Health facility-based prevalence and potential risk factors of autism spectrum disorders in Mali

Background: The prevalence of autism spectrum disorders (ASD) is 1-2% worldwide, 1 in 68 in the U.S, and unknown in Africa. ASD is under-diagnosed in Mali due to stigma and the lack of appropriate human resources and infrastructure.Objective: To determine the ASD frequency and potential risk factors in Mali.Methods: We identified all the health facilities and community-based organizations involved in the ASD diagnosis and management in Bamako. We established an ASD research and awareness platform in Mali, which encompasses community-based organizations and a multidisciplinary team including psychiatrists, psychologists, pediatricians, geneticists, and public health and social science specialists. Through this platform, we performed a survey in health facilities and organizations where patients with ASD are likely to seek care in Bamako. We reviewed the psychiatric patient registry to obtain basic epidemiological profiles of children with ASD, epilepsy and other psychiatric disorders.Results: We found a health facility-based prevalence of ASD of 4.5% (105/2,343) in Bamako. The mean age at the first outpatient visit was 7.64 ± 3.85 years old. First degree consanguinity of 29.5% (31/105) was more frequent in parents of ASD children versus age and sex matched controls OR= 4.37 [1.96-9.76] p=0.0001.Conclusion: Our data suggest that ASD is more common than expected in Mali. The established ASD awareness and research platform may improve the diagnosis and management of ASD by raising ASD awareness, training of Malian clinicians and researchers in early ASD screening and diagnosis, and strengthening research capacity in genomics of ASD and other mental disorders.Keywords: ASD, prevalence, consanguinity, health facilit

Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in Mali

URL : http://www.malariajournal.com/content/9/1/332Background: Artemisinin-based combination therapy (ACT) is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P. falciparum clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), a haemoglobin enzyme deficiency, not yet studied in the same context, but nonetheless is a common in malaria endemic areas, associated with host protection against uncomplicated and severe malaria. The impact of G6PD deficiency on parasite clearance with ACT treatment was compared between G6PD-deficient patients and G6PD-normal group. Methods: Blood samples from children and adults participants (1 to 70 years old) with uncomplicated P. falciparum malaria residing in Kambila, Mali were analysed. Study participants were randomly assigned to receive either artemether-lumefantrine (Coartem®) or artesunate plus mefloquine (Artequin™). A restriction-fragment length polymorphism analysis of PCR-amplified DNA samples was used to identify the (A-) allele of the gene mutation responsible for G6PD deficiency (G6PD*A-). 470 blood samples were thus analysed and of these, DNA was extracted from 315 samples using the QIAamp kit for PCR to identify the G6PD*A- gene. Results

α-Thalassemia Impairs the Cytoadherence of Plasmodium falciparum-Infected Erythrocytes

α-Thalassemia results from decreased production of α-globin chains that make up part of hemoglobin tetramers (Hb; α(2)β(2)) and affects up to 50% of individuals in some regions of sub-Saharan Africa. Heterozygous (-α/αα) and homozygous (-α/-α) genotypes are associated with reduced risk of severe Plasmodium falciparum malaria, but the mechanism of this protection remains obscure. We hypothesized that α-thalassemia impairs the adherence of parasitized red blood cells (RBCs) to microvascular endothelial cells (MVECs) and monocytes--two interactions that are centrally involved in the pathogenesis of severe disease.We obtained P. falciparum isolates directly from Malian children with malaria and used them to infect αα/αα (normal), -α/αα and -α/-α RBCs. We also used laboratory-adapted P. falciparum clones to infect -/-α RBCs obtained from patients with HbH disease. Following a single cycle of parasite invasion and maturation to the trophozoite stage, we tested the ability of parasitized RBCs to bind MVECs and monocytes. Compared to parasitized αα/αα RBCs, we found that parasitized -α/αα, -α/-α and -/-α RBCs showed, respectively, 22%, 43% and 63% reductions in binding to MVECs and 13%, 33% and 63% reductions in binding to monocytes. α-Thalassemia was associated with abnormal display of P. falciparum erythrocyte membrane protein 1 (PfEMP1), the parasite's main cytoadherence ligand and virulence factor, on the surface of parasitized RBCs.Parasitized α-thalassemic RBCs show PfEMP1 display abnormalities that are reminiscent of those on the surface of parasitized sickle HbS and HbC RBCs. Our data suggest a model of malaria protection in which α-thalassemia ameliorates the pro-inflammatory effects of cytoadherence. Our findings also raise the possibility that other unstable hemoglobins such as HbE and unpaired α-globin chains (in the case of β-thalassemia) protect against life-threatening malaria by a similar mechanism

Autism seminary for public engagement: evaluation of knowledge and attitudes of traditional medical practitioners in Mali

Background: Autism spectrum disorders (ASD) are stigmatizing in Africa and traditional medical practitioners occupy the first line of diagnosis and treatment due to the cultural perception of ASD, and the scarcity of conventional health services in Mali. We aimed to assess the knowledge, attitudes, and practices (KAP) concerning autism among traditional medical practitioners in Bamako, Mali. Methods: We conducted a 6-week cross-sectional survey following a 1-day autism awareness seminary on September 9th, 2017 in Bamako. A questionnaire was designed to assess the KAP regarding autism. To assess their practices, parents of autistic children were asked about their experiences with traditional medical practitioners. Results: Of the 37 study participants 67.60% were males and 56.8% had not heard about autism before the seminary. After the seminary, 73% claimed to understand the diagnosis criteria of autism, but only 16.2% could recall symptoms from all the three domains (reciprocal social interaction, verbal and nonverbal communication, and stereotyped behaviors/restricted interests) of a child development impaired by autism. Of traditional medical practitioners, 73% believed autism was caused by devils, God’s will, bad luck and divine punishment of maternal misbehavior; 65% were used to treating mental illness, and 78.4% felt traditional healing was the only treatment option in autism. Negative attitudes towards autistic children were present in 18.9%, suggesting a very strong cultural mindset on autism. Conclusion: Knowledge on autism was poor among traditional medical practitioners. A culturally tailored autism public engagement strategy is necessary to positively change the mindset of Malian traditional medical practitioners.</ns4:p

A novel cytofluorometric assay for the detection and quantification of glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy that affects hundreds of millions of people worldwide, conferring increased risk of neonatal jaundice and oxidant-induced hemolytic anemia. Screening and diagnosis of G6PD deficiency is currently performed using genetic or biochemical assays, the former being cost ineffective in populations with significant allelic heterogeneity and the latter being limited in ability to detect female heterozygotes. Cytochemical assays can obviate these shortcomings, but at the expense of added technical complexity and labor. We describe here a simple, novel cytofluorometric method that extends the classic methemoglobin reduction test, assessing G6PD deficiency at the level of an individual erythrocyte. In preliminary testing in Malian children, there was strong concordance between our method and established genetic and biochemical techniques. The assay is robust and economical and could serve as a screening method as well as a research tool, especially for high-throughput applications such as flow cytometry

Schematic representation of the cytoadherence assay.

<p>Ring-stage parasites from HbAA and HbAS (or HbAC) children were cultured to trophozoites (a), and then purified by magnetic column and inoculated into wildtype donor RBCs (b). After invasion and maturation to trophozoites expressing PfEMP1 (c), parasites from HbAS or HbAC children were compared for binding to MVECs in parallel with those from HbAA children (d).</p

Schematic representation of the cytoadherence assay.

<p>Ring-stage parasites from HbAA and HbAS (or HbAC) children were cultured to trophozoites (a), and then purified by magnetic column and inoculated into wildtype donor RBCs (b). After invasion and maturation to trophozoites expressing PfEMP1 (c), parasites from HbAS or HbAC children were compared for binding to MVECs in parallel with those from HbAA children (d).</p

<it>Plasmodium falciparum </it>clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in Mali

Abstract Background Artemisinin-based combination therapy (ACT) is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P. falciparum clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), a haemoglobin enzyme deficiency, not yet studied in the same context, but nonetheless is a common in malaria endemic areas, associated with host protection against uncomplicated and severe malaria. The impact of G6PD deficiency on parasite clearance with ACT treatment was compared between G6PD-deficient patients and G6PD-normal group. Methods Blood samples from children and adults participants (1 to 70 years old) with uncomplicated P. falciparum malaria residing in Kambila, Mali were analysed. Study participants were randomly assigned to receive either artemether-lumefantrine (Coartem®) or artesunate plus mefloquine (Artequin™). A restriction-fragment length polymorphism analysis of PCR-amplified DNA samples was used to identify the (A-) allele of the gene mutation responsible for G6PD deficiency (G6PD*A-). 470 blood samples were thus analysed and of these, DNA was extracted from 315 samples using the QIAamp kit for PCR to identify the G6PD*A- gene. Results The DNA amplified from 315 samples using PCR showed that G6PD*A- deficiency was present in 56 participants (17.8%). The distribution of the specific deficiency was 1%, 7% and, 9.8% respectively for homozygous, hemizygous, and heterozygous genotypes. Before treatment, the median parasitaemia and other baseline characteristics (mean haemoglobin, sex and age groups) between G6PD deficiency (hemizygous, heterozygous, and homozygous) and G6PD-normal participants were comparable (p > 0.05). After treatment, parasite clearance did not change significantly whether the participants were G6PD deficient or G6PD normal on day 1 (OR = 1.3; CI = 0.70-2.47; p > 0.05) and on day 2 (OR = 0.859; CI = 0.097-7.61; p > 0.05). Conclusions The presence of G6PD deficiency does not appear to significantly influence the clearance of P. falciparum in the treatment of uncomplicated malaria using ACT.</p