Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-6 (of 6 Records) |
Query Trace: Desai MR[original query] |
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Mass testing and treatment on malaria in an area of western Kenya
Samuels AM , Odero NA , Odongo W , Otieno K , Were V , Shi YP , Sang T , Williamson J , Wiegand R , Hamel MJ , Kachur SP , Slutsker L , Lindblade KA , Kariuki SK , Desai MR . Clin Infect Dis 2021 72 (6) 1103-1104 We appreciate the thoughtful commentary provided by Hamer and Miller [1] and are pleased that they arrived at many of the same conclusions that we did; however, we would like to clarify a few points. | | First, we wish to correct the statement that, in our trial, mass testing and treatment (MTaT) was only implemented within the core areas of clusters. Rather, MTaT was implemented throughout intervention clusters, which included a core area ranging between 1 and 3 Km in diameter, and a 300-m buffer. As described, to limit contamination, inclusion criteria for the analytic sample required residence within the core area [2, 3]. |
Malaria chemoprevention in the postdischarge management of severe anemia
Kwambai TK , Dhabangi A , Idro R , Opoka R , Watson V , Kariuki S , Kuya NA , Onyango ED , Otieno K , Samuels AM , Desai MR , Boele van Hensbroek M , Wang D , John CC , Robberstad B , Phiri KS , Ter Kuile FO . N Engl J Med 2020 383 (23) 2242-2254 BACKGROUND: Children who have been hospitalized with severe anemia in areas of Africa in which malaria is endemic have a high risk of readmission and death within 6 months after discharge. No prevention strategy specifically addresses this period. METHODS: We conducted a multicenter, two-group, randomized, placebo-controlled trial in nine hospitals in Kenya and Uganda to determine whether 3 months of malaria chemoprevention could reduce morbidity and mortality after hospital discharge in children younger than 5 years of age who had been admitted with severe anemia. All children received standard in-hospital care for severe anemia and a 3-day course of artemether-lumefantrine at discharge. Two weeks after discharge, children were randomly assigned to receive dihydroartemisinin-piperaquine (chemoprevention group) or placebo, administered as 3-day courses at 2, 6, and 10 weeks after discharge. Children were followed for 26 weeks after discharge. The primary outcome was one or more hospital readmissions for any reason or death from the time of randomization to 6 months after discharge. Conditional risk-set modeling for recurrent events was used to calculate hazard ratios with the use of the Prentice-Williams-Peterson total-time approach. RESULTS: From May 2016 through May 2018, a total of 1049 children underwent randomization; 524 were assigned to the chemoprevention group and 525 to the placebo group. From week 3 through week 26, a total of 184 events of readmission or death occurred in the chemoprevention group and 316 occurred in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.54 to 0.78; P<0.001). The lower incidence of readmission or death in the chemoprevention group than in the placebo group was restricted to the intervention period (week 3 through week 14) (hazard ratio, 0.30; 95% CI, 0.22 to 0.42) and was not sustained after that time (week 15 through week 26) (hazard ratio, 1.13; 95% CI, 0.87 to 1.47). No serious adverse events were attributed to dihydroartemisinin-piperaquine. CONCLUSIONS: In areas with intense malaria transmission, 3 months of postdischarge malaria chemoprevention with monthly dihydroartemisinin-piperaquine in children who had recently received treatment for severe anemia prevented more deaths or readmissions for any reason after discharge than placebo. (Funded by the Research Council of Norway and the Centers for Disease Control and Prevention; ClinicalTrials.gov number, NCT02671175.). |
Impact of community-based mass testing and treatment on malaria infection prevalence in a high transmission area of western Kenya: A cluster randomized controlled trial
Samuels AM , Odero NA , Odongo W , Otieno K , Were V , Shi YP , Sang T , Williamson J , Wiegand R , Hamel MJ , Kachur SP , Slutsker L , Lindblade KA , Kariuki SK , Desai MR . Clin Infect Dis 2020 72 (11) 1927-1935 BACKGROUND: Global gains towards malaria elimination have been heterogeneous and have recently stalled. Interventions targeting afebrile malaria infections may be needed to address residual transmission. We studied the efficacy of repeated rounds of community-based mass testing and treatment (MTaT) on malaria infection prevalence in western Kenya. METHODS: Twenty clusters were randomly assigned to three rounds of MTaT per year for two years or control (standard-of-care for testing and treatment at public health facilities along with government sponsored mass long-lasting insecticidal net (LLIN) distributions). During rounds community health volunteers visited all households in intervention clusters and tested all consenting individuals with a rapid diagnostic test. Those positive were treated with dihydroartemisinin-piperaquine. Cross-sectional community infection prevalence surveys were performed in both study arms at baseline and each year after three rounds of MTaT. The primary outcome was the effect size of MTaT on parasite prevalence by microscopy between arms by year adjusted for age, reported LLIN use, enhanced vegetative index, and socio-economic status. RESULTS: Demographic and behavioral characteristics, including LLIN usage, were similar between arms at each survey. MTaT coverage ranged between 75.0-77.5% and 81.9-94.3% between the three rounds in year 1 and year 2, respectively. The adjusted effect size of MTaT on the prevalence of parasitemia between arms was 0.93 (CI: 0.79-1.08) and 0.92 (0.76-1.10) after year 1 and 2, respectively. CONCLUSIONS: MTaT performed three times per year over two years did not reduce malaria parasite prevalence in this high-transmission area. |
Human direct skin feeding versus membrane feeding to assess the mosquitocidal efficacy of high-dose ivermectin (IVERMAL Trial)
Smit MR , Ochomo EO , Aljayyoussi G , Kwambai TK , Abong'o BO , Bousema T , Waterhouse D , Bayoh NM , Gimnig JE , Samuels AM , Desai MR , Phillips-Howard PA , Kariuki SK , Wang D , Ward SA , Ter Kuile FO . Clin Infect Dis 2018 69 (7) 1112-1119 Background: Ivermectin is being considered for mass-drug-administration for malaria due to its ability to kill mosquitoes feeding on recently treated individuals. In a recent trial, 3-day courses of 300 and 600 mcg/kg/day were shown to kill Anopheles mosquitoes for at least 28 days post-treatment when fed patients' venous blood using membrane-feeding-assays. Direct-skin-feeding on humans may lead to higher mosquito-mortality as ivermectin capillary-concentrations are higher. We compared mosquito-mortality following direct-skin- and membrane-feeding. Methods: We conducted a mosquito feeding study nested within a randomized, double-blind, placebo-controlled trial of 141 adults with uncomplicated malaria in Kenya comparing 3-day ivermectin 0 (n=46), 300 (n=48), or 600 mcg/kg/day (n=47), co-administered with dihydroartemisinin-piperaquine. On post-treatment day-7, direct-skin and membrane-feeding assays were conducted using laboratory-reared Anopheles gambiae s.s.. Mosquito survival was assessed daily for 28-days-post-feeding. Results: Between July-20-2015 and May-7-2016, 69 of 141 patients participated in both direct-skin- and membrane-feeding (placebo n=23, 300mcg/kg/day n=24, 600mcg/kg/day n=22). The 14-day-post-feeding mortality for mosquitoes fed on blood 7-days post-treatment from patients in both ivermectin arms pooled was similar with direct-skin-feeding (n=2,941 mosquitoes) versus membrane-feeding (n=7,380 mosquitoes): cumulative-mortality (RR=0.99, 0.95-1.03, p=0.69) and survival-time (HR=0.96, 0.91-1.02, p=0.19). Results were consistent by sex, body-mass-index, and across the range of ivermectin capillary concentrations studied (0.72-73.9 ng/mL). Conclusions: Direct-skin-feeding and membrane-feeding on day 7 resulted in similar mosquitocidal-effects of ivermectin across a wide range of drug-concentrations, suggesting that the mosquitocidal-effects seen with membrane-feeding accurately reflect those of natural-biting. Membrane-feeding, which is more patient-friendly and ethically acceptable, can likely reliably be used to assess ivermectin's mosquitocidal-efficacy. |
Pharmacokinetics-pharmacodynamics of high-dose ivermectin with dihydroartemisinin-piperaquine on mosquitocidal activity and QT-prolongation (IVERMAL)
Smit MR , Ochomo EO , Waterhouse D , Kwambai TK , Abong'o BO , Bousema T , Bayoh NM , Gimnig JE , Samuels AM , Desai MR , Phillips-Howard PA , Kariuki SK , Wang D , Ter Kuile FO , Ward SA , Aljayyoussi G . Clin Pharmacol Ther 2018 105 (2) 388-401 High-dose ivermectin, co-administered for 3-days with dihydroartemisinin-piperaquine (DP), killed mosquitoes feeding on individuals for at least 28-days post-treatment in a recent trial (IVERMAL), while 7-days was predicted pre-trial. The current study assessed the relationship between ivermectin blood concentrations and the observed mosquitocidal effects against Anopheles gambiae. 3-days ivermectin 0, 300, or 600 mcg/kg/day plus DP was randomly assigned to 141 adults with uncomplicated malaria in Kenya. During 28-days follow-up, 1,393 venous and 335 paired capillary plasma samples, 850 mosquito-cluster mortality rates, and 524 QTcF-intervals were collected. Using pharmacokinetic-pharmacodynamic (PK-PD) modeling, we show a consistent correlation between predicted ivermectin concentrations and observed mosquitocidal-effects throughout the 28-day study duration, without invoking an unidentified mosquitocidal metabolite or drug-drug-interaction. Ivermectin had no effect on piperaquine's pharmacokinetics or QTcF-prolongation. The PK-PD model can be used to design new treatment regimens with predicted mosquitocidal effect. This methodology could be used to evaluate effectiveness of other endectocides. This article is protected by copyright. All rights reserved. |
Safety and mosquitocidal efficacy of high-dose ivermectin when co-administered with dihydroartemisinin-piperaquine in Kenyan adults with uncomplicated malaria (IVERMAL): a randomised, double-blind, placebo-controlled trial
Smit MR , Ochomo EO , Aljayyoussi G , Kwambai TK , Abong'o BO , Chen T , Bousema T , Slater HC , Waterhouse D , Bayoh NM , Gimnig JE , Samuels AM , Desai MR , Phillips-Howard PA , Kariuki SK , Wang D , Ward SA , Ter Kuile FO . Lancet Infect Dis 2018 18 (6) 615-626 BACKGROUND: Ivermectin is being considered for mass drug administration for malaria due to its ability to kill mosquitoes feeding on recently treated individuals. However, standard, single doses of 150-200 mug/kg used for onchocerciasis and lymphatic filariasis have a short-lived mosquitocidal effect (<7 days). Because ivermectin is well tolerated up to 2000 mug/kg, we aimed to establish the safety, tolerability, and mosquitocidal efficacy of 3 day courses of high-dose ivermectin, co-administered with a standard malaria treatment. METHODS: We did a randomised, double-blind, placebo-controlled, superiority trial at the Jaramogi Oginga Odinga Teaching and Referral Hospital (Kisumu, Kenya). Adults (aged 18-50 years) were eligible if they had confirmed symptomatic uncomplicated Plasmodium falciparum malaria and agreed to the follow-up schedule. Participants were randomly assigned (1:1:1) using sealed envelopes, stratified by sex and body-mass index (men: <21 vs >/=21 kg/m(2); women: <23 vs >/=23 kg/m(2)), with permuted blocks of three, to receive 3 days of ivermectin 300 mug/kg per day, ivermectin 600 mug/kg per day, or placebo, all co-administered with 3 days of dihydroartemisinin-piperaquine. Blood of patients taken on post-treatment days 0, 2 + 4 h, 7, 10, 14, 21, and 28 was fed to laboratory-reared Anopheles gambiae sensu stricto mosquitoes, and mosquito survival was assessed daily for 28 days after feeding. The primary outcome was 14-day cumulative mortality of mosquitoes fed 7 days after ivermectin treatment (from participants who received at least one dose of study medication). The study is registered with ClinicalTrials.gov, number NCT02511353. FINDINGS: Between July 20, 2015, and May 7, 2016, 741 adults with malaria were assessed for eligibility, of whom 141 were randomly assigned to receive ivermectin 600 mug/kg per day (n=47), ivermectin 300 mug/kg per day (n=48), or placebo (n=46). 128 patients (91%) attended the primary outcome visit 7 days post treatment. Compared with placebo, ivermectin was associated with higher 14 day post-feeding mosquito mortality when fed on blood taken 7 days post treatment (ivermectin 600 mug/kg per day risk ratio [RR] 2.26, 95% CI 1.93-2.65, p<0.0001; hazard ratio [HR] 6.32, 4.61-8.67, p<0.0001; ivermectin 300 mug/kg per day RR 2.18, 1.86-2.57, p<0.0001; HR 4.21, 3.06-5.79, p<0.0001). Mosquito mortality remained significantly increased 28 days post treatment (ivermectin 600 mug/kg per day RR 1.23, 1.01-1.50, p=0.0374; and ivermectin 300 mug/kg per day 1.21, 1.01-1.44, p=0.0337). Five (11%) of 45 patients receiving ivermectin 600 mug/kg per day, two (4%) of 48 patients receiving ivermectin 300 mug/kg per day, and none of 46 patients receiving placebo had one or more treatment-related adverse events. INTERPRETATION: Ivermectin at both doses assessed was well tolerated and reduced mosquito survival for at least 28 days after treatment. Ivermectin 300 mug/kg per day for 3 days provided a good balance between efficacy and tolerability, and this drug shows promise as a potential new tool for malaria elimination. FUNDING: Malaria Eradication Scientific Alliance (MESA) and US Centers for Disease Control and Prevention (CDC). |
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