Use of a pLDH-based dipstick in the diagnostic and therapeutic follow-up of malaria patients in Mali

<p>Abstract</p> <p>Background</p> <p>Malaria is a major public health problem in Mali and diagnosis is typically based on microscopy. Microscopy requires a well trained technician, a reliable power source, a functioning microscope and adequate supplies. The scarcity of resources of community health centres (CHC) does not allow for such a significant investment in only one aspect of malaria control. In this context, Rapid Diagnostic Tests (RDTs) may improve case management particularly in remote areas.</p> <p>Methods</p> <p>This multicentre study included 725 patients simultaneously screened with OptiMal-IT test and thick smears for malaria parasite detection. While evaluating the therapeutic efficacy of choroquine in 2 study sites, we compared the diagnostic values of thick smear microscopy to OptiMal-IT test applying the WHO 14 days follow-up scheme using samples collected from 344 patients.</p> <p>Results</p> <p>The sensitivity and the specificity of OptiMal-IT compared to thick smear was 97.2% and 95.4%, whereas the positive and negative predictive values were 96.7 and 96.1%, respectively. The percent agreement between the two diagnostic tests was 0.93. The two tests were comparable in detecting malaria at day 0, day 3 and day 14. The only difference was observed at day 7 due to high gametocytemia. Subjectively, health care providers found OptiMal-IT easier to use and store under field conditions.</p> <p>Conclusion</p> <p>OptiMal-IT test revealed similar results when compared to microscopy which is considered the gold standard for malaria diagnostics. The test was found to have a short processing time and was easier to use. These advantages may improve malaria case management by providing a diagnostic and drug efficacy follow-up tool to peripheral health centres with limited resources.</p

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations

Safety and Immunogenicity of an AMA-1 Malaria Vaccine in Malian Adults: Results of a Phase 1 Randomized Controlled Trial

The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria.A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 microg/AS02A 0.25 mL or FMP2.1 50 microg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively.The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site

Plasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes

Following Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one or more severe malaria symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions have yet been drawn. Here, we apply a series of bioinformatic approaches based on P. falciparum’s tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to publicly available transcriptomes of parasites obtained from malaria cases of differing clinical severity across multiple studies. Our analysis shows that within each IDC, the circulation time of infected erythrocytes without sequestering to endothelial cells decreases with increasing parasitaemia or disease severity. Accordingly, we find that the size of circulating infected erythrocytes is inversely related to parasite density and disease severity. We propose that enhanced dhesiveness of infected erythrocytes leads to a rapid increase in parasite burden, promoting higher parasitaemia and increased disease severity

Serologic responses to the PfEMP1 DBL-CIDR head structure may be a better indicator of malaria exposure than those to the DBL-α tag

BackgroundPlasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) antigens play a critical role in host immune evasion. Serologic responses to these antigens have been associated with protection from clinical malaria, suggesting that antibodies to PfEMP1 antigens may contribute to natural immunity. The first N-terminal constitutive domain in a PfEMP1 is the Duffy binding-like alpha (DBL-α) domain, which contains a 300 to 400 base pair region unique to each particular protein (the DBL-α "tag"). This DBL-α tag has been used as a marker of PfEMP1 diversity and serologic responses in malaria-exposed populations. In this study, using sera from a malaria-endemic region, responses to DBL-α tags were compared to responses to the corresponding entire DBL-α domain (or "parent" domain) coupled with the succeeding cysteine-rich interdomain region (CIDR).MethodsA protein microarray populated with DBL-α tags, the parent DBL-CIDR head structures, and downstream PfEMP1 protein fragments was probed with sera from Malian children (aged 1 to 6&nbsp;years) and adults from the control arms of apical membrane antigen 1 (AMA1) vaccine clinical trials before and during a malaria transmission season. Serological responses to the DBL-α tag and the DBL-CIDR head structure were measured and compared in children and adults, and throughout the season.ResultsMalian serologic responses to a PfEMP1's DBL-α tag region did not correlate with seasonal malaria exposure, or with responses to the parent DBL-CIDR head structure in either children or adults. Parent DBL-CIDR head structures were better indicators of malaria exposure.ConclusionsLarger PfEMP1 domains may be better indicators of malaria exposure than short, variable PfEMP1 fragments such as DBL-α tags. PfEMP1 head structures that include conserved sequences appear particularly well suited for study as serologic predictors of malaria exposure

Candidate polymorphisms and severe malaria in a Malian population.

Malaria is a major health burden in sub-Saharan African countries, including Mali. The disease is complex, with multiple genetic determinants influencing the observed variation in response to infection, progression, and severity. We assess the influence of sixty-four candidate loci, including the sickle cell polymorphism (HbS), on severe malaria in a case-control study consisting of over 900 individuals from Bamako, Mali. We confirm the known protective effects of the blood group O and the HbS AS genotype on life-threatening malaria. In addition, our analysis revealed a marginal susceptibility effect for the CD40 ligand (CD40L)+220C allele. The lack of statistical evidence for other candidates may demonstrate the need for large-scale genome-wide association studies in malaria to discover new polymorphisms. It also demonstrates the need for establishing the region-specific repertoire of functional variation in important genes, including the glucose-6-phosphatase deficiency gene, before embarking on focused genotyping

Efficacité de la spiruline comparée aux méthodes classiques dans la lutte contre la malnutrition infantile au Mali

Current context: Malnutrition in the world is currently at the origin of 54% of the deaths of children below äns (1,2). In Mali, according to the EDSM IV, 15% of the children suffer from emaciation and 27% from the children, of ponderal insufficiency. Drank: The goal is to determine the effectiveness of a nutritional recovery containing spiruline as a multi-vitamin natural supplement and multi-microéléments in infantile flours at children from 0 to 59 months malnutris in Sabalibougou, and to compare it with that of fish and flours infantile. Materials and methods: We had 153 old children from 6 to 59 months chosen in 3 centers of health: on the level of ASACO-Sab1 63 children, ASACOSAB 2 62 children, ASACOSAB 3 68 children. The spiruline came from the unit from Safo, and the infantile flours of the UCODAL (simple enriched flour and flour enriched with fish). The protocols were as follows: enriched flour SINBA and Spiruline, enriched flour SINBA, flour enriched with the fish (silure) with 5%. The study lasted 9 weeks. Results: Our study confirmed the effectiveness of the spiruline in the flour compared with the protocols flour alone and flour-fish, in the assumption of responsibility of the severe stages of emaciation and ponderal insufficiency. The spiruline manages to change the severe statute into moderate statute. Concerning anaemia, a favorable evolution is noted with the three protocols. Conclusion: We obtained a weight gain of 136 g per week and a lengthening of 0,537 cm in two months. The improvement of the feeble statute of the children recorded was confirmed independent of the protocol, the age bracket and the sex by the test of Khi-deux. We noted that the mode flour-spiruline is most effective in the assumption of responsibility of the severe states of emaciation with a coefficient of reduction of 7.13, and also of the ponderal insufficiency with a factor of reduction equal to 4,64.Contexte actuel : La malnutrition dans le monde est actuellement à l’origine de près de 54% des décès d’enfants en dessous de 5ans (1,2). Au Mali, d’après l’EDSM IV, 15% des enfants souffrent d’émaciation et 27% des enfants, d’insuffisance pondérale. But : Le but est de déterminer l’efficacité d’une récupération nutritionnelle à base de spiruline en tant que supplément naturel multi-vitaminique et multi-microéléments dans des farines infantiles chez des enfants de 0 à 59 mois malnutris à Sabalibougou, et de la comparer à celle du poisson et des farines infantiles. Matériels et méthodes : Nous avions 153 enfants âgés de 6 à 59 mois choisis dans 3 centres de santé : au niveau de l’ASACO-Sab1 63 enfants, ASACOSAB2 62 enfants, ASACOSAB3 68 enfants. La spiruline provenait de l’unité de Safo, et le farines infantiles de l’UCODAL (farine enrichie simple et farine enrichie au poisson). Les protocoles étaient les suivants : de la farine enrichie SINBA et Spiruline, farine enrichie SINBA, farine enrichie au poisson (silure) à 5%. L’étude a duré 9 semaines. Résultats : Notre étude a confirmé l’efficacité de la spiruline dans la farine comparée aux protocoles farine seule et farine-poisson, dans la prise en charge des stades sévères d’émaciation et d’insuffisance pondérale. La spiruline parvient à faire changer le statut sévère en statut modéré. Concernant l’anémie, une évolution favorable est constatée avec les trois protocoles. Conclusion : Nous avons obtenu un gain de poids de 136 g par semaine et un allongement de 0,537 cm en deux mois. L’amélioration du statut anémique des enfants enregistrée a été confirmée indépendante du protocole, de la tranche d’âge et du sexe par le test du Khi-deux. Nous avons constaté que le régime farine-spiruline est le plus efficace dans la prise en charge des états sévères d’émaciation avec un coefficient de réduction de 7.13, et aussi de l’insuffisance pondérale avec un facteur de réduction égal à 4,64