RESUMEN
BACKGROUND: Global gains toward 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 3 rounds of MTaT per year for 2 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 3 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 socioeconomic status. RESULTS: Demographic and behavioral characteristics, including LLIN usage, were similar between arms at each survey. MTaT coverage across the 3 annual rounds ranged between 75.0% and 77.5% in year 1, and between 81.9% and 94.3% in year 2. The adjusted effect size of MTaT on the prevalence of parasitemia between arms was 0.93 (95% confidence interval [CI], .79-1.08) and 0.92 (95% CI, .76-1.10) after year 1 and year 2, respectively. CONCLUSIONS: MTaT performed 3 times per year over 2 years did not reduce malaria parasite prevalence in this high-transmission area. CLINICAL TRIALS REGISTRATION: NCT02987270.
Asunto(s)
Malaria , Estudios Transversales , Humanos , Kenia/epidemiología , Malaria/diagnóstico , Malaria/tratamiento farmacológico , Malaria/epidemiología , Parasitemia/tratamiento farmacológico , Parasitemia/epidemiología , PrevalenciaRESUMEN
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.).
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Anemia/tratamiento farmacológico , Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Malaria/prevención & control , Quinolinas/uso terapéutico , Cuidados Posteriores , Preescolar , Combinación de Medicamentos , Enfermedades Endémicas , Femenino , Humanos , Lactante , Kenia/epidemiología , Malaria/epidemiología , Masculino , Readmisión del Paciente/estadística & datos numéricos , Uganda/epidemiologíaRESUMEN
Progress with malaria control in western Kenya has stagnated since 2007. Additional interventions to reduce the high burden of malaria in this region are urgently needed. We conducted a two-arm, community-based, cluster-randomized, controlled trial of active case detection and treatment of malaria infections in all residents mass testing and treatment (MTaT) of 10 village clusters (intervention clusters) for two consecutive years to measure differences in the incidence of clinical malaria disease and malaria infections compared with 20 control clusters where MTaT was not implemented. All residents of intervention clusters, irrespective of history of fever or other malaria-related symptoms, were tested three times per year before the peak malaria season using malaria rapid diagnostic tests. All positive cases were treated with dihydroartemisinin-piperaquine. The incidence of clinical malaria was measured through passive surveillance, whereas the cumulative incidence of malaria infection was measured using active surveillance in a cohort comprising randomly selected residents. The incidence of clinical malaria was 0.19 cases/person-year (p-y, 95% CI: 0.13-0.28) in the intervention arm and 0.24 cases/p-y (95% CI: 0.15-0.39) in the control arm (incidence rate ratio [IRR] 0.79, 95% CI: 0.61-1.02). The cumulative incidence of malaria infections was similar between the intervention (2.08 infections/p-y, 95% CI: 1.93-2.26) and control arms (2.19 infections/p-y, 95% CI: 2.02-2.37) with a crude IRR of 0.95 (95% CI: 0.87-1.04). Six rounds of MTaT over 2 years did not have a significant impact on the incidence of clinical malaria or the cumulative incidence of malaria infection in this area of high malaria transmission.
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Antimaláricos/uso terapéutico , Malaria Falciparum/diagnóstico , Adolescente , Artemisininas/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Incidencia , Kenia/epidemiología , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/epidemiología , Malaria Falciparum/transmisión , Masculino , Tamizaje Masivo/métodos , Quinolinas/uso terapéuticoRESUMEN
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 days of ivermectin 300 mcg/kg/day, ivermectin 600 mcg/kg/day, or placebo, all co-administered with 3 days of dihydroartemisinin-piperaquine. On post-treatment day 7, direct skin and membrane feeding assays were conducted using laboratory-reared Anopheles gambiae sensu stricto. 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; 300 mcg/kg/day, n = 24; 600 mcg/kg/day, n = 22). The 14-day post-feeding mortality for mosquitoes fed 7 days post-treatment on blood from pooled patients in both ivermectin arms was similar with direct skin feeding (mosquitoes observed, n = 2941) versus membrane feeding (mosquitoes observed, n = 7380): cumulative mortality (risk ratio 0.99, 95% confidence interval [CI] 0.95-1.03, P = .69) and survival time (hazard ratio 0.96, 95% CI 0.91-1.02, P = .19). Results were consistent by sex, by 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. CLINICAL TRIALS REGISTRATION: NCT02511353.
Asunto(s)
Antiparasitarios/administración & dosificación , Culicidae/efectos de los fármacos , Insecticidas/administración & dosificación , Ivermectina/administración & dosificación , Adulto , Animales , Anopheles/efectos de los fármacos , Antiparasitarios/farmacocinética , Conducta Alimentaria , Femenino , Humanos , Ivermectina/farmacocinética , Malaria/parasitología , Malaria/prevención & control , Masculino , Control de Mosquitos , Adulto JovenRESUMEN
High-dose ivermectin, co-administered for 3 days with dihydroartemisinin-piperaquine (DP), killed mosquitoes feeding on individuals for at least 28 days posttreatment in a recent trial (IVERMAL), whereas 7 days was predicted pretrial. The current study assessed the relationship between ivermectin blood concentrations and the observed mosquitocidal effects against Anopheles gambiae s.s. Three days of ivermectin 0, 300, or 600 mcg/kg/day plus DP was randomly assigned to 141 adults with uncomplicated malaria in Kenya. During 28 days of 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 PKs 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.
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Anopheles , Antimaláricos/farmacología , Antimaláricos/farmacocinética , Artemisininas/farmacología , Artemisininas/farmacocinética , Insecticidas/farmacología , Insecticidas/farmacocinética , Ivermectina/farmacología , Ivermectina/farmacocinética , Malaria/tratamiento farmacológico , Quinolinas/farmacología , Quinolinas/farmacocinética , Adulto , Animales , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Combinación de Medicamentos , Interacciones Farmacológicas , Femenino , Humanos , Kenia , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/epidemiología , Masculino , Resultado del TratamientoRESUMEN
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 µg/kg used for onchocerciasis and lymphatic filariasis have a short-lived mosquitocidal effect (<7 days). Because ivermectin is well tolerated up to 2000 µg/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/m2; women: <23 vs ≥23 kg/m2), with permuted blocks of three, to receive 3 days of ivermectin 300 µg/kg per day, ivermectin 600 µg/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 µg/kg per day (n=47), ivermectin 300 µg/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 µg/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 µg/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 µg/kg per day RR 1·23, 1·01-1·50, p=0·0374; and ivermectin 300 µg/kg per day 1·21, 1·01-1·44, p=0·0337). Five (11%) of 45 patients receiving ivermectin 600 µg/kg per day, two (4%) of 48 patients receiving ivermectin 300 µg/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 µg/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).
Asunto(s)
Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Insecticidas/uso terapéutico , Ivermectina/uso terapéutico , Malaria/tratamiento farmacológico , Quinolinas/farmacología , Adolescente , Adulto , Combinación Albuterol y Ipratropio , Antimaláricos/administración & dosificación , Artemisininas/administración & dosificación , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Insecticidas/administración & dosificación , Insecticidas/efectos adversos , Ivermectina/administración & dosificación , Ivermectina/efectos adversos , Masculino , Persona de Mediana Edad , Quinolinas/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND Primary mediastinal non-seminomatous germ cell tumors (NSGCTs) are aggressive and carry a poor five-year disease free survival rate even with aggressive treatment. We describe a young adult male with primary mediastinal NSGCT presenting with airway obstruction and superior vena cava syndrome (SVCS). CASE REPORT The patient presented with four weeks of nonproductive cough, weight loss, and right-sided pleuritic chest pain. Chest computed topography (CT) imaging demonstrated a right-sided mediastinal mass determined as a yolk sac tumor on biopsy. The patient underwent induction chemotherapy with etoposide and cisplatin for stage III NSGCT. In the interim, he developed SVCS warranting a second cycle of chemotherapy along with intravenous steroids, with notable improvement in symptoms. However, serial alpha-fetoprotein (AFP) measurements showed progressively increasing levels up to a maximum of 18,781 ng/mL indicating treatment failure. He is currently on salvage chemotherapy. CONCLUSIONS Obstruction of the SVC by external compression is often a manifestation of a malignant process in the thorax. SVCS is a medical emergency and occurs in 6% of patients with mediastinal GCTs. Historically, irradiation was initiated without a histologic diagnosis to relieve the life-threatening obstruction. However, newer data suggest that it is acceptable to defer therapy until a full diagnostic workup is completed. This case highlights the malignant nature of primary mediastinal NSGCTs. In addition, inasmuch as SVCS is dramatic in presentation, it is important to recognize that symptomatic obstruction often develops over weeks or longer. In a hemodynamically stable patient, an accurate histologic diagnosis prior to starting treatment is essential in guiding therapy.
Asunto(s)
Neoplasias de Células Germinales y Embrionarias/complicaciones , Síndrome de la Vena Cava Superior/etiología , Neoplasias Testiculares/complicaciones , Obstrucción de las Vías Aéreas/etiología , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Testiculares/patología , Adulto JovenRESUMEN
OBJECTIVE: Mild viral illness, including that following immunization with live attenuated measles virus (LAMV), has been associated with transient decreases in haemoglobin (Hb) and cellular immune response that may persist for several weeks. In areas of intense malaria transmission, such as western Kenya, infants experience a progressive drop in Hb until age 9-10 months and one-third may have Hb < 8 g/dl. These children may be at risk of developing severe anaemia with further haematological insult. The objective of this paper was to determine if immunization with LAMV was associated with increased risk of transient anaemia and malaria infection. METHODS: Data from previous cross-sectional surveys (n = 5970) and one cohort study (n = 546) conducted among pre-school children were analyzed retrospectively. RESULTS: Measles vaccination coverage between 12 and 23 months of age ranged from 44.8% to 62.7%. Hb concentrations in children aged 6-23 months with documented measles immunization within the previous 14 or 30 days (n = 103) were similar to those with no history of measles immunization in the previous 90 days (n = 996); mean differences [95% confidence interval (CI)] by 30 days were: in cross-sectional surveys, -0.49 g/dl (-1.12, 0.14); in the cohort study, -0.032 g/dl (-0.52, 0.46). Similarly, the risk of malaria parasitemia or severe to moderate anaemia did not differ. CONCLUSION: These data do not suggest that the transient decrease in Hb and cellular immune response after immunization with LAMV results in clinically significant changes in the risk of subsequent severe to moderate anaemia or malaria in young children living in malaria-endemic regions.
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Anemia/etiología , Malaria/etiología , Vacuna Antisarampión/efectos adversos , Sarampión/prevención & control , Anemia/epidemiología , Tamaño de la Célula/efectos de los fármacos , Femenino , Hemoglobinas/análisis , Humanos , Lactante , Kenia/epidemiología , Malaria/epidemiología , Masculino , Sarampión/epidemiología , Parasitemia/inducido químicamente , Estudios Retrospectivos , Vacunación/efectos adversos , Vacunas Atenuadas/efectos adversosRESUMEN
In sub-Saharan Africa, the etiology of anemia in early childhood is complex and multifactorial. Three community-based cross-sectional surveys were used to determine the prevalence and severity of anemia. Regression methods were used to compare mean hemoglobin (Hb) concentrations across covariate levels to identify children at risk of low Hb levels in an area with intense malaria transmission. In a random sample of 2,774 children < 36 months old, the prevalence of anemia (Hb < 11g/dL) was 76.1% and 71%, respectively, in villages without and with insecticide-treated bed nets (ITNs); severe-moderate anemia (Hb < 7 g/dL) was observed in 11% (non-ITN) and 8.3% (ITN). The prevalence of anemia, high-density malaria parasitemia (21.7%), microcytosis (34.9%), underweight (21.9%), and diarrhea (54.8%) increased rapidly from age three months onwards and remained high until 35 months of age. Multivariate analyses showed that family size, history of fever, pale body, general body weakness, diarrhea, soil-eating, concurrent fever, stunting, and malaria parasitemia were associated with mean Hb levels. Prevention of severe anemia should start early in infancy and include a combination of micronutrient supplementation, malaria control, and possibly interventions against diarrheal illness.
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Anemia/metabolismo , Hemoglobinas/análisis , Malaria/metabolismo , Anemia/epidemiología , Anemia/parasitología , Preescolar , Estudios Transversales , Femenino , Estado de Salud , Encuestas Epidemiológicas , Hemoglobinas/metabolismo , Humanos , Kenia/epidemiología , Malaria/epidemiología , Malaria/transmisión , Masculino , Anamnesis , Morbilidad , PrevalenciaRESUMEN
PROBLEM/CONDITION: Malaria is caused by any of four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing transmission. In the United States, cases can occur through exposure to infected blood products, by congenital transmission, or by local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. PERIOD COVERED: This report covers cases with onset of illness in 2002. DESCRIPTION OF SYSTEM: Malaria cases confirmed by blood film are reported to local and state health departments by health-care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS). Data from NMSS serve as the basis for this report. RESULTS: CDC received reports of 1,337 cases of malaria with an onset of symptoms in 2002 among persons in the United States or one of its territories. This number represents a decrease of 3.3% from the 1,383 cases reported for 2001. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 52.3%, 25.4%, 2.8%, and 2.8% of cases, respectively. Eleven patients (0.8% of total) were infected by > or =2 species. The infecting species was unreported or undetermined in 213 (15.9%) cases. Compared with 2001, the number of reported malaria cases acquired in Asia (n = 171) and Africa (n = 903) increased by 4.3% and 1.9%, respectively, whereas the number of cases acquired in the Americas (n = 141) decreased by 41.2%. Of 849 U.S. civilians who acquired malaria abroad, 317 (37.3%) reported that they had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Five patients became infected in the United States, one through congenital transmission, one probable transfusion-related, and three whose infection cannot be linked epidemiologically to secondary cases. Eight deaths were attributed to malaria. All deaths were caused by P. falciparum. INTERPRETATION: The 3.3% decrease in malaria cases in 2002, compared with 2001, resulted primarily from a marked decrease in cases acquired in the Americas, but this decrease was offset somewhat by an increase in the number of cases acquired in Africa and Asia. This limited decrease probably represents year-to-year variation in malaria cases, but also could have resulted from local changes in disease transmission, decreased travel to malaria-endemic regions, fluctuation in reporting to state and local health departments, or an increased use of effective antimalarial chemoprophylaxis. In the majority of reported cases, U.S. civilians who acquired infection abroad were not on an appropriate chemoprophylaxis regimen for the country in which they acquired malaria. PUBLIC HEALTH ACTION: Additional information was obtained concerning the eight fatal cases and the five infections acquired in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel, and travelers should use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently experiences a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should include a blood-film test for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning malaria prevention can be obtained from CDC by calling the Malaria Hotline at 770-488-7788 or by accessing CDC's Internet site at http://www.cdc.gov/travel.
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Malaria/epidemiología , Antimaláricos/uso terapéutico , Humanos , Malaria/diagnóstico , Malaria/prevención & control , Vigilancia de la Población , Viaje , Estados Unidos/epidemiologíaRESUMEN
A recent meta-analysis of 14 clinical trials indicated that daily compared with intermittent iron supplementation resulted in significantly greater hematological improvement in pregnant women. No such definitive beneficial effect was demonstrated in preschool children. We compared the efficacy of daily and twice weekly iron supplementation for 6 wk under supervised and unsupervised conditions in the treatment of mild and moderate anemia [hemoglobin (Hb) 50-109 g/L] in children aged 2-59 mo living in a malaria-endemic area of western Kenya. The study was a cluster-randomized trial using a factorial design; participants were aware of the treatment assigned. All children (n = 1049) were administered a single dose of sulfadoxine-pyrimethamine at enrollment followed by 6 wk of daily supervised iron supplementation [3-6 mg/(kg.d)], twice weekly supervised iron supplementation [6-12 mg/(kg.wk)], daily unsupervised iron supplementation, or twice weekly unsupervised iron supplementation. In the supervised groups, Hb concentrations at 6 and 12 wk (6 wk postsupplementation) were significantly higher in children given iron daily rather than twice weekly [mean (95% CI) difference at 6-wk: 4.2 g/L (2.1, 6.4); 12-wk: 4.4 g/L (1.8, 7.0)]. Among the unsupervised groups, Hb concentrations were not different at 6 wk [mean (95% CI) difference: 0.86 g/L (-1.4, 3.1)], but significantly higher at 12 wk for those assigned daily iron [mean (95% CI) difference: 3.4 g/L (0.79, 6.0), P = 0.02]. In this malarious area and after initial antimalarial treatment, 6 wk of daily iron supplementation results in better hematological responses than twice weekly iron supplementation in the treatment of anemia in preschool children, regardless of whether adherence can be ensured.
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Anemia/tratamiento farmacológico , Suplementos Dietéticos , Hierro/administración & dosificación , Anemia/sangre , Antimaláricos/uso terapéutico , Preescolar , Esquema de Medicación , Combinación de Medicamentos , Enfermedades Endémicas , Femenino , Hemoglobinas/metabolismo , Humanos , Lactante , Hierro/efectos adversos , Kenia , Malaria/epidemiología , Masculino , Concentración Osmolar , Pirimetamina/uso terapéutico , Sulfadoxina/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Iron supplementation has been associated with greater susceptibility to malaria and lower hematologic responses in pregnant Gambian women with sickle cell trait (HbAS) than in similar women with the normal (HbAA) phenotype. It is not known whether a similar interaction exists in children. OBJECTIVE: Our aim was to determine the influence of the HbAS phenotype on hematologic responses and malaria after iron supplementation in anemic (hemoglobin: 70-109 g/L) children aged 2-35 mo. DESIGN: We conducted a double-blind, randomized, placebo-controlled trial (HbAS, n = 115; HbAA, n = 408) of intermittent preventive treatment with sulfadoxine pyrimethamine (IPT-SP) at 4 and 8 wk and daily supervised iron for 12 wk. RESULTS: The mean difference in hemoglobin concentrations at 12 wk between children assigned iron and placebo iron, after adjustment for the effect of IPT-SP, was 9.1 g/L (95% CI: 6.4, 11.8) and 8.2 g/L (4.0, 12.4) in HbAA and HbAS children, respectively (P for interaction = 0.68). Although malaria parasitemia and clinical malaria occurred more often in HbAS children in the iron group than in those in the placebo iron group, this difference was not significant; incidence rate ratios were 1.23 (95% CI: 0.64, 2.34) and 1.41 (0.39, 5.00), respectively. The corresponding incidence rate ratios in HbAA children in the same groups were 1.07 (95% CI: 0.77, 1.48) and 0.59 (0.35, 1.01), respectively. The corresponding interactions between the effects of iron and hemoglobin phenotype were not significant. CONCLUSIONS: There was no evidence for a clinically relevant modification by the hemoglobin S phenotype of the effects of iron supplementation in the treatment of mild anemia. The benefits of iron supplementation are likely to outweigh possible risks associated with malaria in children with the HbAA or HbAS phenotype.
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Anemia/complicaciones , Hemoglobinas/análisis , Hierro/efectos adversos , Malaria/epidemiología , Rasgo Drepanocítico , Anemia/tratamiento farmacológico , Antimaláricos/uso terapéutico , Preescolar , Suplementos Dietéticos , Susceptibilidad a Enfermedades , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Lactante , Hierro/administración & dosificación , Kenia , Malaria/prevención & control , Masculino , Fenotipo , Pirimetamina/uso terapéutico , Sulfadoxina/uso terapéuticoRESUMEN
A randomized, placebo-controlled treatment trial was conducted among 546 anemic (hemoglobin concentration, 7-11 g/dL) children aged 2-36 months in an area with intense malaria transmission in western Kenya. All children used bednets and received a single dose of sulfadoxine-pyrimethamine (SP) on enrollment, followed by either intermittent preventive treatment (IPT) with SP at 4 and 8 weeks and daily iron for 12 weeks, daily iron and IPT with SP placebo, IPT and daily iron placebo, or daily iron placebo and IPT with SP placebo (double placebo). The mean hemoglobin concentration at 12 weeks, compared with that for the double-placebo group, was 1.14 g/dL (95% confidence interval [CI], 0.82-1.47 g/dL) greater for the IPT+iron group, 0.79 g/dL (95% CI, 0.46-1.10 g/dL) greater for the iron group, and 0.17 g/dL (95% CI, -0.15-0.49 g/dL) greater for the IPT group. IPT reduced the incidence of malaria parasitemia and clinic visits, but iron did not. The combination of IPT and iron supplementation was most effective in the treatment of mild anemia. Although IPT prevented malaria, the hematological benefit it added to that of a single dose of SP and bednet use was modest.