Malaria In sub-Saharan Africa Research Articles

Characterisation of the epigenetic architecture of the major malaria vector Anopheles arabiensis (Diptera: Culicidae) after treatment with epigenetic modulators and heavy metals

Anopheles arabiensis (a member of the An. gambiae species complex) is a major vector of malaria in sub-Saharan Africa. Despite its disease vector status, there is currently a paucity of epigenetic information for this species. The aim this study was therefore to analyse global epigenetic markers and their response to metal exposure in insecticide susceptible and resistant laboratory strains of An. arabiensis. This was done using commercially available epigenetic marker quantification kits. In order to validate the efficacy of the kits, several kits were assessed to determine whether changes induced by known epigenetic modulators were detectable using these platforms. The efficacy of the dosages used were determined by examining the effect of the dosages used on insecticide resistant phenotypes. Upon confirmation that the dosages used were sufficient to induce a phenotypic change, the effect on epigenetic markers was assessed. Commercial kits were used to quantify 5-methylcysteine (5-mC) and 5-hydroxymethylcysteine (5-hmC) methylation in DNA, m6A methylation in mRNA as well as Histone Acetyl Transferase (HAT) activity. There was a marked difference in the phenotypic response in adult mosquitoes of the insecticide susceptible strain compared to that of its’ resistant counterpart. For males and females of the resistant strain, exposure to nucleic acid modifying drugs typically increased their tolerance to insecticides. The patterns of changes in 5-mC methylation by epigenetic modulators was congruent with previous studies which quantified by mass spectrometry. The two strains differed in methylation patterns under control conditions and responded differentially to larval metal exposure. In the resistant strain, which previously was demonstrated to show increased detoxification enzyme activity and insecticide tolerance after the same treatment, the potential increase in transcriptional activity appeared to be modulated by reduced methylation and increased HAT activity. This study suggests that the commercial epigenetic quantification kits can be used to characterise phenotypic changes in An. arabiensis, and also shows that epigenetic regulation of the response to metal exposure is regulated at the DNA as opposed to the RNA level.

The Pan African Vivax and Ovale Network (PAVON): Refocusing on Plasmodium vivax, ovale and asymptomatic malaria in sub-Saharan Africa.

The recent World Malaria report shows that progress in malaria elimination has stalled. Current data acquisition by NMCPs depend on passive case detection and clinical reports focused mainly on Plasmodium falciparum (Pf). In recent times, several countries in sub-Saharan Africa have reported cases of Plasmodium vivax (Pv) with a considerable number being Duffy negative. The burden of Pv and Plasmodium ovale (Po) appear to be more than acknowledged. Similarly, the contribution of asymptomatic malaria in transmission is hardly considered by NMCPs in Africa. Inclusion of these as targets in malaria elimination agenda is necessary to achieve elimination goal, as these harbor hypnozoites. The Pan African Vivax and Ovale Network (PAVON) is a new consortium of African Scientists working in Africa on the transmission profile of Pv and Po. The group collaborates with African NMCPs to train in Plasmodium molecular diagnostics, microscopy, and interpretation of molecular data from active surveys to translate into policy. Details of the mission, rational and modus operandi of the group are outlined.

Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations.

Pyruvate kinase (PK), encoded by the PKLR gene, is a key player in glycolysis controlling the integrity of erythrocytes. Due to Plasmodium selection, mutations for PK deficiency, which leads to hemolytic anemia, are associated with resistance to malaria in sub-Saharan Africa and with susceptibility to intracellular pathogens in experimental models. In this case-control study, we enrolled 4,555 individuals and investigated whether PKLR single nucleotide polymorphisms (SNPs) putatively selected for malaria resistance are associated with susceptibility to leprosy across Brazil (Manaus–North; Salvador–Northeast; Rondonópolis–Midwest and Rio de Janeiro–Southeast) and with tuberculosis in Mozambique. Haplotype T/G/G (rs1052176/rs4971072/rs11264359) was associated with leprosy susceptibility in Rio de Janeiro (OR = 2.46, p = 0.00001) and Salvador (OR = 1.57, p = 0.04), and with tuberculosis in Mozambique (OR = 1.52, p = 0.07). This haplotype downregulates PKLR expression in nerve and skin, accordingly to GTEx, and might subtly modulate ferritin and haptoglobin levels in serum. Furthermore, we observed genetic signatures of positive selection in the HCN3 gene (xpEHH>2 –recent selection) in Europe but not in Africa, involving 6 SNPs which are PKLR/HCN3 eQTLs. However, this evidence was not corroborated by the other tests (FST, Tajima’s D and iHS). Altogether, we provide evidence that a common PKLR locus in Africans contribute to mycobacterial susceptibility in African descent populations and also highlight, for first, PKLR as a susceptibility gene for leprosy and TB.

Characterization of Anopheles stephensi Odorant Receptor 8, an Abundant Component of the Mouthpart Chemosensory Transcriptome.

Simple SummaryHuman malaria is transmitted by mosquitoes in the genus Anopheles—particularly species that prefer to feed on humans. The mosquito’s sense of smell drives this preference; however, most studies have focused on species native to Sub-Saharan Africa. Malaria vectors in other parts of the world may use different odorants to choose hosts. We, therefore, focused on Anopheles stephensi, the south Asian malaria mosquito, in this study. Mosquitoes have different organs specialized for odor perception, such as the antennae; however, we focused on the mouthparts (primarily the maxillary palp and labella) in this study. We used the RNAseq technique to determine which odor receptors are present in the mouthparts and then focused on one of these receptors: Or8. Using a technique known as the Drosophila empty neuron system, we tested this receptor’s ability to detect different odorants, particularly chemicals emitted by humans. This receptor in An. stephensi detected similar odors to a homologous receptor in an African species, Anopheles gambiae, with the exception of the chemical sulcatone. This chemical is an important attractant in other disease-transmitting mosquitoes and suggests that different mosquito species may be using odors differently to find hosts. Several mosquito species within the genus Anopheles are vectors for human malaria, and the spread of this disease is driven by the propensity of certain species to feed preferentially on humans. The study of olfaction in mosquitoes is important to understand dynamics of host-seeking and host-selection; however, the majority of these studies focus on Anopheles gambiae or An. coluzzii, both vectors of malaria in Sub-Saharan Africa. Other malaria vectors may recognize different chemical cues from potential hosts; therefore, in this study, we investigated An. stephensi, the south Asian malaria mosquito. We specifically focused on the mouthparts (primarily the maxillary palp and labella) that have been much less investigated compared to the antennae but are also important for host-seeking. To provide a broad view of chemoreceptor expression, RNAseq was used to examine the transcriptomes from the mouthparts of host-seeking females, blood-fed females, and males. Notably, AsOr8 had a high transcript abundance in all transcriptomes and was, therefore, cloned and expressed in the Drosophila empty neuron system. This permitted characterization with a panel of odorants that were selected, in part, for their presence in the human odor profile. The responsiveness of AsOr8 to odorants was highly similar to An. gambiae Or8 (AgOr8), except for sulcatone, which was detected by AsOr8 but not AgOr8. Subtle differences in the receptor sensitivity to specific odorants may provide clues to species- or strain-specific approaches to host-seeking and host selection. Further exploration of the profile of An. stephensi chemosensory proteins may yield a better understanding of how different malaria vectors navigate host-finding and host-choice.

CRISPR-mediated knock-in of transgenes into the malaria vector Anopheles funestus.

The ability to introduce mutations, or transgenes, of choice to precise genomic locations has revolutionized our ability to understand how genes and organisms work. In many mosquito species that are vectors of various human diseases, the advent of CRISPR genome editing tools has shed light on basic aspects of their biology that are relevant to their efficiency as disease vectors. This allows a better understanding of how current control tools work and opens up the possibility of novel genetic control approaches, such as gene drives, that deliberately introduce genetic traits into populations. Yet for the Anopheles funestus mosquito, a significant vector of malaria in sub-Saharan Africa and indeed the dominant vector species in many countries, transgenesis has yet to be achieved. We describe herein an optimized transformation system based on the germline delivery of CRISPR components that allows efficient cleavage of a previously validated genomic site and preferential repair of these cut sites via homology-directed repair (HDR), which allows the introduction of exogenous template sequence, rather than end-joining repair. The rates of transformation achieved are sufficiently high that it should be able to introduce alleles of choice to a target locus, and recover these, without the need to include additional dominant marker genes. Moreover, the high rates of HDR observed suggest that gene drives, which employ an HDR-type mechanism to ensure their proliferation in the genome, may be well suited to work in A. funestus.

Stable high-density and maternally inherited Wolbachia infections in Anopheles moucheti and Anopheles demeilloni mosquitoes

SummaryWolbachia, a widespread bacterium that can reduce pathogen transmission in mosquitoes, has recently been reported to be present in Anopheles (An.) species. In wild populations of the An. gambiae complex, the primary vectors of Plasmodium malaria in Sub-Saharan Africa, Wolbachia DNA sequences at low density and infection frequencies have been detected. As the majority of studies have used highly sensitive nested PCR as the only method of detection, more robust evidence is required to determine whether Wolbachia strains are established as endosymbionts in Anopheles species. Here, we describe high-density Wolbachia infections in geographically diverse populations of An. moucheti and An. demeilloni. Fluorescent in situ hybridization localized a heavy infection in the ovaries of An. moucheti, and maternal transmission was observed. Genome sequencing of both Wolbachia strains obtained genome depths and coverages comparable to those of other known infections. Notably, homologs of cytoplasmic incompatibility factor (cif) genes were present, indicating that these strains possess the capacity to induce the cytoplasmic incompatibility phenotype, which allows Wolbachia to spread through host populations. These strains should be further investigated as candidates for use in Wolbachia biocontrol strategies in Anopheles aiming to reduce the transmission of malaria.

Advances and opportunities in malaria population genomics.

Almost 20 years have passed since the first reference genome assemblies were published for Plasmodium falciparum, the deadliest malaria parasite, and Anopheles gambiae, the most important mosquito vector of malaria in sub-Saharan Africa. Reference genomes now exist for all human malaria parasites and nearly half of the ~40 important vectors around the world. As a foundation for genetic diversity studies, these reference genomes have helped advance our understanding of basic disease biology and drug and insecticide resistance, and have informed vaccine development efforts. Population genomic data are increasingly being used to guide our understanding of malaria epidemiology, for example by assessing connectivity between populations and the efficacy of parasite and vector interventions. The potential value of these applications to malaria control strategies, together with the increasing diversity of genomic data types and contexts in which data are being generated, raise both opportunities and challenges in the field. This Review discusses advances in malaria genomics and explores how population genomic data could be harnessed to further support global disease control efforts.

Malaria prevention and treatment awareness and practice among patent medicine vendors (PMVs) in Gombe Metropolis, Nigeria

The ravaging consequences of Malaria in Sub-Saharan Africa (SSA) have been a subject of serious concern to every stakeholder. Literature and anecdotal evidence shows that around 60% of Nigerians seek fever treatment from Patent Medicine Vendors (PMVs) despite the limited formal dispensing knowledge most possess. This study attempts to establish a base line of knowledge, attitude and practices of Malaria control among PMVs in Gombe Metropolis, North Eastern Nigeria. The study was a descriptive cross sectional survey based on structured questionnaires used to collect relevant information from 109 PMVs selected by purposive sampling technique. The result show that 85.3% of the participants in this study correctly identified fever or high body temperature as the common sign of uncomplicated (UC) Malaria, while 70.6% recognized convulsion as one of the main symptoms of severe Malaria. Furthermore, 86.2% of the PMVs also knew that sleeping inside treated nets constitute one of the best ways to prevent Malaria. In the same vein, awareness of change in Malaria treatment policy from monotherapy to Artemisinin based combination therapy (ACT) was high (73.3%) among them. However, those PMVs that had ever undergone some degree of drug dispensing training exhibited a significantly higher level of awareness of change in malaria treatment policy (X2 =17.903, P = 0.000). Although 85.3% of PMVs frequently recommend Arthemeter Lumefantrine (AL) as treatment of uncomplicated Malaria, only 39.4% of the participants would refer severe malaria cases. Even though most Malaria control awareness and practice variables were found to be fairly good among the participants, it is clear from the study that there is the need for enhanced training, monitoring and supervision by the relevant authorities so as to fully harness the vast potential in PMVs.

A Scoping Review of Selected Studies on Predictor Variables Associated with the Malaria Status among Children under Five Years in Sub-Saharan Africa.

Background/Purpose: In recent times, Sub-Saharan Africa (SSA) had been rated by the World Health Organization (WHO) as the most malaria-endemic region in the world. Evidence synthesis of the factors associated with malaria among children aged under-five in SSA is urgently needed. This would help to inform decisions that policymakers and executors in the region need to make for the effective distribution of scarce palliative resources to curb the spread of the illness. This scoping review is aimed at identifying studies that have used multivariate classical regression analysis to determine the predictors associated with malaria among children under five years old in SSA. Methods/Design: The search terms followed population, intervention, comparator, outcome, timing, setting (PICOTS), and were used in searching through the following databases: PubMed, MEDLINE, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Scopus, and Measure DHS. The databases were searched for published articles from January 1990 to December 2020. Results: Among the 1154 studies identified, only thirteen (13) studies met the study’s inclusion criteria. Narrative syntheses were performed on the selected papers to synchronize the various predictors identified. Factors ranging from child-related (age, birth order and use of a bed net), parental/household-related (maternal age and education status, household wealth index) and community-related variables (community wealth status, free bed net distribution) were some of the identified significant predictors. Conclusions: It is timely to have a synthesis of predictors that influence the malaria status of children under-five in SSA. The outcome of the review will increase the knowledge of the epidemiology of morbidity that will form the basis for designing efficient and cost-effective distribution of palliatives and control of malaria in SSA.

A minimal 3D model of mosquito flight behaviour around the human baited bed net

BackgroundAdvances in digitized video-tracking and behavioural analysis have enabled accurate recording and quantification of mosquito flight and host-seeking behaviours, facilitating development of individual (agent) based models at much finer spatial scales than previously possible.MethodsQuantified behavioural parameters were used to create a novel virtual testing model, capable of accurately simulating indoor flight behaviour by a virtual population of host-seeking mosquitoes as they interact with and respond to simulated stimuli from a human-occupied bed net. The model is described, including base mosquito behaviour, state transitions, environmental representation and host stimulus representation.ResultsIn the absence of a bed net and human host bait, flight distribution of the model population was relatively uniform throughout the arena. Introducing an unbaited untreated bed net induced a change in distribution with an increase in landing events on the net surface, predominantly on the sides of the net. Adding the presence of a simulated human bait dramatically impacted flight distribution patterns, exploratory foraging and, the number and distribution of landing positions on the net, which were determined largely by the orientation of the human within. The model replicates experimental results with free-flying living mosquitoes at human-occupied bed nets, where contact occurs predominantly on the top surface of the net. This accuracy is important as it quantifies exposure to the lethal insecticide residues that may be unique to the net roof (or theoretically any other surface). Number of net contacts and height of contacts decreased with increasing attractant dispersal noise.ConclusionsResults generated by the model are an accurate representation of actual mosquito behaviour recorded at and around a human-occupied bed net in untreated and insecticide-treated nets. This fine-grained model is highly flexible and has significant potential for in silico screening of novel bed net designs, potentially reducing time and cost and accelerating the deployment of new and more effective tools for protecting against malaria in sub-Saharan Africa.

Accessing the syndemic of COVID-19 and malaria intervention in Africa

BackgroundThe pandemic of the coronavirus disease 2019 (COVID-19) has caused substantial disruptions to health services in the low and middle-income countries with a high burden of other diseases, such as malaria in sub-Saharan Africa. The aim of this study is to assess the impact of COVID-19 pandemic on malaria transmission potential in malaria-endemic countries in Africa.MethodsWe present a data-driven method to quantify the extent to which the COVID-19 pandemic, as well as various non-pharmaceutical interventions (NPIs), could lead to the change of malaria transmission potential in 2020. First, we adopt a particle Markov Chain Monte Carlo method to estimate epidemiological parameters in each country by fitting the time series of the cumulative number of reported COVID-19 cases. Then, we simulate the epidemic dynamics of COVID-19 under two groups of NPIs: (1) contact restriction and social distancing, and (2) early identification and isolation of cases. Based on the simulated epidemic curves, we quantify the impact of COVID-19 epidemic and NPIs on the distribution of insecticide-treated nets (ITNs). Finally, by treating the total number of ITNs available in each country in 2020, we evaluate the negative effects of COVID-19 pandemic on malaria transmission potential based on the notion of vectorial capacity.ResultsWe conduct case studies in four malaria-endemic countries, Ethiopia, Nigeria, Tanzania, and Zambia, in Africa. The epidemiological parameters (i.e., the basic reproduction number R_0 and the duration of infection D_I) of COVID-19 in each country are estimated as follows: Ethiopia (R_0=1.57, D_I=5.32), Nigeria (R_0=2.18, D_I=6.58), Tanzania (R_0=2.47, D_I=6.01), and Zambia (R_0=2.12, D_I=6.96). Based on the estimated epidemiological parameters, the epidemic curves simulated under various NPIs indicated that the earlier the interventions are implemented, the better the epidemic is controlled. Moreover, the effect of combined NPIs is better than contact restriction and social distancing only. By treating the total number of ITNs available in each country in 2020 as a baseline, our results show that even with stringent NPIs, malaria transmission potential will remain higher than expected in the second half of 2020.ConclusionsBy quantifying the impact of various NPI response to the COVID-19 pandemic on malaria transmission potential, this study provides a way to jointly address the syndemic between COVID-19 and malaria in malaria-endemic countries in Africa. The results suggest that the early intervention of COVID-19 can effectively reduce the scale of the epidemic and mitigate its impact on malaria transmission potential.

Malaria interventions and control programes in Sub-Saharan Africa: A narrative review

Abstract: Malaria transmission and prevalence involves a triangular web of interactions between man, vector, and the environment. Any meaningful effort in malaria control, elimination and or eradication should target weakening and or breaking the forces of interactions within the triangle. In sub-Saharan Africa, effective malaria control programme is encumbered by myriad of challenges. The unabated burden of malaria could be ascribed to efficient malaria vectors with strong niche for ecological expression that maintain high levels of transmission at all seasons. Parasite genotypic heterogeneity, multiple expressions of traits of adaptations to parasitism and unpredictable behavioural changes are the smart ways the infectious agent thrives, persists and expresses ecological niche with scaring symphony. Environmental factors and climatic changes, population movement, deteriorated socioeconomic situation, lack of access to effective and timely antimalarial treatment, use of sub-standard and or fake anti-malarial drugs, self medication and non-compliance to drug dosage are the galvanizing factors to poor intervention outcomes. Above all, for ages, in most settings and communities, there is lack of knowledge regarding the causative agent of malaria. Diversionary factors and misconceptions such as eating too much palm oil, standing in the sun, drinking too much of alcohol, jinxing and witchcraft attacks are brands of porous perceptions on causes and risk factors of malaria. And if a thousand and one sophisticated strategies are put in place to eliminate malaria in sub-Saharan Africa where indigenous and factorial perceptions with rhetorical contrast of ideas hold sway, then, a predictable defeated performance is the expected result. For the sustenance of the gains already recorded in the fight against malaria in sub-Saharan Africa, the role of the community as a strong partnership for change cannot be underestimated.

COVID-19 and malaria in sub-saharan Africa: Holistic diagnostic approaches may promote effective clinical case management

Since the start of 2020 the rapidly escalating number of deaths from confirmed cases of Coronavirus disease (COVID)-19 has become a major global public health concern. With the existing significant burden that malaria poses in sub-Saharan Africa, it is clear that in this low-income region the cumulative effects of SARS-CoV-2 and Plasmodium infections will devastate already fragile national economies. In turn, this will have a severely deleterious impact on under-resourced, overstretched and overwhelmed health care systems. The similarities in the clinical signs and symptoms of these two febrile diseases and the availability of very few COVID-19 molecular diagnostic centres might contribute significantly to the difficulties experienced in the sustainable management of these twin public health threats. Here, decentralization of validated rapid diagnostic kits for parallel testing of suspected cases of COVID-19 and malaria in health care centres is described. We argue that for both urban populations and underserved rural communities in sub-Saharan Africa the use of malaria and COVID-19 rapid tests as a dual holistic diagnostic approach in patient care settings may promote more effective control and facilitate appropriate treatment of each disease.

Endemic Burkitt lymphoma: a complication of asymptomatic malaria in sub-Saharan Africa based on published literature and primary data from Uganda, Tanzania, and Kenya

BackgroundEndemic Burkitt lymphoma (eBL) is an aggressive B cell non-Hodgkin lymphoma associated with antigenic stimulation from Plasmodium falciparum malaria. Whether eBL risk is related to malaria parasite density is unknown. To address this issue, children with eBL, asymptomatic and clinical malaria, as a surrogate of malaria parasite density, were assessed.MethodsMalaria-related laboratory results (parasite density, haemoglobin, platelet count, and white cell count [WBC]) count) were compiled for 4019 eBL cases and 80,532 subjects evaluated for asymptomatic malaria or clinical malaria (severe malaria anaemia, hyperparasitaemia, cerebral malaria, malaria prostration, moderate malaria, and mild malaria) in 21 representative studies published in Africa (mostly East Africa) and 850 eBL cases and 2878 controls with primary data from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) case–control study in Uganda, Tanzania, and Kenya. The average values of malaria-related laboratory results were computed by condition and trends across single-year age groups were assessed using regression and spline models.ResultsOverall, malaria infection or malaria was diagnosed in 37,089 of children compiled from the literature. Children with eBL and asymptomatic parasitaemia/antigenaemia, but not those with clinical malaria, were closest in their mean age (age 7.1–7.2 vs. 7.4–9.8 years), haemoglobin level (10.0–10.4 vs. 11.7–12.3 g/dL), malaria parasite density (2800 vs. 1827–7780 parasites/µL), platelet count (347,000–353,000 vs. 244,000–306,000 platelets/µL), and WBC count (8180–8890 vs. 7100–7410 cells/µL). Parasite density in these two groups peaked between four to five years, then decreased steadily thereafter; conversely, haemoglobin showed a corresponding increase with age. Children with clinical malaria were markedly different: all had an average age below 5 years, had dramatically elevated parasite density (13,905–869,000 parasites/µL) and dramatically decreased platelet count (< 159,000 platelets/µL) and haemoglobin (< 7 g/dL).ConclusionseBL and asymptomatic parasitaemia/antigenaemia, but not clinical malaria, were the most similar conditions with respect to mean age and malaria-related laboratory results. These results suggest that children with asymptomatic parasitaemia/antigenaemia may be the population at risk of eBL.

Mobile Laboratory Reveals the Circulation of Dengue Virus Serotype I of Asian Origin in Medina Gounass (Guediawaye), Senegal.

With the growing success of controlling malaria in Sub-Saharan Africa, the incidence of fever due to malaria is in decline, whereas the proportion of patients with non-malaria febrile illness (NMFI) is increasing. Clinical diagnosis of NMFI is hampered by unspecific symptoms, but early diagnosis is a key factor for both better patient care and disease control. The aim of this study was to determine the arboviral aetiologies of NMFI in low resource settings, using a mobile laboratory based on recombinase polymerase amplification (RPA) assays. The panel of tests for this study was expanded to five arboviruses: dengue virus (DENV), zika virus (ZIKV), yellow fever virus (YFV), chikungunya virus (CHIKV), and rift valley fever virus (RVFV). One hundred and four children aged between one month and 115 months were enrolled and screened. Three of the 104 blood samples of children <10 years presented at an outpatient clinic tested positive for DENV. The results were confirmed by RT-PCR, partial sequencing, and non-structural protein 1 (NS1) antigen capture by ELISA (Biorad, France). Phylogenetic analysis of the derived DENV-1 sequences clustered them with sequences of DENV-1 isolated from Guangzhou, China, in 2014. In conclusion, this mobile setup proved reliable for the rapid identification of the causative agent of NMFI, with results consistent with those obtained in the reference laboratory’s settings.

Spatiotemporal analysis of insecticide-treated net use for children under 5 in relation to socioeconomic gradients in Central and East Africa

BackgroundInsecticide-treated net (ITN) use is the core intervention among the strategies against malaria in sub-Saharan Africa (SSA) and the percentage of ITN ownership has increased from 47% in 2010 to 72% in 2017 across countries in SSA. Regardless of this massive expansion of ITN distribution, considerable gap between ownership and use of ITNs has been reported. Using data from more than 100,000 households in Central and East Africa (CEA) countries, the main aim of this study was to identify barriers associated with low ITN use and conduct geospatial analyses to estimate numbers and locations of vulnerable children living in areas with high malaria and low ITN use.MethodsMain sources of data for this study were the Demographic and Health Surveys and Malaria Indicator Surveys conducted in 11 countries in CEA. Logistic regression models for each country were built to assess the association between ITN ownership or ITN use and several socioeconomic and demographic variables. A density map of children under 5 living in areas at high-risk of malaria and low ITN use was generated to estimate the number of children who are living in these high malaria burden areas.ResultsResults obtained suggest that factors such as the number of members in the household, total number of children in the household, education and place of residence can be key factors linked to the use of ITN for protecting children against malaria in CEA. Results from the spatiotemporal analyses found that although total rates of ownership and use of ITNs across CEA have increased up to 70% and 48%, respectively, a large proportion of children under 5 (19,780,678; 23% of total number of children) still lives in high-risk malaria areas with low use of ITNs.ConclusionThe results indicate that despite substantial progress in the distribution of ITNs in CEA, with about 70% of the households having an ITN, several socioeconomic factors have compromised the effectiveness of this control intervention against malaria, and only about 48% of the households protect their children under 5 with ITNs. Increasing the effective ITN use by targeting these factors and the areas where vulnerable children reside can be a core strategy meant to reducing malaria transmission.

The dance of power and trust-exploring micro-foundational dimensions in the development of global health partnership

The global health system has significantly evolved over the last 30 years, particularly since the UN Millennium Declaration in 2000. The transformation in global healthcare partnerships has been most visible in the area of neglected tropical diseases, where technological innovation is directly linked to social change. Numerous strategic partnerships between different actors, including pharmaceutical companies, global and national health institutions and philanthropic organizations and disease specific foundations populate the landscape of neglected tropical diseases and yet, we know little on relational and structural aspects underpinning the partnerships. Our research uses a rich longitudinal case study – a tripartite public-private partnership formed between a global health organization, a major pharmaceutical company and a research university to develop a new drug for the treatment of malaria in Sub-Saharan Africa. Development of new drugs is central to attain social change in a poverty stricken region. We adopt a micro-foundational perspective in analyzing strategic choices made by the partnership's Product Development Team (PDT) and unravel the dynamic interplay between power–trust relationship in such strategic business partnerships.

Interactions Between Antenatal Sulfadoxine-Pyrimethamine, Drug-Resistant Plasmodium falciparum Parasites, and Delivery Outcomes in Malawi.

Sulfadoxine-pyrimethamine (SP) is used as intermittent preventive therapy in pregnancy (IPTp) for malaria in sub-Saharan Africa. The resistance marker dhps A581G has been associated with reduced IPTp-SP efficacy and enhanced morbidity in SP recipients. We measured SP-resistance allele frequencies in Malawian women participating in a trial comparing IPTp with SP against intermittent screening by rapid diagnostic tests (ISTp). We genotyped polymerase chain reaction-detected parasites using deep sequencing of SP-resistance alleles. Among 125 placental infections, A581G-bearing parasites were associated with reduced birth weight (mean difference [MD], 252 g; 95% confidence interval [CI], 46-457; P = .017). Relative to ISTp, IPTp-SP was associated with higher birth weights in women with wild-type parasites (MD, 116 g; 95% CI, -40 to 272; P = .142) and lower birth weights in women with A581G-bearing parasites (MD, 192 g; 95% CI, -264 to 648; P = .385) (Pinteraction = .033). Similar associations were noted on gestational age (Pinteraction = .075). Amongst only IPTp-SP recipients, relative to women who last received SP > 4 weeks before delivery, recent SP receipt was associated with lower birth weight in women with wild-type parasites (MD, 118 g; 95% CI, -376 to 139; P = .361) and higher birth weight in women with A581G-bearing parasites (MD, 783 g; 95% CI, -20 to 1586; P = .054) (Pinteraction = .005). The effectiveness in birth weight of IPTp-SP is compromised by A581G-bearing parasites, but there was no evidence that the adverse effects of these parasites are exacerbated by antenatal SP. www.isrctn.com/ISRCTN69800930.

Genetic analysis and population structure of the Anopheles gambiae complex from different ecological zones of Burkina Faso

The Anopheles gambiae complex (Diptera: Culicidae) is the most important vector for malaria in Sub-Saharan Africa, besides other vectors such as Anopheles funestus. Malaria vector control should encompass specific identification, genetic diversity and population structure of An. gambiae to design vector control strategies.The aim of this study was to determine the distribution of sibling species of the An. gambiae complex according to climatic regions related to cotton-growing or cotton-free areas by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Then, variation in mitochondrial cytochrome c oxidase 1 (COI) was used to assess the genetic structure within and between populations from our selected ecological zones.At the sibling species level, the following proportions were found across all samples (n = 180): An. coluzzii 65.56%, An. gambiae stricto sensu (s.s). 21.11%, and An. arabiensis 3.33%. Hybrids between An. gambiae s.s. and An. coluzzii (7.78%) and hybrids between An. coluzzii and An. arabiensis (2.22%) were found. The phylogenetic tree and Integer Neighbour-Joining (IntNJ) haplotype network did not reveal any distinct genetic structure pattern related to climatic or agricultural conditions in Burkina Faso. The Fst (Wright's F-statistic) values close to zero showed a free gene flow and no differentiation in An. gambiae complex populations. Furthermore, neutrality indices calculated by Tajima's D, Fu and Li's D⁎, Fu and Li's F⁎, Fu's Fs tests suggested an excess of rare mutations in the populations.Overall, variation in the proportions of An. gambiae s.s., An. coluzzii and An. arabiensis was found according to climatic regions, but COI analysis did not evidence any population structuring of the An. gambiae complex. These scientific contributions can be used as a basis for further in-depth study of the genetic diversity of the An. gambiae complex for epidemiological risk assessment of malaria in Burkina Faso.

All Nets are Equal, But Some Nets are More Equal Than Others

Much of the dramatic decline in malaria in sub-Saharan Africa since 2000 is due to the massive investment in long-lasting insecticide treated nets (LLIN). According to the latest figures from the World Health Organization (WHO), over half of Africa's population now has access to LLIN, increasing from 33% in 2010 to 57% in 2019 (WHO 2019). In 2018 alone, 197 million LLINs were delivered to Africa by manufacturers. Despite this, LLIN coverage has improved only marginally since 2015. The malaria burden worldwide has fallen only slightly from an estimated 231 million cases of malaria in 2017 to 228 million in 2018, and is at a standstill in Africa. WHO policy is to assess candidate 2nd-in-class products for entomological efficacy only. Due to the significant variation in the specifications of the candidates, to generate the required assurance of comparative performance to 1st in class, WHO has designed a non-inferiority trial design to demonstrate whether each candidate 2nd-in-class test product is no worse in experimental hut trials.