What's going on with measles?

Measles is a highly transmissible systemic viral infection associated with substantial mortality primarily due to secondary infections. Measles induces lifelong immunity to reinfection but loss of immunity to other pathogens. An attenuated live virus vaccine is highly effective, but lapses in delivery have resulted in increasing cases worldwide. Although the primary cause of failure to control measles is failure to vaccinate, waning vaccine-induced immunity and the possible emergence of more virulent virus strains may also contribute.

Possible Paths to Measles Eradication: Conceptual Frameworks, Strategies, and Tactics.

Measles elimination refers to the interruption of measles virus transmission in a defined geographic area (e.g., country or region) for 12 months or more, and measles eradication refers to the global interruption of measles virus transmission. Measles eradication was first discussed and debated in the late 1960's shortly after the licensure of measles vaccines. Most experts agree that measles meets criteria for disease eradication, but progress toward national and regional measles elimination has slowed. Several paths to measles eradication can be described, including an incremental path through country-wide and regional measles elimination and phased paths through endgame scenarios and strategies. Infectious disease dynamic modeling can help inform measles elimination and eradication strategies, and all paths would be greatly facilitated by innovative technologies such as microarray patches to improve vaccine access and demand, point-of-contact diagnostic tests to facilitate outbreak responses, and point-of-contact IgG tests to identify susceptible populations. A pragmatic approach to measles eradication would identify and realize the necessary preconditions and clearly articulate various endgame scenarios and strategies to achieve measles eradication with an intensified and coordinated global effort in a specified timeframe, i.e., to "go big and go fast". To encourage and promote deliberation among a broad array of stakeholders, we provide a brief historical background and key considerations for setting a measles eradication goal.

Assessing the relationship between existing childhood, adolescent and adult immunization programmes and national COVID-19 vaccination capacities in 2021.

BACKGROUND: During the COVID-19 pandemic, nearly all countries introduced COVID-19 vaccination programmes. Yet, countries had a wide range of programmatic experiences. This analysis aims to identify national characteristics associated with COVID-19 vaccination programmatic success. METHODS: We used the following outcome measures: the presence of national COVID-19 vaccination capacities and COVID-19 coverage as of December 2021, June 2022, and December 2022. We developed a standardized metric for assessing national COVID-19 vaccination capacities as a proxy for speed of introduction. We developed this metric through adaptation of the WHO Guide for Conducting an Expanded Programme on Immunization Review and consultations with technical experts specializing in vaccine introduction and emergency deployment; monitoring and data; childhood, adolescent and adult programmes; and COVID-19 vaccination roll-out. Through multivariable linear regressions, we evaluated whether having a mature immunization programme for children, adolescents and adults; recent use of emergency vaccination; World Bank income classification; past early adoption of new vaccines; density of the health workforce; and/or trust in science and government were associated with higher COVID-19 vaccination capacities and coverage. RESULTS: The COVID-19 vaccination capacities scores ranged from 0 to 5 points with a global median score of 2 and an interquartile range of 1;4. After adjusting for World Bank income classifications, the presence of a mature influenza vaccination programme was independently correlated with statistically significant higher scores of national COVID-19 vaccination capacities and higher COVID-19 vaccination coverage in December 2021, June 2022, and December 2022. Trust in government was also associated with higher coverage for all three time stamps. CONCLUSIONS: As countries consider how to prepare for and respond to future pandemics, having an adult seasonal influenza vaccination programme, building trust in government, and ensuring equitable access to vaccines supply emerged as key aspects that can benefit from additional national and global focus.

Proteomic approaches for protein kinase substrate identification in Apicomplexa.

Apicomplexa is a phylum of protist parasites, notable for causing life-threatening diseases including malaria, toxoplasmosis, cryptosporidiosis, and babesiosis. Apicomplexan pathogenesis is generally a function of lytic replication, dissemination, persistence, host cell modification, and immune subversion. Decades of research have revealed essential roles for apicomplexan protein kinases in establishing infections and promoting pathogenesis. Protein kinases modify their substrates by phosphorylating serine, threonine, tyrosine, or other residues, resulting in rapid functional changes in the target protein. Post-translational modification by phosphorylation can activate or inhibit a substrate, alter its localization, or promote interactions with other proteins or ligands. Deciphering direct kinase substrates is crucial to understand mechanisms of kinase signaling, yet can be challenging due to the transient nature of kinase phosphorylation and potential for downstream indirect phosphorylation events. However, with recent advances in proteomic approaches, our understanding of kinase function in Apicomplexa has improved dramatically. Here, we discuss methods that have been used to identify kinase substrates in apicomplexan parasites, classifying them into three main categories: i) kinase interactome, ii) indirect phosphoproteomics and iii) direct labeling. We briefly discuss each approach, including their advantages and limitations, and highlight representative examples from the Apicomplexa literature. Finally, we conclude each main category by introducing prospective approaches from other fields that would benefit kinase substrate identification in Apicomplexa.

The 2020 immunization programme landscape: Piloting an assessment metric to evaluate the maturity of national immunization programmes across the life course.

BACKGROUND: The World Health Organization (WHO) encourages countries to provide appropriate vaccinations for children, adolescents, and relevant adult populations. Childhood programme have been the focus of global investments, but recent pandemics have increasingly demonstrated the value of life course vaccination. Our objective is to compare national life course immunization programmatic maturity prior to mass COVID-19 vaccine introduction, the largest adult vaccination programme, globally. As coverage estimates (typically used to assess childhood programmes) are not available for adult vaccinations, this analysis pilots a standardized quantitative metric of programmatic maturity. METHODS: Through consultation with vaccination experts, we developed a standardized approach to assess national immunization programme maturity across the life course. In accordance with expert input, five vaccines were selected to represent delivery across the life course: diphtheria tetanus toxoid and pertussis (DTP); measles (MCV) second dose; human papillomavirus (HPV) final dose; pneumococcal conjugate (PCV) final dose; and seasonal influenza annual dose. Experts recommended inclusion of the following indicators for each vaccine: a legal mandate (national policy), experience delivering the vaccine (programme duration), and vaccine use (uptake for relevant populations). We developed a metric accordingly that provides up to 5 points per vaccine ("vaccine specific maturity score") which when summed forms the "life course maturity score", with a maximum score of 25. We analysed the prevalence of national policies, experience, and use by region and World Bank income group. RESULTS: More than 55% of the 194 WHO Member States had childhood vaccine policies for all three of the vaccines considered (DTP, MCV, and PCV) compared to 60% for HPV (proxy for adolescent vaccination programme) and 52% for seasonal influenza (proxy for adult vaccination programme). Childhood vaccination programmes (e.g., MCV and DTP) had the highest vaccine specific maturity scores, while seasonal influenza and HPV vaccination programmes had much lower scores. The national life course maturity scores ranged from 1 to 23, with a global median of 12 (IQR: 8; 16). DISCUSSION: The piloted metric provides an overview of the maturity of life course immunization programmes. The metric is structured to be a flexible, rapid resource that can be used to assess other combinations of vaccines across the life course. The findings from this paper provide a baseline of immunization programme maturity for childhood, adolescent, and adult vaccination programmes immediately prior to the COVID-19 vaccine introduction. This maturity score, or adaptations of this approach, could be used to monitor the trajectory of national immunization programme maturity across the life course in the years ahead.

Apicomplexan phosphodiesterases in cyclic nucleotide turnover: conservation, function, and therapeutic potential.

Apicomplexa encompasses a large number of intracellular parasites infecting a wide range of animals. Cyclic nucleotide signaling is crucial for a variety of apicomplexan life stages and cellular processes. The cyclases and kinases that synthesize and respond to cyclic nucleotides (i.e., 3',5'-cyclic guanosine monophosphate and 3',5'-cyclic adenosine monophosphate) are highly conserved and essential throughout the parasite phylum. Growing evidence indicates that phosphodiesterases (PDEs) are also critical for regulating cyclic nucleotide signaling via cyclic nucleotide hydrolysis. Here, we discuss recent advances in apicomplexan PDE biology and opportunities for therapeutic interventions, with special emphasis on the major human apicomplexan parasite genera Plasmodium, Toxoplasma, Cryptosporidium, and Babesia. In particular, we show a highly flexible repertoire of apicomplexan PDEs associated with a wide range of cellular requirements across parasites and lifecycle stages. Despite this phylogenetic diversity, cellular requirements of apicomplexan PDEs for motility, host cell egress, or invasion are conserved. However, the molecular wiring of associated PDEs is extremely malleable suggesting that PDE diversity and redundancy are key for the optimization of cyclic nucleotide turnover to respond to the various environments encountered by each parasite and life stage. Understanding how apicomplexan PDEs are regulated and integrating multiple signaling systems into a unified response represent an untapped avenue for future exploration.

COVID-19 vaccine hesitancy, trust, and communication in Sarlahi District, Nepal.

BACKGROUND: Strategies to increase COVID-19 vaccine coverage require an understanding of the extent and drivers of vaccine hesitancy and trust in government related to COVID-19 vaccine programs, especially in low-resource communities. METHODS: We conducted a cross-sectional household survey post-COVID-19 vaccine introduction among adults (n = 362) in four municipalities in Sarlahi District, Nepal from August to December 2022. The survey included modules on participant demographics and socioeconomic factors and vaccine hesitancy, information seeking, and trust in authorities related to COVID-19 vaccination. RESULTS: Of the study participants, 38.4 % expressed hesitancy related to COVID-19 vaccination. The adjusted odds of being "vaccine hesitant" were significantly lower among the older adults (51+ years) relative to younger (<30 years) (aOR: 0.49, CI: 0.24-0.97) and among males relative to females (aOR: 0.51, CI: 0.26, 0.95). The study population highly trusted the government's handling of the COVID-19 pandemic. While for most, self-reported access to vaccination opportunities was high (88.4 %), 70.4 % of participants did not know if vaccines were in stock at their local vaccination facility. Commonly reported statements of misinformation include the vaccine being developed in a rush or too fast (21.5 %), COVID-19 infection can be effectively treated with ayurvedic medicine(16.3 %) and obtaining immunity from natural infection is better than through vaccination (19.9 %). The primary sources of information on COVID-19 programs were family and friends (98.6 %), healthcare professionals (67.7 %), Female Community Health Volunteers (FCHVs) (61.9 %), television (56.4 %), and radio (43.1 %). CONCLUSION: Although many respondents expressed concerns about COVID-19 effectiveness and safety, a high proportion trusted COVID-19 information provided by healthcare workers and approved of the government's response to the pandemic. This study highlights an opportunity to design new evidence-based communication strategies to improve vaccine confidence delivered through frontline government healthcare workers. Approaches could be targeted to certain communities in the region shown to have higher vaccine hesitancy, including younger people and women.

Food and water insecurity in households of children and adolescents living with HIV and receiving care in a rural Zambian hospital: A mixed-methods study.

Approximately 62,000 Zambian children are living with HIV. HIV care and treatment is generally more limited in rural areas, where a heavy reliance on rain-fed subsistence agriculture also places households at risk of food and water insecurity. We nested a mixed methods study with an explanatory sequential design in a clinical cohort of children and adolescents living with HIV (CHIV) in rural Zambia. We used validated questionnaires to assess household food and water insecurity and examined associations between indicators derived from those scales, household characteristics, and HIV treatment adherence and outcomes using log-binomial regression. We identified caregivers and older CHIV from food insecure households for in-depth interviews. Of 186 participants completing assessments, 72% lived in moderately or severely food insecure households and 2% in water insecure households. Food insecurity was more prevalent in households of lower socioeconomic status (80% vs. 59% for higher scores; p = 0.02) and where caregivers had completed primary (79%) vs. secondary school or higher (62%; p = 0.01). No other characteristics or outcomes were associated with food insecurity. Parents limited both the quality and quantity of foods they consumed to ensure food availability for their CHIV. Coping strategies included taking on piecework or gathering wild foods; livestock ownership was a potential buffer. Accessing sufficient clean water was less of a concern. During periods of drought or service interruption, participants travelled further for drinking water and accessed water for other purposes from alternative sources or reduced water use. Community contributions afforded some protection against service interruptions. Overall, while food insecurity was prevalent, strategies used by parents may have protected children from a measurable impact on HIV care or treatment outcomes. Reinforcing social protection programs by integrating livestock ownership and strengthening water infrastructure may further protect CHIV in the case of more extreme food or water system shocks.

Modeling the Cost of Vaccinating a Measles Zero-Dose Child in Zambia Using Three Vaccination Strategies.

Countries with moderate to high measles-containing vaccine coverage face challenges in reaching the remaining measles zero-dose children. There is growing interest in targeted vaccination activities to reach these children. We developed a framework for prioritizing districts for targeted measles and rubella supplementary immunization activities (SIAs) for Zambia in 2020, incorporating the use of the WHO's Measles Risk Assessment Tool (MRAT) and serosurveys. This framework was used to build a model comparing the cost of vaccinating one zero-dose child under three vaccination scenarios: standard nationwide SIA, targeted subnational SIA informed by MRAT, and targeted subnational SIA informed by both MRAT and measles seroprevalence data. In the last scenario, measles seroprevalence data are acquired via either a community-based serosurvey, residual blood samples from health facilities, or community-based IgG point-of-contact rapid diagnostic testing. The deterministic model found that the standard nationwide SIA is the least cost-efficient strategy at 13.75 USD per zero-dose child vaccinated. Targeted SIA informed by MRAT was the most cost-efficient at 7.63 USD per zero-dose child, assuming that routine immunization is just as effective as subnational SIA in reaching zero-dose children. Under similar conditions, a targeted subnational SIA informed by both MRAT and seroprevalence data resulted in 8.17-8.35 USD per zero-dose child vaccinated, suggesting that use of seroprevalence to inform SIA planning may not be as cost prohibitive as previously thought. Further refinement to the decision framework incorporating additional data may yield strategies to better target the zero-dose population in a financially feasible manner.

Malaria Transmission at The Zimbabwe-Mozambique Border: An Observational Study of Parasitemia by Travel History and Household Location.

Cross-border human population movement contributes to malaria transmission in border regions, impeding national elimination. However, its impact in low-to-moderate transmission settings is not well characterized. This community-based study in Mutasa District, Zimbabwe, estimated the association of parasite prevalence with self-reported overnight travel to Mozambique and household distance to the border from 2012-2020. A fully adjusted Poisson regression model with robust variance estimation was fit using active surveillance data. The population attributable fraction of parasite prevalence from overnight travel was also estimated. The relative risk of testing positive for malaria by rapid diagnostic test declined 14% (prevalence ratio [PR] = 0.86, 95% CI = 0.81-0.92) per kilometer from the border up to 12 km away. Travel to Mozambique was associated with a 157% increased risk (PR = 2.57, 95% CI = 1.38-4.78), although only 5.8% of cases were attributable to overnight travel (95% CI = -1.1% to 12.7%), reflecting infrequent overnight trips (1.3% of visits). This study suggests that transmission in eastern Zimbabwe is driven by increasingly conducive social or environmental conditions approaching the border and low levels of importation from overnight travel. Although day trips to Mozambique during peak biting hours were not assessed, the contribution of such trips to ongoing transmission may be significant. Future malaria control efforts should prioritize high coverage of existing interventions and continued support for community health workers and health facilities at the border, which provide free case management.

Genomics reveals heterogeneous Plasmodium falciparum transmission and selection signals in Zambia.

BACKGROUND: Genomic surveillance is crucial for monitoring malaria transmission and understanding parasite adaptation to interventions. Zambia lacks prior nationwide efforts in malaria genomic surveillance among African countries. METHODS: We conducted genomic surveillance of Plasmodium falciparum parasites from the 2018 Malaria Indicator Survey in Zambia, a nationally representative household survey of children under five years of age. We whole-genome sequenced and analyzed 241 P. falciparum genomes from regions with varying levels of malaria transmission across Zambia and estimated genetic metrics that are informative about transmission intensity, genetic relatedness between parasites, and selection. RESULTS: We provide genomic evidence of widespread within-host polygenomic infections, regardless of epidemiological characteristics, underscoring the extensive and ongoing endemic malaria transmission in Zambia. Our analysis reveals country-level clustering of parasites from Zambia and neighboring regions, with distinct separation in West Africa. Within Zambia, identity by descent (IBD) relatedness analysis uncovers local spatial clustering and rare cases of long-distance sharing of closely related parasite pairs. Genomic regions with large shared IBD segments and strong positive selection signatures implicate genes involved in sulfadoxine-pyrimethamine and artemisinin combination therapies drug resistance, but no signature related to chloroquine resistance. Furthermore, differences in selection signatures, including drug resistance loci, are observed between eastern and western Zambian parasite populations, suggesting variable transmission intensity and ongoing drug pressure. CONCLUSIONS: Our findings enhance our understanding of nationwide P. falciparum transmission in Zambia, establishing a baseline for analyzing parasite genetic metrics as they vary over time and space. These insights highlight the urgency of strengthening malaria control programs and surveillance of antimalarial drug resistance.

Malaria is caused by a parasite that is spread to humans via mosquito bites. It is a leading cause of death in children under five years old in sub-Saharan Africa. Analysis of the malaria parasite's complete set of DNA (its genome) can help us to understand transmission of the disease and how this changes in response to different strategies to control the disease. We analyzed the genomes of malaria parasites from children across Zambia. Our study revealed that 77% of children harbored multiple parasite strains, which suggests that local transmission (transmission between people within the same local area) is high. Genetic evidence for long-distance transmission was rarer. Furthermore, our findings suggest parasites are evolving in response to antimalarial drugs. Our study enhances our understanding of malaria dynamics in Zambia and may help to inform strategies for improved surveillance and control.

Genomics reveals heterogeneous Plasmodium falciparum transmission and population differentiation in Zambia and bordering countries.

Genomic surveillance plays a critical role in monitoring malaria transmission and understanding how the parasite adapts in response to interventions. We conducted genomic surveillance of malaria by sequencing 241 Plasmodium falciparum genomes from regions with varying levels of malaria transmission across Zambia. We found genomic evidence of high levels of within-host polygenomic infections, regardless of epidemiological characteristics, underscoring the extensive and ongoing endemic malaria transmission in the country. We identified country-level clustering of parasites from Zambia and neighboring countries, and distinct clustering of parasites from West Africa. Within Zambia, our identity by descent (IBD) relatedness analysis uncovered spatial clustering of closely related parasite pairs at the local level and rare cases of long-distance sharing. Genomic regions with large shared IBD segments and strong positive selection signatures identified genes involved in sulfadoxine-pyrimethamine and artemisinin combination therapies drug resistance, but no signature related to chloroquine resistance. Together, our findings enhance our understanding of P. falciparum transmission nationwide in Zambia and highlight the urgency of strengthening malaria control programs and surveillance of antimalarial drug resistance.

Report from the World Health Organization's immunization and vaccines-related implementation research advisory committee (IVIR-AC) meeting, virtual gathering, 26 February-1 March 2024.

The Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) is the World Health Organization's key standing advisory body to conduct an independent review of research, particularly of transmission and economic modeling analyses that estimate the impact and value of vaccines. From 26th February-1st March 2024, at its first of two semi-annual meetings, IVIR-AC provided feedback and recommendations across four sessions; this report summarizes the proceedings and recommendations from that meeting. Session topics included modeling of the impact and cost-effectiveness of the R21/Matrix-M malaria vaccine, meta-analysis of economic evaluations of vaccines, a global analysis estimating the impact of vaccination over the last 50 years, and modeling the impact of different RTS,S malaria vaccine dose schedules in seasonal settings.

National genomic profiling of Plasmodium falciparum antimalarial resistance in Zambian children participating in the 2018 Malaria Indicator Survey.

The emergence of antimalarial drug resistance is a major threat to malaria control and elimination. Using whole genome sequencing of 282 P. falciparum samples collected during the 2018 Zambia National Malaria Indicator Survey, we determined the prevalence and spatial distribution of known and candidate antimalarial drug resistance mutations. High levels of genotypic resistance were found across Zambia to pyrimethamine, with over 94% (n=266) of samples having the Pfdhfr triple mutant (N51 I , C59 R , and S108 N ), and sulfadoxine, with over 84% (n=238) having the Pfdhps double mutant (A437 G and K540 E ). In northern Zambia, 5.3% (n=15) of samples also harbored the Pfdhps A581 G mutation. Although 29 mutations were identified in Pfkelch13 , these mutations were present at low frequency (<2.5%), and only three were WHO-validated artemisinin partial resistance mutations: P441 L (n=1, 0.35%), V568 M (n=2, 0.7%) and R622 T (n=1, 0.35%). Notably, 91 (32%) of samples carried the E431 K mutation in the Pfatpase6 gene, which is associated with artemisinin resistance. No specimens carried any known mutations associated with chloroquine resistance in the Pfcrt gene (codons 72-76). P. falciparum strains circulating in Zambia were highly resistant to sulfadoxine and pyrimethamine but remained susceptible to chloroquine and artemisinin. Despite this encouraging finding, early genetic signs of developing artemisinin resistance highlight the urgent need for continued vigilance and expanded routine genomic surveillance to monitor these changes.

Diversity and selection analyses identify transmission-blocking antigens as the optimal vaccine candidates in Plasmodium falciparum.

Background: A highly effective vaccine for malaria remains an elusive target, at least in part due to the under-appreciated natural parasite variation. This study aimed to investigate genetic and structural variation, and immune selection of leading malaria vaccine candidates across the Plasmodium falciparum's life cycle. Methods: We analyzed 325 P. falciparum whole genome sequences from Zambia, in addition to 791 genomes from five other African countries available in the MalariaGEN Pf3k Rdatabase. Ten vaccine antigens spanning three life-history stages were examined for genetic and structural variations, using population genetics measures, haplotype network analysis, and 3D structure selection analysis. Findings: Among the ten antigens analyzed, only three in the transmission-blocking vaccine category display P. falciparum 3D7 as the dominant haplotype. The antigens AMA1, CSP, MSP119 and CelTOS, are much more diverse than the other antigens, and their epitope regions are under moderate to strong balancing selection. In contrast, Rh5, a blood stage antigen, displays low diversity yet slightly stronger immune selection in the merozoite-blocking epitope region. Except for CelTOS, the transmission-blocking antigens Pfs25, Pfs48/45, Pfs230, Pfs47, and Pfs28 exhibit minimal diversity and no immune selection in epitopes that induce strain-transcending antibodies, suggesting potential effectiveness of 3D7-based vaccines in blocking transmission. Interpretations: These findings offer valuable insights into the selection of optimal vaccine candidates against P. falciparum. Based on our results, we recommend prioritizing conserved merozoite antigens and transmission-blocking antigens. Combining these antigens in multi-stage approaches may be particularly promising for malaria vaccine development initiatives. Funding: Purdue Department of Biological Sciences; Puskas Memorial Fellowship; National Institute of Allergy and Infectious Diseases (U19AI089680).

Diversity and selection analyses identify transmission-blocking antigens as the optimal vaccine candidates in Plasmodium falciparum.

BACKGROUND: A highly effective vaccine for malaria remains an elusive target, at least in part due to the under-appreciated natural parasite variation. This study aimed to investigate genetic and structural variation, and immune selection of leading malaria vaccine candidates across the Plasmodium falciparum's life cycle. METHODS: We analysed 325 P. falciparum whole genome sequences from Zambia, in addition to 791 genomes from five other African countries available in the MalariaGEN Pf3k Database. Ten vaccine antigens spanning three life-history stages were examined for genetic and structural variations, using population genetics measures, haplotype network analysis, and 3D structure selection analysis. FINDINGS: Among the ten antigens analysed, only three in the transmission-blocking vaccine category display P. falciparum 3D7 as the dominant haplotype. The antigens AMA1, CSP, MSP119 and CelTOS, are much more diverse than the other antigens, and their epitope regions are under moderate to strong balancing selection. In contrast, Rh5, a blood stage antigen, displays low diversity yet slightly stronger immune selection in the merozoite-blocking epitope region. Except for CelTOS, the transmission-blocking antigens Pfs25, Pfs48/45, Pfs230, Pfs47, and Pfs28 exhibit minimal diversity and no immune selection in epitopes that induce strain-transcending antibodies, suggesting potential effectiveness of 3D7-based vaccines in blocking transmission. INTERPRETATION: These findings offer valuable insights into the selection of optimal vaccine candidates against P. falciparum. Based on our results, we recommend prioritising conserved merozoite antigens and transmission-blocking antigens. Combining these antigens in multi-stage approaches may be particularly promising for malaria vaccine development initiatives. FUNDING: Purdue Department of Biological Sciences; Puskas Memorial Fellowship; National Institute of Allergy and Infectious Diseases (U19AI089680).

Temporal genomic analysis of Plasmodium falciparum reveals increased prevalence of mutations associated with delayed clearance following treatment with artemisinin-lumefantrine in Choma District, Southern Province, Zambia.

The emergence of antimalarial drug resistance is an impediment to malaria control and elimination in Africa. Analysis of temporal trends in molecular markers of resistance is critical to inform policy makers and guide malaria treatment guidelines. In a low and seasonal transmission region of southern Zambia, we successfully genotyped 85.5% (389/455) of Plasmodium falciparum samples collected between 2013-2018 from 8 spatially clustered health centres using molecular inversion probes (MIPs) targeting key drug resistance genes. Aside from one sample carrying K13 R622I, none of the isolates carried other World Health Organization-validated or candidate artemisinin partial resistance (ART-R) mutations in K13. However, 13% (CI, 9.6-17.2) of isolates had the AP2MU S160N mutation, which has been associated with delayed clearance following artemisinin combination therapy in Africa. This mutation increased in prevalence between 2015-2018 and bears a genomic signature of selection. During this time period, there was an increase in the MDR1 NFD haplotype that is associated with reduced susceptibility to lumefantrine. Sulfadoxine-pyrimethamine polymorphisms were near fixation. While validated ART-R mutations are rare, a mutation associated with slow parasite clearance in Africa appears to be under selection in southern Zambia.

Report from the World Health Organization's immunization and vaccines related implementation research advisory committee (IVIR-AC) meeting, Geneva, 11-13 September 2023.

Evaluating vaccine-related research is critical to maximize the potential of vaccination programmes. The WHO Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) provides an independent review of research that estimates the performance, impact and value of vaccines, with a particular focus on transmission and economic modelling. On 11-13 September 2023, IVIR-AC was convened for a bi-annual meeting where the committee reviewed research and presentations across eight different sessions. This report summarizes the background information, proceedings and recommendations from that meeting. Sessions ranged in topic from timing of measles supplementary immunization activities, analyses of conditions necessary to meet measles elimination in the South-East Asia region, translating modelled evidence into policy, a risk-benefit analysis of dengue vaccine, COVID-19 scenario modelling in the African region, therapeutic vaccination against human papilloma virus, the Vaccine Impact Modelling Consortium, and the Immunization Agenda 2030 vaccine impact estimates.

Who is missed in a community-based survey: Assessment and implications of biases due to incomplete sampling frame in a community-based serosurvey, Choma and Ndola Districts, Zambia, 2022.

Community-based serological studies are increasingly relied upon to measure disease burden, identify population immunity gaps, and guide control and elimination strategies; however, there is little understanding of the potential for and impact of sampling biases on outcomes of interest. As part of efforts to quantify measles immunity gaps in Zambia, a community-based serological survey using stratified multi-stage cluster sampling approach was conducted in Ndola and Choma districts in May-June 2022, enrolling 1245 individuals. We carried out a follow-up study among individuals missed from the sampling frame of the serosurvey in July-August 2022, enrolling 672 individuals. We assessed the potential for and impact of biases in the community-based serosurvey by i) estimating differences in characteristics of households and individuals included and excluded (77% vs 23% of households) from the sampling frame of the serosurvey and ii) evaluating the magnitude these differences make on healthcare-seeking behavior, vaccination coverage, and measles seroprevalence. We found that missed households were 20% smaller and 25% less likely to have children. Missed individuals resided in less wealthy households, had different distributions of sex and occupation, and were more likely to seek care at health facilities. Despite these differences, simulating a survey in which missed households were included in the sampling frame resulted in less than a 5% estimated bias in these outcomes. Although community-based studies are upheld as the gold standard study design in assessing immunity gaps and underlying community health characteristics, these findings underscore the fact that sampling biases can impact the results of even well-conducted community-based surveys. Results from these studies should be interpreted in the context of the study methodology and challenges faced during implementation, which include shortcomings in establishing accurate and up-to-date sampling frames. Failure to account for these shortcomings may result in biased estimates and detrimental effects on decision-making.