Malaria In sub-Saharan Africa Research Articles

Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2018

BackgroundThe use of artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted first-line ACT for uncomplicated malaria in sub-Saharan Africa (SSA), including mainland Tanzania, where it was introduced in December 2006. The WHO recommends regular assessment to monitor the efficacy of the first-line treatment specifically considering that artemisinin partial resistance was reported in Greater Mekong sub-region and has been confirmed in East Africa (Rwanda and Uganda). The main aim of this study was to assess the efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in mainland Tanzania.MethodsA single-arm prospective anti-malarial drug efficacy trial was conducted in Kibaha, Mlimba, Mkuzi, and Ujiji (in Pwani, Morogoro, Tanga, and Kigoma regions, respectively) in 2018. The sample size of 88 patients per site was determined based on WHO 2009 standard protocol. Participants were febrile patients (documented axillary temperature ≥ 37.5 °C and/or history of fever during the past 24 h) aged 6 months to 10 years. Patients received a 6-dose AL regimen by weight twice a day for 3 days. Clinical and parasitological parameters were monitored during 28 days of follow-up to evaluate the drug efficacy and safety.ResultsA total of 653 children were screened for uncomplicated malaria and 349 (53.7%) were enrolled between April and August 2018. Of the enrolled children, 345 (98.9%) completed the 28 days of follow-up or attained the treatment outcomes. There were no early treatment failures, but recurrent infections were higher in Mkuzi (35.2%) and Ujiji (23%). By Kaplan–Meier analysis of polymerase chain reaction (PCR) uncorrected adequate clinical and parasitological response (ACPR) ranged from 63.4% in Mkuzi to 85.9% in Mlimba, while PCR-corrected ACPR on day 28 varied from 97.6% in Ujiji to 100% in Mlimba. The drug was well tolerated; the commonly reported adverse events were cough, runny nose, and abdominal pain. No serious adverse event was reported.ConclusionThis study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria. The high number of recurrent infections were mainly due to new infections, indicating the necessity of utilizing alternative artemisinin-based combinations, such as artesunate amodiaquine, which provide a significantly longer post-treatment prophylactic effect.

Health systems impacts of the COVID-19 pandemic on malaria control program implementation and malaria burden in Benin: A mixed-method qualitative and mathematical modelling and study.

The COVID-19 pandemic has sent ripple effects across health systems and impacted the burden of many other diseases, such as malaria in sub-Saharan Africa. This study takes a mixed method approach to assess the impact of COVID-19 on malaria control programs in three rural communes in Benin. We conducted individual semi-structured interviews with key informants who play important roles in malaria control in Benin at three levels of the health system-national, health zone, and commune. Using a purposive sampling technique, informants were interviewed regarding their roles in malaria control, the impact of the pandemic on their activities, and the mitigation strategies adopted. Relevant themes were identified by content analysis. We then formulated an agent-based model of malaria epidemiology to assess the impacts of treatment disruption on malaria burden. The key informant interviews revealed that essential aspects of malaria control were upheld in Benin due to the close collaboration of public health practitioners and health care providers at all levels of the health system. There were some disruptions to case management services for malaria at the start of the pandemic due to the public avoiding health centers and a brief shortage of malaria treatment that may not be entirely attributable to the pandemic. Results from the agent-based model suggest that duration, severity, and timing of treatment disruption can impact malaria burden in a synergistic manner, though the effects are small given the relatively mild disruptions observed. This study highlights the importance of top-down leadership in health emergencies, as well as the critical role of community health workers in preventing negative health outcomes for their communities. We also showcased the integration of qualitative research and mathematical models-an underappreciated form of mixed methods research that offer immense value in the continued evaluation of rapidly evolving health emergencies.

Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial

Recently, we found that a new malaria vaccine, R21/Matrix-M, had over 75% efficacy against clinical malaria with seasonal administration in a phase 2b trial in Burkina Faso. Here, we report on safety and efficacy of the vaccine in a phase 3 trial enrolling over 4800 children across four countries followed for up to 18 months at seasonal sites and 12 months at standard sites. We did a double-blind, randomised, phase 3 trial of the R21/Matrix-M malaria vaccine across five sites in four African countries with differing malaria transmission intensities and seasonality. Children (aged 5-36 months) were enrolled and randomly assigned (2:1) to receive 5 μg R21 plus 50 μg Matrix-M or a control vaccine (licensed rabies vaccine [Abhayrab]). Participants, their families, investigators, laboratory teams, and the local study team were masked to treatment. Vaccines were administered as three doses, 4 weeks apart, with a booster administered 12 months after the third dose. Half of the children were recruited at two sites with seasonal malaria transmission and the remainder at standard sites with perennial malaria transmission using age-based immunisation. The primary objective was protective efficacy of R21/Matrix-M from 14 days after third vaccination to 12 months after completion of the primary series at seasonal and standard sites separately as co-primary endpoints. Vaccine efficacy against multiple malaria episodes and severe malaria, as well as safety and immunogenicity, were also assessed. This trial is registered on ClinicalTrials.gov, NCT04704830, and is ongoing. From April 26, 2021, to Jan 12, 2022, 5477 children consented to be screened, of whom 1705 were randomly assigned to control vaccine and 3434 to R21/Matrix-M; 4878 participants received the first dose of vaccine. 3103 participants in the R21/Matrix-M group and 1541 participants in the control group were included in the modified per-protocol analysis (2412 [51·9%] male and 2232 [48·1%] female). R21/Matrix-M vaccine was well tolerated, with injection site pain (301 [18·6%] of 1615 participants) and fever (754 [46·7%] of 1615 participants) as the most frequent adverse events. Number of adverse events of special interest and serious adverse events did not significantly differ between the vaccine groups. There were no treatment-related deaths. 12-month vaccine efficacy was 75% (95% CI 71-79; p<0·0001) at the seasonal sites and 68% (61-74; p<0·0001) at the standard sites for time to first clinical malaria episode. Similarly, vaccine efficacy against multiple clinical malaria episodes was 75% (71-78; p<0·0001) at the seasonal sites and 67% (59-73; p<0·0001) at standard sites. A modest reduction in vaccine efficacy was observed over the first 12 months of follow-up, of similar size at seasonal and standard sites. A rate reduction of 868 (95% CI 762-974) cases per 1000 children-years at seasonal sites and 296 (231-362) at standard sites occurred over 12 months. Vaccine-induced antibodies against the conserved central Asn-Ala-Asn-Pro (NANP) repeat sequence of circumsporozoite protein correlated with vaccine efficacy. Higher NANP-specific antibody titres were observed in the 5-17 month age group compared with 18-36 month age group, and the younger age group had the highest 12-month vaccine efficacy on time to first clinical malaria episode at seasonal (79% [95% CI 73-84]; p<0·001) and standard (75% [65-83]; p<0·001) sites. R21/Matrix-M was well tolerated and offered high efficacy against clinical malaria in African children. This low-cost, high-efficacy vaccine is already licensed by several African countries, and recently received a WHO policy recommendation and prequalification, offering large-scale supply to help reduce the great burden of malaria in sub-Saharan Africa. The Serum Institute of India, the Wellcome Trust, the UK National Institute for Health Research Oxford Biomedical Research Centre, and Open Philanthropy.

Larvacidal effects of methanolic and ethanolic leaf extracts of &lt;i&gt;Xienemia americana&lt;/i&gt; against female &lt;i&gt;Anopheles gambiae&lt;/i&gt; S.L. (Culicidae: Diptera)

Anopheles gambiae complex is the most important vector of malaria in sub-Saharan Africa. It is thought that Nigeria comprises about 45 species of Anopheles mosquitoes of which Anopheles gambiae is the most prevalent. Extract of different concentrations were evaluated at the level of 2.00 3.00, 4.00, 5.00 and 0.00 (Control) mg/ml. Distilled water only was used as control. Twenty (20) larvae were put into four (4) cups containing 100ml of the test solution of each concentration. Larval to pupa mortality were recorded and calculated after 24, 48 and 72h after treatment. Mortality results were used to determine LC50 and LC90 using probit analysis. The larvicidal activity of methanol and Ethanolic extracts of the X. Americana were evaluated on 4th instar larvae of Anopheles gambiae. From the results concentration of X. americana with ethanol has shown high larvicidal effect with 10%, 12%, 3% adult emergence when compare with control. While Methanol concentration reveals low larvicidal effect with 16 % adult emergence. Treatment group X. Americana showed highest survival from pupa to adult (28, 18% and 6%) recorded, this means concentration of ethanol has larvicidal effect against A. gambiae. However, methanol concentration shows low activity with 45, 21 and 16% followed by X. Americana with 18, 15 and 10% recorded the highest larvicidal activity among all the concentrations with methanol respectively. Concentration of 5.0 mL, 12.0 mL, 20.0 mL, 25.0, 30.0mL compare to control group. All the extracts proved to be toxic to the test organism, though there was a remarkable difference in the concentrations and timing of their activity.

Frequency of Blood Donation and Malaria Occurrence among Blood Donors in a Tertiary Hospital, Nigeria

Context: Malaria is a significant cause of morbidity and mortality in Sub-Saharan Africa (SSA). Transfusion transmitted malaria contributes significantly to the burden of malaria in SSA. The safety of blood transfusion as it relates to frequency of blood donation and malaria occurrence on the part of donors is an aspect that has not been properly investigated hence this study.&#x0D; Objectives: This study was conducted to assess the frequency of blood donation and occurrence of malaria among blood donors at OAUTHC, Ile-Ife.&#x0D; Materials and methods: This was a cross-sectional study. Ethical approval was obtained. One hundred and thirty-three consenting blood donors aged between 18-50 years were recruited for the study. Two millilitres of blood were collected from each study participant and immediately transported to the laboratory for processing. Giemsa-stained films of the samples were viewed under the oil immersion objective of the microscope. Questionnaires were administered to the study participants to obtain relevant information. Data generated were analysed using descriptive and inferential statistics with SPSS software version 20. The level of significance was set at p &lt; 0.05.&#x0D; Results: The prevalence of malaria among the blood donors was 21.1% with the highest rate among commercial donors (33.3%) followed by family donors (12.9%) then voluntary donors (11.9%). Evaluation of the frequency of donation showed that malaria occurred more in recurring donors (77.78%) than first time donors (22.22%).&#x0D; Conclusion: Malaria is highly prevalent among blood donors and occurs more in recurring blood donors than first time donors.

Estimated distribution of malaria cases among children in sub-Saharan Africa by specified age categories using data from the Global Burden of Diseases 2019

BackgroundChildren in sub-Saharan Africa (SSA) remain the most vulnerable to malaria and malaria mortality. This study estimated the disease burden and distribution of Plasmodium falciparum malaria among children with age categories (0 to < 2 years, 2 to < 6 years, 6 to < 12 years, ≥ 12 years) in SSA.MethodsData on the number of cases and incidence rates of P. falciparum malaria by age group from the Institute of Health Metrics and Evaluation (GBD 2019) for 11 countries in SSA was employed in this study. The best-fitting distribution of P. falciparum malaria cases by prespecified age categories was derived using a combination of a Log-normal and Weibull distribution.ResultsPlasmodium falciparum malaria was 15.4% for ages 0 to < 2 years, 30.5% for 2 to < 6 years, 17.6% for 6 to < 12 years, and 36.5% for ≥ 12 years based on data from countries in SSA. The results have important implications for the current drive by the FDA and EMA to ensure the representativeness of real-world populations in clinical trials evaluating the safety and efficacy of medication exposure.ConclusionsThe theoretical distributions of P. falciparum malaria will help guide researchers in ensuring that children are appropriately represented in clinical trials and other interventions aiming to address the current burden of malaria in SSA.

The Darc Side of Vivax Malaria in Africa: Unveiling Invasion Pathways into Duffy-Negative Erythroblasts

Background &amp; Objectives: Plasmodium vivax malaria was long thought to be absent from sub-Saharan Africa owing to the high prevalence of people lacking the Duffy antigen receptor for chemokines (DARC) on their erythrocytes. The interaction between P. vivax Duffy binding protein (PvDBP) and DARC is assumed to be the main mechanism used by P. vivax merozoites to invade human erythrocytes. However, the increasing numbers of vivax malaria cases in Duffy-negative African individuals has raised questions about alternative P. vivax invasion pathway(s) other than PvDBP-DARC interaction. Since P. vivax has a tropism for CD71+ immature reticulocytes and the hematopoietic niches of the bone marrow may be a hidden reservoir of P. vivax parasites, we hypothesized that P. vivax merozoites may be able to invade erythroblasts derived from Duffy-positive (DP) and Duffy-negative (DN) individuals. Therefore, our objectives were to (i) investigate the expression of DARC during DP and DN erythropoiesis and (ii) examine the infection of DP and DN erythroblasts with P. vivax merozoites in vitro to study and identify host receptors used by P. vivax to invade erythroblasts. Methods: We performed in vitro erythropoiesis assays (two-phase culture) of genotypically DN and DP erythroid progenitors. Erythroid differentiation, CD71 and DARC expression profiles were monitored using flow cytometry, microscopy, and western blot over time during phase 2. In vitro invasion assays were conducted using DP and DN erythroblasts to investigate whether genotypically DN erythroblasts could be invaded by P. vivax. At D7 of phase 2, we thawed and cultured parasite isolates obtained from two Malagasy and seven Ethiopian patients infected with P. vivax. After approximately 24-30 hours of in vitro maturation (at D8 of phase 2), each P. vivax parasite culture was placed in co-culture with either DP or DN erythroblasts for 24-48 hours. We examined the infection of DP and DN erythroblasts by P. vivax parasites by light and confocal microscopy. Results: Using in vitro erythropoiesis, we show that both genotypically DP and DN erythroblasts have similar kinetics of terminal erythroid differentiation. Moreover, we found similar CD71 expression profiles in both DP and DN erythroblasts. Interestingly, we observed that a subset of DN erythroblasts transiently expressed DARC during erythropoiesis. This was confirmed using both flow cytometry and western blot analysis. In vitro invasion assays conducted on both DP and DN erythroblasts using parasite isolates, showed that P. vivax merozoites were able to invade both DP and DN erythroblasts (Figure 1). We found that all the DP and DN erythroblasts that were infected with P. vivax were CD71+ and DARC+. These results confirm that P. vivax can invade DP and DN erythroblasts expressing both DARC and CD71, irrespective of the origin of the isolates. Conclusion: This study provides the first biological evidence for the ability of P. vivax to invade genotypically DN erythroblasts and highlights that African populations may represent a silent reservoir of P. vivax infections, with major implications for the control and elimination of vivax malaria in sub-Saharan Africa.

Epidemiology of Plasmodium malariae and Plasmodium ovale spp. in Kinshasa Province, Democratic Republic of Congo

Reports suggest non-falciparum species are an underappreciated cause of malaria in sub-Saharan Africa but their epidemiology is ill-defined, particularly in highly malaria-endemic regions. We estimated incidence and prevalence of PCR-confirmed non-falciparum and Plasmodium falciparum malaria infections within a longitudinal study conducted in Kinshasa, Democratic Republic of Congo (DRC) between 2015-2017. Children and adults were sampled at biannual household surveys and routine clinic visits. Among 9,089 samples from 1,565 participants, incidences of P. malariae, P. ovale spp., and P. falciparum infections by 1-year were 7.8% (95% CI: 6.4%-9.1%), 4.8% (95% CI: 3.7%-5.9%) and 57.5% (95% CI: 54.4%-60.5%), respectively. Non-falciparum prevalences were higher in school-age children, rural and peri-urban sites, and P. falciparum co-infections. P. falciparum remains the primary driver of malaria in the DRC, though non-falciparum species also pose an infection risk. As P. falciparum interventions gain traction in high-burden settings, continued surveillance and improved understanding of non-falciparum infections are warranted.

Pooled prevalence and risk factors of malaria among children aged 6-59 months in 13 sub-Saharan African countries: A multilevel analysis using recent malaria indicator surveys.

Every 75 seconds, a child under five dies of malaria. Mainly children, aged between six months and five years, are at the highest risk for malaria. These children lost maternal immunity and did not yet developed specific immunity to the infection. Under the age of five, children bear the highest burden of malaria in Sub-Saharan Africa (SSA). Many individual and community level factors could contribute to malaria prevalence remaining high among under-five children in the region. Thus, this study aimed to assess the pooled prevalence of malaria among children aged 6-59 months and identify potential factors associated with malaria by using recent Malaria Indicator Surveys in 13 SSA countries. Data for this study were drawn from recent 13 Sub-Saharan African countries Malaria Indicator Surveys (MIS). A total weighted sample of 60,541 children aged 6-59 months was included. STATA version 14.2 was used to clean, code and analyze the data. Multilevel logistic regression was employed to identify factors associated with malaria. Adjusted odds ratio with 95% CI and a P value <0.05 was reported to indicate statistical association. Model fitness and comparison were done using Inter cluster correlation coefficient, Median odds ratio, proportional change in variance, and deviance. The pooled prevalence of malaria among children aged 6-59 months was found to be 27.41% (95% CI: 17.94%-36.88%). It ranges from 5.04% in Senegal to 62.57% in Sierra Leone. Aged 36-47 months (AOR = 3.54, 95% CI 3.21-3.91), and 48-59 months (AOR = 4.32, 95% CI 3.91-4.77), mothers attended primary education (AOR = 0.78, 95% CI 0.73-0.84), richer (AOR = 0.35, 95% CI 0.32-0.39), and richest household (AOR = 0.16, 95% CI 0.14-0.19), number of three and more under-five children (AOR = 1.35, 95% CI 1.26-1.45), improved floor material (AOR = 0.65, 95% CI 0.57-0.73), improved wall material (AOR = 0.73, 95% CI 0.64-0.84), improved roof material (AOR = 0.70, 95% CI 0.51-0.93), insecticide-treated bed net (ITN) use (0.56, 95% CI 0.51-0.62), not anemic (AOR = 0.05, 95% CI 0.04-0.06), rural resident (AOR = 2.16, 95% CI 2.06-2.27), high community ITN use (AOR = 0.40, 95% CI 0.24-0.63) and high community poverty (AOR = 2.66, 95% CI 2.53-2.84) were strongly associated with malaria. Almost 3 out of 10 children were infected by malaria in 13 SSA countries. Malaria infection remains one of the main killers of children aged 6-59 months in the SSA. This study revealed that older under-five children living in large families with low incomes in rural areas are most vulnerable to malaria infection. Our results clearly indicate that ITN utilization and improved housing are promising means to effectively prevent malaria infection among children aged 6-59 months. It is therefore important to note that households with low wealth quintiles and rural residents should be prioritized in any mass distribution of ITNs. This has to be accompanied by education using mass media to enhance community awareness.

Outcomes of childhood severe malaria: a comparative of study pre-COVID-19 and COVID-19 periods

BackgroundThe collateral damages from measures adopted to mitigate the coronavirus disease 2019 (COVID-19) pandemic have been projected to negatively impact malaria in sub-Saharan Africa. Herein, we compare the prevalence and outcomes of childhood severe malaria during the pre-COVID-19 and COVID-19 periods at a tertiary health facility in Nigeria.MethodsThis was a retrospective review of cases of severe malaria admitted from 1st January to 31st December 2019 (pre-COVID-19 period) and 1st January to 31st December 2020 (COVID-19 period). We extracted relevant information, including demographics, the duration of symptoms before presentation, forms of severe malaria, and outcomes of hospitalization (discharged or death).ResultsIn the pre-COVID-19 period, there were a total of 2312 admissions to the EPU and 1685 in the COVID-19 period, representing a decline of 27%. In contrast, there were 263 and 292 severe malaria admissions in the pre-COVID-19 and COVID-19 periods, respectively, representing an 11% increase in the absolute number of cases. The prevalence rates were 11.4% in the pre-COVID-19 period and 17.3% in the COVID-19 period, representing an increase of 52% in the percentage differences. The mortality rate in the COVID-19 period was higher than the pre-COVID-19 period ([10.3%; 30/292 vs. 2.3%; 6/263], p 0.001). The death rate increased by 350% during the COVID-19 period. The odds ratio (OR) of a child dying from severe malaria in the COVID-19 era was 4.9 [95% confidence interval (CI): 2.008 to 11.982]. In the COVID-19 era, presentation at a health facility was also delayed (p = 0.029), as were the odds of multiple features of severe malaria manifestations (OR-1.9, 95% CI, 1.107 to 3.269; p = 0.020).ConclusionThis study shows that the prevalence of severe childhood malaria increased by as much as 11.0%, with a disproportionate increase in mortality compared to the pre-pandemic level. Most children with severe malaria presented late with multiple features of severe malaria, probably contributing to the poor hospitalization outcomes (death) observed in this study.

Estimation of Pediatric Dosage of Antimalarial Drugs, Using Pharmacokinetic and Physiological Approach.

Most of the individuals who die of malaria in sub-Saharan Africa are children. It is, therefore, important for this age group to have access to the right treatment and correct dose. Artemether-lumefantrine is one of the fixed dose combination therapies that was approved by the World Health Organization to treat malaria. However, the current recommended dose has been reported to cause underexposure or overexposure in some children. The aim of this article was, therefore, to estimate the doses that can mimic adult exposure. The availability of more and reliable pharmacokinetic data is essential to accurately estimate appropriate dosage regimens. The doses in this study were estimated using the physiological information from children and some pharmacokinetic data from adults due to the lack of pediatric pharmacokinetic data in the literature. Depending on the approach that was used to calculate the dose, the results showed that some children were underexposed, and others were overexposed. This can lead to treatment failure, toxicity, and even death. Therefore, when designing a dosage regimen, it is important to know and include the distinctions in physiology at various phases of development that influence the pharmacokinetics of various drugs in order to estimate the dose in young children. The physiology at each time point during the growth of a child may influence how the drug is absorbed, gets distributed, metabolized, and eliminated. From the results, there is a very clear need to conduct a clinical study to further verify if the suggested (i.e., 0.34 mg/kg for artemether and 6 mg/kg for lumefantrine) doses could be clinically efficacious.

Climate Drivers of Malaria Transmission Seasonality and Their Relative Importance in Sub-Saharan Africa.

A new database of the Entomological Inoculation Rate (EIR) was used to directly link the risk of infectious mosquito bites to climate in Sub-Saharan Africa. Applying a statistical mixed model framework to high-quality monthly EIR measurements collected from field campaigns in Sub-Saharan Africa, we analyzed the impact of rainfall and temperature seasonality on EIR seasonality and determined important climate drivers of malaria seasonality across varied climate settings in the region. We observed that seasonal malaria transmission was within a temperature window of 15°C-40°C and was sustained if average temperature was well above 15°C or below 40°C. Monthly maximum rainfall for seasonal malaria transmission did not exceed 600 in west Central Africa, and 400mm in the Sahel, Guinea Savannah, and East Africa. Based on a multi-regression model approach, rainfall and temperature seasonality were found to be significantly associated with malaria seasonality in all parts of Sub-Saharan Africa except in west Central Africa. Topography was found to have significant influence on which climate variable is an important determinant of malaria seasonality in East Africa. Seasonal malaria transmission onset lags behind rainfall only at markedly seasonal rainfall areas such as Sahel and East Africa; elsewhere, malaria transmission is year-round. High-quality EIR measurements can usefully supplement established metrics for seasonal malaria. The study's outcome is important for the improvement and validation of weather-driven dynamical mathematical malaria models that directly simulate EIR. Our results can contribute to the development of fit-for-purpose weather-driven malaria models to support health decision-making in the fight to control or eliminate malaria in Sub-Saharan Africa.

Burkitt lymphoma risk shows geographic and temporal associations with Plasmodium falciparum infections in Uganda, Tanzania, and Kenya

Endemic Burkitt lymphoma (eBL) is a pediatric cancer coendemic with malaria in sub-Saharan Africa, suggesting an etiological link between them. However, previous cross-sectional studies of limited geographic areas have not found a convincing association. We used spatially detailed data from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) study to assess this relationship. EMBLEM is a case-control study of eBL from 2010 through 2016 in six regions of Kenya, Uganda, and Tanzania. To measure the intensity of exposure to the malaria parasite, Plasmodium falciparum, among children in these regions, we used high-resolution spatial data from the Malaria Atlas Project to estimate the annual number of P.falciparum infections from 2000 through 2016 for each of 49 districts within the study region. Cumulative P. falciparum exposure, calculated as the sum of annual infections by birth cohort, varied widely, with a median of 47 estimated infections per child by age 10, ranging from 4 to 315 infections. eBL incidence increased 39% for each 100 additional lifetime P. falciparum infections (95% CI: 6.10 to 81.04%) with the risk peaking among children aged 5 to 11 and declining thereafter. Alternative models using estimated annual P. falciparum infections 0 to 10 y before eBL onset were inconclusive, suggesting that eBL risk is a function of cumulative rather than recent cross-sectional exposure. Our findings provide population-level evidence that eBL is a phenotype related to heavy lifetime exposure to P. falciparum malaria and support emphasizing the link between malaria and eBL.

The burden of malaria in sub-Saharan Africa and its association with development assistance for health and governance: An exploration of the GBD 2019 study

ABSTRACT Even with a reduced burden of malaria in sub-Saharan Africa (SSA), differences remain in the rate of change among countries and sub-regions. We used data from the Global Burden of Disease Study 2019 to establish the relationship between Development Assistance for Health (DAH) and governance and trends in malaria burden in SSA. The trend was estimated using the Joinpoint regression program and the Institute of Health Metrics and Evaluation’s DAH database, and World Bank Governance Indicators to analyze the DAH and governance respectively from 2000 to 2017 and used two-way fixed effects to establish their association with the trend in the period. The findings showed decreases in SSA’s age-standardised rates for disability-adjusted life years (ASDR) (−47% (95% uncertainty interval (UI) −69% to −14%)), deaths (−38% (95% UI −65% to −3%)), incidence (−35% (95% UI −44% to −25%)), and prevalence (−34% (95% UI −43% to −24%)). Decreases in ASDR were associated with increases in DAH (β −134.18, standard error (SE) 27.26) and governance scores (β −246.19, SE 39.13). The association between reductions in malaria burden and increases in DAH and in governance scores shows the need for accelerated funding of malaria programs and advocacy for better disease governance in malaria-endemic countries. Abbreviations: APC: Annual percentage change; ASDR: Age-standardised disability-adjusted life-year rate; ASIR: Age-standardised incidence rate; ASIR: Age-standardised incidence rate; ASMR: Age-standardised mortality rate; CSSA: Central sub-Saharan Africa; DAH: Development Assistance for Health; DALYs: Disability-adjusted life years; ESSA: Eastern sub-Saharan Africa; GBD: Global burden of disease; GHDx Global Health Data Exchange; IHME: Institute of Health Metrics and Evaluation; SDGs: Sustainable Development Goals; SSA: Sub-Saharan Africa; SSSA: Southern sub-Saharan Africa; UNSD: United Nations Statistics Division; USD: United States dollars; WGI: World Bank Governance Indicators; WHO: World Health Organization; WSSA: Western sub-Saharan Africa

Zoonotic malaria in sub-Saharan Africa: A Mini-Review

Malaria is a serious public health problem worldwide despite concerted efforts to control and eliminate it. Zoonotic malaria is emerging as a big threat to malaria elimination efforts. There is a big knowledge gap in our understanding of zoonotic malaria. It is difficult to adequately detect and identify Plasmodium species responsible for zoonotic malaria with conventional diagnostic tools. Although molecular tools have good sensitivity and specificity to diagnose zoonotic malaria, they are not readily available in resource-limited settings. There is limited data on the epidemiology of zoonotic malaria in sub-Saharan Africa. However, various reports signal for the presence of its risk lurking in the area. Therefore, organized and comprehensive studies are needed to characterize its epidemiology in sub-Saharan Africa to guide strategies of mitigating zoonotic malaria in particular and malaria in general.

Rectal artesunate as pre-referral treatment for severe malaria in sub-Saharan Africa: still a long way to go

Rectal artesunate for pre-referral treatment of severe malaria has been reported as an effective malaria intervention to substantially reduce the risk of death and permanent disability among children younger than 5 years in sub-Saharan Africa, by delaying the progression of disease severity as children seek to access health facilities for adequate treatment.1 However, although well accepted as an intervention,2 reported findings have raised concerns over the effectiveness of rectal artesunate in real-life conditions, which are often associated with shortcomings in terms of referral and quality of care.

Health system readiness and the implementation of rectal artesunate for severe malaria in sub-Saharan Africa: an analysis of real-world costs and constraints

Rectal artesunate, an efficacious pre-referral treatment for severe malaria in children, was deployed at scale in Uganda, Nigeria, and DR Congo. In addition to distributing rectal artesunate, implementation required additional investments in crucial but neglected components in the care for severe malaria. We examined the real-world costs and constraints to rectal artesunate implementation. We collected primary data on baseline health system constraints and subsequent rectal artesunate implementation expenditures. We calculated the equivalent annual cost of rectal artesunate implementation per child younger than 5 years at risk of severe malaria, from a health system perspective, separating neglected routine health system components from incremental costs of rectal artesunate introduction. The largest baseline constraints were irregular health worker supervisions, inadequate referral facility worker training, and inadequate malaria commodity supplies. Health worker training and behaviour change campaigns were the largest startup costs, while supervision and supply chain management accounted for most annual routine costs. The equivalent annual costs of preparing the health system for managing severe malaria with rectal artesunate were US$2·63, $2·20, and $4·19 per child at risk and $322, $219, and $464 per child treated in Uganda, Nigeria, and DR Congo, respectively. Strengthening the neglected, routine health system components accounted for the majority of these costs at 71·5%, 65·4%, and 76·4% of per-child costs, respectively. Incremental rectal artesunate costs accounted for the minority remainder. Although rectal artesunate has been touted as a cost-effective pre-referral treatment for severe malaria in children, its real-world potential is limited by weak and under-financed health system components. Scaling up rectal artesunate or other interventions relying on community health-care providers only makes sense alongside additional, essential health system investments sustained over the long term. Unitaid. For the French translation of the abstract see Supplementary Materials section.

Molecular characterization and genetic authentication assay for Anopheles ‘hemocyte-like’ cell lines 4a-3A and 4a-3B

BackgroundAnopheles cell lines are used in a variety of ways to better understand the major vectors of malaria in sub-Saharan Africa. Despite this, commonly used cell lines are not well characterized, and no tools are available for cell line identification and authentication.MethodsUtilizing whole genome sequencing, genomes of 4a-3A and 4a-3B ‘hemocyte-like’ cell lines were characterized for insertions and deletions (indels) and SNP variation. Genomic locations of distinguishing sequence variation and species origin of the cell lines were also examined. Unique indels were targeted to develop a PCR-based cell line authentication assay. Mitotic chromosomes were examined to survey the cytogenetic landscape for chromosome structure and copy number in the cell lines.ResultsThe 4a-3A and 4a-3B cell lines are female in origin and primarily of Anopheles coluzzii ancestry. Cytogenetic analysis indicates that the two cell lines are essentially diploid, with some relatively minor chromosome structural rearrangements. Whole-genome sequence was generated, and analysis indicated that SNPs and indels which differentiate the cell lines are clustered on the 2R chromosome in the regions of the 2Rb, 2Rc and 2Ru chromosomal inversions. A PCR-based authentication assay was developed to fingerprint three indels unique to each cell line. The assay distinguishes between 4a-3A and 4a-3B cells and also uniquely identifies two additional An. coluzzii cell lines tested, Ag55 and Sua4.0. The assay has the specificity to distinguish four cell lines and also has the sensitivity to detect cellular contamination within a sample of cultured cells.ConclusionsGenomic characterization of the 4a-3A and 4a-3B Anopheles cell lines was used to develop a simple diagnostic assay that can distinguish these cell lines within and across research laboratories. A cytogenetic survey indicated that the 4a-3A and Sua4.0 cell lines carry essentially normal diploid chromosomes, which makes them amenable to CRISPR/Cas9 genome editing. The presented simple authentication assay, coupled with screening for mycoplasma, will allow validation of the integrity of experimental resources and will promote greater experimental reproducibility of results.Graphical abstract

Chemoprevention for the Populations of Malaria Endemic Africa.

Drugs have been used to prevent malaria for centuries, but only recently have they been used on a large scale to prevent malaria in the resident population of malaria endemic areas in sub-Saharan Africa. This paper discusses some of the reasons for the hesitancy in adoption of chemopreventive strategies in sub-Saharan Africa, reasons why this hesitancy has been overcome in recent years and the range of target groups now identified by the World Health Organization as those who can benefit most from chemoprevention. Adoption of carefully targeted chemopreventive strategies could help reverse the recent stagnation in the decline in malaria in sub-Saharan Africa that had been taking place during the previous two decades.

Genomic approaches for monitoring transmission dynamics of malaria: A case for malaria molecular surveillance in Sub-Saharan Africa.

Transmission dynamics is an important indicator for malaria control and elimination. As we move closer to eliminating malaria in Sub-Saharan Africa (sSA), transmission indices with higher resolution (genomic approaches) will complement our current measurements of transmission. Most of the present programmatic knowledge of malaria transmission patterns are derived from assessments of epidemiologic and clinical data, such as case counts, parasitological estimates of parasite prevalence, and Entomological Inoculation Rates (EIR). However, to eliminate malaria from endemic areas, we need to track changes in the parasite population and how they will impact transmission. This is made possible through the evolving field of genomics and genetics, as well as the development of tools for more in-depth studies on the diversity of parasites and the complexity of infections, among other topics. If malaria elimination is to be achieved globally, country-specific elimination activities should be supported by parasite genomic data from regularly collected blood samples for diagnosis, surveillance and possibly from other programmatic interventions. This presents a unique opportunity to track the spread of malaria parasites and shed additional light on intervention efficacy. In this review, various genetic techniques are highlighted along with their significance for an enhanced understanding of transmission patterns in distinct topological settings throughout Sub-Saharan Africa. The importance of these methods and their limitations in malaria surveillance to guide control and elimination strategies, are explored.