cholera have occurred in Kenya since 1971. To more fully understand the epidemiology of cholera in Kenya, we analyzed the genetic relationships among 170 Vibrio cholerae O1 isolates at 5 loci containing variable tandem repeats. The isolates were collected during January 2009-May 2010 from various geographic areas throughout the country. The isolates grouped genetically into 5 clonal complexes, each comprising a series of genotypes that differed by an allelic change at a single locus. No obvious correlation between the geographic locations of the isolates and their genotypes was observed. Nevertheless, geographic differentiation of the clonal complexes occurred. Our analyses showed that multiple genetic lineages of V. cholerae were simultaneously infecting persons in Kenya. This finding is consistent with the simultaneous emergence of multiple distinct genetic lineages of V. cholerae from endemic environmental reservoirs rather than recent introduction and spread by travelers. |
- Page last reviewed:Feb 1, 2024
- Page last updated:Apr 22, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure