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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

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.

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.

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.

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., (Copyright © 2018. Published by Elsevier Ltd.)

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.