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Abstract Background Substandard anti-malarial agents pose a significant challenge to effective malaria control and elimination efforts especially in sub-Saharan Africa. The quality of anti-malarials in most low-and-middle income countries (LMICs) is affected by several factors including inadequate regulation and limited resources. In this study, the pharmacopeial quality of artemether–lumefantrine (AL) in low and high malaria transmission settings in Uganda was assessed. Methods This was a cross-sectional study conducted among randomly selected private drug outlets. The AL anti-malarials available in drug outlets were purchased using overt method. The samples were screened for quality using visual inspection, weight uniformity, content assay and dissolution tests. The assay test was done using liquid chromatography–mass spectrometry (LC–MS). The samples were considered substandard if the active pharmaceutical ingredient (API) content was outside 90–110% range of the label claim. Dissolution test was conducted following United States Pharmacopoeia (USP) method. Data was analysed using descriptive statistics and presented as means with standard deviations, frequencies, and proportions. Correlation between medicine quality and independent variables was determined using Fisher’s exact test of independence at 95% level of significance. Results A total of 74 AL anti-malarial samples were purchased from high (49/74; 66.2%) and low (25/74; 33.8%) malaria transmission settings. The most common batch of AL was LONART, 32.4% (24/74), with 33.8% (25/74) being ‘Green leaf’. Overall prevalence of substandard quality artemether–lumefantrine was 18.9% (14/74; 95% CI: 11.4–29.7). Substandard quality AL was significantly associated with setting (p = 0.002). A total of 10 samples (13.5%) failed artemether content assay test while, 4 samples (5.4%, 4/74) failed the lumefantrine assay test. One sample from a high malaria transmission setting failed both artemether and lumefantrine assay content test. Of the samples that failed artemether assay test, 90% had low (

Abstract Background Many rural communities in Malaysian Borneo and Southeast Asia are at risk of Plasmodium knowlesi malaria. Multiple factors contribute to infection, however, a deep understanding of illness causation and prevention practices among at-risk communities remains limited. This study aims to document local knowledge on malaria causation and preventive practices of rural communities in Sabah, Malaysia, using photovoice—a participatory research method. Methods From January to June 2022, a photovoice study was conducted with rural communities in Matunggong subdistrict, Malaysia, to explore their experiences with and local knowledge of non-human primate malaria and prevention practices. The study included (1) an introductory phase in which participants were introduced to the photovoice method; (2) a documentation phase in which participants captured and narrated photos from their communities; (3) a discussion phase in which participants discussed photos and relevant topics through a series of three focus group discussions (FGDs) per village; and (4) a dissemination phase where selected photos were shared with key stakeholders through a photo exhibition. A purposively selected sample of 26 participants (adults > 18 years old, male, and female) from four villages participated in all phases of the study. The study activities were conducted in Sabah Malay dialect. Participants and the research team contributed to data review and analyses. Results Rural communities in Sabah, Malaysia possess local knowledge that attributes non-human primate malaria to natural factors related to the presence of mosquitoes that bite humans and which carry “kuman-malaria” or malaria parasite. Participants revealed various preventive practises ranging from traditional practises, including burning dried leaves and using plants that produce foul odours, to non-traditional approaches such as aerosols and mosquito repellents. By engaging with researchers and policymakers, the participants or termed as co-researchers in this study, showcased their ability to learn and appreciate new knowledge and perspectives and valued the opportunity to share their voices with policymakers. The study successfully fostered a balance of power dynamics between the co-researchers, research team members and policymakers. Conclusion There were no misconceptions about malaria causation among study participants. The insights from study participants are relevant because of their living experience with the non-human malaria. It is critical to incorporate rural community perspectives in designing locally effective and feasible malaria interventions in rural Sabah, Malaysia. Future research can consider adapting the photovoice methodology for further research with the community toward building locally tailored-malaria strategies. …

Abstract Background Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in sub-Saharan Africa, where most malaria deaths occur. Methods Here, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA). Both major and minor variants were explored in the three conserved-encoding domains of the pfkelch13 gene, the main determinant of ART resistance using a targeted-amplicon deep sequencing (TADS) approach. Results All samples tested in the ex vivo RSA were found to be susceptible to DHA (parasite survival rate 

Abstract Background Intravenous artesunate (AS) is the first-line treatment for patients with severe imported malaria (SIM) worldwide. However, after 10 years of use in France, AS hasn’t yet received marketing authorization.The purpose of this study was to assess the real-life effectiveness and safety of AS in the treatment of SIM in two Hospitals in France. Methods We performed a bicenter retrospective and observational study. All patients treated with AS for SIM between 2014 and 2018 and 2016–2020 were included. The effectiveness of AS was evaluated by parasite clearance, number of deaths, and the length of hospital stay. The real-life safety was assessed by related adverse events (AE) and monitoring of biological blood parameters during the hospital stay and follow-up period. Results 110 patients were included during the six-year study period. 71.8% of patients were parasite-negative of their day 3 thick and thin blood smears after AS treatment. No patients discontinued AS due to an AE and no serious AE were declared. Two cases of delayed post-artesunate hemolysis occurred and required blood transfusions. Conclusion This study highlights effectiveness and safety of AS in non-endemic areas. Administrative procedures must be accelerated in order to obtain full registration and facilitate access to AS in France. …

Abstract Background Intravenous artesunate (AS) is the first-line treatment for patients with severe imported malaria (SIM) worldwide. However, after 10 years of use in France, AS hasn’t yet received marketing authorization.The purpose of this study was to assess the real-life effectiveness and safety of AS in the treatment of SIM in two Hospitals in France. Methods We performed a bicenter retrospective and observational study. All patients treated with AS for SIM between 2014 and 2018 and 2016–2020 were included. The effectiveness of AS was evaluated by parasite clearance, number of deaths, and the length of hospital stay. The real-life safety was assessed by related adverse events (AE) and monitoring of biological blood parameters during the hospital stay and follow-up period. Results 110 patients were included during the six-year study period. 71.8% of patients were parasite-negative of their day 3 thick and thin blood smears after AS treatment. No patients discontinued AS due to an AE and no serious AE were declared. Two cases of delayed post-artesunate hemolysis occurred and required blood transfusions. Conclusion This study highlights effectiveness and safety of AS in non-endemic areas. Administrative procedures must be accelerated in order to obtain full registration and facilitate access to AS in France. …

Abstract Background Malaria is a worldwide infectious disease. For countries that have achieved malaria elimination, the prevention of re-establishment due to infections in returned travellers has become important. The accurate and timely diagnosis of malaria is the key in preventing re-establishment, and malaria rapid diagnostic tests (RDTs) are frequently used due to their convenience. However, the RDT performance in Plasmodium malariae (P. malariae) infection diagnosis remains unknown. Methods This study analysed epidemiological features and diagnosis patterns of imported P. malariae cases from 2013 to 2020 in Jiangsu Province and evaluated the sensitivity of four parasite enzyme lactate dehydrogenase (pLDH)-targeting RDTs (Wondfo, SD BIONLINE, CareStart and BioPerfectus) and one aldolase-targeting RDT(BinaxNOW) for P. malariae detection. Furthermore, influential factors were investigated, including parasitaemia load, pLDH concentration and target gene polymorphisms. Results The median duration from symptom onset to diagnosis among patients with P. malariae infection was 3 days, which was longer than that with Plasmodium falciparum (P. falciparum) infection. The RDTs had a low detection rate (39/69, 56.5%) among P. malariae cases. All tested RDT brands had poor performance in P. malariae detection. All the brands except the worst-performing SD BIOLINE, achieved 75% sensitivity only when the parasite density was higher than 5000 parasites/μL. Both pLDH and aldolase showed relatively conserved and low gene polymorphism rates. Conclusions The diagnosis of imported P. malariae cases was delayed. The RDTs had poor performance in P. malariae diagnosis and may threaten the prevention of malaria re-establishment from returned travellers. The improved RDTs or nucleic acid tests for P. malariae cases are urgently needed for the detection of imported cases in the future. …

Abstract Plasmodium cynomolgi (Pcy), a simian malaria parasite, is a recent perfect example of emerging zoonotic transfer in human. This review summarizes the current knowledge on the epidemiology of natural Pcy infections in humans, mosquitoes and monkeys, along with its biological, clinical and drug sensitivity patterns. Knowledge gaps and further studies on Pcy in humans are also discussed. This parasite currently seems to be geographically limited in South-East Asia (SEA) with a global prevalence in human ranging from 0 to 1.4%. The Pcy infections were reported in local SEA populations and European travelers, and range from asymptomatic carriage to mild/moderate attacks with no evidence of pathognomonic clinical and laboratory patterns but with Pcy strain-shaped clinical differences. Geographical distribution and competence of suitable mosquito vectors and non-primate hosts, globalization, climate change, and increased intrusion of humans into the habitat of monkeys are key determinants to emergence of Pcy parasites in humans, along with its expansion outside SEA. Sensitization/information campaigns coupled with training and assessment sessions of microscopists and clinicians on Pcy are greatly needed to improve data on the epidemiology and management of human Pcy infection. There is a need for development of sensitive and specific molecular tools for individual diagnosis and epidemiological studies. The development of safe and efficient anti-hypnozoite drugs is the main therapeutic challenge for controlling human relapsing malaria parasites. Experience gained from P. knowlesi malaria, development of integrated measures and strategies—ideally with components related to human, monkeys, mosquito vectors, and environment—could be very helpful to prevent emergence of Pcy malaria in humans through disruption of transmission chain from monkeys to humans and ultimately contain its expansion in SEA and potential outbreaks in a context of malaria elimination. …

Although tafenoquine plus dihydroartemisinin–piperaquine was statistically superior to dihydroartemisinin–piperaquine alone for the radical cure of P vivax malaria, the benefit was not clinically meaningful. This contrasts with previous studies in which tafenoquine plus chloroquine was clinically superior to chloroquine alone for radical cure of P vivax malaria.

AbstractBackgroundDespite scale-up of seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SP-AQ) in children

Abstract Background The unmet demand for effective malaria transmission-blocking agents targeting the transmissible stages of Plasmodium necessitates intensive discovery efforts. In this study, a bioactive bisbenzylisoquinoline (BBIQ), isoliensinine, from Cissampelos pariera (Menispermaceae) rhizomes was identified and characterized for its anti-malarial activity. Methods Malaria SYBR Green I fluorescence assay was performed to evaluate the in vitro antimalarial activity against D6, Dd2, and F32-ART5 clones, and immediate ex vivo (IEV) susceptibility for 10 freshly collected P. falciparum isolates. To determine the speed- and stage-of-action of isoliensinine, an IC50 speed assay and morphological analyses were performed using synchronized Dd2 asexuals. Gametocytocidal activity against two culture-adapted gametocyte-producing clinical isolates was determined using microscopy readouts, with possible molecular targets and their binding affinities deduced in silico. Results Isoliensinine displayed a potent in vitro gametocytocidal activity at mean IC50gam values ranging between 0.41 and 0.69 µM for Plasmodium falciparum clinical isolates. The BBIQ compound also inhibited asexual replication at mean IC50Asexual of 2.17 µM, 2.22 µM, and 2.39 µM for D6, Dd2 and F32-ART5 respectively, targeting the late-trophozoite to schizont transition. Further characterization demonstrated a considerable immediate ex vivo potency against human clinical isolates at a geometric mean IC50IEV = 1.433 µM (95% CI 0.917–2.242). In silico analyses postulated a probable anti-malarial mechanism of action by high binding affinities for four mitotic division protein kinases; Pfnek1, Pfmap2, Pfclk1, and Pfclk4. Additionally, isoliensinine was predicted to possess an optimal pharmacokinetics profile and drug-likeness properties. Conclusion These findings highlight considerable grounds for further exploration of isoliensinine as an amenable scaffold for malaria transmission-blocking chemistry and target validation. …

Abstract Background Reducing the risk of recurrent Plasmodium vivax malaria is critical for malaria control and elimination. Primaquine (PQ) is the only widely available drug against P. vivax dormant liver stages, but is recommended as a 14-day regimen, which can undermine adherence to a complete course of treatment. Methods This is a mixed-methods study to assess socio-cultural factors influencing adherence to a 14-day PQ regimen in a 3-arm, treatment effectiveness trial in Papua, Indonesia. The qualitative strand, consisting of interviews and participant observation was triangulated with a quantitative strand in which trial participants were surveyed using a questionnaire. Results Trial participants differentiated between two types of malaria: tersiana and tropika, equivalent to P. vivax and Plasmodium falciparum infection, respectively. The perceived severity of both types was similar with 44.0% (267/607) perceiving tersiana vs. 45.1% (274/607) perceiving tropika as more severe. There was no perceived differentiation whether malaria episodes were due to a new infection or relapse; and 71.3% (433/607) acknowledged the possibility of recurrence. Participants were familiar with malaria symptoms and delaying health facility visit by 1–2 days was perceived to increase the likelihood of a positive test. Prior to health facility visits, symptoms were treated with leftover drugs kept at home (40.4%; 245/607) or bought over the counter (17.0%; 103/607). Malaria was considered to be cured with ‘blue drugs’ (referring to dihydroartemisinin-piperaquine). Conversely, ‘brown drugs,’ referring to PQ, were not considered malaria medication and instead were perceived as supplements. Adherence to malaria treatment was 71.2% (131/184), in the supervised arm, 56.9% (91/160) in the unsupervised arm and 62.4% (164/263) in the control arm; p = 0.019. Adherence was 47.5% (47/99) among highland Papuans, 51.7% (76/147) among lowland Papuans, and 72.9% (263/361) among non-Papuans; p 

Abstract Background Malaria remains one of the most serious public health problems in sub-Saharan Africa and Mozambique is the world\'s fourth largest contributor, with 4.7% of disease cases and 3.6% of total deaths due to malaria. Its control relies on the fight against the vector and treatment of confirmed cases with anti-malarial drugs. Molecular surveillance is an important tool for monitoring the spread of anti-malarial drug resistance. Methods A cross-sectional study recruited 450 participants with malaria infection detected by Rapid Diagnostic Tests, from three different study sites (Niassa, Manica and Maputo) between April and August 2021. Correspondent blood samples were collected on filter paper (Whatman® FTA® cards), parasite DNA extracted and pfk13 gene sequenced using Sanger method. SIFT software (Sorting Intolerant From Tolerant) was used, predict whether an amino acid substitution affects protein function. Results No pfkelch13-mediated artemisinin resistance gene mutation was detected in this study settings. However, non-synonymous mutations were detected at prevalence of 10.2%, 6% and 5% in Niassa, Manica and Maputo, respectively. Most (56.3%) of the reported non-synonymous mutations were due to substitution at the first base of the codon, 25% at the second base and 18.8% at the third base. Additionally, 50% of non-synonymous mutations showed a SIFTscore bellow cut off value of 0.05, therefore, they were predicted to be deleterious. Conclusion These results do not show an emergence of artemisinin resistance cases in Mozambique. However, the increased number of novel non-synonymous mutations highlights the relevance of increasing the number of studies focused on the molecular surveillance of artemisinin resistance markers, for its early detection. …

Research Letter - Microscopic Evidence of Malaria Infection in Visceral Tissue from Medici Family, Italy…

Abstract Background For blood-stage malaria vaccine development, the in vitro growth inhibition assay (GIA) has been widely used to evaluate functionality of vaccine-induced antibodies (Ab), and Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage antigen. However, precision, also called “error of assay (EoA)”, in GIA readouts and the source of EoA has not been evaluated systematically. Methods In the Main GIA experiment, 4 different cultures of P. falciparum 3D7 parasites were prepared with red blood cells (RBC) collected from 4 different donors. For each culture, 7 different anti-RH5 Ab (either monoclonal or polyclonal Ab) were tested by GIA at two concentrations on three different days (168 data points). To evaluate sources of EoA in % inhibition in GIA (%GIA), a linear model fit was conducted including donor (source of RBC) and day of GIA as independent variables. In addition, 180 human anti-RH5 polyclonal Ab were tested in a Clinical GIA experiment, where each Ab was tested at multiple concentrations in at least 3 independent GIAs using different RBCs (5,093 data points). The standard deviation (sd) in %GIA and in GIA50 (Ab concentration that gave 50%GIA) readouts, and impact of repeat assays on 95% confidence interval (95%CI) of these readouts was estimated. Results The Main GIA experiment revealed that the RBC donor effect was much larger than the day effect, and an obvious donor effect was also observed in the Clinical GIA experiment. Both %GIA and log-transformed GIA50 data reasonably fit a constant sd model, and sd of %GIA and log-transformed GIA50 measurements were calculated as 7.54 and 0.206, respectively. Taking the average of three repeat assays (using three different RBCs) reduces the 95%CI width in %GIA or in GIA50 measurements by ~ half compared to a single assay. Conclusions The RBC donor effect (donor-to-donor variance on the same day) in GIA was much bigger than the day effect (day-to-day variance using the same donor’s RBC) at least for the RH5 Ab evaluated in this study; thus, future GIA studies should consider the donor effect. In addition, the 95%CI for %GIA and GIA50 shown here help when comparing GIA results from different samples/groups/studies; therefore, this study supports future malaria blood-stage vaccine development. …

Abstract Background Malaria remains a public health concern globally. Resistance to anti-malarial drugs has consistently threatened the gains in controlling the malaria parasites. Currently, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are the treatment regimens against Plasmodium falciparum infections in many African countries, including Kenya. Recurrent infections have been reported in patients treated with AL or DP, suggesting the possibility of reinfection or parasite recrudescence associated with the development of resistance against the two therapies. The Plasmodium falciparum cysteine desulfurase IscS (Pfnfs1) K65 selection marker has previously been associated with decreased lumefantrine susceptibility. This study evaluated the frequency of the Pfnfs1 K65 resistance marker and associated K65Q resistant allele in recurrent infections collected from P. falciparum-infected individuals living in Matayos, Busia County, in western Kenya. Methods Archived dried blood spots (DBS) of patients with recurrent malaria infection on clinical follow-up days after treatment with either AL or DP were used in the study. After extraction of genomic DNA, PCR amplification and sequencing analysis were employed to determine the frequencies of the Pfnfs1 K65 resistance marker and K65Q mutant allele in the recurrent infections. Plasmodium falciparum msp1 and P. falciparum msp2 genetic markers were used to distinguish recrudescent infections from new infections. Results The K65 wild-type allele was detected at a frequency of 41% while the K65Q mutant allele was detected at a frequency of 22% in the recurrent samples. 58% of the samples containing the K65 wild-type allele were AL treated samples and while 42% were DP treated samples. 79% of the samples with the K65Q mutation were AL treated samples and 21% were DP treated samples. The K65 wild-type allele was detected in three recrudescent infections (100%) identified from the AL treated samples. The K65 wild-type allele was detected in two recrudescent DP treated samples (67%) while the K65Q mutant allele was identified in one DP treated (33%) recrudescent sample. Conclusions The data demonstrate a higher frequency of the K65 resistance marker in patients with recurrent infection during the study period. The study underscores the need for consistent monitoring of molecular markers of resistance in regions of high malaria transmission. …

Abstract Background Malaria remains a common course of morbidity in many sub-Saharan African countries. While treatment options have improved in recent times, inappropriate prescription seems conventional among providers, increasing the burden on patients and society. This study examined the cost of inappropriate prescriptions for uncomplicated malaria treatment in Ghana. Methods This study used retrospective data collected from January to December 2016 in 27 selected facilities, under different ownership in three regions of the country, mainly Volta, Upper East and Brong Ahafo. Stratified random sampling technique was used to extract 1625 outpatient folders of patients diagnosed and treated for malaria. Two physicians independently reviewed patient folders according to the stated diagnoses. Malaria prescriptions were described as inappropriate when they do not adhere to the standard treatment guidelines. The economic cost was mainly treatment cost which was sourced as medication cost. Total and average costs for country were calculated using sample estimates and the total number of uncomplicated malaria cases that received inappropriate prescriptions. Results The study revealed that patients received an average of two prescriptions per malaria episode. Artemether-lumefantrine (AL) was the major malaria medication (79.5%) prescribed to patients. Other medications usually antibiotics and vitamins and minerals were included in the prescription. More than 50% of prescribers did not follow the guidelines for prescribing medications to clients. By facility type, inappropriate prescription was high in the CHPS compounds (59.1%) and by ownership, government (58.3%), private (57.5%) and mission facilities (50.7%). Thus, about 55% of malaria prescriptions were evaluated as inappropriate during the review period, which translates into economic cost of approximately US$4.52 million for the entire country in 2016. The total cost of inappropriate prescription within the study sample was estimated at US$1,088.42 while the average cost was US$1.20. Conclusion Inappropriate prescription for malaria is a major threat to malaria management in Ghana. It presents a huge economic burden to the health system. Training and strict enforcement of prescribers’ adherence to the standard treatment guideline is highly recommended. …

IntroductionIn Liberia, emergency care is still in its early development. In 2019, two emergency care and triage education sessions were done at J. J. Dossen Hospital in Southeastern Liberia. The observational study objectives evaluated key process outcomes before and after the educational interventions. MethodsEmergency department paper records from 1 February 2019 to 31 December 2019 were retrospectively reviewed. Simple descriptive statistics were used to describe patient demographics and 2 analyses were used to test for significance. ORs were calculated for key predetermined process measures. ResultsThere were 8222 patient visits recorded that were included in our analysis. Patients in the post-intervention 1 group had higher odds of having a documented full set of vital signs compared with the baseline group (16% vs 3.5%, OR: 5.4 (95% CI: 4.3 to 6.7)). After triage implementation, patients who were triaged were 16 times more likely to have a full set of vitals compared with those who were not triaged. Similarly, compared with the baseline group, patients in the post-intervention 1 group had higher odds of having a glucose documented if they presented with altered mental status or a neurologic complaint (37% vs 30%, OR: 1.7 (95% CI: 1.3 to 2.2)), documented antibiotic administration if they had a presumed bacterial infection (87% vs 35%, OR: 12.8 (95% CI: 8.8 to 17.1)), documented malaria test if presenting with fever (76% vs 61%, OR: 2.05 (95% CI: 1.37 to 3.08)) or documented repeat set of vitals if presenting with shock (25% vs 6.6%, OR: 8.85 (95% CI: 1.67 to 14.06)). There was no significant difference in the above process outcomes between the education interventions. ConclusionThis study showed improvement in most process measures between the baseline and post-intervention 1 groups, benefits that persisted post-intervention 2, thus supporting the importance of short-course education interventions to durably improve facility-based care. …

by Giuseppina Ortu, Gilda Grard, Fanny Parenton, Marc Ruello, Marie-Claire Paty, Guillaume André Durand, Youssouf Hassani, Henriette De Valk, Harold Noël, Unono Wa Maore group Chikungunya is an arboviral disease causing arthralgia which may develop into a debilitating chronic arthritis. In Mayotte, a French overseas department in the Indian Ocean, a chikungunya outbreak was reported in 2006, affecting a third of the population. We aimed at assessing the chikungunya seroprevalence in this population, after over a decade from that epidemic. A multi-stage cross sectional household-based study exploring socio-demographic factors, and knowledge and attitude towards mosquito-borne disease prevention was carried out in 2019. Blood samples from participants aged 15–69 years were taken for chikungunya IgG serological testing. We analyzed associations between chikungunya serological status and selected factors using Poisson regression models, and estimated weighted and adjusted prevalence ratios (w/a PR). The weighted seroprevalence of chikungunya was 34.75% (n = 2853). Seropositivity for IgG anti-chikungunya virus was found associated with living in Mamoudzou (w/a PR = 1.49, 95%CI: 1.21–1.83) and North (w/a PR = 1.41, 95%CI: 1.08–1.84) sectors, being born in the Comoros islands (w/a PR = 1.30, 95%CI: 1.03–1.61), being a student or unpaid trainee (w/a PR = 1.35, 95%CI: 1.01–1.81), living in precarious housing (w/a PR = 1.30, 95%CI: 1.02–1.67), accessing water streams for bathing (w/a PR = 1.72, 95%CI: 1.1–2.7) and knowing that malaria is a mosquito-borne disease (w/a PR = 1.42, 95%CI: 1.21–1.83). Seropositivity was found inversely associated with high education level (w/a PR = 0.50, 95%CI: 0.29–0.86) and living in households with access to running water and toilets (w/a PR = 0.64, 95%CI: 0.51–0.80) (n = 1438). Our results indicate a long-lasting immunity from chikungunya exposure. However, the current population seroprevalence is not enough to protect from future outbreaks. Individuals naïve to chikungunya and living in precarious socio-economic conditions are likely to be at high risk of infection in future outbreaks. To prevent and prepare for future chikungunya epidemics, it is essential to address socio-economic inequalities as a priority, and to strengthen chikungunya surveillance in Mayotte.

by Hitoshi Kawada, Yukiko Higa, Shinji Kasai Pyrethroid resistance in Aedes aegypti is widespread in southern Vietnam because the photostable 2nd generation pyrethroids have been used in large amounts over extensive areas for malaria and dengue vector control. In our previous report in 2009, F1534C, one of the point mutations in the voltage-sensitive sodium channel (VSSC) in Ae. aegypti, was widespread at high frequency in south and central area. However, no significant correlation between the frequency of F1534C and pyrethroid susceptibility was detected primarily because the F1534C mutation frequency in the southern highland area was very low, despite that the bioassay indicated high pyrethroid resistance. The point mutation in the VSSC, L982W, which was not the target mutation in our previous study, was recently determined to be an important mutation causing high-pyrethroid resistance in Vietnamese Ae. aegypti. In the present study, a re-investigation of L982W in the mosquito samples collected in 2006–2008 revealed a greater distribution of this mutation (allelic percentage 59.2%) than F1534C (21.7%) and the greater proportion of homozygous L982W as compared to F1534C provided a plausible answer to the question concerning the unknown resistance factor in the southern highland area. L982W frequencies were uniformly higher in the southern part of Vietnam, including the highland area with a significantly high positive correlation with pyrethroid resistance in Ae. aegypti.

Abstract Background Sickle cell trait (SCT) refers to the carriage of one abnormal copy of the β-globin gene, the HbS allele. SCT offers protection against malaria, controlling parasite density and preventing progression to symptomatic malaria. However, it remains unclear whether SCT also affects transmission stages and mosquito infection parameters. Deciphering the impact of the SCT on human to mosquito malaria transmission is key to understanding mechanisms that maintain the trait in malaria endemic areas. Methods The study was conducted from June to July 2017 among asymptomatic children living in the locality of Mfou, Cameroon. Blood samples were collected from asymptomatic children to perform malaria diagnosis by microscopy, Plasmodium species by PCR and hemoglobin typing by RFLP. Infectiousness of gametocytes to mosquitoes was assessed by membrane feeding assays using blood from gametocyte carriers of HbAA and HbAS genotypes. A zero-inflated model was fitted to predict distribution of oocysts in mosquitoes according to hemoglobin genotype of the gametocyte source. Results Among the 1557 children enrolled in the study, 314 (20.16%) were of the HbAS genotype. The prevalence of children with P. falciparum gametocytes was 18.47% in HbAS individuals and 13.57% in HbAA, and the difference is significant (χ2 = 4.61, P = 0.032). Multiplicity of infection was lower in HbAS gametocyte carriers (median = 2 genotypes/carrier in HbAS versus 3.5 genotypes/carrier in HbAA, Wilcoxon sum rank test = 188, P = 0.032). Gametocyte densities in the blood donor significantly influenced mosquito infection prevalence in both HbAS and HbAA individuals. The HbAS genotype had no significant effect on mosquito infection outcomes when using immune or naïve serum in feeding assays. In AB replacement feeding experiments, the odds ratio of mosquito infection for HbAA blood as compared to HbAS was 0.56 (95% CI 0.29–1.10), indicating a twice higher risk of infection in mosquitoes fed on gametocyte-containing blood of HbAS genotype. Conclusion Plasmodium transmission stages were more prevalent in SCT individuals. This may reflect the parasite’s enhanced investment in the sexual stage to increase their survival rate when asexual replication is impeded. The public health impact of our results points the need for intensive malaria control interventions in areas with high prevalence of HbAS. The similar infection parameters in feeding experiments where mosquitoes received the original serum from the blood donor indicated that immune responses to gametocyte surface proteins occur in both HbAS and HbAA individuals. The higher risk of infection in mosquitoes fed on HbAS blood depleted of immune factors suggests that changes in the membrane properties in HbAS erythrocytes may impact on the maturation process of gametocytes within circulating red blood cells. …

Haemosporidian species (see Glossary) are a diverse clade of vector-borne protist symbionts found in almost all terrestrial ecosystems [1–3]. All the species belonging to the order Haemosporida (Phylum Apicomplexa) have heteroxenous life cycles (Figure 1) that occur in two types of host, invertebrates from the order Diptera, and three classes of vertebrates: Reptilia, Aves, and Mammalia [1–17].

Abstract Background In Gabon, children under 5 years of age and pregnant women are the populations who are most at risk of malaria. Despite the presence of accessible health facilities, the community-based management of childhood fever remains a very common practice in Gabon, which may have serious consequences on child health. As such, the objective of this descriptive cross-sectional survey is to assess the mothers’ perception and knowledge of malaria and its severity. Methods Different households were selected using the simple random sampling method. Results A total of 146 mothers from different households were interviewed in the city of Franceville, in southern Gabon. Among the households interviewed, 75.3% had a low monthly income (below the minimum monthly income of $272.73). Among the respondents, 98.6% of mothers had heard of malaria and 55.5% had heard of severe malaria. Regarding preventive measures, 83.6% of mothers used an insecticide-treated net as a means of protection. Self-medication was practiced by 68.5% of women (100/146). Discussion The use of health facilities was motivated by better care, the decision of the head of the family, but above all by the severity of the disease. Women identified fever as the main symptom of malaria, which could be beneficial for a quicker and more efficient management of the disease in children. Malaria educational campaigns should also increase awareness of severe forms of malaria and its manifestations. This study shows that Gabonese mothers react quickly when their children have fever. However, several external factors lead them to practice self-medication as a first resort. In this survey population, the practice of self-medication did not depend on social status, marital status, level of education, on the young age or inexperience of mothers (p > 0.05). Conclusions The data revealed that mothers may underestimate severe malaria and delay medical care by self-medicating, which can have detrimental effects for children and hinder the regression of the disease. …

Abstract Background Over the past decade, implementation of multiple malaria control strategies in most countries has largely contributed to advance the global malaria elimination agenda. Nevertheless, in some regions, seasonal epidemics may adversely affect the health of local populations. In South Africa, Plasmodium falciparum malaria is still present, with the Vhembe District experiencing an incidence rate of 3.79 cases/1000 person-years in 2018, particularly in the Limpopo River Valley, bordering Zimbabwe. To elucidate the complexity of the mechanisms involved in local regular malaria outbreaks, a community-based survey was implemented in 2020 that focused on the relationship between housing conditions and malaria risky behaviours. Methods The community-based cross-sectional survey was conducted among the population of three study sites in the Vhembe District, which were selected based on malaria incidence rate, social and health characteristics of inhabitants. The household survey used a random sampling strategy, where data were collected through face-to-face questionnaires and field notes; to described the housing conditions (housing questionnaire), and focus on individual behaviours of household members. Statistical analyses were performed combining hierarchical classifications and logistic regressions. Results In this study, 398 households were described, covering a population of 1681 inhabitants of all ages, and 439 adults who participated in community-based survey. The analysis of situations at risk of malaria showed that the influence of contextual factors, particularly those defined by the type of habitat, was significant. Housing conditions and poor living environments were factors of malaria exposure and history, regardless of site of investigation, individual preventive behaviours and personal characteristics of inhabitants. Multivariate models showed that, considering all personal characteristics or behaviours of inhabitants, housing conditions such as overcrowding pressures were significantly associated with individual malaria risk. Conclusions The results showed the overwhelming weight of social and contextual factors on risk situations. Considering the Fundamental Causes Theory, malaria control policies based on health behaviour prevention, should reinforce access to care or promoting health education actions. Overarching economic development interventions in targeted geographical areas and populations have to be implemented, so that malaria control and elimination strategies can be efficiently and effectively managed. …

Abstract Background In Nigeria, declining responsiveness to artemether–lumefantrine (AL), the artemisinin-based combination therapy (ACT) of choice since 2005, has been reported. Pyronaridine–artesunate (PA) is a newer fixed-dose ACT recently prequalified by the WHO for the treatment of uncomplicated falciparum malaria. However, PA data from the Nigerian pediatric population is scarce. Therefore, the efficacy and safety of PA and AL using the WHO 28-day anti-malarial therapeutic efficacy study protocol in Ibadan, southwest Nigeria, were compared. Methods In an open-labelled, randomized, controlled clinical trial, 172 children aged 3–144 months with a history of fever and microscopically confirmed uncomplicated Plasmodium falciparum malaria were enrolled in southwest Nigeria. Enrollees were randomly assigned to receive PA or AL at standard dosages according to body weight for 3 days. Venous blood was obtained for hematology, blood chemistry, and liver function tests on days 0, 3, 7, and 28 as part of the safety evaluation. Results 165 (95.9%) of the enrolled individuals completed the study. About half (52.3%; 90/172) of enrollees were male. Eighty-seven (50.6%) received AL, while 85 (49.4%) received PA. Day 28, adequate clinical and parasitological response for PA was 92.7% [(76/82) 95% CI 83.1, 95.9] and 71.1% [(59/83) 95% CI 60.4, 79.9] for AL (0.001). Fever and parasite clearance were similar in both groups. Two of six and eight of 24 parasite recurrences were observed among PA- and AL-treated children, respectively. PCR-corrected Day-28 cure rates for PA were 97.4% (76/78) and 88.1% (59/67) for AL (= 0.04) in the per-protocol population after new infections were censored. Hematological recovery at day 28 was significantly better among PA-treated patients (34.9% 2.8) compared to those treated with AL (33.1% 3.0) (0.002). Adverse events in both treatment arms were mild and similar to the symptoms of malaria infection. Blood chemistry and liver function tests were mostly within normal limits, with an occasional marginal rise. Conclusion PA and AL were well-tolerated. PA was significantly more efficacious than AL in both the PCR-uncorrected and PCR-corrected per-protocol populations during this study. The results of this study support the inclusion of PA in the anti-malarial treatment guidelines in Nigeria. Retrospective trial registration Clinicaltrials.gov: NCT05192265. …

Abstract Background Post malarial neurological syndrome (PMNS) occurs as a sequel of cerebral malaria which is the most deadly form of severe malaria. In holo-endemic regions (areas of high malarial transmission) all forms of severe malaria as well as cerebral malaria usually occur in children and those who are semi or non-immune like pregnant women, migrants as well as tourists. It also occurs in hypo-endemic regions (areas of limited malarial transmission with low immunity) and malaria- free zones. Survivors however may have neurologic complications after recovery. PMNS has been reported in many parts of the world. Being a sequel to cerebral malaria, it is uncommon in adults who were born and reside in a holo-endemic region all their lives. Case report This is the case of an 18 year old Gambian who has lived in The Gambia all his life that had PMNS five days after recovery from cerebral malaria. Methods This was a predominantly web based literature search. The search comprise all case reports, original articles and reviews on PMNS or neurological deficits associated with malaria or noted after malaria infection. The search engines used were Google, Yahoo and Google scholar. Results A total of 62 papers were found. These were used for this review of the literature. Conclusion Cerebral malaria also occurs in adults in holo-endemic areas though rare and some of the survivors may develop PMNS. It is commoner in the youth age group. There is need for further studies since the youth may be a possible new ‘vulnerable group’ in holoendemic areas. This may lead to the widening the targeted group for malaria control in the regions of high malarial transmission. …

IntroductionVaccination is a potentially critical component of efforts to arrest development and dissemination of antimicrobial resistance (AMR), though little is known about vaccination impact within low-income and middle-income countries. This study will evaluate the impact of vaccination on reducing carriage prevalence of resistant Streptococcus pneumoniae and extended spectrum beta-lactamase-producing Escherichia coli and Klebsiella species. We will leverage two large ongoing cluster-randomised vaccine evaluations in Malawi assessing; first, adding a booster dose to the 13-valent pneumococcal conjugate vaccine (PCV13) schedule, and second, introduction of the RTS,S/AS01 malaria vaccine. Methods and analysisSix cross-sectional surveys will be implemented within primary healthcare centres (n=3000 users of outpatient facilities per survey) and their local communities (n=700 healthy children per survey): three surveys in Blantyre district (PCV13 component) and three surveys in Mangochi district (RTS,S/AS01 component). We will evaluate antibiotic prescription practices and AMR carriage in children ≤3 years. For the PCV13 component, surveys will be conducted 9, 18 and 33 months following a 3+0 to 2+1 schedule change. For the RTS,S/AS01 component, surveys will be conducted 32, 44 and 56 months post-RTS,S/AS01 introduction. Six health centres in each study component will be randomly selected for study inclusion. Between intervention arms, the primary outcome will be the difference in penicillin non-susceptibility prevalence among S. pneumoniae nasopharyngeal carriage isolates in healthy children. The study is powered to detect an absolute change of 13 percentage points (ie, 35% vs 22% penicillin non-susceptibility). Ethics and disseminationThis study has been approved by the Kamuzu University of Health Sciences (Ref: P01-21-3249), University College London (Ref: 18331/002) and University of Liverpool (Ref: 9908) Research Ethics Committees. Parental/caregiver verbal or written informed consent will be obtained prior to inclusion or recruitment in the health centre-based and community-based activities, respectively. Results will be disseminated via the Malawi Ministry of Health, WHO, peer-reviewed publications and conference presentations. …

In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks\' gestation or increase birthweight.

Abstract Background Sickle cell trait (SCT) refers to the carriage of one abnormal copy of the β-globin gene, the HbS allele. SCT offers protection against malaria, controlling parasite density and preventing progression to symptomatic malaria. However, it remains unclear whether SCT also affects transmission stages and mosquito infection parameters. Deciphering the impact of the SCT on human to mosquito malaria transmission is key to understanding mechanisms that maintain the trait in malaria endemic areas. Methods The study was conducted from June to July 2017 among asymptomatic children living in the locality of Mfou, Cameroon. Blood samples were collected from asymptomatic children to perform malaria diagnosis by microscopy, Plasmodium species by PCR and hemoglobin typing by RFLP. Infectiousness of gametocytes to mosquitoes was assessed by membrane feeding assays using blood from gametocyte carriers of HbAA and HbAS genotypes. A zero-inflated model was fitted to predict distribution of oocysts in mosquitoes according to hemoglobin genotype of the gametocyte source. Results Among the 1557 children enrolled in the study, 314 (20.16%) were of the HbAS genotype. The prevalence of children with P. falciparum gametocytes was 18.47% in HbAS individuals and 13.57% in HbAA, and the difference is significant (χ2 = 4.61, P = 0.032). Multiplicity of infection was lower in HbAS gametocyte carriers (median = 2 genotypes/carrier in HbAS versus 3.5 genotypes/carrier in HbAA, Wilcoxon sum rank test = 188, P = 0.032). Gametocyte densities in the blood donor significantly influenced mosquito infection prevalence in both HbAS and HbAA individuals. The HbAS genotype had no significant effect on mosquito infection outcomes when using immune or naïve serum in feeding assays. In AB replacement feeding experiments, the odds ratio of mosquito infection for HbAA blood as compared to HbAS was 0.56 (95% CI 0.29–1.10), indicating a twice higher risk of infection in mosquitoes fed on gametocyte-containing blood of HbAS genotype. Conclusion Plasmodium transmission stages were more prevalent in SCT individuals. This may reflect the parasite’s enhanced investment in the sexual stage to increase their survival rate when asexual replication is impeded. The public health impact of our results points the need for intensive malaria control interventions in areas with high prevalence of HbAS. The similar infection parameters in feeding experiments where mosquitoes received the original serum from the blood donor indicated that immune responses to gametocyte surface proteins occur in both HbAS and HbAA individuals. The higher risk of infection in mosquitoes fed on HbAS blood depleted of immune factors suggests that changes in the membrane properties in HbAS erythrocytes may impact on the maturation process of gametocytes within circulating red blood cells. …

Proceedings of the National Academy of Sciences, Volume 120, Issue 19, May 2023.

Abstract Background Paleomicrobiological data have clarified that Plasmodium spp. was circulating in the past in southern European populations, which are now devoid of malaria. The aim of this study was to evaluate the efficacy of immunodetection and, more particularly, rapid diagnostic tests (RDT), in order to further assess Plasmodium infections in ancient northern European populations. Methods A commercially available RDT, PALUTOP® + 4 OPTIMA, which is routinely used to detect malaria, was used to detect Plasmodium antigens from proteins recovered from ancient specimens extracted from 39 dental pulp samples. These samples were collected from 39 individuals who were buried in the sixth century, near the site of the current Palace of Versailles in France. Positive and negative controls were also used. Antigens detected were quantified using chemiluminescence imaging system analysis. Results Plasmodium antigens were detected in 14/39 (35.9%) individuals, including Plasmodium vivax antigens in 11 individuals and Plasmodium falciparum antigens co-detected in two individuals, while Pan-Plasmodium antigens were detected in three individuals. Controls all yielded expected results. Conclusions The data reported here showed that RDTs are a suitable tool for detecting Plasmodium spp. antigens in ancient dental pulp samples, and demonstrated the existence of malaria in Versailles, France, in the sixth century. Plasmodium vivax, which is regarded as being responsible for an attenuated form of malaria and less deadly forms, was the most prevalent species. This illustrates, for the first time in ancient populations, co-infection with P. falciparum, bringing into question the climate-driven ecosystems prevailing at that time in the Versailles area. …

Abstract There has been a significant reduction in malaria morbidity and mortality worldwide from 2000 to 2019. However, the incidence and mortality increased again in 2020 due to the disruption to services during the COVID-19 pandemic. Surveillance to reduce the burden of malaria, eliminate the disease and prevent its retransmission is, therefore, crucial. The 1-3-7 approach proposed by China has played an important role in eliminating malaria, which has been internationally popularized and adopted in some countries to help eliminate malaria. This review summarizes the experience and lessons of 1-3-7 approach in China and its application in other malaria-endemic countries, so as to provide references for its role in eliminating malaria and preventing retransmission. This approach needs to be tailored and adapted according to the region condition, considering the completion, timeliness and limitation of case-based reactive surveillance and response. It is very important to popularize malaria knowledge, train staff, improve the capacity of health centres and monitor high-risk groups to improve the performance in eliminating settings. After all, remaining vigilance in detecting malaria cases and optimizing surveillance and response systems are critical to achieving and sustaining malaria elimination. …

Abstract Background In Alibori and Donga, two departments of high malaria incidence of Northern Benin, pirimiphos-methyl, mixture deltamethrin + clothianidin, as well as clothianidin were used at large scale for IRS. The present study aimed to assess the residual efficacy of these products. Methods Immatures of Anopheles gambiae sensu lato (s.l.) collected in the communes of Kandi and Gogounou (Department of Alibori), Djougou and Copargo (Department of Donga) were reared until adulthood. Females aged 2–5 days were used for susceptibility tube tests following the WHO protocol. The tests were conducted with deltamethrin (0.05%), bendiocarb (0.1%), pirimiphos-methyl (0.25%) and clothianidin (2% weight per volume). For cone tests performed on cement and mud walls, the An. gambiae Kisumu susceptible strain was used. After the quality control of the IRS performed 1-week post-campaign, the evaluation of the residual activity of the different tested insecticides/mixture of insecticides was conducted on a monthly basis. Results Over the three study years, deltamethrin resistance was observed in all the communes. With bendiocarb, resistance or possible resistance was observed. In 2019 and 2020, full susceptibility to pirimiphos-methyl was observed, while possible resistance to the same product was detected in 2021 in Djougou, Gogounou and Kandi. With clothianidin, full susceptibility was observed 4–6 days post-exposure. The residual activity lasted 4–5 months for pirimiphos-methyl, and 8–10 months for clothianidin and the mixture deltamethrin + clothianidin. A slightly better efficacy of the different tested products was observed on cement walls compared to the mud walls. Conclusion Overall, An. gambiae s.l. was fully susceptible to clothianidin, while resistance/possible resistance was observed the other tested insecticides. In addition, clothianidin-based insecticides showed a better residual activity compared to pirimiphos-methyl, showing thus their ability to provide an improved and prolonged control of pyrethroid resistant vectors. …

Abstract Background Millions of dollars have been spent in fighting malaria in Namibia. However, malaria remains a major public health concern in Namibia, mostly in Kavango West and East, Ohangwena and Zambezi region. The primary goal of this study was to fit a spatio-temporal model that profiles spatial variation in malaria risk areas and investigate possible associations between disease risk and environmental factors at the constituency level in highly risk northern regions of Namibia. Methods Malaria data, climatic data, and population data were merged and Global spatial autocorrelation statistics (Moran’s I) was used to detect the spatial autocorrelation of malaria cases while malaria occurrence clusters were identified using local Moran statistics. A hierarchical Bayesian CAR model (Besag, York and Mollie’s model “BYM”) known to be the best model for modelling the spatial and temporal effects was then fitted to examine climatic factors that might explain spatial/temporal variation of malaria infection in Namibia. Results Average rainfall received on an annual basis and maximum temperature were found to have a significant spatial and temporal variation on malaria infection. Every mm increase in annual rainfall in a specific constituency in each year increases annual mean malaria cases by 0.6%, same to average maximum temperature. The posterior means of the time main effect (year t) showed a visible slightly increase in global trend from 2018 to 2020. Conclusion The study discovered that the spatial temporal model with both random and fixed effects best fit the model, which demonstrated a strong spatial and temporal heterogeneity distribution of malaria cases (spatial pattern) with high risk in most of the Kavango West and East outskirt constituencies, posterior relative risk (RR: 1.57 to 1.78). …

Abstract Background Malaria is the leading cause of morbidity and mortality among infants and children under-five in sub-Saharan Africa. In the Sahel, seasonal malaria chemoprevention (SMC) is delivered door-to-door in monthly cycles. In each cycle, children are administered sulfadoxine–pyrimethamine (SP) plus amodiaquine (AQ) on Day 1 by community distributors, and AQ on Day 2 and Day 3 by caregivers. Non-adherence to AQ administration by caregivers has implications for emergence of antimalarial resistance. Methods Predictors of non-adherence to administration of AQ on Day 2 and Day 3 among caregivers of children aged 3–59 months who had received Day 1 SP and AQ during the last 2020 SMC cycle (n = 12,730) were analysed using data from SMC coverage surveys in Nigeria, Burkina Faso and Togo, and fitting multivariate random-effects logistic regression models. Results Previous adverse reaction to SMC medicines by eligible children (OR: 0.29, 95% CI 0.24–0.36, p 

AbstractBackgroundThe northwestern border of Thailand is an area of low seasonal malaria transmission. Until recent successful malaria elimination activities, malaria was a major cause of morbidity and mortality. Historically the incidences of symptomatic Plasmodium falciparum and Plasmodium vivax malaria were approximately similar.MethodsAll malaria cases managed in the Shoklo Malaria Research Unit along the Thailand-Myanmar border between 2000 and 2016 were reviewed.ResultsThere were 80,841 consultations for symptomatic P. vivax and 94,467 for symptomatic P. falciparum malaria. Overall 4,844 (5.1%) patients with P. falciparum malaria were admitted to field hospitals, of whom 66 died, compared with 278 (0.34%) with P. vivax malaria, of whom four died (three were diagnosed with sepsis, so the contribution of malaria to their fatal outcomes is uncertain). Applying the 2015 “World Health Organization severe malaria criteria”, 68/80,841 (0.08%) of P. vivax and 1,482/94,467 (1.6%) of P. falciparum admissions were classified as severe. Overall, patients with P. falciparum malaria were 15 (95% CI 13.2-16.8) times more likely than P. vivax to require hospital admission, 19 (95% CI 14.6-23.8) times more likely to develop severe malaria, and at least 14 (95% CI 5.1-38.7) times more likely to die.ConclusionsIn this area both P. falciparum and P. vivax infections were important causes of hospitalization, but life-threatening P. vivax illness was rare.

With huge demand for new malaria vaccines, Gavi is concerned that scaling up production and affordability pose a formidable challenge. John Zarocostas reports from Geneva.

by Janet Storm, Grazia Camarda, Michael J. Haley, David Brough, Kevin N. Couper, Alister G. Craig Monocytes contribute to the pro-inflammatory immune response during the blood stage of a Plasmodium falciparum infection, but their precise role in malaria pathology is not clear. Besides phagocytosis, monocytes are activated by products from P. falciparum infected erythrocytes (IE) and one of the activation pathways is potentially the NLR family pyrin domain containing 3 (NLRP3) inflammasome, a multi-protein complex that leads to the production of interleukin (IL)-1β. In cerebral malaria cases, monocytes accumulate at IE sequestration sites in the brain microvascular and the locally produced IL-1β, or other secreted molecules, could contribute to leakage of the blood-brain barrier. To study the activation of monocytes by IE within the brain microvasculature in an in vitro model, we co-cultured IT4var14 IE and the monocyte cell line THP-1 for 24 hours and determined whether generated soluble molecules affect barrier function of human brain microvascular endothelial cells, measured by real time trans-endothelial electrical resistance. The medium produced after co-culture did not affect endothelial barrier function and similarly no effect was measured after inducing oxidative stress by adding xanthine oxidase to the co-culture. While IL-1β does decrease barrier function, barely any IL-1β was produced in the co- cultures, indicative of a lack of or incomplete THP-1 activation by IE in this co-culture model.

by Nicholas Ekow Thomford, Akwasi Anyanful, Richmond Owusu Ateko, Dee Blackhurst, Robert Peter Biney, Dennis Boadi, Samuel Badu Nyarko, Martins Ekor, George Boateng Kyei Background Apolipoprotein E is involved in lipid transport and clearance of lipoprotein through low-density lipoprotein receptors (LDLR). ApoE variation has been linked to cardiovascular disease (CVD) risk. There are 3 isoforms of ApoE which originate from two non-synonymous single nucleotide polymorphisms denoted as ε2, ε3 and ε4. The ε2 isoform is implicated in higher levels of atherogenic lipoprotein with the ε4 isoform causing LDLR downregulation. This leads to variable effects and differential CVD risk. Malaria and HIV are life-threatening diseases affecting several countries globally especially in sub-Saharan Africa. Parasite and viral activities have been implicated in lipid dysregulation leading to dyslipidaemia. This study examined ApoE variation and CVD risk assessment in malaria and HIV patients. Methods We compared 76 malaria-only, 33 malaria-HIV coinfected, 21-HIV-only and 31 controls from a tertiary health facility in Ghana. Fasting venous blood samples were taken for ApoE genotyping and lipid measurements. Clinical and laboratory data were collected with ApoE genotyping performed using Iplex Gold microarray and PCR-RFLP. Cardiovascular disease risk was calculated using the Framingham BMI and cholesterol risk and Qrisk3 tools. Results The frequency of C/C genotype for rs429358 was 9.32%, whiles T/T genotype for rs7412 was found in 2.48% of all participants. ε3/ε3 was the most distributed ApoE genotype accounting for 51.55% of the total participants whiles ε2/ε2 was found in 2.48% of participants, with 1 in malaria-only and 3 in HIV-only patients. There was a significant association between ε4+ and high TG (OR = 0.20, CI; 0.05–0.73; p = 0.015), whiles ε2+ was significantly associated with higher BMI (OR; 0.24, CI; 0.06–0.87; p = 0.030) and higher Castelli Risk Index II in females (OR = 11.26, CI; 1.37–92.30; p = 0.024). A higher proportion of malaria-only participants had a moderate to high 10-year CVD risk. Conclusion Overall malaria patients seem to have a higher CVD risk though the means through which this occurs may be poorly understood. ε2/ε2 genotypes was observed in our population at a lower frequency. Further studies are vital to determine CVD risk in malaria and how this occurs. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 108 Issue: 5 Pages: 868-870 …

Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 108 Issue: 5 Pages: 968-976 …

Proceedings of the National Academy of Sciences, Volume 120, Issue 18, May 2023.

Abstract Background The Republic of Djibouti is a malaria endemic country that was in pre-elimination phase in 2006–2012. From 2013, however, malaria has re-emerged in the country, and its prevalence has been increasing every year. Given the co-circulation of several infectious agents in the country, the assessment of malaria infection based on microscopy or histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDT) has shown its limitations. This study, therefore, aimed to assess the prevalence of malaria among febrile patients in Djibouti city using more robust molecular tools. Methods All suspected malaria cases reported to be microscopy-positive were randomly sampled (n = 1113) and included in four health structures in Djibouti city over a 4-year period (2018–2021), mainly during the malaria transmission season (January–May). Socio-demographic information was collected, and RDT was performed in most of the included patients. The diagnosis was confirmed by species-specific nested polymerase chain reaction (PCR). Data were analysed using Fisher’s exact test and kappa statistics. Results In total, 1113 patients with suspected malaria and available blood samples were included. PCR confirmed that 788/1113 (70.8%) were positive for malaria. Among PCR-positive samples, 656 (83.2%) were due to Plasmodium falciparum, 88 (11.2%) Plasmodium vivax, and 44 (5.6%) P. falciparum/P. vivax mixed infections. In 2020, P. falciparum infections were confirmed by PCR in 50% (144/288) of negative RDTs. After the change of RDT in 2021, this percentage decreased to 17%. False negative RDT results were found more frequently (P 

Abstract Background Understanding malaria epidemiology is a critical step toward efficient malaria control and elimination. The objective of this meta-analysis was to derive robust estimates of malaria prevalence and Plasmodium species from studies conducted in Mauritania and published since 2000. Methods The present review followed the PRISMA guidelines. Searches were conducted in various electronic databases such as PubMed, Web of Science, and Scopus. To obtain pooled prevalence of malaria, meta-analysis was performed using the DerSimonian-Laird random-effects model. Methodological quality of eligible prevalence studies was assessed using Joanna Briggs Institute tool. Inconsistency and heterogeneity between studies were quantified by the I2 index and Cochran’s Q test. Publication bias was assessed with funnel plots and Egger’s regression tests. Results A total of 16 studies with a good individual methodological quality were included and analysed in this study. The overall random effects pooled prevalence of malaria infection (symptomatic and asymptomatic) across all included studies was 14.9% (95% confidence interval [95% CI]: 6.64, 25.80, I2 = 99.8%, P 

Abstract Background Intermittent Preventive Treatment of malaria in infants (IPTi) is a malaria control strategy consisting of the administration of an anti-malarial drug alongside routine immunizations. So far, this is being implemented nationwide in Sierra Leone only. IPTi has been renamed as Perennial Malaria Chemoprevention -PMC-, accounting for its recently recommended expansion into the second year of life. Before starting a pilot implementation on PMC, the currently implemented strategy and malaria prevalence were assessed in young children in selected areas of Sierra Leone. Methods A cross-sectional, community-based, multi-stage cluster household survey was conducted from November to December 2021 in selected districts of the Northern and northwestern provinces of Sierra Leone among 10–23 months old children, whose caretakers gave written informed consent to participate in the survey. Coverage of IPTi and malaria prevalence—assessed with rapid diagnostic tests—were calculated using percentages and 95% confidence intervals weighted for the sampling design and adjusted for non-response within clusters. Factors associated with RDT + and iPTi coverage were also assessed. Results A total of 720 children were recruited. Coverage of three IPTi doses was 50.57% (368/707; 95% CI 45.38–55.75), while prevalence of malaria infection was 28.19% (95% CI 24.81–31.84). Most children had received IPTi1 (80.26%, 574/707; 95% CI 75.30–84.44), and IPTi2 (80.09%, 577/707; 95% CI 76.30–83.40) and over half of the children also received IPTi3 (57.72%, 420/707; 95% CI 53.20–62.11). The uptake of each IPTi dose was lower than that of the vaccines administered at the same timepoint at all contacts. Conclusion In Sierra Leone, half of the children received the three recommended doses of IPTi indicating an increase in its uptake compared to previous data of just a third of children receiving the intervention. However, efforts need to be made in improving IPTi coverage, especially in the planned expansion of the strategy into the second year of life following recent WHO guidelines. …

Abstract Background Indoor residual spraying (IRS) has been the main tool used to control malaria. Reducing the life span and the density of the vector mosquitoes are direct effects of IRS towards restricting malaria transmission. Residents must not wash or re-plaster walls after the spray application for at least 6 months to fight against malaria with IRS. This study sought to assess the alteration of the sprayed wall after the IRS operation and associated factors among households in the Boricha district. Methods Community-based cross-sectional study was conducted among 608 households selected using multi-stage sampling. A structured interviewer-administered questionnaire was used to collect data. Data were analysed by SPSS version 25. Both bivariable and multivariable logistic regression analysis was done. Finally, the strength of the association was measured based on AOR with 95% CI and statistical significance was declared at a p-value less than 0.05. Result From the total of 608 sprayed houses included in the study, 37.3% (95% CI: 33.41% – 41.15%) were found to have altered sprayed walls. The highest class of wealth index category (AOR = 2.50; 95% CI: 1.19, 5.16), low level of comprehensive knowledge about IRS (AOR = 6.08; 95% CI: 3.37, 10.94), did not get information within 2 weeks before spray (AOR = 2.09; 95% CI: 1.43, 3.05), absence of supervision after the spray operation (AOR = 1.77; 95% CI: 1.27, 2.73) and walking distance to nearest health facility (AOR = 2.39; 95% CI: 1.63, 3.35) remained significant factors of altering of the sprayed wall after IRS. Conclusion The prevalence of alteration was relatively high. The highest socio-economic status, poor knowledge about indoor residual spraying, lack of information about IRS within two weeks before spray, absence of supervision after IRS, and walking distance of more than 30 min to reach the nearest health post were the factors affecting the alteration status of the sprayed wall. Future efforts to focus on successive awareness creation activities should be done before and after IRS operation to the community by concerned bodies. …

Abstract Background Over the past decade, the incidence of malaria has steadily declined in Myanmar, with Plasmodium vivax becoming predominant. The resilience of P. vivax to malaria control is attributed to the parasite’s ability to form hypnozoites in the host’s liver, which can cause relapse. Primaquine is used to eliminate hypnozoites but can cause haemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. It is thus necessary to estimate the frequency and variant types of G6PD deficiency in areas where primaquine will be widely used for P. vivax elimination. Methods In this study, a descriptive cross-sectional survey was conducted to determine the prevalence of G6PD deficiency in a population residing in Nay Pyi Taw, Myanmar, using a standard spectrophotometric assay, a rapid diagnostic test (RDT), Biosensor, and by genotyping G6PD variants. Results G6PD enzyme activity was determined from 772 leukocyte-depleted samples, with an adjusted male median G6PD activity value of 6.3 U/g haemoglobin. Using a cut-off value of 30% enzyme activity, the overall prevalence of G6PD deficiency was 10.8%. Genotyping of G6PD variants was performed for 536 samples, of which 131 contained mutations. The Mahidol variant comprised the majority, and males with the Mahidol variant showed lower G6PD enzyme activity. The G6PD Andalus variant, which has not been reported in Myanmar before, was also identified in this study. Conclusion This study provides a G6PD enzyme activity reference value for the Myanmar population and further information on the prevalence and variants of G6PD deficiency among the Myanmar population; it also evaluates the feasibility of G6PD deficiency tests. …

Abstract Background Artemisinin-based combination therapy (ACT) is the most effective treatment for malaria, and has significantly reduced morbimortality. Polymorphisms associated with the Plasmodium falciparum Kelch gene (Pfkelch13) have been associated with delayed parasite clearance even with ACT treatment. Methods The Pfkelch13 gene was sequenced from P. falciparum infected patients (n = 159) with uncomplicated malaria in Niger. An adequate clinical and parasitological response (ACPR) was reported in 155 patients. Four (n = 4) patients had treatment failure (TF) that were not reinfections—two of which had late parasitological failures (LPF) and two had late clinical failures (LCF). Results Thirteen single nucleotide polymorphisms (SNPs) were identified of which seven were non-synonymous (C469R, T508S, R515T, A578S, I465V, I437V, F506L,), and three were synonymous (P443P, P715P, L514L). Three SNP (C469R, F506L, P715P) were present before ACT treatment, while seven mutations (C469R, T508S, R515T, L514L, P443P, I437V, I465V) were selected by artemether/lumefantrine (AL)—five of which were non-synonymous (C469R, T508S, R515T, I437V, I465V). Artesunate/amodiaquine (ASAQ) has selected any mutation. One sample presented three cumulatively non-synonymous SNPs—C469R, T508S, R515T. Conclusions This study demonstrates intra-host selection of Pfkelch13 gene by AL. The study highlights the importance of LCF and LPF parasites in the selection of resistance to ACT. Further studies using gene editing are required to confirm the potential implication of resistance to ACT with the most common R515T and T508S mutations. It would also be important to elucidate the role of cumulative mutations. …

The human malaria parasite, P. falciparum, prevents progress toward global health equity and causes over half a million annual deaths mainly in infants and pregnant women of sub-Saharan Africa [1]. Over the past few decades, this mortality has been reduced by interventions including artemisinin-based combination therapies, insecticidal nets, and rapid diagnostic tests. However, further progress has been hindered by the spread of antimalarial resistance and the lack of highly effective vaccines. Furthermore, the parasite seems to adapt to survive in areas with low transmission and persists as asymptomatic infections that are often missed by diagnostics [2,3].

Abstract Background Methods for evaluating efficacy of core malaria interventions in experimental and operational settings are well established but gaps exist for spatial repellents (SR). The objective of this study was to compare three different techniques: (1) collection of blood-fed mosquitoes (feeding), (2) human landing catch (HLC), and (3) CDC light trap (CDC-LT) collections for measuring the indoor protective efficacy (PE) of the volatile pyrethroid SR product Mosquito Shield™ Methods The PE of Mosquito Shield™ against a wild population of pyrethroid-resistant Anopheles arabiensis mosquitoes was determined via feeding, HLC, or CDC-LT using four simultaneous 3 by 3 Latin squares (LS) run using 12 experimental huts in Tanzania. On any given night each technique was assigned to two huts with control and two huts with treatment. The LS were run twice over 18 nights to give a sample size of 72 replicates for each technique. Data were analysed by negative binomial regression. Results The PE of Mosquito Shield™ measured as feeding inhibition was 84% (95% confidence interval (CI) 58–94% [Incidence Rate Ratio (IRR) 0.16 (0.06–0.42), p