RESUMEN
BACKGROUND: Malnutrition amongst under-fives remains common in resource-poor countries and is resistant to current interventions. New opportunities have emerged to target "environmental enteric dysfunction" (EED) that refers to the abnormal gut structure and function that results from colonisation of the gut with pathogenic microbes and compromises nutrition and growth in early life. Although the gut microbiome may provide a defence against ingested gut pathogens through colonisation resistance, its development is adversely affected by multiple environmental factors. Dietary supplements of pro- or synbiotics may build the resilience of the gut microbiome against these environmental factors and boost colonisation resistance. We aim to assess whether dietary supplementation of newborns in rural Kenya with pro/synbiotics prevents or ameliorates EED and improves growth. METHODS: Six hundred newborns less than 4 days old will be recruited from Homa Bay County Teaching and Referral Hospital, western Kenya. Newborns will be randomly allocated, stratified by HIV exposure, in a 1:1:1:1 ratio to one of 4 study arms to receive either of two synbiotics, a probiotic or no supplement. Supplements will be given daily for 10 days and then weekly until 6 months of age. Participants will be followed until the age of 2 years. The primary outcome is systemic inflammation at 6 months assessed by plasma alpha-1-acid glycoprotein. Secondary outcomes include biomarkers of gut health and growth, anthropometric indices, morbidity and mortality. DISCUSSION: As dietary supplements with pro- or synbiotics may improve gut health and can be administered in early life, our findings may inform the package of interventions to prevent malnutrition and improve growth in Africa and similar low-resource settings. TRIAL REGISTRATION: Pan African Clinical Trials Registry, Trial number: PACTR202003893276712. Date: 02/03/2020 https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9798.
Asunto(s)
Microbioma Gastrointestinal , Desnutrición , Probióticos , Simbióticos , Preescolar , Humanos , Lactante , Recién Nacido , Kenia , Probióticos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: HIV, syphilis, malaria and anaemia are leading preventable causes of adverse pregnancy outcomes in sub-Saharan Africa yet testing coverage for conditions other than HIV is low. Availing point-of-care tests (POCTs) at rural antenatal health facilities (dispensaries) has the potential to improve access and timely treatment. Fundamental to the adoption of and adherence to new diagnostic approaches are healthcare workers' and pregnant women's (end-users) buy-in. A qualitative approach was used to capture end-users' experiences of using POCTs for HIV, syphilis, malaria and anaemia to assess the appropriateness, acceptability and feasibility of integrated testing for ANC. METHODS: Seven dispensaries were purposively selected to implement integrated point-of-care testing for eight months in western Kenya. Semi-structured interviews were conducted with 18 healthcare workers (14 nurses, one clinical officer, two HIV testing counsellors, and one laboratory technician) who were trained, had experience doing integrated point-of-care testing, and were still working at the facilities 8-12 months after the intervention began. The interviews explored acceptability and relevance of POCTs to ANC, challenges with testing, training and supervision, and healthcare workers' perspectives of client experiences. Twelve focus group discussions with 118 pregnant women who had attended a first ANC visit at the study facilities during the intervention were conducted to explore their knowledge of HIV, syphilis, malaria, and anaemia, experience of ANC point-of-care testing services, treatments received, relationships with healthcare workers, and experience of talking to partners about HIV and syphilis results. RESULTS: Healthcare workers reported that they enjoyed gaining new skills, were enthusiastic about using POCTs, and found them easy to use and appropriate to their practice. Initial concerns that performing additional testing would increase their workload in an already strained environment were resolved with experience and proficiency with the testing procedures. However, despite having the diagnostic tools, general health system challenges such as high client to healthcare worker volume ratio, stock-outs and poor working conditions challenged the delivery of adequate counselling and management of the four conditions. Pregnant women appreciated POCTs, but reported poor healthcare worker attitudes, drug stock-outs, and fear of HIV disclosure to their partners as shortcomings to their ANC experience in general. CONCLUSION: This study provides insights on the acceptability, appropriateness, and feasibility of integrating POCTs into ANC services among end-users. While the innovation was desired and perceived as beneficial, future scale-up efforts would need to address health system weaknesses if integrated testing and subsequent effective management of the four conditions are to be achieved.
Asunto(s)
Anemia , Prestación Integrada de Atención de Salud , Infecciones por VIH , Malaria , Satisfacción del Paciente , Pruebas en el Punto de Atención , Atención Prenatal , Adulto , Anemia/terapia , Femenino , Infecciones por VIH/tratamiento farmacológico , Conocimientos, Actitudes y Práctica en Salud , Humanos , Kenia , Malaria/terapia , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Investigación Cualitativa , Sífilis/terapiaRESUMEN
BACKGROUND: In sub-Saharan Africa, HIV, syphilis, malaria and anaemia are leading preventable causes of adverse pregnancy outcomes. In Kenya, policy states women should be tested for all four conditions (malaria only if febrile) at first antenatal care (ANC) visit. In practice, while HIV screening is conducted, coverage of screening for the others is suboptimal and early pregnancy management of illnesses is compromised. This is particularly evident at rural dispensaries that lack laboratories and have parallel programmes for HIV, reproductive health and malaria, resulting in fractured and inadequate care for women. METHODS: A longitudinal eight-month implementation study integrating point-of-care diagnostic tests for the four conditions into routine ANC was conducted in seven purposively selected dispensaries in western Kenya. Testing proficiency of healthcare workers was observed at initial training and at three monthly intervals thereafter. Adoption of testing was compared using ANC register data 8.5 months before and eight months during the intervention. Fidelity to clinical management guidelines was determined by client exit interviews with success defined as ≥90% adherence. FINDINGS: For first ANC visits at baseline (n = 529), testing rates were unavailable for malaria, low for syphilis (4.3%) and anaemia (27.8%), and near universal for HIV (99%). During intervention, over 95% of first attendees (n = 586) completed four tests and of those tested positive, 70.6% received penicillin or erythromycin for syphilis, 65.5% and 48.3% received cotrimoxazole and antiretrovirals respectively for HIV, and 76.4% received artemether/lumefantrine, quinine or dihydroartemisinin-piperaquine correctly for malaria. Iron and folic supplements were given to nearly 90% of women but often at incorrect doses. CONCLUSIONS: Integrating point-of-care testing into ANC at dispensaries with established HIV testing programmes resulted in a significant increase in testing rates, without disturbing HIV testing rates. While more cases were detected and treated, treatment fidelity still requires strengthening and an integrated monitoring and evaluation system needs to be established.
Asunto(s)
Anemia/diagnóstico , Suplementos Dietéticos , Infecciones por VIH/diagnóstico , Malaria/diagnóstico , Complicaciones Hematológicas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Sífilis/diagnóstico , Adulto , Anemia/tratamiento farmacológico , Anemia/metabolismo , Antibacterianos/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Antimaláricos/uso terapéutico , Combinación Arteméter y Lumefantrina/uso terapéutico , Artemisininas/uso terapéutico , Eritromicina/uso terapéutico , Femenino , Ácido Fólico/administración & dosificación , Adhesión a Directriz , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Personal de Salud , Humanos , Hierro de la Dieta/administración & dosificación , Kenia , Ensayos de Aptitud de Laboratorios/estadística & datos numéricos , Estudios Longitudinales , Malaria/tratamiento farmacológico , Malaria/metabolismo , Penicilinas/uso terapéutico , Pruebas en el Punto de Atención/estadística & datos numéricos , Embarazo , Complicaciones Hematológicas del Embarazo/diagnóstico , Complicaciones Hematológicas del Embarazo/metabolismo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/metabolismo , Atención Prenatal/estadística & datos numéricos , Quinina/uso terapéutico , Quinolinas/uso terapéutico , Sífilis/tratamiento farmacológico , Sífilis/metabolismo , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
Reducing adverse birth outcomes due to malaria in pregnancy (MIP) is a global health priority. However, there are few safe and effective interventions. l-Arginine is an essential amino acid in pregnancy and an immediate precursor in the biosynthesis of nitric oxide (NO), but there are limited data on the impact of MIP on NO biogenesis. We hypothesized that hypoarginemia contributes to the pathophysiology of MIP and that l-arginine supplementation would improve birth outcomes. In a prospective study of pregnant Malawian women, we show that MIP was associated with lower concentrations of l-arginine and higher concentrations of endogenous inhibitors of NO biosynthesis, asymmetric and symmetric dimethylarginine, which were associated with adverse birth outcomes. In a model of experimental MIP, l-arginine supplementation in dams improved birth outcomes (decreased stillbirth and increased birth weight) compared with controls. The mechanism of action was via normalized angiogenic pathways and enhanced placental vascular development, as visualized by placental microcomputerized tomography imaging. These data define a role for dysregulation of NO biosynthetic pathways in the pathogenesis of MIP and support the evaluation of interventions to enhance l-arginine bioavailability as strategies to improve birth outcomes.
Asunto(s)
Malaria/tratamiento farmacológico , Placenta/efectos de los fármacos , Animales , Arginina/análogos & derivados , Arginina/metabolismo , Arginina/uso terapéutico , Femenino , Humanos , Malaria/sangre , Malaria/metabolismo , Ratones , Óxido Nítrico/metabolismo , Placenta/metabolismo , Embarazo , Resultado del Embarazo , Estudios ProspectivosRESUMEN
BACKGROUND: In western Kenya, maternal mortality is a major public health problem estimated at 730/100,000 live births, higher than the Kenyan national average of 488/100,000 women. Many women do not attend antenatal care (ANC) in the first trimester, half do not receive 4 ANC visits. A high proportion use traditional birth attendants (TBA) for delivery and 1 in five deliver unassisted. The present study was carried out to ascertain why women do not fully utilise health facility ANC and delivery services. METHODS: A qualitative study using 8 focus group discussions each consisting of 8-10 women, aged 15-49 years. Thematic analysis identified the main barriers and facilitators to health facility based ANC and delivery. RESULTS: Attending health facility for ANC was viewed positively. Three elements of care were important; testing for disease including HIV, checking the position of the foetus, and receiving injections and / or medications. Receiving a bed net and obtaining a registration card were also valuable. Four barriers to attending a health facility for ANC were evident; attitudes of clinic staff, long clinic waiting times, HIV testing and cost, although not all women felt the cost was prohibitive being worth it for the health of the child. Most women preferred to deliver in a health facility due to better management of complications. However cost was a barrier, and a reason to visit a TBA because of flexible payment. Other barriers were unpredictable labour and transport, staff attitudes and husbands' preference. CONCLUSIONS: Our findings suggest that women in western Kenya are amenable to ANC and would be willing and even prefer to deliver in a healthcare facility, if it were affordable and accessible to them. However for this to happen there needs to be investment in health promotion, and transport, as well as reducing or removing all fees associated with antenatal and delivery care. Yet creating demand for service will need to go alongside investment in antenatal services at organisational, staffing and facility level in order to meet both current and future increase in demand.
Asunto(s)
Aceptación de la Atención de Salud/estadística & datos numéricos , Atención Prenatal , Adolescente , Adulto , Instituciones de Atención Ambulatoria , Actitud del Personal de Salud , Femenino , Grupos Focales , Humanos , Kenia/epidemiología , Salud Materna/estadística & datos numéricos , Persona de Mediana Edad , Partería/métodos , Embarazo , Resultado del Embarazo/epidemiología , Atención Prenatal/métodos , Atención Prenatal/estadística & datos numéricos , Investigación Cualitativa , Servicios de Salud Reproductiva/estadística & datos numéricos , Factores SocioeconómicosRESUMEN
INTRODUCTION: Malaria prevention and iron supplementation are associated with improved maternal and infant outcomes. However, evidence from studies in children suggests iron may adversely modify the risk of malaria. We reviewed the evidence in pregnancy of the association between malaria and markers of iron status, iron supplementation or parenteral treatment. METHODS AND FINDINGS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, and the Malaria in Pregnancy library to identify studies that investigated the association between iron status, iron treatment or supplementation during pregnancy and malaria. Thirty one studies contributed to the analysis; 3 experimental and 28 observational studies. Iron supplementation was not associated with an increased risk of P. falciparum malaria during pregnancy or delivery in Africa (summary Relative Riskâ=â0.89, 95% Confidence Interval (CI) 0.66-1.20, I(2)â=â78.8%, 5 studies). One study in Asia reported an increased risk of P. vivax within 30 days of iron supplementation (e.g. adjusted Hazard Ratioâ=â1.75, 95% CI 1.14-2.70 for 1-15 days), but not after 60 days. Iron deficiency (based on ferritin and C-reactive protein) was associated with lower odds for malaria infection (summary Odds Ratioâ=â0.35, 0.24-0.51, I(2)â=â59.2%, 5 studies). With the exception of the acute phase protein ferritin, biomarkers of iron deficiency were generally not associated with malaria infection. CONCLUSIONS: Iron supplementation was associated with a temporal increase in P vivax, but not with an increased risk of P. falciparum; however, data are insufficient to rule out the potential for an increased risk of P. falciparum. Iron deficiency was associated with a decreased malaria risk in pregnancy only when measured with ferritin. Until there is more evidence, it is prudent to provide iron in combination with malaria prevention during pregnancy.
Asunto(s)
Suplementos Dietéticos/efectos adversos , Hierro/efectos adversos , Malaria Falciparum/inducido químicamente , Complicaciones Parasitarias del Embarazo/inducido químicamente , Biomarcadores/sangre , Femenino , Ferritinas/metabolismo , Humanos , Infusiones Parenterales , Deficiencias de Hierro , Malaria Falciparum/sangre , Malaria Falciparum/diagnóstico , Parasitemia/sangre , Embarazo , Complicaciones Parasitarias del Embarazo/sangre , Complicaciones Parasitarias del Embarazo/diagnóstico , Receptores de Transferrina/sangre , Factores de Riesgo , Solubilidad , Transferrina/metabolismoRESUMEN
BACKGROUND: Understanding the socio-cultural context and perceptions of adverse pregnancy outcomes is important for informing the best approaches for public health programs. This article describes the perceptions, beliefs and health-seeking behaviours of women from rural western Kenya regarding congenital anomalies and miscarriages. METHODS: Ten focus group discussions (FGDs) were undertaken in a rural district in western Kenya in September 2010. The FGDs included separate groups consisting of adult women of childbearing age, adolescent girls, recently pregnant women, traditional birth attendants and mothers of children with a birth defect. Participants were selected purposively. A deductive thematic framework approach using the questions from the FGD guides was used to analyse the transcripts. RESULTS: There was substantial overlap between perceived causes of miscarriages and congenital anomalies and these were broadly categorized into two groups: biomedical and cultural. The biomedical causes included medications, illnesses, physical and emotional stresses, as well as hereditary causes. Cultural beliefs mostly related to the breaking of a taboo or not following cultural norms. Mothers were often stigmatised and blamed following miscarriage, or the birth of a child with a congenital anomaly. Often, women did not seek care following miscarriage unless there was a complication. Most reported that children with a congenital anomaly were neglected either because of lack of knowledge of where care could be sought or because these children brought shame to the family and were hidden from society. CONCLUSION: The local explanatory model of miscarriage and congenital anomalies covered many perceived causes within biomedical and cultural beliefs. Some of these fuelled stigmatisation and blame of the mother. Understanding of these beliefs, improving access to information about the possible causes of adverse outcomes, and greater collaboration between traditional healers and healthcare providers may help to reduce stigma and increase access to formal healthcare providers.
Asunto(s)
Aborto Espontáneo/psicología , Anomalías Congénitas/psicología , Conocimientos, Actitudes y Práctica en Salud , Percepción , Población Rural , Aborto Espontáneo/etiología , Adolescente , Adulto , Anomalías Congénitas/etiología , Cultura , Femenino , Grupos Focales , Humanos , Kenia , Persona de Mediana Edad , Embarazo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: It is unknown whether iron supplementation in human immunodeficiency virus (HIV)-infected children living in regions with high infection pressure is safe or beneficial. A 2-arm, double-blind, randomized, controlled trial was conducted to examine the effects of iron supplementation on hemoglobin, HIV disease progression, and morbidity. METHODS: HIV-infected Malawian children aged 6-59 months with moderate anemia (hemoglobin level, 7.0-9.9 g/dL) were randomly assigned to receive 3 mg/kg/day of elemental iron and multivitamins (vitamins A, C, and D) or multivitamins alone for 3 months. Participants were followed for 6 months. RESULTS: A total of 209 children were randomly assigned to treatment, and 196 (93.8%) completed 6 months of follow-up. Iron supplementation was associated with greater increases in hemoglobin concentrations (adjusted mean difference [aMD], 0.60; 95% confidence interval [CI], .06-1.13; P = .03) and reduced the risk of anemia persisting for up to 6 months follow-up (adjusted prevalence ratio, 0.59; 95% CI, .38-.92; P = .02). Children who received iron had a better CD4 percentage response at 3 months (aMD, 6.00; 95% CI, 1.84-10.16; P = .005) but an increased incidence of malaria at 6 months (incidence rate, 120.2 vs 71.7; adjusted incidence rate ratio [aIRR], 1.81 [95% CI, 1.04-3.16]; P = .04), especially during the first 3 months (incidence rate, 78.1 vs 36.0; aIRR, 2.68 [95% CI, 1.08-6.63]; P = .03). CONCLUSIONS: Iron supplementation in anemic HIV-infected children has beneficial effects on hemoglobin, anemia, and immunity but increases the risk of malaria. Thus, iron supplementation in HIV-infected children living in malaria-endemic areas should only be provided in combination with adequate protection from malaria. CLINICAL TRIALS REGISTRATION: ISRCTN-62947977.
Asunto(s)
Anemia/tratamiento farmacológico , Anemia/virología , Infecciones por VIH/sangre , Hierro/administración & dosificación , Adulto , Anemia/parasitología , Preescolar , Suplementos Dietéticos , Método Doble Ciego , Femenino , Infecciones por VIH/parasitología , Infecciones por VIH/virología , Humanos , Lactante , Hierro/efectos adversos , Malaria Falciparum/sangre , Malaria Falciparum/parasitología , Malaria Falciparum/virología , Malaui , Masculino , Madres , Plasmodium falciparum/aislamiento & purificación , Riesgo , Vitaminas/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: Poor utilisation of facility-based antenatal and delivery care services in Kenya hampers reduction of maternal mortality. Studies suggest that the participation of men in antenatal and delivery care is associated with better health care seeking behaviour, yet many reproductive health programs do not facilitate their involvement. This qualitative study conducted in rural Western Kenya, explored men's perceptions of antenatal and delivery care services and identified factors that facilitated or constrained their involvement. METHODS: Eight focus group discussions were conducted with 68 married men between 20-65 years of age in May 2011. Participants were of the Luo ethnic group residing in Asembo, western Kenya. The area has a high HIV-prevalence and polygamy is common. A topic guide was used to guide the discussions and a thematic framework approach for data analysis. RESULTS: Overall, men were positive in their views of antenatal and delivery care, as decision makers they often encouraged, some even 'forced', their wives to attend for antenatal or delivery care. Many reasons why it was beneficial to accompany their wives were provided, yet few did this in practice unless there was a clinical complication. The three main barriers relating to cultural norms identified were: 1) pregnancy support was considered a female role; and the male role that of provider; 2) negative health care worker attitudes towards men's participation, and 3) couple unfriendly antenatal and delivery unit infrastructure. CONCLUSION: Although men reported to facilitate their wives' utilisation of antenatal and delivery care services, this does not translate to practice as adherence to antenatal-care schedules and facility based delivery is generally poor. Equally, reasons proffered why they should accompany their wives are not carried through into practice, with barriers outweighing facilitators. Recommendations to improve men involvement and potentially increase services utilisation include awareness campaigns targeting men, exploring promotion of joint HIV testing and counselling, staff training, and design of couple friendly antenatal and delivery units.
Asunto(s)
Parto Obstétrico/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Conducta Paterna , Atención Prenatal/estadística & datos numéricos , Servicios de Salud Rural/estadística & datos numéricos , Adulto , Anciano , Actitud del Personal de Salud , Toma de Decisiones , Femenino , Grupos Focales , Identidad de Género , Costos de la Atención en Salud , Ambiente de Instituciones de Salud , Conocimientos, Actitudes y Práctica en Salud/etnología , Hospitales , Humanos , Kenia , Masculino , Persona de Mediana Edad , Partería/economía , Cooperación del Paciente/etnología , Percepción , Embarazo , Adulto JovenRESUMEN
UNLABELLED: Sulfadoxine-pyrimethamine (SP) inhibits folate metabolism by the malaria parasite. We investigated the association between folate levels and SP failure in pregnant women. Data from a trial to assess the effect that folate supplementation has on SP failure in 467 pregnant women were analyzed. Plasma folate levels were determined at enrollment and at day 7. High baseline folate levels, high parasite densities, and age <20 years were risk factors for SP failure. High-dose (5 mg daily) folate supplementation or high folate levels at day 7 were independent risk factors. Therefore, pregnant women receiving SP should receive low-/moderate-dose folate supplementation. TRIAL REGISTRATION: http://www.clinicaltrials.gov identifier: NCT00130065.
Asunto(s)
Antimaláricos/uso terapéutico , Suplementos Dietéticos , Ácido Fólico/administración & dosificación , Ácido Fólico/sangre , Malaria/tratamiento farmacológico , Complicaciones Parasitarias del Embarazo/tratamiento farmacológico , Pirimetamina/uso terapéutico , Sulfadoxina/uso terapéutico , Adulto , Animales , Combinación de Medicamentos , Femenino , Humanos , Kenia , Embarazo , Factores de Riesgo , Análisis de Supervivencia , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the effect of routine antenatal haematinic supplementation programmes and intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) in Kenya. METHODS: Anaemia [haemoglobin (Hb) <11 g/dl), severe anaemia (Hb <8 g/dl) and placental malaria were compared among women with known HIV status who delivered at a provincial hospital after study enrolment in the third trimester during three consecutive periods: period 1, no routine intervention (reference); period 2, routine haematinic supplementation (60 mg elementary iron three times/day, folic acid 5 mg once daily) and period 3, haematinics and IPT with SP. RESULTS: Among 3108 participants, prevalence of placental malaria, anaemia and severe anaemia postpartum was 16.7%, 53.6% and 12.7%, respectively. Compared with period 1, women in period 2 were less anaemic [adjusted odds ratio (AOR), 95% confidence interval anaemia: 0.56, 0.47-0.67; severe anaemia 0.37, 0.28-0.49] and shared a similar prevalence of placental malaria (AOR 1.07, 0.86-1.32). Women in period 3 were also less anaemic (AOR anaemia: 0.43, 0.35-0.53 and severe anaemia: 0.43, 0.31-0.59), and had less placental malaria (AOR 0.56, 0.42-0.73). The effect of intervention did not differ significantly by HIV status. CONCLUSION: The haematinic supplementation programme was associated with significant reductions in anaemia in HIV-seropositive and HIV-seronegative women. The subsequent introduction of IPT was associated with halving of malaria, but no additional haematological benefit over haematinics.
Asunto(s)
Anemia/prevención & control , Seropositividad para VIH/complicaciones , Hematínicos/administración & dosificación , Malaria/prevención & control , Complicaciones Hematológicas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Adulto , Anemia/epidemiología , Antimaláricos/administración & dosificación , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Ácido Fólico/administración & dosificación , Seronegatividad para VIH , Seropositividad para VIH/epidemiología , Humanos , Hierro/administración & dosificación , Kenia/epidemiología , Malaria/epidemiología , Embarazo , Complicaciones Hematológicas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Tercer Trimestre del Embarazo , Prevalencia , Pirimetamina/administración & dosificación , Sulfadoxina/administración & dosificación , Resultado del TratamientoRESUMEN
OBJECTIVES: Sulfadoxine-pyrimethamine (SP) is an antimalarial drug that acts on the folate metabolism of the malaria parasite. We investigated whether folate (FA) supplementation in a high or a low dose affects the efficacy of SP for the treatment of uncomplicated malaria in pregnant women. DESIGN: This was a randomized, placebo-controlled, double-blind trial. SETTING: The trial was carried out at three hospitals in western Kenya. PARTICIPANTS: The participants were 488 pregnant women presenting at their first antenatal visit with uncomplicated malaria parasitaemia (density of >or= 500 parasites/microl), a haemoglobin level higher than 7 g/dl, a gestational age between 17 and 34 weeks, and no history of antimalarial or FA use, or sulfa allergy. A total of 415 women completed the study. INTERVENTIONS: All participants received SP and iron supplementation. They were randomized to the following arms: FA 5 mg, FA 0.4 mg, or FA placebo. After 14 days, all participants continued with FA 5 mg daily as per national guidelines. Participants were followed at days 2, 3, 7, 14, 21, and 28 or until treatment failure. OUTCOME MEASURES: The outcomes were SP failure rate and change in haemoglobin at day 14. RESULTS: The proportion of treatment failure at day 14 was 13.9% (19/137) in the placebo group, 14.5% (20/138) in the FA 0.4 mg arm (adjusted hazard ratio [AHR], 1.07; 98.7% confidence interval [CI], 0.48 to 2.37; p = 0.8), and 27.1% (38/140) in the FA 5 mg arm (AHR, 2.19; 98.7% CI, 1.09 to 4.40; p = 0.005). The haemoglobin levels at day 14 were not different relative to placebo (mean difference for FA 5 mg, 0.17 g/dl; 98.7% CI, -0.19 to 0.52; and for FA 0.4 mg, 0.14 g/dl; 98.7% CI, -0.21 to 0.49). CONCLUSIONS: Concomitant use of 5 mg FA supplementation compromises the efficacy of SP for the treatment of uncomplicated malaria in pregnant women. Countries that use SP for treatment or prevention of malaria in pregnancy need to evaluate their antenatal policy on timing or dose of FA supplementation.
RESUMEN
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.
Asunto(s)
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
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.
Asunto(s)
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.
Asunto(s)
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
Health facility ledgers of 11 rural health facilities in western Kenya were reviewed to evaluate diagnostic and prescribing practices. Clinics lacked laboratory facilities. Of 14,267 sick child visits (SCVs), 76% were diagnosed with malaria and/or upper respiratory infections. Other diagnoses were recorded in less than 5% of SCVs. Although two-thirds of malaria cases were diagnosed with co-infections, less than 3% were concomitantly diagnosed with anemia. Chloroquine and penicillin constituted 94% of prescriptions. Half of children given a sole diagnosis of measles or pneumonia were prescribed chloroquine, and 22% of children with a sole diagnosis of malaria were given penicillin. Antimalarials other than chloroquine were rarely prescribed. Only 12% of children diagnosed with anemia were prescribed iron supplementation, while 53% received folic acid. This study highlights limited diagnostic and prescribing practices and a lack of adherence to national treatment guidelines in rural western Kenya.
Asunto(s)
Servicios de Salud del Niño/estadística & datos numéricos , Prescripciones de Medicamentos , Servicios de Salud Rural/estadística & datos numéricos , Factores de Edad , Población Negra , Preescolar , Prescripciones de Medicamentos/estadística & datos numéricos , Etnicidad , Humanos , Lactante , Recién Nacido , Kenia , Malaria/diagnóstico , Malaria/tratamiento farmacológico , Malaria/epidemiología , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiologíaRESUMEN
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.
Asunto(s)
Anemia/tratamiento farmacológico , Hierro/uso terapéutico , Malaria/prevención & control , Pirimetamina/uso terapéutico , Sulfadoxina/uso terapéutico , Anemia/sangre , Preescolar , Método Doble Ciego , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Hemoglobinas/análisis , Humanos , Lactante , Kenia , Malaria/epidemiología , Masculino , Análisis Multivariante , Resultado del TratamientoRESUMEN
Plasmodium falciparum has developed resistance to almost all routinely used antimalarial drugs. Sulfadoxine-pyrimethamine (SP) has replaced chloroquine as first-line treatment of uncomplicated malaria infection in Kenya but resistance to SP is already reported. The addition of artemisinin derivatives to SP may delay the development of drug resistance, improve cure rates, and reduce transmission. The efficacy and safety of artesunate plus SP in the treatment of uncomplicated P. falciparum malaria was evaluated in a randomized trial of 600 children at Siaya District Hospital, western Kenya between October 1999 and March 2000. Children aged < 5 years were randomly assigned to receive SP alone (1.25 mg/kg based on pyrimethamine), or in combination with artesunate (4 mg/kg/d) for either 1 or 3 d. Parasitological failure by days 14 and 28 (polymerase chain reaction [PCR]-corrected for new infections) were the primary endpoints. Treatment failure rates by day 14 were 25.5% in the SP alone group, 16.2% (risk difference [delta]-9.3%, 95% CI -17.3 to -1.2%, P= 0.027) in the 1-dose artesunate group, and 9.4% (delta-16.2%, 95% CI -23.6 to -8.7%, P< 0.001) in the 3-dose artesunate group. Corresponding rates by day 28 were 46.0% in the SP alone group, 38.2% (delta-7.8%, 95% CI -17.7 to 2.1%, P= 0.16) in the 1-dose artesunate group, and 26.0% (delta-20.0%, 95% CI -29.4 to -10.6%, P < 0.001) in the 3-dose artesunate group. The artesunate and SP combination was well tolerated. There were no serious drug-related adverse events. Parasite clearance and gametocyte carriage were reduced significantly in both combination groups compared with SP alone. Three days of artesunate were required to reduce significantly the risk of treatment failure by day 28. However, the high background rate of parasitological failure with SP may make this combination unsuitable for widespread use in Kenya.
Asunto(s)
Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Pirimetamina/uso terapéutico , Sesquiterpenos/uso terapéutico , Sulfadoxina/uso terapéutico , Antimaláricos/efectos adversos , Artemisininas/efectos adversos , Artesunato , Preescolar , Método Doble Ciego , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Fiebre/tratamiento farmacológico , Genotipo , Humanos , Lactante , Recién Nacido , Kenia , Malaria Falciparum/sangre , Masculino , Pirimetamina/efectos adversos , Sesquiterpenos/efectos adversos , Sulfadoxina/efectos adversos , Resultado del TratamientoRESUMEN
The role of maternal and pediatric infection with human immunodeficiency virus type 1 (HIV-1) and malaria as risk factors for anemia was determined in a birth cohort of infants born to mothers participating in a study of the interaction between placental malaria and HIV infection, in Kisumu, Kenya. Between June 1996 and April 2000, 661 infants born to 467 HIV-seropositive and 194 HIV-seronegative mothers were monitored monthly from birth. At each visit a questionnaire was completed and a blood sample was collected for the determination of hemoglobin levels and detection of malaria and HIV. Anemia was common and increased from 13.6% at one month to 75% at six months and remained high throughout the second half of infancy. Placental malaria, infant malaria, and HIV infection of the infant were all associated with infant anemia in a multivariate model, adjusting for other co-variates found to be associated with infant anemia. The HIV-infected infants with malaria parasitemia had lower mean hemoglobin levels compared with HIV-uninfected infants, or HIV-infected infants without malaria, suggesting that HIV-infected infants are particularly vulnerable to the adverse consequences of malaria at this age. Early detection and prompt treatment of infant malaria and treatment of anemia as part of the study protocol failed to prevent most of the infants from becoming anemic. Although not proven effective in this study, micronutrient supplementation should be prospectively assessed in HIV-infected infants as a means of preventing anemia.