Malaria treatment in remote areas of Mali: use of modern and traditional medicines, patient outcome

Use of official health services often remains low despite great efforts to improve quality of care. Are informal treatments responsible for keeping a number of patients away from standard care, and if so, why? Through a questionnaire survey with proportional cluster samples, we studied the case histories of 952 children in Bandiagara and Sikasso areas of Mali. Most children with reported uncomplicated malaria were first treated at home (87%) with modern medicines alone (40%), a mixture of modern and traditional treatments (33%), or traditional treatment alone (27%). For severe episodes (224 cases), a traditional treatment alone was used in 50% of the cases. Clinical recovery after uncomplicated malaria was above 98% with any type of treatment. For presumed severe malaria, the global mortality rate was 17%; it was not correlated with the type of treatment used (traditional or modern, at home or elsewhere). In the study areas, informal treatments divert a high proportion of patients away from official health services. Patients' experience that outcome after standard therapeutic itineraries is not better than after alternative care may help to explain low use of official health services. We need to study whether some traditional treatments available in remote villages should be considered real, recommendable first ai

Organomegaly in Mali before and after praziquantel treatment. A possible association with Schistosoma haematobium.

Continuous exposure to schistosome-infested water results in acute and chronic morbidity in all ages. We analysed occurence of organomegaly via ultrasonography and investigated a possible additive effect of dual-dose drug administration in 401 Schistosoma haematobium infected individuals from a highly endemic area in Mali. Mean intensity of infection at baseline (22.0 eggs per 10 ml) was reduced to 0.22 eggs per 10 ml 9 weeks after treatment (both treatments combined). Odds of persistent infection among those given dual-dose treatment was 41% of that in people given single dose (b = 0.41; p = 0.05; 95% CI 0.17-1.00), but after two years, 70.7% of the 157 participants, who completed the survey, were re-infected with no significant difference in prevalence and intensity of infection between treatment groups. Resolution of organomegaly occurred in all age groups after treatment. A novel association between Schistosoma haematobium infection and moderate portal vein enlargement was found in 35% (n: 55). Severe portal vein diameter enlargement was found in 3.2%. After two years, moderate hepatomegaly was present in 50.6%, moderate splenomegaly in 45.6% and moderate portal vein diameter enlargement in 19%. A subsequent dose of PZQ did not provide any additional long-term advantages

Uptake of plasmodium falciparum gametocytes during mosquito bloodmeal by direct and membrane feeding

Plasmodium falciparum remains one of the leading causes of child mortality, and nearly half of the world’s population is at risk of contracting malaria. While pathogenesis results from replication of asexual forms in human red blood cells, it is the sexually differentiated forms, gametocytes, which are responsible for the spread of the disease. For transmission to succeed, both mature male and female gametocytes must be taken up by a female Anopheles mosquito during its blood meal for subsequent differentiation into gametes and mating inside the mosquito gut. Observed circulating numbers of gametocytes in the human host are often surprisingly low. A pre-fertilization behavior, such as skin sequestration, has been hypothesized to explain the efficiency of human-to-mosquito transmission but has not been sufficiently tested due to a lack of appropriate tools. In this study, we describe the optimization of a qPCR tool that enables the relative quantification of gametocytes within very small input samples. Such a tool allows for the quantification of gametocytes in different compartments of the host and the vector that could potentially unravel mechanisms that enable highly efficient malaria transmission. We demonstrate the use of our gametocyte quantification method in mosquito blood meals from both direct skin feeding on Plasmodium gametocyte carriers and standard membrane feeding assay. Relative gametocyte abundance was not different between mosquitoes fed through a membrane or directly on the skin suggesting that there is no systematic enrichment of gametocytes picked up in the skin

Artemether–lumefantrine with or without single-dose primaquine and sulfadoxine–pyrimethamine plus amodiaquine with or without single-dose tafenoquine to reduce Plasmodium falciparum transmission: a phase 2, single-blind, randomised clinical trial in Ouelessebougou, Mali

Background: Artemether–lumefantrine is widely used for uncomplicated Plasmodium falciparum malaria; sulfadoxine–pyrimethamine plus amodiaquine is used for seasonal malaria chemoprevention. We aimed to determine the efficacy of artemether–lumefantrine with and without primaquine and sulfadoxine–pyrimethamine plus amodiaquine with and without tafenoquine for reducing gametocyte carriage and transmission to mosquitoes. Methods: In this phase 2, single-blind, randomised clinical trial conducted in Ouelessebougou, Mali, asymptomatic individuals aged 10–50 years with P falciparum gametocytaemia were recruited from the community and randomly assigned (1:1:1:1) to receive either artemether–lumefantrine, artemether–lumefantrine with a single dose of 0·25 mg/kg primaquine, sulfadoxine–pyrimethamine plus amodiaquine, or sulfadoxine–pyrimethamine plus amodiaquine with a single dose of 1·66 mg/kg tafenoquine. All trial staff other than the pharmacist were masked to group allocation. Participants were not masked to group allocation. Randomisation was done with a computer-generated randomisation list and concealed with sealed, opaque envelopes. The primary outcome was the median within-person percent change in mosquito infection rate in infectious individuals from baseline to day 2 (artemether–lumefantrine groups) or day 7 (sulfadoxine–pyrimethamine plus amodiaquine groups) after treatment, assessed by direct membrane feeding assay. All participants who received any trial drug were included in the safety analysis. This study is registered with ClinicalTrials.gov, NCT05081089. Findings: Between Oct 13 and Dec 16, 2021, 1290 individuals were screened and 80 were enrolled and randomly assigned to one of the four treatment groups (20 per group). The median age of participants was 13 (IQR 11–20); 37 (46%) of 80 participants were female and 43 (54%) were male. In individuals who were infectious before treatment, the median percentage reduction in mosquito infection rate 2 days after treatment was 100·0% (IQR 100·0–100·0; n=19; p=0·0011) with artemether–lumefantrine and 100·0% (100·0–100·0; n=19; p=0·0001) with artemether–lumefantrine with primaquine. Only two individuals who were infectious at baseline infected mosquitoes on day 2 after artemether–lumefantrine and none at day 5. By contrast, the median percentage reduction in mosquito infection rate 7 days after treatment was 63·6% (IQR 0·0–100·0; n=20; p=0·013) with sulfadoxine–pyrimethamine plus amodiaquine and 100% (100·0–100·0; n=19; p<0·0001) with sulfadoxine–pyrimethamine plus amodiaquine with tafenoquine. No grade 3–4 or serious adverse events occurred. Interpretation: These data support the effectiveness of artemether–lumefantrine alone for preventing nearly all mosquito infections. By contrast, there was considerable post-treatment transmission after sulfadoxine–pyrimethamine plus amodiaquine; therefore, the addition of a transmission-blocking drug might be beneficial in maximising its community impact. Funding: Bill & Melinda Gates Foundation

Pyronaridine-artesunate or dihydroartemisinin-piperaquine combined with single low-dose primaquine to prevent Plasmodium falciparum malaria transmission in Ouélessébougou, Mali: a four-arm, single-blind, phase 2/3, randomised trial.

BACKGROUND: Pyronaridine-artesunate is the most recently licensed artemisinin-based combination therapy. WHO has recommended that a single low dose of primaquine could be added to artemisinin-based combination therapies to reduce Plasmodium falciparum transmission in areas aiming for elimination of malaria or areas facing artemisinin resistance. We aimed to determine the efficacy of pyronaridine-artesunate and dihydroartemisinin-piperaquine with and without single low-dose primaquine for reducing gametocyte density and transmission to mosquitoes. METHODS: We conducted a four-arm, single-blind, phase 2/3, randomised trial at the Ouélessébougou Clinical Research Unit of the Malaria Research and Training Centre of the University of Bamako (Bamako, Mali). Participants were aged 5-50 years, with asymptomatic P falciparum malaria mono-infection and gametocyte carriage on microscopy, haemoglobin density of 9·5 g/dL or higher, bodyweight less than 80 kg, and no use of antimalarial drugs over the past week. Participants were randomly assigned (1:1:1:1) to one of four treatment groups: pyronaridine-artesunate, pyronaridine-artesunate plus primaquine, dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus primaquine. Treatment allocation was concealed to all study staff other than the trial pharmacist and treating physician. Dihydroartemisinin-piperaquine and pyronaridine-artesunate were administered as per manufacturer guidelines over 3 days; primaquine was administered as a single dose in oral solution according to bodyweight (0·25 mg/kg; in 1 kg bands). The primary endpoint was percentage reduction in mosquito infection rate (percentage of mosquitoes surviving to dissection that were infected with P falciparum) at 48 h after treatment compared with baseline (before treatment) in all treatment groups. Data were analysed per protocol. This trial is now complete, and is registered with ClinicalTrials.gov, NCT04049916. FINDINGS: Between Sept 10 and Nov 19, 2019, 1044 patients were assessed for eligibility and 100 were enrolled and randomly assigned to one of the four treatment groups (n=25 per group). Before treatment, 66 (66%) of 100 participants were infectious to mosquitoes, with a median of 15·8% (IQR 5·4-31·9) of mosquitoes becoming infected. In individuals who were infectious before treatment, the median percentage reduction in mosquito infection rate 48 h after treatment was 100·0% (IQR 100·0 to 100·0) for individuals treated with pyronaridine-artesunate plus primaquine (n=18; p<0·0001) and dihydroartemisinin-piperaquine plus primaquine (n=15; p=0·0001), compared with -8·7% (-54·8 to 93·2) with pyronaridine-artesunate (n=17; p=0·88) and 50·4% (13·8 to 70·9) with dihydroartemisinin-piperaquine (n=16; p=0·13). There were no serious adverse events, and there were no significant differences between treatment groups at any point in the frequency of any adverse events (Fisher's exact test p=0·96) or adverse events related to study drugs (p=0·64). The most common adverse events were headaches (40 events in 32 [32%] of 100 participants), rhinitis (31 events in 30 [30%]), and respiratory infection (20 events in 20 [20%]). INTERPRETATION: These data support the use of single low-dose primaquine as an effective supplement to dihydroartemisinin-piperaquine and pyronaridine-artesunate for blocking P falciparum transmission. The new pyronaridine-artesunate plus single low-dose primaquine combination is of immediate relevance to regions in which the containment of partial artemisinin and partner-drug resistance is a growing concern and in regions aiming to eliminate malaria. FUNDING: The Bill & Melinda Gates Foundation. TRANSLATIONS: For the French, Spanish and Swahilil translations of the abstract see Supplementary Materials section

Caractéristiques cliniques des syndromes parkinsoniens avec tremblement rentrant dans le cadre des "scans without evidence of dopaminergic deficit"

INTRODUCTION : 4 à 15% des patients présentant les critères diagnostics actuels pour la maladie de Parkinson (MPI) ont une imagerie fonctionnelle dopaminergique normale. La majorité de ces patients, nommés Scans Without Evidence of Dopaminergic Deficit (SWEDDs), auraient un tremblement d origine dystonique. Notre objectif était de déterminer des caractéristiques cliniques et polygraphiques spécifiques permettant de suspecter un SWEDD trémulant devant un syndrome parkinsonien évocateur d une MPI. PATIENTS ET METHODE : il s agit d une étude rétrospective cas-contrôle portant sur 16 patients SWEDDs avec tremblement suivis au CHU d Amiens. Nous avons étudié les caractéristiques démographiques et cliniques, les données de l anamnèse et de l évolution, le degré de sensibilité aux traitements médicamenteux et à l alcool, les antécédents familiaux de tremblement ou de comorbidité psychiatrique, les données de la polygraphie du tremblement. Tous les DaTSCAN avaient été relus par le même opérateur. RESULTATS : un tremblement focal, spécifique de tâche, irrégulier en fréquence et en amplitude et un syndrome parkinsonien peu évolutif, fluctuant, s améliorant spontanément au cours du suivi et de sévérité moindre sont caractéristiques des patients SWEDDs trémulants. Les SWEDDs trémulants présentent pour la plupart des caractéristiques de tremblement dystonique, de tremblement psychogène et plus rarement de tremblement essentiel. L exploration polygraphique du tremblement ne constitue pas une aide majeure au diagnostic des SWEDDs trémulants. CONCLUSION : les patients SWEDDs trémulants présentent des caractéristiques cliniques spécifiques permettant de les différencier des patients parkinsoniens avant la réalisation du DaTSCAN.OBJECTIVE : 4 to 15 % of the patients fulfilling the current diagnosis criteria for Idiopathic Parkinson s Disease (IPD) have normal dopamine transporter (DaT) functional imaging. Most of these patients, named Scans Without Evidence of Dopaminergic Deficit (SWEDDs), might have dystonic tremor. Our objective was to determine which specific clinical and electrophysiological features enable to suspect a tremulous SWEDD when confronted to a parkinsonian syndrome suggesting IPD. PATIENTS AND METHODS : this is a retrospective case-control study of 16 tremulous SWEDDs patients followed-up in the Amiens University Hospital. We studied demographics, clinical features, the disease history and course, the alcohol and treatment responsiveness, the family history of tremor, the presence of psychiatric comorbidities and the tremor electrophysiological analysis datas. All the DaT-SPECT scans (DaTSCANs) were rewied by the same operator. RESULTS : a focal, task-specific tremor, with irregular frequency and amplitude; and a static or fluctuating parkinsonian syndrome, spontaneously remittent and with mild severity are characteristic of tremulous SWEDDs. Most of tremulous SWEDDs patients have dystonic tremor, psychogenic tremor and less frequently, essential tremor. The electrophysiological analysis of tremor could not help for the diagnosis of tremulous SWEDDs. CONCLUSION : tremulous SWEDDs patients have specific clinical features which allow distinguishing them from parkinsonian patients before the realization of the DaTSCAN.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Mean female and male body size, survival and insemination rate in relation to Genetic/Environmental treatment in the within-form mating experiment (1^st experiment).

<p>The insemination rate of females of each treatment exposed to Field/Field Mopti males.</p><p>Here the insemination rate of Field/Field Mopti females exposed to males of each treatment group.</p><p>Values in brackets are 95% confidence intervals and sample sizes are indicated in italics.</p

Mean wing length (mm) in females (dark bars) and males (light bars) from the 4 Genetic/Environmental treatments in the 2011 assortative mating experiment.

<p>For each gender, levels labelled with different letters differed significantly in pairwise statistical comparisons (Tukey test). Error bars are 95% confidence intervals.</p

Nominal logistic regressions of the effects of Year, Genetic/Environmental treatment, and Enclosure on female and male survival in within-form mating experiment (1^st experiment).

<p>Square brackets indicate effect nesting.</p><p>Sample sizes were 900 females and 900 males.</p