The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study.

BACKGROUND: The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa. METHODS: We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12-18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2-10 years (PfPR2-10) and ranges from 3% to 65% PfPR2-10. FINDINGS: Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815-333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868-405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4-48) in perennial settings and $6 (3-63) in seasonal settings and the incremental cost per DALY averted was $34 (29-139) in perennial settings and $30 (22-172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR2-10. INTERPRETATION: Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa. FUNDING: The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy.

Marburg virus disease outbreaks, mathematical models, and disease parameters: a systematic review.

The 2023 Marburg virus disease outbreaks in Equatorial Guinea and Tanzania highlighted the importance of better understanding this lethal pathogen. We did a systematic review (PROSPERO CRD42023393345) of peer-reviewed articles reporting historical outbreaks, modelling studies, and epidemiological parameters focused on Marburg virus disease. We searched PubMed and Web of Science from database inception to March 31, 2023. Two reviewers evaluated all titles and abstracts with consensus-based decision making. To ensure agreement, 13 (31%) of 42 studies were double-extracted and a custom-designed quality assessment questionnaire was used for risk of bias assessment. We present detailed information on 478 reported cases and 385 deaths from Marburg virus disease. Analysis of historical outbreaks and seroprevalence estimates suggests the possibility of undetected Marburg virus disease outbreaks, asymptomatic transmission, or cross-reactivity with other pathogens, or a combination of these. Only one study presented a mathematical model of Marburg virus transmission. We estimate an unadjusted, pooled total random effect case fatality ratio of 61·9% (95% CI 38·8-80·6; I2=93%). We identify epidemiological parameters relating to transmission and natural history, for which there are few estimates. This systematic review and the accompanying database provide a comprehensive overview of Marburg virus disease epidemiology and identify key knowledge gaps, contributing crucial information for mathematical models to support future Marburg virus disease epidemic responses.

Embedding Usage Sensors in Point-of-Use Water Treatment Devices: Sensor Design and Application in Limpopo, South Africa.

Health benefits from point-of-use (POU) water treatment devices come only with consistent use. Embedded sensors can measure the consistency of POU-device use and can provide insights about improving it. We demonstrate both potentials with data from SmartSpouts: accelerometer-based sensors embedded in spigot handles that record the duration and timing of use. In the laboratory, most sensor readings correlated well (>0.98) with manually timed water withdrawals. In the field, SmartSpouts measured >60,000 water withdrawals across 232 households in Limpopo, South Africa. Sensors proved critical to understanding consistent use; surveys overestimated it by 53 percentage points. Sensor data showed when households use POU devices (evening peaks and delayed weekend routines) and user preferences (safe storage over filters). We demonstrate analytically and with data that (i) consistent use (e.g., 7 continuous days) is extremely sensitive to single-day use prevalence and (ii) use prevalence affects the performance of contact-time-based POU devices, exemplified with silver tablets. Deployed SmartSpouts had limitations, including memory overflows and confounding device relocation with water withdrawal. Nevertheless, SmartSpouts provided useful and objective data on the prevalence of single-day and consistent use. Considerably less expensive than alternatives, SmartSpouts enable an order of magnitude increase in how many POU-device sensors can be deployed.

Demographic and Social Factors Associated with COVID-19 Vaccination Initiation Among Adults Aged ≥65 Years - United States, December 14, 2020-April 10, 2021.

Compared with other age groups, older adults (defined here as persons aged ≥65 years) are at higher risk for COVID-19-associated morbidity and mortality and have therefore been prioritized for COVID-19 vaccination (1,2). Ensuring access to vaccines for older adults has been a focus of federal, state, and local response efforts, and CDC has been monitoring vaccination coverage to identify and address disparities among subpopulations of older adults (2). Vaccine administration data submitted to CDC were analyzed to determine the prevalence of COVID-19 vaccination initiation among adults aged ≥65 years by demographic characteristics and overall. Characteristics of counties with low vaccination initiation rates were quantified using indicators of social vulnerability data from the 2019 American Community Survey.* During December 14, 2020-April 10, 2021, nationwide, a total of 42,736,710 (79.1%) older adults had initiated vaccination. The initiation rate was higher among men than among women and varied by state. On average, counties with low vaccination initiation rates (<50% of older adults having received at least 1 vaccine dose), compared with those with high rates (≥75%), had higher percentages of older adults without a computer, living in poverty, without Internet access, and living alone. CDC, state, and local jurisdictions in partnerships with communities should continue to identify and implement strategies to improve access to COVID-19 vaccination for older adults, such as assistance with scheduling vaccination appointments and transportation to vaccination sites, or vaccination at home if needed for persons who are homebound.† Monitoring demographic and social factors affecting COVID-19 vaccine access for older adults and prioritizing efforts to ensure equitable access to COVID-19 vaccine are needed to ensure high coverage among this group.

Comparison of anthropometric data quality in children aged 6-23 and 24-59 months: lessons from population-representative surveys from humanitarian settings.

BACKGROUND: Ensuring the quality of anthropometry data is paramount for getting accurate estimates of malnutrition prevalence among children aged 6-59 months in humanitarian and refugee settings. Previous reports based on data from Demographic and Health Surveys suggested systematic differences in anthropometric data quality between the younger and older groups of preschool children. METHODS: We analyzed 712 anthropometric population-representative field surveys from humanitarian and refugee settings conducted during 2011-2018. We examined and compared the quality of five anthropometric indicators in children aged 6-23 months and children aged 24-59 months: weight for height, weight for age, height for age, body mass index for age and mid-upper arm circumference (MUAC) for age. Using the z-score distribution of each indicator, we calculated the following parameters: standard deviation (SD), percentage of outliers, and measures of distribution normality. We also examined and compared the quality of height, weight, MUAC and age measurements using missing data and rounding criteria. RESULTS: Both SD and percentage of flags were significantly smaller on average in older than in younger age group for all five anthropometric indicators. Differences in SD between age groups did not change meaningfully depending on overall survey quality or on the quality of age ascertainment. Over 50% of surveys overall did not deviate significantly from normality. The percentage of non-normal surveys was higher in older than in the younger age groups. Digit preference score for weight, height and MUAC was slightly higher in younger age group, and for age slightly higher in the older age group. Children with reported exact date of birth (DOB) had much lower digit preference for age than those without exact DOB. SD, percentage flags and digit preference scores were positively correlated between the two age groups at the survey level, such as those surveys showing higher anthropometry data quality in younger age group also tended to show higher quality in older age group. CONCLUSIONS: There should be an emphasis on increased rigor of training survey measurers in taking anthropometric measurements in the youngest children. Standardization test, a mandatory component of the pre-survey measurer training and evaluation, of 10 children should include at least 4-5 children below 2 years of age.

Impact of Low-Cost Point-of-Use Water Treatment Technologies on Enteric Infections and Growth among Children in Limpopo, South Africa.

Enteric infections early in life have been associated with poor linear growth among children in low-resource settings. Point-of-use water treatment technologies provide effective and low-cost solutions to reduce exposure to enteropathogens from drinking water, but it is unknown whether the use of these technologies translates to improvements in child growth. We conducted a community-based randomized controlled trial of two water treatment technologies to estimate their effects on child growth in Limpopo, South Africa. We randomized 404 households with a child younger than 3 years to receive a silver-impregnated ceramic water filter, a silver-impregnated ceramic tablet, a safe-storage water container alone, or no intervention, and these households were followed up quarterly for 2 years. We estimated the effects of the interventions on linear and ponderal growth, enteric infections assessed by quantitative molecular diagnostics, and diarrhea prevalence. The silver-impregnated ceramic water filters and tablets consistently achieved approximately 1.2 and 3 log reductions, respectively, in total coliform bacteria in drinking water samples. However, the filters and tablets were not associated with differences in height (height-for-age z-score differences compared with no intervention: 0.06, 95% CI: -0.29, 0.40, and 0.00, 95% CI: -0.35, 0.35, respectively). There were also no effects of the interventions on weight, diarrhea prevalence, or enteric infections. Despite their effectiveness in treating drinking water, the use of the silver-impregnated ceramic water filters and tablets did not reduce enteric infections or improve child growth. More transformative water, sanitation, and hygiene interventions that better prevent enteric infections are likely needed to improve long-term child growth outcomes.