Publications by authors named "Khuzwayo Jere"

Article Synopsis
  • The Rotarix® vaccine was introduced in Malawi's national immunization program in October 2012, and a study analyzed data on children under 5 with acute gastroenteritis from January 2012 to June 2022, comparing it to pre-vaccination data from 1997 to 2009.
  • Post-vaccine introduction, there was a significant decline in cases of rotavirus-associated gastroenteritis (RVGE), with vaccine coverage exceeding 90% by mid-2014 but dropping during the COVID-19 pandemic before rebounding.
  • The estimated overall vaccine effectiveness was modest at 36.0%, peaking in 2014 and being highest among infants at 52.5%, demonstrating the need
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  • Researchers have identified the first two enterotoxigenic E. coli (ETEC) genomes from Malawi, isolated in 2014.
  • These genomes were taken from the feces of children who were infected but did not show symptoms.
  • The genomes contain a version of the heat-labile toxin found in pigs, but lack any recognized ETEC colonization factors.
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High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This study investigated the association between maternal serum antibodies and vaccine response in infants administered the RV3-BB vaccine.

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  • * The outbreak was primarily caused by the ST69 strain (7PET lineage) displaying mainly the O1 Ogawa serotype, with minor presence of other serotypes, indicating a recent importation from Asia.
  • * Genetic analysis revealed that the outbreak strains carried specific antimicrobial resistance and virulence traits that contributed to the severity of the outbreak, highlighting the connection between the cyclones and the introduction of new cholera strains.
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Background: Rotarix rotavirus vaccine was introduced into the Malawi national immunization program in October 2012. We used a previously developed mathematical models to estimate overall vaccine effectiveness over a 10-year period following rotavirus vaccine introduction.

Methods: We analyzed data on children <5 years old hospitalized with acute gastroenteritis in Blantyre, Malawi from January 2012 to June 2022, compared to pre-vaccination data.

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Background: is a leading cause of acute watery diarrhea, dysentery, and diarrhea-attributed linear growth faltering, a precursor to stunting and lifelong morbidity. Several promising vaccines are in development and field efficacy trials will require a consortium of potential vaccine trial sites with up-to-date diarrhea incidence data.

Methods: The Enterics for Global Health (EFGH) surveillance study will employ facility-based enrollment of diarrhea cases aged 6-35 months with 3 months of follow-up to establish incidence rates and document clinical, anthropometric, and financial consequences of diarrhea at 7 country sites (Mali, Kenya, The Gambia, Malawi, Bangladesh, Pakistan, and Peru).

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  • qPCR is a more efficient method for detecting pathogens in clinical samples than traditional culture methods, which often miss cases, leading to underestimation of disease burden by 2- to 3-fold.
  • The Enterics for Global Health (EFGH) study will use a TaqMan Array Card (TAC) to detect and differentiate various pathogens and antimicrobial resistance genes, analyzing samples from rectal swabs or stool.
  • The high sensitivity of TAC allows for better estimation of disease burden caused by specific pathogens, which is important for influencing health policy and designing future clinical trials.
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  • Molecular diagnostics have revealed a higher prevalence of shigellosis from human fecal samples than traditional culture methods, highlighting the need for improved identification of its causes.* -
  • The study involves testing dried blood spots for specific antibodies to determine immune responses in individuals with shigellosis and comparing these responses among various case types to identify patterns.* -
  • The findings aim to enhance our understanding of shigellosis, establish baseline immunity, and ultimately aid in the development of effective vaccines against diarrhea.*
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  • The study aims to improve the detection of bacterial diarrhea episodes by using fecal inflammatory biomarkers, which could help in deciding when antibiotics are needed.
  • A systematic review was conducted to analyze previous research on the effectiveness of these biomarkers, focusing on their sensitivity and specificity in identifying different bacteria associated with diarrhea.
  • The Enterics for Global Health (EFGH) study plans to test specific biomarkers in stool samples from various countries and develop prediction scores to better categorize diarrhea types using advanced detection methods like qPCR.
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Background: Malawi is among 7 countries participating in the Enterics for Global Health (EFGH) surveillance study, which aims to determine the incidence of medically attended diarrhea attributed to , a leading bacterial cause of diarrhea in children in low-resource settings.

Methods: We describe the EFGH study site in the densely populated informal settlement of Ndirande Township, Blantyre, Malawi. We explore the site's geographical location, demographic characteristics, and the healthcare-seeking behavior of its population, particularly for childhood diarrhea.

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Background: is a major cause of diarrhea in young children worldwide. Multiple vaccines targeting are in development, and phase 3 clinical trials are imminent to determine efficacy against shigellosis.

Methods: The Enterics for Global Health (EFGH) surveillance study is designed to determine the incidence of medically attended shigellosis in 6- to 35-month-old children in 7 resource-limited settings.

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  • Oral drug absorption, particularly of clofazimine, can be significantly affected by diarrhea associated with infections like cryptosporidiosis in HIV-infected adults.
  • A population pharmacokinetic model using data from a study of 23 participants revealed that severe diarrhea can reduce clofazimine bioavailability by more than sixfold.
  • Understanding these effects is crucial for optimizing dosing regimens to improve treatment outcomes for patients experiencing gastrointestinal issues.
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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.

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The immunogenicity and effectiveness of oral rotavirus vaccines (ORVs) against severe rotavirus-associated gastroenteritis are impaired in low- and middle-income countries (LMICs) where the burden of disease is highest. Determining risk factors for impaired ORV response may help identify strategies to enhance vaccine effectiveness. In this study, we use metagenomic sequencing to provide a high-resolution taxonomic analysis of stool samples collected at 6 weeks of age (coinciding with the first ORV dose) during a prospective study of ORV immunogenicity in India and Malawi.

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is an increasingly recognized etiological agent of acute gastroenteritis. Here, we report five draft genomes of isolated from suspected cholera cases during the 2022-2023 cholera outbreak in Malawi.

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Article Synopsis
  • Cryptosporidium is a gut pathogen that particularly affects people with weakened immune systems, such as those with HIV, and the CRYPTOFAZ trial in Malawi tested clofazimine's effectiveness for treating this infection.
  • The study used various diagnostic methods, including qPCR and ELISA, to examine 586 individuals and monitor those who were part of the trial for pathogen shedding and other co-infections.
  • The findings revealed that while qPCR was more sensitive for detecting Cryptosporidium, ELISA had more variable results; additionally, a new Cryptosporidium species was found, and enterotoxigenic E. coli was also linked to diarrhea in some participants.
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Background: Maternal breastmilk is a source of pre- and pro-biotics that impact neonatal gut microbiota colonization. Because oral rotavirus vaccines (ORVs) are administered at a time when infants are often breastfed, breastmilk microbiota composition may have a direct or indirect influence on vaccine take and immunogenicity.

Methods: Using standardized methods across sites, we compared breastmilk microbiota composition in relation to geographic location and ORV response in cohorts prospectively followed from birth to 18 weeks of age in India (n = 307), Malawi (n = 119), and the United Kingdom ([UK] n = 60).

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G3 rotaviruses rank among the most common rotavirus strains worldwide in humans and animals. However, despite a robust long-term rotavirus surveillance system from 1997 at Queen Elizabeth Central Hospital in Blantyre, Malawi, these strains were only detected from 1997 to 1999 and then disappeared and re-emerged in 2017, 5 years after the introduction of the Rotarix rotavirus vaccine. Here, we analysed representative twenty-seven whole genome sequences (G3P[4], = 20; G3P[6], = 1; and G3P[8], = 6) randomly selected each month between November 2017 and August 2019 to understand how G3 strains re-emerged in Malawi.

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  • Research shows that while CD4 T cells provide strong immune protection against rotavirus in animal studies, their effectiveness in humans is still uncertain.
  • In a study of children in Malawi, those with rotavirus infections had more memory T helper cells during their illness, but showed little evidence of specific CD4 T cells that produce key antiviral cytokines (IFN-γ and TNF-α) during acute and recovery phases.
  • Overall, the study found that vaccinated Malawian children exhibited limited production of these important antiviral T cells after confirmed rotavirus infection.
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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.

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Rotavirus genotypes are species specific. However, interspecies transmission is reported to result in the emergence of new genotypes. A cross-sectional study of 242 households with 281 cattle, 418 goats, 438 pigs, and 258 humans in Uganda was undertaken between 2013 and 2014.

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  • The 13th African Rotavirus Symposium was a virtual event hosted by the University of Nairobi and the Kenya Paediatric Association on November 3-4, 2021, focusing on rotavirus research and prevention in Africa.
  • The symposium included scientific presentations on diarrheal disease burdens, genomic studies of rotavirus strains, and the clinical evaluation of new vaccines, against the backdrop of COVID-19 travel restrictions.
  • As of the meeting, 42 out of 54 African countries had implemented rotavirus vaccination, but significant challenges remain in realizing the full benefits, given that Africa holds about 80% of global rotavirus mortality.
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The transient upsurge of G2P[4] group A rotavirus (RVA) after Rotarix vaccine introduction in several countries has been a matter of concern. To gain insight into the diversity and evolution of G2P[4] strains in South Africa pre- and post-RVA vaccination introduction, whole-genome sequencing was performed for RVA positive faecal specimens collected between 2003 and 2017 and samples previously sequenced were obtained from GenBank (=103; 56 pre- and 47 post-vaccine). Pre-vaccine G2 sequences predominantly clustered within sub-lineage IVa-1.

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Background: Binding and neutralising anti-Spike antibodies play a key role in immune defence against SARS-CoV-2 infection. Since it is known that antibodies wane with time and new immune-evasive variants are emerging, we aimed to assess the dynamics of anti-Spike antibodies in an African adult population with prior SARS-CoV-2 infection and to determine the effect of subsequent COVID-19 vaccination.

Methods: Using a prospective cohort design, we recruited adults with prior laboratory-confirmed mild/moderate COVID-19 in Blantyre, Malawi, and followed them up for 270 days (n = 52).

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