• Abolishing user fees for children and pregnant women trebled uptake of malaria-related interventions in Kangaba, Mali.

      Ponsar, Frédérique; Van Herp, Michel; Zachariah, Rony; Gerard, Séco; Philips, Mit; Jouquet, Guillaume; Analysis and advocacy unit, Médecins sans Frontieres, Brussels Operational Centre, Brussels, Belgium. fredponsar@hotmail.com (2011-11)
      Malaria is the most common cause of morbidity and mortality in children under 5 in Mali. Health centres provide primary care, including malaria treatment, under a system of cost recovery. In 2005, Médecins sans Frontieres (MSF) started supporting health centres in Kangaba with the provision of rapid malaria diagnostic tests and artemisinin-based combination therapy. Initially MSF subsidized malaria tests and drugs to reduce the overall cost for patients. In a second phase, MSF abolished fees for all children under 5 irrespective of their illness and for pregnant women with fever. This second phase was associated with a trebling of both primary health care utilization and malaria treatment coverage for these groups. MSF's experience in Mali suggests that removing user fees for vulnerable groups significantly improves utilization and coverage of essential health services, including for malaria interventions. This effect is far more marked than simply subsidizing or providing malaria drugs and diagnostic tests free of charge. Following the free care strategy, utilization of services increased significantly and under-5 mortality was reduced. Fee removal also allowed for more efficient use of existing resources, reducing average cost per patient treated. These results are particularly relevant for the context of Mali and other countries with ambitious malaria treatment coverage objectives, in accordance with the United Nations Millennium Development Goals. This article questions the effectiveness of the current national policy, and the effectiveness of reducing the cost of drugs only (i.e. partial subsidies) or providing malaria tests and drugs free for under-5s, without abolishing other related fees. National and international budgets, in particular those that target health systems strengthening, could be used to complement existing subsidies and be directed towards effective abolition of user fees. This would contribute to increasing the impact of interventions on population health and, in turn, the effectiveness of aid.
    • Adapting Reactive Case Detection Strategies for falciparum Malaria in a Low-Transmission Area in Cambodia.

      Rossi, G; Van den Bergh, R; Nguon, C; Debackere, M; Vernaeve, L; Khim, N; Kim, S; Menard, D; De Smet, M; Kindermans, JM (Oxford University Press, 2018-01-06)
      Reactive case detection around falciparum malaria cases in Cambodia presents a low output. We improved it by including individuals occupationally coexposed with index case patients and using polymerase chain reaction-based diagnosis. The positivity rate increased from 0.16% to 3.9%.
    • Adherence to a Combination of Artemether and Lumefantrine (Coartem) in Kajo Keji, Southern Sudan.

      Depoortere, E; Salvador, E T C; Stivanello, E; Bisoffi, Z; Guthmann, J P; Epicentre, 42 bis boulevard Richard Lenoir, 75011 Paris, France. evelyn.depoortere@brussels.msf.org (Published by: Maney Publishing, 2004-09)
    • Adherence to a Six-Dose Regimen of Artemether-Lumefantrine for Treatment of Uncomplicated Plasmodium Falciparum Malaria in Uganda.

      Fogg, C; Bajunirwe, F; Piola, P; Biraro, S; Checchi, F; Kiguli, J; Namiiro, P; Musabe, J; Kyomugisha, A; Guthmann, J P; Epicentre, Paris, France. (Published by: American Society of Tropical Medicine and Hygiene, 2004-11)
      Measuring baseline levels of adherence and identifying risk factors for non-adherence are important steps before the introduction of new antimalarials. In Mbarara in southwestern Uganda, we assessed adherence to artemether-lumefantrine (Coartem) in its latest World Health Organization blister formulation. Patients with uncomplicated Plasmodium falciparum malaria were prescribed artemether-lumefantrine and received an explanation of how to take the following five doses at home. A tablet count was made and a questionnaire was completed during a home visit. Among 210 analyzable patients, 21 (10.0%) were definitely or probably non-adherent, whereas 189 (90.0%) were probably adherent. Age group was not associated with adherence. Lack of formal education was the only factor associated with non-adherence after controlling for confounders (odds ratio = 3.1, 95% confidence interval [CI] = 1.1-9.7). Mean lumefantrine blood levels were lower among non-adherent (n = 16) (2.76 microg/mL, 95% CI = 1.06-4.45) than among adherent (n = 171) (3.19 microg/mL, 95% CI = 2.84-3.54) patients, but this difference was not statistically significant. The high adherence to artemether-lumefantrine found in our study suggest that this drug is likely to be very effective in Mbarara provided that patients receive clear dosage explanations.
    • Adherence to Artemisinin Combination Therapy for the treatment of uncomplicated malaria in the Democratic Republic of the Congo

      Siddiqui, M Ruby; Willis, Andrew; Bil, Karla; Singh, Jatinder; Mukomena Sompwe, Eric; Ariti, Cono (F1000Research, 2015-02-24)
      Between 2011 and 2013 the number of recorded malaria cases had more than doubled, and between 2009 and 2013 had increased almost 4-fold in MSF-OCA (Médecins sans Frontières - Operational Centre Amsterdam) programmes in the Democratic Republic of the Congo (DRC). The reasons for this rise are unclear. Incorrect intake of Artemisinin Combination Therapy (ACT) could result in failure to treat the infection and potential recurrence. An adherence study was carried out to assess whether patients were completing the full course of ACT. One hundred and eight malaria patients in Shamwana, Katanga province, DRC were visited in their households the day after ACT was supposed to be completed. They were asked a series of questions about ACT administration and the blister pack was observed (if available). Sixty seven (62.0%) patients were considered probably adherent. This did not take into account the patients that vomited or spat their pills or took them at the incorrect time of day, in which case adherence dropped to 46 (42.6%). The most common reason that patients gave for incomplete/incorrect intake was that they were vomiting or felt unwell (10 patients (24.4%), although the reasons were not recorded for 22 (53.7%) patients). This indicates that there may be poor understanding of the importance of completing the treatment or that the side effects of ACT were significant enough to over-ride the pharmacy instructions. Adherence to ACT was poor in this setting. Health education messages emphasising the need to complete ACT even if patients vomit doses, feel unwell or their health conditions improve should be promoted.
    • Adherence to the combination of sulphadoxine-pyrimethamine and artesunate in the Maheba refugee settlement, Zambia.

      Depoortere, E; Guthmann, J P; Sipilanyambe, N; Nkandu, E; Fermon, F; Balkan, S; Legros, D; Epicentre, Paris, France. evelyn.depoortere@msf.be (Wiley-Blackwell, 2004-01)
      Artemisinin-based combination therapy (ACT) is one strategy recommended to increase cure rates in malaria and to contain resistance to Plasmodium falciparum. In the Maheba refugee settlement, children aged 5 years or younger with a confirmed diagnosis of uncomplicated falciparum malaria are treated with the combination of sulphadoxine-pyrimethamine (1 day) and artesunate (3 days). To measure treatment adherence, home visits were carried out the day after the last treatment dose. Patients who had any treatment dose left were considered certainly non-adherent. Other patients' classification was based on the answers to the questionnaire: patients whose caretakers stated the child had received the treatment regimen exactly as prescribed were considered probably adherent; all other patients were considered probably non-adherent. Reasons for non-adherence were assessed. We found 21.2% (95% CI [15.0-28.4]) of the patients to be certainly non-adherent, 39.4% (95% CI [31.6-47.6]) probably non-adherent, and 39.4% (95% CI [31.6-47.6]) probably adherent. Insufficient explanation by the dispenser was identified as an important reason for non-adherence. When considering the use of ACT, the issue of patient adherence remains challenging. However, it should not be used as an argument against the introduction of ACT. For these treatment regimens to remain efficacious on a long-term basis, specific and locally adapted strategies need to be implemented to ensure completion of the treatment.
    • Antimalarial efficacy of chloroquine, amodiaquine, sulfadoxine-pyrimethamine, and the combinations of amodiaquine + artesunate and sulfadoxine-pyrimethamine + artesunate in Huambo and Bie provinces, central Angola.

      Guthmann, J P; Ampuero, J; Fortes, F; Van Overmeir, C; Gaboulaud, V; Tobback, S; Dunand, J; Saraiva, N; Gillet, P; Franco, J; Denoncin, A; Van Herp, M; Balkan, S; Dujardin, J C C; D'Alessandro, U; Legros, D; Epicentre, 42 bis, Boulevard Richard Lenoir, 75011 Paris, France. jguthmann@epicentre.msf.org (Elsevier, 2005-07)
      We studied three antimalarial treatments in Caala and Kuito, Angola, in 2002 and 2003. We tested chloroquine (CQ), amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP) in Caala, and AQ, SP and the combinations AQ+artesunate (AQ+AS) and SP+artesunate (SP+AS) in Kuito. A total of 619 children (240 in Caala, 379 in Kuito) with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days, with PCR genotyping to distinguish recrudescence from reinfection. PCR-corrected failure proportions at day 28 were very high in the CQ group (83.5%, 95% CI 74.1-90.5), high in the SP groups (Caala: 25.3%, 95% CI 16.7-35.8; Kuito: 38.8%, 95% CI 28.4-50.0), around 20% in the AQ groups (Caala: 17.3%, 95% CI 10.0-27.2; Kuito: 21.6%, 95% CI 14.3-30.6) and very low in the artemisinin-based combination groups (1.2%, 95% CI 0.0-6.4 for each combination AQ+AS and SP+AS). These results show that CQ and SP are no longer efficacious in Caala and Kuito and that the moderate efficacy of AQ is likely to be compromised in the short term if used as monotherapy. We recommend the use of AQ with AS, though this combination might not have a long useful therapeutic life because of AQ resistance.
    • Antimalarial efficacy of sulfadoxine-pyrimethamine, amodiaquine and a combination of chloroquine plus sulfadoxine-pyrimethamine in Bundi Bugyo, western Uganda.

      Checchi, F; Piola, P; Kosack, C; Ardizzoni, E; Klarkowski, D; Kwezi, E; Priotto, G; Balkan, S; Bakyaita, N; Brockman, A; Guthmann, J P; Epicentre, Paris, France. fchecci@epicentre.msf.org (Wiley-Blackwell, 2004-04)
      We report below an in vivo antimalarial efficacy study conducted in 2002 in Bundi Bugyo, a district of western Uganda housing a large displaced population. We tested sulfadoxine-pyrimethamine (SP), amodiaquine (AQ) and the combination chloroquine plus SP (CQ + SP). A total of 268 children with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days according to WHO recommendations, with PCR genotyping to distinguish late recrudescences from re-infections. PCR-adjusted failure proportions at day 28 were 37.0% (34/92, 95% CI 27.1-47.7) in the SP group, 20.6% (14/68, 95% CI 11.7-32.1) in the AQ group and 22.8% (18/79, 95% CI 14.1-33.6) in the CQ + SP group. Early failures were particularly frequent in the SP group (15.2%). Clearance of gametocytes was slower in the SP and CQ + SP groups than in the AQ group. This study suggests that, in Bundi Bugyo, CQ + SP (Uganda's first-line regimen) will need to be replaced by a more efficacious regimen. Across Uganda, the deployment of SP containing combinations may not be a feasible long-term strategy. For Bundi Bugyo, we recommend a combination of artesunate and AQ. Our study also confirms previous findings that resistance is considerably underestimated by 14-day follow-ups. Antimalarial policy decisions should therefore be based on 28-day studies, with PCR adjustment to distinguish re-infections.
    • Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis

      Kloprogge, F; Workman, L; Borrmann, S; Tékété, M; Lefèvre, G; Hamed, K; Piola, P; Ursing, J; Kofoed, PE; Mårtensson, A; Ngasala, B; Björkman, A; Ashton, M; Friberg Hietala, S; Aweeka, F; Parikh, S; Mwai, L; Davis, T; Karunajeewa, H; Salman, S; Checchi, F; Fogg, C; Newton, PN; Mayxay, M; Deloron, P; Faucher, JF; Nosten, F; Ashley, EA; McGready, R; van Vugt, M; Proux, S; Price, RN; Karbwang, J; Ezzet, F; Bakshi, R; Stepniewska, K; White, NJ; Guerin, PJ; Barnes, KI; Tarning, J (Public Library of Science, 2018-06)
      The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations.
    • Artemether-Lumefantrine to treat Malaria in pregnancy is associated with reduced placental Haemozoin deposition compared to Quinine in a randomized controlled trial

      Muehlenbachs, Atis; Nabasumba, Carolyn; McGready, Rose; Turyakira, Eleanor; Tumwebaze, Benon; Dhorda, Mehul; Nyehangane, Dan; Nalusaji, Aisha; Nosten, Franois; Guerin, Philippe J; Piola, Patrice; Department of Pathology, University of Washington, Box 357470, 1959 NE Pacific Street, Seattle, WA, USA. amuehlen@u.washington.edu (2012-05-03)
      Data on efficacy of artemisinin-based combination therapy (ACT) to treat Plasmodium falciparum during pregnancy in sub-Saharan Africa is scarce. A recent open label, randomized controlled trial in Mbarara, Uganda demonstrated that artemether-lumefantrine (AL) is not inferior to quinine to treat uncomplicated malaria in pregnancy. Haemozoin can persist in the placenta following clearance of parasites, however there is no data whether ACT can influence the amount of haemozoin or the dynamics of haemozoin clearance.
    • Artesunate + amodiaquine and artesunate + sulphadoxine-pyrimethamine for treatment of uncomplicated malaria in Democratic Republic of Congo: a clinical trial with determination of sulphadoxine and pyrimethamine-resistant haplotypes.

      Swarthout, T D; van den Broek, I; Kayembe, G; Montgomery, J; Pota, H; Roper, C; Médecins Sans Frontières, London, UK. (Wiley-Blackwell, 2006-10)
      We undertook a trial of artesunate + amodiaquine (AS + AQ) and artesunate + sulphadoxine-pyrimethamine (AS + SP) in 180 children of age 6-59 months with uncomplicated malaria in Democratic Republic of Congo. Children were randomly allocated to receive 3 days observed treatment of AS + AQ (n = 90) or 3 days of AS + SP (n = 90). Primary efficacy outcomes were 28-day parasite recurrence rates, and recrudescence rates were adjusted by genotyping to distinguish new infection and recrudescence. In addition, we determined the prevalence of molecular markers of resistance to sulphadoxine and pyrimethamine. Day 28 parasite recurrence rates were 16.9% (14/83; 95% CI: 9.5-26.7) in the AS + AQ group and 34.6% (28/81; 95% CI: 24.3-46.0) in the AS + SP group (P = 0.009). After PCR correction, recrudescence rates were 6.7% (5/74; 95% CI: 2.2-15.1) for AS + AQ and 19.7% (13/66; 95% CI: 10.9-31.3) for AS + SP (P = 0.02). There was no significant difference between the two arms in time to parasite clearance, fever clearance and gametocyte clearance. Parasite genotyping showed high frequencies of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) molecular SP-resistance markers, with 57% of the samples showing more than three mutations linked to SP resistance, and 27% with triple-dhfr/double-dhps haplotype, confirming that SP treatment failure rates are likely to be high. AS + AQ had significantly higher efficacy than AS + SP. These results contributed to the subsequent change to AS + AQ as first-line regimen in the country. Efforts to properly implement the new protocol and maintain adherence at acceptable levels should include health staff and patient sensitization. The 6.8% recrudescence rate indicates that AS + AQ should be monitored closely until a more effective artemisinin combination therapy regimen is needed and can be introduced.
    • Artesunate and sulfadoxine-pyrimethamine combinations for the treatment of uncomplicated Plasmodium falciparum malaria in Uganda: a randomized, double-blind, placebo-controlled trial.

      Priotto, G; Kabakyenga, J K; Pinoges, L; Ruiz, A; Eriksson, T; Coussement, F; Ngambe, T; Taylor, W R J; Perea, W; Guthmann, J P; Olliaro, P; Legros, D; Epicentre, 8 rue Saint Sabin, 75011 Paris, France. gpriotto@epicentre.msf.org (Elsevier, 2008-01-25)
      Drug-resistant malaria is spreading in Africa. The few available drugs might be safeguarded if combined with an artemisinin derivative. We investigated the efficacy, safety, and tolerability of 2 combinations of artesunate with sulfadoxine-pyrimethamine (SP) in a mesoendemic region in Uganda with SP resistance, from September 1999 to June 2000. In a randomized, double-blind, placebo-controlled trial, 420 children aged 6-59 months with uncomplicated Plasmodium falciparum malaria were assigned SP alone (25 mg/kg sulfadoxine, 1.25 mg/kg pyrimethamine) or combined with artesunate (AS; 4 mg/kg/d) for either 1 d (SPAS1) or 3 d (SPAS3). Children were followed-up for 28 d. Day 14 cure rates were 84.6% (99/117) with SPAS3 and 61.9% (73/118) with SPAS1 compared with 55.8% (86/154) with SP. Corresponding day 28 results were 74.4% (87/117) and 45.2% (52/115) compared with 40.5% (62/153). A significant improvement was obtained with the addition of 3 d, but not 1 d, of artesunate (risk ratio [RR] = 1.5, 95% CI 1.3-1.8 at 14 d and RR = 1.8, 95% CI 1.5-2.3 at 28 d). Both AS regimens achieved significantly faster parasite clearance and lower gametocyte carriage. All drug regimens were well tolerated, but SP alone was ineffective. Treatment efficacy improved with SPAS3 but the cure rate at day 28 was modest. The combinations were well tolerated and safe. In areas where SP resistance is prevalent other combinations should be considered.
    • Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial

      Dondorp, Arjen M; Fanello, Caterina I; Hendriksen, Ilse C E; Gomes, Ermelinda; Seni, Amir; Chhaganlal, Kajal D; Bojang, Kalifa; Olaosebikan, Rasaq; Anunobi, Nkechinyere; Maitland, Kathryn; Kivaya, Esther; Agbenyega, Tsiri; Nguah, Samuel Blay; Evans, Jennifer; Gesase, Samwel; Kahabuka, Catherine; Mtove, George; Nadjm, Behzad; Deen, Jacqueline; Mwanga-Amumpaire, Juliet; Nansumba, Margaret; Karema, Corine; Umulisa, Noella; Uwimana, Aline; Mokuolu, Olugbenga A; Adedoyin, Olanrewaju T; Johnson, Wahab B R; Tshefu, Antoinette K; Onyamboko, Marie A; Sakulthaew, Tharisara; Ngum, Wirichada Pan; Silamut, Kamolrat; Stepniewska, Kasia; Woodrow, Charles J; Bethell, Delia; Wills, Bridget; Oneko, Martina; Peto, Tim E; von Seidlein, Lorenz; Day, Nicholas P J; White, Nicholas J; AQUAMAT group; Hospital Central da Beira, Beira, Mozambique; MRC laboratories, Banjul, The Gambia; Komfo Anokye Hospital, Kumasi, Ghana; Kilifi District General Hospital, Kilifi, Kenya; Magunga District Hospital, NIMR-Korogwe Research Laboratory, Tanga, Tanzania; Teule Designated District Hospital, Muheza, Tanzania; NIMR-Amani Centre, Tanga, Tanzania; Malaria Control Program, Ministry of Health, Kigali, Rwanda; University of Ilorin Teaching Hospital, Ilorin, Nigeria; Mbarara University of Science and Technology and Epicentre Research Base, Mbarara, Uganda; Kinshasa School of Public Health—Kingasani Research Centre, Kinshasa, Democratic Republic of the Congo; Mahidol Oxford Tropical MedicineResearch Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Menzies School of Health Research, Casuarina, NT, Australia; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; KEMRI—CDC Kisumu, Kisumu Kenya (2010-11-08)
      Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in African children with severe malaria.
    • Assessing antimalarial efficacy in a time of change to artemisinin-based combination therapies: The role of Médecins Sans Frontières

      Guthmann, J P; Checchi, F; van den Broek, I; Balkan, S; Van Herp, M; Comte, E; Bernal, O; Kindermans, J M; Venis, S; Legros, D; Guerin, P J; Epicentre, Paris, France; Departement de Maladies Infectieuses, Institut de Veille Sanitaire, Saint Maurice, France; Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medecins Sans Frontieres, London, United Kingdom; Medecins Sans Frontieres, Amsterdam, The Netherlands; Centre for Infectious Disease Control, National Institute of Public Health and the Environment, Bilthoven, The Netherlands; Medecins Sans Frontieres, Paris, France; Medecins Sans Frontieres, Brussels, Belgium; Medecins Sans Frontieres, Geneva, Switzerland; Medecins Sans Frontieres, Barcelona, Spain; Disease Control in Emergencies, Department of Epidemic and Pandemic Alert and Response, World Health Organization, Geneva, Switzerland (Public Library of Science (PLoS), 2008-08-05)
    • Assessing the Asymptomatic Reservoir and Dihydroartemisinin-Piperaquine Effectiveness in a Low Transmission Setting Threatened by Artemisinin Resistant Plasmodium Falciparum

      Falq, G; Van Den Bergh, R; De Smet, M; Etienne, W; Nguon, C; Rekol, H; Imwong, M; Dondorp, A; Kindermans, JM (BioMed Central, 2016-09-01)
      In Cambodia, elimination of artemisinin resistance through direct elimination of the Plasmodium falciparum parasite may be the only strategy. Prevalence and incidence at district and village levels were assessed in Chey Saen district, Preah Vihear province, North of Cambodia. Molecular and clinical indicators for artemisinin resistance were documented.
    • Assessment of three new parasite lactate dehydrogenase (pan-pLDH) tests for diagnosis of uncomplicated malaria.

      Fogg, C; Twesigye, R; Batwala, V; Piola, P; Nabasumba, C; Kiguli, J; Mutebi, F; Hook, C; Guillerm, M; Moody, A; Guthmann, J P; Epicentre, 8 rue Saint Sabin, 75011, Paris, France. carolefogg@yahoo.co.uk (Elsevier, 2008-01)
      A study to assess the diagnostic capabilities of three parasite lactate dehydrogenase (pan-pLDH) tests, Vistapan), Carestart and Parabank), was conducted in Uganda. An HRP2 test, Paracheck-Pf), and a Giemsa-stained blood film were performed with the pLDH tests for outpatients with suspected malaria. In total, 460 subjects were recruited: 248 with positive blood films and 212 with negative blood films. Plasmodium falciparum was present in 95% of infections. Sensitivity above 90% was shown by two pLDH tests, Carestart (95.6%) and Vistapan (91.9%), and specificity above 90% by Parabank (94.3%) and Carestart (91.5%). Sensitivity decreased with low parasitaemia (chi(2) trend, P<0.001); however, all tests achieved sensitivity >90% with parasitaemia > or =100/microl. All tests had good inter-reader reliability (kappa>0.95). Two weeks after diagnosis, 4-10% of pLDH tests were still positive compared with 69.7% of the HRP2 tests. All tests had similar ease of use. In conclusion, two pLDH tests performed well in diagnosing P. falciparum malaria, and all pLDH tests became negative after treatment more quickly than the HRP2. Therefore the rapid test of choice for use with artemisinin-combination therapies in this area would be one of these new pLDH tests.
    • Assessment of two malaria rapid diagnostic tests in children under five years of age, with follow-up of false-positive pLDH test results, in a hyperendemic falciparum malaria area, Sierra Leone.

      Gerstl, Sibylle; Dunkley, Sophie; Mukhtar, Ahmed; De Smet, Martin; Baker, Samuel; Maikere, Jacob (2010-01-21)
      ABSTRACT: BACKGROUND: Most malaria rapid diagnostic tests (RDTs) use HRP2 detection, including Paracheck-Pf(R), but their utility is limited by persistent false positivity after treatment. PLDH-based tests become negative more quickly, but sensitivity has been reported below the recommended standard of 90%. A new pLDH test, CareStartTM three-line P.f/PAN-pLDH, claims better sensitivity with continued rapid conversion to negative. The study aims were to 1) compare sensitivity and specificity of CareStartTM to Paracheck-Pf(R) to diagnose falciparum malaria in children under five years of age, 2) assess how quickly false-positive CareStartTM tests become negative and 3) evaluate ease of use and inter-reader agreement of both tests. METHODS: Participants were included if they were aged between two and 59 months, presenting to a Medecins Sans Frontieres community health centre in eastern Sierra Leone with suspected malaria defined as fever (axillary temperature > 37.5degreesC) and/or history of fever in the previous 72 hours and no signs of severe disease. The same capillary blood was used for the RDTs and the blood slide, the latter used as the gold standard reference. All positive participants were treated with supervised artesunate and amodiaquine treatment for three days. Participants with a persistent false-positive CareStartTM, but a negative blood slide on Day 2, were followed with repeated CareStartTM and blood slide tests every seven days until CareStartTM became negative or a maximum of 28 days. RESULTS: Sensitivity of CareStartTM was 99.4% (CI 96.8-100.0, 168/169) and of Paracheck-Pf(R), 98.8% (95% CI 95.8-99.8, 167/169). Specificity of CareStartTM was 96.0% (CI 91.9-98.4, 167/174) and of Paracheck-Pf(R), 74.7% (CI 67.6-81.0, 130/174) (p<0.001). Neither test showed any change in sensitivity with decreasing parasitaemia. Of the 155 eligible follow-up CareStartTM participants, 63.9% (99/155) had a false-positive test on day 2, 21.3% (33/155) on day 7, 5.8% (9/155) on day 14, 1.9% (3/155) on day 21 and 0.6% (1/155) on day 28. The median time for test negativity was seven days. CareStartTM was as easy to use and interpret as Paracheck-Pf(R) with excellent inter-reader agreement. CONCLUSIONS: Both RDTs were highly sensitive, met WHO standards for the detection of falciparum malaria monoinfections where parasitaemia was >100 parasites/mul and were easy to use. CareStartTM persistent false positivity decreased quickly after successful anti-malarial treatment, making it a good choice for a RDT for a hyperendemic falciparum malaria area.
    • Association Between HRP–2/pLDH Rapid Diagnostic Test Band Positivity and Malaria–related Anemia at a Peripheral Health Facility in Western Uganda

      Boyce, Ross; Reyes, Raquel; Ntaro, Moses; Mulogo, Edgar; Matte, Michael; Boum, Yap; Siedner, Mark J. (Edinburgh University Global Health Society, 2015-07-06)
    • Barriers to prompt and effective treatment of malaria in northern Sri Lanka.

      Reilley, B; Abeyasinghe, R; Pakianathar, M V; Medecins sans Frontieres, Colombo, Sri Lanka. (Wiley-Blackwell, 2002-09)
      BACKGROUND: For the past 18 years, northern Sri Lanka has been affected by armed ethnic conflict. This has had a heavy impact on displacement of civilians, health delivery services, number of health professionals in the area and infrastructure. The north of Sri Lanka has a severe malaria burden, with less than 5% of the national population suffering 34% of reported cases. Health care providers investigated treatment-seeking behaviour and levels of treatment failure believed to be the result of lack of adherence to treatment. METHODS: Pre- and post-treatment interviews with patients seeking treatment in the outpatient department (OPD) and focus groups. RESULTS: A total of 271 persons completed interviews: 54.4% sought treatment within 2 days of the onset of symptoms, and 91.9% self-treated with drugs with prior to seeking treatment, mainly with paracetamol. Self-treatment was associated with delaying treatment (RR 3.55, CI 1.23-10.24, P=0.002). In post-treatment interviews, self-reported default was 26.1%. The main reasons for not taking the entire regimen were side-effects (57.6%) and disappearance of symptoms (16.7%). Focus groups indicated some lack of confidence in chloroquine treatment and prophylaxis, and scant enthusiasm for prevention methods. CONCLUSIONS: A number of factors contribute to a lack of access and a lower quality of care for malaria: lack of medical staff and facilities because of the fighting; lack of confidence in treatment, and perception of malaria as a routine illness. Prevention efforts need to take into account certain beliefs and practices to be successful.
    • Can timely vector control interventions triggered by atypical environmental conditions prevent malaria epidemics? A case-study from wajir county, kenya.

      Maes, Peter; Harries, Anthony D; Van den Bergh, Rafael; Noor, Abdisalan; Snow, Robert W; Tayler-Smith, Katherine; Hinderaker, Sven Gudmund; Zachariah, Rony; Allan, Richard (Public Library of Science, 2014-04-03)
      Atypical environmental conditions with drought followed by heavy rainfall and flooding in arid areas in sub-Saharan Africa can lead to explosive epidemics of malaria, which might be prevented through timely vector-control interventions.