• Electrocardiographic safety evaluation of dihydroartemisinin piperaquine in the treatment of uncomplicated falciparum malaria.

      Mytton, O T; Ashley, E A; Peto, L; Price, R N; La, Y; Hae, R; Singhasivanon, P; White, N J; Nosten, F; Shoklo Malaria Research Unit, Mae Sot, Thailand. (American Society of Tropical Medicine and Hygiene, 2007-09)
      Dihydroartemisinin-piperaquine (DP) could become a leading fixed combination malaria treatment worldwide. Although there is accumulating evidence of efficacy and safety from clinical trials, data on cardiotoxicity are limited. In two randomized controlled trials in Thailand, 56 patients had ECGs performed before treatment, 4 hours after the first dose, and 4 hours after the last dose. The mean (95% CI) changes in QTc interval (Bazett's correction) were 2 (-6 to 9) ms and 14 (7 to 21) ms, respectively. These small changes on the third day of treatment are similar to those observed elsewhere in the convalescent phase following antimalarial treatment with drugs known to have no cardiac effects and are therefore likely to result from recovery from acute malaria and not the treatment given. At therapeutic doses, DP does not have clinically significant effects on the electrocardiogram.
    • Emergence of Plasmodium falciparum triple mutant in Cambodia.

      Rossi, G; De Smet, M; Khim, N; Kindermans, JM; Menard, D (Elsevier, 2017-12)
    • Encouraging Impact Following 2.5 Years of Reinforced Malaria Control Interventions in a Hyperendemic Region of the Republic of Guinea

      Tiffany, A; Moundekeno, FP; Traoré, A; Haile, M; Sterk, E; Guilavogui, T; Genton, B; Serafini, M; Grais, RFF (BioMed Central, 2016-05-28)
      Malaria is one of the principal causes of morbidity and mortality in the Republic of Guinea, particularly in the highly endemic regions. To assist in malaria control efforts, a multi-component malaria control intervention was implemented in the hyperendemic region of Guéckédou Prefecture. The coverage of the intervention and its impact on malaria parasite prevalence were assessed.
    • Environmental risk factors for clinical malaria: a case-control study in the Grau region of Peru.

      Guthmann, J P; Hall, A J; Jaffar, S; Palacios, A; Lines, J; Llanos-Cuentas, A; Department of Infectious and Tropical Disease, Infectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, UK. jguthmann@epicentre.msf.org (2001)
      The role of environmental risk factors in clinical malaria has been studied mainly in Africa and Asia, few investigations have been carried out in Latin America. Field observations in northern coastal Peru, where the prevalence of malaria is high during the agricultural season, suggested that the risk of disease varied according to the characteristics of the house and the house environment. Environmental determinants of the risk of clinical malaria were therefore investigated through a case-control study: 323 clinical cases of malaria, recruited through community-based active case-finding, and 969 age-, sex- and village-matched controls were recruited into the study over a period of 12 months ending June 1997. Residual spraying of houses in the previous 6 months, living more than 100 m from a canal, a level of education equal to primary school or above and working in agriculture conferred significant protection from the risk of developing clinical malaria. The presence of spaces between the wall and roof in the subject's bedroom (eaves) and a house aged > 4 years statistically significantly increased the risk of disease. Based on these results we discuss possible control measures for malaria in this area of the country.
    • Erratum to: An Optimised Age-Based Dosing Regimen For Single Low-Dose Primaquine For Blocking Malaria Transmission in Cambodia

      Leang, R; Khu, NH; Mukaka, M; Debackere, M; Tripura, R; Kheang, ST; Chy, S; Kak, N; Buchy, P; Tarantola, A; et al. (BioMed Central, 2016-12-20)
    • Estimating antimalarial drugs consumption in Africa before the switch to artemisinin-based combination therapies (ACTs)

      Kindermans, Jean-Marie; Vandenbergh, Daniel; Vreeke, Ed; Olliaro, Piero; D'Altilia, Jean-Pierre; AEDES Foundation, Brussels, Belgium; Médecins Sans Frontières, Brussels, Belgium; UNICEF/UNDP/WB/WHO Special Programme for Research & Training in Tropical Diseases (TDR), Geneva, Switzerland (2007-07-10)
      BACKGROUND: Having reliable forecasts is critical now for producers, malaria-endemic countries and agencies in order to adapt production and procurement of the artemisinin-based combination treatments (ACTs), the new first-line treatments of malaria. There is no ideal method to quantify drug requirements for malaria. Morbidity data give uncertain estimations. This study uses drug consumption to provide elements to help estimate quantities and financial requirements of ACTs. METHODS: The consumption of chloroquine, sulphadoxine/pyrimethamine and quinine both through the private and public sector was assessed in five sub-Saharan Africa countries with different epidemiological patterns (Senegal, Rwanda, Tanzania, Malawi, Zimbabwe). From these data the number of adult treatments per capita was calculated and the volumes and financial implications derived for the whole of Africa. RESULTS: Identifying and obtaining data from the private sector was difficult. The quality of information on drug supply and distribution in countries must be improved. The number of adult treatments per capita and per year in the five countries ranged from 0.18 to 0.50. Current adult treatment prices for ACTs range US$ 1-1.8. Taking the upper range for both volumes and costs, the highest number of adult treatments consumed for Africa was estimated at 314.5 million, corresponding to an overall maximum annual need for financing ACT procurement of US$ 566.1 million. In reality, both the number of cases treated and the cost of treatment are likely to be lower (projections for the lowest consumption estimate with the least expensive ACT would require US $ 113 million per annum). There were substantial variations in the market share between public and private sources among these countries (the public sector share ranging from 98% in Rwanda to 33% in Tanzania). CONCLUSION: Additional studies are required to build a more robust methodology, and to assess current consumptions more accurately in order to better quantify volumes and finances for production and procurement of ACTs.
    • Evaluation of the Deki Reader™, an automated RDT reader and data management device, in a household survey setting in low malaria endemic southwestern Uganda

      Oyet, C; Roh, ME; Kiwanuka, GN; Orikiriza, P; Wade, M; Parikh, S; Mwanga-Amumpaire, J; Boum, Y (BioMed Central, 2017-11-07)
      Early diagnosis of suspected malaria cases with a rapid diagnostic test (RDT) has been shown to be an effective malaria control tool used in many resource-constrained settings. However, poor quality control and quality assurance hinder the accurate reporting of malaria diagnoses. Recent use of a portable, battery operated RDT reader (Deki Reader™, Fio Corporation) has shown to have high agreement with visual inspection across diverse health centre settings, however evidence of its feasibility and usability during cross sectional surveys are limited. This study aimed to evaluate the performance of the Deki Reader™ in a cross-sectional survey of children from southwestern Uganda.
    • Evaluation of three parasite lactate dehydrogenase-based rapid diagnostic tests for the diagnosis of falciparum and vivax malaria

      Ashley, Elizabeth A; Touabi, Malek; Ahrer, Margareta; Hutagalung, Robert; Htun, Khayae; Luchavez, Jennifer; Dureza, Christine; Proux, Stephane; Leimanis, Mara; Lwin, Myo Min; et al. (2009-10-27)
      BACKGROUND: In areas where non-falciparum malaria is common rapid diagnostic tests (RDTs) capable of distinguishing malaria species reliably are needed. Such tests are often based on the detection of parasite lactate dehydrogenase (pLDH). METHODS: In Dawei, southern Myanmar, three pLDH based RDTs (CareStart Malaria pLDH (Pan), CareStart Malaria pLDH (Pan, Pf) and OptiMAL-IT)were evaluated in patients presenting with clinically suspected malaria. Each RDT was read independently by two readers. A subset of patients with microscopically confirmed malaria had their RDTs repeated on days 2, 7 and then weekly until negative. At the end of the study, samples of study batches were sent for heat stability testing. RESULTS: Between August and November 2007, 1004 patients aged between 1 and 93 years were enrolled in the study. Slide microscopy (the reference standard) diagnosed 213 Plasmodium vivax (Pv) monoinfections, 98 Plasmodium falciparum (Pf) mono-infections and no malaria in 650 cases. The sensitivities (sens) and specificities (spec), of the RDTs for the detection of malaria were- CareStart Malaria pLDH (Pan) test: sens 89.1% [CI95 84.2-92.6], spec 97.6% [CI95 96.5-98.4]. OptiMal-IT: Pf+/- other species detection: sens 95.2% [CI95 87.5-98.2], spec 94.7% [CI95 93.3-95.8]; non-Pf detection alone: sens 89.6% [CI95 83.6-93.6], spec 96.5% [CI95 94.8-97.7]. CareStart Malaria pLDH (Pan, Pf): Pf+/- other species: sens 93.5% [CI95 85.4-97.3], spec 97.4% [95.9-98.3]; non-Pf: sens 78.5% [CI95 71.1-84.4], spec 97.8% [CI95 96.3-98.7]. Inter-observer agreement was excellent for all tests (kappa > 0.9). The median time for the RDTs to become negative was two days for the CareStart Malaria tests and seven days for OptiMAL-IT. Tests were heat stable up to 90 days except for OptiMAL-IT (Pf specific pLDH stable to day 20 at 35 degrees C). CONCLUSION: None of the pLDH-based RDTs evaluated was able to detect non-falciparum malaria with high sensitivity, particularly at low parasitaemias. OptiMAL-IT performed best overall and would perform best in an area of high malaria prevalence among screened fever cases. However, heat stability was unacceptable and the number of steps to perform this test is a significant drawback in the field. A reliable, heat-stable, highly sensitive RDT, capable of diagnosing all Plasmodium species has yet to be identified.
    • Evaluation of Three Rapid Tests for Diagnosis of P. Falciparum and P. Vivax Malaria in Colombia.

      van den Broek, I; Hill, O; Gordillo, F; Angarita, B; Hamade, P; Counihan, H; Guthmann, J P; Médecins sans Frontières (MSF), London, UK. ingrid_vandenbroek@yahoo.com (2006-12)
      The diagnostic capacity of three malaria rapid diagnostic tests (RDTs), NOW-Malaria-ICT, OptiMAL-IT, and Paracheck-Pf, was evaluated against expert microscopy in Colombia. We tested 896 patients, of whom microscopy confirmed 139 P. falciparum, 279 P. vivax, and 13 mixed P.f/P.v infections and 465 negatives. Paracheck-Pf and NOW-malaria-ICT were more accurate in detecting P. falciparum (sensitivities 90.8% and 90.1%, respectively) in comparison with Optimal-IT (83.6%). NOW showed an acceptable Pf detection rate at low densities (< 500/microL), but resulted in a higher proportion of false positives. For P. vivax diagnosis, Optimal-IT had a higher sensitivity than NOW (91.0% and 81.4%, respectively). The choice between the two Pf/Pv detecting RDTs balances P. falciparum and P. vivax detection rates. Considering some degree of P. falciparum overtreatment and failure to detect all P. vivax cases as more acceptable than missing some cases of P. falciparum, we recommend careful implementation of NOW-malaria-ICT in areas where microscopy is lacking. The price is however still a constraint.
    • Evidence basis for antimalarial policy change in Sierra Leone: five in vivo efficacy studies of chloroquine, sulphadoxine-pyrimethamine and amodiaquine.

      Checchi, F; Roddy, P; Kamara, S; Williams, A; Morineau, G; Wurie, A R; Hora, B; Lamotte, N; Baerwaldt, T; Heinzelmann, A; et al. (Wiley-Blackwell, 2005-02)
      OBJECTIVES: To provide nationally relevant information on the antimalarial efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) in Sierra Leone, with a view to updating antimalarial policy in the country. METHODS: Between October 2002 and May 2003, standard WHO methodology for in vivo efficacy assessment was used in five sites to study the therapeutic response of 6-59 months old uncomplicated Plasmodium falciparum malaria cases treated with CQ (n = 247), SP (n = 353) or AQ (n = 434). Follow-up was of 28 days, with polymerase chain reaction genotyping to distinguish late recrudescences from re-infections. RESULTS: Overall 85.3% of patients reached an analysable endpoint. CQ failure proportions were very high, ranging from 39.5% (95% CI: 25.0-55.6) in Kabala to 78.8% (65.3-88.9) in Kailahun. Early failures under CQ were frequent. SP efficacy was also disappointing, with failure from 23.2% (13.9-34.9) in Kabala to 46.1% (35.4-57.0) in Kailahun. AQ resistance was more moderate, ranging from 5.4% (1.8-12.1) in Makeni to 29.8% (20.3-40.8) in Kailahun, with almost no early failures. AQ also provided more rapid fever and parasite clearance. CONCLUSION: In a consensus meeting organized by the Ministry of Health and Sanitation, and based on these findings, artesunate (AS) + AQ and artemether-lumefantrine (Coartemtrade mark) were identified as the only options to rapidly replace CQ. The choice fell on AS + AQ because of expected high efficacy, lower cost in a blister presentation, and the absence of safety data on artemether-lumefantrine in pregnancy. Donor support is required to support this policy change. Throughout Africa, as SP resistance increases, these two regimens are probably the only options available while newer combinations are developed. Efficacy studies should focus on testing AQ and AS + AQ.
    • Falciparum Malaria and Climate Change in the Northwest Frontier Province of Pakistan.

      Bouma, M J; Dye, C; van der Kaay, H J; Medecins Sans Frontieres-Holland, Amsterdam, The Netherlands. (Published by: American Society of Tropical Medicine and Hygiene, 1996-08)
      Following a striking increase in the severity of autumnal outbreaks of Plasmodium falciparum during the last decade in the Northwest Frontier Province (NWFP) of Pakistan, the role of climatologic variables was investigated. A multivariate analysis showed that during the transmission season of P. falciparum, the amount of rainfall in September and October, the temperature in November and December, and the humidity in December were all correlated (r2 = 0.82) with two measures of P. falciparum, the falciparum rate (percent of slides examined positive for P. falciparum) since 1981 and the annual P. falciparum proportion (percent of all malaria infections diagnosed as P. falciparum) since 1978. Climatologic records since 1876 show an increase in mean November and December temperatures by 2 degrees C and 1.5 degrees C, respectively, and in October rainfall. Mean humidity in December has also been increasing since 1950. These climatologic changes in the area appear to have made conditions for transmission of P. falciparum more favorable, and may account for the increase in incidence observed in the NWFP in recent years.
    • Field Application of SD Bioline Malaria Ag Pf/Pan Rapid Diagnostic Test for Malaria in Greece

      Tseroni, Maria; Pervanidou, Danai; Tserkezou, Persefoni; Rachiotis, George; Pinaka, Ourania; Baka, Agoritsa; Georgakopoulou, Theano; Vakali, Annita; Dionysopoulou, Martha; Terzaki, Irene; et al. (Public Library of Science, 2015-03-24)
      Greece, a malaria-free country since 1974, has experienced re-emergence of Plasmodium vivax autochthonous malaria cases in some agriculture areas over the last three years. In early 2012, an integrated control programme (MALWEST Project) was launched in order to prevent re-establishment of the disease. In the context of this project, the rapid diagnostic tests (RDT) of SD Bioline Malaria Ag Pf/Pan that detects hrp-2 and pan-LDH antigens were used. The aim of this study was to assess the field application of the RDT for the P. vivax diagnosis in comparison to light microscopy and polymerase chain reaction (PCR). A total of 955 samples were tested with all three diagnostic tools. Agreement of RDT against microscopy and PCR for the diagnosis of P. vivax was satisfactory (K value: 0.849 and 0.976, respectively). The sensitivity, specificity and positive predictive value of RDT against PCR was 95.6% (95% C.I.: 84.8-99.3), 100% (95% C.I.: 99.6-100.0) and 100% (95% CI: 91.7-100.0) respectively, while the sensitivity, specificity and positive predictive value of RDT against microscopic examination was 97.4% (95% C.I.: 86.1-99.6), 99.4% (95% C.I.: 98.6-99.8) and 86.1% (95% CI: 72.1-94.7), respectively. Our results indicate that RDT performed satisfactory in a non-endemic country and therefore is recommended for malaria diagnosis, especially in areas where health professionals lack experience on light microscopy.
    • Focusing on quality patient care in the new global subsidy for malaria medicines.

      Moon, S; Pérez Casas, C; Kindermans, J M; de Smet, M; von Schoen-Angerer, T; Giorgio Ruffolo Doctoral Research Fellow, Sustainability Science Program, Center for International Development, Kennedy School of Government, Harvard University, Cambridge, Massachusetts, USA. (2009-07-21)
      Tido von Schoen-Angerer and colleagues discuss the new Affordable Medicines Facility for malaria (AMFm), which subsidizes and facilitates access to artemisinin-based combination therapy, and what mechanisms are needed to ensure it stays focused on quality patient care.
    • Forecasting malaria incidence based on monthly case reports and environmental factors in Karuzi, Burundi, 1997-2003.

      Gomez-Elipe, A; Otero, A; Van Herp, M; Aguirre-Jaime, A; Public Health Department, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 2, 28029 Madrid, Spain. agomez.elipe@gmail.com (BMC, 2007)
      BACKGROUND: The objective of this work was to develop a model to predict malaria incidence in an area of unstable transmission by studying the association between environmental variables and disease dynamics. METHODS: The study was carried out in Karuzi, a province in the Burundi highlands, using time series of monthly notifications of malaria cases from local health facilities, data from rain and temperature records, and the normalized difference vegetation index (NDVI). Using autoregressive integrated moving average (ARIMA) methodology, a model showing the relation between monthly notifications of malaria cases and the environmental variables was developed. RESULTS: The best forecasting model (R2adj = 82%, p < 0.0001 and 93% forecasting accuracy in the range +/- 4 cases per 100 inhabitants) included the NDVI, mean maximum temperature, rainfall and number of malaria cases in the preceding month. CONCLUSION: This model is a simple and useful tool for producing reasonably reliable forecasts of the malaria incidence rate in the study area.
    • Free treatment, rapid diagnostic tests and malaria village workers can hasten the progress towards achieving the malaria related Millennium Development Goals: The MSF experience from Chad, Sierra-Leone and Mali.

      Tayler-Smith K; Kociejowski A; de Lamotte N; Gerard S; Ponsar F; Philips M; Zachariah R; Operational Research Unit and Advocacy Unit, MSF OCB, and MSF UK (PAGEPress, 2011-03)
    • Geographical distribution of selected and putatively neutral SNPs in Southeast Asian malaria parasites.

      Anderson, T J C; Nair, S; Sudimack, D; Williams, J T; Mayxay, M; Newton, P N; Guthmann, J P; Smithuis, F M; Tran, T H; van den Broek, I; et al. (2005-12)
      Loci targeted by directional selection are expected to show elevated geographical population structure relative to neutral loci, and a flurry of recent papers have used this rationale to search for genome regions involved in adaptation. Studies of functional mutations that are known to be under selection are particularly useful for assessing the utility of this approach. Antimalarial drug treatment regimes vary considerably between countries in Southeast Asia selecting for local adaptation at parasite loci underlying resistance. We compared the population structure revealed by 10 nonsynonymous mutations (nonsynonymous single-nucleotide polymorphisms [nsSNPs]) in four loci that are known to be involved in antimalarial drug resistance, with patterns revealed by 10 synonymous mutations (synonymous single-nucleotide polymorphisms [sSNPs]) in housekeeping genes or genes of unknown function in 755 Plasmodium falciparum infections collected from 13 populations in six Southeast Asian countries. Allele frequencies at known nsSNPs underlying resistance varied markedly between locations (F(ST) = 0.18-0.66), with the highest frequencies on the Thailand-Burma border and the lowest frequencies in neighboring Lao PDR. In contrast, we found weak but significant geographic structure (F(ST) = 0-0.14) for 8 of 10 sSNPs. Importantly, all 10 nsSNPs showed significantly higher F(ST) (P < 8 x 10(-5)) than simulated neutral expectations based on observed F(ST) values in the putatively neutral sSNPs. This result was unaffected by the methods used to estimate allele frequencies or the number of populations used in the simulations. Given that dense single-nucleotide polymorphism (SNP) maps and rapid SNP assay methods are now available for P. falciparum, comparing genetic differentiation across the genome may provide a valuable aid to identifying parasite loci underlying local adaptation to drug treatment regimes or other selective forces. However, the high proportion of polymorphic sites that appear to be under balancing selection (or linked to selected sites) in the P. falciparum genome violates the central assumption that selected sites are rare, which complicates identification of outlier loci, and suggests that caution is needed when using this approach.
    • Glucose-6-Phosphate Dehydrogenase Deficiency, Chlorproguanil-Dapsone with Artesunate and Post-treatment Haemolysis in African children treated for uncomplicated Malaria

      Van Malderen, Carine; Van Geertruyden, Jean-Pierre; Machevo, Sonia; González, Raquel; Bassat, Quique; Talisuna, Ambrose; Yeka, Adoke; Nabasumba, Carolyn; Piola, Patrice; Daniel, Atwine; et al. (2012-04-30)
      Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children<5 years of age with uncomplicated malaria.
    • Heterogeneous decrease in malaria prevalence in children over a six-year period in south-western Uganda.

      De Beaudrap, Pierre; Nabasumba, Carolyn; Grandesso, Francesco; Turyakira, Eleanor; Schramm, Birgit; Boum, Yap; Etard, Jean-François; Epicentre Mbarara Research Base, Mbarara, Uganda. pierre.debeaudrap@epicentre.msf.org (2011-05-18)
      Malaria is a major public health problem, especially for children. However, recent reports suggest a decline in the malaria burden. The aim of this study was to assess the change in the prevalence of malaria infection among children below five years of age between 2004 and 2010 in a mesoendemic area of Uganda and to analyse the risk factors of malaria infection.
    • High Burden of Malaria and Anemia Among Tribal Pregnant Women in a Chronic Conflict Corridor in India

      Corrêa, G; Das, M; Kovelamudi, R; Jaladi, N; Pignon, C; Vysyaraju, K; Yedla, U; Laxmi, V; Vemula, P; Gowthami, V; et al. (BioMed Central, 2017-06-20)
      With more than 200 million cases a year, malaria is an important global health concern, especially among pregnant women. The forested tribal areas of Andhra Pradesh, Telangana and Chhattisgarh in India are affected by malaria and by an on-going chronic conflict which seriously limits access to health care. The burden of malaria and anemia among pregnant women in these areas is unknown; moreover there are no specific recommendations for pregnant women in the Indian national malaria policy. The aim of this study is to measure the burden of malaria and anemia among pregnant women presenting in mobile clinics for antenatal care in a conflict-affected corridor in India.
    • High Efficacy of Two Artemisinin-Based Combinations (Artesunate + Amodiaquine and Artemether + Lumefantrine) in Caala, Central Angola.

      Guthmann, J P; Cohuet, S; Rigutto, C; Fortes, F; Saraiva, N; Kiguli, J; Kyomuhendo, J; Francis, M; Noël, F; Mulemba, M; et al. (Published by: American Society of Tropical Medicine and Hygiene, 2006-07)
      In April 2004, 137 children 6-59 months of age with uncomplicated Plasmodium falciparum (Pf) malaria (Caala, Central Angola) were randomized to receive either artemether-lumefantrine (Coartem) or artesunate + amodiaquine (ASAQ). After 28 days of follow-up, there were 2/61 (3.2%) recurrent parasitemias in the Coartem group and 4/64 (6.2%) in the ASAQ group (P = 0.72), all classified as re-infections after PCR genotyping (cure rate = 100% [95%CI: 94-100] in both groups). Only one patient (ASAQ group) had gametocytes on day 28 versus five (Coartem) and three (ASAQ) at baseline. Compared with baseline, anemia was significantly improved after 28 days of follow-up in both groups (Coartem: from 54.1% to 13.4%; ASAQ: from 53.1% to 15.9%). Our findings are in favor of a high efficacy of both combinations in Caala. Now that Coartem has been chosen as the new first-line anti-malarial, the challenge is to insure that this drug is available and adequately used.