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Background: Malaria is a leading health threat for low to middle-income countries and around 1.8 billion people in the Southeast Asian region and 870 million people in the Western Pacific region remain at risk of contracting malaria. Traditional medicine/traditional healer (TM/TH) use is prominent amongst populations in low- to middle-income countries and constitutes an important issue influencing and potentially challenging effective, safe and coordinated prevention and treatment strategies around malaria. This paper presents the first critical review of literature on the use of TM/TH for malaria prevention and treatment in low- to middle-income countries in the Asia-Pacific region. Methods: A comprehensive search of English language, peer-reviewed literature reporting TM and/or TH use for malaria or among people in malaria-endemic areas in low- to middle-income Asia-Pacific countries published between 2003 and 2014 was undertaken. Results: Twenty-eight papers reporting 27 studies met the inclusion criteria. Prevalence of TM/TH use for malaria treatment ranged from 1 to 40.1%. A majority of studies conducted in rural/remote areas reported higher prevalence of TM/TH use than those conducted in mixed areas of urban, semi-urban, rural, and remote areas. Those utilizing TM/TH for malaria are more likely to be: women, people with lower educational attainment, people with lower household income, those with farming occupations, and those from ethnic minorities (identified from only three studies). The majority of adult participants delayed seeking treatment from a health centre or conventional providers while initially practicing TH use. The most common reasons for TM/TH use for malaria across the Asia-Pacific region are a lack of accessibility to conventional health services (due to geographical and financial barriers), faith in traditional treatment, and the perception of lower severity of malaria symptoms. Conclusion: This review has provided crucial insights into the prevalence and profile of TM/TH use for malaria. Those managing and providing conventional programmes, treatment and care for malaria in the Asia-Pacific should remain mindful of the possible use of TM/TH amongst community members and patients. [ABSTRACT FROM AUTHOR]

Background: Glucose-6-phosphate dehydrogenase deficiency (G6PD), an x-linked inherited enzymopathy, is a barrier to malaria control because primaquine cannot be readily applied for radical cure in individuals with the condition. In endemic areas, including in Afghanistan, the G6PD status of vivax patients is not routinely determined so the drug is rarely, if ever, prescribed even though it is included as a recommended treatment in local, regional and global guidelines. This study assessed the prevalence and genotype of G6PD deficiency in Afghan populations and examined the need for routine G6PD testing as a malaria treatment and control tool. Methods: A cross-sectional household survey was conducted using random sampling in five Afghan cities to determine the prevalence of G6PD deficiency in Afghan ethnic groups. Filter-paper blood spots were analysed for phenotypic G6PD deficiency using a fluorescent spot test. Molecular analysis was conducted to identify the genetic basis of the disorder. Results: Overall, 45/1,436 (3.1%) people were G6PD deficient, 36/728 (5.0%) amongst males and 9/708 (1.3%) amongst females. Amongst males the prevalence was highest in the Pashtun ethnic group (10%, 26/260) while in Tajik males it was 8/250 (3.2%); in Hazara males it was 1/77 (1.3%) and in Uzbek males is was 0/125. Genetic testing in those with deficiency showed that all were of the Mediterranean type (Med-) characterized by a C-T change at codon 563 of the G6PD gene. Conclusion: Prevalence of G6PD deficiency in Afghanistan varies considerably by ethnic group and is predominantly of the Mediterranean type. G6PD deficient individuals are susceptible to potentially severe and lifethreatening haemolysis after standard primaquine treatment. If the aim of increasing access to radical treatment of vivax is to be successful reliable G6PD testing needs to be made routinely available within the health system. [ABSTRACT FROM AUTHOR]

Background: Intermittent preventive treatment (IPT) has recently been accepted as an important component of the malaria control strategy. Intermittent preventive treatment for children (IPTc) combined with timely treatment of malaria related febrile illness at home to reduce parasite prevalence and malaria morbidity in children aged between six and 60 months in a coastal community in Ghana. This paper reports persistence of reduced parasitaemia two years into the intervention. The baseline and year-one-evaluation findings were published earlier. Objective: The main objective in the second year was to demonstrate whether the two interventions would further reduce parasite prevalence and malaria-related febrile illness in the study population. Methods: This was an intervention study designed to compare baseline and evaluation findings without a control group. The study combined home-based delivery of intermittent preventive treatment for children (IPTc) aged 6 - 60 months and home treatment of suspected febrile malaria-related illness within 24 hours. All children aged 6 - 60 months received home-based delivery of intermittent preventive treatment using amodiaquine + artesunate, delivered at home by community assistants every four months (6 times in 24 months). Malaria parasite prevalence surveys were conducted before the first and after the third and sixth IPTc to the children. The evaluation surveys were done four months after the third and sixth IPTc was given. Results: Parasite prevalence which reduced from 25% to 3.0% at year-one evaluation had reduced further from 3% to 1% at year-two-evaluation. At baseline, 13.8% of the children were febrile (axilary temperature of ≥37.5°C) compared to 2.2% at year-one-evaluation while 2.1% were febrile at year-two-evaluation. Conclusion: The year-two-evaluation result indicates that IPTc given three times in a year (every four months) combined with timely treatment of febrile malaria illness, is effective to reduce malaria parasite prevalence in children aged 6 to 60 months in the study community. This must give hope to malaria control programme managers in sub-Saharan Africa where the burden of the disease is most debilitating. [ABSTRACT FROM AUTHOR]

Brazil currently contributes 42 % of all malaria cases reported in the Latin America and the Caribbean, a region where major progress towards malaria elimination has been achieved in recent years. In 2014, malaria burden in Brazil (143,910 microscopically confirmed cases and 41 malaria-related deaths) has reached its lowest levels in 35 years, Plasmodium falciparum is highly focal, and the geographic boundary of transmission has considerably shrunk. Transmission in Brazil remains entrenched in the Amazon Basin, which accounts for 99.5 % of the country's malaria burden. This paper reviews major lessons learned from past and current malaria control policies in Brazil. A comprehensive discussion of the scientific and logistic challenges that may impact malaria elimination efforts in the country is presented in light of the launching of the Plan for Elimination of Malaria in Brazil in November 2015. Challenges for malaria elimination addressed include the high prevalence of symptomless and submicroscopic infections, emerging anti-malarial drug resistance in P. falciparum and Plasmodium vivax and the lack of safe anti-relapse drugs, the largely neglected burden of malaria in pregnancy, the need for better vector control strategies where Anopheles mosquitoes present a highly variable biting behaviour, human movement, the need for effective surveillance and tools to identify foci of infection in areas with low transmission, and the effects of environmental changes and climatic variability in transmission. Control actions launched in Brazil and results to come are likely to influence control programs in other countries in the Americas. [ABSTRACT FROM AUTHOR]

Sri Lanka has reached zero indigenous malaria cases in November 2012, two years before its targeted deadline for elimination. Currently, the biggest threat to the elimination efforts are the risk of resurgence of malaria due to imported cases. This paper describes two clusters of imported malaria infections reported in 2013 and 2014, one among a group of Pakistani asylum-seekers resident in Sri Lanka, and the other amongst local fishermen who returned from Sierra Leone. The two clusters studied reveal the potential impact of imported malaria on the risk of reintroducing the disease, as importation is the only source of malaria in the country at present. In the event of a case occurring, detection is a major challenge both amongst individuals returning from malaria endemic countries and the local population, as malaria is fast becoming a "forgotten" disease amongst health care providers. In spite of a very good coverage of diagnostic services (microscopy and rapid diagnostic tests) throughout the country, malaria is being repeatedly overlooked by health care providers even when individuals present with fever and a recent history of travel to a malaria endemic country. Given the high receptivity to malaria in previously endemic areas of the country due to the prevalence of the vector mosquito, such cases pose a significant threat for the reintroduction of malaria to Sri Lanka. The challenges faced by the Anti Malaria Campaign and measures taken to prevent the resurgence of malaria are discussed here. [ABSTRACT FROM AUTHOR]

Background: Haemoparasites in feral pigeons have been studied in several countries but no data are available from Italy. The aim of this work was to evaluate the prevalence and diversity of Haemoproteus spp./Plasmodium spp. and Leucocytozoon spp. in feral pigeons from northwest Italy, as well as the association between infection and host age or sex. Methods: Feral pigeons were collected during a regional culling programme from the Piedmont region (northwest Italy) and subjected to necropsy. Infections were detected from DNA extracted from the spleen following a nested PCR protocol. The association between sex or age and infection status was evaluated using the chi-squared test for independence or Fisher's exact test. Results: Out of 51 animals, 15 were positive for Haemoproteus/Plasmodium spp. and eight for Leucocytozoon spp., with a significant difference between haemoparasites prevalence. There was no significant association between age or sex and infection status. The coinfection with different haemoparasites was very significant (p < 0.01), showing a greater relative risk to be infected by a second haemoparasite in birds already infected, in particular in male and in adult pigeons. DNA sequencing of Leucocytozoon spp. showed six different lineages in pigeons, and one of Haemoproteus and Plasmodium, respectively. Conclusions: Blood parasites are continuously circulating around the world, and the results presented in the paper suggest that cross infection of feral pigeons with haemoparasites typical of other migratory or nonmigratory bird species is possible. Moreover, the geographical location of Italy along the main migratory routes is a crucial factor to be considered for migratory birds, because they can be affected by blood parasites detected in feral pigeons, and vice versa. [ABSTRACT FROM AUTHOR]

Background: Rapid diagnostic tests (RDTs) detecting histidine-rich protein 2 (PfHRP2) antigen are used to identify individuals with Plasmodium falciparum infection even in low transmission settings seeking to achieve elimination. However, these RDTs lack sensitivity to detect low-density infections, produce false negatives for P. falciparum strains lacking pfhrp2 gene and do not detect species other than P. falciparum. Methods: Results of a PfHRP2-based RDT and Plasmodium nested PCR were compared in a region of declining malaria transmission in southern Zambia using samples from community-based, cross-sectional surveys from 2008 to 2012. Participants were tested with a PfHRP2-based RDT and a finger prick blood sample was spotted onto filter paper for PCR analysis and used to prepare blood smears for microscopy. Species-specific, real-time, quantitative PCR (q-PCR) was performed on samples that tested positive either by microscopy, RDT or nested PCR. Results: Of 3,292 total participants enrolled, 12 (0.4%) tested positive by microscopy and 42 (1.3%) by RDT. Of 3,213 (98%) samples tested by nested PCR, 57 (1.8%) were positive, resulting in 87 participants positive by at least one of the three tests. Of these, 61 tested positive for P. falciparum by q-PCR with copy numbers ≤ 2 x 10³ copies/μL, 5 were positive for both P. falciparum and Plasmodium malariae and 2 were positive for P. malariae alone. RDT detected 32 (53%) of P. falciparum positives, failing to detect three of the dual infections with P. malariae. Among 2,975 participants enrolled during a low transmission period between 2009 and 2012, sensitivity of the PfHRP2-based RDT compared to nested PCR was only 17%, with specificity of >99%. The pfhrp gene was detected in 80% of P. falciparum positives; however, comparison of copy number between RDT negative and RDT positive samples suggested that RDT negatives resulted from low parasitaemia and not pfhrp2 gene deletion. Conclusions: Low-density P. falciparum infections not identified by currently used PfHRP2-based RDTs and the inability to detect non-falciparum malaria will hinder progress to further reduce malaria in low transmission settings of Zambia. More sensitive and specific diagnostic tests will likely be necessary to identify parasite reservoirs and achieve malaria elimination. [ABSTRACT FROM AUTHOR]

Background Over the last decade, the incidence of confirmed malaria has declined significantly in Nepal. The aim of this paper is to assess the spatio-temporal distribution of malaria and its association with climatic factors and vector control interventions in two high-risk districts of Nepal. Methods Hotspot analysis was used to visualize the spatio-temporal variation of malaria incidence over the years at village level and generalized additive mixed models were fitted to assess the association of malaria incidence with climatic variables and vector control interventions. Results Opposing trends of malaria incidence were observed in two high-risk malaria districts of eastern and far-western Nepal after the introduction of long-lasting insecticidal nets (LLINs). The confirmed malaria incidence was reduced from 2.24 per 10,000 in 2007 to 0.31 per 10,000 population in 2011 in Morang district but increased from 3.38 to 8.29 per 10,000 population in Kailali district. Malaria hotspots persisted mostly in the same villages of Kailali district, whereas in Morang district malaria hotspots shifted to new villages after the introduction of LLINs. A 1° C increase in minimum and mean temperatures increased malaria incidence by 27% (RR =1.27, 95% CI =1.12-1.45) and 25% (RR =1.25, 95% CI =1.11-1.43), respectively. The reduction in malaria incidence was 25% per one unit increase of LLINs (RR =0.75, 95% CI =0.62-0.92). The incidence of malaria was 82% lower in Morang than in Kailali district (RR =0.18, 95% CI =0.11-0.33). Conclusions The study findings suggest that LLIN coverage should be scaled up to entire districts rather than high-incidence foci only. Climatic factors should be considered for malaria microstratification, mosquito repellents should be prescribed for those living in forests, forest fringe and foothills and have regular visits to forests, and imported cases should be controlled by establishing fever check posts at border crossings. [ABSTRACT FROM AUTHOR]

Background After years of disuse of chloroquine (CQ) as first-line anti-malarial drug in Ghana, reports from molecular studies conducted in parts of the country indicate varying prevalence of T76 mutation in the pfcrt gene. This situation has several health implications, one being that mutations that confer resistance to CQ have been reported to show substantial cross-resistance to other anti-malarial drugs. It is important to identify some of the factors contributing to the continuous presence of CQ resistance markers in the country. This study determined the prevalence of T76 mutation in pfcrt gene of Plasmodium falciparum isolates collected from selected areas of the Central region of Ghana and correlated with the level of CQ use in these areas. Methods Plasmodium falciparum DNA was extracted from collected blood-blot filter paper samples in the study sites. The prevalence of T76 point mutation in pfcrt gene was assessed using nested PCR followed by RFLP. CQ from pharmacy and chemical shops was obtained using mystery buying method. The extent of CQ use by the participants was determined by measuring the level of the drug in their urine samples using the Saker-Solomon method. Results Of the 214 P. falciparum isolates analysed, 71.9% were found to have T76 mutation of pfcrt gene. The study revealed that 14.49% of community pharmacies and chemical shops had stocks of CQ for sale while 16.9% of the participants had CQ in their urine samples. There is five times more risks of becoming infected with CQ resistant strain for staying in an area where CQ is stocked for sale [RR = 0.20, p < 0.0001] and thirteen times more risks of having CQ-resistant mutant from those who still use CQ than non-users [OR = 0.08, p < 0.0001]. Conclusion This study has shown that high variation in the prevalence of T76 mutations of P. falciparum is linked with the level of CQ stocking and usage within study area. [ABSTRACT FROM AUTHOR]

Background: Prompt and effective malaria diagnosis not only alleviates individual suffering, but also decreases malaria transmission at the community level. The commonly used diagnostic methods, microscopy and rapid diagnostic tests, are usually insensitive at very low-density parasitaemia. Molecular techniques, on the other hand, allow the detection of low-level, sub-microscopic parasitaemia. This study aimed to explore the presence of sub-microscopic Plasmodium falciparum infections using polymerase chain reaction (PCR). The PCR-based parasite prevalence was compared against microscopy and rapid diagnostic test (RDT). Methods: This study used 1,453 blood samples collected from clinical patients and sub-clinical subjects to determine the prevalence of sub-microscopic P. falciparum carriages. Subsets of RDT and microscopy negative blood samples were tested by PCR while all RDT and microscopically confirmed P. falciparum-infected samples were subjected to PCR. Finger-prick blood samples spotted on filter paper were used for parasite genomic DNA extraction. Results: The prevalence of sub-microscopic P. falciparum carriage was 19.2% (77/400) (95% CI = 15. 4-23.1). Microscopy-based prevalence of P. falciparum infection was 3.7% (54/1,453) while the prevalence was 6.9% (100/1,453) using RDT alone. Using microscopy and PCR, the estimated parasite prevalence was 20.6% if PCR were performed in 1,453 blood samples. The prevalence was estimated to be 22.7% if RDT and PCR were used. Of 54 microscopically confirmed P. falciparum-infected subjects, PCR detected 90.7% (49/54). Out of 100 RDT-confirmed P. falciparum infections; PCR detected 80.0% (80/100). The sensitivity of PCR relative to microscopy and RDT was, therefore, 90.7% and 80%, respectively. The sensitivity of microscopy and RDT relative to PCR was 16.5 (49/299) and 24.2% (80/330), respectively. The overall PCR-based prevalence of P. falciparum infection was 5.6- and 3.3 fold higher than that determined by microscopy and RDT, respectively. None of the sub-microscopic subjects had severe anaemia, though 29.4% had mild anaemia (10-11.9 g/dl). Conclusions: Asymptomatic, low-density malaria infection was common in the study area and PCR may be a better tool for measuring Plasmodium prevalence than microscopy and RDT. The inadequate sensitivity of the diagnostic methods to detect substantial number of sub-microscopic parasitaemia would undoubtedly affect malaria control efforts, making reduction of transmission more difficult. RDT and microscopy-based prevalence studies and subsequent reports of reduction in malaria incidence underestimate the true pictures of P. falciparum infections in the community. PCR, on the other hand, seems to have reasonable sensitivity to detect a higher number of infected subjects with low and sub-microscopic parasite densities than RDTs or microscopy. [ABSTRACT FROM AUTHOR]

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Background: Plasmodium falciparum gametocytes are vital to sustaining malaria transmission. Parasite densities, multiplicity of infection as well as asexual genotype are features that have been found to influence gametocyte production. Measurements of the prevalence of Plasmodium sp. gametocytes may serve as a tool to monitor the success of malaria eradication efforts. Methods: Whole blood was collected from 112 children aged between 6 months and 13 years with uncomplicated P. falciparum malaria attending three health facilities in southern Ghana from June to August, 2014 before (day 0) and 4 days after completion of anti-malaria drug treatment (day 7). Malaria parasites were observed by microscopy and polymerase chain reaction (PCR); submicroscopic gametocyte carriage was measured by a Pfs25 (PF3D7_1031000) mRNA real time reverse transcriptase polymerase chain reaction (RT-PCR). Parasite genotyping was performed on gDNA extracted from dried filter paper blood blots by amplification of the polymorphic regions of msp1 (PF3D7_0930300) and msp2 (PF3D7_0206800) using PCR. Results: Microscopy estimated 3.1% (3/96) of the total population to carry gametocytes on day 0, which decreased to 2.1% (2/96) on day 7. In contrast, reverse transcriptase-real time PCR (RT-PCR) analysis of a subset of 35 samples estimated submicroscopic gametocyte carriage to be as high as 77% (27/35) using primers specific for Pfs25 (CT < 35) on day 0 and by day 7 this only declined to 60% (21/35). Genotyping the msp2 gene identified higher levels of MOI than the msp1 gene. Conclusions: Although below detection by microscopy, gametocyte prevalence at submicroscopic levels are high in this region and emphasize the need for more effective elimination approaches like the development of transmissionblocking vaccines and safer gametocytocidal drugs. [ABSTRACT FROM AUTHOR]

Background: The prevalence of malaria parasites in adults in Africa is less well researched than in children. Therefore, a demographic surveillance site was used to conduct a household survey of adults in the malaria endemic area of Maseno division in Kisumu County near Lake Victoria. Methods: A random survey of 1,190 adults living in a demographic health surveillance site in a malaria endemic area of 70,805 population size was conducted, measuring presence of malaria parasites by slide microscopy. Data were analysed using STATA to calculate the prevalence of malaria and associated risk factors. Results: The adult prevalence of presence of malaria parasites in Maseno was 28% (95% CI: 25.4-31.0%). Gender was a significant sociodemographic risk factor in both univariate (OR 1.5, p = 0.005) and multivariate (OR 1.4, p = 0.019) analyses. Females were 50% more likely to have malaria than men. Conclusions: Presence of malaria parasites is common in the adult population of this endemic area, and the rate is greatly increased in women. The presence of such an adult pool of malaria parasites represents a key reservoir factor in transmission of parasites to children, and is relevant for plans to eradicate malaria. [ABSTRACT FROM AUTHOR]

Background: Malaria was once one of the most serious public health problems in China. However, the disease burden has sharply declined and epidemic areas have shrunk after the implementation of an integrated malaria control and elimination strategy, especially since 2000. In this review, the lessons were distilled from the Chinese national malaria elimination programme and further efforts to mitigate the challenges of malaria resurgence are being discussed. Methods: A retrospective evaluation was performed to assess the changes in malaria epidemic patterns from 1950 to 2017 at national level. The malaria data before 2004 were collected from paper-based annual reports. After 2004, each of the different cases from the Infectious Diseases Information Reporting Management System (IDIRMS) was closely examined and scrutinized. An additional documenting system, the National Information Management System for Malaria, established in 2012 to document the interventions of three parasitic diseases, was also examined to complete the missing data from IDIRMS. Results: From 1950 to 2017, the occurrence of indigenous malaria has been steeply reduced, and malaria-epidemic regions have substantially shrunk, especially after the launch of the national malaria elimination programme. There were approximately 30 million malaria cases annually before 1949 with a mortality rate of 1%. A total of 5999 indigenous cases were documented from 2010 to 2016, with a drastic reduction of 99% over the 6 years (2010, n = 4262; 2016, n = 3). There were indigenous cases reported in 303 counties from 18 provinces in 2010, but only 3 indigenous cases were reported in 2 provinces nationwide in 2016. While in 2017, for the first time, zero indigenous case was reported in China, and only 7 of imported cases were in individuals who died of Plasmodium falciparum infection. Conclusion: Malaria elimination in China is a country-led and country-owned endeavour. The country-own efforts were a clear national elimination strategy, supported by two systems, namely a case-based surveillance and response system and reference laboratory system. The country-led efforts were regional and inter-sectoral collaboration as well as sustained monitoring and evaluation. However, there are still some challenges, such as the maintenance of non-transmission status, the implementation of a qualified verification and assessment system, and the management of imported cases in border areas, through regional cooperation. The findings from this review can probably help improving malaria surveillance systems in China, but also in other elimination countries. [ABSTRACT FROM AUTHOR]

Background: Artemisinin-based combinations differ in their impact on gametocyte prevalence and density. This study assessed female and male gametocyte dynamics after treating children with uncomplicated Plasmodium falciparum malaria with either pyronaridine–artesunate (PA) or artemether–lumefantrine (AL). Methods: Kenyan children with uncomplicated Plasmodium falciparum malaria were included and randomly assigned to PA or AL treatment. Filter paper blood samples were collected as a source of RNA for quantitative reverse-transcription PCR (qRT-PCR) and nucleic acid sequence based amplification (QT-NASBA) to detect female gametocytes (targeting Pfs25 mRNA). Male gametocytes were detected by qRT-PCR (targeting PfMGET mRNA). Duration of gametocyte carriage, the female and male gametocyte response and the agreement between qRT-PCR and QT-NASBA were determined. Results: The mean duration of female gametocyte carriage was significantly longer for PA (4.9 days) than for AL (3.8 days) as estimated by QT-NASBA (P = 0.036), but this difference was less clear when determined by Pfs25 qRT-PCR (4.5 days for PA and 3.7 for AL, P = 0.166). qRT-PCR based female gametocyte prevalence decreased from 100% (75/75) at baseline to 6.06% (4/66) at day 14 in the AL group and from 97.7% (83/85) to 13.9% (11/79) in the PA group. Male gametocyte prevalence decreased from 41.3% (31/75) at baseline to 19.7% (13/66) at day 14 in the AL group and from 35.3% (30/85) to 22.8% (18/79) in the PA group. There was good agreement between Pfs25 qRT-PCR and QT-NASBA female gametocyte prevalence (0.85, 95% CI 0.82–0.87). Conclusions: This study indicates that female gametocyte clearance may be slightly faster after AL compared to PA. Male gametocytes showed similar post-treatment clearance between study arms. Future studies should further address potential differences between the post-treatment transmission potential after PA compared to AL. Trial registration This study is registered at clinicaltrials.gov under NCT02411994. Registration date: 8 April 2015. https://clinicaltrials.gov/ct2/show/NCT02411994?term=pyronaridine-artesunate&cond=Malaria&cntry=KE&rank=1 [ABSTRACT FROM AUTHOR]

Background: Drug resistance contributes to the global malaria burden. Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) polymorphisms confer resistance to sulphadoxinepyrimethamine (SP). Methods: The study assessed the frequency of SP resistance-conferring polymorphisms in Plasmodium falciparumpositive samples from two clinical studies in Lambaréné. Their role on treatment responses and transmission potential was studied in an efficacy open-label clinical trial with a 28-day follow-up in 29 children under five with uncomplicated malaria. Results: SP was well tolerated by all subjects in vivo. Three subjects were excluded from per-protocol analysis. PCR-corrected, 12/26 (46%) achieved an adequate clinical and parasitological response, 13/26 (50%) were late parasitological failures, while 1/26 (4%) had an early treatment failure, resulting in early trial discontinuation. Of 106 isolates, 98 (92%) carried the triple mutant dhfr haplotype. Three point mutations were found in dhps in a variety of haplotypic configurations. The 437G + 540E double mutant allele was found for the first time in Gabon. Conclusions: There is a high prevalence of dhfr triple mutant with some dhps point mutations in Gabon, in line with treatment failures observed, and molecular markers of SP resistance should be closely monitored. [ABSTRACT FROM AUTHOR]

Background: In 2017, nearly 80% of malaria morbidity and mortality occurred in sub-Saharan African (SSA) countries and India. Rapid diagnostic tests (RDTs), especially those targeting histidine-rich protein 2 (PfHRP2) of Plasmodium falciparum, have become an important diagnostic tool in these malaria-endemic areas. However, the chances of RDT-oriented successful treatment are increasingly jeopardized by the appearance of mutants with deletions in pfhrp2 and pfhrp3 genes. This systematic review and meta-analysis determines the prevalence of field P. falciparum isolates with deletion in pfhrp2 and/or pfhrp3 genes and their proportion among false-negative results in the PfHRP2-based RDTs in SSA and India. Methods: Eight electronic databases were used for searching potentially relevant publications for the systematic review analysis, wherein the main methodological aspects of included studies were analysed and some missing links in the included studies were identified. Results: A total of 19 studies were included, 16 from SSA and 3 from India. The pooled prevalence of pfhrp2 deletions was 8 and 5% while 16 and 4% for pfhrp3 gene deletions in Africa and India, respectively. The pooled proportion of pfhrp2 gene deletions found among false negative PfHRP2-based RDTs results was about 27.0 and 69.0% in Africa and India, respectively. Conclusions: This review study indicates a relatively high proportion of both pfhrp2/3 genes deletions in P. falciparum isolates and among false-negative malaria cases using PfHRP2-based RDT results in SSA and India. Recently the deletions in pfhrp2/3 genes have also been reported from two African countries (Nigeria and Sudan). This review emphasizes the importance of more extensive studies and standardization of studies addressing the pfhrp2/3 gene deletions in malarious areas. [ABSTRACT FROM AUTHOR]

Background: Malaria is highly prevalent in many parts of India and is mostly caused by the parasite species Plasmodium vivax followed by Plasmodium falciparum. Chloroquine (CQ) is the first-line treatment for blood stage P. vivax parasites, but cases of drug resistance to CQ have been reported from India. One of the surveillance strategies which is used to monitor CQ drug resistance, is the analysis of single nucleotide polymorphisms (SNPs) of the associated gene markers. Susceptibility to CQ can also be determined by copy number assessment of multidrug resistant gene (mdr-1). The current study has examined the prevalence of SNPs in P. vivax orthologs of P. falciparum chloroquine resistant and multi-drug resistant genes (pvcrt-o and pvmdr-1, respectively) and pvmdr-1 copy number variations in isolates from the highly endemic Mangaluru city near the South Western Coastal region of India. Methods: A total of 140 blood samples were collected from P. vivax infected patients attending Wenlock Hospital Mangaluru during July 2014 to January 2016. Out of these 140 samples, sequencing was carried out for 54 (38.5%) and 85 (60.7%) isolates for pvcrt-o and pvmdr-1, respectively. Single nucleotide polymorphisms (SNPs) in the pvcrt-o and pvmdr-1 genes were analysed by direct sequencing method, while copy number variations of 60 isolates (42. 8%) were determined by real time PCR. Results: Out of 54 clinical isolates analysed for pvcrt-o, three (5.6%) showed K10 insertion and the rest had wild type sequence. This is the first report to show K10 insertion in P. vivax isolates from India. Further, out of 85 clinical isolates of P. vivax analysed for mutations in pvmdr-1 gene, only one isolate had wild type sequence (~ 1%) while the remaining (99%) carried mutant alleles. Seven non-synonymous mutations with two novel mutations (I946V and Y1028C) were observed. Of all the observed mutations in pvmdr-1 gene, T958M was most highly prevalent (present in 90% of samples) followed by F1076L (76%), and Y976F (7%). Amplification of pvmdr-1 gene was observed in 31.6% of the isolates, out of 60 amplified. Conclusion: The observed variations both in pvmdr-1 and pvcrt-o genes indicate a trend towards parasite acquiring CQ resistance in this endemic area. [ABSTRACT FROM AUTHOR]

Background: Bed nets reduce malaria-related illness and deaths, by forming a protective barrier around people sleeping under them. When impregnated with long-lasting insecticide formulations they also repel or kill mosquitoes attempting to feed upon sleeping humans, and can even suppress entire populations of malaria vectors that feed predominantly upon humans. Nevertheless, an epidemiological study in 2012 demonstrated higher malaria prevalence among bed net users than non-users in urban Dar es Salaam, Tanzania. Methods: Focus group discussions were conducted with women from four selected wards of Dar es Salaam city, focusing on four major themes relating to bed net use behaviours: (1) reasons for bed net use, (2) reasons for not using bed nets, (3) stimuli or reminders for people to use a bed net (4) perceived reasons for catching malaria while using a bed net. An analytical method by framework grouping of relevant themes was used address key issues of relevance to the study objectives. Codes were reviewed and grouped into categories and themes. Results: All groups said the main reason for bed net use was protection against malaria. Houses with well-screened windows, with doors that shut properly, and that use insecticidal sprays against mosquitoes, were said not to use bed nets, while frequent attacks from malaria was the main stimulus for people to use bed nets. Various reasons were mentioned as potential reasons that compromise bed net efficacy, the most common of which were: (1) bed net sharing by two or more people, especially if one occupant tends to come to bed late at night, and does not tuck in the net 71%; (2) one person shares the bed but does not use the net, moving it away from the side on which s/ he sleeps 68%; (3) ineffective usage habits, called ulalavi, in which a sprawling sleeper either touches the net while sleeping up against it or leaves a limb hanging outside of it 68%. Less common reasons mentioned included: (1) Small bed nets which become un-tucked at night (31%); (2) Bed nets with holes large enough to allow mosquitoes to pass (28%); and (3) Going to bed late after already being bitten outdoors (24%). Conclusions: Behaviours associated with bed net use like; bed sharing, bed net non compliant-bedfellow, sleeping pattern like ulalavi and some physical bed net attributes compromise its effectiveness and supposedly increase of malaria infection to bed net users. While some well-screened houses looked to instigate low malaria prevalence to non-bed net users. [ABSTRACT FROM AUTHOR]

Background: Malaria prevalence continues to decline across sub-Saharan Africa as a result of various intervention strategies. However, the diseases still poses a public health concern in the region. While symptomatic malaria is recognized and treated, asymptomatic infections become increasingly important for interrupting transmission. A cross-sectional survey was conducted to assess malaria prevalence in symptomatic and asymptomatic children in Kiwangwa ward in Bagamoyo District in Tanzania. Methods: Four hundred school-aged children in Kiwanga ward were recruited in the study; 200 from Kiwangwa dispensary and 200 from nearby schools. Primary health parameters were examined and blood samples collected and examined for Plasmodium falciparum prevalence using rapid diagnostic test (RDT), light microscopy (LM) and reverse transcription quantitative PCR (RT-qPCR) targeting transcripts of A-type 18s rRNA of P. falciparum. Gametocytes were detected by LM and RT-qPCR targeting transcripts of gametocyte specific marker, Pfs25. Results: Overall P. falciparum prevalence was 73.3, 40.8 and 36.3% by RT-qPCR, RDT and LM in the study area, respectively (P < 0.001). As expected symptomatic children had a significantly higher prevalence of 89, 67.5 and 64.5% by qPCR, RDT and LM, compared to 57.5, 14 and 8% in the asymptomatic group, respectively. However, gametocyte prevalence in asymptomatic individuals was higher by both LM (2%) and qPCR (14%) than in symptomatic individuals LM (0.5%) and qPCR (3%). Conclusions: A substantial difference in prevalence of symptomatic and asymptomatic infections observed in Kiwangwa ward underpins the use of molecular tools in malaria surveillance aiming at estimating prevalence and transmission. Notably, the higher gametocytaemia observed in asymptomatic children indicates the reservoir infections and points to the need for detection and treatment of both asymptomatic and symptomatic malaria. [ABSTRACT FROM AUTHOR]

Background: Glucose-6-phosphate dehydrogenase (G6PD) is a rate limiting enzyme of the pentose phosphate pathway and is closely associated with the haemolytic disorders among patients receiving anti-malarial drugs, such as primaquine. G6PD deficiency (G6PDd) is an impending factor for radical treatment of malaria which affects the clearance of gametocytes from the blood and subsequent delay in the achievement of malaria elimination. The main objective of this study was to assess the prevalence of G6PD deficiency in six malaria endemic districts in Southern Nepal. Methods: A cross-sectional population based prevalence survey was conducted in six malaria endemic districts of Nepal, during April-Dec 2013. A total of 1341 blood samples were tested for G6PDd using two different rapid diagnostic test kits (Binax-Now® and Care Start™). Equal proportions of participants from each district (n ≥ 200) were enrolled considering ethnic and demographic representation of the population groups. Results: Out of total 1341 blood specimens collected from six districts, the overall prevalence of G6PDd was 97/1341; 7.23% on Binax Now and 81/1341; 6.0% on Care Start test. Higher prevalence was observed in male than females [Binax Now: male 10.2%; 53/521 versus female 5.4%; 44/820 (p = 0.003) and Care Start: male 8.4%; 44/521 versus female 4.5%; 37/820 (p = 0.003)]. G6PDd was higher in ethnic groups Rajbanshi (11.7%; 19/162) and Tharu (5.6%; 56/1005) (p = 0.006), major inhabitant of the endemic districts. Higher prevalence of G6PDd was found in Jhapa (22/224; 9.8%) and Morang districts (18/225; 8%) (p = 0.031). In a multivariate analysis, male were found at more risk for G6PDd than females, on Binax test (aOR = 1.97; CI 1.28-3.03; p = 0.002) and Care Start test (aOR = 1.86; CI 1.16-2.97; p = 0.009). Conclusions: The higher prevalence of G6PDd in certain ethnic group, gender and geographical region clearly demonstrates clustering of the cases and ascertained the risk groups within the population. This is the first study in Nepal which identified the vulnerable population groups for G6PDd in malaria endemic districts. The finding of this study warrants the need for G6PDd testing in vulnerable population groups in endemic districts, and also facilitates use of primaquine in mass supporting timely progress for malaria elimination. [ABSTRACT FROM AUTHOR]

Background: In the past two decades, there has been a reported decline in malaria in Ghana and the rest of the world; yet it remains the number one cause of mortality and morbidity. Human immuno-deficiency virus (HIV) and sickle cell disease (SCD) share a common geographical space with malaria in sub-Saharan Africa and an interaction between these three conditions has been suggested. This study determined the Plasmodium falciparum and non-P. falciparum status of symptomatic and non-symptomatic residents of Mpraeso in the highlands of Kwahu-South district of Ghana based on evidence of current national decline. The influence of HIV and SCD on malaria was also determined. Methods: Participants were 354 symptomatic patients visiting the Kwahu Government Hospital and 360 asymptomatic residents of the district capital. This cross-sectional study was conducted during the minor rainy season (October--December 2014). Rapid diagnostic tests (RDT), blood film microscopy and real-time polymerase chain reaction assessment of blood were done. Participants who tested positive with RDT were treated with artemisininbased combination therapy; and assessment of venous blood was repeated 7 days after treatment. HIV screening and haemoglobin genotyping was done. Univariate and multivariate regression analysis was used to determine the influence of SCD and HIV. Results: Plasmodium falciparum was prevalent at 124/142 (87.3%). Plasmodium malariae was the only non-falciparum species detected at 18/142 (12.7%). HIV and SCD did not significantly increase odds of malaria infection. However, the use of ITN and recent anti-malarial intake significantly decreased the odds of being malaria infected by 0.45-fold and 0.46-fold respectively. Conclusion: Plasmodium falciparum and P. malariae infection are the prevailing species in the study area; albeit varying from the national average. HIV and SCD were not associated with the risk of having malaria. [ABSTRACT FROM AUTHOR]

Background: A malaria hotspot in the southeastern region of Mauritania, near the Malian border, may hamper malaria control strategies. The objectives were to estimate the prevalence of genetic polymorphisms associated with drug resistance in Plasmodium falciparum isolates and establish baseline data. Methods: The study was conducted in two malaria-endemic areas in Hodh Elgharbi, situated in the Malian-Mauritanian border area. Blood samples were collected from symptomatic patients. Single nucleotide polymorphisms in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps were genotyped using PCR-restriction fragment length polymorphism, DNA sequencing and primer extension. The Pfmdr1 gene copy number was determined by real-time PCR. Results: Of 280 P. falciparum-infected patients, 193 (68.9%) carried the Pfcrt 76T mutant allele. The Pfmdr1 86Y and 184F mutations were found in 61 (23.1%) of 264 isolates and 167 (67.6%) of 247 samples that were successfully genotyped, respectively. Pfmdr1 mutant alleles 1034C, 1042D and 1246Y were rarely observed. Of 102 P. falciparum isolates analysed, ten (9.8%) had more than one copy of Pfmdr1 gene. The prevalence of isolates harbouring at least triple mutant Pfdhfr 51I, 59R, 108 N/T was 42% (112/268), of which 42 (37.5%) had an additional Pfdhps 437G mutation. The Pfdhps 540E mutation was observed in four isolates (1.5%), including three associated with Pfdhfr triple mutant. Only two quintuple mutants (Pfdhfr-51I-59R-108N Pfdhps-437G-540E) were observed. Conclusions: The observed mutations in Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt may jeopardize the future of seasonal malaria chemoprevention based on amodiaquine-sulfadoxine-pyrimethamine, intermittent preventive treatment for pregnant women using sulfadoxine-pyrimethamine, and treatment with artesunate-amodiaquine. Complementary studies should be carried out to document the distribution, origin and circulation of P. falciparum populations in this region and more widely in the country to assess the risk of the spread of resistance. [ABSTRACT FROM AUTHOR]

Background: Plasmodium falciparum genetic polymorphisms that mediate altered drug sensitivity may impact upon virulence. In a cross-sectional study, Ugandan children with infections mutant at pfcrt K76T, pfmdr1 N86Y, or pfmdr1 D1246Y had about one-fourth the odds of symptomatic malaria compared to those with infections with wild type (WT) sequences. However, results may have been confounded by greater likelihood in those with symptomatic disease of higher density mixed infections and/or recent prior treatment that selected for WT alleles. Methods: Polymorphisms in samples from paired episodes of asymptomatic and symptomatic parasitaemia in 114 subjects aged 4-11 years were followed longitudinally in Tororo District, Uganda. Paired episodes occurred within 3-12 months of each other and had no treatment for malaria in the prior 60 days. The prevalence of WT, mixed, and mutant alleles was determined using multiplex ligase detection reaction-fluorescent microsphere assays. Results: Considering paired episodes in the same subject, the odds of symptomatic malaria were lower for infections with mutant compared to WT or mixed sequence at N86Y (OR 0.26, 95% CI 0.09-0.79, p = 0.018), but not K76T or D1246Y. However, symptomatic episodes (which had higher densities) were more likely than asymptomatic to be mixed (for N86Y OR 2.0, 95% CI 1.04-4.0, p = 0.036). Excluding mixed infections, the odds of symptomatic malaria were lower for infections with mutant compared to WT sequence at N86Y (OR 0.33, 95% CI 0.11-0.98, p = 0.046), but not the other alleles. However, if mixed genotypes were grouped with mutants in this analysis or assuming that mixed infections consisted of 50% WT and 50% mutant genotypes, the odds of symptomatic infection did not differ between infections that were mutant or WT at the studied alleles. Conclusions: Although infections with only the mutant pfmdr1 86Y genotype were associated with symptomatic infection, this association could primarily be explained by greater parasite densities and therefore greater prevalence of mixed infections in symptomatic children. These results indicate limited association between the tested polymorphisms and risk of symptomatic disease and highlight the value of longitudinal studies for assessing associations between parasite factors and clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Cambodia has seen a marked reduction in the incidence of Plasmodium falciparum over the past decade without a corresponding decline in Plasmodium vivax incidence. It is unknown to what extent local transmission is sustained by a chain of clinical and sub-clinical infections or by continued re-introduction via migration. Using an ultrasensitive molecular technique, 20 villages in western Cambodia were surveyed to detect the low season prevalence of P. falciparum and P. vivax and local treatment records were reviewed. Methods: During March to May 2015 cross-sectional surveys were conducted in 20 villages in Battambang, western Cambodia. Demographic and epidemiological data and venous blood samples were collected from 50 randomly selected adult volunteers in each village. Blood was tested for Plasmodium infections by rapid diagnostic test (RDT), microscopy and high volume (0.5 ml packed red blood cell) quantitative polymerase chain reaction (uPCR). Positive samples were analysed by nested PCR to determine the Plasmodium species. Malaria case records were collected from the Provincial Health Department and village malaria workers to determine incidence and migration status. Results: Among the 1000 participants, 91 (9.1%) were positive for any Plasmodium infection by uPCR, seven (0.7%) by microscopy, and two (0.2%) by RDT. uPCR P. vivax prevalence was 6.6%, P. falciparum 0.7%, and undetermined Plasmodium species 1.8%. Being male (adjusted OR 2.0; 95% CI 1.2-3.4); being a young adult <30 years (aOR 2.1; 95% CI 1.3- 3.4); recent forest travel (aOR 2.8; 95% CI 1.6-4.8); and, a history of malaria (aOR 5.2; 95% CI 2.5-10.7) were independent risk factors for parasitaemia. Of the clinical malaria cases diagnosed by village malaria workers, 43.9% (297/634) and 38.4% (201/523) were among migrants in 2013 and in 2014, respectively. Plasmodium vivax prevalence determined by uPCR significantly correlated with vivax malaria incidences in both 2014 and 2015 (p = 0.001 and 0.002, respectively), whereas no relationship was observed in falciparum malaria (p = 0.36 and p = 0.59, respectively). Discussion: There was heterogeneity in the malaria parasite reservoir between villages, and Plasmodium prevalence correlated with subsequent malaria incidence. The association was attributable chiefly to P. vivax infections, which were nine-fold more prevalent than P. falciparum infections. In the absence of a radical cure with 8-aminoquinolines, P. vivax transmission will continue even as P. falciparum prevalence declines. Migration was associated with over a third of incident cases of clinical malaria. [ABSTRACT FROM AUTHOR]

Background: Although malaria has been traditionally regarded as less of a problem in urban areas compared to neighbouring rural areas, the risk of malaria infection continues to exist in densely populated, urban areas of Africa. Despite the recognition that urbanization influences the epidemiology of malaria, there is little consensus on urbanization relevant for malaria parasite mapping. Previous studies examining the relationship between urbanization and malaria transmission have used products defining urbanization at global/continental scales developed in the early 2000s, that overestimate actual urban extents while the population estimates are over 15 years old and estimated at administrative unit level. Methods and results: This study sought to discriminate an urbanization definition that is most relevant for malaria parasite mapping using individual level malaria infection data obtained from nationally representative householdbased surveys. Boosted regression tree (BRT) modelling was used to determine the effect of urbanization on malaria transmission and if this effect varied with urbanization definition. In addition, the most recent high resolution population distribution data was used to determine whether population density had significant effect on malaria parasite prevalence and if so, could population density replace urban classifications in modelling malaria transmission patterns. The risk of malaria infection was shown to decline from rural areas through peri-urban settlements to urban central areas. Population density was found to be an important predictor of malaria risk. The final boosted regression trees (BRT) model with urbanization and population density gave the best model fit (Tukey test p value <0.05) compared to the models with urbanization only. Conclusion: Given the challenges in uniformly classifying urban areas across different countries, population density provides a reliable metric to adjust for the patterns of malaria risk in densely populated urban areas. Future malaria risk models can, therefore, be improved by including both population density and urbanization which have both been shown to have significant impact on malaria risk in this study. [ABSTRACT FROM AUTHOR]

Background: After increasing coverage of malaria interventions, malaria prevalence remains high in Malawi. Previous studies focus on the impact of malaria interventions among children under 5 years old. However, in Malawi, the prevalence of infection is highest in school-aged children (SAC), ages 5 to 15 years. This study examined the interaction between age group and insecticide-treated net (ITN) use for preventing individual and community-level infection in Malawi. Methods: Six cross-sectional surveys were conducted in the rainy and dry seasons in southern Malawi from 2012 to 2014. Data were collected on household ITN usage and demographics. Blood samples for detection of Plasmodium falciparum infection were obtained from all household members present and over 6 months of age. Generalized linear mixed models were used to account for clustering at the household and community level. Results: There were 17,538 observations from six surveys. The association between ITN use and infection varied by season in SAC, but not in other age groups. The adjusted odds ratio (OR) for infection comparing ITN users to nonusers among SAC in the rainy season and dry season was 0.78 (95% CI 0.56, 1.10) and 0.51 (0.35, 0.74), respectively. The effect of ITN use did not differ between children under five and adults. Among all non-SACs the OR for infection was 0.78 (0.64, 0.95) in those who used ITNs compared to those that did not. Community net use did not protect against infection. Conclusions: Protection against infection with ITN use varies by age group and season. Individual estimates of protection are moderate and a community-level effect was not detected. Additional interventions to decrease malaria prevalence are needed in Malawi. [ABSTRACT FROM AUTHOR]

Background: The malaria burden in sub-Saharan Africa (SSA) has fallen substantially. Nevertheless, malaria remains a serious health concern, and Uganda ranks third in SSA in total malaria burden. Epidemiological studies of adult malaria in Uganda are scarce and little is known about rates of malaria in non-pregnant adult women. This pilot study assessed malaria prevalence among adult women from Wakiso district, historically a highly malaria endemic region. Methods: Adult women using public health services were screened for malaria, HIV and pregnancy. A physician selected subset of women presenting to the Outpatient Department of Entebbe General Hospital (EGH) with current fever (axillary temperature ≥37.5 ºC) or self-reporting fever during the previous 24 h, and a positive thick smear for malaria in the EGH laboratory were enrolled (n = 86). Women who self-identified as pregnant or HIV-positive were excluded from screening. Malaria infection was then assessed using HRP2/pLDH rapid diagnostic tests (RDTs) in all participants. Repeat microscopy and PCR were performed at a research laboratory for a subset of participants. In addition, 104 women without a history of fever were assessed for asymptomatic parasitaemia using RDT, and a subset of these women screened for parasitaemia using microscopy (40 women) and PCR (40 women). Results: Of 86 women diagnosed with malaria by EGH, only two (2.3%) had malaria confirmed using RDT, subsequently identified as a Plasmodium falciparum infection by research microscopy and PCR. Subset analysis of hospital diagnosed RDT-negative participants detected one sub-microscopic infection with Plasmodium ovale. Compared to RDT, sensitivity, specificity and PPV of hospital microscopy were 100% (CI 19.8-100), 0% (CI 0-5.32) and 2.33% (CI 0.403-8.94) respectively. Compared to PCR, sensitivity, specificity and PPV of hospital microscopy were 100% (CI 31.0-100), 0% (CI 0-34.5) and 23.1% (CI 6.16-54.0), respectively. No malaria was detected among asymptomatic women using RDT, research microscopy or PCR. Conclusions: Malaria prevalence among adult women appears to be low in Wakiso, but is masked by high rates of malaria overdiagnosis. More accurate malaria testing is urgently needed in public hospitals in this region to identify true causes of febrile illness and reduce unnecessary provision of anti-malarial therapy. [ABSTRACT FROM AUTHOR]

Background: In endemic areas, many people experience asymptomatic Plasmodium infections, particularly older children and adults, but their transmission contribution is unknown. Though not the exclusive determinant of infectiousness, transmission from humans to mosquitoes requires blood meals containing gametocytes. Gametocytes often occur at submicroscopic densities, challenging measurement in human populations. More sensitive molecular techniques allow better characterization of gametocyte epidemiologic patterns. Methods: Approximately 30 households were selected from each of eight sites in southern Malawi during two crosssectional surveys. Blood was sampled from 623 people during the dry season and 896 the following rainy season. Among people PCR-positive for Plasmodium falciparum, mature gametocytes were detected by qRT-PCR. Regression models evaluated predictors of gametocyte carriage and density in the total population and among those with PCRpositive infections. Results: The prevalence of gametocyte carriage by molecular testing was 3.5% during the dry season and 8.6% during the rainy season, and by microscopy 0.8 and 3.3%, respectively. Nearly half of PCR-positive infections carried gametocytes, regardless of recent symptom status. Among P. falciparum-infected people, only living in unfinished houses and age were significantly associated with gametocyte presence. Infected people in unfinished houses had higher odds of carrying gametocytes (OR 2.24, 95% CI 1.16-4.31), and 31% (95% CI 3-65%) higher gametocyte density than those in finished houses. School-age children (5-15 years), had higher odds than adults (≥16 years) of having gametocytes when infected (OR 2.77, 95% CI 1.47-5.19), but 31% (95% CI 11-47%) lower gametocyte density. Children <5 years did not have significantly higher odds of gametocyte carriage or density when infected than adults. Conclusions: School-age children frequently carry gametocytes in communities of southern Malawi and represent an under-recognized reservoir of infection. Malaria elimination strategies should address these frequently asymptomatic reservoirs, especially in highly endemic areas. Improved household construction may also reduce the infectious reservoir. [ABSTRACT FROM AUTHOR]

Background: Malaria continues to be an important cause of morbidity and mortality in Madagascar. It has been estimated that the malaria burden costs Madagascar over $52 million annually in terms of treatment costs, lost productivity and prevention expenses. One of the key malaria prevention strategies of the Government of Madagascar consists of large-scale mass distribution campaigns of long-lasting insecticide-treated bed nets (LLIN). Although there is ample evidence that child mortality has decreased in Madagascar, it is unclear whether increases in LLIN ownership have contributed to this decline. This study analyses multiple recent cross-sectional survey data sets to examine the association between household bed net ownership and all-cause child mortality. Results: Data on household-level bed net ownership confirm that the percentage of households that own one or more bed nets increased substantially following the 2009 and 2010 mass LLIN distribution campaigns. Additionally, all-cause child mortality in Madagascar has declined during the period 2008-2013. Bed net ownership was associated with a 22% reduction in the all-cause child mortality hazard in Madagascar. Conclusions: Mass bed net distributions contributed strongly to the overall decline in child mortality in Madagascar during the period 2008-2013. However, the decline was not solely attributable to increases in bed net coverage, and nets alone were not able to eliminate most of the child mortality hazard across the island. [ABSTRACT FROM AUTHOR]

Background: This study was conducted in Bura irrigation scheme in Tana River County and the pastoral area in Ijara, Garissa County in the eastern Kenya to establish the knowledge, attitude and practices on malaria transmission, control and management, and determine malaria prevalence and the associated risk factors. Methods: A cross sectional survey design that involved 493 randomly selected people from 334 households was used between November and December 2013. All the randomly selected people were screened for malaria parasites using rapid diagnostic test (RDT)—Carestart™ malaria HRP2 (pf ) kit. A questionnaire was administered to determine potential risk factors and perceptions on malaria exposure within a period of 2 months prior to the survey. Two logistic regression models were fitted to the data; one used the RDT results while the other used data from the questionnaire survey. Results: Using RDT, the prevalence of malaria was 4.68 % (95 % CI: 1.48-7.88 %) and 0.31 % (-0.30 to 0.92 %) in irrigated and non-irrigated areas, respectively. From the questionnaires, 14.62 % (9.27-19.97 %) and 23.91 % (19.23- 28.60 %) of the participants perceived to have had malaria in the irrigated and pastoral areas, respectively. The main malaria control measure was the use of bed nets: average of three nets per household in Bura irrigation scheme and one in Ijara. Artemether-lumefantrine was the main drug of choice mainly in the irrigated area while sulfadoxine- pyrimethamine was likely to be used in the non-irrigated area. Households located >5 km from the nearest health facility had higher prevalence of Plasmodium infection than those located ≤5 km. Conclusion: The residents of Bura irrigation scheme were more likely to be infected compared to those living in the non-irrigated area of Ijara. However, those in the non-irrigated area were more likely to be treated or use over-the-counter medication for perceived malaria illnesses compared to those in the irrigated area. There is a need, therefore, to formulate effective ways of managing malaria especially in irrigated areas and build capacity on differential diagnosis for malaria, especially in the pastoral areas. [ABSTRACT FROM AUTHOR]

Background: The East African highlands are fringe regions between stable and unstable malaria transmission. What factors contribute to the heterogeneity of malaria exposure on different spatial scales within larger foci has not been extensively studied. In a comprehensive, community-based cross-sectional survey an attempt was made to identify factors that drive the macro- and micro epidemiology of malaria in a fringe region using parasitological and serological outcomes. Methods: A large cross-sectional survey including 17,503 individuals was conducted across all age groups in a 100 km2 area in the Western Kenyan highlands of Rachuonyo South district. Households were geo-located and prevalence of malaria parasites and malaria-specific antibodies were determined by PCR and ELISA. Household and individual risk-factors were recorded. Geographical characteristics of the study area were digitally derived using high-resolution satellite images. Results: Malaria antibody prevalence strongly related to altitude (1350-1600 m, p < 0.001). A strong negative association with increasing altitude and PCR parasite prevalence was found. Parasite carriage was detected at all altitudes and in all age groups; 93.2 % (2481/2663) of malaria infections were apparently asymptomatic. Malaria parasite prevalence was associated with age, bed net use, house construction features, altitude and topographical wetness index. Antibody prevalence was associated with all these factors and distance to the nearest water body. Conclusion: Altitude was a major driver of malaria transmission in this study area, even across narrow altitude bands. The large proportion of asymptomatic parasite carriers at all altitudes and the age-dependent acquisition of malaria antibodies indicate stable malaria transmission; the strong correlation between current parasite carriage and serological markers of malaria exposure indicate temporal stability of spatially heterogeneous transmission. [ABSTRACT FROM AUTHOR]

Background: Malaria hotspots, areas with consistently higher than average transmission, may become increasingly common as malaria declines. This phenomenon, currently observed in The Gambia, may be caused by several factors, including some related to the local vectors, whose contribution is poorly understood. Methods: Using WHO susceptibility bioassays, insecticide resistance status was determined in vector populations sampled from six pairs of villages across The Gambia, each pair contained a low and high prevalence village. Results: Three vector species were observed (23.5 % Anopheles arabiensis, 31.2 % Anopheles gambiae, 43.3 % Anopheles coluzzii and 2.0 % An. coluzzii × An. gambiae hybrids). Even at a fine scale, significant differences in species composition were detected within village pairs. Resistance to both DDT and deltamethrin was more common in An. gambiae, most markedly in the eastern part of The Gambia and partly attributable to differing frequencies of resistance mutations. The Vgsc-1014F target site mutation was strongly associated with both DDT (OR = 256.7, (95 % CI 48.6-6374.3, p < 0.001) and deltamethrin survival (OR = 9.14, (95 % CI 4.24-21.4, p < 0.001). A second target site mutation, Vgsc-1575Y, which co-occurs with Vgsc-1014F, and a metabolic marker of resistance, Gste2-114T, conferred additional survival benefits to both insecticides. DDT resistance occurred significantly more frequently in villages with high malaria prevalence (p = 0.025) though this did not apply to deltamethrin resistance. Conclusion: Whilst causality of relationships requires further investigation, variation in vector species and insecticide resistance in The Gambia is associated with malaria endemicity; with a notably higher prevalence of infection and insecticide resistance in the east of the country. In areas with heterogeneous malaria transmission, the role of the vector should be investigated to guide malaria control interventions. [ABSTRACT FROM AUTHOR]

Background: Malaria transmission, primarily mediated by Anopheles gambiae, persists in Dar es Salaam (DSM) despite high coverage with bed nets, mosquito-proofed housing and larviciding. New or improved vector control strategies are required to eliminate malaria from DSM, but these will only succeed if they are delivered to the minority of locations where residual transmission actually persists. Hotspots of spatially clustered locations with elevated malaria infection prevalence or vector densities were, therefore, mapped across the city in an attempt to provide a basis for targeting supplementary interventions. Methods: Two phases of a city-wide population-weighted random sample of cross-sectional household surveys of malaria infections were complemented by two matching phases of geographically overlapping, high-resolution, longitudinal vector density surveys; spanning 2010-2013. Spatial autocorrelations were explored using Moran's I and hotspots were detected using flexible spatial scan statistics. Results: Seven hotspots of spatially clustered elevated vector density and eight of malaria infection prevalence were detected over both phases. Only a third of vectors were collected in hotspots in phase 1 (30 %) and phase 2 (33 %). Malaria prevalence hotspots accounted for only half of malaria infections detected in phase 1 (55 %) and phase 2 (47 %). Three quarters (76 % in phase 1 and 74 % in phase 2) of survey locations with detectable vector populations were outside of hotspots. Similarly, more than half of locations with higher infection prevalence (>10 %) occurred outside of hotspots (51 % in phase 1 and 54 % in phase 2). Vector proliferation hazard (exposure to An. gambiae) and malaria infection risk were only very loosely associated with each other (Odds ratio (OR) [95 % Confidence Interval (CI)] = 1.56 [0.89, 1.78], P = 0.52)). Conclusion: Many small, scattered loci of local malaria transmission were haphazardly scattered across the city, so interventions targeting only currently identifiable spatially aggregated hotspots will have limited impact. Routine, spatially comprehensive, longitudinal entomological and parasitological surveillance systems, with sufficient sensitivity and spatial resolution to detect these scattered loci, are required to eliminate transmission from this typical African city. Intervention packages targeted to both loci and hotspots of transmission will need to suppress local vector proliferation, treat infected residents and provide vulnerable residents with supplementary protective measures against exposure. [ABSTRACT FROM AUTHOR]

Background: In Kinshasa, malaria remains a major public health problem but its spatial epidemiology has not been assessed for decades now. The city's growth and transformation, as well as recent control measures, call for an update. To identify highly exposed communities and areas where control measures are less critically needed, detailed risk maps are required to target control and optimize resource allocation. Methods: In 2009 (end of the dry season) and 2011 (end of the rainy season), two cross-sectional surveys were conducted in Kinshasa to determine malaria prevalence, anaemia, history of fever, bed net ownership and use among children 6-59 months. Geo-referenced data for key parameters were mapped at the level of the health area (HA) by means of a geographic information system (GIS). Results: Among 7517 children aged 6-59 months from 33 health zones (HZs), 6661 (3319 in 2009 and 3342 in 2011) were tested for both malaria (by Rapid Diagnostic Tests) and anaemia, and 856 (845 in 2009 and 11 in 2011) were tested for anaemia only. Fifteen HZs were sampled in 2009, 25 in 2011, with seven HZs sampled in both surveys. Mean prevalence for malaria and anaemia was 6.4 % (5.6-7.4) and 65.1 % (63.7-66.6) in 2009, and 17.0 % (15.7-18.3) and 64.2 % (62.6-65.9) in 2011. In two HZs sampled in both surveys, malaria prevalence was 14.1 % and 26.8 % in Selembao (peri-urban), in the 2009 dry season and 2011 rainy season respectively, and it was 1.0 % and 0.8 % in Ngiri Ngiri (urban). History of fever during the preceding two weeks was 13.2 % (12.5-14.3) and 22.3 % (20.8-23.4) in 2009 and 2011. Household ownership of at least one insecticide-treated net (ITN) was 78.7 % (77.4-80.0) and 65.0 % (63.7-66.3) at both time points, while use was 57.7 % (56.0-59.9) and 45.0 % (43.6-46.8), respectively. Conclusions: This study presents the first malaria risk map of Kinshasa, a mega city of roughly 10 million inhabitants and located in a highly endemic malaria zone. Prevalence of malaria, anaemia and reported fever was lower in urban areas, whereas low coverage of ITN and sub-optimal net use were frequent in peri-urban areas. [ABSTRACT FROM AUTHOR]

Background: Approximately 15 % of all deaths in Africa among children under five years old are due to malaria, a preventable and treatable disease. A prevailing sociological theory holds that resources (including knowledge, money, power, prestige, or beneficial social connections) are particularly relevant when diseases are susceptible to effective prevention. This study examines the role of socioeconomic inequalities by broadly predicting malaria knowledge and use of preventive technology among women aged 15-49, and malaria among children aged 6-59 months in Madagascar. Methods: Data came from women aged 15-49 years (N = 8279) interviewed by Madagascar's 2011/2013 Malaria Indicator Studies, and their children aged under five years (N = 7644). Because geographic location may be associated with socioeconomic factors and exposure to malaria, multilevel models were used to account for unobserved geographic and administrative variation. Models also account for observed social, economic, demographic, and seasonal factors. Results: Prevalence among children four years old and younger was 7.8 %. Results showed that both mother's education and household wealth strongly influence knowledge about and efforts to prevent and treat malaria. Analyses also revealed that the prevalence of malaria among children aged 6-59 months was determined by household wealth (richest vs poorest: OR = 0.25, 95 % CI [0.10, 0.64]) and maternal education (secondary vs none: OR = 0.51, 95 % CI [0.28, 0.95]). Conclusions: Malaria may be subject to socio-economic forces arising from a broad set of behavioural and geographic determinants, even after adjusting for geographic risk factors and seasonality. Nearly 21 % of the sample lacked primary schooling. To improve malaria reduction efforts, broad-based interventions may need to attack inequalities to ensure that knowledge, prevention and treatment are improved among those who are most vulnerable. [ABSTRACT FROM AUTHOR]

Background: Although the epidemiology of malaria has been based primarily on microscopy and rapid diagnostic tests, molecular methods are necessary to understand the complexity of natural infection in regions where transmission is intense and simultaneous infection with multiple parasite genotypes is common such as sub-Saharan Africa. Methods: To compare microscopic and molecular estimates of the incidence and clearance of Plasmodium falciparum infection, we followed 80 children monthly for 1 year in the village of Bancoumana in Mali. Results and discussion: Similar seasonal patterns were observed with both methods (rainy season peak, dry season nadir), although molecular methods detected more infections than microscopy (571 vs 331 in 906 specimens), more new infections (311 vs 104 during 829 person-months) and spontaneous clearance events (317 vs 116) and found higher incidence (0.38 vs 0.13 new genotypes/person/month, p < 0.001) and spontaneous clearance rates (0.38 vs 0.14 genotypes cleared/person/month, p < 0.001). These differences were greatest for persistently-infected subjects in whom neither new infections nor the clearance of old infections could be detected by microscopy (0.71 new infections and 0.73 cleared infections per month using molecular methods vs 0.000 by microscopy, p < 0.001). Conclusions: Molecular methods provide information about genetic diversity, the intensity of transmission and spontaneous clearance in the absence of drug treatment that cannot be obtained by microscopy. They will be necessary to evaluate the efficacy of vaccines, drugs and other control strategies for diseases such as malaria in which simultaneous infection with more than one organism (genotype) is common. [ABSTRACT FROM AUTHOR]

Background: Malaria in Southeast Asia frequently clusters along international borders. For example, while most of Thailand is malaria free, the border region shared with Myanmar continues to have endemic malaria. This spatial pattern is the result of complex interactions between landscape, humans, mosquito vectors, and malaria parasites. An understanding of these complex ecological and socio-cultural interactions is important for designing and implementing malaria elimination efforts in the region. This article offers an ecological perspective on the malaria situation along the Thailand-Myanmar border. Discussion: This border region is long (2000 km), mountainous, and the environment ranges from thick forests to growing urban settlements and wet-rice fields. It is also a biologically diverse region. All five species of malaria known to naturally infect humans are present. At least three mosquito vector species complexes, with widely varying behavioural characteristics, exist in the area. The region is also a hub for ethnic diversity, being home to over ten different ethnolinguistic groups, several of which have been engaged in conflict with the Myanmar government now for over half a century. Given the biological and ethnic diversity, as well as the complex socio-political context, malaria control and elimination in the region is challenging. Conclusion: Despite these complexities, multipronged approaches including collaborations with multiple local organizations, quick access to diagnosis and treatment, prevention of mosquito bites, radical cure of parasites, and mass drug administration appear to be drastically decreasing Plasmodium falciparum infections. Such approaches remain crucial as the region moves toward elimination of P. falciparum and potentially Plasmodium vivax. [ABSTRACT FROM AUTHOR]

Background: Malaria programmes estimate changes in prevalence to evaluate their efficacy. In this study, parasite genetic data was used to explore how the demography of the parasite population can inform about the processes driving variation in prevalence. In particular, how changes in treatment and population movement have affected malaria prevalence in an area with seasonal malaria. Methods: Samples of Plasmodium falciparum collected over 8 years from a population in Turbo, Colombia were genotyped at nine microsatellite loci and three drug-resistance loci. These data were analysed using several population genetic methods to detect changes in parasite genetic diversity and population structure. In addition, a coalescent- based method was used to estimate substitution rates at the microsatellite loci. Results: The estimated mean microsatellite substitution rates varied between 5.35 × 10−3 and 3.77 × 10−2 substitutions/locus/month. Cluster analysis identified six distinct parasite clusters, five of which persisted for the full duration of the study. However, the frequencies of the clusters varied significantly between years, consistent with a small effective population size. Conclusions: Malaria control programmes can detect re-introductions and changes in transmission using rapidly evolving microsatellite loci. In this population, the steadily decreasing diversity and the relatively constant effective population size suggest that an increase in malaria prevalence from 2004 to 2007 was primarily driven by local rather than imported cases. [ABSTRACT FROM AUTHOR]

Background: As indicators of burden of malaria have substantially decreased in The Gambia, reaching a pre-elimination status may be attainable. Achieving this goal requires in-depth understanding of the current burden of Plasmodium falciparum infection. Methods: A nationwide cross-sectional survey was conducted in 2012 to determine the prevalence of P. falciparum infection, and to describe its heterogeneity and associated risk factors. Finger-prick blood samples were collected for microscopy, species-specific PCR and haemoglobin measurement. Results: A total of 9,094 participants were included and median age was 11.9 years (IQR 5, 28). Overall prevalence of P. falciparum was 16.01 % with marked heterogeneity between sites (4.32-36.75 %) and within villages in each site (1.63-49.13 %). Across all sites, 51.17 % (745/1,456) of infections were asymptomatic and 35.61 % (448/1,258) were sub-microscopic. The odds of P. falciparum infection were higher in older children; 5-15 years (OR = 1.90; 95 % CI 1.60-2.26), adults (OR = 1.48; 95 % CI 1.24-1.78) and participants with moderate anaemia (OR = 1.62; 95 % CI 1.32-1.99). Conclusions: The current malaria control interventions are not sufficient to interrupt transmission in The Gambia as malaria prevalence is still relatively high in the eastern part of the country. New interventions aiming at interrupting transmission are needed and should be urgently evaluated. [ABSTRACT FROM AUTHOR]

Background: Though essential to the development and evaluation of national malaria control programmes, precise enumeration of the clinical illness burden of malaria in endemic countries remains challenging where local surveillance systems are incomplete. Strategies to infer annual incidence rates from parasite prevalence survey compilations have proven effective in the specific case of Plasmodium falciparum, but have yet to be developed for Plasmodium vivax. Moreover, defining the relationship between P. vivax prevalence and clinical incidence may also allow levels of endemicity to be inferred for areas where the information balance is reversed, that is, incident case numbers are more widely gathered than parasite surveys; both applications ultimately facilitating cartographic estimates of P. vivax transmission intensity and its ensuring disease burden. Methods: A search for active case detection surveys was conducted and the recorded incidence values were matched to local, contemporary parasite rate measures and classified to geographic zones of differing relapse phenotypes. A hierarchical Bayesian model was fitted to these data to quantify the relationship between prevalence and incidence while accounting for variation among relapse zones. Results: The model, fitted with 176 concurrently measured P. vivax incidence and prevalence records, was a linear regression of the logarithm of incidence against the logarithm of age-standardized prevalence. Specific relationships for the six relapse zones where data were available were drawn, as well as a pooled overall relationship. The slope of the curves varied among relapse zones; zones with short predicted time to relapse had steeper slopes than those observed to contain long-latency relapse phenotypes. Conclusions: The fitted relationships, along with appropriate uncertainty metrics, allow for estimates of clinical incidence of known confidence to be made from wherever P. vivax prevalence data are available. This is a prerequisite for cartographic-based inferences about the global burden of morbidity due to P. vivax, which will be used to inform control efforts. [ABSTRACT FROM AUTHOR]

Background: Southwestern Uganda has high malaria heterogeneity despite moderate vector control and other interventions. Moreover, the early biting transmission and increased resistance to insecticides might compromise strategies relying on vector control. Consequently, monitoring of vector behaviour and insecticide efficacy is needed to assess the effectiveness of strategies aiming at malaria control. This eventually led to an entomological survey in two villages with high malaria prevalence in this region. Methods: During rainy, 2011 and dry season 2012, mosquitoes were collected in Engari and Kigorogoro, Kazo subcounty, using human landing collection, morning indoor resting collection, pyrethrum spray collection and larval collection. Circumsporozoite protein of Plasmodium falciparum sporozoites in female Anopheles mosquitoes was detected using ELISA assay. Bioassays to monitor Anopheles resistance to insecticides were performed. Results: Of the 1,021 female Anopheles species captured, 62% (632) were Anopheles funestus and 36% (371) were Anopheles gambiae s.l. The most common species were Anopheles gambiae s.l. in Engari (75%) and A. funestus in Kigorogoro (83%). Overall, P. falciparum prevalence was 2.9% by ELISA. The daily entomological inoculation rates were estimated at 0.17 and 0.58 infected bites/person/night during rainy and dry season respectively in Engari, and 0.81 infected bites/person/night in Kigorogoro during dry season. In both areas and seasons, an unusually early evening biting peak was observed between 6 - 8 p.m. In Engari, insecticide bioassays showed 85%, 34% and 12% resistance to DDT during the rainy season, dry season and to deltamethrin during the dry season, respectively. In Kigorogoro, 13% resistance to DDT and to deltamethrin was recorded. There was no resistance observed to bendiocarb and pirimiphos methyl. Conclusions: The heterogeneity of mosquito distribution, entomological indicators and resistance to insecticides in villages with high malaria prevalence highlight the need for a long-term vector control programme and monitoring of insecticide resistance in Uganda. The early evening biting habits of Anopheles combined with resistance to DDT and deltamethrin observed in this study suggest that use of impregnated bed nets alone is insufficient as a malaria control strategy, urging the need for additional interventions in this area of high transmission. [ABSTRACT FROM AUTHOR]

Background: A report of the chloroquine and amodiaquine resistance pfcrt-SVMNT haplotype in Tanzania raises concern about high-level resistance to the artesunate-amodiaquine combination treatment widely employed in Africa. Mutations in the pfmdr1 multi-drug resistance gene may also be associated with resistance, and a highly polymorphic microsatellite (ms-4760) of the pfnhe1 gene involved in quinine susceptibility has not been surveyed in Tanzania. Methods: A total of 234 samples collected between 2003 - 2006 from an observational birth cohort of young children in Muheza, Tanzania were analysed. In these children, 141 cases of P. falciparum infections were treated with AQ and 93 episodes were treated with QN. Haplotypes of pfcrt and pfmdr1 were determined by a Taqman assay, and ms-4760 repeats in pfnhe1 were assessed by nested PCR amplification and direct sequencing. Parasite population diversity was evaluated using microsatellite markers on five different chromosomes. Results: The pfcrt-CVIET haplotype was present alone in 93.6% (219/234) of the samples over the study period; the wild-type chloroquine- and amodiaquine-sensitive haplotype pfcrt-CVMNK was present in 4.3% (10/234) of the samples; and both haplotypes were present in 2.1% (5/234) of the samples. No significant change in wild-type pfcrt-CVMNK prevalence was evident over the 4-year period of the study. The pfcrt-SVMNT haplotype associated with high-level amodiaquine resistance was not detected in this study. The pfmdr1 locus was genotyped in 178 of these samples. The pfmdr1-YYNY haplotype predominated in 67.4% (120/178) of infections and was significantly associated with the pfcrt-CVIET haplotype. All samples carried the wild-type pfmdr1-N1042 codon. The ms-4760 repeat on pfnhe1 locus displayed 12 distinct haplotypes with ms-4760-1 predominating in the population. Analysis of these haplotypes showed no association of a particular haplotype with quinine treatment outcome. Conclusion: The pfcrt-CVIET chloroquine resistance haplotype dominated in the collection of P. falciparum samples from Muheza. The pfcrt-SVMNT haplotype, which threatens the efficacy of amodiaquine and was reported in the same time period from Korogwe, Tanzania, 40 Km from Muheza, was not detected. Relative low prevalence of pfcrt-SVMNT in Africa may result from genetic or other factors rendering P. falciparum less supportive of this haplotype than in South America or other regions. [ABSTRACT FROM AUTHOR]

Background: Evidence for decreasing chloroquine (CQ) efficacy against Plasmodium vivax has been reported from many endemic countries in the world. In Ethiopia, P. vivax accounts for 40% of all malaria cases and CQ is the first-line drug for vivax malaria. Mutations in multidrug resistance 1 (pvmdr-1) and K10 insertion in the pvcrt-o genes have been identified as possible molecular markers of CQ-resistance (CQR) in P. vivax. Despite reports of CQ treatment failures, no data are currently available on the prevalence of molecular markers of P. vivax resistance in Ethiopia. The objective of this study was to determine the prevalence of mutations in the pvmdr-1 and K10 insertion in the pvcrt-o genes. Methods: A total of 36 P. vivax clinical isolates were collected from West Arsi district in Ethiopia. Sequencing was used to analyse polymorphisms of the pvcrt-o and pvmdr-1 genes. Results: Sequencing results of the pvmdr-1 fragment showed the presence of two non-synonymous mutations at positions 976 and 1076. The Y → F change at codon 976 (TAC → TTC) was observed in 21 (75%) of 28 the isolates while the F → L change (at codon 1076), which was due to a single mutation (TTT → CTT), was observed in 100% of the isolates. Of 33 samples successfully amplified for the pvcrt-o, the majority of the isolates (93.9%) were wild type, without K10 insertion. Conclusions: High prevalence of mutations in candidate genes conferring CQR in P. vivax was identified. The fact that CQ is still the first-line treatment for vivax malaria, the significance of mutations in the pvcrt-o and pvmdr-1 genes and the clinical response of the patients' to CQ treatment and whether thus an association exists between point mutations of the candidate genes and CQR requires further research in Ethiopia. [ABSTRACT FROM AUTHOR]

Background: Malaria risk maps play an increasingly important role in disease control planning, implementation, and evaluation. The construction of these maps using modern geospatial techniques relies on covariate grids: continuous surfaces quantifying environmental factors that partially explain spatial heterogeneity in malaria endemicity. Although crucial, past variable selection processes for this purpose have often been subjective and ad-hoc, with many covariates used in modeling with little quantitative justification. Methods: This research consists of an extensive covariate construction and selection process for predicting Plasmodium falciparum parasite rates (PfPR) in Africa for years 2000-2012. First, a literature review was conducted to establish a comprehensive list of covariates used for malaria mapping. Second, a library of covariate data was assembled to reflect this list, a process that included the construction of multiple, temporally dynamic datasets. Third, the resulting set of covariates was leveraged to create more than 50 million possible covariate terms via factorial combinations of different spatial and temporal aggregations, transformations, and pairwise interactions. Fourth, the expanded set of covariates was reduced via successive selection criteria to yield a robust covariate subset that was assessed using an out-of-sample validation approach. Results: The final covariate subset included predominately dynamic covariates and it substantially out-performed earlier sets used by the Malaria Atlas Project (MAP) for creating global malaria risk maps, with the pseudo-R² value for the out-of-sample validation increasing from 0.43 to 0.52. Dynamic covariates improved the model, with 17 of the 20 new covariates consisting of monthly or annual products, but the selected covariates were typically interaction terms that included both dynamic and synoptic datasets. Thus the interplay between normal (i.e., long-term averages) and immediate conditions may be key for characterizing environmental controls on parasite rate. Conclusions: This analysis represents the first effort to systematically audit covariate utility for malaria mapping and then derive an objective, empirically based set of environmental covariates for modeling PfPR. The new covariates produce more reliable representations of malaria risk patterns and how they are changing through time, and these covariates will be used to characterize spatially and temporally varying environmental conditions affecting PfPR within a geostatistical-modeling framework, thus building upon previous research by MAP that produced global malaria maps for 2007 and 2010. [ABSTRACT FROM AUTHOR]

Background In the last decade, an important scale-up was observed in malaria control interventions. Madagascar entered the process for pre-elimination in 2007. Policy making needs operational indicators, but also indicators about effectiveness and impact of malaria control interventions (MCI). This study is aimed at providing data about malaria infection, morbidity, and mortality, and MCI in Madagascar. Methods Two nationwide surveys were simultaneously conducted in 2012-2013 in Madagascar: a study about non-complicated clinical malaria cases in 31 sentinel health facilities, and a cross-sectional survey (CSS) in 62 sites. The CSS encompassed interviews, collection of biological samples and verbal autopsies (VA). Data from CSS were weighted for age, sex, malaria transmission pattern, and population density. VA data were processed with InterVA- 4 software. Results CSS included 15,746 individuals of all ages. Parasite rate (PR) as measured by rapid diagnostic tests was 3.1%, and was significantly higher in five to 19 year olds, in males, poorer socio-economic status (SES) quintiles and rural areas. Long-lasting insecticidal nets (LLIN) use was 41.7% and was significantly lower in five to 19 year olds, males and wealthier SES quintiles. Proportion of persons covered by indoor residual spraying (IRS) was 66.8% in targeted zones. Proportion of persons using other insecticides than IRS was 22.8%. Coverage of intermittent preventive treatment during pregnancy was 21.5%. Exposure to information, education and communication messages about malaria was significantly higher in wealthier SES for all media but information meetings. The proportion of fever case managements considered as appropriate with regard to malaria was 15.8%. Malaria was attributed as the cause of death in 14.0% of 86 VA, and 50% of these deaths involved persons above the age of five years. The clinical case study included 818 cases of which people above the age of five accounted for 79.7%. In targeted zones, coverage of LLIN and IRS were lower in clinical cases than in general population. Conclusions This study provides valuable data for the evaluation of effectiveness and factors affecting MCI. MCI and evaluation surveys should consider the whole population and not only focus on under-fives and pregnant women in pre-elimination or elimination strategies. [ABSTRACT FROM AUTHOR]

Background The widespread use of insecticide-treated nets (LLINs) leads to the development of vector resistance to insecticide. This resistance can reduce the effectiveness of LLIN-based interventions and perhaps reverse progress in reducing malaria morbidity. To prevent such difficulty, it is important to know the real impact of resistance in the effectiveness of mosquito nets. Therefore, an assessment of LLIN efficacy was conducted in malaria prevention among children in high and low resistance areas. Methods The study was conducted in four rural districts and included 32 villages categorized as low or high resistance areas in Plateau Department, south-western Benin. Larvae collection was conducted to measure vector susceptibility to deltamethrin and knockdown resistance (kdr) frequency. In each resistance area, around 500 children were selected to measure the prevalence of malaria infection as well as the prevalence of anaemia associated with the use of LLINs. Results Observed mortalities of Anopheles gambiae s.s population exposed to deltamethrin ranged from 19 to 96%. Knockdown resistance frequency was between 38 and 84%. The prevalence of malaria infection in children under five years was 22.4% (19.9-25.1). This prevalence was 17.3% (14.2-20.9) in areas of high resistance and 27.1% (23.5-31.1) in areas of low resistance (p = 0.04). Eight on ten children that were aged six - 30 months against seven on ten of those aged 31-59 months were anaemic. The anaemia observed in the six to 30-month old children was significantly higher than in the 31-59 month old children (p = 0.00) but no difference associated with resistance areas was observed (p = 0.35). The net use rate was 71%. The risk of having malaria was significantly reduced (p < 0.05) with LLIN use in both low and high resistance areas. The preventive effect of LLINs in high resistance areas was 60% (95% CI: 40-70), and was significantly higher than that observed in low resistance areas (p < 0.05). Conclusion The results of this study showed that the resistance of malaria vectors seems to date not have affected the impact of LLINs and the use of LLINs was highly associated with reduced malaria prevalence irrespective of resistance. [ABSTRACT FROM AUTHOR]

Background Recent efforts of accelerated malaria control towards the long-term goal of elimination had significant impacts in reducing malaria transmission. While these efforts need to be sustained over time, a scenario of low transmission could bring about changes in individual disease risk perception, hindering adherence to protective measures, and affecting disease-related knowledge. The goal of this study was to investigate the potential impact of a successful malaria vector control intervention on bed net usage and malaria-related knowledge. Methods Dar es Salaam's Urban Malaria Control Program was launched in 2004 with the aim of developing a sustainable larviciding intervention. Larviciding was scaled-up using a steppedwedge design. Cross-sectional and longitudinal data were collected using a randomized cluster sampling design (2004-2008). Prevalence ratios (PR) for the effect of the larviciding intervention on bed net usage (N = 64,537) and household heads' knowledge of malaria symptoms and transmission (N = 11,254) were obtained from random effects regression models. Results The probability that individuals targeted by larviciding had used a bed net was reduced by 5% as compared to those in non-intervention areas (PR = 0.95; 95% credible intervals (CrI): 0.94-0.97) and the magnitude of this effect increased with time. Larviciding also led to a decline in household heads' knowledge of malaria symptoms (PR = 0.88; 95% CrI: 0.83- 0.92) but no evidence of effect on knowledge of malaria transmission was found. Conclusion Successful control interventions could bring about further challenges to sustaining gains in reducing malaria transmission if not accompanied by strategies to avoid changes in individual knowledge and behaviour. This study points to two major research gaps. First, there is an urgent need to gather more evidence on the extent to which countries that have achieved significant decline in malaria transmission are also observing changes in individual behaviour and knowledge. Second, multidisciplinary assessments that combine quantitative and qualitative data, utilizing theories of health behaviour and theories of knowledge, are needed to optimize efforts of national malaria control programmes, and ultimately contribute to sustained reduction in malaria transmission. [ABSTRACT FROM AUTHOR]

Background The close relationship between vector-borne diseases and their environment is well documented, especially for diseases with water-dependent vectors such as avian malaria. Mosquitoes are the primary vectors of avian malaria and also the definitive hosts in the disease life cycle. Factors pertinent to mosquito ecology are likely to be influential to observed infection patterns; such factors include rainfall, season, temperature, and water quality. Methods The influence of mosquito abundance and occurrence on the prevalence of Plasmodium spp. in the Ploceidae family (weavers) was examined, taking into account factors with an indirect influence upon mosquito ecology. Mosquitoes and weaver blood samples were simultaneously collected in the Western Cape, South Africa over a two-year period, and patterns of vector abundance and infection prevalence were compared. Dissolved oxygen, pH, temperature and salinity measurements were taken at 20 permanent waterbodies. Rainfall during this period was also quantified using remotely sensed data from up to 6 months prior to sampling months. Results Sixteen wetlands had weavers infected with avian malaria. More than half of the mosquitoes caught were trapped at one site; when this site was excluded, the number of mosquitoes trapped did not vary significantly between sites. The majority of mosquitoes collected belonged to the predominant vector species group for avian malaria (Culex culex species complex). Seasonal variation occurred in infection and mosquito prevalence, water pH and water temperature, with greater variability observed in summer than in winter. There was a significant correlation of infection prevalence with rainfall two months prior to sampling months. Mosquito prevalence patterns across the landscape also showed a close relationship to patterns of rainfall. Contrary to predictions, a pattern of asynchronous co-variation occurred between mosquito prevalence and infection prevalence. Conclusion Overall, salinity, rainfall, and mosquito prevalence and season were the most influential vector-related factors on infection prevalence. After comparison with related studies, the tentative conclusion drawn was that patterns of asynchronous variation between malaria prevalence and mosquito abundance were concurrent with those reported in lag response patterns. [ABSTRACT FROM AUTHOR]

Background: Development strategies in Ethiopia have largely focused on the expansion of irrigated agriculture in the last decade to reduce poverty and promote economic growth. However, such irrigation schemes can worsen the socio-economic state by aggravating the problem of mosquito-borne diseases. In this study, the effect of agro-ecosystem practices on malaria prevalence and the risk of malaria transmission by the primary vector mosquito, Anopheles arabiensis, in Ethiopia were investigated. Methods: In three villages in western Ethiopia practising large-scale sugarcane irrigation, traditional smallholder irrigation and non-irrigated farming, cross-sectional parasitological surveys were conducted during the short rains, after the long rains and during the dry season. Entomological surveys were undertaken monthly (February 2010-January 2011) in each village using light traps, pyrethrum spray collections and artificial pit shelters. Results: Malaria prevalence and the risk of transmission by An. arabiensis assessed by the average human biting rate, mean sporozoite rate and estimated annual entomological inoculation rate were significantly higher in the irrigated sugarcane agro-ecosystem compared to the traditionally irrigated and non-irrigated agro-ecosystems. The average human biting rate was significantly elevated by two-fold, while the mean sporozoite rate was 2.5-fold higher, and the annual entomological inoculation rate was 4.6 to 5.7-fold higher in the irrigated sugarcane compared to the traditional and non-irrigated agro-ecosystems. Active irrigation clearly affected malaria prevalence by increasing the abundance of host seeking Anopheles mosquitoes year-round and thus increasing the risk of infective bites. The year-round presence of sporozoite-infected vectors due to irrigation practices was found to strengthen the coupling between rainfall and risk of malaria transmission, both on- and off-season. Conclusion: This study demonstrates the negative impact of large-scale irrigation expansion on malaria transmission by increasing the abundance of mosquito vectors and indicates the need for effective vector monitoring and control strategies in the implementation of irrigation projects. [ABSTRACT FROM AUTHOR]