• '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.
    • Identifying exceptional malaria occurrences in the absence of historical data in South Sudan: a method validation

      Benedetti, G; White, RA; Akello Pasquale, H; Stassjins, J; van den Boogaard, W; Owiti, P; Van den Bergh, R (International Union Against Tuberculosis and Lung Disease, 2019-09-21)
      Background: Detecting unusual malaria events that may require an operational intervention is challenging, especially in endemic contexts with continuous transmission such as South Sudan. Médecins Sans Frontières (MSF) utilises the classic average plus standard deviation (AV+SD) method for malaria surveillance. This and other available approaches, however, rely on antecedent data, which are often missing. Objective: To investigate whether a method using linear regression (LR) over only 8 weeks of retrospective data could be an alternative to AV+SD. Design: In the absence of complete historical malaria data from South Sudan, data from weekly influenza reports from 19 Norwegian counties (2006–2015) were used as a testing data set to compare the performance of the LR and the AV+SD methods. The moving epidemic method was used as the gold standard. Subsequently, the LR method was applied in a case study on malaria occurrence in MSF facilities in South Sudan (2010–2016) to identify malaria events that required a MSF response. Results: For the Norwegian influenza data, LR and AV+SD methods did not perform differently (P  0.05). For the South Sudanese malaria data, the LR method identified historical periods when an operational response was mounted. Conclusion: The LR method seems a plausible alternative to the AV+SD method in situations where retrospective data are missing.
    • Identifying malaria control issues: a district hospital-based evaluation.

      Kimerling, M; Houth, H; Hilderbrand, K; Goubert, L; MSF Holland-Belgium, Phnom Penh, Cambodia. (1995-12)
      Chuk district hospital is centrally located in a rural malarious region in southern Cambodia. It was the site of a hospital-based evaluation (KAP assessment and in vivo i.v. quinine/oral tetracycline drug study) done to identify relevant issues for establishing a rational malaria control strategy. The KAP assessment identified the young, male forest worker as the highest risk group. Of 112 study patients, 73% were male and 82% reported various forest activities. The primary reason found for patient delay (8.9 days) in seeking hospital care was self-treatment at home (N = 102, 91%) with drugs purchased through private sellers (104/105). Using the 7-day WHO field test methodology, resistance rates were calculated (N = 22); S1/R1, 73%; R1, 9%; R2, 0%; R3, 18%. A modified version of the 7-day test was used to calculate its utility in this particular rural setting. It showed a negative predictive value of 93% and a positive predictive value of 71%. The case fatality rate for the study period was 2.7%. Information from this study, which correlates a confirmed malaria diagnosis with prior patient behavior and response to anti-malarial therapy, is intended for realizing the goals set forth by the national malaria control program.
    • Impact and Lessons Learned from Mass Drug Administrations of Malaria Chemoprevention during the Ebola Outbreak in Monrovia, Liberia, 2014

      Kuehne, A; Tiffany, A; Lasry, E; Janssens, M; Besse, C; Okonta, C; Larbi, K; Pah, AC; Danis, K; Porten, K (Public Library of Science, 2016-08-31)
      In October 2014, during the Ebola outbreak in Liberia healthcare services were limited while malaria transmission continued. Médecins Sans Frontières (MSF) implemented a mass drug administration (MDA) of malaria chemoprevention (CP) in Monrovia to reduce malaria-associated morbidity. In order to inform future interventions, we described the scale of the MDA, evaluated its acceptance and estimated the effectiveness.
    • Impact of malaria during pregnancy on pregnancy outcomes in a Ugandan prospective cohort with intensive malaria screening and prompt treatment

      De Beaudrap, Pierre; Turyakira, Eleanor; White, Lisa J; Nabasumba, Carolyn; Tumwebaze, Benon; Muehlenbachs, Atis; Guérin, Philippe J; Boum, Yap; McGready, Rose; Piola, Patrice; et al. (BioMed Central, 2013-04-24)
      Malaria in pregnancy (MiP) is a major public health problem in endemic areas of sub-Saharan Africa and has important consequences on birth outcome. Because MiP is a complex phenomenon and malaria epidemiology is rapidly changing, additional evidence is still required to understand how best to control malaria. This study followed a prospective cohort of pregnant women who had access to intensive malaria screening and prompt treatment to identify factors associated with increased risk of MiP and to analyse how various characteristics of MiP affect delivery outcomes.
    • Imported Malaria Including HIV and Pregnant Woman Risk Groups: Overview of the Case of a Spanish City 2004-2014

      Fernández López, María; Ruiz Giardín, Jose Manuel; San Martín López, Juan Víctor; Jaquetti, Jerónimo; García Arata, Isabel; Jiménez Navarro, Carolina; Cabello Clotet, Noemi (BioMed Central, 2015-09-17)
      Arrival of inmigrants from malaria endemic areas has led to a emergence of cases of this parasitic disease in Spain. The objective of this study was to analyse the high incidence rate of imported malaria in Fuenlabrada, a city in the south of Madrid, together with the frequent the lack of chemoprophylaxis, for the period between 2004 and 2014. Both pregnant women and HIV risk groups have been considered.
    • 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; et al. (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.
    • In vivo assessment of drug efficacy against Plasmodium falciparum malaria: duration of follow-up.

      Stepniewska, K; Taylor, W R J; Mayxay, M; Price, R; Smithuis, F; Guthmann, J P; Barnes, K; Myint, H Y; Adjuik, M; Olliaro, P; et al. (2004-11)
      To determine the optimum duration of follow-up for the assessment of drug efficacy against Plasmodium falciparum malaria, 96 trial arms from randomized controlled trials (RCTs) with follow-up of 28 days or longer that were conducted between 1990 and 2003 were analyzed. These trials enrolled 13,772 patients, and participating patients comprised 23% of all patients enrolled in RCTs over the past 40 years; 61 (64%) trial arms were conducted in areas where the rate of malaria transmission was low, and 58 (50%) trial arms were supported by parasite genotyping to distinguish true recrudescences from reinfections. The median overall failure rate reported was 10% (range, 0 to 47%). The widely used day 14 assessment had a sensitivity of between 0 and 37% in identifying treatment failures and had no predictive value. Assessment at day 28 had a sensitivity of 66% overall (28 to 100% in individual trials) but could be used to predict the true failure rate if either parasite genotyping was performed (r(2) = 0.94) or if the entomological inoculation rate was known. In the assessment of drug efficacy against falciparum malaria, 28 days should be the minimum period of follow-up.
    • In Vivo Efficacy of Artesunate-Amodiaquine and Artemether-Lumefantrine for the Treatment of Uncomplicated Falciparum Malaria: an Open-Randomized, Non-Inferiority Clinical Trial in South Kivu, Democratic Republic of Congo

      de Wit, M; Funk, AL; Moussally, K; Nkuba, DA; Siddiqui, R; Bil, K; Piriou, E; Bart, A; Bahizi Bizoza, P; Bousema, T (BioMed Central (Springer Science), 2016)
      Between 2009 and 2012, malaria cases diagnosed in a Médecins sans Frontières programme have increased fivefold in Baraka, South Kivu, Democratic Republic of the Congo (DRC). The cause of this increase is not known. An in vivo drug efficacy trial was conducted to determine whether increased treatment failure rates may have contributed to the apparent increase in malaria diagnoses.
    • In vivo parasitological measures of artemisinin susceptibility

      Stepniewska, Kasia; Ashley, Elizabeth; Lee, Sue J; Anstey, Nicholas; Barnes, Karen I; Binh, Tran Quang; D'Alessandro, Umberto; Day, Nicholas P J; de Vries, Peter J; Dorsey, Grant; et al. (2010-01-19)
      Parasite clearance data from 18,699 patients with falciparum malaria treated with an artemisinin derivative in areas of low (n=14,539), moderate (n=2077), and high (n=2083) levels of malaria transmission across the world were analyzed to determine the factors that affect clearance rates and identify a simple in vivo screening measure for artemisinin resistance. The main factor affecting parasite clearance time was parasite density on admission. Clearance rates were faster in high-transmission settings and with more effective partner drugs in artemisinin-based combination treatments (ACTs). The result of the malaria blood smear on day 3 (72 h) was a good predictor of subsequent treatment failure and provides a simple screening measure for artemisinin resistance. Artemisinin resistance is highly unlikely if the proportion of patients with parasite densities of <100,000 parasites/microL given the currently recommended 3-day ACT who have a positive smear result on day 3 is <3%; that is, for n patients the observed number with a positive smear result on day 3 does not exceed (n + 60)/24.
    • Independent Origin of Plasmodium falciparum Antifolate Super-Resistance, Uganda, Tanzania, and Ethiopia.

      Alifrangis, Michael; Nag, Sidsel; Schousboe, Mette L; Ishengoma, Deus; Lusingu, John; Pota, Hirva; Kavishe, Reginald A; Pearce, Richard; Ord, Rosalynn; Lynch, Caroline; et al. (2014-08)
      Super-resistant Plasmodium falciparum threatens the effectiveness of sulfadoxine-pyrimethamine in intermittent preventive treatment for malaria during pregnancy. It is characterized by the A581G Pfdhps mutation on a background of the double-mutant Pfdhps and the triple-mutant Pfdhfr. Using samples collected during 2004-2008, we investigated the evolutionary origin of the A581G mutation by characterizing microsatellite diversity flanking Pfdhps triple-mutant (437G+540E+581G) alleles from 3 locations in eastern Africa and comparing it with double-mutant (437G+540E) alleles from the same area. In Ethiopia, both alleles derived from 1 lineage that was distinct from those in Uganda and Tanzania. Uganda and Tanzania triple mutants derived from the previously characterized southeastern Africa double-mutant lineage. The A581G mutation has occurred multiple times on local Pfdhps double-mutant backgrounds; however, a novel microsatellite allele incorporated into the Tanzania lineage since 2004 illustrates the local expansion of emergent triple-mutant lineages.
    • Influence of rapid malaria diagnostic tests on treatment and health outcome in fever patients, Zanzibar: a crossover validation study

      Msellem, Mwinyi I; Mårtensson, Andreas; Rotllant, Guida; Bhattarai, Achuyt; Strömberg, Johan; Kahigwa, Elizeus; Garcia, Montse; Petzold, Max; Olumese, Peter; Ali, Abdullah; et al. (2009-04-28)
      BACKGROUND: The use of rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria is being suggested to improve diagnostic efficiency in peripheral health care settings in Africa. Such improved diagnostics are critical to minimize overuse and thereby delay development of resistance to artemisinin-based combination therapies (ACTs). Our objective was to study the influence of RDT-aided malaria diagnosis on drug prescriptions, health outcomes, and costs in primary health care settings. METHODS AND FINDINGS: We conducted a cross-over validation clinical trial in four primary health care units in Zanzibar. Patients of all ages with reported fever in the previous 48 hours were eligible and allocated alternate weeks to RDT-aided malaria diagnosis or symptom-based clinical diagnosis (CD) alone. Follow-up was 14 days. ACT was to be prescribed to patients diagnosed with malaria in both groups. Statistical analyses with multilevel modelling were performed. A total of 1,887 patients were enrolled February through August 2005. RDT was associated with lower prescription rates of antimalarial treatment than CD alone, 361/1005 (36%) compared with 752/882 (85%) (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.03-0.05, p<0.001). Prescriptions of antibiotics were higher after RDT than CD alone, i.e., 372/1005 (37%) and 235/882 (27%) (OR 1.8, 95%CI 1.5-2.2, p<0.001), respectively. Reattendance due to perceived unsuccessful clinical cure was lower after RDT 25/1005 (2.5%), than CD alone 43/882 (4.9%) (OR 0.5, 95% CI 0.3-0.9, p = 0.005). Total average cost per patient was similar: USD 2.47 and 2.37 after RDT and CD alone, respectively. CONCLUSIONS: RDTs resulted in improved adequate treatment and health outcomes without increased cost per patient. RDTs may represent a tool for improved management of patients with fever in peripheral health care settings. TRIAL REGISTRATION: (Clinicaltrials.gov) NCT00549003.
    • 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; et al. (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.
    • Internal quality control of the malaria microscopy diagnosis for 10 laboratories on the Thai-Myanmar border.

      Hemme, F; Gay, F; Medecins Sans Frontières, French Section, Mae Sot, Thailand. (1998-09)
      On the Thai-Myanmar border, where multidrug resistance to anti-malaria medications is a major problem, a quality control program for diagnostic laboratories has been set up. This study examines the "passive" screening performed in 10 laboratories. Monthly evaluation of the quality of thick and thin smear practice, Giemsa staining and microscopy took place during the year 1994. Considering the general context and the methodology applied, the evaluation of performance and strategy of the malaria diagnostic test showed satisfactory results for all 10 laboratories. Performance of technics = 64% (62-66) to 96% (95-97); Sensitivity = 92.6 (91.5-95.5) to 96.6% (95.8-99.0); Specificity = 93.5% (91.4-95.5) to 98.3% (97.6-99.0); Predictive Positive Value = 92.0% (90.9-93.1) to 98.3% (97.6-99.0); Predictive Negative Value = 94.3% (93.0-95.6) to 98.5% (98.0-99.0). The study underlines the importance of a reliable quality control method for microscopy diagnosis of malaria in hyperendemic areas, with Plasmodium falciparum as the main species. A high level of input from the international laboratory technician, performing training, follow-up and evaluation was required. The need for adequate training of national technicians and supervisors, especially regarding long-term sustainability, is stressed. The type of program presented can be used as a model for similar projects in developing countries.
    • Last line of defence

      de Smet, M (2009-06-20)
    • 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.
    • Long-lasting insecticide-treated net usage in eastern Sierra Leone - the success of free distribution.

      Gerstl, Sibylle; Dunkley, Sophie; Mukhtar, Ahmed; Maes, Peter; De Smet, Martin; Baker, Samuel; Maikere, Jacob; Médecins Sans Frontières-United Kingdom, London, UK. (2010-02-09)
      Summary Objective Médecins Sans Frontières (MSF) runs a malaria control project in Bo and Pujehun districts (population 158 000) that includes the mass distribution, routine delivery and demonstration of correct use of free, long-lasting insecticide-treated nets (LLINs). In 2006/2007, around 65 000 LLINs were distributed. The aim of this follow-up study was to measure LLIN usage and ownership in the project area. Methods Heads of 900 randomly selected households in 30 clusters were interviewed, using a standardized questionnaire, about household use of LLINs. The condition of any LLIN was physically assessed. Results Of the 900 households reported, 83.4% owning at least one LLIN. Of the 16.6% without an LLIN, 91.9% had not participated in the MSF mass distribution. In 94.1% of the households reporting LLINs, the nets were observed hanging correctly over the beds. Of the 1135 hanging LLINs, 75.2% had no holes or 10 or fewer finger-size holes. The most common source of LLINs was MSF (75.2%). Of the 4997 household members, 67.2% reported sleeping under an LLIN the night before the study, including 76.8% of children under 5 years and 73.0% of pregnant women. Conclusion Our results show that MSF achieved good usage with freely distributed LLINs. It is one of the few areas where results almost achieve the new targets set in 2005 by Roll Back Malaria to have at least 80% of pregnant women and children under 5 years using LLINs by 2010.
    • Low efficacy of the combination artesunate plus amodiaquine for uncomplicated falciparum malaria among children under 5 years in Kailahun, Sierra Leone.

      Grandesso, F; Hagerman, A; Kamara, S; Lam, E; Checchi, F; Balkan, S; Scollo, G; Durand, R; Guthmann, J P; Epicentre, Paris, France. (Wiley-Blackwell, 2006-07)
      OBJECTIVE: In 2004, Sierra Leone adopted artesunate plus amodiaquine as first-line antimalarial treatment. We evaluated the efficacy of this combination in Kailahun, where a previous study had shown 70.2% efficacy of amodiaquine in monotherapy. METHODS: Method and outcome classification of the study complied with WHO guidelines. Children 6-59 months with uncomplicated malaria were followed-up for 28 days. PCR genotyping was used to distinguish recrudescence from reinfection. Reinfections were reclassified as cured. RESULTS: Of 172 children who were referred to the study clinic, 126 satisfied inclusion criteria and were enrolled. No early treatment failures were reported. The day 14, efficacy was 98.2% (95% CI: 93.8-99.8). Of 65 recurrent parasitaemias analysed by PCR, 17 were recrudescences. The PCR-adjusted day 28 efficacy was 84.5% (95% CI: 76.4-90.7). All true failures occurred in the last 8 days of follow-up. Of 110 children who completed the 28-day follow-up, 54 (49.1%) experienced a novel infection. CONCLUSION: The efficacy of this combination was disappointing. The high reinfection rate suggested little prophylactic effect. In Kailahun a more efficacious combination might be necessary in the future. The efficacy of AS + AQ needs to be monitored in Kailahun and in the other regions of Sierra Leone.
    • Low referral completion of rapid diagnostic test-negative patients in community-based treatment of malaria in Sierra Leone.

      Thomson, Anna; Khogali, Mohammed; de Smet, Martin; Reid, Tony; Mukhtar, Ahmed; Peterson, Stefan; von Schreeb, Johan; Division of Global Health, Karolinska Institutet, Stockholm, Sweden. anna.thomson@stockholm.msf.org. (2011-05)
      ABSTRACT:
    • 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)