Rotavirus Genotypes in Hospitalized Children With Acute Gastroenteritis Before and After Rotavirus Vaccine Introduction in Blantyre, Malawi, 1997-2019.

BACKGROUND: Rotavirus vaccine (Rotarix [RV1]) has reduced diarrhea-associated hospitalizations and deaths in Malawi. We examined the trends in circulating rotavirus genotypes in Malawi over a 22-year period to assess the impact of RV1 introduction on strain distribution. METHODS: Data on rotavirus-positive stool specimens among children aged <5 years hospitalized with diarrhea in Blantyre, Malawi before (July 1997-October 2012, n = 1765) and after (November 2012-October 2019, n = 934) RV1 introduction were analyzed. Rotavirus G and P genotypes were assigned using reverse-transcription polymerase chain reaction. RESULTS: A rich rotavirus strain diversity circulated throughout the 22-year period; Shannon (H') and Simpson diversity (D') indices did not differ between the pre- and postvaccine periods (H' P < .149; D' P < .287). Overall, G1 (n = 268/924 [28.7%]), G2 (n = 308/924 [33.0%]), G3 (n = 72/924 [7.7%]), and G12 (n = 109/924 [11.8%]) were the most prevalent genotypes identified following RV1 introduction. The prevalence of G1P[8] and G2P[4] genotypes declined each successive year following RV1 introduction, and were not detected after 2018. Genotype G3 reemerged and became the predominant genotype from 2017 onward. No evidence of genotype selection was observed 7 years post-RV1 introduction. CONCLUSIONS: Rotavirus strain diversity and genotype variation in Malawi are likely driven by natural mechanisms rather than vaccine pressure.

Etiology of Diarrhea Among Hospitalized Children in Blantyre, Malawi, Following Rotavirus Vaccine Introduction: A Case-Control Study.

Despite rotavirus vaccination, diarrhea remains a leading cause of child mortality. We collected stool specimens from 684 children <5 years of age hospitalized with diarrhea (cases) and 527 asymptomatic community controls for 4 years after rotavirus vaccine introduction in Malawi. Specimens were tested for 29 pathogens, using polymerase chain reaction analysis. Three or more pathogens were detected in 71% of cases and 48% of controls. Pathogens significantly associated with diarrhea included rotavirus (in 34.7% of cases and 1.5% of controls), enteric adenovirus (in 29.1% and 2.7%, respectively), Cryptosporidium (in 27.8% and 8.2%, respectively), heat-stable enterotoxin-producing Escherichia coli (in 21.2% and 8.5%, respectively), typical enteropathogenic E. coli (in 18.0% and 8.3%, respectively), and Shigella/enteroinvasive E. coli (in 15.8% and 5.7%, respectively). Additional interventions are required to prevent diarrhea due to rotavirus and other common causal pathogens.

Utilizing river and wastewater as a SARS-CoV-2 surveillance tool to predict trends and identify variants of concern in settings with limited formal sewage systems.

The COVID-19 pandemic continues to impact health systems globally and robust surveillance is critical for pandemic control, however not all countries can sustain community surveillance programs. Wastewater surveillance has proven valuable in high-income settings, but little is known about how river and informal sewage in low-income countries can be used for environmental surveillance of SARS-CoV-2. In Malawi, a country with limited community-based COVID-19 testing capacity, we explored the utility of rivers and wastewater for SARS-CoV-2 surveillance. From May 2020 - January 2022, we collected water from up to 112 river or informal sewage sites/month, detecting SARS-CoV-2 in 8.3% of samples. Peak SARS-CoV-2 detection in water samples predated peaks in clinical cases. Sequencing of water samples identified the Beta, Delta, and Omicron variants, with Delta and Omicron detected well in advance of detection in patients. Our work highlights wastewater can be used for detecting emerging waves, identifying variants of concern and function as an early warning system in settings with no formal sewage systems.

Utilizing river and wastewater as a SARS-CoV-2 surveillance tool in settings with limited formal sewage systems.

The COVID-19 pandemic has profoundly impacted health systems globally and robust surveillance has been critical for pandemic control, however not all countries can currently sustain community pathogen surveillance programs. Wastewater surveillance has proven valuable in high-income settings, but less is known about the utility of water surveillance of pathogens in low-income countries. Here we show how wastewater surveillance of SAR-CoV-2 can be used to identify temporal changes and help determine circulating variants quickly. In Malawi, a country with limited community-based COVID-19 testing capacity, we explore the utility of rivers and wastewater for SARS-CoV-2 surveillance. From May 2020-May 2022, we collect water from up to 112 river or defunct wastewater treatment plant sites, detecting SARS-CoV-2 in 8.3% of samples. Peak SARS-CoV-2 detection in water samples predate peaks in clinical cases. Sequencing of water samples identified the Beta, Delta, and Omicron variants, with Delta and Omicron detected well in advance of detection in patients. Our work highlights how wastewater can be used to detect emerging waves, identify variants of concern, and provide an early warning system in settings with no formal sewage systems.

Cost of wastewater-based environmental surveillance for SARS-CoV-2: Evidence from pilot sites in Blantyre, Malawi and Kathmandu, Nepal.

Environmental surveillance of rivers and wastewater for SARS-CoV-2 detection has been explored as an innovative way to surveil the pandemic. This study estimated the economic costs of conducting wastewater-based environmental surveillance for SARS-CoV-2 to inform decision making if countries consider continuing these efforts. We estimated the cost of two SARS-CoV-2 environmental surveillance pilot studies conducted in Blantyre, Malawi, and Kathmandu, Nepal. The cost estimation accounted for the consumables, equipment, and human resource time costs used for environmental surveillance from sample selection until pathogen detection and overhead costs for the projects. Costs are reported in 2021 US$ and reported as costs per month, per sample and person per year. The estimated costs for environmental surveillance range from $6,175 to $8,272 per month (Blantyre site) and $16,756 to $30,050 (Kathmandu site). The number of samples processed per month ranged from 84 to 336 at the Blantyre site and 96 to 250 at the Kathmandu site. Consumables costs are variable costs influenced by the number of samples processed and are a large share of the monthly costs for ES (ranging from 39% to 72%). The relatively higher costs per month for the Kathmandu site were attributable to the higher allocation of dedicated human resources and equipment to environmental surveillance for SARS-CoV-2 compared to the Blantyre site where these resources were shared with other activities. The average cost per sample ranged from $25 to $74 (Blantyre) and $120 to $175 (Kathmandu). There were associated economies of scale for human resources and equipment costs with increased sample processing and sharing of resources with other activities. The cost per person in the catchment area per year ranged from $0.07 to $0.10 in Blantyre and $0.07 to $0.13 in Kathmandu. Environmental surveillance may be a low-cost early warning signal for SARS-CoV-2 that can complement other SARS-CoV2 monitoring efforts.

Reduction in Severity of All-Cause Gastroenteritis Requiring Hospitalisation in Children Vaccinated against Rotavirus in Malawi.

Rotavirus is the major cause of severe gastroenteritis in children aged <5 years. Introduction of the G1P[8] Rotarix® rotavirus vaccine in Malawi in 2012 has reduced rotavirus-associated hospitalisations and diarrhoeal mortality. However, the impact of rotavirus vaccine on the severity of gastroenteritis presented in children requiring hospitalisation remains unknown. We conducted a hospital-based surveillance study to assess the impact of Rotarix® vaccination on the severity of gastroenteritis presented by Malawian children. Stool samples were collected from children aged <5 years who required hospitalisation with acute gastroenteritis from December 2011 to October 2019. Gastroenteritis severity was determined using Ruuska and Vesikari scores. Rotavirus was detected using enzyme immunoassay. Rotavirus genotypes were determined using nested RT-PCR. Associations between Rotarix® vaccination and gastroenteritis severity were investigated using adjusted linear regression. In total, 3159 children were enrolled. After adjusting for mid-upper arm circumference (MUAC), age, gender and receipt of other vaccines, all-cause gastroenteritis severity scores were 2.21 units lower (p < 0.001) among Rotarix®-vaccinated (n = 2224) compared to Rotarix®-unvaccinated children (n = 935). The reduction in severity score was observed against every rotavirus genotype, although the magnitude was smaller among those infected with G12P[6] compared to the remaining genotypes (p = 0.011). Each one-year increment in age was associated with a decrease of 0.43 severity score (p < 0.001). Our findings provide additional evidence on the impact of Rotarix® in Malawi, lending further support to Malawi's Rotarix® programme.