Abstract Background The rate of physical deterioration of long-lasting insecticidal nets (LLINs) varies by household practices, net brand and environment. One way to sustain the protection provided by LLINs against malaria is through day-to-day care, and repairing holes as and when they occur. To ensure LLIN coverage is high between mass campaigns and, as international donor funds decrease, personal responsibility to maintain nets in good condition is becoming more important. This study aimed to understand local barriers and motivators to net care and repair in southern Tanzania in a community that receives free LLINs through a school-based distribution mechanism. Methods Qualitative research methods were applied in a rural and peri-urban village in Ruangwa district. Focus group discussions (FGDs) were conducted for five groups of 8–12 participants; (1) key informants, (2) young men (18–24 years old), (3) women (> 18 years) with children under the age of five, (4) older men (> 25 years), and (5) older women with or without children (> 25 years). In each village, five men, five women with or without children, and five women with children under the age of five were recruited for in-depth interviews (IDIs). After each IDI and FGD with women with young children, participants were guided through a participatory activity. The study also counted the number and size of holes in nets currently used by IDI participants to determine their physical degradation status. Results A general willingness to care and repair mosquito nets was observed in Ruangwa district for the love of a good night’s sleep free of mosquito bites or noises. Net care was preferred over repair, especially among women who were the primary caretakers. The main motivation to look after nets was protection against mosquito bites and malaria. Washing nets occurred as frequently as every other week in some households to ensure cleanliness, which prevented other dirt-related problems such as sneezing and headaches. Barriers to net care included care not being a priority in the day-to-day activities and lack of net retreatment kits. Net repair was reported to be a temporary measure and necessary as soon as a hole was identified. However, during the net assessment and participatory activity, it became clear that people did not actually repair smaller holes. Protection against mosquitoes, malaria and cost saving from replacing nets were identified as motivators for net repair. Barriers to net repair included it not being a priority to repair holes that could be tucked under the mattress and lack of knowledge on when to repair nets. Conclusion In Ruangwa, net care was defined as overall net maintenance, such as cleanliness, and not directly associated with the prevention of damage as reported in other studies. Net repair was reported as a temporary measure before the acquisition of a new net, hence not a priority in a busy household. Inconsistencies were observed between reported intentions to repair mosquito nets and current net condition. Targeted education through health facilities and community change agents are potential means to overcome barriers to net care and repair.…

Millat-Martinez, P., Ila, R., Laman, M., Robinson, L., Karunajeewa, H., Abel, H., Pulai, K., Sanz, S., Manning, L., Moore, B., Bassat, Q., Mitja, O.

Background: Mass drug administration (MDA) of sequential rounds of antimalarial drugs is being considered as a tool for malaria elimination. As an effective and long-acting antimalarial, Dihydroartemisinin-piperaquine (DHA/PQP) appears suitable as a candidate for MDA. However, absence of cardiac safety data following repeated administration hinders its use in the extended schedules proposed for MDA.Methods: We conducted an interventional study in Lihir Island, Papua New Guinea, with healthy individuals aged 3 to 60 years who received a standard 3-day course of DHA/PQP on 3 consecutive months. Twelve-lead electrocardiography (ECG) readings were conducted pre-dose and 4h after the final dose of each month. The primary safety endpoint was QTc (using Fridericia’s correction; QTcF) prolongation from baseline to 4h post-dosing. We compared the difference in prolongation between the third course post-dose and the first course post-dose.Results: Of 84 enrolled participants, 69 (82%) completed all treatment courses and ECG measurements. The average increase in QTcF was 19.6 ms (SD 17.8) and 17.1 ms (SD 17.1) for the first-course and third-course post-dosing ECGs [risk difference -2.4 (95%CI - 6.9 to 2.1), p=0.285], respectively. We recorded QTcF prolongation >60 ms from baseline in 3 (4.3%) and 2 (2.9%) participants after the first course and third course (p=1.00), respectively. No participants had QTcF intervals >500 ms at any time point.Conclusions: Three consecutive monthly courses of DHA/PQP were as safe as a single course. The absence of cumulative cardiotoxicity with repeated dosing support the use of monthly DHA/PQP as part of malaria elimination strategies.…

Abstract Background Severe malaria in children is often associated with long-term behavioural and cognitive problems. A sizeable minority of children go on to experience repeated malaria due to the high transmission and infection rates in the region. The purpose of this study was to explore caregivers’ experiences of parenting a child with a history of severe malaria followed by repeated episodes of uncomplicated malaria in comparison to healthy community children. Methods Thirty-one caregivers were enrolled in the study. These included caregivers of children previously exposed to severe malaria and who had experienced repeated uncomplicated malaria attacks (SM with RMA, n = 15), caregivers of children exposed to severe malaria who did not experience repeated episodes (SM, n = 10), and caregivers of healthy community children (CC, n = 6) were purposively selected. Results Thematic-content analysis generated eight areas of concern, six of which were noted only by caregivers of children with SM or SM with RMA: (1) a sense of helplessness; (2) challenges with changes in behaviour; (3) responses to a child’s behaviour; (4) family life disruptions, including breakdown of relationships and inadequate male-spouse involvement in child care; (5) disagreements in seeking healthcare; (6) societal burden; and two by caregivers of children with SM, SM with RMA and also CC; (7) concern about academic achievement; and, (8) balancing work and family life. Conclusions The study findings suggest that severe malaria, especially when followed by repeated malaria episodes, affects not only children who have the illness but also their caregivers. The effects on caregivers can decrease their social functioning and isolate them from other parents and may disrupt families. Interventions to support caregivers by counselling the ongoing problems that might be expected in children who have had severe malaria and repeated episodes of malaria, and how to manage these problems, may provide a way to improve behavioural and mental health outcomes for those children and their caregivers.…

Abstract Background Haiti and the Dominican Republic, the only two Caribbean countries with endemic malaria transmission, are committed to eliminating malaria. With a Plasmodium falciparum prevalence under 1% and a highly focal transmission, the efforts towards elimination in Haiti will include several community-based interventions that must be tailored to the local sociocultural context to increase their uptake. However, little is known about local community perceptions regarding malaria and the planned elimination interventions. The aim of this study is to develop a robust understanding of how to tailor, implement and promote malaria elimination strategies in Haiti. Methods A cross-sectional qualitative study was conducted December 2015–August 2016 in Grande-Anse and the North Department in Haiti. Data collection included key informant interviews (n = 51), in-depth interviews (n = 15) and focus group discussions (n = 14) with health workers, traditional healers, teachers, priests or pastors, informal community leaders, public officials, and community members. Following a grounded theory approach, transcripts were coded and analysed using content analysis. Coded text was sorted by the types of interventions under consideration by the malaria elimination programme. Results The level of knowledge about malaria was low. Many participants noted community beliefs about malaria being caused by magical phenomena in addition to vector-borne transmission. Participants described malaria as a problem rooted in the environment, with vector control the most noted method of prevention. Though participants noted malaria a severe disease, it ranked lower than other health problems perceived as more acute. Access barriers to healthcare were described including a lack of bed nets. Some distrust about pills, tests, and foreigners in general was expressed, and in few cases linked to previous experience with malaria campaigns under dictatorial regimes. Conclusions There are several potential barriers and opportunities to implement community-based malaria elimination interventions in rural Haiti. Elimination efforts should include the collaboration of voodoo priests and other traditional healers, be coupled with solutions to wider community concerns or other health interventions, and learn from previous or similar programmes, such as the campaign to eliminate lymphatic filariasis. It is essential to engage with communities and gain their trust to successfully implement targeted aggressive elimination activities.…

Natalie E Hofmann, Maria Gruenberg, Elma Nate, Alice Ura, Daniela Rodriguez-Rodriguez, Mary Salib, Ivo Mueller, Thomas A Smith, Moses Laman, Leanne J Robinson, Ingrid Felger

Almost all potentially transmitting parasite carriers were identified with us-qPCR on fingerprick blood volumes. Analysing larger blood volumes revealed a large pool of ultra-low-density P falciparum and P vivax infections, which are unlikely to be transmitted. Therefore, current RDTs cannot replace molecular diagnostics for identifying potential P falciparum transmitters.

Titus H Divala, Randy G Mungwira, Patricia M Mawindo, Osward M Nyirenda, Maxwell Kanjala, Masiye Ndaferankhande, Lufina E Tsirizani, Rhoda Masonga, Francis Muwalo, Gail E Potter, Jessie Kennedy, Jaya Goswami, Blair J Wylie, Atis Muehlenbachs, Lughano Ndovie, Priscilla Mvula, Yamikani Mbilizi, Tamiwe Tomoka, Miriam K Laufer

Chloroquine administered as intermittent therapy did not provide better protection from malaria and related adverse effects compared with intermittent sulfadoxine-pyrimethamine in a setting of high resistance to sulfadoxine-pyrimethamine. Chloroquine chemoprophylaxis might provide benefit in protecting against malaria during pregnancy, but studies with larger sample sizes are needed to confirm these results.

John Zarocostas

African leaders launch a continent-wide Zero Malaria Starts with Me campaign to spur response in the face of a setback in progress in the fight against the disease. John Zarocostas reports.

Yoelis Yepes-Pérez, Carolina López, Carlos Fernando Suárez, Manuel Alfonso Patarroyo

by Yoelis Yepes-Pérez, Carolina López, Carlos Fernando Suárez, Manuel Alfonso Patarroyo Malaria is an infectious disease caused by parasites from the genus Plasmodium (P. falciparum and P. vivax are responsible for 90% of all clinical cases); it is widely distributed throughout the world’s tropical and subtropical regions. The P. vivax Pv12 protein is involved in invasion, is expressed on merozoite surface and has been recognised by antibodies from individuals exposed to the disease. In this study, B- and T-cell epitopes from Pv12 were predicted and characterised to advance in the design of a peptide-based vaccine against malaria. For evaluating the humoral response of individuals exposed to natural P. vivax infection from two endemic areas in Colombia, BepiPred-1.0 software was used for selecting B-cell epitopes. B-cell epitope 39038 displayed the greatest recognition by naturally-acquired antibodies and induced an IgG2/IgG4 response. NetMHCIIpan-3.1 prediction software was used for selecting peptides having high affinity binding for HLA-DRβ1* allele lineages and this was confirmed by in-vitro binding assays. T-epitopes 39113 and 39117 triggered a memory T-cell response (Stimulation Index≥2) and significant cytokine production. Combining in-silico, in-vitro and functional assays, two Pv12 protein regions (containing peptides 39038, 39040, 39113 and 39117) have thus been characterised as promising vaccine candidates against P. vivax malaria.

Abstract Background The decline in the efficacy of artemisinin-based combination treatment (ACT) in some endemic regions threatens the progress towards global elimination of malaria. Molecular surveillance of drug resistance in malaria-endemic regions is vital to detect the emergence and spread of mutant strains. Methods We observed 89 malaria patients for the efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum infections in Lagos, Nigeria and determined the prevalence of drug resistant strains in the population. Parasite clearance rates were determined by microscopy and the highly sensitive var gene acidic terminal sequence (varATS) polymerase chain reaction for 65 patients with samples on days 0, 1, 3, 7, 14, 21 and 28 after commencement of treatment. The genomic finger print of parasite DNA from pre- and post-treatment samples were determined using 24 nuclear single nucleotide polymorphisms (SNP) barcode for P. falciparum. Drug resistance associated alleles in chloroquine resistance transporter gene (crt-76), multidrug resistance genes (mdr1–86 and mdr1–184), dihydropteroate synthase (dhps-540), dihydrofolate reductase (dhfr-108) and kelch domain (K-13580) were genotyped by high resolution melt analysis of polymerase chain reaction (PCR) fragments. Results By varATS qPCR, 12 (18.5%) of the participants had detectable parasite DNA in their blood three days after treatment, while eight (12.3%) individuals presented with genotypable day 28 parasitaemia. Complexity of infection (CoI) was 1.30 on day 0 and 1.34 on day 28, the mean expected heterozygosity (HE) values across all barcodes were 0.50 ± 0.05 and 0.56 ± 0.05 on days 0 and 28 respectively. Barcode (π) pairwise comparisons showed high genetic relatedness of day 0 and day 28 parasite isolates in three (37.5%) of the eight individuals who presented with re-appearing infections. Crt-76 mutant allele was present in 38 (58.5%) isolates. The mdr1–86 mutant allele was found in 56 (86.2%) isolates. No mutation in the K-13580 was observed. Conclusions Persistence of DNA-detectable parasitaemia in more than 18% of cases after treatment and indications of genetic relatedness between pre- and post-treatment infections warrants further investigation of a larger population for signs of reduced ACT efficacy in Nigeria.…

Abstract This opinion article deals with the diagnostic clinical challenges faced by clinicians or health care workers in malaria-endemic areas when a severely sick child presents to the clinic with fever, coma or respiratory distress. Indeed, the coexistence of malaria with other severe infections like meningitis, invasive bacterial infection or pneumonia makes appropriate treatment allocation a matter of life and death. The use of biomarkers has been proposed as a potential solution to this problem. The arrival of high-throughput technologies allowed thousands of molecules (transcripts, proteins and metabolites) to be been screened in clinical samples from large cohorts of well/characterised patients. The major aim of these studies was to identify biomarkers that inform important decisions: should this child be referred to hospital? Should antibiotics, anti-malarials, or both, be administered? There is a large discrepancy between the number of biomarker discovery studies published and the number of biomarkers that have been clinically validated, let alone implemented. This article reflects on the many opportunities and obstacles encountered in biomarker research in malaria-endemic areas.…

Abstract Background Although the use of induced blood stage malaria infection has proven to be a valuable tool for testing the efficacy of vaccines and drugs against Plasmodium falciparum, a limiting factor has been the availability of Good Manufacturing Practice (GMP)—compliant defined P. falciparum strains for in vivo use. The aim of this study was to develop a cost-effective method for the large-scale production of P. falciparum cell banks suitable for use in clinical trials. Methods Genetically-attenuated parasites (GAP) were produced by targeted deletion of the gene encoding the knob associated histidine rich protein (kahrp) from P. falciparum strain 3D7. A GAP master cell bank (MCB) was manufactured by culturing parasites in an FDA approved single use, closed system sterile plastic bioreactor. All components used to manufacture the MCB were screened to comply with standards appropriate for in vivo use. The cryopreserved MCB was subjected to extensive testing to ensure GMP compliance for a phase 1 investigational product. Results Two hundred vials of the GAP MCB were successfully manufactured. At harvest, the GAP MCB had a parasitaemia of 6.3%, with 96% of parasites at ring stage. Testing confirmed that all release criteria were met (sterility, absence of viral contaminants and endotoxins, parasite viability following cryopreservation, identity and anti-malarial drug sensitivity of parasites). Conclusion Large-scale in vitro culture of P. falciparum parasites using a wave bioreactor can be achieved under GMP-compliant conditions. This provides a cost-effective methodology for the production of malaria parasites suitable for administration in clinical trials.…

Abstract Background Achieving vector control targets is a key step towards malaria elimination. Because of variations in reporting of progress towards vector control targets in 2013, the coverage of these vector control interventions in Namibia was assessed. Methods Data on 9846 households, representing 41,314 people, collected in the 2013 nationally-representative Namibia Demographic and Health Survey were used to explore the coverage of two vector control methods: indoor residual spraying (IRS) and insecticide-treated nets (ITNs). Regional data on Plasmodium falciparum parasite rate in those aged 2–10 years (PfPR2–10), obtained from the Malaria Atlas Project, were used to provide information on malaria transmission intensity. Poisson regression analyses were carried out exploring the relationship between household interventions and PfPR2–10, with fully adjusted models adjusting for wealth and residence type and accounting for regional and enumeration area clustering. Additionally, the coverage as a function of government intervention zones was explored and models were compared using log-likelihood ratio tests. Results Intervention coverage was greatest in the highest transmission areas (PfPR2–10 ≥ 5%), but was still below target levels of 95% coverage in these regions, with 27.6% of households covered by IRS, 32.3% with an ITN and 49.0% with at least one intervention (ITN and/or IRS). In fully adjusted models, PfPR2–10 ≥ 5% was strongly associated with IRS (RR 14.54; 95% CI 5.56–38.02; p 

Abstract Background Despite the development of resistance to Plasmodium falciparum malaria, sulfadoxine–pyrimethamine is still effective for intermittent preventive treatment of malaria in pregnancy (IPTp). In Tanzania, more than 10 years have passed since sulfadoxine–pyrimethamine and sulfamethopyrazine–pyrimethamine (SPs) were reserved for IPTp only. However, the retail pharmaceutical outlet dispensers’ knowledge and their compliance with the policies have not been recently explored. Therefore, this study was designed to investigate dispensers’ knowledge about these medications together with their actual dispensing practices, a decade since they were limited for IPTp use only. Methods This descriptive cross-sectional study was conducted between February and July 2017 in all municipalities of Dar-es-Salaam city. Data were collected by direct interviews using a structured questionnaire to assess knowledge and a simulated client approach was used to assess the actual practice of medicine dispensers. Data analysis was done by using SPSS version 20 and Chi square test was used to test significant differences in proportions between different categorical variables. A p-value of less than 0.05 was considered to be statistically significant. Results A random sample of 422 medicine dispensers participated in this study whereby 185 (43.8%) were from community pharmacies and 237 (56.2%) from accredited drug dispensing outlets. The study revealed that SPs were available in 76% of the community pharmaceutical outlets in Dar es Salaam. In general majority of the dispensers (64%) had moderate to high knowledge about SPs and their indication. About 80% of the dispensers were aware that SP is reserved for IPTp. However, irrespective of the level of knowledge, almost all dispensers (92%) were willing to dispense the medicines for the purpose of treating malaria, contrary to the current Tanzania malaria treatment guideline. Conclusion Majority of the medicine dispensers in the community pharmaceutical outlets were knowledgeable about SPs and their indications. Disappointingly, almost all dispensers irrespective of their levels of knowledge were willing to dispense SPs for treatment of malaria contrary to the available treatment guidelines.…

Abstract Background The detection of submicroscopic infections in low prevalence settings has become an increasingly important challenge for malaria elimination strategies. The current field rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria are inadequate to detect low-density infections. Therefore, there is a need to develop more sensitive field diagnostic tools. In parallel, a highly sensitive laboratory reference assay will be essential to evaluate new diagnostic tools. Recently, the highly sensitive Alere™ Malaria Ag P.f ELISA (HS ELISA) was developed to detect P. falciparum histidine-rich protein 2 (HRP2) in clinical whole blood specimens. In this study, the analytical and clinical performance of the HS ELISA was determined using recombinant P. falciparum HRP2, P. falciparum native culture parasites, and archived highly pedigreed clinical whole blood specimens from Karen village, Myanmar and Nagongera, Uganda. Results The HS ELISA has an analytical sensitivity of less than 25 pg/mL and shows strong specificity for P. falciparum HRP2 when tested against P. falciparum native culture strains with pfhrp2 and pfhrp3 gene deletions. Additionally, the Z′-factor statistic of 0.862 indicates the HS ELISA as an excellent, reproducible assay, and the coefficients of variation for inter- and intra-plate testing, 11.76% and 2.51%, were acceptable. Against clinical whole blood specimens with concordant microscopic and PCR results, the HS ELISA showed 100% (95% CI 96.4–100) diagnostic sensitivity and 97.9% (95% CI 94.8–99.4) diagnostic specificity. For P. falciparum positive specimens with HRP2 concentrations below 400 pg/mL, the sensitivity and specificity were 100% (95% CI 88.4–100) and 88.9% (95% CI 70.8–97.6), respectively. The overall sensitivity and specificity for all 352 samples were 100% (CI 95% 96–100%) and 97.3% (CI 95% 94–99%). Conclusions The HS ELISA is a robust and reproducible assay. The findings suggest that the HS ELISA may be a useful tool as an affordable reference assay for new ultra-sensitive HRP2-based RDTs.…

Abstract Background Radical cure of Plasmodium vivax malaria requires treatment with a blood schizonticide and a hypnozoitocide (primaquine) to eradicate the dormant liver stages. There has been uncertainty about the operational effectiveness and optimum dosing of the currently recommended 14-day primaquine (PQ) course. Methods A two centre, randomized, open-label, two arm study was conducted in South India. Patients were randomized to receive either high dose (0.5 mg base/kg body weight) or conventional dose (0.25 mg/kg) PQ for 14 days. Plasma concentrations of PQ and carboxyprimaquine (CPQ) on the 7th day of treatment were measured by reverse phase high performance liquid chromatography. Study subjects were followed up for 6 months. Recurrent infections were genotyped using capillary fragment length polymorphism of two PCR-amplified microsatellite markers (MS07 and MS 10). Results Fifty patients were enrolled. Baseline characteristics and laboratory features did not differ significantly between the groups. Mean age of the study population was 42 ± 16.0 years. Recurrences 80–105 days later occurred in 4 (8%) patients, two in each the groups. All recurrences had the same microsatellite genotype as that causing the index infection suggesting all were relapses. One relapse was associated with low CPQ concentrations suggesting poor adherence. Conclusions This small pilot trial supports the effectiveness of the currently recommended lower dose (0.25 mg/kg/day) 14 day PQ regimen for the radical cure of vivax malaria in South India. Trial registration Clinical Trials Registry-India, CTRI/2017/03/007999. Registered 3 March 2017, http://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&compid=19&EncHid=82755.86366.…

Abstract Background Artemether–lumefantrine (AL) and artesunate–amodiaquine are first-line treatment for uncomplicated malaria in many endemic countries, including Mali. Dihydroartemisinin–piperaquine (DHA–PQ) is also an alternative first-line artemisinin-based combination therapy, but only few data are available on DHA–PQ efficacy in sub-Saharan Africa. The main aim of this study was to compare clinical efficacy of DHA–PQ versus AL, using the World Health Organization (WHO) 42-day in vivo protocol. Methods The efficacy of three-dose regimens of DHA–PQ was compared to AL combination in a randomized, comparative open label trial using the WHO 42-day follow-up protocol from 2013 to 2015 in Doneguebougou and Torodo, Mali. The primary endpoint was to access the PCR-corrected Adequate Clinical and Parasitological Responses at day 28. Results A total of 317 uncomplicated malaria patients were enrolled, with 159 in DHA–PQ arm and 158 in AL arm. The parasite positivity rate decreased from 68.4% (95% CI 60.5–75.5) on day 1 to 3.8% (95% CI 1.4–8.1) on day 2 for DHA–PQ and 79.8% (95% CI 72.3–85.7) on day 1 to 9.5% (95% CI 5.4–15.2) on day 2 for AL, (p = 0.04). There was a significant difference in the uncorrected ACPR between DHA–PQ and AL, both at 28-day and 42-day follow-up with 97.4% (95% CI 93.5–99.3) in DHA–PQ vs 84.5% (95% CI 77.8–89.8) in AL (p 

Abstract Background Plasmodium vivax is the most geographically widespread of the human malaria parasites, causing 50,000 to 100,000 deaths annually. Plasmodium vivax parasites have the unique feature of forming dormant liver stages (hypnozoites) that can reactivate weeks or months after a parasite-infected mosquito bite, leading to new symptomatic blood stage infections. Efforts to eliminate P. vivax malaria likely will need to target the persistent hypnozoites in the liver. Therefore, research on P. vivax liver stages necessitates a marker for clearly distinguishing between actively replicating parasites and dormant hypnozoites. Hypnozoites possess a densely fluorescent prominence in the parasitophorous vacuole membrane (PVM) when stained with antibodies against the PVM-resident protein Upregulated in Infectious Sporozoites 4 (PvUIS4), resulting in a key feature recognizable for quantification of hypnozoites. Thus, PvUIS4 staining, in combination with the characteristic small size of the parasite, is currently the only hypnozoite-specific morphological marker available. Results Here, the generation and validation of a recombinant monoclonal antibody against PvUIS4 (α-rUIS4 mAb) is described. The variable heavy and light chain domains of an α-PvUIS4 hybridoma were cloned into murine IgG1 and IgK expression vectors. These expression plasmids were co-transfected into HEK293 cells and mature IgG was purified from culture supernatants. It is shown that the α-rUIS4 mAb binds to its target with high affinity. It reliably stains the schizont PVM and the hypnozoite-specific PVM prominence, enabling the visual differentiation of hypnozoites from replicating liver stages by immunofluorescence assays in different in vitro settings, as well as in liver sections from P. vivax infected liver-chimeric mice. The antibody functions reliably against all four parasite isolates tested and will be an important tool in the identification of the elusive hypnozoite. Conclusions The α-rUIS4 mAb is a versatile tool for distinguishing replicating P. vivax liver stages from dormant hypnozoites, making it a valuable resource that can be deployed throughout laboratories worldwide.…

Abstract Background Artemisinin-resistant Plasmodium falciparum has been reported throughout the Greater Mekong subregion and threatens to disrupt current malaria control efforts worldwide. Polymorphisms in kelch13 have been associated with clinical and in vitro resistance phenotypes; however, several studies suggest that the genetic determinants of resistance may involve multiple genes. Current proposed mechanisms of resistance conferred by polymorphisms in kelch13 hint at a connection to an autophagy-like pathway in P. falciparum. Results A SNP in autophagy-related gene 18 (atg18) was associated with long parasite clearance half-life in patients following artemisinin-based combination therapy. This gene encodes PfAtg18, which is shown to be similar to the mammalian/yeast homologue WIPI/Atg18 in terms of structure, binding abilities, and ability to form puncta in response to stress. To investigate the contribution of this polymorphism, the atg18 gene was edited using CRISPR/Cas9 to introduce a T38I mutation into a k13-edited Dd2 parasite. The presence of this SNP confers a fitness advantage by enabling parasites to grow faster in nutrient-limited settings. The mutant and parent parasites were screened against drug libraries of 6349 unique compounds. While the SNP did not modulate the parasite’s susceptibility to any of the anti-malarial compounds using a 72-h drug pulse, it did alter the parasite’s susceptibility to 227 other compounds. Conclusions These results suggest that the atg18 T38I polymorphism may provide additional resistance against artemisinin derivatives, but not partner drugs, even in the absence of kelch13 mutations, and may also be important in parasite survival during nutrient deprivation.…

Abstract Background Anopheles sacharovi is a dominant malaria vector species in South Europe and the Middle East which has a highly plastic behaviour at both adult and larval stages. Such plasticity has prevented this species from eradication by several anti-vector campaigns. The development of new genome-based strategies for vector control will benefit from genome sequencing and physical chromosome mapping of this mosquito. Although a cytogenetic photomap for chromosomes from salivary glands of An. sacharovi has been developed, no cytogenetic map suitable for physical genome mapping is available. Methods Mosquitoes for this study were collected at adult stage in animal shelters in Armenia. Polytene chromosome preparations were prepared from ovarian nurse cells. Fluorescent in situ hybridization (FISH) was performed using PCR amplified probes. Results This study constructed a high-quality standard photomap for polytene chromosomes from ovarian nurse cells of An. sacharovi. Following the previous nomenclature, chromosomes were sub-divided into 39 numbered and 119 lettered sub-divisions. Chromosomal landmarks for the chromosome recognition were described. Using FISH, 4 PCR-amplified genic probes were mapped to the chromosomes. The positions of the probes demonstrated gene order reshuffling between An. sacharovi and Anopheles atroparvus which has not been seen cytologically. In addition, this study described specific chromosomal landmarks that can be used for the cytotaxonomic diagnostics of An. sacharovi based on the banding pattern of its polytene chromosomes. Conclusions This study constructed a high-quality standard photomap for ovarian nurse cell chromosomes of An. sacharovi and validated its utility for physical genome mapping. Based on the map, cytotaxonomic features for identification of An. sacharovi have been described. The cytogenetic map constructed in this study will assist in creating a chromosome-based genome assembly for this mosquito and in developing cytotaxonomic tools for identification of other species from the Maculipennis group.…

Robert, M. G., Foguim Tsombeng, F., Gendrot, M., Mosnier, J., Amalvict, R., Benoit, N., Torrentino-Madamet, M., Pradines, B., the French National Reference Centre for Imported Malaria Study Group

Resistance to piperaquine has been associated with the amplification of the plasmepsin 2 gene in Cambodia. None of the 175 African isolates that we analyzed had plasmepsin 2 gene amplification (piperaquine inhibitory concentration 50% ranged from 0.94 to 137.5 nM), suggesting a low level of piperaquine reduced susceptibility prevalence in Africa. Additionally, the few isolates with reduced susceptibility to piperaquine did not harbor amplification of the plasmepsin 2 gene.…

Rodrigues Gomes, L., Lavigne, A., Peterka, C. L., Brasil, P., Menard, D., Tadeu Daniel-Ribeiro, C., Ferreira-da-Cruz, M. d. F.

P. falciparum ART-resistant parasites can be evaluated examining polymorphisms in the Kelch (PfK13) domain. 69 samples from falciparum malaria patients were analyzed. All samples were from Brazilian endemic areas of the following states: Acre (n=14), Amapá (n=15), Amazonas (n=30) and Pará (n=10). After DNA alignment with the 3D7 reference sequence all samples were found to be wild-type. These data provide a baseline on PfK13 and reinforce the pertinence of ACTs treatment in Brazilian areas.…

Rachel D. Savage, Laura C. Rosella, Natasha S. Crowcroft, Maureen Horn, Kamran Khan, Monali Varia

by Rachel D. Savage, Laura C. Rosella, Natasha S. Crowcroft, Maureen Horn, Kamran Khan, Monali Varia An ongoing challenge of estimating the burden of infectious diseases known to disproportionately affect migrants (e.g. malaria, enteric fever) is that many health information systems, including reportable disease surveillance systems, do not systematically collect data on migrant status and related factors. We explored whether health administrative data linked to immigration records offered a viable alternative for accurately identifying cases of hepatitis A, malaria and enteric fever in Ontario, Canada. Using linked health care databases generated by Ontario’s universal health care program, we constructed a cohort of medically-attended individuals with presumed hepatitis A, malaria or enteric fever in Peel region using diagnostic codes. Immigrant status was ascertained using linked immigration data. The sensitivity and positive predictive value (PPV) of diagnostic codes was evaluated through probabilistic linkage of the cohort to Ontario’s reportable disease surveillance system (iPHIS) as the reference standard. Linkage was successful in 90.0% (289/321) of iPHIS cases. While sensitivity was high for hepatitis A and enteric fever (85.8% and 83.7%) and moderate for malaria (69.0%), PPV was poor for all diseases (0.3–41.3%). The accuracy of diagnostic codes did not vary by immigrant status. A dated coding system for outpatient physician claims and exclusion of new immigrants not yet eligible for health care were key challenges to using health administrative data to identify cases. Despite this, we show that linkages of health administrative and immigration records with reportable disease surveillance data are feasible and have the potential to bridge important gaps in estimating burden using either data source independently.  …

Rambhatla J, Turner L, Manning L, et al.

AbstractBackgroundPlasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates parasite sequestration in postcapillary venules in P. falciparum malaria. PfEMP1 types can be classified based on their cysteine-rich interdomain region (CIDR) domains. Antibodies to different PfEMP1 types develop gradually after repeated infections as children age, and antibodies to specific CIDR types may confer protection.MethodsLevels of immunoglobulin G to 35 recombinant CIDR domains were measured by means of Luminex assay in acute-stage (baseline) and convalescent-stage plasma samples from Papua New Guinean children with severe or uncomplicated malaria and in healthy age-matched community controls.ResultsAt baseline, antibody levels were similar across the 3 groups. After infection, children with severe malaria had higher antibody levels than those with uncomplicated malaria against the endothelial protein C receptor (EPCR) binding CIDRα1 domains, and this difference was largely confined to older children. Antibodies to EPCR-binding domains increased from presentation to follow-up in severe malaria, but not in uncomplicated malaria.ConclusionsThe acquisition of antibodies against EPCR-binding CIDRα1 domains of PfEMP1 after a severe malaria episode suggest that EPCR-binding PfEMP1 may have a role in the pathogenesis of severe malaria in Papua New Guinea.

Yohanna Kambai Avong, Bolajoko Jatau, Ritmwa Gurumnaan, Nanfwang Danat, James Okuma, Istifanus Usman, Dennis Mordi, Blessing Ukpabi, Gbenga Ayodele Kayode, Saswata Dutt, Osman El-Tayeb, Bamgboye Afolabi, Isah Ambrose, Oche Agbaji, Adeline Osakwe, Ali Ibrahim, Comfort Ogar, Helga Nosiri, Eunice B. Avong, Victor Adekanmbi, Olalekan Uthman, Alash’le Abimiku, Yetunde O. Oni, Charles Olalekan Mensah, Patrick Dakum, Kamau Edward Mberu, Olumide A. T. Ogundahunsi

by Yohanna Kambai Avong, Bolajoko Jatau, Ritmwa Gurumnaan, Nanfwang Danat, James Okuma, Istifanus Usman, Dennis Mordi, Blessing Ukpabi, Gbenga Ayodele Kayode, Saswata Dutt, Osman El-Tayeb, Bamgboye Afolabi, Isah Ambrose, Oche Agbaji, Adeline Osakwe, Ali Ibrahim, Comfort Ogar, Helga Nosiri, Eunice B. Avong, Victor Adekanmbi, Olalekan Uthman, Alash’le Abimiku, Yetunde O. Oni, Charles Olalekan Mensah, Patrick Dakum, Kamau Edward Mberu, Olumide A. T. Ogundahunsi Background Adverse Drug Reactions (ADRs) are a major clinical and public health problem world-wide. The prompt reporting of suspected ADRs to regulatory authorities to activate drug safety surveillance and regulation appears to be the most pragmatic measure for addressing the problem. This paper evaluated a pharmacovigilance (PV) training model that was designed to improve the reporting of ADRs in public health programs treating the Human Immunodeficiency Virus (HIV), Tuberculosis (TB) and Malaria. Methods A Structured Pharmacovigilance and Training Initiative (SPHAR-TI) model based on the World Health Organization accredited Structured Operational Research and Training Initiative (SOR-IT) model was designed and implemented over a period of 12 months. A prospective cohort design was deployed to evaluate the outcomes of the model. The primary outcomes were knowledge gained and Individual Case Safety Reports (ICSR) (completed adverse drug reactions monitoring forms) submitted, while the secondary outcomes were facility based Pharmacovigilance Committees activated and health facility healthcare workers trained by the participants. Results Fifty-five (98%) participants were trained and followed up for 12 months. More than three quarter of the participants have never received training on pharmacovigilance prior to the course. Yet, a significant gain in knowledge was observed after the participants completed a comprehensive training for six days. In only seven months, 3000 ICSRs (with 100% completeness) were submitted, 2,937 facility based healthcare workers trained and 46 Pharmacovigilance Committees activated by the participants. Overall, a 273% increase in ICSRs submission to the National Agency for Food and Drug Administration and Control (NAFDAC) was observed. Conclusion Participants gained knowledge, which tended to increase the reporting of ADRs. The SPHAR-TI model could be an option for strengthening the continuous reporting of ADRs in public health programs in resource limited settings.…

Abstract Background The degree to which insecticide-treated net (ITN) supply accounts for age and gender disparities in ITN use among household members is unknown. This study explores the role of household ITN supply in the variation in ITN use among household members in sub-Saharan Africa. Methods Data was from Malaria Indicator Surveys or Demographic and Health Surveys collected between 2011 and 2016 from 29 countries in sub-Saharan Africa. The main outcome was ITN use the previous night. Other key variables included ITN supply (nets/household members), age and gender of household members. Analytical methods included logistic regressions and meta-regression. Results Across countries, the median (range) of the percentage of households with enough ITNs was 30.7% (8.5–62.0%). Crude analysis showed a sinusoidal pattern in ITN use across age groups of household members, peaking at 0–4 years and again around 30–40 years and dipping among people between 5–14 and 50+ years. This sinusoidal pattern was more pronounced in households with not enough ITNs compared to those with enough ITNs. ITN use tended to be higher in females than males in households with not enough ITNs while use was comparable among females and males in households with enough ITNs. After adjusting for wealth quintile, residence and region, among households with not enough ITNs in all countries, the odds of ITN use were consistently higher among children under 5 years and non-pregnant women 15–49 years. Meta-regressions showed that across all countries, the mean adjusted odds ratio (aOR) of ITN use among children under 5 years, pregnant and non-pregnant women aged 15–49 years and people 50 years and above was significantly higher than among men aged 15–49 years. Among these household members, the relationship was attenuated when there were enough ITNs in the household (dropping 0.26–0.59 points) after adjusting for geographical zone, household ITN supply, population ITN access, and ITN use:access ratio. There was no significant difference in mean aOR of ITN use among school-aged children compared to men aged 15–49 years, regardless of household ITN supply. Conclusions This study demonstrated that having enough ITNs in the household increases level of use and decreases existing disparities between age and gender groups. ITN distribution via mass campaigns and continuous distribution channels should be enhanced as needed to ensure that households have enough ITNs for all members, including men and school-aged children.…

Abstract Background Much of the extensive research regarding transmission of malaria is underpinned by mathematical modelling. Compartmental models, which focus on interactions and transitions between population strata, have been a mainstay of such modelling for more than a century. However, modellers are increasingly adopting agent-based approaches, which model hosts, vectors and/or their interactions on an individual level. One reason for the increasing popularity of such models is their potential to provide enhanced realism by allowing system-level behaviours to emerge as a consequence of accumulated individual-level interactions, as occurs in real populations. Methods A systematic review of 90 articles published between 1998 and May 2018 was performed, characterizing agent-based models (ABMs) relevant to malaria transmission. The review provides an overview of approaches used to date, determines the advantages of these approaches, and proposes ideas for progressing the field. Results The rationale for ABM use over other modelling approaches centres around three points: the need to accurately represent increased stochasticity in low-transmission settings; the benefits of high-resolution spatial simulations; and heterogeneities in drug and vaccine efficacies due to individual patient characteristics. The success of these approaches provides avenues for further exploration of agent-based techniques for modelling malaria transmission. Potential extensions include varying elimination strategies across spatial landscapes, extending the size of spatial models, incorporating human movement dynamics, and developing increasingly comprehensive parameter estimation and optimization techniques. Conclusion Collectively, the literature covers an extensive array of topics, including the full spectrum of transmission and intervention regimes. Bringing these elements together under a common framework may enhance knowledge of, and guide policies towards, malaria elimination. However, because of the diversity of available models, endorsing a standardized approach to ABM implementation may not be possible. Instead it is recommended that model frameworks be contextually appropriate and sufficiently described. One key recommendation is to develop enhanced parameter estimation and optimization techniques. Extensions of current techniques will provide the robust results required to enhance current elimination efforts.…

Abstract Background An estimated 30 million women give birth annually in malaria endemic areas of sub-Saharan Africa. Malaria in pregnancy is associated with an increased risk of adverse maternal and infant outcomes. To combat the adverse effects of MiP, the World Health Organization (WHO) recommends the provision of intermittent preventive treatment in pregnancy with sulfadoxine–pyrimethamine (IPTp–SP) in areas of moderate to high malaria transmission. In 2012, the WHO updated its policy with respect to IPTp administration to recommend administration at each antenatal care visit in the second and third trimesters, with a minimum of three, rather than two, doses. While rapid improvements in coverage were expected, gains have occurred more slowly than anticipated. Methods The President’s Malaria Initiative (PMI) assessed IPTp uptake before and after countries implemented the new WHO policy, and assessed how long it took for implementation to occur, using a combination of data from household surveys, routine health management information systems, and programmatic data provided to PMI. Results It took an average of 2 years for countries to complete the process of revising their IPTp policies, and it was not until 2015 that all 17 PMI countries had updated their policies. Policy dissemination and training had not been completed in several countries as of early 2018, and only seven countries had fully implemented the new policy including updating their antenatal care registers to collect information on IPTp3+ coverage. The coverage of IPTp1+, 2+, and 3+ has increased by 19, 16, and 13 percentage points since the revised IPTp policy adoption. Discussion Overall, coverage of both IPTp2+ and IPTp3+ has improved in recent years. The change in policy from a minimum of two to a minimum of three doses has likely contributed to these improvements. Progress has been slow, likely related to the complicated process of policy adoption exacerbated by the lag in measurement through national household surveys. The impact of future policy changes may be more readily seen if the policy change and implementation process were more streamlined and coordinated between key stakeholders (National Malaria Control Programmes and Reproductive Health Programmes), with more real-time data reporting.…

Abstract Background The study of malaria transmission requires the experimental infection of mosquitoes with Plasmodium gametocytes. In the laboratory, this is achieved using artificial membrane feeding apparatus that simulate body temperature and skin of the host, and so permit mosquito feeding on reconstituted gametocyte-containing blood. Membrane feeders either use electric heating elements or complex glass chambers to warm the infected blood; both of which are expensive to purchase and can only be sourced from a handful of specialized companies. Presented and tested here is a membrane feeder that can be inexpensively printed using 3D-printing technology. Results Using the Plasmodium falciparum laboratory strain NF54, three independent standard membrane feeding assays (SMFAs) were performed comparing the 3D-printed feeder against a commercial glass feeder. Exflagellation rates did not differ between the two feeders. Furthermore, no statistically significant difference was found in the oocyst load nor oocyst intensity of Anopheles stephensi mosquitoes (mean oocyst range 1.3–6.2 per mosquito; infection prevalence range 41–79%). Conclusions Open source provision of the design files of the 3D-printed feeder will facilitate a wider range of laboratories to perform SMFAs in laboratory and field settings, and enable them to freely customize the design to their own requirements.…

Abstract Background Anopheles sinensis is an important vector for the spread of malaria in China. Olfactory-related behaviours, particularly oviposition site seeking, offer opportunities for disrupting the disease-transmission process. Results This is the first report of the identification and characterization of AsinOrco and AsinOR10 in An. sinensis. AsinOrco and AsinOR10 share 97.49% and 90.37% amino acid sequence identity, respectively, with related sequences in Anopheles gambiae. A functional analysis demonstrated that AsinOrco- and AsinOR10-coexpressing HEK293 cells were highly sensitive to 3-methylindole, but showed no significant differences in response to other test odorants when compared to DMSO. Conclusions AsinOrco was characterized as a new member of the Orco ortholog subfamily. AsinOR10, which appears to be a member of the OR2-10 subfamily, is directly involved in identification of oviposition sites. This finding will help to elucidate the molecular mechanisms underlying olfactory signaling in An. sinensis and provide many more molecular targets for eco-friendly pest control.…

Abstract Malaria is a major cause of anaemia in tropical areas. Malaria infection causes haemolysis of infected and uninfected erythrocytes and bone marrow dyserythropoiesis which compromises rapid recovery from anaemia. In areas of high malaria transmission malaria nearly all infants and young children, and many older children and adults have a reduced haemoglobin concentration as a result. In these areas severe life-threatening malarial anaemia requiring blood transfusion in young children is a major cause of hospital admission, particularly during the rainy season months when malaria transmission is highest. In severe malaria, the mortality rises steeply below an admission haemoglobin of 3 g/dL, but it also increases with higher haemoglobin concentrations approaching the normal range. In the management of severe malaria transfusion thresholds remain uncertain. Prevention of malaria by vector control, deployment of insecticide-treated bed nets, prompt and accurate diagnosis of illness and appropriate use of effective anti-malarial drugs substantially reduces the burden of anaemia in tropical countries.…

Abstract Background Viet Nam has made tremendous progress towards reducing mortality and morbidity associated with malaria in recent years. Despite the success in malaria control, there has been a recent increase in cases in some provinces. In order to understand the changing malaria dynamics in Viet Nam and measure progress towards elimination, the aim of this study was to describe and quantify spatial and temporal trends of malaria by species at district level across the country. Methods Malaria case reports at the Viet Nam National Institute of Malariology, Parasitology, and Entomology were reviewed for the period of January 2009 to December 2015. The population of each district was obtained from the Population and Housing Census-2009. A multivariate (insecticide-treated mosquito nets [ITN], indoor residual spraying [IRS], maximum temperature), zero-inflated, Poisson regression model was developed with spatial and spatiotemporal random effects modelled using a conditional autoregressive prior structure, and with posterior parameters estimated using Bayesian Markov chain Monte Carlo simulation with Gibbs sampling. Covariates included in the models were coverage of intervention (ITN and IRS) and maximum temperature. Results There was a total of 57,713 Plasmodium falciparum and 32,386 Plasmodium vivax cases during the study period. The ratio of P. falciparum to P. vivax decreased from 4.3 (81.0% P. falciparum; 11,121 cases) in 2009 to 0.8 (45.0% P. falciparum; 3325 cases) in 2015. Coverage of ITN was associated with decreased P. falciparum incidence, with a 1.1% (95% credible interval [CrI] 0.009%, 1.2%) decrease in incidence for 1% increase in the ITN coverage, but this was not the case for P. vivax, nor was it the case for IRS coverage. Maximum temperature was associated with increased incidence of both species, with a 4% (95% CrI 3.5%, 4.3%) and 1.6% (95% CrI 0.9%, 2.0%) increase in P. falciparum and P. vivax incidence for a temperature increase of 1 °C, respectively. Temporal trends of P. falciparum and P. vivax incidence were significantly higher than the national average in Central and Central-Southern districts. Conclusion Interventions (ITN distribution) and environmental factors (increased temperature) were associated with incidence of P. falciparum and P. vivax during the study period. The factors reviewed were not exhaustive, however the data suggest distribution of resources can be targeted to areas and times of increased malaria transmission. Additionally, changing distribution of the two predominant malaria species in Viet Nam will require different programmatic approaches for control and elimination.…

Abstract Background Malaria is a major mosquito transmitted, blood-borne parasitic disease that afflicts humans. The disease causes anaemia and other clinical complications, which can lead to death. Plasmodium vivax is known for its reticulocyte host cell specificity, but many gaps in disease details remain. Much less is known about the closely related species, Plasmodium cynomolgi, although it is naturally acquired and causes zoonotic malaria. Here, a computational model is developed based on longitudinal analyses of P. cynomolgi infections in nonhuman primates to investigate the erythrocyte dynamics that is pertinent to understanding both P. cynomolgi and P. vivax malaria in humans. Methods A cohort of five P. cynomolgi infected Rhesus macaques (Macaca mulatta) is studied, with individuals exhibiting a plethora of clinical outcomes, including varying levels of anaemia. A discrete recursive model with age structure is developed to replicate the dynamics of P. cynomolgi blood-stage infections. The model allows for parasitic reticulocyte preference and assumes an age preference among the mature RBCs. RBC senescence is modelled using a hazard function, according to which RBCs have a mean lifespan of 98 ± 21 days. Results Based on in vivo data from three cohorts of macaques, the computational model is used to characterize the reticulocyte lifespan in circulation as 24 ± 5 h (n = 15) and the rate of RBC production as 2727 ± 209 cells/h/µL (n = 15). Analysis of the host responses reveals a pre-patency increase in the number of reticulocytes. It also allows the quantification of RBC removal through the bystander effect. Conclusions The evident pre-patency increase in reticulocytes is due to a shift towards the release of younger reticulocytes, which could result from a parasite-induced factor meant to increase reticulocyte availability and satisfy the parasite’s tropism, which has an average value of 32:1 in this cohort. The number of RBCs lost due to the bystander effect relative to infection-induced RBC losses is 62% for P. cynomolgi infections, which is substantially lower than the value of 95% previously determined for another simian species, Plasmodium coatneyi.…

Abstract Background The mechanisms of activation and regulation of T lymphocytes and their cytokines in malaria caused by Plasmodium vivax are complex and poorly understood. Previous data suggest that T cells balance protective immune responses with immune mediated pathology in malaria. This study investigates the lymphocytic profile of patients infected with P. vivax by identifying and quantifying the specific sub-populations of Th1, Th2, Th17 and Treg cells and observing the correlation between parasitaemia and the number of platelets. Methods A cross-sectional study was carried out in an endemic area of the state of Acre, Brazil. In order to obtain identification and quantification of lymphocyte sub-populations through flow cytometry, blood samples were collected from 50 individuals infected with P. vivax and 20 non-infected controls. To differentiate Th1 from Th2, the presence of cytokines IL-4 and TNF was examined by enzyme-linked immunosorbent assay. Utilizing the Mann–Whitney and Spearman coefficient tests, comparison and correlation analysis were rendered to test the parasitaemia and the number of platelets relationship. Results The data indicate that individuals infected with P. vivax present a significant reduction in Th1, Th2 and Th17 cell sub-populations when compared to the non-infected control group. A negative correlation exists between parasitaemia and platelet counts in individuals infected with P. vivax. There is no correlation of parasitaemia or thrombocytopaenia with any sub-population of T lymphocytes analysed. Interestingly, patients with serum Th1 cytokine profile present inversely proportional parasitaemia to the increase in the number of Th1, Th2, Th17 and Treg cells while patients with serum Th2 cytokine profile present directly proportional parasitaemia to the increase in number of Th1 and Th2 cells. Regarding the number of platelets, patients with serum Th1 cytokine profile show a correlation directly proportional to the Th17 sub-population. In contrast, platelet counts are directly proportional only to Treg and activated Treg cells in patients with serum Th2 cytokine profile. Conclusions During the P. vivax infection patients with serum Th1 versus Th2 cytokine profile present different biological mechanisms for activating the immune system against parasite load.…

Abstract Background Malaria is one of the major public health problems worldwide. In Ethiopia, there is a significant decline in disease burden; however, the overall trend of malaria prevalence is not studied or well-documented in different localities. Hence, the initiation of this study was to analyse the 5-year trends of malaria prevalence in Ataye, North Shoa, Ethiopia. Methods A retrospective laboratory record review was conducted in Ataye Hospital, North-Shoa, Ethiopia. Malaria data reported from 2013 to 2017 were carefully reviewed from January to March 2018. Results A total of 31,810 blood films were prepared and examined from malaria-suspected patients at Ataye District Hospital from 2013 to 2017. Of the examined blood films, 2670 (8.4%) were microscopically confirmed malaria cases. The trend of malaria prevalence in the present study seems non- fluctuating. Plasmodium falciparum and Plasmodium vivax accounted for 2087 (78.2%) and 557 (20.9%) cases, respectively. From total positive cases, 1.0% of cases were mixed P. falciparum/P. vivax infections, and that no Plasmodium malariae and Plasmodium ovale infections were found by malaria microscopists. Malaria cases were higher in males 1584 (5.0%) than females 1086 (3.4%). With regard to age groups, higher numbers of malaria cases were observed in age group 15–45 years old. Malaria cases were high in spring (September to December), which is a peak malaria transmission period in Ethiopia. Conclusion Malaria is still among the major public health problems in the country. P. falciparum is the dominant species in the study area followed by P. vivax. Enhancing malaria detection and speciation skill of laboratory personnel and scaling up malaria control and prevention activities are very crucial to significantly reduce the burden of malaria in the study area.…

Phubeth Ya-Umphan, Dominique Cerqueira, Gilles Cottrell, Daniel M. Parker, Freya J. I. Fowkes, Francois Nosten and Vincent Corbel

Abstract. Timely identification and treatment of malaria transmission “hot spots” is essential to achieve malaria elimination. Here we investigate the relevance of using an Anopheles salivary biomarker to estimate Plasmodium falciparum malaria exposure risk along the Thailand–Myanmar border to guide malaria control. Between May 2013 and December 2014, > 9,000 blood samples collected in a cluster randomized control trial were screened with serological assays to measure the antibody responses to Anopheles salivary antigen (gSG6-P1) and P. falciparum malaria antigens (circumsporozoite protein, merozoite surface protein 119 [MSP-119]). Plasmodium falciparum infections were monitored through passive and active case detection. Seroprevalence to gSG6-P1, MSP-119, and CSP were 71.8% (95% Confidence interval [CI]: 70.9, 72.7), 68.6% (95% CI: 67.7, 69.5), and 8.6% (95% CI: 8.0, 9.2), respectively. Multivariate analysis showed that individuals with the highest Ab response to gSG6-P1 had six times the odds of being positive to CSP antigens (P < 0.001) and two times the odds of P. falciparum infection compared with low gSG6-P1 responders (P = 0.004). Spatial scan statistics revealed the presence of clusters of gSG6-P1 that partially overlapped P. falciparum infections. The gSG6-P1 salivary biomarker represents a good proxy for estimating P. falciparum malaria risk and could serve to implement hot spot–targeted vector control interventions to achieve malaria elimination.…

Abstract Background The widespread use of artemisinin-based combination therapy (ACT) and long-lasting insecticide-treated nets (LLINs) has led to an impressive decrease of malaria burden these recent years in Africa. However, some new challenges about the future of malaria control and elimination efforts have appeared. Among these challenges, the loss and—or—the only partial acquisition of anti-Plasmodium immunity among exposed populations lead to an increase of the age at risk of malaria. Indeed, older children and adults may become more vulnerable to malaria. Studies about malaria among adults seemed, therefore, important. This study investigated the evolution of malaria morbidity in adults of Dielmo (Senegal) before and after the implementation of LLINs. Methods From August 2007 to July 2015, a longitudinal study involving adults above 15 years old was carried out in Dielmo, where ACT was introduced in June 2006 and LLINs in July 2008. In July 2011 and August 2014, all LLINs were renewed. The presence of each person in the village was monitored daily. Thick smears associated lately with rapid diagnosis test (RDT) and quantitative polymerase chain reaction methods were performed for all cases of fever. To assess malaria prevalence, thick smears and RDT were performed quarterly in all individuals. Malaria risks factors were assessed using negative binomial regression mixed-model based on person-trimester observations. Results Malaria morbidity among adults has decreased significantly since the implementation of LLINs in Dielmo. However, malaria resurgences have occurred twice during the 7 years of LLINs use. During these malaria resurgences, the overall incidence of malaria among adults was similar to the incidence during the year before the implementation of LLINs (adjusted incidence rate ratio [95% CI] aIRR = 1.04 [0.66–1.64], p = 0.88 and aIRR = 1.16 [0.74–1.80], p = 0.52 during the first and the second malaria resurgence period, respectively). Younger adults were most vulnerable during these malaria upsurges as the incidence of malaria increased significantly among them (χ2 = 5.2; p = 0.02). Conclusion Malaria among adults especially younger adults should deserve more attention in the areas where malaria was previously endemic as they became vulnerable probably because of the partial acquisition and—or—the loss of anti-Plasmodium relative immunity and the non regular use of LLINs.…

Kieran S. O’Brien, Abdou Amza, Boubacar Kadri, Baido Nassirou, Sun Y. Cotter, Nicole E. Stoller, Sheila K. West, Robin L. Bailey, Travis C. Porco, Bruce D. Gaynor, Thomas M. Lietman and Catherine E. Oldenburg

Abstract. The complex relationship between malnutrition and malaria affects morbidity and mortality in children younger than 5 years, particularly in parts of sub-Saharan Africa where these conditions occur together seasonally. Previous research on this relationship has been inconclusive. Here, we examine the association between anthropometric indicators and malaria infection in a population-based sample of children younger than 5 years in Niger. This cross-sectional study is a secondary analysis of a cluster-randomized trial comparing treatment strategies for trachoma in Niger. We included children aged 6–60 months residing in the 48 communities enrolled in the trial who completed anthropometric and malaria infection assessments at the final study visit. We evaluated the association between anthropometric indicators, including height-for-age z-score (HAZ) and weight-for-age z-score (WAZ) and indicators of malaria infection, including malaria parasitemia and clinical malaria. In May 2013, we collected data from 1,649 children. Of these, 780 (47.3%) were positive for malaria parasitemia and 401 (24.3%) had clinical malaria. In models of malaria parasitemia, the adjusted odds ratio (aOR) was 1.05 (95% confidence interval [CI]: 1.00–1.10) for HAZ and 1.07 (95% CI: 0.99, 1.15) for WAZ. In models of clinical malaria, the aOR was 1.07 (95% CI: 1.02–1.11) for HAZ and 1.09 (95% CI: 1.01–1.19) for WAZ. Overall, we did not find evidence of an association between most anthropometric indicators and malaria infection. Greater height may be associated with an increased risk of clinical malaria.…

Ne Myo Aung, Phyo Pyae Nyein, Thu Ya Htut, Zaw Win Htet, Tint Tint Kyi, Nicholas M. Anstey, Mar Mar Kyi and Josh Hanson

Abstract. It has been believed that concomitant bacteremia is uncommon in adults hospitalized with falciparum malaria. Accordingly, the World Health Organization treatment guidelines presently only recommended additional antibacterial therapy in these patients if they have a clinical syndrome compatible with serious bacterial infection. Admission blood cultures were collected from 20 consecutive adults in Myanmar, hospitalized with a positive immunochromatographic test and blood film, suggesting a diagnosis of falciparum malaria; four (20%) had bacteremia with a clinically significant pathogen. These case series’ data were pooled with a previously published multicenter study from Myanmar which had also collected blood cultures in adults hospitalized with a diagnosis of falciparum malaria. Among 87 patients in the two studies, 13 (15%) had clinically significant bacteremia on admission, with Gram-negative organisms in 10 (77%) and Staphylococcus aureus in the remaining three (23%). Bacteremic patients had more severe disease than non-bacteremic patients (median [interquartile range] respiratory coma acidosis malaria score 2 [1–4] versus 1 [1–2], P = 0.02) and were more likely to die (2/13 [15%] versus 1/74 [1%], P = 0.01). However, bacterial coinfection was suspected clinically in a minority of bacteremic patients (5/13 [38%] compared with 13/70 [19%] of non-bacteremic patients, P = 0.11). Concomitant bacteremia in adults diagnosed with falciparum malaria may be more common than previously believed and is difficult to identify clinically in resource-poor settings. Death is more common in these patients, suggesting that clinicians should have a lower threshold for commencing empirical antibacterial therapy in adults diagnosed with falciparum malaria in these locations than is presently recommended.…

Lloyd, Y. M., Fang, R., Bobbili, N., Vanda, K., Ngati, E., Sanchez-Quintero, M. J., Salanti, A., Chen, J. J., Leke, R. G. F., Taylor, D. W.

Plasmodium falciparum infections are serious in pregnant women, because VAR2CSA allows parasitized erythrocytes to sequester in the placenta causing placental malaria. In endemic areas, women have substantial malarial immunity prior to pregnancy, including antibodies to merozoite antigens, but only produce antibodies to VAR2CSA during pregnancy. The current study sought to determine the importance of antibodies to VAR2CSA and merozoite antigens in pregnant women in Yaoundé, Cameroon, where malaria transmission is relatively low. A total of 1,377 archival plasma samples collected at delivery were selected (1:3 ratio for PM-positive [PM+] to PM-negative [PM-]) and screened for antibodies to full length VAR2CSA and 7 merozoite antigens. Results showed that many PM+ women and most PM- women lacked antibodies to VAR2CSA at delivery. Among PM+ women, antibodies to VAR2CSA were associated with a reduced risk of having high placental parasitemia (OR=0.432; CI: 0.272, 0.687; p=0.0004) and low birthweight babies (OR=0.444; CI: 0.247, 0.799; p=0.0068), even during first pregnancies. Among antibodies to the 7 merozoite antigens: AMA1, EBA-175, MSP142, MSP2, MSP3 MSP11 and Pf41, only antibodies to MSP3, EBA-175 and Pf41 were associated with reduced risk for high placental parasitemias (p=0.0389, 0.0291, and 0.0211, respectively) and antibodies to EBA-175 with reduced risk of premature deliveries (p=0.0211). However, after adjusting for multiple comparisons significance declined. Thus, in PM+ women, antibodies to VAR2CSA were associated with lower placental parasitemias and reduced prevalence of LBW babies in this low transmission setting.…

Chan J, Boyle M, Moore K, et al.

AbstractBackgroundSequestration of Plasmodium falciparum–infected erythrocytes (IEs) in the microvasculature contributes to pathogenesis of severe malaria in children. This mechanism is mediated by antigens expressed on the IE surface. However, knowledge of specific targets and functions of antibodies to IE surface antigens that protect against severe malaria is limited.MethodsAntibodies to IE surface antigens were examined in a case-control study of young children in Papua New Guinea presenting with severe or uncomplicated malaria (n = 448), using isolates with a virulent phenotype associated with severe malaria, and functional opsonic phagocytosis assays. We used genetically modified isolates and recombinant P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains to quantify PfEMP1 as a target of antibodies associated with disease severity.ResultsAntibodies to the IE surface and recombinant PfEMP1 domains were significantly higher in uncomplicated vs severe malaria and were boosted following infection. The use of genetically modified P. falciparum revealed that PfEMP1 was a major target of antibodies and that PfEMP1-specific antibodies were associated with reduced odds of severe malaria. Furthermore, antibodies promoting the opsonic phagocytosis of IEs by monocytes were lower in those with severe malaria.ConclusionsFindings suggest that PfEMP1 is a dominant target of antibodies associated with reduced risk of severe malaria, and function in part by promoting opsonic phagocytosis.

M.J. Delves, F. Angrisano, A.M. Blagborough

Malaria remains a major global health challenge. Appropriate use of current antimalarial tools has reduced the disease burden, but morbidity and mortality remain unacceptably high. It is widely accepted that, to achieve long-term control/eradication, it will be necessary to use interventions that inhibit the transmission of parasites to mosquitoes – these tools are termed transmission-blocking interventions (TBIs). This article aims to outline the rationale for the development of TBIs, with a focus on transmission-blocking drugs and (parasite-derived) transmission-blocking vaccines.

Elizabeth Kemigisha, Deborah Nanjebe, Yap Boum II, Céline Langendorf, Said Aberrane, Dan Nyehangane, Fabienne Nackers, Yolanda Mueller, Rémi Charrel, Richard A. Murphy, Anne-Laure Page, Juliet Mwanga-Amumpaire

by Elizabeth Kemigisha, Deborah Nanjebe, Yap Boum II, Céline Langendorf, Said Aberrane, Dan Nyehangane, Fabienne Nackers, Yolanda Mueller, Rémi Charrel, Richard A. Murphy, Anne-Laure Page, Juliet Mwanga-Amumpaire Acute central nervous system (CNS) infections in children in sub-Saharan Africa are often fatal. Potential contributors include late presentation, limited diagnostic capacity and inadequate treatment. A more nuanced understanding of treatment practices with a goal of optimizing such practices is critical to prevent avoidable case fatality. We describe empiric antimicrobial treatment, antibiotic resistance and treatment adequacy in a prospective cohort of 459 children aged two months to 12 years hospitalised for suspected acute CNS infections in Mbarara, Uganda, from 2009 to 2012. Among these 459 children, 155 had a laboratory-confirmed diagnosis of malaria (case-fatality rate [CFR] 14%), 58 had bacterial infections (CFR 24%) and 6 children had mixed malaria and bacterial infections (CFR 17%). Overall case fatality was 18.1% (n = 83). Of 219 children with laboratory-confirmed malaria and/or bacterial infections, 182 (83.1%) received an adequate antimalarial and/or antibiotic on the day of admission and 211 (96.3%) within 48 hours of admission. The proportion of those receiving adequate treatment was similar among survivors and non-survivors. All bacterial isolates were sensitive to ceftriaxone except one Escherichia coli isolate with extended-spectrum beta-lactamase (ESBL). The observed high mortality was not a result of inadequate initial antimicrobial treatment at the hospital. The epidemiology of CNS infection in this setting justifies empirical use of a third-generation cephalosporin, however antibiotic resistance should be monitored closely.

Dennis Adu-Gyasi, Kwaku Poku Asante, Sabastina Amoako, Nicholas Amoako, Love Ankrah, David Dosoo, Samuel Kofi Tchum, George Adjei, Oscar Agyei, Seeba Amenga-Etego, Seth Owusu-Agyei

by Dennis Adu-Gyasi, Kwaku Poku Asante, Sabastina Amoako, Nicholas Amoako, Love Ankrah, David Dosoo, Samuel Kofi Tchum, George Adjei, Oscar Agyei, Seeba Amenga-Etego, Seth Owusu-Agyei Background Rapid diagnostic test (RDT) kits have been useful tools to screen for the presence of infection with malaria parasites. Despite the improvement, false results from RDTs present a greater challenge. The need for quality test kits is desirable. We evaluated the diagnostic accuracy of three malaria RDTs. Method The team consented and enrolled 754 participants from the two major public hospitals in Kintampo districts of Ghana from June 2014 to August 2014. Venous blood samples were obtained by trained personnel and samples were screened for malaria using CareStart and SD Bioline HRP2 and HRP2 with pLDH based RDTs with blood slides for malaria microscopy as “gold standard”. Geometric mean parasite densities were estimated and parasite densities were used to estimate the quantitative limits of the RDTs. The sensitivities, specificities and other performance criteria were calculated using statistical analytical software. Result The median age of participants was 21 (range 5–31) years. There were 28.6% (215/752) were males and 71.4% (537/752) were females. Comparing with microscopy, the sensitivity, specificity, positive predictive value, negative predictive value and the ROC were for CareStart (HRP2), 98.2%, 66.5%, 82.6%, 95.6%, 0.82; for CareStart (HRP2/pLDH) 98.2%, 66.5%, 82.6%, 95.6%, 0.82 and for SD-Bioline (HRP2/pLDH) RDTs 98.2%, 69.2%, 84.2%, 96.0%, 0.84 respectively. The performance for all the kits were acceptable at a cut-off of 25 or more parasites/μl of blood. Conclusions The diagnostic performance of the three malaria RDTs was acceptable, according to the World Health Organisation criteria, to detect densities ≥25 parasite/μl of blood. The RDTs with HRP2/pLDH targets were comparable to those with only HRP2 and could successfully substitute current and commonly used HRP2-based RDTs.…

Abstract Background/methods Insecticide-treated nets (ITNs) are the primary tool for malaria vector control in sub-Saharan Africa, and have been responsible for an estimated two-thirds of the reduction in the global burden of malaria in recent years. While the ultimate goal is high levels of ITN use to confer protection against infected mosquitoes, it is widely accepted that ITN use must be understood in the context of ITN availability. However, despite nearly a decade of universal coverage campaigns, no country has achieved a measured level of 80% of households owning 1 ITN for 2 people in a national survey. Eighty-six public datasets from 33 countries in sub-Saharan Africa (2005–2017) were used to explore the causes of failure to achieve universal coverage at the household level, understand the relationships between the various ITN indicators, and further define their respective programmatic utility. Results The proportion of households owning 1 ITN for 2 people did not exceed 60% at the national level in any survey, except in Uganda’s 2014 Malaria Indicator Survey (MIS). At 80% population ITN access, the expected proportion of households with 1 ITN for 2 people is only 60% (p = 0.003 R2 = 0.92), because individuals in households with some but not enough ITNs are captured as having access, but the household does not qualify as having 1 ITN for 2 people. Among households with 7–9 people, mean population ITN access was 41.0% (95% CI 36.5–45.6), whereas only 6.2% (95% CI 4.0–8.3) of these same households owned at least 1 ITN for 2 people. On average, 60% of the individual protection measured by the population access indicator is obscured when focus is put on the household “universal coverage” indicator. The practice of limiting households to a maximum number of ITNs in mass campaigns severely restricts the ability of large households to obtain enough ITNs for their entire family. Conclusions The two household-level indicators—one representing minimal coverage, the other only ‘universal’ coverage—provide an incomplete and potentially misleading picture of personal protection and the success of an ITN distribution programme. Under current ITN distribution strategies, the global malaria community cannot expect countries to reach 80% of households owning 1 ITN for 2 people at a national level. When programmes assess the success of ITN distribution activities, population access to ITNs should be considered as the better indicator of “universal coverage,” because it is based on people as the unit of analysis.…

Abstract Background Plasmodium vivax is the predominant malaria species in northern Mauritania. Molecular data on P. vivax isolates circulating in West Africa are scarce. The present study analysed molecular markers associated with resistance to antifolates (Pvdhfr and Pvdhps), chloroquine (Pvmdr1), and artemisinin (Pvk12) in P. vivax isolates collected in two cities located in the Saharan zone of Mauritania. Methods Blood samples were obtained from P. vivax-infected patients recruited for chloroquine therapeutic efficacy study in 2013 and febrile patients spontaneously consulting health facilities in Nouakchott and Atar in 2015–2016. Fragments of Pvdhfr (codons 13, 33, 57, 58, 61, 117, and 174), Pvdhps (codons 382, 383, 512, 553, and 585), Pvmdr1 (codons 976 and 1076) and Pvk12 (codon 552) genes were amplified by PCR and sequenced. Results Most of the isolates in Nouakchott (126/154, 81.8%) and Atar (44/45, 97.8%) carried the wild-type Pvdhfr allelic variant (IPFSTSI). In Nouakchott, all mutants (28/154; 18.2%) had double Pvdhfr mutations in positions 58 and 61 (allelic variant IPFRMSI), whereas in Atar only 1 isolate was mutant (S117N, allelic variant IPFSTNI). The wild-type Pvdhps allelic variant (SAKAV) was found in all tested isolates (Nouakchott, n = 93; Atar, n = 37). Few isolates in Nouakchott (5/115, 4.3%) and Atar (3/79, 3.8%) had the mutant Pvmdr1 allele 976F or 1076L, but not both, including in pre-treatment isolates obtained from patients treated successfully with chloroquine. All isolates (59 in Nouakchott and 48 in Atar) carried the wild-type V552 allele in Pvk12. Conclusions Polymorphisms in Pvdhfr, Pvdhps, Pvmdr1, and Pvk12 were limited in P. vivax isolates collected recently in Nouakchott and Atar. Compared to the isolates collected in Nouakchott in 2007–2009, there was no evidence for selection of mutants. The presence of one, but not both, of the two potential markers of chloroquine resistance in Pvmdr1 in pre-treatment isolates did not influence the clinical outcome, putting into question the role of Pvmdr1 mutant alleles 976F and 1076L in treatment failure. Molecular surveillance is an important component of P. vivax malaria control programme in the Saharan zone of Mauritania to predict possible emergence of drug-resistant parasites.…

Abstract Background Malaria control largely depends on availability of highly efficacious drugs, however, over the years, has been threatened by emergence of drug resistance. It is, therefore, important to monitor the impact of recurrent anti-malarial treatment on the long-term efficacy of anti-malarial regimens, especially in sub-Saharan African countries with high malaria transmission. Evaluation of parasite clearance following treatment of severe malaria with intravenous artesunate among patients in Eastern Uganda, was performed, as a contribution to monitoring anti-malarial effectiveness. Methods Parasite clearance data obtained from a clinical trial whose objective was to evaluate the 42-day parasitological treatment outcomes and safety following treatment of severe malaria with intravenous artesunate plus artemisinin-based combination therapy among patients attending Tororo District Hospital in Eastern Uganda, were analysed. Serial blood smears were performed at 0, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24 h, followed by 6-hourly blood smears post start of treatment until 6 h post the first negative blood smear when parasite clearance was achieved. Study endpoints were; parasite clearance half-life (the time required for parasitaemia to decrease by 50% based on the linear portion of the parasite clearance slope) and parasite clearance time (time required for complete clearance of initial parasitaemia). Results One hundred and fifty participants with severe malaria were enrolled. All participants were treated with intravenous artesunate. All study participants tolerated artesunate well with rapid recovery from symptoms and ability to take oral mediation within 24 h. No immediate adverse events were recorded. The median (IQR) number of days to complete parasite clearance was of 2 (1–2). The median (IQR) time to clear 50% and 99% parasites was 4.8 (3.61–7.10) and 17.55 (14.66–20.66) h, respectively. The median estimated clearance rate constant per hour was 0.32. The median (IQR) slope half-life was 2.15 (1.64, 2.61) h. Conclusion Parasite clearance following treatment with intravenous artesunate was rapid and adequate. This finding provides supportive evidence that resistance to artemisinins is unlikely to have emerged in this study area. Continuous monitoring of artemisinin effectiveness for malaria treatment should be established in high malaria transmission areas in sub-Saharan Africa where spread of resistance would be disastrous. Trial registration The study was registered with the Pan African Clinical Trial Registry (PACTR201110000321348). Registered 7th October 2011, http://www.pactr.org/)…

Abstract Background In a context of increasing resistance of both vectors toward main classes of insecticides used in public health and parasites toward anti-malarial drugs, development of new and complementary molecules or control approaches is fundamental to achieve the objective of controlling or even eliminating malaria. Concerning vector control, the sterile insect technique and other genetic control approaches are among promising complementary tools in an integrated management strategy for malaria control. These approaches rely not only on a good understanding of vector biology (especially during larval stages), but also on the availability of adequate supplies and protocols for efficient mosquito rearing. The aim of this study was to assess the factors impacting the life history of Anopheles coluzzii mosquitoes at the larval stage, in the context of genetic and sterile insect approaches to control malaria vectors. Methods The effect of different larval diets and larval rearing densities on the development of An. coluzzii were evaluated in the laboratory. Emergence rate (ER), pre-imaginal developmental time (DT) and adult wing length (WL) were measured under different food regimes. Four diets were tested among which three were provided by the Insect Pest Control Laboratory (IPCL) of the FAO/IAEA Joint division. Results Data showed significant differences in the quality of the different diets and suggested a negative density dependence in all three life history parameters measured under tested rearing conditions. ER and WL increased with food availability, but decreased with increasing larval density. Conversely DT was shortened with increasing food availability but increased with larval density. These data demonstrates intraspecific larval competition modulated by food amount and space availability. Of the four diets tested, the one made of a mix of tuna meal, bovine liver powder, brewer’s yeast, squid liver powder and vitamin mix (diet 2) yielded the best results as it produced a good balance between ER, DT and WL. Food availability for optimal development (highest survival at shortest time) was in the range of 180–400 µg/larvae/day for the three diets provided by the IPCL. Conclusion There is an interaction between diet type, diet concentration and larval density. Best results in terms of optimal larvae development parameters happen when moderately high values of those three variables are observed.…

Aaron I. Schneiderman, Yasmin S. Cypel, Erin K. Dursa and Robert M. Bossarte

Abstract. Mefloquine (Lariam®; Roche Holding AG, Basel, Switzerland) has been linked to acute neuropsychiatric side effects. This is a concern for U.S. veterans who may have used mefloquine during recent Southwest Asia deployments. Using data from the National Health Study for a New Generation of U.S. Veterans, a population-based study of U.S. veterans who served between 2001 and 2008, we investigated associations between self-reported use of antimalarial medications and overall physical and mental health (MH) using the twelve-item short form, and with other MH outcomes using the post-traumatic stress disorder Checklist-17 and the Patient Health Questionnaire (anxiety, major depression, and self-harm). Multivariable logistic regression was performed to examine associations between health measures and seven antimalarial drug categories: any antimalarial, mefloquine, chloroquine, doxycycline, primaquine, mefloquine plus any other antimalarial, and any other antimalarial or antimalarial combination while adjusting for the effects of deployment and combat exposure. Data from 19,487 veterans showed that although antimalarial use was generally associated with higher odds of negative health outcomes, once deployment and combat exposure were added to the multivariable models, the associations with each of the MH outcomes became attenuated. A positive trend was observed between combat exposure intensity and prevalence of the five MH outcomes. No significant associations were found between mefloquine and MH measures. These data suggest that the poor physical and MH outcomes reported in this study population are largely because of combat deployment exposure.…

Imwong M, Madmanee , Suwannasin K, et al.

AbstractBackgroundIn Southeast Asia, Plasmodium knowlesi, a parasite of long-tailed macaques (Macaca fascicularis), is an important cause of human malaria. Plasmodium cynomolgi also commonly infects these monkeys, but only one naturally acquired symptomatic human case has been reported previously.MethodsMalariometric studies involving 5422 subjects (aged 6 months to 65 years) were conducted in 23 villages in Pailin and Battambang, western Cambodia. Parasite detection and genotyping was conducted on blood samples, using high-volume quantitative PCR (uPCR).ResultsAsymptomatic malaria parasite infections were detected in 1361 of 14732 samples (9.2%). Asymptomatic infections with nonhuman primate malaria parasites were found in 21 individuals living close to forested areas; P. cynomolgi was found in 11, P. knowlesi was found in 8, and P. vivax and P. cynomolgi were both found in 2. Only 2 subjects were female, and 14 were men aged 20–40 years. Geometric mean parasite densities were 3604 parasites/mL in P. cynomolgi infections and 52488 parasites/mL in P. knowlesi infections. All P. cynomolgi isolates had wild-type dihydrofolate reductase genes, in contrast to the very high prevalence of mutations in the human malaria parasites. Asymptomatic reappearance of P. cynomolgi occurred in 2 subjects 3 months after the first infection.ConclusionsAsymptomatic naturally acquired P. cynomolgi and P. knowlesi infections can both occur in humans.Clinical Trials RegistrationNCT01872702.

Diva da Silva Tavares, Vanessa Riesz Salgado, José Carlos Miranda, Paulo R. R. Mesquita, Frederico de Medeiros Rodrigues, Manoel Barral-Netto, Jailson Bittencourt de Andrade, Aldina Barral

by Diva da Silva Tavares, Vanessa Riesz Salgado, José Carlos Miranda, Paulo R. R. Mesquita, Frederico de Medeiros Rodrigues, Manoel Barral-Netto, Jailson Bittencourt de Andrade, Aldina Barral Background Many studies have investigated what could attract insects of medical importance and a crucial role has lately been attributed to human skin odors. Most of these researches have been concerned with mosquitoes, e.g., vectors of dengue and malaria. Little is known about volatile organic compounds (VOCs) from human skin odors and their effects on leishmania vectors. Objective The present study aimed to identify the VOCs from human skin that can be attractive to female anthropophilic phlebotomine sandflies. Results Forty-two VOCs were identified from skin odors of 33 male volunteers, seven of which were tested in wind tunnel assays employing field-captured phlebotomine sandflies (75.4% identified as Lutzomyia intermedia). Hexane and (E)-oct-3-en-1-ol (octenol) were used as negative and positive controls, respectively. 2-Phenylacetaldehyde (hereafter called phenylacetaldehyde), 6-methylhept-5-en-2-one (also known as sulcatone), nonadecane and icosane were found to activate female phlebotomine sandflies, but only phenylacetaldehyde, 6-methylhepten-5-en-2-one and icosane elicited attraction responses. Conclusions These results suggest that phenylacetaldehyde, 6-methylhepten-5-en-2-one and icosane may be suitable candidates for attractiveness experimentation in the field which can be an important tool to develop strategies concerning human beings protection against phlebotomine sandflies bites and consequently against leishmaniasis.…