SummaryAdding low-dose primaquine to malaria treatment reduced gametocyte carriage by 73%. Patients who received primaquine had more frequent hemoglobinuria and there was a greater reduction in haemoglobin concentration in G6PD-deficient patients. One patient who received primaquine developed moderately severe anemia.
SummaryBackground-Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malariaendemic settings.Methods-We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4-97·9) at day 28 and 96·0% (95·6-96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86-0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5-96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3-96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 Findings-We included 61 studies done between Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts days of treatment (adjusted OR 0·92, 95% CI 0·85-0·99; p=0·037 for every 1 mg/kg increase in total artemether dose).Interpretation-The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups.Funding-Bill & Melinda Gates Foundation. IntroductionArtemisinin-based combination therapies are the first-line treatment for uncomplicated Plasmodium falciparum malaria in most malaria-endemic countries, 1 and they have been advocated to counter the threat of antimalarial drug resistance by delaying its emergence and spread. 2 As such, artemisinin-based combination therapies are a key component of malaria elimination efforts. 3The combination of artemether and lumefantrine was originally introduced as a four-dose regimen that proved to be efficacious in studies done in China, 4 Africa, 5 and India; 6 however, after detailed pharmacokinetic-pharmacodynamic assess...
Respiratory tract infections (RTIs) are common among Hajj pilgrims, but risk factors for RTIs and respiratory pathogen acquisition during the Hajj are not clearly identified. Based on previous studies, most frequent pathogens acquired by Hajj pilgrims were investigated: rhinovirus, human coronaviruses, influenza viruses, Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Haemophilus influenzae. 485 pilgrims were included. 82.1% presented with RTIs. Respiratory chronic diseases were associated with cough, Influenza-like illness (ILI) and the acquisition of H. influenzae. Vaccination against invasive pneumococcal diseases (IPD) and influenza was associated with a decrease in the acquisition of S. pneumoniae and prevalence of ILI (aRR = 0.53, 95%CI [0.39–0.73] and aRR = 0.69, 95%CI [0.52–0.92] respectively). Individuals carrying rhinovirus and H. influenzae-S. pneumoniae together were respectively twice and five times more likely to have respiratory symptoms. Individual with H. influenzae-K. pneumoniae carriage were twice (p = 0.04) as likely to develop a cough. The use of disposable handkerchiefs was associated with a decrease in the acquisition of S. aureus (aRR = 0.75, 95%CI [0.57–0.97]). Results could be used to identify pilgrims at increased risk of RTIs and acquisition of respiratory pathogens. Results also confirm the effectiveness of influenza and IPD vaccinations in reducing ILI symptoms and acquisition of S. pneumoniae carriage respectively.
BackgroundArtesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria.MethodsIndividual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites.ResultsForty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites.ConclusionsThere was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0301-z) contains supplementary material, which is available to authorized users.
Mycetoma is a neglected tropical disease caused by various actinomycetes or fungi. The disease is characterized by the formation of tumor like-swellings and grains. Senegal is an endemic country where mycetoma cases are under-or misdiagnosed due to the lack of capacities and knowledge among health workers and the community; and where the management of eumycetoma, burdened by a high amputation rate, is currently inadequate. This study aimed to update data on the epidemiology of mycetoma cases diagnosed in three hospital centres in Senegal over a 10 years-period. A total of 193 patients, diagnosed from 2008 to 2018, were included in the study. The most frequent presentation was eumycetoma (47.2%); followed by actinomycetoma (36.8%); it remained undetermined in 16.1% of the patients. The mean age was 38.3 years (68.4% of the patients were between 15 and 45 years-old); the male: female ratio was a 2.94; and most were farmers. One hundred fifty-six (80.8%) patients had used phytotherapy before attending the hospital. Mycetoma was mainly located to the lower limbs (91.2%). Grains were observed in 85% of the patients; including white (25.6%) and yellow (4.3%) grains. The etiological diagnosis was complex, resulting in negative direct microscopy, culture and/or histopathology findings, which explains that 16.1% remained uncharacterized. In most of cases, actinomycetoma were treated with a combination of cotrimoxazole, amoxicillin/clavulanic acid, and streptomycin; whereas eumycetoma cases were treated with terbinafine. The surgery was done in 100 (51.8%) of the patients including 9 in actinomycetoma, 78 in eumycetoma and 13 in undetermined form. The high number of uncharacterized mycetoma in this study, the delay in attending a qualified health-care facility, and the lack of available adequate antifungal drug, point out the need to strengthen mycetoma management capacities in Senegal.
Early diagnosis is essential to control cryptococcosis, and countries should prioritize widespread and reliable access to rapid diagnostic cryptococcus antigen assays. But it is important to make available conventional methods (India ink and culture) in the maximum of laboratory in regional health facilities.
BackgroundIn Senegal, a significant decrease of malaria transmission intensity has been noted the last years. Parasitaemia has become lower and, therefore, more difficult to detect by microscopy. In the context of submicroscopic parasitaemia, it has become relevant to rely on relevant malaria surveillance tools to better document malaria epidemiology in such settings. Serological markers have been proposed as an essential tool for malaria surveillance. This study aimed to evaluate the sero-epidemiological situation of Plasmodium falciparum malaria in two sentinel sites in Senegal.MethodsCross-sectional surveys were carried out in Velingara (south Senegal) and Keur Soce (central Senegal) between September and October 2010. Children under 10 years old, living in these areas, were enrolled using two-level, random sampling methods. P. falciparum infection was diagnosed using microscopy. P. falciparum antibodies against circumsporozoite protein (CSP), apical membrane protein (AMA1) and merozoite surface protein 1_42 (MSP1_42) were measured by ELISA method. A stepwise logistic regression analysis was done to assess factors associated with P. falciparum antibodies carriage.ResultsA total of 1,865 children under 10 years old were enrolled. The overall falciparum malaria prevalence was 4.99% with high prevalence in Velingara of 10.03% compared to Keur Soce of 0.3%. Symptomatic malaria cases (fever associated with parasitaemia) represented 17.37%. Seroprevalence of anti-AMA1, anti-MSP1_42 and anti-CSP antibody was 38.12, 41.55 and 40.38%, respectively. The seroprevalence was more important in Velingara and increased with age, active malaria infection and area of residence.ConclusionThe use of serological markers can contribute to improved malaria surveillance in areas with declining malaria transmission. This study provided useful baseline information about the sero-epidemiological situation of malaria in Senegal and can contribute to the identification of malaria hot spots in order to concentrate intervention efforts.Trial registration number: PACTR201305000551876 (http://www.pactr.org).
BackgroundCommunity case management of malaria (CCMm) and seasonal malaria chemoprevention (SMC) are anti-malarial interventions that can lead to substantial reduction in malaria burden acting in synergy. However, little is known about the social acceptability of these interventions. A study was undertaken to assess whether combining the interventions would be an acceptable approach to malaria control for community health workers (CHWs).MethodsSixty-one interviews and six focus group discussions were conducted nested in a cluster-randomized trial assessing the impact of combining CCMm and SMC in a rural area of Senegal. Participants consisted of: (i) members of village associations, (ii) members of families who had access to the interventions as well as members of families who did not access the interventions, (iii) CHWs, and (iv) community leaders, e g, religious guides and village chiefs.ResultsThe interventions were acceptable to the local population and perceived as good strategy to make health care services available to community members and thus, to reduce the delays in access to anti-malarial treatment as well as expenses related to patients’ transfer to the health post. The use of malaria rapid diagnostic test (RDT) contributed to improving CHWs diagnostic capacity as well as malaria treatment practices. Study participants notified RDT and drugs stock-out as the major risk for sustainability of the intervention at community level.ConclusionCombining CCMm and SMC is a well accepted, community-based approach that can contribute to control malaria in areas where malaria transmission is seasonal.
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