Impact of six-month COVID-19 travel moratorium on Plasmodium falciparum prevalence on Bioko Island, Equatorial Guinea.

Importation of malaria infections is a suspected driver of sustained malaria prevalence on areas of Bioko Island, Equatorial Guinea. Quantifying the impact of imported infections is difficult because of the dynamic nature of the disease and complexity of designing a randomized trial. We leverage a six-month travel moratorium in and out of Bioko Island during the initial COVID-19 pandemic response to evaluate the contribution of imported infections to malaria prevalence on Bioko Island.

Assessing the daily natural history of asymptomatic Plasmodium infections in adults and older children in Katakwi, Uganda: a longitudinal cohort study.

Background: Low-density asymptomatic Plasmodium infections are prevalent in endemic areas, but little is known about their natural history. The trajectories of these infections and their propensity to fluctuate to undetectable densities can affect detection in clinical trials and field studies. We aimed to classify the natural history of these infections in a high transmission area over 29 days.

18S Ribosomal RNA Biomarker Clearance After Food and Drug Administration-Approved Antimalarial Treatment in Controlled Human Malaria Infection Trials.

Background: Sensitive molecular assays, such as quantitative reverse-transcription polymerase chain reaction (qRT-PCR) of 18S ribosomal RNA (rRNA), are increasingly the primary method of detecting infections in controlled human malaria infection (CHMI) trials. However, thick blood smears (TBSs) remain the main method for confirming clearance of parasites after curative treatment, in part owing to uncertainty regarding biomarker clearance rates.

Methods: For this analysis, 18S rRNA qRT-PCR data were compiled from 127 -infected participants treated with chloroquine or atovaquone-proguanil in 6 CHMI studies conducted in Seattle, Washington, over the past decade.

Safety and Immunogenicity of Radiation-Attenuated PfSPZ Vaccine in Equatoguinean Infants, Children, and Adults.

The radiation-attenuated Plasmodium falciparum sporozoites (PfSPZ) Vaccine has demonstrated safety and immunogenicity in 5-month-old to 50-year-old Africans in multiple trials. Except for one, each trial has restricted enrollment to either infants and children or adults < 50 years old. This trial was conducted in Equatorial Guinea and assessed the safety, tolerability, and immunogenicity of three direct venous inoculations of 1.

Identifying individual, household and environmental risk factors for malaria infection on Bioko Island to inform interventions.

Background: Since 2004, malaria transmission on Bioko Island has declined significantly as a result of the scaling-up of control interventions. The aim of eliminating malaria from the Island remains elusive, however, underscoring the need to adapt control to the local context. Understanding the factors driving the risk of malaria infection is critical to inform optimal suits of interventions in this adaptive approach.

Rethinking detection of pre-existing and intervening infections in malaria clinical trials.

Pre-existing and intervening low-density infections complicate the conduct of malaria clinical trials. These infections confound infection detection endpoints, and their immunological effects may detract from intended vaccine-induced immune responses. Historically, these infections were often unrecognized since infrequent and often analytically insensitive parasitological testing was performed before and during trials.

Feasibility of community at-home dried blood spot collection combined with pooled reverse transcription PCR as a viable and convenient method for malaria epidemiology studies.

Background: Many Plasmodium infections in endemic regions exist at densities below the limit of detection of standard diagnostic tools. These infections threaten control efforts and may impact vaccine and therapeutic drug studies. Simple, cost-effective methods are needed to study the natural history of asymptomatic submicroscopic parasitaemia.

Case fatality risk of diarrhoeal pathogens: a systematic review and meta-analysis.

Background: Estimates of the relative contribution of different pathogens to all-cause diarrhoea mortality are needed to inform global diarrhoea burden models and prioritize interventions. We aimed to investigate and estimate heterogeneity in the case fatality risk (CFR) of different diarrhoeal pathogens.

Methods: We conducted a systematic review and meta-analysis of studies that reported cases and deaths for 15 enteric pathogens published between 1990 and 2019.

Application of dried blood spot sample pooling strategies for Plasmodium 18S rRNA biomarker testing to facilitate identification of infected persons in large-scale epidemiological studies.

Background: Plasmodium 18S rRNA is a sensitive biomarker for detecting Plasmodium infection in human blood. Dried blood spots (DBS) are a practical sample type for malaria field studies to collect, store, and transport large quantities of blood samples for diagnostic testing. Pooled testing is a common way to reduce reagent costs and labour.

Clustering of subpatent infections in households with asymptomatic rapid diagnostic test-positive cases in Bioko Island, Equatorial Guinea independent of travel to regions of higher malaria endemicity: a cross-sectional study.

Background: Prevalence of falciparum malaria on Bioko Island remains high despite sustained, intensive control. Progress may be hindered by high proportions of subpatent infections that are not detected by rapid diagnostic tests (RDT) but contribute to onward transmission, and by imported infections. Better understanding of the relationship between subpatent infections and RDT-detected infections, and whether this relationship is different from imported versus locally acquired infections, is imperative to better understand the sources of infection and mechanisms of transmission to tailor more effective interventions.

Immunogenicity and Protective Efficacy of Radiation-Attenuated and Chemo-Attenuated PfSPZ Vaccines in Equatoguinean Adults.

sporozoite (PfSPZ) Vaccine (radiation-attenuated, aseptic, purified, cryopreserved PfSPZ) and PfSPZ-CVac (infectious, aseptic, purified, cryopreserved PfSPZ administered to subjects taking weekly chloroquine chemoprophylaxis) have shown vaccine efficacies (VEs) of 100% against homologous controlled human malaria infection (CHMI) in nonimmune adults. sporozoite-CVac has never been assessed against CHMI in African vaccinees. We assessed the safety, immunogenicity, and VE against homologous CHMI of three doses of 2.

Immunogenicity of Alternative Dosing Schedules for HPV Vaccines among Adolescent Girls and Young Women: A Systematic Review and Meta-Analysis.

Alternative dosing schedules for licensed human papilloma virus (HPV) vaccines, particularly single dose and extended intervals between doses (>12 months), are being considered to address vaccine shortages and improve operational flexibility. We searched PUBMED/MEDLINE for publications reporting immunogenicity data following administration of one of the licensed HPV vaccines (2vHPV, 4vHPV, and 9vHPV) to females aged 9-26 years. We conducted non-inferiority analyses comparing alternative to standard schedules using mixed effects meta-regression controlling for baseline HPV status and disaggregated by vaccine, subtype, time point, and age group (9-14 and 15-26 years).

The Equatoguinean Malaria Vaccine Initiative: From the Launching of a Clinical Research Platform to Malaria Elimination Planning in Central West Africa.

Fifteen years of investment in malaria control on Bioko Island, Equatorial Guinea (EG), dramatically reduced malaria-associated morbidity and mortality, but the impact has plateaued. To progress toward elimination, EG is investing in the development of a malaria vaccine. We assessed the unique public-private partnership that has had such a significant impact on malaria on Bioko Island and now added a major effort on malaria vaccine development.

Mapping and enumerating houses and households to support malaria control interventions on Bioko Island.

Background: Housing mapping and household enumeration are essential for the planning, implementation, targeting, and monitoring of malaria control interventions. In many malaria endemic countries, control efforts are hindered by incomplete or non-existent housing cartography and household enumeration. This paper describes the development of a comprehensive mapping and enumeration system to support the Bioko Island Malaria Control Project (BIMCP).

Human mobility patterns and malaria importation on Bioko Island.

Malaria burden on Bioko Island has decreased significantly over the past 15 years. The impact of interventions on malaria prevalence, however, has recently stalled. Here, we use data from island-wide, annual malaria indicator surveys to investigate human movement patterns and their relationship to Plasmodium falciparum prevalence.

Trends in parasite prevalence following 13 years of malaria interventions on Bioko island, Equatorial Guinea: 2004-2016.

Background: Whilst there have been substantial reductions in malaria transmission over the past decade, in many countries in West and Central Africa the malaria burden remains high. Monitoring and evaluation of malaria transmission trends and intervention strategies are key elements for malaria control programmes. This study uses a time series of annual malaria indicator surveys to track the progress of malaria control in Bioko Island, Equatorial Guinea, over a 13 year period of intensive interventions.

Advancing Global Health through Development and Clinical Trials Partnerships: A Randomized, Placebo-Controlled, Double-Blind Assessment of Safety, Tolerability, and Immunogenicity of PfSPZ Vaccine for Malaria in Healthy Equatoguinean Men.

Equatorial Guinea (EG) has implemented a successful malaria control program on Bioko Island. A highly effective vaccine would be an ideal complement to this effort and could lead to halting transmission and eliminating malaria. Sanaria PfSPZ Vaccine ( sporozoite Vaccine) is being developed for this purpose.

Prevalence of substandard and falsified artemisinin-based combination antimalarial medicines on Bioko Island, Equatorial Guinea.

Introduction: Poor-quality artemisinin-containing antimalarials (ACAs), including falsified and substandard formulations, pose serious health concerns in malaria endemic countries. They can harm patients, contribute to the rise in drug resistance and increase the public's mistrust of health systems. Systematic assessment of drug quality is needed to gain knowledge on the prevalence of the problem, to provide Ministries of Health with evidence on which local regulators can take action.

Outdoor biting by Anopheles mosquitoes on Bioko Island does not currently impact on malaria control.

Background: There have been many recent reports that the rate of outdoor biting by malaria vectors has increased. This study examined the impact this might have on malaria transmission by assessing the association between exposure to outdoor bites and malaria infection on Bioko Island, Equatorial Guinea.

Methods: Responses to questions about time spent outside the previous night from a malaria indicator survey were combined with human landing catch measurements of hourly rates of outdoor and indoor biting for the whole island to estimate the number of outdoor and indoor bites received by each survey respondent.

Infection importation: a key challenge to malaria elimination on Bioko Island, Equatorial Guinea.

Background: The impact of importation of falciparum malaria from mainland Equatorial Guinea on malaria infection in non-travellers and travellers on Bioko Island was examined.

Methods: Malaria indicator surveys were conducted in 2013 and 2014 to assess the association between malaria infection and travel to the mainland. Infection in non-travellers was compared in neighbourhoods of high travel and neighbourhoods of low travel.

A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus.

Chronic infection with hepatitis C virus (HCV) is a common cause of liver cirrhosis and cancer. We performed RNA sequencing in primary human hepatocytes activated with synthetic double-stranded RNA to mimic HCV infection. Upstream of IFNL3 (IL28B) on chromosome 19q13.