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Background: As South Africa strives to achieve malaria elimination by 2018 (zero local cases) the country needs to strengthen its disease surveillance system by reducing the timeliness from case diagnosis to notification of key stakeholders in the malaria programme. This study evaluated the feasibility of a 24-h mobile reporting system, designed for speeding up malaria notifications, from primary healthcare facilities to district, provincial, and national malaria programmes in South Africa. Methods: A prospective descriptive study utilizing primary data collected from structured interviews with healthcare workers in public healthcare facilities was used to compare two reporting systems (24-h mobile reporting system and the paper-based reporting system) in malaria endemic provinces (Limpopo, Mpumalanga and KwaZulu-Natal). Data on completeness of reporting, simplicity, user acceptability and technical limitations were analysed. A Wilcoxon signed-rank test was used to compare the time difference between the two reporting systems. Results: There were 1819 cases of malaria reported through the paper-based system, and 63.2% (1149) of those cases were also reported through the 24-h mobile reporting system. Out of the 272 healthcare workers who were interviewed, 40% (108) had seen malaria patients and reported a case through the 24-h mobile reporting system. The median time for cases to be reported through the 24-h mobile reporting system was significantly shorter at < 1 day (range < 1 to 31 days) compared to the paper-based system at 3 days (range 2 to > 39 days) (p < 0.001). It was found that 26% (28) were able to use the system and send reports within 2 min, 94% (256) were willing to continue to use the system. Of the 108 healthcare workers who reported a case, 18.5% (20) experienced network challenges. Conclusions: The 24-h mobile reporting system is user friendly and trained healthcare workers are willing to use the system, despite network limitations. The 24-h mobile reporting system reduces the time required for diagnosed cases to be notified by the health care facility to district, provincial and national levels. The 24-h mobile reporting system is a feasible option for malaria notification in South Africa and will assist with early detection of malaria outbreaks. [ABSTRACT FROM AUTHOR]

Background: In 2019, an estimated 409,000 people died of malaria and most of them were young children in sub-Saharan Africa. In a bid to combat malaria epidemics, several technological innovations that have contributed significantly to malaria response have been developed across the world. This paper presents a systematized review and identifies key technological innovations that have been developed worldwide targeting different areas of the malaria response, which include surveillance, microplanning, prevention, diagnosis and management. Methods: A systematized literature review which involved a structured search of the malaria technological innovations followed by a quantitative and narrative description and synthesis of the innovations was carried out. The malaria technological innovations were electronically retrieved from scientific databases that include PubMed, Google Scholar, Scopus, IEEE and Science Direct. Additional innovations were found across grey sources such as the Google Play Store, Apple App Store and cooperate websites. This was done using keywords pertaining to different malaria response areas combined with the words "innovation or technology" in a search query. The search was conducted between July 2021 and December 2021. Drugs, vaccines, social programmes, and apps in non-English were excluded. The quality of technological innovations included was based on reported impact and an exclusion criterion set by the authors. Results: Out of over 1000 malaria innovations and programmes, only 650 key malaria technological innovations were considered for further review. There were web-based innovations (34%), mobile-based applications (28%), diagnostic tools and devices (25%), and drone-based technologies (13%. Discussion and conclusion: This study was undertaken to unveil impactful and contextually relevant malaria innovations that can be adapted in Africa. This was in response to the existing knowledge gap about the comprehensive technological landscape for malaria response. The paper provides information that countries and key malaria control stakeholders can leverage with regards to adopting some of these technologies as part of the malaria response in their respective countries. The paper has also highlighted key drivers including infrastructural requirements to foster development and scaling up of innovations. In order to stimulate development of innovations in Africa, countries should prioritize investment in infrastructure for information and communication technologies and also drone technologies. These should be accompanied by the right policies and incentive frameworks. [ABSTRACT FROM AUTHOR]

Gene drive mosquitoes are increasingly considered a potential transformational tool for vector control of malaria mosquitoes. As part of efforts to promote responsible research in this field, a number of guidance documents have been published by the World Health Organization, National Academies and expert groups. While virtually all recent guidance documents on gene drive research stress the importance of stakeholder engagement activities, no specific guidelines on implementing them have been established. Target Malaria, a not-for-profit research consortium developing a vector-control gene drive approach to eliminate malaria, has reflected on how its stakeholder engagement strategy translates engagement guidance documents into practice. The project analysed and addressed the tension between the context specificities and the international recommendations. The engagement strategy combines published recommendations for responsible gene drive research, information collected from the local context where the project operates and a set of principles guiding the choices made. This strategy was first developed during the early phases of the project's research, years ahead of any activities with gene drive mosquitoes in those countries of operations. These earlier activities, and their related engagement, allow the project to develop and adapt an engagement strategy appropriate for potential gene drive research in its field site countries. This paper offers a description of a stakeholder engagement strategy operationalization based on (1) adaptation to stakeholder preferences, (2) inclusiveness and (3) empowerment and accountability. The authors hope to offer concrete examples to support other projects with the development and implementation of their engagement strategies with particular attention to the co-development principle. [ABSTRACT FROM AUTHOR]

Background: More than 90% of malaria cases occur in Africa where the disease is transmitted by Anopheles gambiae and Anopheles arabiensis. This study evaluated the anti-mosquito properties of Juniperus virginiana (JVO) and Pelargonium roseum (PRO) essential oils (EOs) against larvae and adults of An. gambiae sensu lato (s.l.) from East Africa in laboratory and semi-field conditions. Methods: EOs was extracted from the aerial green parts of Asian herbs by hydrodistillation. Their constituents were characterized by gas chromatography-mass spectrometry (GC-MS). Larvicidal activities of JVO, PRO, and PRO components [citronellol (CO), linalool (LO), and geraniol (GO)] were investigated against An. gambiae sensu stricto (s.s.). The percentage of knockdown effects and mortality rates of all oils were also evaluated in the adults of susceptible An. gambiae s.s. and permethrin-resistant An. arabiensis. Results: GC-MS analyses identified major constituents of JVO (sabinene, dl-limonene, β-myrcene, bornyl acetate, and terpinen-4-ol) and PRO (citronellol, citronellyl formate, L-menthone, linalool, and geraniol). Oils showed higher larvicidal activity in the laboratory than semi-field trials. The LC50 values for JVO/PRO were computed as 10.82–2.89/7.13–0.9 ppm and 10.75–9.06/13.63–8.98 ppm in laboratory and semi-field environments, respectively at exposure time of 24–72 h. The percentage of knockdown effects of the oils were also greater in An. gambiae s.s. than in An. arabiensis. Filter papers impregnated with JVO (100 ppm) and PRO (25 ppm) displayed 100% mortality rates for An. gambiae s.s. and 3.75% and 90% mortality rates, for An. arabiensis populations, respectively. Each component of CO, LO, and GO exhibited 98.13%, 97.81%, and 87.5%, respectively, and a mixture of the PRO components indicated 94.69% adult mortality to permethrin-resistant An. arabiensis. Conclusions: The findings of this study show that PRO and its main constituents, compared to JVO, have higher anti-mosquito properties in terms of larvicidal, knockdown, and mortality when applied against susceptible laboratory and resistant wild populations of An. gambiae s.l. Consequently, these oils have the potential for the development of new, efficient, safe, and affordable agents for mosquito control. [ABSTRACT FROM AUTHOR]

The article presents findings of a research conducted on examining factors affecting access to health care for malaria in Africa. It focuses on attributes of patients and their communities that act as barriers to access, including education level, financial and cultural factors. It addresses the need to learn about provider characteristics that encourage patients to attend their health services.

Background: A malaria slide bank (MSB) is a useful asset for any malaria microscopy testing laboratory to have access to. However, it is not feasible for every country to have its own MSB. If countries are able to pool their resources, a regional MSB is a viable solution. This paper describes the methodology, costing and lessons learnt of establishing and maintaining an MSB over a 3-year period, for a Southern Africa Development Community region. Methods: A national reference laboratory in South Africa was granted funding for setting up the MSB; it possessed experienced staff and suitable resources. Two additional full-time personnel were employed to carry out the activities of this project. Strict protocols for donor/patient blood sample screening, smear preparation, mass staining, quality control and slide validation were followed. Slides from the MSB were used for training and proficiency testing purposes. The initial and recurrent yearly costs to set up and maintain the MSB were calculated. Results: Over 35 months, 154 batches (26,623 slides) were prepared; the majority were Plasmodium falciparum. Ninety-two percent (141/154) of batches passed internal quality control, and 89% (93/104) passed external validation. From these slides, two training slide sets and six proficiency testing slide sets were sent out. The initial year's cost to establish an MSB was calculated at approximately $165,000, and the recurrent year-on-year cost was $130,000. Conclusions: The key components for maintaining a high-quality MSB are consistent funding, competent staff and adherence to standardized protocols. Travel to malaria-endemic areas for access to non-falciparum malaria species, and dilution of P. falciparum blood to desired parasite densities, are extremely useful to ensure variety. The MSB created here supported multiple laboratories in eight countries, and has the potential to expand. [ABSTRACT FROM AUTHOR]

Malaria remains a major cause of morbidity and mortality in Africa, particularly in children under five years of age. Availability of effective anti-malarial drug treatment is a cornerstone for malaria control and eventual malaria elimination. Artemisinin-based combination therapy (ACT) is worldwide the first-line treatment for uncomplicated falciparum malaria, but the ACT drugs are starting to fail in Southeast Asia because of drug resistance. Resistance to artemisinins and their partner drugs could spread from Southeast Asia to Africa or emerge locally, jeopardizing the progress made in malaria control with the increasing deployment of ACT in Africa. The development of triple artemisinin-based combination therapy (TACT) could contribute to mitigating the risks of artemisinin and partner drug resistance on the African continent. However, there are pertinent ethical and practical issues that ought to be taken into consideration. In this paper, the most important ethical tensions, some implementation practicalities and preliminary thoughts on addressing them are discussed. The discussion draws upon data from randomized clinical studies using TACT combined with ethical principles, published literature and lessons learned from the introduction of artemisinin-based combinations in African markets. [ABSTRACT FROM AUTHOR]

Background: Human landing catches (HLC) are an entomological collection technique in which humans are used as attractants to capture medically relevant host-seeking mosquitoes. The use of this method has been a topic of extensive debate for decades mainly due to ethical concerns. Many alternatives to HLC have been proposed; however, no quantitative review and meta-analysis comparing HLC to outdoor alternative trapping methods has been conducted. Methods: A total of 58 comparisons across 12 countries were identified. We conducted a meta-analysis comparing the standardized mean difference of Anopheles captured by HLC and alternative traps. To explain heterogeneity, three moderators were chosen for analysis: trap type, location of study, and species captured. A meta-regression was fit to understand how the linear combination of moderators helped in explaining heterogeneity. The possibility of biased results due to publication bias was also explored. Results: Random-effects meta-analysis showed no statistically significant difference in the mean difference of Anopheles collected. Moderator analysis was conducted to determine the effects of trap type, geographical location of study, and the species of Anopheles captured. On average, tent-based traps captured significantly more Anopheles than outdoor HLC (95% CI: [−.9065, − 0.0544]), alternative traps in Africa captured on average more mosquitoes than outdoor HLC (95% CI: [− 2.8750, − 0.0294]), and alternative traps overall captured significantly more Anopheles gambiae s.l. than outdoor HLC (95% CI: [− 4.4613, − 0.2473]) on average. Meta-regression showed that up to 55.77% of the total heterogeneity found can be explained by a linear combination of the three moderators and the interaction between trap type and species. Subset analysis on An. gambiae s.l. showed that light traps specifically captured on average more of this species than HLC (95% CI: [− 18.3751, − 1.0629]). Publication bias likely exists. With 59.65% of studies reporting p-values less than 0.025, we believe there is an over representation in the literature of results indicating that alternative traps are superior to outdoor HLC. Conclusions: Currently, there is no consensus on a single "magic bullet" alternative to outdoor HLC. The diversity of many alternative trap comparisons restricts potential metrics for comparisons to outdoor HLC. Further standardization and specific question-driven trap evaluations that consider target vector species and the vector control landscape are needed to allow for robust meta-analyses with less heterogeneity and to develop data-driven decision-making tools for malaria vector surveillance and control. [ABSTRACT FROM AUTHOR]

A literature review for operational research on malaria control and elimination was conducted using the term 'malaria' and the definition of operational research (OR). A total of 15 886 articles related to malaria were searched between January 2008 and June 2013. Of these, 582 (3.7%) met the definition of operational research. These OR projects had been carried out in 83 different countries. Most OR studies (77%) were implemented in Africa south of the Sahara. Only 5 (1%) of the OR studies were implemented in countries in the pre-elimination or elimination phase. The vast majority of OR projects (92%) were led by international or local research institutions, while projects led by National Malaria Control Programmes (NMCP) accounted for 7.8%. With regards to the topic under investigation, the largest percentage of papers was related to vector control (25%), followed by epidemiology/transmission (16.5%) and treatment (16.3%). Only 19 (3.8%) of the OR projects were related to malaria surveillance. Strengthening the capacity of NMCPs to conduct operational research and publish its findings, and improving linkages between NMCPs and research institutes may aid progress towards malaria elimination and eventual eradication world-wide. [ABSTRACT FROM AUTHOR]

Background: The presence of counterfeits and sub-standards in African medicines market is a dramatic problem that causes many deaths each year. The increase of the phenomenon of pharmaceutical counterfeiting is due to the rise of the illegal market and to the impossibility to purchase branded high cost medicines. Methods: In this paper the results of a quality control on antimalarial tablet samples purchased in the informal market in Congo, Burundi and Angola are reported. The quality control consisted in the assay of active substance by means of validated liquid chromatographic methods, uniformity of mass determination, disintegration and dissolution tests. Moreover, a general evaluation on label and packaging characteristics was performed. Results: The results obtained on thirty antimalarial tablet samples containing chloroquine, quinine, mefloquine, sulphadoxine and pyrimethamine showed the presence of different kinds of problems: a general problem concerning the packaging (loose tablets, packaging without Producer name, Producer Country and sometimes without expiry date); low content of active substance (in one sample); different, non-declared, active substance (in one sample); sub-standard technological properties and very low dissolution profiles (in about 50% of samples). This last property could affect the bioavailability and bioequivalence in comparison with branded products and could be related to the use of different excipients in formulation or bad storage conditions. Conclusion: This paper evidences that the most common quality problem in the analysed samples appears to be the low dissolution profile. Here it is remarked that the presence of the right active substance in the right quantity is not a sufficient condition for a good quality drug. Dissolution test is not less important in a quality control and often evidences in vitro possible differences in therapeutic efficacy among drugs with the same active content. Dissolution profile can be dramatically affected by the choice of excipients in the oral solid formulation and, in many cases, is out of specifications due to the absence of formulation studies by producers of developing countries. [ABSTRACT FROM AUTHOR]

Background: Quality of artemisinin-based combination therapy (ACT) is important for ensuring malaria parasite clearance and protecting the efficacy of artemisinin-based therapies. The extent to which non quality-assured ACT (non-QAACT), or those not granted global regulatory approval, are available and used to treat malaria in endemic countries is poorly documented. This paper uses national and sub-national medicine outlet surveys conducted in eight study countries (Benin, Kinshasa and Kantanga [Democratic Republic of the Congo, DRC], Kenya, Madagascar, Nigeria, Tanzania, Uganda and Zambia) between 2009 and 2015 to describe the non-QAACT market and to document trends in availability and distribution of non-QAACT in the public and private sector. Results: In 2014/15, non-QAACT were most commonly available in Kinshasa (83%), followed by Katanga (53%), Nigeria (48%), Kenya (42%), and Uganda (33%). Non-QAACT accounted for 20% of the market share in the private sector in Kenya, followed by Benin and Uganda (19%), Nigeria (12%) and Zambia (8%); this figure was 27% in Katanga and 40% in Kinshasa. Public sector non-QAACT availability and distribution was much lower, with the exception of Zambia (availability, 85%; market share, 32%). Diverse generics and formulations were available, but non-QAACT were most commonly artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHA PPQ), in tablet formulation, imported, and distributed in urban areas at either pharmacies or drug stores. The number of unique manufacturers supplying non-QAACT to each country ranged from 9 in Uganda to 92 in Nigeria. Conclusions: Addressing the availability and distribution of non-QAACT will require effective private sector engagement and evidence-based strategies to address provider and consumer demand for these products. Given the variation in non-QAACT markets observed across the eight study countries, active efforts to limit registration, importation and distribution of non-QAACT must be tailored to the country context, and will involve addressing complex and challenging aspects of medicine registration, private sector pharmaceutical regulation, local manufacturing and drug importation. These efforts may be critical not only to patient health and safety, but also to effective malaria control and protection of artemisinin drug efficacy in the face of spreading resistance. [ABSTRACT FROM AUTHOR]

Background: Malaria continues to be a serious public health problem particularly in Africa. Many people infected with malaria do not access effective treatment due to high price. At the same time many individuals receiving malaria drugs do not suffer from malaria because of the common practice of presumptive diagnosis. A global subsidy on artemisinin-based combination therapy (ACT) has recently been suggested to increase access to the most effective malaria treatment. Methods: Following the recommendation by World Health Organization that parasitological testing should be performed before treatment and ACT prescribed to confirmed cases only, it is investigated in this paper if a subsidy on malaria rapid diagnostic tests (RDTs) should be incorporated. A model is developed consisting of a representative individual with fever suspected to be malaria, seeking care at a specialized drug shop where RDTs, ACT medicines, and cheap, less effective anti-malarials are sold. Assuming that the individual has certain beliefs of the accuracy of the RDT and the probability that the fever is malaria, the model predicts the diagnosis-treatment behaviour of the individual. Subsidies on RDTs and ACT are introduced to incentivize appropriate behaviour: choose an RDT before treatment and purchase ACT only if the test is positive. Results: Solving the model numerically suggests that a combined subsidy on both RDT and ACT is cost minimizing and improves diagnosis-treatment behaviour of individuals. For certain beliefs, such as low trust in RDT accuracy and strong belief that a fever is malaria, subsidization is not sufficient to incentivize appropriate behaviour. Conclusions: A combined subsidy on both RDT and ACT rather than a single subsidy is likely required to improve diagnosis-treatment behaviour among individuals seeking care for malaria in the private sector. [ABSTRACT FROM AUTHOR]

Background: In children with cerebral malaria (CM) admission blood lactate has previously guided intravenous fluid therapy and been validated as a prognostic biomarker associated with death. The usefulness of post-admission measurements of blood lactate in children with CM is less clear. The strength of association between blood lactate and neurological sequelae in CM survivors, as well as the optimal duration of post-admission measurements of blood lactate to identify children at higher risk of adverse outcomes is unknown. Methods: A retrospective cohort study of 1674 Malawian children with CM hospitalized from 2000 to 2018 who had blood lactate measurements every 6 h for the first 24 h after admission was performed. The strength of association between admission lactate or values measured at any time point in the first 24 h post-admission and outcomes (mortality and neurological morbidity in survivors) was estimated. The duration of time after admission that lactate remained a valid prognostic biomarker was assessed. Results: When lactate is analysed as a continuous variable, children with CM who have higher values at admission have a 1.05-fold higher odds (95% CI 0.99–1.11) of death compared to those with lower lactate values. Children with higher blood lactate at 6 h have 1.16-fold higher odds (95% CI 1.09–1.23) of death, compared to those with lower values. If lactate levels are dichotomized into hyperlactataemic (lactate > 5.0 mmol/L) or not, the strength of association between admission lactate and mortality increases (OR = 2.49, 95% CI 1.47–4.22). Blood lactate levels obtained after 18 h post-admission are not associated with outcomes. Similarly, the change in lactate concentrations through time during the first 24 h of hospital admission is not associated with outcomes. Blood lactate during hospitalization is not associated with adverse neurologic outcomes in CM survivors. Conclusions: In children with CM, blood lactate is associated with death but not neurologic morbidity in survivors. To comprehensively estimate prognosis, blood lactate in children with CM should be assessed at admission and for 18 h afterwards. [ABSTRACT FROM AUTHOR]

Background: Though Plasmodium vivax is the second most common malaria species to infect humans, it has not traditionally been considered a major human health concern in central Africa given the high prevalence of the human Duffy-negative phenotype that is believed to prevent infection. Increasing reports of asymptomatic and symptomatic infections in Duffy-negative individuals throughout Africa raise the possibility that P. vivax is evolving to evade host resistance, but there are few parasite samples with genomic data available from this part of the world. Methods: Whole genome sequencing of one new P. vivax isolate from the Democratic Republic of the Congo (DRC) was performed and used in population genomics analyses to assess how this central African isolate fits into the global context of this species. Results: Plasmodium vivax from DRC is similar to other African populations and is not closely related to the non-human primate parasite P. vivax-like. Evidence is found for a duplication of the gene PvDBP and a single copy of PvDBP2. Conclusion: These results suggest an endemic P. vivax population is present in central Africa. Intentional sampling of P. vivax across Africa would further contextualize this sample within African P. vivax diversity and shed light on the mechanisms of infection in Duffy negative individuals. These results are limited by the uncertainty of how representative this single sample is of the larger population of P. vivax in central Africa. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic malaria transmission has become a public health concern across malaria-endemic Africa including Ethiopia. Specifically, Plasmodium vivax is more efficient at transmitting earlier in the infection and at lower densities than Plasmodium falciparum. Consequently, a greater proportion of individuals infected with P. vivax can transmit without detectable gametocytaemia. Mass treatment of livestock with macrocyclic lactones (MLs), e.g., ivermectin and doramectin, was suggested as a complementary malaria vector tool because of their insecticidal effects. However, the effects of MLs on P. vivax in Anopheles arabiensis has not yet been fully explored. Hence, comparative in-vitro susceptibility and ex-vivo studies were conducted to evaluate the effects of ivermectin, doramectin and moxidectin sub-lethal concentrations on P. vivax oocyst development in An. arabiensis. Methods: The 7-day sub-lethal concentrations of 25% (LC25) and 5% (LC5) were determined from in-vitro susceptibility tests on female An. arabiensis in Hemotek® membrane feeding assay. Next, an ex-vivo study was conducted using P. vivax gametocytes infected patient's blood spiked with the LC25 and LC5 of the MLs. At 7-days post-feeding, each mosquito was dissected under a dissection stereo microscope, stained with 0.5% (w/v) mercurochrome solution, and examined for the presence of P. vivax oocysts. Statistical analysis was based on a generalized mixed model with binomially distributed error terms. Results: A 7-day lethal concentration of 25% (LC25, in ng/mL) of 7.1 (95% CI: [6.3;8.0]), 20.0 (95%CI:[17.8;22.5]) and 794.3 (95%CI:[716.4;1516.3]) were obtained for ivermectin, doramectin and moxidectin, respectively. Similarly, a lethal concentration of 5% (LC5, in ng/mL) of 0.6 (95% CI: [0.5;0.7]), 1.8 (95% CI:[1.6;2.0]) and 53.7 (95% CI:[ 48.4;102.5]) were obtained respectively for ivermectin, doramectin and moxidectin. The oocyst prevalence in treatment and control groups did not differ significantly (p > 0.05) from each other. Therefore, no direct effect of ML endectocides on P. vivax infection in An. arabiensis mosquitoes was observed at the sub-lethal concentration (LC25 and LC5). Conclusions: The effects of ivermectin and doramectin on malaria parasite is more likely via indirect effects, particularly by reducing the vectors lifespan and causing mortality before completing the parasite's sporogony cycle or reducing their vector capacity as it affects the locomotor activity of the mosquito. [ABSTRACT FROM AUTHOR]

Background: Decreased efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria has been previously reported in patients with sickle cell disease (SCD). The main purpose of this study was to investigate the in vitro susceptibility of isolates to dihydro-artemisinin (DHA) to provide a hypothesis to explain this treatment failure. Methods: Isolates were collected from patients attending health centres in Abidjan with uncomplicated P. falciparum malaria. The haemoglobin type has been identified and in vitro drug sensitivity tests were conducted with the ring stage assay and maturation inhibition assay. Results: 134 isolates were obtained. Parasitaemia and haemoglobin levels at inclusion were lower in patients with haemoglobin HbSS and HbSC than in patients with normal HbAA. After ex vivo RSA and drug inhibition assays, the lowest rate of parasitic growth was found with isolates from HbAS red cells. Conversely, a significantly higher survival rate of parasites ranging from 15 to 34% were observed in isolates from HbSS. Isolates with in vitro reduced DHA sensitivity correlate with lower RBC count and haematocrit and higher parasitaemia at inclusion compared to those with isolates with normal DHA sensitivity. However, this decrease of in vitro sensitivity to DHA was not associated with Kelch 13-Propeller gene polymorphism. Conclusion: This study highlights an in vitro decreased sensitivity to DHA, for isolates collected from HbSS patients, not related to the Pfkelch13 gene mutations. These results are in line with recent studies pointing out the role of the redox context in the efficacy of the drug. Indeed, SCD red cells harbour a highly different ionic and redox context in comparison with normal red cells. This study offers new insights into the understanding of artemisinin selective pressure on the malaria parasite in the context of haemoglobinopathies in Africa. [ABSTRACT FROM AUTHOR]

Background: The widespread use of pyrethroid insecticides in Africa has led to the development of strong resistance in Anopheles mosquitoes. Introducing new active ingredients can contribute to overcome this phenomenon and ensure the effectiveness of vector control strategies. Transfluthrin is a polyfluorinated pyrethroid whose structural conformation was thought to prevent its metabolism by cytochrome P450 monooxygenases in malaria vectors, thus representing a potential alternative for managing P450-mediated resistance occurring in the field. In this study, a controlled selection was used to compare the dynamics of resistance between transfluthrin and the widely used pyrethroid deltamethrin in the mosquito Anopheles gambiae. Then, the associated molecular mechanisms were investigated using target-site mutation genotyping and RNA-seq. Methods: A field-derived line of An. gambiae carrying resistance alleles at low frequencies was used as starting material for a controlled selection experiment. Adult females were selected across 33 generations with deltamethrin or transfluthrin, resulting in three distinct lines: the Delta-R line (selected with deltamethrin), the Transflu-R line (selected with transfluthrin) and the Tiassale-S line (maintained without selection). Deltamethrin and transfluthrin resistance levels were monitored in each selected line throughout the selection process, as well as the frequency of the L1014F kdr mutation. At generation 17, cross-resistance to other public health insecticides was investigated and transcriptomes were sequenced to compare gene transcription variations and polymorphisms associated with adaptation to each insecticide. Results: A rapid increase in resistance to deltamethrin and transfluthrin was observed throughout the selection process in each selected line in association with an increased frequency of the L1014F kdr mutation. Transcriptomic data support a broader response to transfluthrin selection as compared to deltamethrin selection. For instance, multiple detoxification enzymes and cuticle proteins were specifically over-transcribed in the Transflu-R line including the known pyrethroid metabolizers CYP6M2, CYP9K1 and CYP6AA1 together with other genes previously associated with resistance in An. gambiae. Conclusion: This study confirms that recurrent exposure of adult mosquitoes to pyrethroids in a public health context can rapidly select for various resistance mechanisms. In particular, it indicates that in addition to target site mutations, the polyfluorinated pyrethroid transfluthrin can select for a broad metabolic response, which includes some P450s previously associated to resistance to classical pyrethroids. This unexpected finding highlights the need for an in-depth study on the adaptive response of mosquitoes to newly introduced active ingredients in order to effectively guide and support decision-making programmes in malaria control. [ABSTRACT FROM AUTHOR]

Background: Attractive targeted sugar bait (ATSB) is a novel approach to vector control, offering an alternative mode of insecticide delivery via the insect alimentary canal, with potential to deliver a variety of compounds new to medical entomology and malaria control. Its potential to control mosquitoes was recently demonstrated in major field trials in Africa. The pyrrole chlorfenapyr is an insecticide new to malaria vector control, and through its unique mode of action—disruption of ATP mediated energy transfer in mitochondria—it may have direct action on energy transfer in the flight muscle cells of mosquitoes. It may also have potential to disrupt mitochondrial function in malarial parasites co-existing within the infected mosquito. However, little is known about the impact of such compounds on vector competence in mosquitoes responsible for malaria transmission. Methods: In this study, ATSBs containing chlorfenapyr insecticide and, as a positive control, the anti-malarial drugs artemether/lumefantrine (A/L) were compared for their effect on Plasmodium falciparum development in wild pyrethroid-resistant Anopheles gambiae sensu stricto (s.s.) and for their capacity to reduce vector competence. Female mosquitoes were exposed to ATSB containing either sublethal dose of chlorfenapyr (CFP: 0.025%) or concentrations of A/L ranging from 0.4/2.4 mg/ml to 2.4/14.4 mg/ml, either shortly before or after taking infective blood meals. The impact of their component compounds on the prevalence and intensity of P. falciparum infection were compared between treatments. Results: Both the prevalence and intensity of infection were significantly reduced in mosquitoes exposed to either A/L or chlorfenapyr, compared to unexposed negative control mosquitoes. The A/L dose (2.4/14.4 mg/ml) totally erased P. falciparum parasites: 0% prevalence of infection in female mosquitoes exposed compared to 62% of infection in negative controls (df = 1, χ2 = 31.23 p < 0.001). The dose of chlorfenapyr (0.025%) that killed < 20% females in ATSB showed a reduction in oocyte density of 95% per midgut (0.18/3.43 per midgut). Conclusion: These results are evidence that chlorfenapyr, in addition to its direct killing effect on the vector, has the capacity to block Plasmodium transmission by interfering with oocyte development inside pyrethroid-resistant mosquitoes, and through this dual action may potentiate its impact under field conditions. [ABSTRACT FROM AUTHOR]

Background: Cooperation between China and Africa is deepening, and business, trade, and people-to-people exchanges are growing closer together, especially in the infrastructure construction field. At the same time, malaria has become a serious health concern for Chinese construction workers in Africa, who are at increased risk of infection and complications due to lack of immunity and exposure to high-transmission environments. One of the biggest challenges in fighting malaria is their lack of knowledge and misinterpretations about the disease, which can impact their need for interventions, adherence to treatments, and health services. This study aims to determine the perception and interpretation of malaria among Chinese construction workers in sub-Saharan Africa. Methods: Semi-structured interviews were conducted with 20 Chinese construction workers in sub-Saharan Africa. Some early respondents initially made contact through two Chinese construction companies in Africa, while the rest of the participants were engaged via a snowball method by the early participants. NVivo10, a qualitative research data management software and a thematic approach, was used to analyze the data and create themes. In order to achieve the general study goals, an inductive content analysis was applied. Results: The study classified participants' perceptions and interpretations of malaria into four categories: flu-like malaria, the rumors of malaria, the hard-to-explain confusion about malaria, and the special interpretation of malaria. Conclusion: Malaria poses major health issues to Chinese construction workers in sub-Saharan Africa who lack immunity and live in an environment of high transmission. Their dearth of awareness and misunderstanding of malaria impacts their prevention and treatment behaviors and health outcomes. This study adopts qualitative methods to examine their perceptions and interpretations of malaria, which can serve as a source for future health management strategies. [ABSTRACT FROM AUTHOR]

Background: Malaria and dengue fever are the leading causes of acute, undifferentiated febrile illness. In Africa, misdiagnosis of dengue fever as malaria is a common scenario. Through a systematic review of the published literature, this study seeks to estimate the prevalence of dengue and malaria coinfection among acute undifferentiated febrile diseases in Africa. Methods: Relevant publications were systematically searched in the PubMed, Cochrane Library, and Google Scholar until May 19, 2023. A random-effects meta-analysis and meta-regression were used to summarize and examine the prevalence estimates. Results: Twenty-two studies with 22,803 acute undifferentiated febrile patients from 10 countries in Africa were included. The meta-analysis findings revealed a pooled prevalence of malaria and dengue coinfection of 4.2%, with Central Africa having the highest rate (4.7%), followed by East Africa (2.7%) and West Africa (1.6%). Continent-wide, Plasmodium falciparum and acute dengue virus coinfection prevalence increased significantly from 0.9% during 2008–2013 to 3.8% during 2014–2017 and to 5.5% during 2018–2021 (p = 0.0414). Conclusion: There was a high and increasing prevalence of malaria and acute dengue virus coinfection in Africa. Healthcare workers should bear in mind the possibility of dengue infection as a differential diagnosis for acute febrile illness, as well as the possibility of coexisting malaria and dengue in endemic areas. In addition, high-quality multicentre studies are required to verify the above conclusions. Protocol registration number: CRD42022311301. [ABSTRACT FROM AUTHOR]

Background The Affordable Medicines Facility - malaria (AMFm), implemented at national scale in eight African countries or territories, subsidized quality-assured artemisinin combination therapy (ACT) and included communication campaigns to support implementation and promote appropriate anti-malarial use. This paper reports private for-profit provider awareness of key features of the AMFm programme, and changes in provider knowledge of appropriate malaria treatment. Methods This study had a non-experimental design based on nationally representative surveys of outlets stocking anti-malarials before (2009/10) and after (2011) the AMFm roll-out. Results Based on data from over 19,500 outlets, results show that in four of eight settings, where communication campaigns were implemented for 5-9 months, 76%-94% awareness of the AMFm 'green leaf' logo, 57%-74% awareness of the ACT subsidy programme, and 52%- 80% awareness of the correct recommended retail price (RRP) of subsidized ACT were recorded. However, in the remaining four settings where communication campaigns were implemented for three months or less, levels were substantially lower. In six of eight settings, increases of at least 10 percentage points in private for-profit providers' knowledge of the correct first-line treatment for uncomplicated malaria were seen; and in three of these the levels of knowledge achieved at endline were over 80%. Conclusions The results support the interpretation that, in addition to the availability of subsidized ACT, the intensity of communication campaigns may have contributed to the reported levels of AMFm-related awareness and knowledge among private for-profit providers. Future subsidy programmes for anti-malarials or other treatments should similarly include communication activities. [ABSTRACT FROM AUTHOR]

Background: Malaria in pregnancy is one of the most common preventable causes of maternal and neonatal morbidity and mortality in sub-Saharan Africa. To prevent its adverse effects, such as maternal anaemia, placental parasitaemia and low birth weight (LBW) neonates, the World Health Organization recommends effective malaria case management, use of insecticide-treated bed nets and intermittent preventive therapy in pregnancy (IPTp). Sulphadoxine-pyrimethamine (SP) has been the standard for IPTp in several countries, but parasite resistance to SP is growing. Therefore, new IPTp therapies are urgently needed. One candidate being evaluated for IPTp is a fixed-dose combination of azithromycin and chloroquine (AZCQ). This paper describes the challenges and the innovative solutions implemented in designing and conducting a pivotal AZCQ-IPTp trial, sponsored by Pfizer Inc and co-funded by Pfizer Inc and the Medicines for Malaria Venture. Methods: The AZCQ-IPTp pivotal trial is a multicentre, multicountry, phase III, open-label, randomized superiority study of AZCQ-IPTp versus SP-IPTp in pregnant women of sub-Saharan Africa. The trial was designed to meet stringent regulatory agency scientific advice and IPTp policy makers' recommendations, and incorporates an innovative adaptive design to manage programme risk, maintain the operating characteristics of the study and optimize resources. The trial's novel composite primary endpoint is the proportion of participants with a suboptimal pregnancy outcome (abortion [≤28 weeks], stillbirths [>28 weeks], premature [<37 weeks] deliveries, LBW [<2,500 g] live neonates, missing neonatal birth weight data or loss to follow-up). The study employs a prospective group sequential design with three unblinded analyses when 50%, 70% and 100% of participants achieve the primary endpoint; the study team will remain blinded to the analyses until after the completion of the study. The number of participants randomized will be adaptive, based on the blinded review of the observed pooled primary endpoint data across the two treatment arms, when approximately 1,000 participants complete the primary endpoint assessments. Results: This study is ongoing and expected to complete in 2014. Conclusion: This report describes the unique challenges and innovative solutions implemented in designing and conducting this pivotal AZCQ-IPTp trial, which may serve as a prototype for future IPTp and other studies involving similar conditions. [ABSTRACT FROM AUTHOR]

Background: Community-delivered models have been widely used to reduce the burden of malaria. This review aimed to explore different community-delivered models and their relative effectiveness in terms of coverage and malaria-metric outcomes in order to inform the design and implementation of Community Health Worker (CHW) programmes for malaria control and elimination. Methods: A systematic review of studies investigating the impact of community-delivered models on coverage and malaria-metric (parasitaemia and hyperparasitaemia, malaria case and mortality, anaemia, and fever) outcomes compared to non- community-delivered models was undertaken by searching in five databases of published papers and grey literature databases. Data were extracted from studies meeting inclusion and quality criteria (assessed using relevant tools for the study design) by two independent authors. Meta-analyses were performed where there was sufficient homogeneity in effect and stratified by community-delivered models to assess the impact of each model on coverage and malaria-metric outcomes. Results: 28 studies were included from 7042 records identified. The majority of studies (25/28) were performed in high transmission settings in Africa and there was heterogeneity in the type of, and interventions delivered as part of the community-delivered models. Compared to non- community-delivered models, community-delivered models increased coverage of actual bed net usage (Relative Risk (RR) = 1.64 95% CI 1.39, 1.95), intermittent preventive treatment in pregnancy (RR = 1.36 95% CI 1.29, 1.44) and appropriate and timely treatment of febrile children, and improved malaria-metric outcomes such as malaria mortality (RR = 0.58 95% CI 0.52, 0.65). However, the considerable heterogeneity was found in the impact of community-delivered models in reducing, parasitaemia and hyperparasitaemia prevalence, anaemia incidence, fever prevalence and malaria caseload. Statistical comparisons of different community-delivered models were not undertaken due to the heterogeneity of the included studies in terms of method and interventions provided. Conclusion: Overall, the community-delivered model is effective in improving the coverage of malaria interventions and reducing malaria-associated mortality. The heterogeneity of the community-delivered models and their impact on malaria-metric indices suggests that evidence for context-specific solutions is required. In particular, community-delivered models for malaria elimination, integrated with services for other common primary health problems, are yet to be evaluated. [ABSTRACT FROM AUTHOR]

Background: In the advent of increasing international collaborative research involving participants drawn from populations with diverse cultural backgrounds, community engagement becomes very critical for the smooth conduction of the research. The African Malaria Network Trust (AMANET) is a pan-African non-governmental organization that sponsors and technically supports malaria vaccine trials in various African countries. Case description: AMANET sponsored phase Ib or IIb clinical trials of several malaria vaccine candidates in various Africa countries. In Burkina Faso, Mali and Tanzania trials of the merozoite surface protein 3 - in its Long Synthetic Peptide configuration (MSP3 LSP) - were conducted. In Mali, the apical membrane antigen 1 (AMA1) was tested, while a hybrid of glutamate rich protein (GLURP) and MSP3 (GMZ2) was tested in Gabon. AMANET recognizes the importance of engaging with the communities from which trial participants are drawn, hence community engagement was given priority in all project activities conducted in the various countries. Discussion and evaluation: Existing local social systems were used to engage the communities from which clinical trial participants were drawn. This article focuses on community engagement activities employed at various AMANET-supported clinical trial sites in different countries, highlighting subtle differences in the approaches used. The paper also gives some general pros and cons of community engagement. Conclusions: Community engagement enables two-way sharing of accurate information and ideas between researchers and researched communities, which helps to create an environment conducive to smooth research activities with enhanced sense of research ownership by the communities. [ABSTRACT FROM AUTHOR]

Background: There have been a number of interventions to date aimed at improving malaria diagnostic accuracy in sub-Saharan Africa. Yet, limited success is often reported for a number of reasons, especially in rural settings. This paper seeks to provide a framework for applied research aimed to improve malaria diagnosis using a combination of the established methods, participatory action research and social entrepreneurship. Methods: This case study introduces the idea of using the social entrepreneurship approach (SEA) to create innovative and sustainable applied health research outcomes. The following key elements define the SEA: (1) identifying a locally relevant research topic and plan, (2) recognizing the importance of international multi-disciplinary teams and the incorporation of local knowledge, (3) engaging in a process of continuous innovation, adaptation and learning, (4) remaining motivated and determined to achieve sustainable long-term research outcomes and, (5) sharing and transferring ownership of the project with the international and local partner. Evaluation: The SEA approach has a strong emphasis on innovation lead by local stakeholders. In this case, innovation resulted in a unique holistic research program aimed at understanding patient, laboratory and physician influences on accurate diagnosis of malaria. An evaluation of milestones for each SEA element revealed that the success of one element is intricately related to the success of other elements. Conclusions: The SEA will provide an additional framework for researchers and local stakeholders that promotes innovation and adaptability. This approach will facilitate the development of new ideas, strategies and approaches to understand how health issues, such as malaria, affect vulnerable communities. [ABSTRACT FROM AUTHOR]

The global malaria situation, especially in Africa, and the problems frequently encountered in chemical control of vectors such as insecticide resistance, emphasize the urgency of research, development and implementation of new vector control technologies that are applicable at regional and local levels. The successful application of the sterile insect technique (SIT) for the control of the New World screw-worm Cochliomyia hominivorax and several species of fruit flies has given impetus to the use of this method for suppression or elimination of malaria vectors in some areas of Africa including Northern State of Sudan. The research and development phase of the Northern State feasibility study has been started. Sudanese stakeholders are working side-by-side with the International Atomic Energy Agency in the activities of this important phase. Several ethical, legal and social issues associated with this approach arose during this phase of the project. They need to be seriously considered and handled with care. In this paper, these issues are described, and the current and proposed activities to overcome potential hurdles to ensure success of the project are listed. [ABSTRACT FROM AUTHOR]

Background: Larval control of malaria vectors has been historically successful in reducing malaria transmission, but largely fell out of favour with the introduction of synthetic insecticides and bed nets. However, an integrated approach to malaria control, including larval control methods, continues to be the best chance for success, in view of insecticide resistance, the behavioural adaptation of the vectors to changing environments and the difficulties of reaching the poorest populations most at risk,. Laboratory studies investigating the effects of neem seed (Azadirachta indica) extracts on Anopheles larvae have shown high rates of larval mortality and reductions in adult longevity, as well as low potential for resistance development. Methods: This paper describes a method whereby seeds of the neem tree can be used to reduce adult Anopheles gambiae s.l. abundance in a way that is low cost and can be implemented by residents of rural villages in western Niger. The study was conducted in Banizoumbou village, western Niger. Neem seeds were collected from around the village. Dried seeds were ground into a coarse powder, which was then sprinkled onto known Anopheles larvae breeding habitats twice weekly during the rainy season 2007. Adult mosquitoes were captured on a weekly basis in the village and captures compared to those from 2005 and 2006 over the same period. Adult mosquitoes were also captured in a nearby village, Zindarou, as a control data set and compared to those from Banizoumbou. Results: It was found that twice-weekly applications of the powder to known breeding habitats of Anopheles larvae in 2007 resulted in 49% fewer adult female Anopheles gambiae s.l. mosquitoes in Banizoumbou, compared with previous captures under similar environmental conditions and with similar habitat characteristics in 2005 and 2006. The productivity of the system in 2007 was found to be suppressed compared to the mean behaviour of 2005 and 2006 in Banizoumbou, whereas no change was found in Zindarou. Conclusion: With a high abundance of neem plants in many villages in this area, the results of this study suggest that larval control using neem seed powder offers a sustainable additional tool for malaria vector control in the Sahel region of Niger. [ABSTRACT FROM AUTHOR]

Malaria remains a major public health threat to more than 600 million Africans and its control is recognized as critical to achieving the Millennium Development Goals. The greatest burden of malaria in Africa occurs in the endemic regions where the disease pathogen is continuously present in the community. These regions are characterized by an environment that is conducive to interactions between the Anopheles mosquito, malaria parasites and human hosts, as well as housing of generally poor quality, which offers little zrotection from mosquito-human contact. Epidemic malaria tends to occur along the zeographical margins of endemic regions, when the equilibrium between the human, parasite and mosquito vector populations is occasionally disturbed and a sharp but temporary increase in disease incidence results. When malaria control measures are inadequate, as is the case in much of sub-Saharan Africa, the disease distribution is losely linked with seasonal patterns of the climate and local environment. In the absence of good epidemiological data on malaria distribution in Africa, climate information has long been used to develop malaria risk maps that illustrate the boundaries of 'climatic suitability for endemic transmission.' The best known of these are produced by the Pan-African-based MARA Collaboration. This paper describes the development of additional malaria suitability maps which have been produced in an online, interactive format to enable temporal information (i.e., seasonality of climate conditions) to be queried and displayed along with spatial information. These maps and the seasonal information that they contain should be useful to the malaria control and health service communities for their planning and operational activities. [ABSTRACT FROM AUTHOR]

Background: Vector control tools are urgently needed to control malaria transmission in Africa. A native strain of Chromobacterium sp. from Burkina Faso was recently isolated and preliminarily named Chromobacterium anophelis sp. nov. IRSSSOUMB001. In bioassays, this bacterium showed a promising virulence against adult mosquitoes and reduces their blood feeding propensity and fecundity. The current study assessed the entomopathogenic effects of C. anophelis IRSSSOUMB001 on larval stages of mosquitoes, as well as its impacts on infected mosquitoes reproductive capacity and trans-generational effects. Methods: Virulence on larvae and interference with insemination were assayed by co-incubation with C. anophelis IRSSSOUMB001 at a range of 104 to 108 cfu/ml. Trans-generational effects were determined by measuring body size differences of progeny from infected vs. uninfected parent mosquitoes using wing size as a proxy. Results: Chromobacterium anophelis IRSSSOUMB001 killed larvae of the pyrethroid-resistant Anopheles coluzzii with LT80 of ~ 1.75 ± 0.14 days at 108 cfu/ml in larval breeding trays. Reproductive success was reduced as a measure of insemination rate from 95 ± 1.99% to 21 ± 3.76% for the infected females. There was a difference in wing sizes between control and infected mosquito offsprings from 2.55 ± 0.17 mm to 2.1 ± 0.21 mm in infected females, and from 2.43 ± 0.13 mm to 1.99 ± 0.15 mm in infected males. Conclusions: This study showed that C. anophelis IRSSSOUMB001 was highly virulent against larvae of insecticide-resistant Anopheles coluzzii, and reduced both mosquito reproduction capacity and offspring fitness. Additional laboratory, field, safety and social acceptance studies are needed to draw firm conclusions about the practical utility of this bacterial strain for malaria vector control. [ABSTRACT FROM AUTHOR]

The selection of point mutation at codon 164 (from isoleucine to leucine) of the dihydrofolate reductase (DHFR) enzyme in Plasmodium falciparum is associated with high sulfadoxine / pyrimethamine (SP) resistance. Using the yeast expression system that allows the detection of dhfr allele present at low level, the presence of this mutation had previously been reported between 1998-1999 in Muheza, Tanzania, an area of high SP resistance. Eighty five P. falciparum isolates, obtained from the same area between 2002 and 2003, were analysed for the presence of Leu-164 mutation, using standard protocol based on PCR-RFLP. None of the isolates had the Leu-164 mutation. [ABSTRACT FROM AUTHOR]

Background: Insecticidal mosquito-proof netting screens could combine the best features of insecticide-treated nets (ITNs) and indoor residual spraying (IRS), the two most important front line vector control interventions in Africa today, and also overcome the most important limitations of these methods. This study engaged members of a rural Tanzanian community in developing and evaluating simple, affordable and scalable procedures for installing readily available screening materials on eave gaps and windows of their own houses, and then treating those screens with a widely used IRS formulation of the organophosphate insecticide pirimiphos-methyl (PM). Methods: A cohort of 54 households recruited upon consent, following which the structural features and occupant demographics of their houses were surveyed. Indoor mosquito densities were surveyed longitudinally, for approximately 3 months before and over 5 months after participatory house modification and screening using locally available materials. Each house was randomly assigned to one of three study arms: (1) No screens installed until the end of the study (negative control), (2) untreated screens installed, and (3) screened installed and then treated with PM, the insecticidal activity of which was subsequently assessed using standard cone assays. Results: Almost all (52) recruited households participated until the end, at which point all houses had been successfully screened. In most cases, screening was only installed after making enabling structural modifications that were accepted by the enrolled households. Compared to unscreened houses, houses with either treated or untreated screens both almost entirely excluded Anopheles arabiensis (Relative reduction (RR) ≥ 98%, P < < 0.0001), the most abundant local malaria vector. However, screens were far less effective against Culex quinquefasciatus (RR ≤ 46%, P < < 0.0001), a non-malaria vector causing considerable biting nuisance, regardless of their treatment status. While PM did not augment household level protection by screens against either mosquito species (P = 0.676 and 0.831, respectively), 8 months after treatment it still caused 73% and 89% mortality among susceptible insectary-reared Anopheles gambiae following exposures of 3 and 30 min, respectively. Conclusions: Participatory approaches to mosquito proofing houses may be acceptable and effective, and installed screens may be suitable targets for residual insecticide treatments. [ABSTRACT FROM AUTHOR]

Background: Insecticide-treated nets (ITN) have largely been distributed via mass distribution campaigns. Since 2011, however, the World Health Organization (WHO) has recommended additional ITN distribution via routine antenatal care (ANC) and expanded programme on immunization (EPI) services. Countries have begun to implement these routine facility-based distribution strategies, but inconsistently, and there is little research on outcomes of these new programmes. This paper investigates the impact of ITN distribution policies on children's net use, comparing countries with different policies in place. Methods: Demographic Health Surveys from 25 countries in Africa were used to analyse household ITN ownership, and ITN use among children under 5 years of age. Countries were categorized in terms of the ITN facility-based distribution policies in place, based on nationally reported policies and distribution data provided to the WHO. The analysis was conducted for individual countries and then pooled with all countries in each category weighted equally to present the average country experience, by ITN distribution policy. Results: Household ITN ownership, children's ITN use, and children's ITN use in households with at least one ITN increase with each additional routine facility-based distribution policy. An average of 54.0% of children slept under an ITN in countries with ITN distribution via ANC and EPI, compared to 34.3% and 24.7% in countries with ITN distribution via ANC only, or no facility-based distribution, respectively. Linear regression found a 13% increase in net use among children under 5, on average, with each additional ITN distribution policy. Conclusion: ITN distribution via ANC and EPI can not only assist countries in maintaining ITN ownership and use, but may be extremely effective at increasing ITN ownership and use. There is also an additional benefit associated with combined ANC and EPI-based ITN distribution, compared to ANC distribution alone. [ABSTRACT FROM AUTHOR]

Background: Independent emergence and spread of artemisinin-resistant Plasmodium falciparum malaria have recently been confirmed in Africa, with molecular markers associated with artemisinin resistance increasingly detected. Surveillance to promptly detect and effectively respond to anti-malarial resistance is generally suboptimal in Africa, especially in low transmission settings where therapeutic efficacy studies are often not feasible due to recruitment challenges. However, these communities may be at higher risk of anti-malarial resistance. Methods: From March 2018 to February 2020, a sequential mixed-methods study was conducted to evaluate the feasibility of the near-real-time linkage of individual patient anti-malarial resistance profiles with their case notifications and treatment response reports, and map these to fine scales in Nkomazi sub-district, Mpumalanga, a pre-elimination area in South Africa. Results: Plasmodium falciparum molecular marker resistance profiles were linked to 55.1% (2636/4787) of notified malaria cases, 85% (2240/2636) of which were mapped to healthcare facility, ward and locality levels. Over time, linkage of individual malaria case demographic and molecular data increased to 75.1%. No artemisinin resistant validated/associated Kelch-13 mutations were detected in the 2385 PCR positive samples. Almost all 2812 samples assessed for lumefantrine susceptibility carried the wildtype mdr86ASN and crt76LYS alleles, potentially associated with decreased lumefantrine susceptibility. Conclusion: Routine near-real-time mapping of molecular markers associated with anti-malarial drug resistance on a fine spatial scale provides a rapid and efficient early warning system for emerging resistance. The lessons learnt here could inform scale-up to provincial, national and regional malaria elimination programmes, and may be relevant for other antimicrobial resistance surveillance. [ABSTRACT FROM AUTHOR]

Supplementary tools are required to address the limitations of insecticide-treated nets (ITNs) and indoor residual spraying (IRS), which are currently the core vector control methods against malaria in Africa. The eave ribbons technology exploits the natural house-entry behaviours of major malaria vectors to deliver mosquitocidal or repellent actives around eave spaces through which the Anopheles mosquitoes usually enter human dwellings. They confer protection by preventing biting indoors and in the peri-domestic outdoor spaces, and also killing a significant proportion of the mosquitoes. Current versions of eave ribbons are made of low-cost hessian fabric infused with candidate insecticides and can be easily fitted onto multiple house types without any additional modifications. This article reviews the evidence for efficacy of the technology, and discusses its potential as affordable and versatile supplementary approach for targeted and efficient control of mosquito-borne diseases, particularly malaria. Given their simplicity and demonstrated potential in previous studies, future research should investigate ways to optimize scalability and effectiveness of the ribbons. It is also important to assess whether the ribbons may constitute a less-cumbersome, but more affordable substitute for other interventions, such as IRS, by judiciously using lower quantities of selected insecticides targeted around eave spaces to deliver equivalent or greater suppression of malaria transmission. [ABSTRACT FROM AUTHOR]

Background: Malaria parasites that carry the DHFR-mutation I164L are not only highly resistant to sulfadoxine-pyrimethamine but also to the new antimalarial drug chlorproguanil-dapsone. The spread of this mutation in Africa would result in a public health disaster since there is a lack of effective alternatives that are both affordable and safe. Up to now, this mutation has only been described in Asian and Latin-American countries. The objective of this study was to assess the prevalence of this mutation in African isolates of Plasmodium falciparum that have been imported into Europe through travellers. Methods: TropNetEurop is a network for the surveillance of travel-associated diseases and seems to cover approximately 12% of all malaria cases imported into Europe. Within this network we screened 277 imported African isolates of P. falciparum with the help of PCR- and enzymedigestion-methods for the antifolate-resistant mutation I164L. Results: The I164L mutation was not detected in any of the isolates tested. Discussion: Continuous molecular surveillance of mutations in P. falciparum, as it is practised within TropNetEurop, is an essential tool for the understanding and early detection of the spread of antimalarial drug resistance in Africa. [ABSTRACT FROM AUTHOR]

Background: The emergence of insecticide resistance is a major threat to malaria control programmes in Africa, with many different factors contributing to insecticide resistance in its vectors, Anopheles mosquitoes. CYP6M2 has previously been recognized as an important candidate in cytochrome P450-mediated detoxification in Anopheles. As it has been implicated in resistance against pyrethroids, organochlorines and carbamates, its broad metabolic activity makes it a potential agent in insecticide cross-resistance. Currently, allelic variation within the Cyp6m2 gene remains unknown. Methods: Here, Illumina whole-genome sequence data from Phase 2 of the Anopheles gambiae 1000 Genomes Project (Ag1000G) was used to examine genetic variation in the Cyp6m2 gene across 16 populations in 13 countries comprising Anopheles gambiae and Anopheles coluzzii mosquitoes. To identify whether these alleles show evidence of selection either through potentially modified enzymatic function or by being linked to variants that change the transcriptional profile of the gene, hierarchical clustering of haplotypes, linkage disequilibrium, median joining networks and extended haplotype homozygosity analyses were performed. Results: Fifteen missense biallelic substitutions at high frequency (defined as > 5% frequency in one or more populations) are found, which fall into five distinct haplotype groups that carry the main high frequency variants: A13T, D65A, E328Q, Y347F, I359V and A468S. Despite consistent reports of Cyp6m2 upregulation and metabolic activity in insecticide resistant Anophelines, no evidence of directional selection is found occurring on these variants or on the haplotype clusters in which they are found. Conclusion: These results imply that emerging resistance associated with Cyp6m2 is potentially driven by distant regulatory loci such as transcriptional factors rather than by its missense variants, or that other genes are playing a more significant role in conferring metabolic resistance. [ABSTRACT FROM AUTHOR]

Background: The over-distributed pattern of malaria transmission has led to attempts to define malaria "hotspots" that could be targeted for purposes of malaria control in Africa. However, few studies have investigated the use of routine health facility data in the more stable, endemic areas of Africa as a low-cost strategy to identify hotspots. Here the objective was to explore the spatial and temporal dynamics of fever positive rapid diagnostic test (RDT) malaria cases routinely collected along the Kenyan Coast. Methods: Data on fever positive RDT cases between March 2018 and February 2019 were obtained from patients presenting to six out-patients health-facilities in a rural area of Kilifi County on the Kenyan Coast. To quantify spatial clustering, homestead level geocoded addresses were used as well as aggregated homesteads level data at enumeration zone. Data were sub-divided into quarterly intervals. Kulldorff's spatial scan statistics using Bernoulli probability model was used to detect hotspots of fever positive RDTs across all ages, where cases were febrile individuals with a positive test and controls were individuals with a negative test. Results: Across 12 months of surveillance, there were nine significant clusters that were identified using the spatial scan statistics among RDT positive fevers. These clusters included 52% of all fever positive RDT cases detected in 29% of the geocoded homesteads in the study area. When the resolution of the data was aggregated at enumeration zone (village) level the hotspots identified were located in the same areas. Only two of the nine hotspots were temporally stable accounting for 2.7% of the homesteads and included 10.8% of all fever positive RDT cases detected. Conclusion: Taking together the temporal instability of spatial hotspots and the relatively modest fraction of the malaria cases that they account for; it would seem inadvisable to re-design the sub-county control strategies around targeting hotspots. [ABSTRACT FROM AUTHOR]

Background: Imported malaria parasites with anti-malarial drug resistance (ADR) from Africa is a serious public health challenge in non-malarial regions, including Wuhan, China. It is crucial to assess the ADR status in African Plasmodium falciparum isolates from imported malaria cases, as this will provide valuable information for rational medication and malaria control. Methods: During 2017–2019, a cross-sectional study was carried out in Wuhan, China. Peripheral blood 3 ml of returned migrant workers from Africa was collected. The target fragments from pfcrt, pfmdr1, and k13 propeller (pfk13) genes were amplified, sequenced, and analysed. Results: In total, 106 samples were collected. Subsequently, 98.11% (104/106), 100% (106/106), and 86.79% (92/106) of these samples were successfully amplified and sequenced for the pfcrt (72–76), pfmdr1, and pfk13 genes, respectively. The prevalence of the pfcrt 76 T, pfmdr1 86Y, and pfmdr1 184F mutations was 9.62, 4.72, and 47.17%, respectively. At codons 72–76, the pfcrt locus displayed three haplotypes, CVMNK (wild-type), CVIET (mutation type), CV M/I N/E K/T (mixed type), with 87.50%, 9.62%, and 2.88% prevalence, respectively. For the pfmdr1 gene, NY (wild type), NF and YF (mutant type), N Y/F, Y Y/F, and N/Y Y/F (mixed type) accounted for 34.91, 43.40, 3.77, 15.09, 0.94, and 1.89% of the haplotypes, respectively. A total of 83 isolates with six unique haplotypes were found in pfcrt and pfmdr1 combined haplotypes, of which NY-CVMNK and NF-CVMNK accounted for 40.96% (34/83) and 43.37% (36/83), respectively. Furthermore, 90 cases were successfully sequenced (84.91%, 90/106) at loci 93, 97, 101, and 145, and 78 cases were successfully sequenced (73.58%, 78/106) at loci 343, 353, and 356 for pfcrt. However, the mutation was observed only in locus 356 with 6.41%. For pfk13, mutations reported in Southeast Asia (at loci 474, 476, 493, 508, 527, 533, 537, 539, 543, 553, 568, 574, 578, and 580) and Africa (at loci 550, 561, 575, 579, and 589) were not observed. Conclusions: The present data from pfcrt and pfmdr1 demonstrate that anti-malarial drugs including chloroquine, amodiaquine, and mefloquine, remain effective against malaria treatment in Africa. The new mutations in pfcrt related to piperaquine resistance remain at relatively low levels. Another source of concern is the artemether-lumefantrine resistance-related profiles of N86 and 184F of pfmdr1. Although no mutation in pfk13 is detected, molecular surveillance must continue. [ABSTRACT FROM AUTHOR]

Background: The emergence and spread of multidrug resistance poses a significant risk to malaria control and eradication goals in the world. There has been no indigenous malaria cases reported in China since 2017, and China is approaching national malaria elimination. Therefore, anti-malarial drug resistance surveillance and tracking the emergence and spread of imported drug-resistant malaria cases will be necessary in a post-elimination phase in China. Methods: Dried blood spots were obtained from Plasmodium falciparum-infected cases returned from Africa to China between 2012 and 2015, prior to anti-malarial drug treatment. Whole DNA were extracted and known polymorphisms relating to drug resistance of pfcrt, pfmdr1 gene, and the propeller domain of pfk13 were evaluated by nested PCR and sequencing. The haplotypes and prevalence of these three genes were evaluated separately. Chi-squared test and Fisher's exact test were used to evaluate differences among the different sub-regions of Africa. A P value < 0.05 was used to evaluate differences with statistical significance. The maps were created using ArcGIS. Results: A total of 731 P. falciparum isolates were sequenced at the pfcrt locus. The wild type CVMNK was the most prevalent haplotype with prevalence of 62.8% and 29.8% of the isolates showed the triple mutant haplotype CVIET. A total of 434 P. falciparum isolates were successfully sequenced and pfmdr1 allelic variants were observed in only codons 86, 184 and 1246. Twelve haplotypes were identified and the prevalence of the wild type pfmdr1 NYD was 44.1%. The single mutant pfmdr1 in codons 86 and 184 was predominant but the haplotype NYY with single mutation in codon 1246 was not observed. The double mutant haplotype YFD was common in Africa. About 1,357 isolates were successfully sequenced of pfk13-propeller domain, the wild type was found in 1,308 samples (96.4%) whereby 49 samples (3.6%) had mutation in pfk13. Of 49 samples with pfk13 mutations, 22 non-synonymous and 4 synonymous polymorphic sites were confirmed. The A578S was the most common mutation in pfk13-propeller domain and three mutations associated with artemisinin resistance (M476I, R539T, P553L) were identified in three isolates. Conclusion: This study provides evidence that could give insight into potential issues with anti-malarial drug resistance to inform national drug policy in China in order to treat imported cases. [ABSTRACT FROM AUTHOR]

Background: In clinical trials of therapy for uncomplicated Plasmodium falciparum, there are usually some patients who fail treatment even in the absence of drug resistance. Treatment failures, which can be due to recrudescence or re-infection, are categorized as 'clinical' or 'parasitological' failures, the former indicating that symptoms have returned. Asymptomatic recrudescence has public health implications for continued malaria transmission and may be important for the spread of drug-resistant malaria. As the number of recrudescences in an individual trial is often low, it is difficult to assess how commonplace asymptomatic recrudescence is, and with what factors it is associated. Methods: A systematic literature review was carried out on clinical trials of artemether-lumefantrine (AL) in patients seeking treatment for symptomatic uncomplicated falciparum malaria, and information on symptoms during treatment failure was recorded. Only treatment failures examined by polymerase chain reaction (PCR) were included, so as to exclude re-infections. A multivariable Bayesian regression model was used to explore factors potentially explaining the proportion of recrudescent infections which are symptomatic across the trials included in the study. Results: Across 60 published trials, including 9137 malaria patients, 37.8% [95% CIs (26.6–49.4%)] of recrudescences were symptomatic. A positive association was found between transmission intensity and the observed proportion of recrudescences that were asymptomatic. Symptoms were more likely to return in trials that only enrolled children aged < 72 months [odds ratio = 1.62, 95% CIs (1.01, 2.59)]. However, 84 studies had to be excluded from this analysis, as recrudescences were not specified as symptomatic or asymptomatic. Conclusions: AL, the most widely used treatment for uncomplicated P. falciparum in Africa, remains a highly efficacious drug in most endemic countries. However in the small proportion of patients where AL does not clear parasitaemia, the majority of patients do not develop symptoms again and thus would be unlikely to seek another course of treatment. This continued asymptomatic parasite carriage in patients who have been treated may have implications for drug-resistant parasites being introduced into high-transmissions settings. [ABSTRACT FROM AUTHOR]

Background: Bed nets are the commonest malaria prevention tool and arguably the most cost-effective. Their efficacy is because they prevent mosquito bites (a function of physical durability and integrity), and kill mosquitoes (a function of chemical content and mosquito susceptibility). This essay follows the story of bed nets, insecticides and malaria control, and asks whether the nets must always have insecticides. Methods: Key attributes of untreated or pyrethroid-treated nets are examined alongside observations of their entomological and epidemiological impacts. Arguments for and against adding insecticides to nets are analysed in contexts of pyrethroid resistance, personal-versus-communal protection, outdoor-biting, need for local production and global health policies. Findings: Widespread resistance in African malaria vectors has greatly weakened the historical mass mosquitocidal effects of insecticide-treated nets (ITNs), which previously contributed communal benefits to users and non-users. Yet ITNs still achieve substantial epidemiological impact, suggesting that physical integrity, consistent use and population-level coverage are increasingly more important than mosquitocidal properties. Pyrethroid-treatment remains desirable where vectors are sufficiently susceptible, but is no longer universally necessary and should be re-examined alongside other attributes, e.g. durability, coverage, acceptability and access. New ITNs with multiple actives or synergists could provide temporary relief in some settings, but their performance, higher costs, and drawn-out innovation timelines do not justify singular emphasis on insecticides. Similarly, sub-lethal insecticides may remain marginally-impactful by reducing survival of older mosquitoes and disrupting parasite development inside the mosquitoes, but such effects vanish under strong resistance. Conclusions: The public health value of nets is increasingly driven by bite prevention, and decreasingly by lethality to mosquitoes. For context-appropriate solutions, it is necessary to acknowledge and evaluate the potential and cost-effectiveness of durable untreated nets across different settings. Though ~ 90% of malaria burden occurs in Africa, most World Health Organization-prequalified nets are manufactured outside Africa, since many local manufacturers lack capacity to produce the recommended insecticidal nets at competitive scale and pricing. By relaxing conditions for insecticides on nets, it is conceivable that non-insecticidal but durable, and possibly bio-degradable nets, could be readily manufactured locally. This essay aims not to discredit ITNs, but to illustrate how singular focus on insecticides can hinder innovation and sustainability. [ABSTRACT FROM AUTHOR]

Background: Placental malaria is associated with increased risk of adverse perinatal outcomes. While primigravidity has been reported as a risk factor for placental malaria, little is known regarding the relationship between gravidity, symptomatology and timing of Plasmodium falciparum infection and the development of placental malaria. Methods: The aim of this study was to investigate the relationship between the development of placental malaria and gravidity, timing of infection, and presence of symptoms. This is a secondary analysis of data from a double-blind randomized control trial of intermittent preventive therapy during pregnancy in Uganda. Women were enrolled from 12 to 20 weeks gestation and followed through delivery. Exposure to malaria parasites was defined as symptomatic (fever with positive blood smear) or asymptomatic (based on molecular detection of parasitaemia done routinely every 4 weeks). The primary outcome was placental malaria diagnosed by histopathology, placental blood smear, and/or placental blood loop-mediated isothermal amplification. Multivariate analyses were performed using logistic regression models. Subgroup analysis was performed based on the presence of symptomatic malaria, gravidity, and timing of infection. Results: Of the 228 patients with documented maternal infection with malaria parasites during pregnancy, 101 (44.3%) had placental malaria. Primigravidity was strongly associated with placental malaria (aOR 8.90, 95% CI 4.34–18.2, p < 0.001), and each episode of malaria was associated with over a twofold increase in placental malaria (aOR 2.35, 95% CI 1.69–3.26, p < 0.001). Among multigravid women, the odds of placental malaria increased by 14% with each advancing week of gestation at first documented infection (aOR 1.14, 95% CI 1.02–1.27, p = 0.02). When stratified by the presence of symptoms, primigravidity was only associated with placental malaria in asymptomatic women, who had a 12-fold increase in the odds of placental malaria (aOR 12.19, 95% CI 5.23–28.43, p < 0.001). Conclusions: Total number of P. falciparum infections in pregnancy is a significant predictor of placental malaria. The importance of timing of infection on the development of placental malaria varies based on gravidity. In primigravidas, earlier asymptomatic infections were more frequently identified in those with placental malaria, whereas in multigravidas, parasitaemias detected later in gestation were associated with placental malaria. Earlier initiation of an effective intermittent preventive therapy may help to prevent placental malaria and improve birth outcomes, particularly in primigravid women. [ABSTRACT FROM AUTHOR]

Background: Artemisinin-based combination therapy (ACT) resistant Plasmodium falciparum represents an increasing threat to Africa. Extended ACT regimens from standard 3 to 6 days may represent a means to prevent its development and potential spread in Africa. Methods: Standard 3-day treatment with artemether–lumefantrine (control) was compared to extended 6-day treatment and single low-dose primaquine (intervention); in a randomized controlled, parallel group, superiority clinical trial of patients aged 1–65 years with microscopy confirmed uncomplicated P. falciparum malaria, enrolled in Bagamoyo district, Tanzania. The study evaluated parasite clearance, including proportion of PCR detectable P. falciparum on days 5 and 7 (primary endpoint), cure rate, post-treatment prophylaxis, safety and tolerability. Clinical, and laboratory assessments, including ECG were conducted during 42 days of follow-up. Blood samples were collected for parasite detection (by microscopy and PCR), molecular genotyping and pharmacokinetic analyses. Kaplan–Meier survival analyses were done for both parasite clearance and recurrence. Results: A total of 280 patients were enrolled, 141 and 139 in the control and intervention arm, respectively, of whom 121 completed 42 days follow-up in each arm. There was no difference in proportion of PCR positivity across the arms at day 5 (80/130 (61.5%) vs 89/134 (66.4%), p = 0.44), or day 7 (71/129 (55.0%) vs 70/134 (52.2%), p = 0.71). Day 42 microscopy determined cure rates (PCR adjusted) were 97.4% (100/103) and 98.3% (110/112), p = 0.65, in the control and intervention arm, respectively. Microscopy determined crude recurrent parasitaemia during follow-up was 21/121 (17.4%) in the control and 14/121 (11.6%) in the intervention arm, p = 0.20, and it took 34 days and 42 days in the respective arms for 90% of the patients to remain without recurrent parasitaemia. Lumefantrine exposure was significantly higher in intervention arm from D3 to D42, but cardiac, biochemical and haematological safety was high and similar in both arms. Conclusion: Extended 6-day artemether–lumefantrine treatment and a single low-dose of primaquine was not superior to standard 3-day treatment for ACT sensitive P. falciparum infections but, importantly, equally efficacious and safe. Thus, extended artemether–lumefantrine treatment may be considered as a future treatment regimen for ACT resistant P. falciparum, to prolong the therapeutic lifespan of ACT in Africa. Trial registration ClinicalTrials.gov, NCT03241901. Registered July 27, 2017 https://clinicaltrials.gov/show/NCT03241901 [ABSTRACT FROM AUTHOR]

Background: Malaria transmission has recently fallen in many parts of Africa, but systematic descriptions of infection and disease across all age groups are rare. Here, an epidemiological investigation of parasite prevalence, the incidence of fevers associated with infection, severe hospitalized disease and mortality among children older than 6 months and adults on the Kenyan coast is presented. Methods: A prospective fever surveillance was undertaken at 6 out-patients (OPD) health-facilities between March 2018 and February 2019. Four community-based, cross sectional surveys of fever history and infection prevalence were completed among randomly selected homestead members from the same communities. Paediatric and adult malaria at Kilifi county hospital was obtained for the 12 months period. Rapid Diagnostic Tests (CareStart™ RDT) to detect HRP2-specific to Plasmodium falciparum was used in the community and the OPD, and microscopy in the hospital. Crude and age-specific incidence rates were computed using Poisson regression. Results: Parasite prevalence gradually increased from childhood, reaching 12% by 9 years of age then declining through adolescence into adulthood. The incidence rate of RDT positivity in the OPD followed a similar trend to that of infection prevalence in the community. The incidence of hospitalized malaria from the same community was concentrated among children aged 6 months to 4 years (i.e. 64% and 70% of all hospitalized and severe malaria during the 12 months of surveillance, respectively). Only 3.7% (12/316) of deaths were directly attributable to malaria. Malaria mortality was highest among children aged 6 months–4 years at 0.57 per 1000 person-years (95% CI 0.2, 1.2). Severe malaria and death from malaria was negligible above 15 years of age. Conclusion: Under conditions of low transmission intensity, immunity to disease and the fatal consequences of infection appear to continue to be acquired in childhood and faster than anti-parasitic immunity. There was no evidence of an emerging significant burden of severe malaria or malaria mortality among adults. This is contrary to current modelled approaches to disease burden estimation in Africa and has important implications for the targeting of infection prevention strategies based on chemoprevention or vector control. [ABSTRACT FROM AUTHOR]

Background: While sub-microscopic malarial infections are frequent and potentially deleterious during pregnancy, routine molecular detection is still not feasible. This study aimed to assess the performance of a Histidine Rich Protein 2 (HRP2)-based ultrasensitive rapid diagnostic test (uRDT, Alere Malaria Ag Pf) for the detection of infections of low parasite density in pregnant women. Methods: This was a retrospective study based on samples collected in Benin from 2014 to 2017. A total of 942 whole blood samples collected in 327 women in the 1st and 3rd trimesters and at delivery were tested by uRDT, conventional RDT (cRDT, SD BIOLINE Malaria Ag Pf), microscopy, quantitative polymerase chain-reaction (qPCR) and Luminex-based suspension array technology targeting P. falciparum HRP2. The performance of each RDT was evaluated using qPCR as reference standard. The association between infections detected by uRDT, but not by cRDT, with poor maternal and birth outcomes was assessed using multivariate regression models. Results: The overall positivity rate detected by cRDT, uRDT, and qPCR was 11.6% (109/942), 16.2% (153/942) and 18.3% (172/942), respectively. Out of 172 qPCR-positive samples, 68 were uRDT-negative. uRDT had a significantly better sensitivity (60.5% [52.7–67.8]) than cRDT (44.2% [36.6–51.9]) and a marginally decreased specificity (93.6% [91.7–95.3] versus 95.7% [94.0–97.0]). The gain in sensitivity was particularly high (33%) and statistically significant in the 1st trimester. Only 28 (41%) out of the 68 samples which were qPCR-positive, but uRDT-negative had detectable but very low levels of HRP2 (191 ng/mL). Infections that were detected by uRDT but not by cRDT were associated with a 3.4-times (95%CI 1.29–9.19) increased risk of anaemia during pregnancy. Conclusions: This study demonstrates the higher performance of uRDT, as compared to cRDTs, to detect low parasite density P. falciparum infections during pregnancy, particularly in the 1st trimester. uRDT allowed the detection of infections associated with maternal anaemia. [ABSTRACT FROM AUTHOR]

Background: African Traditional Medicine (ATM) is used for the healthcare of about 80% of the rural populations of the continent of Africa. The practices of ATM make use of plant-products, which are known to contain plant-based secondary metabolites or natural products (NPs), likely to play key roles in drug discovery, particularly as lead compounds. For various reasons, including resistance of strains of Plasmodium to known anti-malarial drugs, local African populations often resort to plant-based treatments and/or a combination of this and standard anti-malarial regimens. Emphasis has been laid in this review to present the anti-malarial virtue of the most recently published phytochemicals or natural products, which have been tested by in vitro and in vivo assays. Methods: The data was based on the current version of the African Compound Libraries, which are constantly being updated based on inputs from journal articles and student theses (M.Sc/Ph.D) from African University libraries. Emphasis was laid on data published after 2012. In order to carry out the original data collection, currently being included in the African Compounds Database, individual journal websites were queried using the country names in Africa as search terms. Over 40,000 articles "hits" were originally retrieved, then reduced to about 9000 articles. The retained articles/theses was further queried with the search terms "malaria", "malarial", "plasmodium", "plasmodial" and a combination of them, resulting in over 500 articles. Those including compounds with anti-malarial activities for which the measured activities fell within the established cut off values numbered 55, which were all cited in the review as relevant references. Results and discussion: Pure compounds derived from African medicinal plants with demonstrated anti-malarial/antiplasmodial properties with activities ranging from "very active" to "weakly active" have been discussed. The majority of the 187 natural products were terpenoids (30%), followed by flavonoids (22%), alkaloids (19%) and quinones (15%), with each of the other compound classes being less than 5% of the entire compound collection. It was also observed that most of the plant species from which the compounds were identified were of the families Rubiaceae, Meliaceae and Asphodelaceae. The review is intended to continue laying the groundwork for an African-based anti-malarial drug discovery project. [ABSTRACT FROM AUTHOR]

Background: Malaria continues to be a disease of massive burden in Africa, and the public health resources targeted at surveillance, prevention, control, and intervention comprise large outlays of expense. Malaria transmission is largely constrained by the suitability of the climate for Anopheles mosquitoes and Plasmodium parasite development. Thus, as climate changes, shifts in geographic locations suitable for transmission, and differing lengths of seasons of suitability will occur, which will require changes in the types and amounts of resources. Methods: The shifting geographic risk of malaria transmission was mapped, in context of changing seasonality (i.e. endemic to epidemic, and vice versa), and the number of people affected. A published temperature-dependent model of malaria transmission suitability was applied to continental gridded climate data for multiple future AR5 climate model projections. The resulting outcomes were aligned with programmatic needs to provide summaries at national and regional scales for the African continent. Model outcomes were combined with population projections to estimate the population at risk at three points in the future, 2030, 2050, and 2080, under two scenarios of greenhouse gas emissions (RCP4.5 and RCP8.5). Results: Estimated geographic shifts in endemic and seasonal suitability for malaria transmission were observed across all future scenarios of climate change. The worst-case regional scenario (RCP8.5) of climate change predicted an additional 75.9 million people at risk from endemic (10-12 months) exposure to malaria transmission in Eastern and Southern Africa by the year 2080, with the greatest population at risk in Eastern Africa. Despite a predominance of reduction in season length, a net gain of 51.3 million additional people is predicted be put at some level of risk in Western Africa by midcentury. Conclusions: This study provides an updated view of potential malaria geographic shifts in Africa under climate change for the more recent climate model projections (AR5), and a tool for aligning findings with programmatic needs at key scales for decision-makers. In describing shifting seasonality, it was possible to capture transitions between endemic and epidemic risk areas, to facilitate the planning for interventions aimed at year-round risk versus anticipatory surveillance and rapid response to potential outbreak locations. [ABSTRACT FROM AUTHOR]

Background: Insecticide-treated nets (ITNs) are losing efficacy against pyrethroid-resistant malaria vector populations throughout Africa. Safeguarding bed net efficacy, vital for effective malaria control, requires greater knowledge of mosquito–ITN interactions and how this impacts on the mosquito. Methods: A purpose-built benchtop apparatus with a closed 10 cm cubic chamber (the 'Baited-box') was used to video record behaviour of individual free-flying female Anopheles gambiae during approach and blood-feeding on a human hand through untreated nets and ITNs at close range. Time and duration of defined behavioural events, and knockdown and mortality at 1- and 24-h post-exposure respectively, were recorded for pyrethroid susceptible and resistant mosquitoes. Results: Using three human volunteers differing in relative attractiveness to mosquitoes, 328 mosquitoes were individually tested. There were no significant differences between response rates to ITNs and untreated nets (P > 0.1) or between resistant (Tiassalé) and susceptible (Kisumu) mosquito strains, at untreated nets (P = 0.39) or PermaNet 2.0 (P = 1). The sequence of behavioural events from host-seeking to completion of blood-feeding was consistent in all tests but duration and start time of events involving net contact were reduced or delayed respectively with ITNs. Blood-feeding durations at untreated nets (means from 4.25 to 8.47 min (95% confidence interval (CI) = 3.39–9.89) at 3 human volunteers) were reduced by 37–50% at PermaNet 2.0, in susceptible (mean 2.59–4.72 min, 95% CI = 1.54–5.5, P = < 0.05) and resistant (mean 4.20 min, 95% CI = 3.42–4.97, P = 0.01) strains. Total accumulated net contact was approximately 50% lower at PermaNet and Olyset ITNs (P < 0.0001) in susceptible (two of the three volunteers) and resistant mosquitoes. Times prior to first net contact were similar at untreated nets and ITNs (P > 0.2), and neither ITN type showed detectable spatial repellency. After initial contact, blood-feeding commenced later at Olyset (mean 2.76 min, 95% CI = 1.74–3.76, P = 0.0009) and PermaNet (mean 2.4 min, 95% CI = 1.52–3.33, P = 0.0058) than untreated netting (mean 0.68 min, 95% CI = 0.42–0.94). Conclusions: The baited box offers a simple method for detailed characterization of mosquito behavioural responses to insecticidal nets, for comparing entomological modes of action between nets and for defining the behavioural responses of particular mosquito strains or populations. The device has potential as a screening assay in the search for novel net treatments and for investigations into behavioural resistance mechanisms. [ABSTRACT FROM AUTHOR]

Background: Malaria is a major public health problem in Cameroon. The study of the genetic diversity within parasite population is essential for understanding the mechanism underlying malaria pathology and to determine parasite clones profile in an infection, for proper malaria control strategies. The objective of this study was to perform a molecular characterization of highly polymorphic genetic markers of Plasmodium falciparum, and to determine allelic distribution with their influencing factors valuable to investigate malaria transmission dynamics in Cameroon. Methods: A total of 350 P. falciparum clinical isolates were characterized by genotyping block 2 of msp-1, block 3 of msp-2, and region II of glurp gene using nested PCR and DNA sequencing between 2012 and 2013. Results: A total of 5 different genotypes with fragment sizes ranging from 597 to 817 bp were recorded for GLURP. Overall, 16 MSP-1 genotypes, including K1, MAD20 and RO33 were identified, ranging from 153 to 335 bp. A peculiarity about this study is the RO33 monomorphic pattern revealed among the Pfmsp-1 allelic type. Again, this study identified 27 different Pfmsp-2 genotypes, ranging from 140 to 568 bp in size, including 15 belonging to the 3D7-type and 12 to the FC27 allelic families. The analysis of the MSP-1 and MSP-2 peptides indicates that the region of the alignment corresponding K1 polymorphism had the highest similarity in the MSP1and MSP2 clade followed by MAD20 with 93% to 100% homology. Therefore, population structure of P. falciparum isolates is identical to that of other areas in Africa, suggesting that vaccine developed with K1 and MAD20 of Pfmsp1 allelic variant could be protective for Africa children but these findings requires further genetic and immunological investigations. The multiplicity of infection (MOI) was significantly higher (P < 0.05) for Pfmsp-2 loci (3.82), as compare with Pfmsp-1 (2.51) and heterozygotes ranged from 0.55 for Pfmsp-1 to 0.96 for Pfmsp-2. Conclusion: High genetic diversity and allelic frequencies in P. falciparum isolates indicate a persisting high level of transmission. This study advocate for an intensification of the malaria control strategies in Cameroon. Trial registration This study was approved by Cameroon National Ethics Committee. It is a randomized controlled trial retrospectively registered in NIH U.S. National Library of Medicine, ClinicalTrials.gov on the 28/11/2016 at https://clinicaltrials.gov/ct2/show/NCT02974348 with the registration number NCT02974348 [ABSTRACT FROM AUTHOR]

Recent publications and statements have drawn attention to a sustainable system of managing malaria control interventions globally but especially on the Continent of Africa. Arbitrary and unstable governments often interfere with health programmes, causing upsurges in malaria transmission as well as other health issues. A well-run health infrastructure will deal with public health as a whole. This commentary follows historical conditions in Zimbabwe where much original work on malaria control was initiated and implemented and where unstable conditions happened through local politics. These periodic conditions of instability on the ground challenge the current philosophical thrust to eradication and stress the need and role of an established and well-staffed health infrastructure in each country. Such facilities should be well staffed and supplied with drugs and point-of care diagnostic tests to manage malaria and should be sustained to serve the community even after tools that can eradicate malaria are developed. [ABSTRACT FROM AUTHOR]