Monovalent Rotavirus Vaccine Effectiveness Against Rotavirus Hospitalizations Among Children in Zimbabwe.

BACKGROUND: Rotavirus is a leading cause of mortality among children <5 years old. We evaluated monovalent rotavirus vaccine effectiveness (VE) under conditions of routine use at 2 surveillance sites in Harare, Zimbabwe, after vaccine introduction in May 2014. METHODS: Children aged <5 years hospitalized or treated in the accident and emergency department (A&E) for acute watery diarrhea were enrolled for routine surveillance. Copies of vaccination cards were collected to document vaccination status. Among children age-eligible to receive rotavirus vaccine, we estimated VE, calculated as 1 - odds ratio, using a test-negative case-control design. RESULTS: We included 903 rotavirus-positive cases and 2685 rotavirus-negative controls in the analysis; 99% had verified vaccination status. Rotavirus-positive children had more severe diarrhea than rotavirus-negative children; 61% of cases and 46% of controls had a Vesikari score ≥11 (P < .01). Among cases and controls, 31% and 37%, respectively, were stunted for their age (P < .01). Among children 6-11 months old, adjusted 2-dose VE against hospitalization or treatment in A&E due to rotavirus of any severity was 61% (95% confidence interval [CI], 21%-81%) and 68% (95% CI, 13%-88%) against severe rotavirus disease. Stratified by nutritional status, adjusted VE was 45% (95% CI, -148% to 88%) among stunted infants and 71% (95% CI, 29%-88%) among infants with a normal height for age. CONCLUSIONS: Monovalent rotavirus vaccine is effective in preventing hospitalizations due to severe rotavirus diarrhea among infants in Zimbabwe, providing additional evidence for countries considering rotavirus vaccine introduction that live, oral rotavirus vaccines are effective in high-child-mortality settings.

Etiology of Severe Acute Watery Diarrhea in Children in the Global Rotavirus Surveillance Network Using Quantitative Polymerase Chain Reaction.

Background: The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction. Methods: We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children <5 years of age during 2013-2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs). Results: Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%-44.3%]), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9-15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8-9.2]), Cryptosporidium (AF, 5.8 [95% CI, 4.0-7.6]), Shigella (AF, 4.7 [95% CI, 2.8-6.9]), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0-6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9-5.5]) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%-61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%-30.4%) in age-eligible children. Conclusions: Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea.

Baseline Inflammatory Biomarkers Identify Subgroups of HIV-Infected African Children With Differing Responses to Antiretroviral Therapy.

BACKGROUND: Identifying determinants of morbidity and mortality may help target future interventions for human immunodeficiency virus (HIV)-infected children. METHODS: CD4(+) T-cell count, HIV viral load, and levels of biomarkers (C-reactive protein, tumor necrosis factor α [TNF-α], interleukin 6 [IL-6], and soluble CD14) and interleukin 7 were measured at antiretroviral therapy (ART) initiation in the ARROW trial (case-cohort design). Cases were individuals who died, had new or recurrent World Health Organization clinical stage 4 events, or had poor immunological response to ART. RESULTS: There were 115 cases (54 died, 45 had World Health Organization clinical stage 4 events, and 49 had poor immunological response) and 485 controls. Before ART initiation, the median ages of cases and controls were 8.2 years (interquartile range [IQR], 4.4-11.4 years) and 5.8 years (IQR, 2.3-9.3 years), respectively, and the median percentages of lymphocytes expressing CD4 were 4% (IQR, 1%-9%) and 13% (IQR, 8%-18%), respectively. In multivariable logistic regression, cases had lower age-associated CD4(+) T-cell count ratio (calculated as the ratio of the subject's CD4(+) T-cell count to the count expected in healthy individuals of the same age; P < .0001) and higher IL-6 level (P = .002) than controls. Clustering biomarkers and age-associated CD4(+) and CD8(+) T-cell count ratios identified 4 groups of children. Group 1 had the highest frequency of cases (41% cases; 16% died) and profound immunosuppression; group 2 had similar mortality (23% cases; 15% died), but children were younger, with less profound immunosuppression and high levels of inflammatory biomarkers and malnutrition; group 3 comprised young children with moderate immunosuppression, high TNF-α levels, and high age-associated CD8(+) T-cell count ratios but lower frequencies of events (12% cases; 7% died); and group 4 comprised older children with low inflammatory biomarker levels, lower HIV viral loads, and good clinical outcomes (11% cases; 5% died). CONCLUSIONS: While immunosuppression is the major determinant of poor outcomes during ART, baseline inflammation is an additional important factor, identifying a subgroup of young children with similar mortality. Antiinflammatory interventions may help improve outcomes.

Trends of rubella incidence during a 5-year period of case based surveillance in Zimbabwe.

BACKGROUND: Rubella is a disease of public health significance owing to its adverse effects during pregnancy and on pregnancy outcomes. Women who contract rubella virus during pregnancy may experience complications such as foetal death or give birth to babies born with congenital rubella syndrome. Vaccination against rubella is the most effective and economical approach to control the disease, and to avoid the long term effects and high costs of care for children with congenital rubella syndrome as well as to prevent death from complications. Zimbabwe commenced rubella surveillance in 1999, despite lacking a rubella vaccine in the national Expanded Programme on Immunization, as per the World Health Organization recommendation to establish a surveillance system to estimate the disease burden before introduction of a rubella vaccine. The purpose of this analysis is to describe the disease trends and population demographics of rubella cases that were identified through the Zimbabwe national measles and rubella case-based surveillance system during a 5-year period between 2007 and 2011. METHODS: Data from the Zimbabwe National Measles Laboratory for the 5-year study period were analysed for age, sex, district of origin, seasonality, and rubella IgM serostatus. RESULTS: A total of 3428 serum samples from cases of suspected measles in all administrative districts of the country were received by the laboratory during this period. Cases included 51% males and 49% females. Of these, 2999 were tested for measles IgM of which 697 (23.2%) were positive. Of the 2302 measles IgM-negative samples, 865 (37.6%) were rubella IgM-positive. Ninety-eight percent of confirmed rubella cases were children younger than 15 years of age. Most infections occurred during the dry season. CONCLUSIONS: The national case-based surveillance revealed the disease burden and trends of rubella in Zimbabwe. These data add to the evidence for introducing rubella-containing vaccine into the national immunization programme.

Whole-genome analyses of DS-1-like human G2P[4] and G8P[4] rotavirus strains from Eastern, Western and Southern Africa.

Group A rotaviruses (RVAs) with distinct G and P genotype combinations have been reported globally. We report the genome composition and possible origin of seven G8P[4] and five G2P[4] human RVA strains based on the genetic evolution of all 11 genome segments at the nucleotide level. Twelve RVA ELISA positive stool samples collected in the representative countries of Eastern, Southern and West Africa during the 2007-2012 surveillance seasons were subjected to sequencing using the Ion Torrent PGM and Illumina MiSeq platforms. A reference-based assembly was performed using CLC Bio's clc_ref_assemble_long program, and full-genome consensus sequences were obtained. With the exception of the neutralising antigen, VP7, all study strains exhibited the DS-1-like genome constellation (P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2) and clustered phylogenetically with reference strains having a DS-1-like genetic backbone. Comparison of the nucleotide and amino acid sequences with selected global cognate genome segments revealed nucleotide and amino acid sequence identities of 81.7-100 % and 90.6-100 %, respectively, with NSP4 gene segment showing the most diversity among the strains. Bayesian analyses of all gene sequences to estimate the time of divergence of the lineage indicated that divergence times ranged from 16 to 44 years, except for the NSP4 gene where the lineage seemed to arise in the more distant past at an estimated 203 years ago. However, the long-term effects of changes found within the NSP4 genome segment should be further explored, and thus we recommend continued whole-genome analyses from larger sample sets to determine the evolutionary mechanisms of the DS-1-like strains collected in Africa.

The impact of viraemia on inflammatory biomarkers and CD4+ cell subpopulations in HIV-infected children in sub-Saharan Africa.

OBJECTIVE: To determine the impact of virological control on inflammation and cluster of differentiation 4 depletion among HIV-infected children initiating antiretroviral therapy (ART) in sub-Saharan Africa. DESIGN: Longitudinal cohort study. METHODS: In a sub-study of the ARROW trial (ISRCTN24791884), we measured longitudinal HIV viral loads, inflammatory biomarkers (C-reactive protein, tumour necrosis factor alpha, interleukin 6 (IL-6), soluble CD14) and (Uganda only) whole blood immunophenotype by flow cytometry in 311 Zimbabwean and Ugandan children followed for median 3.5 years on first-line ART. We classified each viral load measurement as consistent suppression, blip/post-blip, persistent low-level viral load or rebound. We used multi-level models to estimate rates of increase or decrease in laboratory markers, and Poisson regression to estimate the incidence of clinical events. RESULTS: Overall, 42% children experienced viral blips, but these had no significant impact on immune reconstitution or inflammation. Persistent detectable viraemia occurred in one-third of children and prevented further immune reconstitution, but had little impact on inflammatory biomarkers. Virological rebound to ≥5000 copies/ml was associated with arrested immune reconstitution, rising IL-6 and increased risk of clinical disease progression. CONCLUSIONS: As viral load testing becomes more available in sub-Saharan Africa, repeat testing algorithms will be required to identify those with virological rebound, who need switching to prevent disease progression, whilst preventing unnecessary second-line regimen initiation in the majority of children with detectable viraemia who remain at low risk of disease progression.

Strain-level analysis of gut-resident pro-inflammatory viridans group Streptococci suppressed by long-term cotrimoxazole prophylaxis among HIV-positive children in Zimbabwe.

Antimicrobials have become a mainstay of healthcare in the past century due to their activity against pathogens. More recently, it has become clear that they can also affect health via their impact on the microbiota and inflammation. This may explain some of their clinical benefits despite global increases in antimicrobial resistance (AMR) and reduced antimicrobial effectiveness. We showed in a randomized controlled trial of stopping versus continuing cotrimoxazole prophylaxis among HIV-positive Zimbabwean children taking antiretroviral therapy (ART), that continuation of cotrimoxazole persistently suppressed gut-resident viridans group streptococcal species (VGS) that were associated with intestinal inflammation. In this addendum, we provide a broader overview of how antibiotics can shape the microbiota and use high read-depth whole metagenome sequencing data from our published study to investigate whether (i) the impact of cotrimoxazole on gut VGS and (ii) VGS associated inflammation, is attributable to strain-level variability. We focus on S. salivarius, the VGS species that was most prevalent in the cohort and for which there was sufficient genome coverage to differentiate strains. We demonstrate that suppression of S. salivarius by cotrimoxazole is not strain specific, nor did stool concentration of the pro-inflammatory mediator myeloperoxidase vary by S. salivarius strain. We also show that gut-resident S. salivarius strains present in this study population are distinct from common oral strains. This is the first analysis of how cotrimoxazole prophylaxis used according to international treatment guidelines for children living with HIV influences the gut microbiome at the strain-level. We also provide a detailed review of the literature on the mechanisms by which suppression of VGS may act synergistically with cotrimoxazole's anti-inflammatory effects to reduce gut inflammation. A greater understanding of the sub-clinical effects of antibiotics offers new insights into their responsible clinical use.

Brief Report: Cessation of Long-Term Cotrimoxazole Prophylaxis in HIV-Infected Children Does Not Alter the Carriage of Antimicrobial Resistance Genes.

BACKGROUND: Cotrimoxazole (CTX) is a broad-spectrum antimicrobial, combining trimethoprim and sulfamethoxazole. CTX prophylaxis reduces mortality and morbidity among people living with HIV in regions with high prevalence of bacterial infections and malaria. The Antiretroviral research for Watoto trial evaluated the effect of stopping versus continuing CTX prophylaxis in sub-Saharan Africa. METHODS: In this study, 72 HIV-infected Zimbabwean children, on antiretroviral therapy, provided fecal samples at 84 and 96 weeks after randomization to continue or stop CTX. DNA was extracted for whole metagenome shotgun sequencing, with sequencing reads mapped to the Comprehensive Antibiotic Resistance Database to identify CTX and other antimicrobial resistance genes. RESULTS: There were minimal differences in the carriage of CTX resistance genes between groups. The dfrA1 gene, conferring trimethoprim resistance, was significantly higher in the continue group (P = 0.039) and the tetA(P) gene conferring resistance to tetracycline was significantly higher in the stop group (P = 0.013). CTX prophylaxis has a role in shaping the resistome; however, stopping prophylaxis does not decrease resistance gene abundance. CONCLUSIONS: No differences were observed in resistance gene carriage between the stop and continue groups. The previously shown multi-faceted protective effects of CTX in antiretroviral research for Watoto trial clinical outcomes are not outweighed by the risk of multi-drug resistance gene selection due to prophylaxis. These findings are reassuring, given current recommendations for long-term CTX prophylaxis among children living with HIV in sub-Saharan Africa to decrease mortality and morbidity.

Cost estimates of diarrhea hospitalizations among children <5 years old in Zimbabwe.

INTRODUCTION: Diarrhoea is a leading killer of children <5 years old, accounting for 480,000 deaths in 2017. Zimbabwe introduced Rotarix into its vaccination program in 2014. In this evaluation, we estimate direct medical, direct non-medical, and indirect costs attributable to a diarrhea hospitalization in Zimbabwe after rotavirus vaccine introduction. METHODS: Children <5 years old admitted to Harare Central Hospital from June 2018 to April 2019 with acute watery diarrhea were eligible for this evaluation. A 3-part structured questionnaire was used to collect data by interview from the child's family and by review of the medical record. A stool specimen was also collected and tested for rotavirus. Direct medical costs were the sum of medications, consumables, diagnostic tests, and service delivery costs. Direct non-medical costs were the sum of transportation, meals and lodging for caregivers. Indirect costs are the lost income for household members. RESULTS: A total of 202 children were enrolled with a median age of 12 months (IQR: 7-21) and 48 (24%) had malnutrition. Children were sick for a median of 2 days and most had received outpatient medical care prior to admission. The median monthly household income was higher for well-nourished children compared to malnourished children (p < 0.001). The median total cost of a diarrhea illness resulting in hospitalization was $293.74 (IQR: 188.42, 427.89). Direct medical costs, with a median of $251.74 (IQR: 155.42, 390.96), comprised the majority of the total cost. Among children who tested positive for rotavirus, the median total illness cost was $243.78 (IQR: 160.92, 323.84). The median direct medical costs were higher for malnourished than well-nourished children (p < 0.001). CONCLUSION: Direct medical costs are the primary determinant of diarrhea illness costs in Zimbabwe. The descriptive findings from this evaluation are an important first step in calculating the cost effectiveness of rotavirus vaccine.

Inflammatory biomarkers in HIV-infected children hospitalized for severe malnutrition in Uganda and Zimbabwe.

OBJECTIVES: A proportion of HIV-infected children with advanced disease develop severe malnutrition soon after antiretroviral therapy (ART) initiation. We tested the hypothesis that systemic inflammation underlies the pathogenesis of severe malnutrition in HIV-infected children. DESIGN: Cross-sectional laboratory substudy in 613 HIV-infected children initiating ART in Uganda and Zimbabwe. METHODS: We measured C-reactive protein (CRP), TNFα, IL-6 and soluble CD14 by ELISA in cryopreserved plasma at baseline (pre-ART) and week-4 (children with severe malnutrition only). Independent associations between baseline biomarkers and subsequent hospitalization for severe malnutrition were identified using multivariable fractional polynomial logistic regression. RESULTS: Compared with children without severe malnutrition (n = 574, median age 6.3 years, median baseline weight-for-age Z-score -2.2), children hospitalized for severe malnutrition post-ART (n = 39, median age 2.3 years, median baseline weight-for-age Z-score -4.8) had higher baseline CRP [median 13.5 (interquartile range 5.5, 41.1) versus 4.1 (1.4, 14.4) mg/l; P = 0.003] and IL-6 [median 9.2 (6.7, 15.6) versus 5.9 (4.6, 9.3) pg/ml; P < 0.0001], but similar overall TNFα, soluble CD14 and HIV viral load (all P > 0.06). In a multivariable model, higher pre-ART IL-6, lower TNFα and lower weight-for-age were independently associated with subsequent hospitalization for severe malnutrition. Between weeks 0 and 4, there was a significant rise in CRP, IL-6 and soluble CD14, and fall in TNFα and HIV viral load in children hospitalized for severe malnutrition (all P < 0.02). CONCLUSION: Pre-ART IL-6 and TNFα were more strongly associated with hospitalization for severe malnutrition than CD4 cell count or viral load, highlighting the importance of inflammation at the time of ART initiation in HIV-infected children.

Cotrimoxazole reduces systemic inflammation in HIV infection by altering the gut microbiome and immune activation.

Long-term cotrimoxazole prophylaxis reduces mortality and morbidity in HIV infection, but the mechanisms underlying these clinical benefits are unclear. Here, we investigate the impact of cotrimoxazole on systemic inflammation, an independent driver of HIV mortality. In HIV-positive Ugandan and Zimbabwean children receiving antiretroviral therapy, we show that plasma inflammatory markers were lower after randomization to continue (n = 144) versus stop (n = 149) cotrimoxazole. This was not explained by clinical illness, HIV progression, or nutritional status. Because subclinical enteropathogen carriage and enteropathy can drive systemic inflammation, we explored cotrimoxazole effects on the gut microbiome and intestinal inflammatory biomarkers. Although global microbiome composition was unchanged, viridans group Streptococci and streptococcal mevalonate pathway enzymes were lower among children continuing (n = 36) versus stopping (n = 36) cotrimoxazole. These changes were associated with lower fecal myeloperoxidase. To isolate direct effects of cotrimoxazole on immune activation from antibiotic effects, we established in vitro models of systemic and intestinal inflammation. In vitro cotrimoxazole had modest but consistent inhibitory effects on proinflammatory cytokine production by blood leukocytes from HIV-positive (n = 16) and HIV-negative (n = 8) UK adults and reduced IL-8 production by gut epithelial cell lines. Collectively we demonstrate that cotrimoxazole reduces systemic and intestinal inflammation both indirectly via antibiotic effects on the microbiome and directly by blunting immune and epithelial cell activation. Synergy between these pathways may explain the clinical benefits of cotrimoxazole despite high antimicrobial resistance, providing further rationale for extending coverage among people living with HIV in sub-Saharan Africa.

Distribution of rotavirus genotypes associated with acute diarrhoea in Zimbabwean children less than five years old before and after rotavirus vaccine introduction.

BACKGROUND: Sentinel surveillance for diarrhoea is important to monitor changes in rotavirus epidemiological trends and circulating genotypes among children under 5 years before and after vaccine introduction. The Zimbabwe Ministry of Health and Child Care introduced rotavirus vaccine in national immunization program in May 2014. METHODS: Active hospital-based surveillance for diarrhoea was conducted at 3 sentinel sites from 2008 to 2016. Children aged less than 5 years, who presented with acute gastroenteritis as a primary illness and who were admitted to a hospital ward or treated at the emergency unit, were enrolled and had a stool specimen collected and tested for rotavirus by enzyme immunoassay (EIA). Genotyping of positive stools was performed using reverse-transcription polymerase chain reaction and genotyping assays. Pre-vaccine introduction, 10% of all positive stool specimens were genotyped and all adequate positive stools were genotyped post-vaccine introduction. RESULTS: During the pre-vaccine period, a total of 6491 acute gastroenteritis stools were collected, of which 3016 (46%) tested positive for rotavirus and 312 (10%) of the rotavirus positive stools were genotyped. During the post-vaccine period, a total of 3750 acute gastroenteritis stools were collected, of which 937 (25%) tested positive for rotavirus and 784 (84%) were genotyped. During the pre-vaccine introduction the most frequent genotype was G9P[8] (21%) followed by G2P[4] (12%), G1P[8] (6%), G2P[6] (5%), G12P[6] (4%), G9P[6] (3%) and G8P[4] (3%). G1P[8] (30%) was most dominant two years after vaccine introduction followed by G9P[6] (20%), G2P[4] (15%), G9P[8] (11%) and G1P[6] (4%). CONCLUSION: The decline in positivity rate is an indication of early vaccine impact. Diversity of circulating strains underscores the importance of continued monitoring and strain surveillance after vaccine introduction.

Reduction in Diarrhea- and Rotavirus-related Healthcare Visits Among Children <5 Years of Age After National Rotavirus Vaccine Introduction in Zimbabwe.

BACKGROUND: In Zimbabwe, rotavirus accounted for 41%-56% of acute diarrhea hospitalizations before rotavirus vaccine introduction in 2014. We evaluated rotavirus vaccination impact on acute diarrhea- and rotavirus-related healthcare visits in children. METHODS: We examined monthly and annual acute diarrhea and rotavirus test-positive hospitalizations and Accident and Emergency Department visits among children <60 months of age at 3 active surveillance hospitals during 2012-2016; we compared prevaccine introduction (2012-2013) with postvaccine introduction (2015 and 2016) data for 2 of the hospitals. We examined monthly acute diarrhea hospitalizations by year and age group for 2013-2016 from surveillance hospital registers and monthly acute diarrhea outpatient visits reported to the Ministry of Health and Child Care during 2012-2016. RESULTS: Active surveillance data showed winter seasonal peaks in diarrhea- and rotavirus-related visits among children <60 months of age during 2012-2014 that were substantially blunted in 2015 and 2016 after vaccine introduction; the percentage of rotavirus test-positive visits followed a similar seasonal pattern and decrease. Hospital register data showed similar pre-introduction seasonal variation and post-introduction declines in diarrhea hospitalizations among children 0-11 and 12-23 months of age. Monthly variation in outpatient diarrhea-related visits mirrored active surveillance data patterns. At 2 surveillance hospitals, the percentage of rotavirus-positive visits declined by 40% and 43% among children 0-11 months of age and by 21% and 33% among children 12-23 months of age in 2015 and 2016, respectively. CONCLUSION: Initial reductions in diarrheal illness among children <60 months of age, particularly among those 0-11 months of age, after vaccine introduction are encouraging. These early results provide evidence to support continued rotavirus vaccination and rotavirus surveillance in Zimbabwe.

Whole genome detection of rotavirus mixed infections in human, porcine and bovine samples co-infected with various rotavirus strains collected from sub-Saharan Africa.

Group A rotaviruses (RVA) are among the main global causes of severe diarrhea in children under the age of 5years. Strain diversity, mixed infections and untypeable RVA strains are frequently reported in Africa. We analysed rotavirus-positive human stool samples (n=13) obtained from hospitalised children under the age of 5years who presented with acute gastroenteritis at sentinel hospital sites in six African countries, as well as bovine and porcine stool samples (n=1 each), to gain insights into rotavirus diversity and evolution. Polyacrylamide gel electrophoresis (PAGE) analysis and genotyping with G-(VP7) and P-specific (VP4) typing primers suggested that 13 of the 15 samples contained more than 11 segments and/or mixed G/P genotypes. Full-length amplicons for each segment were generated using RVA-specific primers and sequenced using the Ion Torrent and/or Illumina MiSeq next-generation sequencing platforms. Sequencing detected at least one segment in each sample for which duplicate sequences, often having distinct genotypes, existed. This supported and extended the PAGE and RT-PCR genotyping findings that suggested these samples were collected from individuals that had mixed rotavirus infections. The study reports the first porcine (MRC-DPRU1567) and bovine (MRC-DPRU3010) mixed infections. We also report a unique genome segment 9 (VP7), whose G9 genotype belongs to lineage VI and clusters with porcine reference strains. Previously, African G9 strains have all been in lineage III. Furthermore, additional RVA segments isolated from humans have a clear evolutionary relationship with porcine, bovine and ovine rotavirus sequences, indicating relatively recent interspecies transmission and reassortment. Thus, multiple RVA strains from sub-Saharan Africa are infecting mammalian hosts with unpredictable variations in their gene segment combinations. Whole-genome sequence analyses of mixed RVA strains underscore the considerable diversity of rotavirus sequences and genome segment combinations that result from a complex evolutionary history involving multiple host species.

Human parasitic protozoa in drinking water sources in rural Zimbabwe and their link to HIV infection.

OBJECTIVE: We aimed to perform a risk assessment in a rural setting, where drinking water is obtained from both protected and unprotected deep or shallow wells, boreholes and springs. Water is consumed untreated and this poses a risk of acquiring waterborne infections that may cause diarrhea. METHODS: The study included 113 study participants who volunteered in Chiweshe rural community (Musarara village) in Mashonaland Central Province in Zimbabwe. There were 34 (30%) males and 79 (70%) females with ages ranging from 2 to 89 years. HIV counseling was carried out at the communal meeting and testing was done at home visits. Stool and drinking water samples were collected from 104 subjects. Routine laboratory methods were used to examine for parasitic infections. RESULTS: Only 29 (25.7%) of participants were confirmed HIV positive using 2 rapid serology tests; eighty-four (74.3%) were negative. Diarrheic stool samples were observed in 17 (16.3%) participants and of these 5 (29.4%) were HIV seropositive. Several parasites were isolated from stool samples: G. duodenalis 6 (5.7%), E. histolytica/dispar 19 (18.2%), C. parvum, 8 (7.6%) and C. cayetanensis 23 (22.1%). Eleven out of 30 (36.6%) water bodies had protozoan parasites: G. duodenalis 2 (6.6%), E. histolytica 4 (13.3%), C. parvum 1 (3.3%), C. cayetanensis 3 (10%), E. coli 1 (3.3%). CONCLUSION: The water sources were being used without treatment and were shown to pose a risk for acquiring diarrheagenic protozoan parasites.

Epidemiologic and genotypic characteristics of rotavirus strains detected in children less than 5 years of age with gastroenteritis treated at 3 pediatric hospitals in Zimbabwe during 2008-2011.

BACKGROUND: In anticipation of rotavirus vaccine introduction, the Zimbabwe Ministry of Health initiated rotavirus surveillance in 2008 to describe the rotavirus epidemiological trends and circulating genotypes among children <5 years of age. METHODS: Active hospital-based surveillance for diarrhea was conducted at 3 sentinel sites from January 2008 to December 2011. Children aged <5 years, who presented with acute gastroenteritis as a primary illness and who were admitted to a hospital ward or treated at the emergency unit, were enrolled in the surveillance program and had a stool specimen collected and tested for rotavirus by enzyme immunoassay. Genotyping of a sample of positive specimens was performed using reverse-transcription polymerase chain reaction. RESULTS: A total of 3728 faecal samples were collected and tested during the 4 year surveillance period and 1804 (48.5%) tested rotavirus positive. The highest prevalence of rotavirus diarrhea was found during the dry, cool season. Rotavirus positivity peaked in children 3-17 months of age with almost 80% of cases. Compared with rotavirus-negative cases, rotavirus-positive cases were more likely to be dehydrated (26% vs. 14%, P ≤ 0.001) and have vomiting (77% vs. 57%, P ≤ 0.001) and less likely to have fever (17% vs. 24%, P = 0.03). G9P[8] (43.3%), G1P[8] (11.8%), G2P[4] (8.7%), G2P[6] (8.7%) and G12P[6] (8.7%) were the most common genotypes detected. DISCUSSION: Rotavirus causes a significant disease burden among children <5 years of age in Zimbabwe. This active surveillance system can serve as a platform to monitor the impact of rotavirus vaccine on disease burden following vaccine introduction.