Search

The causes of diarrhea after 10 years of rotavirus vaccination in Rwanda were investigated with real-time polymerase chain reaction in 496 children with diarrhea and 298 without. Rotavirus was detected in 11% of children with diarrhea (odds ratio, 2.48; P = .002). Comparison of population attributable fractions (PAFs) shows that Shigella (PAF, 11%) and enterotoxigenic Escherichia coli producing labile toxin (PAF, 12%) have replaced rotavirus as the main causative agents. The PAF for rotavirus had declined from 41% prevaccination to 6.5% postvaccination, indicating that rotavirus has become one among several similarly important causes of childhood diarrhea in Rwanda. A rotavirus genotype shift to G3P[8] points at the importance of continued genotype surveillance., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: To assess whether viral, bacterial, metabolic, and autoimmune diseases are missed by conventional diagnostics among children with severe acute encephalopathy in sub-Saharan Africa., Study Design: One hundred thirty-four children (6 months to 18 years) presenting with nontraumatic coma or convulsive status epilepticus to 1 of 4 medical referral centers in Uganda, Malawi, and Rwanda were enrolled between 2015 and 2016. Locally available diagnostic tests could be supplemented in 117 patients by viral, bacterial, and 16s quantitative polymerase chain reaction testing, metagenomics, untargeted metabolomics, and autoimmune immunohistochemistry screening., Results: Fourteen (12%) cases of viral encephalopathies, 8 (7%) cases of bacterial central nervous system (CNS) infections, and 4 (4%) cases of inherited metabolic disorders (IMDs) were newly identified by additional diagnostic testing as the most likely cause of encephalopathy. No confirmed cases of autoimmune encephalitis were found. Patients for whom additional diagnostic testing aided causal evaluation (aOR 3.59, 90% CI 1.57-8.36), patients with a viral CNS infection (aOR 7.91, 90% CI 2.49-30.07), and patients with an IMD (aOR 9.10, 90% CI 1.37-110.45) were at increased risk for poor outcome of disease., Conclusions: Viral and bacterial CNS infections and IMDs are prevalent causes of severe acute encephalopathy in children in Uganda, Malawi, and Rwanda that are missed by conventional diagnostics and are associated with poor outcome of disease. Improved diagnostic capacity may increase diagnostic yield and might improve outcome of disease., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Rotavirus vaccination has reduced mortality and hospital admissions due to rotavirus diarrhoea, but its effect on rotavirus infections and the impact of rotavirus genotypes are still unclear. Real-time PCR was used to detect rotavirus and other pathogens in faeces samples from children below five years of age with acute diarrhoea, collected before (n = 827) and after (n = 807, 92% vaccinated) the introduction of vaccination in Rwanda in 2012. Rotavirus was genotyped by targeting VP7 to identify G1, G2, G3, G4, G9 and G12 and VP4 to identify P[4], P[6] and P[8]. In vaccinated children, rotavirus infections were rarer (34% vs. 47%) below 12 months of age, severe dehydration was less frequent, and rotavirus was more often found as a co-infecting agent. (79% vs 67%, p = 0.004). Norovirus genogroup II, astrovirus, and sapovirus were significantly more often detected in vaccinated children. The predominant rotavirus genotypes were G2P[4] and G12P[6] in 2009-2010 (50% and 12%), G9P[8] and G1P[8] in 2011-2012 (51% and 22%), and G12P[8] in 2014-2015 (63%). Rotavirus vaccination in Rwanda has reduced the severity of rotavirus gastroenteritis and rotavirus infection frequency during the first year of life. Rotavirus infections were frequent in vaccinated children with diarrhoea, often as co-pathogen. Rotavirus genotype changes might be unrelated to vaccination because shifts were observed also before its introduction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kabayiza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Polymorphisms in the interferon lambda gene locus ( IFNL ) such as the IFNL4 genetic variants rs12979860 and rs368234815 are predictive of resolution of hepatitis C virus infection, but information about the impact of these variants in other infections is scarce. This study aimed at determining the potential impact of IFNL4 variation for the clearance of respiratory tract pathogens in Rwandan children (≤5 years old, n = 480) seeking medical care for acute respiratory infections. Nasopharyngeal swabs were retrieved from all children at the first hospital referral and from 161 children at follow-up visits 2 weeks later. The swabs were analyzed for pathogens by real-time PCR and for host cell IFNL4 genotype at rs12979860 and rs368234815 . Approximately 1/3 of the children were homozygous for the rs12979860 T allele and the rs368234815 ΔG allele, which are overrepresented in subjects of African descent. These IFNL4 variants were significantly associated with reduced clearance of RNA viruses. Our results suggest that IFNL4 genotypes that are common among subjects of African descent may determine inefficacious clearance of RNA viruses from the respiratory tract., (Copyright © 2019 Rugwizangoga, Andersson, Kabayiza, Nilsson, Ármannsdóttir, Aurelius, Nilsson, Hellstrand, Lindh and Martner.)

Background: The Rwanda Human Resources for Health Program (HRH Program) is a 7-year (2012-2019) health professional training initiative led by the Government of Rwanda with the goals of training a large, diverse, and competent health workforce and strengthening the capacity of academic institutions in Rwanda., Methods: The data for this organizational case study was collected through official reports from the Rwanda Ministry of Health (MoH) and 22 participating US academic institutions, databases from the MoH and the College of Medicine and Health Sciences (CMHS) in Rwanda, and surveys completed by the co-authors., Results: In the first 5 years of the HRH Program, a consortium of US academic institutions has deployed an average of 99 visiting faculty per year to support 22 training programs, which are on track to graduate almost 4600 students by 2019. The HRH Program has also built capacity within the CMHS by promoting the recruitment of Rwandan faculty and the establishment of additional partnerships and collaborations with the US academic institutions., Conclusion: The milestones achieved by the HRH Program have been substantial although some challenges persist. These challenges include adequately supporting the visiting faculty; pairing them with Rwandan faculty (twinning); ensuring strong communication and coordination among stakeholders; addressing mismatches in priorities between donors and implementers; the execution of a sustainability strategy; and the decision by one of the donors not to renew funding beyond March 2017. Over the next 2 academic years, it is critical for the sustainability of the 22 training programs supported by the HRH Program that the health-related Schools at the CMHS significantly scale up recruitment of new Rwandan faculty. The HRH Program can serve as a model for other training initiatives implemented in countries affected by a severe shortage of health professionals., (© 2018 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Enteric coinfections among children in low-income countries are very common, but it is not well known if specific pathogen combinations are associated or have clinical importance. In this analysis, feces samples from children in Rwanda and Zanzibar less than 5 years of age, with ( N = 994) or without ( N = 324) acute diarrhea, were analyzed by real-time polymerase chain reaction targeting a wide range of pathogens. Associations were investigated by comparing co-detection and mono-detection frequencies for all pairwise pathogen combinations. More than one pathogen was detected in 840 samples (65%). A negative association (coinfections being less common than expected from probability) was observed for rotavirus in combination with Shigella , Campylobacter , or norovirus genogroup II, but only in patients, which is statistically expected for agents that independently cause diarrhea. A positive correlation was observed, in both patients and controls, between Ct (threshold cycle) values for certain virulence factor genes in enteropathogenic Escherichia coli (EPEC) ( eae and bfpA ) and toxin genes in enterotoxigenic E. coli ( eltB and estA ), allowing estimation of how often these genes were present in the same bacteria. A significant positive association in patients only was observed for Shigella and EPEC -eae , suggesting that this coinfection might interact in a manner that enhances symptoms. Although interaction between pathogens that affect symptoms is rare, this work emphasizes the importance and difference in interpretation of coinfections depending on whether they are positively or negatively associated.

Background: The enormous burden of critical illness in resource-limited settings has led to a growing interest in paediatric critical care in these regions. However, published data on the practice of critical care and patient outcomes in these settings are scant., Objective: This study sought to identify risk factors associated with mortality in the newly established Paediatric Intensive Care Unit (PICU) at Kigali University Teaching Hospital (KUTH) in Rwanda and test the predictive ability of a newly devised mortality risk score, the modified PRISM (MP) score., Methods: All admissions to the PICU at KUTH from October 2012 to October 2014 were included. Demographic and physiological data on each patient were gathered and each was assigned a MP score. This prospective cross-sectional study examined the association between the characteristics and physiological status of these patients and mortality. Using logistic regression, factors associated with mortality in the PICU were analysed., Results: A total of 213 children were admitted to the PICU during the study period. Three patients were excluded because of missing data. Of this total, 59% were male, 25% were neonates and nearly 60% were moderately to severely malnourished. The overall mortality rate was 50%. On bivariate analysis, factors associated with increased mortality were male sex, use of vasoactive medications, a MP score ≥ 5, a discharge diagnosis of septic shock, and malnutrition on admission. On multivariate analysis, only the use of vasoactive drugs [odds ratio (OR) 12.24, 95% confidence interval (CI) 4.4-35.4, p < 0.001] and MP score ≥ 5 (OR 16.1, CI 6.3-40.8, p < 0.001) were associated with mortality., Conclusion: The observed mortality rate was in the range reported in other resource-limited settings. The initial attempt to create and implement a risk of mortality tool for this setting determined a score that could identify those patients at higher risk of mortality. In PICUs in resource-limited settings, the gathering of data and use of severity of illness tools could improve care in a number of ways.

Acute gastroenteritis is a main cause of disease and death among children in low-income countries. The causality rates and pathogenic characteristics of putative aetiological agents remain insufficiently known. We used real-time PCR targeting 16 diarrhoeagenic agents to analyse stool samples from children ≤5.0 years old with acute diarrhoea in Rwanda. Among the 880 children (median age 14.2 months; 41% female) at least one pathogen was detected in 92% and two or more agents in 63% of cases. Rotavirus was detected in 36.9%, adenovirus in 39.7%, enterotoxigenic Escherichia coli (ETEC) with genes for labile (eltB) or stable (estA) toxin in 31.3% and 19.0%, E. coli with eae or bfpA genes in 25.2% and 14.2%, Shigella in 17.5% and Cryptosporidium in 7.8%. Rotavirus and ETEC-estA were associated with more severe dehydration than diarrhoea due to other causes. Shigella was associated with bloody stools and higher CRP. Microbial loads (Ct values) of rotavirus, ETEC-estA and Shigella were associated with severity of symptoms. Rotavirus, ETEC-estA and E. coli with bfpA were associated with younger age, Shigella with older age. Antibiotic treatment was given to 42% and was associated with dehydration, fever and CRP, but not with pathogen. We conclude that rotavirus and ETEC-estA were the most important causes of diarrhoea with dehydration, that Shigella caused bloody diarrhoea but less severe dehydration, that microbial loads of rotavirus, ETEC-estA and Shigella were associated with severity of symptoms, and that antibiotic use was frequent and in poor agreement with microbiological findings., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Background: Knowledge about causes of acute diarrhea among children in developing countries is insufficient. Molecular methods might improve diagnostics of infectious gastroenteritis, but due to the high sensitivity, findings may be difficult to interpret., Methods: Feces samples from Rwandan children 0.5-5.0 years of age, with diarrhea for <96 hours (patients, n = 544) or without diarrhea for 14 days (controls, n = 162), were analyzed by real-time polymerase chain reaction targeting 17 pathogens., Results: At least 1 agent was detected in 94% of patients and in 79% of controls, with higher rates in sick children for rotavirus (42% vs. 2%, P < 0.0001) and enterotoxigenic Escherichia coli (ETEC)-estA (21% vs. 9%, P = 0.0006). Detection rates did not differ significantly for adenovirus (39% vs. 36%), ETEC-eltB (29% vs. 30%), Campylobacter (14% vs. 17%) or Shigella (13% vs. 10%), but for Shigella the threshold cycle (Ct) values were lower (pathogen loads were higher) in sick children than in controls. By multivariate analysis, including gender and age, detection of rotavirus (P < 0.0001), ETEC-estA (P = 0.001), Shigella (P = 0.004) and norovirus genogroup II (P = 0.009) was associated with symptomatic infection, and a Ct value below a cutoff (in the range 28-29) improved identification of ETEC-estA, Shigella and norovirus genogroup II., Conclusion: Real-time polymerase chain reaction can detect essentially all diarrheagenic agents, and provides Ct values that improve identification of clinically relevant infections.

Background: Molecular diagnostics have emerged as an efficient and feasible alternative for broad detection of pathogens in faeces. However, collection of stool samples is often impractical in both clinical work and in epidemiology studies. The aim of this study was to investigate the diagnostic performance of rectal swabs as compared with traditional faeces samples for detection of enteric agents by PCR., Method: Three hundred twenty-six pairs of rectal swab and stool samples, obtained from Rwandan children aged 0.5-4.99 years, with or without diarrhoea, were analysed by multiple real-time PCR amplifying 3 viral, 6 bacterial and one protozoan target., Results: For all agents there was a significant correlation (R2 0.31-0.85) between Ct values in faeces and rectal swabs. For most agents the Ct values, a marker for target concentration, were significantly lower (by 1-3 cycles) in faeces, indicating pathogen content up to ten times higher than in rectal swabs. Despite this, there was no significant difference in detection rate between faeces and rectal swabs for any agent, reflecting that pathogen concentration was far above the limit of detection in the majority of cases., Conclusion: The similar detection rates and the Ct value correlations as compared with traditional faeces samples indicate that rectal swabs are accurate for real-time PCR-based identification of enteric agents and may be used also for quantitative estimation of pathogen load.

Background: Infections caused by human enteroviruses (EVs) are often asymptomatic or mild, although they may cause more severe illnesses as meningitis and acute flaccid paralysis. EVs have globally posed a threat to children, and outbreaks of aseptic meningitis and hand, foot and mouth disease are frequently reported., Objective: To identify EV strains circulating among healthy children in a small community in Limbe, Cameroon two years apart., Study Design: Species and EV types were obtained by partial 5'UTR-VP4 and VP1 sequencing of RNA from stool samples collected in October 2009 and September 2011 from 150 children in Cameroon., Results: In all, 74 children (49%) were infected with 28 different types of EV. There were 29 (54%) infected children in 2009, and 45 (47%) in 2011. There was a significant difference between detected species of EV, with 15 (47%) children infected with EV-A in 2009, and 22 (71%) with EV-B in 2011 (p=0.0001). In 2009, one child was infected by a divergent EV, which was most similar to EV-A90. Based on the complete VP1 sequence, it was shown to be a new EV designated EV-A119., Conclusion: The current study shows a high heterogeneity of circulating EV types among children in Limbe, Cameroon, and a previously not described shift in predominating EV species., (Copyright © 2013 Elsevier B.V. All rights reserved.)