• Complex interactions between malaria and malnutrition: a systematic literature review

      Das, D; Grais, R F; Okiro, E A; Stepniewska, K; Mansoor, R; van der Kam, S; Terlouw, D J; Tarning, J; Barnes, K I; Guerin, P J (BMC, 2018-10-29)
      Despite substantial improvement in the control of malaria and decreased prevalence of malnutrition over the past two decades, both conditions remain heavy burdens that cause hundreds of thousands of deaths in children in resource-poor countries every year. Better understanding of the complex interactions between malaria and malnutrition is crucial for optimally targeting interventions where both conditions co-exist. This systematic review aimed to assess the evidence of the interplay between malaria and malnutrition.
    • Using ante-natal clinic prevalence data to monitor temporal changes in malaria incidence in a humanitarian setting in the Democratic Republic of Congo.

      Hellewell, J; Walker, P; Ghani, A; Rao, B; Churcher, TS (BMC, 2018-08-29)
      The number of clinical cases of malaria is often recorded in resource constrained or conflict settings as a proxy for disease burden. Interpreting case count data in areas of humanitarian need is challenging due to uncertainties in population size caused by security concerns, resource constraints and population movement. Malaria prevalence in women visiting ante-natal care (ANC) clinics has the potential to be an easier and more accurate metric for malaria surveillance that is unbiased by population size if malaria testing is routinely conducted irrespective of symptoms.
    • 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.
    • 'I could not join because I had to work for pay.': A qualitative evaluation of falciparum malaria pro-active case detection in three rural Cambodian villages

      Taffon, P; Rossi, G; Kindermans, JM; Van den Bergh, R; Nguon, C; Debackere, M; Vernaeve, L; De Smet, M; Venables, E (Public Library of Science, 2018-04-12)
      Pro-active case detection (Pro-ACD), in the form of voluntary screening and treatment (VSAT) following community mobilisation about 'asymptomatic malaria', is currently being evaluated as a tool for Plasmodium falciparum elimination in Preah Vihear Province, Cambodia.
    • Molecular markers of resistance to amodiaquine plus sulfadoxine-pyrimethamine in an area with seasonal malaria chemoprevention in south central Niger

      Grais, RF; Laminou, IM; Woi-Messe, L; Makarimi, R; Bouriema, SH; Langendorf, C; Amambua-Ngwa, A; D'Alessandro, U; Guérin, PJ; Fandeur, T; Sibley, CH (BioMed Central, 2018-02-27)
      In Niger, malaria transmission is markedly seasonal with most of the disease burden occurring in children during the rainy season. Seasonal malaria chemoprevention (SMC) with amodiaquine plus sulfadoxine-pyrimethamine (AQ + SP) is recommended in the country to be administered monthly just before and during the rainy season. Moreover, clinical decisions on use of SP for intermittent preventive treatment in pregnancy (IPTp) now depend upon the validated molecular markers for SP resistance in Plasmodium falciparum observed in the local parasite population. However, little is known about molecular markers of resistance for either SP or AQ in the south of Niger. To address this question, clinical samples which met clinical and biological criteria, were collected in Gabi, Madarounfa district, Maradi region, Niger in 2011-2012 (before SMC implementation). Molecular markers of resistance to pyrimethamine (pfdhfr), sulfadoxine (pfdhps) and amodiaquine (pfmdr1) were assessed by DNA sequencing.
    • Community participation during two mass anti-malarial administrations in Cambodia: lessons from a joint workshop

      Peto, TJ; Debackere, M; Etienne, W; Vernaeve, L; Tripura, R; Falq, G; Davoeung, C; Nguon, C; Rekol, H; von Seidlein, L; Dondorp, AM; Sanann, N; Cheah, PY; De Smet, M; Pell, C; Kindermans, JM (BioMed Central, 2018-01-27)
      Two mass drug administrations (MDA) against falciparum malaria were conducted in 2015-16, one as operational research in northern Cambodia, and the other as a clinical trial in western Cambodia. During an April 2017 workshop in Phnom Penh the field teams from Médecins Sans Frontières and the Mahidol-Oxford Tropical Medicine Research Unit discussed lessons for future MDAs.
    • Efficacy of artesunate-amodiaquine, dihydroartemisinin-piperaquine and artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Maradi, Niger

      Grandesso, F; Guindo, O; Woi Messe, L; Makarimi, R; Traore, A; Dama, S; Laminou, IM; Rigal, J; de Smet, M; Ouwe Missi Oukem-Boyer, O; Doumbo, OK; Djimdé, A; Etard, JF (BioMed Central, 2018-01-25)
      Malaria endemic countries need to assess efficacy of anti-malarial treatments on a regular basis. Moreover, resistance to artemisinin that is established across mainland South-East Asia represents today a major threat to global health. Monitoring the efficacy of artemisinin-based combination therapies is of paramount importance to detect as early as possible the emergence of resistance in African countries that toll the highest burden of malaria morbidity and mortality.
    • Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa

      Taylor, WR; Naw, HK; Maitland, K; Williams, TN; Kapulu, M; D'Alessandro, U; Berkley, JA; Bejon, P; Okebe, J; Achan, J; Amambua, AN; Affara, M; Nwakanma, D; van Geertruyden, JP; Mavoko, M; Lutumba, P; Matangila, J; Brasseur, P; Piola, P; Randremanana, R; Lasry, E; Fanello, C; Onyamboko, M; Schramm, B; Yah, Z; Jones, J; Fairhurst, RM; Diakite, M; Malenga, G; Molyneux, M; Rwagacondo, C; Obonyo, C; Gadisa, E; Aseffa, A; Loolpapit, M; Henry, MC; Dorsey, G; John, C; Sirima, SB; Barnes, KI; Kremsner, P; Day, NP; White, NJ; Mukaka, M (BioMed Central, 2018-01-18)
      In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa.
    • Closing in on the Reservoir: Proactive Case Detection in High-Risk Groups as a Strategy to Detect Plasmodium falciparum Asymptomatic Carriers in Cambodia

      Rossi, Gabriele; Vernaeve, Lieven; Van den Bergh, Rafael; Nguon, Chea; Debackere, Mark; Abello Peiri, Carme; Van, Vuthea; Khim, Nimol; Kim, Saorin; Eam, Rotha; Ken, Malen; Khean, Chanra; De Smet, Martin; Menard, Didier; Kindermans, Jean-Marie (Oxford University Press, 2018-01-18)
      In the frame of elimination strategies of Plasmodium falciparum (Pf), active case detection has been recommended as complementary approach to the existing passive case detection programs. We trialed a polymerase chain reaction (PCR)-based active detection strategy targeting asymptomatic individuals, named proactive case detection (PACD), with the aim of assessing its feasibility, the extra yield of Pf infections, and the at-risk population for Pf carriage status.
    • Emergence of Plasmodium falciparum triple mutant in Cambodia.

      Rossi, G; De Smet, M; Khim, N; Kindermans, JM; Menard, D (Elsevier, 2017-12)
    • Seasonal Malaria Chemoprevention: successes and missed opportunities

      Coldiron, ME; Von Seidlein, L; Grais, RF (BioMed Central, 2017-11-28)
      Seasonal malaria chemoprevention (SMC) was recommended in 2012 for young children in the Sahel during the peak malaria transmission season. Children are given a single dose of sulfadoxine/pyrimethamine combined with a 3-day course of amodiaquine, once a month for up to 4 months. Roll-out and scale-up of SMC has been impressive, with 12 million children receiving the intervention in 2016. There is evidence of its overall benefit in routine implementation settings, and a meta-analysis of clinical trial data showed a 75% decrease in clinical malaria compared to placebo. SMC is not free of shortcomings. Its target zone includes many hard-to-reach areas, both because of poor infrastructure and because of political instability. Treatment adherence to a 3-day course of preventive treatment has not been fully documented, and could prove challenging. As SMC is scaled up, integration into a broader, community-based paradigm which includes other preventive and curative activities may prove beneficial, both for health systems and for recipients.
    • 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.
    • Malaria in an Internally Displaced Persons Camp in the Democratic Republic of the Congo

      Brooks, H; Jean Paul, M; Claude, K; Houston, S; Hawkes, M (Oxford University Press, 2017-08-01)
    • 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; Sharma, H; Remartinez, D; Kalon, S; de Polnay, K; De Smet, M; Isaakidis, P (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.
    • Intermittent Preventive Treatment for Malaria Among Children in a Refugee Camp in Northern Uganda: Lessons Learned

      Coldiron, M; Lasry, E; Bouhenia, M; Das, D; Okui, P; Nyehangane, D; Mwanga, J; Langendorf, C; Elder, G; Salumu, L; Grais, R (BioMed Central, 2017-05-23)
      Northern Uganda hosts a large population of refugees from South Sudan, and malaria is one of the major health problems in the area. In 2015, intermittent preventive treatment for malaria (IPTc) was implemented in two refugee camps among children aged 6 months to 14 years. Three distributions of dihydroartemisinin-piperaquine (DP) were conducted at 8-week intervals. The first dose was directly administered at IPTc distribution sites and the second and third doses were given to caregivers to administer at home. A multi-faceted evaluation was implemented, including coverage surveys, malaria prevalence surveys, reinforced surveillance, and pharmacovigilance. Programme coverage exceeded 90% during all three distributions with a total of 40,611 participants. Compared to same period during the previous year (only available data), the incidence of malaria in the target populations was reduced (IRR 0.73, 95% CI 0.69-0.77 among children under 5 years old; IRR 0.70, 95% CI 0.67-0.72 among children aged 5-14 years). Among those not targeted for intervention, the incidence between the 2 years increased (IRR 1.49, 95% CI 1.42-1.56). Cross-sectional surveys showed a prevalence of parasitaemia (microscopy or PCR) of 12.9-16.4% (95% CI 12.6-19.3) during the intervention, with the highest prevalence among children aged 5-14 years, but with a large increase 8 weeks after the final distribution. A total of 57 adverse events were reported during the intervention period, including one severe adverse event (death from varicella). Adverse events were of mild to moderate severity, and were mainly dermatologic and gastrointestinal. This is the first documentation of an IPTc programme in a refugee camp. The positive impact of DP on the incidence of malaria, together with its favourable safety profile, should lead to further use of IPTc in similar settings. Expanding coverage groups and decreasing intervals between distributions might provide more benefit, but would need to be balanced with the operational implications of a broader, more frequent distribution schedule.
    • Improving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm

      Murungi, M; Fulton, T; Reyes, R; Matte, M; Ntaro, M; Mulogo, E; Nyehangane, D; Juliano, J; Siedner, M; Boum, Y; Boyce, R (American Society for Microbiology, 2017-05)
      Poor specificity may negatively impact rapid diagnostic test (RDT)-based diagnostic strategies for malaria. We performed real-time PCR on a subset of subjects who had undergone diagnostic testing with a multiple-antigen (histidine-rich protein 2 and pan-lactate dehydrogenase pLDH [HRP2/pLDH]) RDT and microscopy. We determined the sensitivity and specificity of the RDT in comparison to results of PCR for the detection of Plasmodium falciparum malaria. We developed and evaluated a two-step algorithm utilizing the multiple-antigen RDT to screen patients, followed by confirmatory microscopy for those individuals with HRP2-positive (HRP2+)/pLDH-negative (pLDH-) results. In total, dried blood spots (DBS) were collected from 276 individuals. There were 124 (44.9%) individuals with an HRP2+/pLDH+ result, 94 (34.1%) with an HRP2+/pLDH- result, and 58 (21%) with a negative RDT result. The sensitivity and specificity of the RDT compared to results with real-time PCR were 99.4% (95% confidence interval [CI], 95.9 to 100.0%) and 46.7% (95% CI, 37.7 to 55.9%), respectively. Of the 94 HRP2+/pLDH- results, only 32 (34.0%) and 35 (37.2%) were positive by microscopy and PCR, respectively. The sensitivity and specificity of the two-step algorithm compared to results with real-time PCR were 95.5% (95% CI, 90.5 to 98.0%) and 91.0% (95% CI, 84.1 to 95.2), respectively. HRP2 antigen bands demonstrated poor specificity for the diagnosis of malaria compared to that of real-time PCR in a high-transmission setting. The most likely explanation for this finding is the persistence of HRP2 antigenemia following treatment of an acute infection. The two-step diagnostic algorithm utilizing microscopy as a confirmatory test for indeterminate HRP2+/pLDH- results showed significantly improved specificity with little loss of sensitivity in a high-transmission setting.
    • Local Constraints to Access Appropriate Malaria Treatment in the Context of Parasite Resistance in Cambodia: a Qualitative Study

      Verschuere, J; Decroo, T; Lim, D; Kindermans, JM; Nguon, C; Huy, R; Alkourdi, Y; Peeters Grietens, K; Gryseels, C (BioMed Central, 2017-02-17)
      Despite emerging drug resistance in Cambodia, artemisinin-based combination therapy (ACT) is still the most efficacious therapy. ACT is available free of charge in the Cambodian public sector and at a subsidized rate in the private sector. However, un- and mistreated cases in combination with population movements may lead to the further spread of resistant parasites, stressing the importance of understanding how the perceived aetiology of malaria and associated health-seeking behaviour may delay access to appropriate treatment. A qualitative study explored these factors after an epidemiological survey confirmed parasite resistance in Preah Vihear province.
    • 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; Menard, D; Roca-Felterer, A; Fairhurst, RM; Kheng, S; Muth, S; Ngak, S; Dondorp, AM; White, NJ; Taylor, WR (BioMed Central, 2016-12-20)
    • 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; Menard, D; Roca-Felterer, A; Fairhurst, RM; Kheng, S; Muth, S; Ngak, S; Dondorp, AM; White, NJ; Taylor, WRJ (BioMed Central, 2016-10-27)
      In 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested, leaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based SLDPQ regimen for Cambodia, the country most affected by ARPf.