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.
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