• Short report: molecular markers associated with Plasmodium falciparum resistance to sulfadoxine-pyrimethamine in the Democratic Republic of Congo.

      Cohuet, S; Bonnet, M; Van Herp, M; Van Overmeir, C; D'Alessandro, U; Guthmann, J P; Epicentre, Paris, France; Médecins Sans Frontières, Brussels, Belgium; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium. (2006-07)
      Sulfadoxine-pyrimethamine (SP) is the first line antimalarial treatment in the Democratic Republic of Congo. Using polymerase chain reaction, we assessed the prevalence of mutations in the dihydrofolate reductase (dhfr) (codons 108, 51, 59) and dihydropteroate synthase (dhps) (codons 437, 540) genes of Plasmodium falciparum, which have been associated with resistance to pyrimethamine and sulfadoxine, respectively. Four hundred seventy-four patients were sampled in Kilwa (N = 138), Kisangani (N = 112), Boende (N = 106), and Basankusu (N = 118). The proportion of triple mutations dhfr varied between sites but was always > 50%. The proportion of dhps double mutations was < 20%, with some sites as low as 0.9%. A quintuple mutation was present in 12.8% (16/125) samples in Kilwa; 11.9% (13/109) in Kisangani, 2.9% (3/102) in Boende, and 0.9% (1/112) in Basankusu. These results suggest high resistance to pyrimethamine alone or combined with sulfadoxine. Adding artesunate to SP does not seem a valid alternative to the current monotherapy.
    • A significant increase in kdr in Anopheles gambiae is associated with an intensive vector control intervention in Burundi highlands.

      Protopopoff, N; Verhaeghen, K; Van Bortel, W; Roelants, P; Marcotty, T; Baza, D; D'Alessandro, U; Coosemans, M; Department of Parasitology, Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium. nprotopopoff@itg.be (2008-12)
      OBJECTIVES AND METHODS: In Burundi, the occurrence of the knock down resistance (kdr) mutation in Anopheles gambiae sensu lato (s.l.) was determined for six consecutive years within the framework of a vector control programme. Findings were also linked with the insecticide resistance status observed with bioassay in An. gambiae s.l. and An. funestus. RESULTS: The proportion of An. gambiae s.l. carrying the East Leu-Ser kdr mutation was 1% before the spraying intervention in 2002; by 2007 it was 86% in sprayed valleys and 67% in untreated valleys. Multivariate analysis showed that increased risk of carrying the kdr mutation is associated with spraying interventions, location and time. In bioassays conducted between 2005 and 2007 at five sites, An. funestus was susceptible to permethrin, deltamethrin and DDT. Anopheles gambiae s.l. remained susceptible or tolerant to deltamethrin and resistant to DDT and permethrin, but only when kdr allele carriers reached 90% of the population. CONCLUSIONS: The cross-resistance against DDT and permethrin in Karuzi suggests a possible kdr resistance mechanism. Nevertheless, the homozygous resistant genotype alone does not entirely explain the bioassay results, and other mechanisms conferring resistance cannot be ruled out. After exposure to all three insecticides, homozygote individuals for the kdr allele dominate among the surviving An. gambiae s.l. This confirms the potential selection pressure of pyrethroids on kdr mutation. However, the high occurrence of the kdr mutation, even at sites far from the sprayed areas, suggests a selection pressure other than that exerted by the vector control programme.
    • 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; et al. (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.
    • Sociocultural and Structural Factors Contributing to Delays in Treatment for Children with Severe Malaria: A Qualitative Study in Southwestern Uganda

      Sundararajan, Radhika; Mwanga-Amumpaire, Juliet; Adrama, Harriet; Tumuhairwe, Jackline; Mbabazi, Sheilla; Mworozi, Kenneth; Carroll, Ryan; Bangsberg, David; Boum, Yap; Ware, Norma C (American Society of Tropical Medicine and Hygiene, 2015-03-23)
      Malaria is a leading cause of pediatric mortality, and Uganda has the highest incidences in the world. Increased morbidity and mortality are associated with delays to care. This qualitative study sought to characterize barriers to prompt allopathic care for children hospitalized with severe malaria in the endemic region of southwestern Uganda. Minimally structured, qualitative interviews were conducted with guardians of children admitted to a regional hospital with severe malaria. Using an inductive and content analytic approach, transcripts were analyzed to identify and define categories that explain delayed care. These categories represented two broad themes: sociocultural and structural factors. Sociocultural factors were 1) interviewee's distinctions of "traditional" versus "hospital" illnesses, which were mutually exclusive and 2) generational conflict, where deference to one's elders, who recommended traditional medicine, was expected. Structural factors were 1) inadequate distribution of health-care resources, 2) impoverishment limiting escalation of care, and 3) financial impact of illness on household economies. These factors perpetuate a cycle of illness, debt, and poverty consistent with a model of structural violence. Our findings inform a number of potential interventions that could alleviate the burden of this preventable, but often fatal, illness. Such interventions could be beneficial in similarly endemic, low-resource settings.
    • Spatial targeted vector control in the highlands of Burundi and its impact on malaria transmission.

      Protopopoff, N; Van Bortel, W; Marcotty, T; Van Herp, M; Maes, P; Baza, D; D'Alessandro, U; Coosemans, M; Department of Parasitology, Prince Leopold Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium. nprotopopoff@itg.be (BMC, 2007)
      BACKGROUND: Prevention of malaria epidemics is a priority for African countries. The 2000 malaria epidemic in Burundi prompted the government to implement measures for preventing future outbreaks. Case management with artemisinin-based combination therapy and malaria surveillance were nationally improved. A vector control programme was initiated in one of the most affected highland provinces. The focal distribution of malaria vectors in the highlands was the starting point for designing a targeted vector control strategy. The objective of this study was to present the results of this strategy on malaria transmission in an African highland region. METHODS: In Karuzi, in 2002-2005, vector control activities combining indoor residual spraying and long-lasting insecticidal nets were implemented. The interventions were done before the expected malaria transmission period and targeted the valleys between hills, with the expectation that this would also protect the populations living at higher altitudes. The impact on the Anopheles population and on malaria transmission was determined by nine cross-sectional surveys carried out at regular intervals throughout the study period. RESULTS: Anopheles gambiae s.l. and Anopheles funestus represented 95% of the collected anopheline species. In the valleys, where the vector control activities were implemented, Anopheles density was reduced by 82% (95% CI: 69-90). Similarly, transmission was decreased by 90% (95% CI: 63%-97%, p = 0.001). In the sprayed valleys, Anopheles density was further reduced by 79.5% (95% CI: 51.7-91.3, p < 0.001) in the houses with nets as compared to houses without them. No significant impact on vector density and malaria transmission was observed in the hill tops. However, the intervention focused on the high risk areas near the valley floor, where 93% of the vectors are found and 90% of the transmission occurs. CONCLUSION: Spatial targeted vector control effectively reduced Anopheles density and transmission in this highland district. Bed nets have an additional effect on Anopheles density though this did not translate in an additional impact on transmission. Though no impact was observed in the hilltops, the programme successfully covered the areas most at risk. Such a targeted strategy could prevent the emergence and spread of an epidemic from these high risk foci.
    • Spatial targeted vector control is able to reduce malaria prevalence in the highlands of Burundi.

      Protopopoff, N; Van Bortel, W; Marcotty, T; Van Herp, M; Maes, P; Baza, D; D'Alessandro, U; Coosemans, M; Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium. nprotopopoff@itg.be (American Society of Tropical Medicine and Hygiene, 2008-07)
      In a highland province of Burundi, indoor residual spraying and long-lasting insecticidal net distribution were targeted in the valley, aiming also to protect the population living on the hilltops. The impact on malaria indicators was assessed, and the potential additional effect of nets evaluated. After the intervention--and compared with the control valleys--children 1-9 years old in the treated valleys had lower risks of malaria infection (odds ratio, OR: 0.55), high parasite density (OR: 0.48), and clinical malaria (OR: 0.57). The impact on malaria prevalence was even higher in infants (OR: 0.14). Using nets did not confer an additional protective effect to spraying. Targeted vector control had a major impact on malaria in the high-risk valleys but not in the less-exposed hilltops. Investment in targeted and regular control measures associated with effective case management should be able to control malaria in the highlands.
    • Successful introduction of artesunate combination therapy is not enough to fight malaria: results from an adherence study in Sierra Leone.

      Gerstl, Sibylle; Dunkley, Sophie; Mukhtar, Ahmed; Baker, Samuel; Maikere, Jacob; Médecins Sans Frontières (MSF) UK, 67-74 Saffron Hill, London EC1N 8QX, UK. (2010-02-01)
      A study to measure adherence to artesunate and amodiaquine (AS+AQ) therapy in patients treated for uncomplicated malaria in community health centres (CHC) was conducted in Sierra Leone. Patients/caretakers were interviewed and remaining AS+AQ tablets at home after the last treatment dose were counted. Persons leaving CHCs with an AS+AQ prescription were also interviewed (exit interviews). In total, 118 patients were visited at home: 27 (22.9%) had one or more tablets left and were classed as certainly non-adherent; 34 (28.8%) were probably non-adherent [reported incorrect (n=27) or incomplete (n=7) intake]; and 57 (48.3%) were probably adherent. The main reasons for incomplete intake were sickness after one dose of AS+AQ, no food available for drug intake and forgetting to take them. For incorrect intake, reasons were vomiting after drug intake and incorrect instructions given by the CHC. Eighty-one percent of probably adherent patients reported following instructions given to them. In exit interviews, 82% of patients or caretakers of patients were able to repeat AS+AQ intake instructions correctly. Adherence to antimalarial treatment should not be taken for granted. Instructions on correct AS+AQ use should include discussion of disease symptoms as well as possible treatment side effects and how to manage them. Other factors are more difficult to influence, such as patients forgetting to take the treatment.
    • Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda.

      Checchi, F; Piola, P; Fogg, C; Bajunirwe, F; Biraro, S; Grandesso, F; Ruzagira, E; Babigumira, J; Kigozi, I; Kiguli, J; et al. (BioMed Central, 2006)
      BACKGROUND: A six-dose antimalarial regimen of artemether-lumefantrine (A/L) may soon become one of the most widely used drug combination in Africa, despite possible constraints with adherence and poor absorption due to inadequate nutrition, and a lack of pharmacokinetic and effectiveness data. METHODS: Within a trial of supervised versus unsupervised A/L treatment in a stable Ugandan Plasmodium falciparum transmission setting, plasma lumefantrine concentrations were measured in a subset of patients on day 3 (C [lum]day3) and day 7 (C [lum]day7) post-inclusion. Predictors of lumefantrine concentrations were analysed to show how both C [lum]day7 and the weight-adjusted lumefantrine dose affect 28-day recrudescence and re-infection risks. The implications of these novel findings are discussed in terms of the emergence of lumefantrine-resistant strains in Africa. RESULTS: C [lum]day3 and C [lum]day7 distributions among 241 supervised and 238 unsupervised patients were positively skewed. Unsupervised treatment and decreasing weight-adjusted lumefantrine dose were negatively associated with C [lum]day3. Unsupervised treatment and decreasing age showed strong negative associations with C [lum]day7. Both models were poorly predictive (R-squared < 0.25). There were no recrudescences in either arm, but decreasing lumefantrine dose per Kg resulted in up to 13-fold higher adjusted risks of re-infection. Re-infections occurred only among patients with C [lum]day7 below 400 ng/mL (p < 0.001). CONCLUSION: Maintaining the present six-dose regimen and ensuring high adherence and intake are essential to maximize the public health benefits of this valuable drug combination.
    • Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial.

      Piola, P; Fogg, C; Bajunirwe, F; Biraro, S; Grandesso, F; Ruzagira, E; Babigumira, J; Kigozi, I; Kiguli, J; Kyomuhendo, J; et al. (Elsevier, 2005-04-23)
      BACKGROUND: The six-dose regimen of artemether-lumefantrine is effective and is among combination therapies prioritised to replace antimalarials that no longer work in Africa. However, its effectiveness has not been assessed in the field, and could be compromised by poor adherence, incorrect timing of doses, and insufficient intake of fatty foods with every dose. Our aim, therefore, was to assess the effectiveness of artemether-lumefantrine prescribed under routine outpatient conditions, compared with its efficacy when given under supervision to inpatients with acute uncomplicated falciparum malaria. METHODS: We did a randomised trial to compare the efficacy, safety, and pharmacokinetics of artemether-lumefantrine when given in a supervised (all doses observed with fatty-food intake; n=313) or unsupervised (first dose supervised followed by outpatient treatment with nutritional advice; n=644) setting to patients of all ages (weight >10 kg) with acute, uncomplicated falciparum malaria in Mbarara, Uganda. Our primary endpoint was 28 day, PCR-adjusted, parasitological cure rate. Analysis was by intention to treat and evaluability analysis. FINDINGS: 38 patients were lost to follow-up and one withdrew consent. Day-28 cure rates were 97.7% (296 of 303) and 98.0% (603 of 615) in the supervised and unsupervised groups, respectively. We recorded 15 non-severe, drug-related adverse events, all of which resolved. INTERPRETATION: Artemether-lumefantrine has a high cure rate irrespective of whether given under supervision with food or under conditions of routine clinic practice. If used as first-line treatment, artemether-lumefantrine could make a substantial contribution to malaria control in Africa, though cost is an issue.
    • Suppression of circulating IgD+CD27+ memory B cells in infants living in a malaria-endemic region of Kenya

      Asito, Amolo S; Piriou, Erwan; Jura, Walter GZO; Ouma, Collins; Odada, Peter S; Ogola, Sidney; Fiore, Nancy; Rochford, Rosemary; Maseno University, Maseno, Kenya; Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya; SUNY Upstate Medical University, Syracuse, NY; Medecins Sans Frontieres-Operational Centre Amsterdam, Amsterdam, The Netherlands (BioMed Central, 2011-12-13)
      Background: Plasmodium falciparum infection leads to alterations in B cell subset distribution. During infancy, development of peripheral B cell subsets is also occurring. However, it is unknown if infants living a malaria endemic region have alterations in B cell subsets that is independent of an age effect. Methods: To evaluate the impact of exposure to P. falciparum on B cell development in infants, flow cytometry was used to analyse the distribution and phenotypic characteristic of B cell subsets in infant cohorts prospectively followed at 12, 18 and 24 months from two geographically proximate regions in western Kenya with divergent malaria exposure i.e. Kisumu (malaria-endemic, n = 24) and Nandi (unstable malaria transmission, n = 21). Results: There was significantly higher frequency and absolute cell numbers of CD19+ B cells in Kisumu relative to Nandi at 12(p = 0.0440), 18(p = 0.0210) and 24 months (p = 0.0493). No differences were observed between the infants from the two sites in frequencies of naïve B cells (IgD+CD27-) or classical memory B cells (IgD-CD27+). However, immature transitional B cells (CD19+CD10+CD34-) were higher in Kisumu relative to Nandi at all three ages. In contrast, the levels of non-class switched memory B cells (CD19+IgD+CD27+) were significantly lower overall in Kisumu relative to Nandi at significantly at 12 (p = 0.0144), 18 (p = 0.0013) and 24 months (p = 0.0129). Conclusions: These data suggest that infants living in malaria endemic regions have altered B cell subset distribution. Further studies are needed to understand the functional significance of these changes and long-term impact on ability of these infants to develop antibody responses to P. falciparum and heterologous infections.
    • The Efficacy of Chloroquine for the Treatment of Acute, Uncomplicated, Plasmodium Falciparum Malaria in Laos.

      Guthmann, J P; Kasparian, S; Phetsouvanh, R; Nathan, N; Garcia, M; Phompida, S; Brockman, A; Gastellu-Etchegorry, M; Legros, D; Epicentre, 8 rue Saint Sabin, 75011 Paris, France. jguthmann@epicentre.msf.org (Published by: Maney Publishing, 2002-09)
      To assess the local efficacy of chloroquine for the treatment of acute, uncomplicated, Plasmodium falciparum malaria, children and adults from Sekong province (an area of Laos with a low intensity of transmission) were tested in a 28-day, in-vivo study. Complete data were collected from 88 of the 102 subjects enrolled between October 1999 and September 2000. After genotypic analysis to distinguish recrudescing infections from re-infections, 35 (39.7%, with a 95% confidence interval of 29.5%-50.7%) of these 88 patients were considered treatment failures. These results seriously question the use of chloroquine as the first-line treatment for P. falciparum malaria in the study area.
    • Timing of Malaria in Pregnancy and Impact on Infant Growth and Morbidity: a Cohort Study in Uganda

      De Beaudrap, P; Turyakira, E; Nabasumba, C; Tumwebaze, B; Piola, P; Boum Ii, Y; McGready, R (BioMed Central, 2016-02-16)
      Malaria in pregnancy (MiP) is a major cause of fetal growth restriction and low birth weight in endemic areas of sub-Saharan Africa. Understanding of the impact of MiP on infant growth and infant risk of malaria or morbidity is poorly characterized. The objective of this study was to describe the impact of MIP on subsequent infant growth, malaria and morbidity.
    • Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia

      Schramm, Birgit; Valeh, Parastou; Baudin, Elisabeth; Mazinda, Charles S; Smith, Richard; Pinoges, Loretxu; Sundaygar, Timothy; Zolia, Yah M; Jones, Joel J; Comte, Eric; et al. (BioMed Central, 2013-07-17)
      Safety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal.
    • Transmission of Plasmodium vivax in South-Western Uganda: Report of Three Cases in Pregnant Women

      Dhorda, Mehul; Nyehangane, Dan; Rénia, Laurent; Piola, Patrice; Guerin, Philippe J; Snounou, Georges; Epicentre, Mbarara, Uganda; Institut National de la Sante´ et de la Recherche Medicale,Paris, France; Universite´ Pierre et Marie Curie, Faculte´ de Me´decine Pitie´-Salpeˆ trie` re, Paris, France; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore; Epicentre, Paris, France; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom (2011-05-13)
      Plasmodium vivax is considered to be rare in the predominantly Duffy negative populations of Sub-Saharan Africa, as this red blood cell surface antigen is essential for invasion by the parasite. However, despite only very few reports of molecularly confirmed P. vivax from tropical Africa, serological evidence indicated that 13% of the persons sampled in Congo had been exposed to P. vivax. We identified P. vivax by microscopy in 8 smears from Ugandan pregnant women who had been enrolled in a longitudinal study of malaria in pregnancy. A nested polymerase chain reaction (PCR) protocol was used to detect and identify the Plasmodium parasites present. PCR analysis confirmed the presence of P. vivax for three of the women and analysis of all available samples from these women revealed clinically silent chronic low-grade vivax infections for two of them. The parasites in one woman carried pyrimethamine resistance-associated double non-synonymous mutations in the P. vivax dihydrofolate reductase gene. The three women found infected with P. vivax were Duffy positive as were nine of 68 women randomly selected from the cohort. The data presented from these three case reports is consistent with stable transmission of malaria in a predominantly Duffy negative African population. Given the substantial morbidity associated with vivax infection in non-African endemic areas, it will be important to investigate whether the distribution and prevalence of P. vivax have been underestimated in Sub-Saharan Africa. This is particularly important in the context of the drive to eliminate malaria and its morbidity.
    • Two-Year Scale-Up of Seasonal Malaria Chemoprevention Reduced Malaria Morbidity among Children in the Health District of Koutiala, Mali.

      Maiga, H; Gaudart, J; Sagara, I; Diarra, M; Bamadio, A; Djimde, M; Coumare, S; Sangare, B; Dicko, Y; Tembely, A; et al. (MDPI, 2020-09-11)
      Background: Previous controlled studies demonstrated seasonal malaria chemoprevention (SMC) reduces malaria morbidity by >80% in children aged 3-59 months. Here, we assessed malaria morbidity after large-scale SMC implementation during a pilot campaign in the health district of Koutiala, Mali. Methods: Starting in August 2012, children received three rounds of SMC with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ). From July 2013 onward, children received four rounds of SMC. Prevalence of malaria infection, clinical malaria and anemia were assessed during two cross-sectional surveys conducted in August 2012 and June 2014. Investigations involved 20 randomly selected clusters in 2012 against 10 clusters in 2014. Results: Overall, 662 children were included in 2012, and 670 in 2014. Children in 2014 versus those surveyed in 2012 showed reduced proportions of malaria infection (12.4% in 2014 versus 28.7% in 2012 (p = 0.001)), clinical malaria (0.3% versus 4.2%, respectively (p < 0.001)), and anemia (50.1% versus 67.4%, respectively (p = 0.001)). A propensity score approach that accounts for environmental differences showed that SMC conveyed a significant protective effect against malaria infection (IR = 0.01, 95% CI (0.0001; 0.09), clinical malaria (OR = 0.25, 95% CI (0.06; 0.85)), and hemoglobin concentration (β = 1.3, 95% CI (0.69; 1.96)) in 2012 and 2014, respectively. Conclusion: SMC significantly reduced frequency of malaria infection, clinical malaria and anemia two years after SMC scale-up in Koutiala.
    • Unresponsiveness to AmBisome in some Sudanese patients with kala-azar.

      Mueller, M; Ritmeijer, K; Balasegaram, M; Koummuki, Y; Santana, M R; Davidson, R N; Medécins Sans Frontières, Plantage Middenlaan 14, 1018 DD Amsterdam, The Netherlands. (Elsevier, 2007-01)
      In Sudan, two treatments are currently registered for visceral leishmaniasis: sodium stibogluconate (SSG) as first line and liposomal amphotericin B (AmBisome) as second line. We present 64 patients (52 relapse cases to SSG, 12 new but complicated cases) treated with AmBisome in eastern Sudan. AmBisome was administered at 2.5-8.2mg/kg (15-49mg/kg in total) per dose six times (days 1, 2, 3, 5, 10, 15) as an intravenous infusion. We measured outcome according to clinical response and parasitological clearance (lymph node aspiration). Patient outcomes fell into three groups: group 1, clinical responders (cured) with a negative test of cure (n=35); group 2, clinical responders with a positive test of cure (n=19); group 3, clinical non-responders (failures) with a positive test of cure (n=10). Of the 10 failures, six were already relapse cases. All of group 3, and 15 from group 2, were also treated with additional SSG (20mg/kg intramuscularly daily for 30-50 d) with resulting clinical and parasitological improvement. Parasite persistence and clinical failure were associated with a higher parasite density on admission (P<0.002) and underlying immunosuppressive disease: tuberculosis (three cases) or HIV (two cases). Because AmBisome monotherapy may fail in Sudan, a combination of AmBisome and SSG is recommended for relapse cases.
    • 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.
    • Validity, reliability and ease of use in the field of five rapid tests for the diagnosis of Plasmodium falciparum malaria in Uganda.

      Guthmann, J P; Ruiz, A; Priotto, G; Kiguli, J; Bonte, L; Legros, D; Epicentre, 4 rue Saint Sabin, 75011 Paris, France. jguthmann@epicentre.msf.org (Elsevier, 2008-02-14)
      A study was conducted to measure the overall performance of several rapid diagnostic tests for Plasmodium falciparum infection, in order to select the most appropriate test to be used in the field. A total of 742 patients attending the out-patient department of Mbarara Hospital with a clinical suspicion of malaria were included in the study. For each patient, a thick/thin film and 5 rapid tests based on the detection of histidine-rich protein II (HRP-II) (Paracheck Pf dipstick and device, ParaHIT f, Malaria Rapid and BIO P.F.) were performed. Outcomes were validity, inter-reader reliability and 'ease of use in the field', measured by both the general characteristics of the test and by the opinion of the readers. About half (57%) of the patients were positive for P. falciparum. The Paracheck Pf (dipstick and device) was considered as the most appropriate for the use in the field, being sensitive (97%), moderately specific (88%), reliable (kappa coefficient = 0.97), easy to use and cheap (about US$ 0.5/test). The ParaHIT f represented a good alternative.
    • Varying efficacy of artesunate+amodiaquine and artesunate+sulphadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in the Democratic Republic of Congo: a report of two in-vivo studies

      Bonnet, Maryline; Broek, Ingrid van den; van Herp, Michel; Urrutia, Pedro Pablo Palma; van Overmeir, Chantal; Kyomuhendo, Juliet; Ndosimao, Célestin Nsibu; Ashley, Elizabeth; Guthmann, Jean-Paul; Epicentre, Geneva, Switzerland; Epicentre, Paris, France; Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; Médecins Sans Frontières, Brussels, Belgium; Médecins Sans Frontières, Barcelona, Spain; Prince Leopold Institute of Tropical Medicine, Department of Parasitology, Antwerp, Belgium; Mbarara University of Science and Technology, Mbarara, Uganda; National Malaria Control Programme, Kinshasa, Democratic Republic of Congo; Unité des Maladies à Prévention Vaccinale, Département des Maladies Infectieuses, Institut de Veille Sanitaire, Saint-Maurice cedex, France (2009-10-08)
      BACKGROUND: Very few data on anti-malarial efficacy are available from the Democratic Republic of Congo (DRC). DRC changed its anti-malarial treatment policy to amodiaquine (AQ) and artesunate (AS) in 2005. METHODS: The results of two in vivo efficacy studies, which tested AQ and sulphadoxine-pyrimethamine (SP) monotherapies and AS+SP and AS+AQ combinations in Boende (Equatorial province), and AS+SP, AS+AQ and SP in Kabalo (Katanga province), between 2003 and 2004 are presented. The methodology followed the WHO 2003 protocol for assessing the efficacy of anti-malarials in areas of high transmission. RESULTS: Out of 394 included patients in Boende, the failure rates on day 28 after PCR-genotyping adjustment of AS+SP and AS+AQ were estimated as 24.6% [95% CI: 16.6-35.5] and 15.1% [95% CI: 8.6-25.7], respectively. For the monotherapies, failure rates were 35.9% [95% CI: 27.0-46.7] for SP and 18.3% [95% CI: 11.6-28.1] for AQ. Out of 207 patients enrolled in Kabalo, the failure rate on day 28 after PCR-genotyping adjustment was 0 [1-sided 95% CI: 5.8] for AS+SP and AS+AQ [1-sided 95% CI: 6.2]. It was 19.6% [95% CI: 11.4-32.7] for SP monotherapy. CONCLUSION: The finding of varying efficacy of the same combinations at two sites in one country highlights one difficulty of implementing a uniform national treatment policy in a large country. The poor efficacy of AS+AQ in Boende should alert the national programme to foci of resistance and emphasizes the need for systems for the prospective monitoring of treatment efficacy at sentinel sites in the country.
    • Vector control in a malaria epidemic occurring within a complex emergency situation in Burundi: a case study.

      Protopopoff, N; Van Herp, M; Maes, P; Reid, T; Baza, D; D'Alessandro, U; Van Bortel, W; Coosemans, M; Department of Parasitology, Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium. nprotopopoff@itg.be (BMC, 2007)
      BACKGROUND: African highlands often suffer of devastating malaria epidemics, sometimes in conjunction with complex emergencies, making their control even more difficult. In 2000, Burundian highlands experienced a large malaria outbreak at a time of civil unrest, constant insecurity and nutritional emergency. Because of suspected high resistance to the first and second line treatments, the provincial health authority and Médecins Sans Frontières (Belgium) decided to implement vector control activities in an attempt to curtail the epidemic. There are few reported interventions of this type to control malaria epidemics in complex emergency contexts. Here, decisions and actions taken to control this epidemic, their impact and the lessons learned from this experience are reported. CASE DESCRIPTION: Twenty nine hills (administrative areas) were selected in collaboration with the provincial health authorities for the vector control interventions combining indoor residual spraying with deltamethrin and insecticide-treated nets. Impact was evaluated by entomological and parasitological surveys. Almost all houses (99%) were sprayed and nets use varied between 48% and 63%. Anopheles indoor resting density was significantly lower in treated as compared to untreated hills, the latter taken as controls. Despite this impact on the vector, malaria prevalence was not significantly lower in treated hills except for people sleeping under a net. DISCUSSION: Indoor spraying was feasible and resulted in high coverage despite being a logistically complex intervention in the Burundian context (scattered houses and emergency situation). However, it had little impact on the prevalence of malaria infection, possibly because it was implemented after the epidemic's peak. Nevertheless, after this outbreak the Ministry of Health improved the surveillance system, changed its policy with introduction of effective drugs and implementation of vector control to prevent new malaria epidemics. CONCLUSION: In the absence of effective drugs and sufficient preparedness, present study failed to demonstrate any impact of vector control activities upon the course of a short-duration malaria epidemic. However, the experience gained lead to increased preparedness and demonstrated the feasibility of vector control measures in this specific context.