Publications by authors named "Nigel Cunliffe"

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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  • - MERS-CoV, with a high mortality rate, causes severe respiratory illness, highlighting the urgent need for effective therapeutic vaccines against the virus.
  • - This review analyzes immune responses in the upper and lower respiratory tracts to MERS-CoV, focusing on key players such as macrophages, T cells, and B cells that produce antiviral substances to combat infection.
  • - While innate and adaptive immune systems show potential to control MERS-CoV, research on human mucosal immune responses is limited due to the lack of relevant tissue studies, indicating a need for deeper investigation.
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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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Background: Comparative costs of public health interventions provide valuable data for decision making. However, the availability of comprehensive and context-specific costs is often limited. The Enterics for Global Health (EFGH) surveillance study-a facility-based diarrhea surveillance study across 7 countries-aims to generate evidence on health system and household costs associated with medically attended diarrhea in children.

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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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  • The EFGH surveillance study aims to accurately estimate diarrhea incidence in children aged 6-35 months by considering both the population at risk and those who don't seek medical care.
  • It will utilize a combination of facility-based surveillance and population-based surveys to determine the size of the target population and healthcare-seeking behaviors.
  • The study design addresses challenges like discrepancies in coverage, seasonal changes, and variations in health-seeking behavior to improve the accuracy of its findings over a 24-month period.
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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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Social distancing interrupted transmission patterns of contact-driven infectious agents such as norovirus during the Covid-19 pandemic. Since routine surveillance of norovirus was additionally disrupted during the pandemic, traditional naïve forecasts that rely only on past public health surveillance data may not reliably represent norovirus activity. This study investigates the use of statistical modelling to predict the number of norovirus laboratory reports in England 4-weeks ahead of time before and during Covid-19 pandemic thus providing insights to inform existing practices in norovirus surveillance in England.

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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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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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Background: Histo-blood group antigens (HBGAs) may influence immune responses to rotavirus vaccination.

Methods: HBGA phenotyping was determined by detection of antigens A, B, H and Lewis a and b in saliva using enzyme-linked immunosorbent assay. Secretor status was confirmed by lectin antigen assay if A, B and H antigens were negative or borderline (OD ± 0.

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Background: Norovirus is associated with approximately 18% of the global burden of gastroenteritis and affects all age groups. There is currently no licensed vaccine or available antiviral treatment. However, well-designed early warning systems and forecasting can guide nonpharmaceutical approaches to norovirus infection prevention and control.

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Background: In the UK approximately a quarter of the population experience infectious intestinal disease (IID) each year. However, only 2% present to primary care, preventing a true determination of community burden and pathogen aetiology. The aim of this pilot study was to gauge public acceptability of a technology-mediated platform for reporting episodes of IID and for providing stool samples.

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Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalisations associated with diarrhoea in children <5 years of age has been reported. There is growing evidence to suggest that live-attenuated vaccines also provide protection against other infections beyond the vaccine-targeted pathogens. These so called off-target effects of vaccination have been associated with the tuberculosis vaccine Bacille Calmette Guérin (BCG), measles, oral polio and recently salmonella vaccines, and are thought to be mediated by modified innate and possibly adaptive immunity.

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Objective: Assess characteristics of clinical pneumonia after introduction of pneumococcal conjugate vaccine (PCV), by HIV exposure status, in children hospitalised in a governmental hospital in Malawi.

Methods And Findings: We evaluated 1139 children ≤5 years old hospitalised with clinical pneumonia: 101 HIV-exposed, uninfected (HEU) and 1038 HIV-unexposed, uninfected (HUU). Median age was 11 months (IQR 6-20), 59% were male, median mid-upper arm circumference (MUAC) was 14 cm (IQR 13-15) and mean weight-for-height z score was -0.

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Background: Rotarix (GlaxoSmithKline) oral rotavirus vaccine is licensed as 2 doses in the first 6 months of life. In settings with high child mortality rates, clinical protection conferred by 2 doses of Rotarix is reduced. We assessed vaccine immune response when an additional dose of Rotarix was given to Australian Aboriginal children 6 to <12 months old.

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