A CLINICAL STUDY OF FALCIPARUM MALARIA - 302 CASES.
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ABSTRACT:
SUBMITTER: Nandi B
PROVIDER: S-EPMC5531211 | biostudies-other | 1998 Jan
REPOSITORIES: biostudies-other
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Project description:Each year, thousands of cases of uncomplicated malaria are imported into Europe by travellers. Atovaquone-proguanil (AP) has been one of the first-line regimens used in France for uncomplicated malaria for almost ten years. While AP's efficacy and tolerance were evaluated in several trials, its use in "real life" conditions has never been described. This study aimed to describe outcome and tolerance after AP treatment in a large cohort of travellers returning from endemic areas.Between September 2002 and January 2007, uncomplicated malaria treated in nine French travel clinics with AP were followed for 30 days after AP initiation. Clinical and biological data were collected at admission and during the follow-up.A total of 553 patients were included. Eighty-eight percent of them were born in Africa, and 61.8% were infected in West Africa, whereas 0.5% were infected in Asia. Migrants visiting friends and relatives (VFR) constituted 77.9% of the patients, the remainder (32.1%) were backpackers. Three-hundred and sixty-four patients (66%) fulfilled follow-up at day 7 and 265 (48%) completed the study at day 30. Three patients had treatment failure. One-hundred and seventy-seven adverse drug reactions (ADR) were reported during the follow-up; 115 (77%) of them were digestive ADR. Backpackers were more likely to experiment digestive ADR compared to VFR (OR = 3.8; CI 95% [1.8-8.2]). Twenty patients had to be switched to another regimen due to ADR.This study seems to be the largest in terms of number of imported uncomplicated malaria cases treated by AP. The high rate of reported digestive ADR is striking and should be taken into account in the follow-up of patients since it could affect their adherence to the treatment. Beside AP, artemisinin combination therapy (ACT) is now recommended as first-line regimen. A comparison of AP and ACT, in terms of efficacy and tolerance, would be useful.
| S-EPMC3831254 | biostudies-other
Project description:Interest in mapping the global distribution of malaria is motivated by a need to define populations at risk for appropriate resource allocation and to provide a robust framework for evaluating its global economic impact. Comparison of older and more recent malaria maps shows how the disease has been geographically restricted, but it remains entrenched in poor areas of the world with climates suitable for transmission. Here we provide an empirical approach to estimating the number of clinical events caused by Plasmodium falciparum worldwide, by using a combination of epidemiological, geographical and demographic data. We estimate that there were 515 (range 300-660) million episodes of clinical P. falciparum malaria in 2002. These global estimates are up to 50% higher than those reported by the World Health Organization (WHO) and 200% higher for areas outside Africa, reflecting the WHO's reliance upon passive national reporting for these countries. Without an informed understanding of the cartography of malaria risk, the global extent of clinical disease caused by P. falciparum will continue to be underestimated.
| S-EPMC3128492 | biostudies-literature
Project description:BackgroundClinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria.MethodsThree datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African 'AQUAMAT' trial comparing artesunate and quinine (children), and the Vietnamese 'AQ' study (adults) comparing artemether with quinine. The absolute change, relative change, slope of the normalization over time, and time to normalization were derived from sequential measurements of plasma lactate and coma score, and validated for their use as surrogate endpoint, including the proportion of treatment effect on mortality explained (PTE) by these surrogate measures.ResultsImprovements in lactate concentration or coma scores over the first 24 hours of admission, were strongly prognostic for survival in all datasets. In hyperlactataemic patients in the AQ study (n = 173), lower mortality with artemether compared to quinine closely correlated with faster reduction in plasma lactate concentration, with a high PTE of the relative change in plasma lactate at 8 and 12 hours of 0.81 and 0.75, respectively. In paediatric patients enrolled in the 'AQUAMAT' study with cerebral malaria (n = 785), mortality was lower with artesunate compared to quinine, but this was not associated with faster coma recovery.ConclusionsThe relative changes in plasma lactate concentration assessed at 8 or 12 hours after admission are valid surrogate endpoints for severe malaria studies on antimalarial drugs or adjuvant treatments aiming at improving the microcirculation. Measures of coma recovery are not valid surrogate endpoints for mortality.
| S-EPMC5215574 | biostudies-literature
Project description:ObjectivesTo quantify geographical concentration of falciparum malaria cases in the UK at a hospital level. To assess potential delay-to-treatment associated with hub-and-spoke distribution of artesunate in severe cases.DesignObservational study using national and hospital data.Setting and participants3520 patients notified to the Malaria Reference Laboratory 2008-2010, 34 patients treated with intravenous artesunate from a tropical diseases centre 2002-2010.Main outcome measuresGeographical location of falciparum cases notified in the UK. Diagnosis-to-treatment times for intravenous artesunate.ResultsEight centres accounted for 43.9% of the UK's total cases; notifications from 107 centres accounted for 10.2% of cases; 51.5% of hospitals seeing malaria notified 5 or fewer cases in 3 years. Centres that saw <10 cases/year treat 26.3% of malaria cases; 6.1% of cases are treated in hospitals seeing <2 cases/year. Concentration of falciparum malaria was highest in Greater London (1925, 54.7%), South East (515, 14.6%), East of England (402, 11.4%) and North West (192, 5.4%). The North East and Northern Ireland each notified 5 or fewer cases per year. Median diagnosis-to-treatment time was 1 h (range 0.5-5) for patients receiving artesunate in the specialist centre; 7.5 h (range 4-26) for patients receiving it in referring hospitals via the hub-and-spoke system (p=0.02); 25 h (range 9-45) for patients receiving it on transfer to the regional centre from a referring hospital (p=0.002).ConclusionsMost UK hospitals see few cases of falciparum malaria and geographical distances are significant. Over 25% of cases are seen in hospitals where malaria is rare, although 60% are seen in hospitals seeing over 50 cases over 3 years. A hub-and-spoke system minimises drug wastage and ensures availability in centres seeing most cases but is associated with treatment delays elsewhere. As with all observational studies, there are limitations, which are discussed.
| S-EPMC3533059 | biostudies-literature
Project description:BackgroundFor rapid initiation of anti-malarial treatment and prevention of complications, early diagnosis and risk stratification is important in patients with Plasmodium falciparum malaria. Routine laboratory values do not correlate well with disease severity. The aim of this study was to determine the diagnostic and prognostic value of several biomarkers related to inflammation; endothelial and cardiac dysfunction; coagulation, and haemolysis in imported P. falciparum malaria.MethodsIn a prospective case-control study, 79 adult travellers with both uncomplicated and complicated P. falciparum malaria were included between 2007 and 2011. Forty-one healthy subjects were included as controls. Blood samples were obtained within 24 hours after first consultation to assess routine laboratory values as well as markers related to inflammation (PAPP-A, copeptin, CRP), endothelial activation (MPO, elastase-2, endothelin-1, sICAM-1, sVCAM-1), cardiac function (NT-proBNP, MR-proANP), coagulation (fibrinogen, D-dimers, platelet count), and haemolysis (LDH). Prognostic performance was assessed using the receiver operating characteristic curve (area under the curve = AUROC).ResultsTwelve (15.2%) patients had severe P. falciparum malaria. In the patient group, significant thrombocytopaenia was found, all other markers but PAPP-A were significantly elevated. Diagnostic performance was best for CRP with an AUROC of 1.00, followed by MPO (0.99), D-dimers (0.98), elastase-2 (0.98), and sICAM-1 (0.98). Biomarker levels did not correlate well with disease severity.ConclusionThe combination of travel history, fever prior to blood sampling, and CRP serum levels above or below 10.8 mg/l upon hospital admission, best discriminated between malaria patients and control persons. None of the biomarkers studied predicted the presence or the development of malaria complications, neither at the time of admission, nor during hospitalization.
| S-EPMC3724717 | biostudies-literature
Project description:To define the impact of asymptomatic malaria, we pursued a systems approach integrating antibody responses, mass cytometry, and transcriptional profiling of individuals experiencing symptomatic and asymptomatic P. falciparum infection. Defined populations of classical and atypical memory B cells and a TH2 cell bias were associated with reduced risk of clinical malaria. Despite these protective responses, asymptomatic malaria featured an immunosuppressive transcriptional signature with upregulation of pathways involved in the inhibition of T cell function, and CTLA-4 as a predicted regulator in these processes.
2022-02-21 | GSE181179 | GEO
Project description:Malaria still continues to be the most important parasitic disease worldwide, affecting 228 million people and causing 405,000 deaths each year. In this retrospective study during 2013 to 2018, we documented the incidence of imported malaria infection and evaluated the impact of malaria preventive measures in Kuwait, a non-endemic country. The epidemiologic and demographic data of all malaria cases was collected from the Infectious Diseases Hospital, Kuwait where all suspected cases of malaria are referred for confirmation and therapeutic intervention. The diagnosis of malaria infection was done by microscopy of Giemsa stained blood films. Selected samples were retested with BinaxNOW® Malaria rapid test and molecular assay to reconfirm the Plasmodium spp. or mixed infection. Overall, 1913 (25.9%) malaria cases were detected, 81.5% of which were among male subjects. Male subjects had higher incidence of P. vivax malaria (113; 91.1%) and mixed infection with P. falciparum and P. vivax (1245; 90.0%) compared to females who had higher rate of P. falciparum infection (52.4%). An overwhelming majority of malaria cases (1895; 99.1%) were detected among expatriates from malaria-endemic countries; India (1012; 52.9%), Pakistan (390; 20.4%), Afghanistan (94; 4.9%) and African countries (313; 16.3%). Only 18 cases involved Kuwaiti nationals, all with a history of travel to African countries. The majority of malaria cases were detected during the summer and fall months (May-October). Our data showed that the incidence rate of imported malaria cases was stable during 2013 to 2018, however, the incidence of total malaria cases showed a declining trend over the years. This study confirms that the preventive program has been successful in reducing the incidence of imported malaria infections in Kuwait. The most striking finding of this study was high incidence of mixed infection with P. falciparum and P. vivax, with almost all (97%) cases among workers from India.
| S-EPMC7732060 | biostudies-literature
Project description:The need to expand malaria diagnosis capabilities alongside policy requirements for mandatory testing before treatment motivates exploration of noninvasive rapid diagnostic tests (RDTs). We report the outcome of the first cross-sectional, single-blind clinical performance evaluation of a urine malaria test (UMT) for diagnosis of Plasmodium falciparum malaria in febrile patients. Matched urine and finger-prick blood samples from participants ?2 years of age with fever (axillary temperature of ?37.5°C) or with a history of fever in the preceding 48 h were tested with UMT and microscopy (as the gold standard). BinaxNOW (Pf and Pan versions) blood RDTs were done to assess relative performance. Urinalysis and rheumatoid factor (RF) tests were conducted to evaluate possible interference. Diagnostic performance characteristics were computed at 95% confidence intervals (CIs). Of 1,800 participants screened, 1,691 were enrolled; of these 566 (34%) were febrile, and 1,125 (66%) were afebrile. Among enrolled participants, 341 (20%) tested positive by microscopy, 419 (25%) were positive by UMT, 676 (40%) were positive by BinaxNOW Pf, and 368 (22%) were positive by BinaxNow Pan. UMT sensitivity among febrile patients (for whom the test was indicated) was 85%, and specificity was 84%. Among febrile children ?5 years of age, UMT sensitivity was 93%, and specificity was 83%. The area under the receiver-operator characteristic curve (AUC) of UMT (0.84) was not significantly different from that of BinaxNOW Pf (0.86) or of BinaxNOW Pan (0.87), indicating that the tests do not differ in overall performance. Gender, seasons, and RF did not impact UMT performance. Leukocytes, hematuria, and urobilinogen concentrations in urine were associated with lower UMT specificities. UMT performance was comparable to that of the BinaxNOW Pf/Pan tests, making UMT a promising tool to expand malaria testing in public and private health care settings where there are challenges to blood-based malaria diagnosis testing.
| S-EPMC5228238 | biostudies-literature
Project description:The epidemiology of malaria makes surveillance-based methods of estimating its disease burden problematic. Cartographic approaches have provided alternative malaria burden estimates, but there remains widespread misunderstanding about their derivation and fidelity. The aims of this study are to present a new cartographic technique and its application for deriving global clinical burden estimates of Plasmodium falciparum malaria for 2007, and to compare these estimates and their likely precision with those derived under existing surveillance-based approaches.In seven of the 87 countries endemic for P. falciparum malaria, the health reporting infrastructure was deemed sufficiently rigorous for case reports to be used verbatim. In the remaining countries, the mapped extent of unstable and stable P. falciparum malaria transmission was first determined. Estimates of the plausible incidence range of clinical cases were then calculated within the spatial limits of unstable transmission. A modelled relationship between clinical incidence and prevalence was used, together with new maps of P. falciparum malaria endemicity, to estimate incidence in areas of stable transmission, and geostatistical joint simulation was used to quantify uncertainty in these estimates at national, regional, and global scales. Combining these estimates for all areas of transmission risk resulted in 451 million (95% credible interval 349-552 million) clinical cases of P. falciparum malaria in 2007. Almost all of this burden of morbidity occurred in areas of stable transmission. More than half of all estimated P. falciparum clinical cases and associated uncertainty occurred in India, Nigeria, the Democratic Republic of the Congo (DRC), and Myanmar (Burma), where 1.405 billion people are at risk. Recent surveillance-based methods of burden estimation were then reviewed and discrepancies in national estimates explored. When these cartographically derived national estimates were ranked according to their relative uncertainty and replaced by surveillance-based estimates in the least certain half, 98% of the global clinical burden continued to be estimated by cartographic techniques.Cartographic approaches to burden estimation provide a globally consistent measure of malaria morbidity of known fidelity, and they represent the only plausible method in those malaria-endemic countries with nonfunctional national surveillance. Unacceptable uncertainty in the clinical burden of malaria in only four countries confounds our ability to evaluate needs and monitor progress toward international targets for malaria control at the global scale. National prevalence surveys in each nation would reduce this uncertainty profoundly. Opportunities for further reducing uncertainty in clinical burden estimates by hybridizing alternative burden estimation procedures are also evaluated.
| S-EPMC2885984 | biostudies-literature
Project description:Malaria remains a major cause of childhood deaths in resource-limited settings. In the absence of an effective vaccine, drugs and other interventions have played very significant roles in combating the scourge of malaria. The recent reports of resistance to artemisinin necessitate the need for new antimalarial drugs with novel mechanisms of action. Towards the development of new, affordable and easily accessible antimalarial drugs for endemic regions, the Medicines for Malaria Venture (MMV) assembled a total of 400 active antimalarial compounds called the Malaria Box. The potency and the efficacy of the Malaria Box Compounds have been determined mainly using laboratory strains of P. falciparum. This study investigated the potency of twenty compounds from the Malaria Box against four clinical isolates from Ghana, using optimized in vitro growth inhibitory assays. Seven out of the 20 compounds screened had 50% inhibitory concentration (IC50) below 500 nM. The most active among the selected compounds was MMV006087 (average IC50 of 30.79 nM). Variations in the potency of the Malaria Box Compounds were observed between P. falciparum clinical isolates and Dd2 strain. We also investigated the sensitivity of the clinical isolates to chloroquine and artesunate. The N093 clinical isolate was found to be resistant to chloroquine but showed high sensitivity to artesunate. The results underscore the importance of including clinical isolates with different drug-resistant backgrounds, in addition to laboratory strains, in validating potential compounds during antimalarial compound screening programs.
| S-EPMC5683671 | biostudies-literature