Malaria Journal - Latest Articles

Artemether-lumefantrine treatment failure despite adequate lumefantrine day 7 concentration in a traveller with Plasmodium falciparum malaria after returning from Tanzania

Anna Färnert — 2012-05-25T00:00:00Z

Artemether-lumefantrine is currently first-line therapy of Plasmodium falciparum malaria in many countries. This report describes a treatment failure despite adequate drug concentrations in a traveller returning from sub-Saharan Africa. Genotyping confirmed recrudescence and suggested reduced sensitivity. Potential sub-optimal effect of artemetherlumefantrine highlights the need to follow non-immune individuals the weeks after treatment.

Quantitative detection of PfHRP2 in saliva of malaria patients in the Philippines

Andrew Fung — 2012-05-25T00:00:00Z

Background: Malaria is a global health priority with a heavy burden of fatality and morbidity. Improvements in field diagnostics are needed to support the agenda for malaria elimination. Saliva has shown significant potential for use in non-invasive diagnostics, but the development of off-the-shelf saliva diagnostic kits requires best practices for sample preparation and quantitative insight on the availability of biomarkers and the dynamics of immunoassay in saliva. This pilot study measured the levels of the PfHRP2 in patient saliva to inform the development of salivary diagnostic tests for malaria. Methods: Matched samples of blood and saliva were collected between January and May, 2011 from eight patients at Palawan Baptist Hospital in Roxas, Palawan, Philippines. Parasite density was determined from thick-film blood smears. Concentrations of PfHRP2 in saliva of malaria-positive patients were measured using a custom chemiluminescent ELISA in microtitre plates. Sixteen negative-control patients were enrolled at UCLA. A substantive difference between this protocol and previous related studies was that saliva samples were stabilized with protease inhibitors. Results: Of the eight patients with microscopically confirmed P. falciparum malaria, seven tested positive for PfHRP2 in the blood using rapid diagnostic test kits, and all tested positive for PfHRP2 in saliva. All negative-control samples tested negative for salivary Pf HRP2. On a binary-decision basis, the ELISA greed with microscopy with 100 % sensitivity and 100 % specificity. Salivary levels of PfHRP2 ranged from 17 to 1,167 pg/mL in the malaria-positive group. Conclusion: Saliva is a promising diagnostic fluid for malaria when protein degradation and matrix effects are mitigated. Systematic quantitation of other malaria biomarkers in saliva would identify those with the best clinical relevance and suitability for off-the-shelf diagnostic kits.

Efficacy of fixed-dose combination artesunateamodiaquine versus artemether-lumefantrine for uncomplicated childhood plasmodium falciparum malaria in democratic republic of congo: a randomized non-inferiority trial

Emmanuelle Espié — 2012-05-25T00:00:00Z

Background: In 2005, the Democratic Republic of Congo (DRC) adopted artesunate and amodiaquine (ASAQ) as first-line anti-malarial treatment. In order to compare the efficacy of the fixeddose formulation ASAQ versus artemether-lumefantrine (AL), a randomized, non-inferiority open-label trial was conducted in Katanga. Methods: Children aged six and 59 months with uncomplicated Plasmodium falciparum malaria were enrolled and randomly allocated into one of the two regimens. The risk of recurrent parasitaemia by day 42, both unadjusted and adjusted by PCR genotyping to distinguish recrudescence from new infection, was analysed. Results: Between April 2008 and March 2009, 301 children were included: 156 with ASAQ and 145 with AL. No early treatment failures were reported. Among the 256 patients followed-up at day 42, 32 patients developed late clinical or parasitological failure (9.9% (13/131) in the ASAQ group and 15.2% (19/125) in the AL group). After PCR correction, cure rates were 98.3% (95%CI, 94.1-99.8) in the ASAQ group and 99.1% (95%CI, 94.9-99.9) in the AL group (difference 0.7%, one sided 95% CI 3.1). Kaplan-Meier PCR-adjusted cure rates were similar. Both treatment regimens were generally well tolerated. Conclusion: Both ASAQ and AL are highly effective and currently adequate as he first-line treatment of uncomplicated falciparum malaria in this area of Katanga, DRC. However, in a very large country, such as DRC, and because of possible emergence of resistance from other endemic regions, surveillance of efficacy of artemisinin-based combination treatments, including other evaluations of the resistance of ASAQ, need to be done in other provinces.Trial registrationThe protocol was registered with the clinicaltrials.gov, open clinical trial registry under the identifier number NCT01567423.

Suppression of erythroid development in vitro by Plasmodium vivax

Tasanee Panichakul — 2012-05-24T00:00:00Z

Background: Severe anaemia due to dyserythropoiesis has been documented in patients infected withPlasmodium vivax, however the mechanism responsible for anaemia in vivax malaria ispoorly understood. In order to better understand the role of P. vivax infection in anaemia theinhibition of erythropoiesis using haematopoietic stem cells was investigated. Methods: Haematopoietic stem cells/CD34+ cells, isolated from normal human cord blood were used togenerate growing erythroid cells. Exposure of CD34+ cells and growing erythroid cells to P.vivax parasites either from intact or lysed infected erythrocytes (IE) was examined for theeffect on inhibition of cell development compared with untreated controls. Results: Both lysed and intact infected erythrocytes significantly inhibited erythroid growth. Thereduction of erythroid growth did not differ significantly between exposure to intact andlysed IE and the mean growth relative to unexposed controls was 59.4 +/- 5.2 for lysed IE and57 +/- 8.5% for intact IE. Interestingly, CD34+ cells/erythroid progenitor cells were susceptibleto the inhibitory effect of P. vivax on cell expansion. Exposure to P. vivax also inhibitederythroid development, as determined by the reduced expression of glycophorin A (28.1%)and CD 71 (43.9%). Moreover, vivax parasites perturbed the division of erythroid cells, asmeasured by the Cytokinesis Block Proliferation Index, which was reduced to 1.35 +/- 0.05 (Pvalue< 0.01) from a value of 2.08 +/- 0.07 in controls. Neither TNF-a nor IFN-g was detectedin the culture medium of erythroid cells treated with P. vivax, indicating that impairederythropoiesis was independent of these cytokines. Conclusions: This study shows for the first time that P. vivax parasites inhibit erythroid developmentleading to ineffective erythropoiesis and highlights the potential of P. vivax to cause severeanaemia.

An affordable, quality-assured community-based system for high-resolution entomological surveillance of vector mosquitoes that reflects human malaria infection risk patterns

Prosper Chaki — 2012-05-24T00:00:00Z

Background: More sensitive and scalable entomological surveillance tools are required to monitor low levels of transmission that are increasingly common across the tropics, particularly where vector control has been successful. A large-scale larviciding programme in urban Dar es Salaam, Tanzania is supported by a community-based (CB) system for trapping adult mosquito densities to monitor programme performance.MethodologyAn intensive and extensive CB system for routine, longitudinal, programmatic surveillance of malaria vectors and other mosquitoes using the Ifakara Tent Trap (ITT-C) was developed in Urban Dar es Salaam, Tanzania, and validated by comparison with quality assurance (QA) surveys using either ITT-C or human landing catches (HLC), as well as a cross-sectional survey of malaria parasite prevalence in the same housing compounds. Results: Community-based ITT-C had much lower sensitivity per person-night of sampling than HLC (Relative Rate (RR) [95% Confidence Interval (CI)] = 0.079 [0.051, 0.121], P < 0.001 for Anopheles gambiae s.l. and 0.153 [0.137, 0.171], P < 0.001 for Culicines) but only moderately differed from QA surveys with the same trap (0.536 [0.406,0.617], P = 0.001 and 0.747 [0.677,0.824], P < 0.001, for An. gambiae or Culex respectively). Despite the poor sensitivity of the ITT per night of sampling, when CB-ITT was compared with QA-HLC, it proved at least comparably sensitive in absolute terms (171 versus 169 primary vectors caught) and cost-effective (153US$ versus 187US$ per An. gambiae caught) because it allowed more spatially extensive and temporally intensive sampling (4284 versus 335 trap nights distributed over 615 versus 240 locations with a mean number of samples per year of 143 versus 141). Despite the very low vectors densities (Annual estimate of about 170 An gambiae s.l bites per person per year), CB-ITT was the only entomological predictor of parasite infection risk (Odds Ratio [95% CI] = 4.43[3.027,7. 454] per An. gambiae or Anopheles funestus caught per night, P =0.0373).Discussion and conclusionCB trapping approaches could be improved with more sensitive traps, but already offer a practical, safe and affordable system for routine programmatic mosquito surveillance and clusters could be distributed across entire countries by adapting the sample submission and quality assurance procedures accordingly.

Quality of life and satisfaction with life of malaria patients in context of acceptance of the disease: quantitative studies

Katarzyna Van Damme-Ostapowicz — 2012-05-22T00:00:00Z

Background: Health status is one of the basic factors of a high quality of life and the problem of theacceptance of illness is important for adaptation to the limitations imposed by it. The purposeof the study was the evaluation of the quality of life, satisfaction with life and the acceptanceof illness by malaria patients, as well as the discovery of a relationship between studiedparameters. Methods: The study was undertaken in August 2010, on 120 Nigerian patients with confirmed malaria.A method of diagnostic survey, based on standardized scales - Acceptance of Illness Scale,The Satisfaction With Life Scale and a standardized survey questionnaire World HealthOrganization Quality of Life/BREF - was used in this study. Descriptive statistics, variabilityrange, 95% confidence interval, correlation analysis, Spearman's non-parametric correlationcoefficient, Mann-Whitney test and Kruskal-Wallis test were applied and the, so called, teststatistics was calculated, followed by the calculation of the test probability p. Results ofanalyses were presented in a box graph, and a graph of dispersion. Results: A dominating share in the adjective scale of the AIS scale was the category of "noacceptance", given by 71.7% of respondents. The average level of a "somatic domain" was41.7, and of a "social domain" was 62.8. The mean satisfaction of life evaluation in theSWLS scale was 18 points. The correlation between acceptance of the disease and quality oflife for the psychological domain was 0.39***, and between acceptance of the disease andsatisfaction with life was 0.40***. The correlation between satisfaction with life and qualityof life for the psychological domain was 0.65***, and between satisfaction with life andquality of life for the environment domain was 0.60***. The mean level of AIS for thestudied population of men was 16.5, and test probability: p = 0.0014**, and for theenvironment domain the level was 50, and the test probability: p = 0.0073**. For quality oflife in the social sphere the test probability: p = 0.0013** in relatively older individuals. Conclusion: The majority of people do not accept their condition. Evaluation of the quality of life was thehighest in the social domain, and the lowest in the somatic domain. There is a statisticallysignificant correlation between the level of acceptance of illness and the quality of life andsatisfaction with life. The strongest correlation is found between satisfaction with life and theevaluation of the quality of life in psychological and environmental domains. Men evaluatetheir quality of life in the environmental domain higher and demonstrate a higher acceptanceof their disease. There is a correlation regarding a significantly higher quality of life in thesocial sphere in relatively older people.

Characterizing the spatial and temporal variation of malaria incidence in Bangladesh, 2007

Heidi Reid — 2012-05-21T00:00:00Z

Background: Malaria remains a significant health problem in Bangladesh affecting 13 of 64 districts. Therisk of malaria is variable across the endemic areas and throughout the year. A betterunderstanding of the spatial and temporal patterns in malaria risk and the determinantsdriving the variation are crucial for the appropriate targeting of interventions under theNational Malaria Control and Prevention Programme. Methods: Numbers of Plasmodium falciparum and Plasmodium vivax malaria cases reported by monthin 2007, across the 70 endemic thanas (sub-districts) in Bangladesh, were assembled fromhealth centre surveillance reports. Bayesian Poisson regression models of incidence wereconstructed, with fixed effects for monthly rainfall, maximum temperature and elevation, andrandom effects for thanas, with a conditional autoregressive prior spatial structure. Results: The annual incidence of reported cases was 34.0 and 9.6 cases/10,000 population for P.falciparum and P. vivax respectively and the population of the 70 malaria-endemic thanaswas approximately 13.5 million in 2007. Incidence of reported cases for both types of malariawas highest in the mountainous south-east of the country (the Chittagong Hill Tracts).Models revealed statistically significant positive associations between the incidence ofreported P. vivax and P. falciparum cases and rainfall and maximum temperature. Conclusions: The risk of P. falciparum and P. vivax was spatially variable across the endemic thanas ofBangladesh and also highly seasonal, suggesting that interventions should be targeted andtimed according to the risk profile of the endemic areas. Rainfall, temperature and elevationare major factors driving the spatiotemporal patterns of malaria in Bangladesh.

Post-treatment haemolysis in severe imported malaria after intravenous artesunate: case report of three patients with hyperparasitaemia

Thierry Rolling — 2012-05-17T00:00:00Z

Parenteral artesunate has been shown to be a superior treatment option compared toparenteral quinine in adults and children with severe malaria. Little evidence, however, isavailable on long-term safety. Recently, cases of late-onset haemolysis after parenteraltreatment with artesunate have been reported in European travellers with importedPlasmodium falciparum malaria. Therefore, an extended follow-up of adult patients treatedfor severe imported malaria was started in August 2011 at the University Medical CenterHamburg-Eppendorf.Until January 2012, three patients with hyperparasitaemia (range: 14-21%) were included foranalysis. In all three patients, delayed haemolysis was detected in the second week after thefirst dose of intravenous artesunate. Reticulocyte production index remained inadequatelylow in the 7 - 14 days following the first dose of artesunate despite rapid parasite clearance.Post-treatment haemolysis after parenteral artesunate may be of clinical relevance inparticular in imported severe malaria characterized by high parasite levels. Extended followupof at least 30 days including controls of haematological parameters after artesunatetreatment seems to be indicated. Further investigations are needed to assess frequency andpathophysiological background of this complication.

Toll-like receptor 9 (TLR9) polymorphism associated with symptomatic malaria: a cohort study

Ahmeddin Omar — 2012-05-17T00:00:00Z

Background: In areas mesoendemic for malaria transmission, symptomatic individuals play a significantrole as reservoirs for malaria infection. Understanding the pathogenesis of symptomaticmalaria is important in devising tools for augmenting malaria control. In this study, the effectof TLR9 polymorphisms on susceptibility to symptomatic malaria was investigated amongGhanaian children. Methods: Four hundred and twenty nine (429) healthy Ghanaian children, aged three to eleven years(3-11 years), were enrolled into a cohort study and actively followed up for symptomaticmalaria for one year. Four TLR9 single nucleotide polymorphisms (SNPs) namely: rs187084(C-1486 T), rs5743836(C-1237 T), rs352139 (G + 1174A) and rs352140 (G + 2848A) weregenotyped by direct sequencing, and their attributable and relative risks for symptomaticmalaria determined. TLR9 haplotypes were inferred using the PHASE software and analysedfor the risk of symptomatic malaria. A luciferase assay was performed to investigate whetherthe TLR9 haplotypes influence TLR9 promoter activity. Results: The rs352139 GG genotype showed a significantly increased relative risk of 4.8 forsymptomatic malaria (P = 0.0024) and a higher mean parasitaemia (P = 0.04). Conversely,the rs352140 GG genotype showed a significantly reduced relative risk of 0.34 (P = 0.048).TLR9 haplotypes analyses showed that TTAG haplotype was significantly associated withreduced relative risk of 0.2 for symptomatic malaria (P = 4x10-6) and a lower meanparasitaemia (0.007), while CTGA haplotype had an increased relative risk of 3.3 (P =0.005). Functional luciferase reporter gene expression assay revealed that the TTA haplotypehad a significantly higher promoter activity than the CCG, CTG and TCG haplotypes. Conclusions: Taken together, these findings indicate a significant association of TLR9 genepolymorphisms with symptomatic malaria among Ghanaian children in Dangme-Westdistrict.

Efficacy of ICON(R) Maxx in the laboratory and against insecticide-resistant Anopheles gambiae in central Cote d'Ivoire

Mirko Winkler — 2012-05-15T00:00:00Z

Background: Long-lasting treatment kits, designed to transform untreated nets into long-lasting insecticidal nets (LLINs), may facilitate high coverage with LLINs where non-treated nets are in place. In this study, the efficacy of ICON(R) Maxx (Syngenta) was evaluated under laboratory conditions and in an experimental hut trial in central Cote d'Ivoire, where Anopheles gambiae s.s. are resistant to pyrethroid insecticides. Methods: In the laboratory, polyester and polyethylene net samples were treated with ICON(R) Maxx, washed up to 20 times and their efficacy determined in World Health Organization (WHO) cone assays against a susceptible laboratory An. gambiae s.s. colony. Over a 12-month period, the polyester nets were evaluated in a hut trial to determine mosquito deterrence, induced exophily, blood-feeding inhibition and mortality. Results: In the laboratory, ICON(R) Maxx-treated polyethylene nets showed higher efficacy against pyrethroid-susceptible mosquitoes than polyester nets. After 20 washings, insecticidal efficacy in bioassays was 59.4% knockdown (KD) and 22.3% mortality for polyethylene, and 55.3% KD and 17.9% mortality for polyester nets. In experimental huts, treated nets showed strong deterrence, induced exophily and an over three-fold reduction in blood-fed mosquitoes. More than half (61.8%) of the mosquitoes entering the huts with treated nets were found dead the next morning despite high levels of KD resistance. After washing the treated nets, KD and mortality rates were close to or exceeded predefined WHO thresholds in cone bioassays. Conclusion: In contrast to previous laboratory investigation, ICON(R) Maxx-treated nets showed only moderate KD and mortality rates. However, under semi-field conditions, in an area where mosquitoes are resistant to pyrethroids, ICON(R) Maxx showed high deterrence, induced exophily and provided a significant reduction in blood-feeding rates; features that are likely to have a positive impact in reducing malaria transmission. The WHO cone test may not always be a good proxy for predicting product performance under field conditions.