Preventing Malaria During Pregnancy in Epidemic-prone Areas.

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and cost-effectiveness of three alternative strategies for the prevention of malaria during pregnancy in an epidemic-prone area of low transmission in the East African Highlands. The strategies being compared are: intermittent preventive treatment with sulfadoxine-pyrimethamine (IPT-SP) an insecticide treated net (ITN), and intermittent preventive treatment with SP plus an ITN In addition to the main individually-randomised trial, outcome data was subsequently also gathered on pregnant women whose houses where sprayed with indoor residual insecticides (IRS) as part of a non-randomised district-wide control programme to compare the impact of IRS with the three intervention arms.

Detailed Description
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Susceptibility to malaria infection during pregnancy and the severity of clinical manifestation are determined by the level of pre-pregnancy immunity, which depends on intensity and stability of malaria transmission. Most intervention trials to prevent malaria during pregnancy have been conducted in areas of intense transmission. The results of trials conducted in high-transmission areas may not be applicable to low transmission areas, where malaria is less frequent but the risk of spontaneous abortion and stillbirth is very high in women of all parities due to lack of sufficient malaria immunity. Routine chemoprophylaxis is generally not recommended in areas of unstable malaria transmission. However, intermittent treatment with an effective anti-malarial drug may be beneficial, especially during periods of malaria transmission. Little work has been carried out amongst pregnant women living in areas of low and unstable transmission in Africa. No data are available on the cost-effectiveness of malaria control in low transmission settings. This study will compare the efficacy and cost effectiveness of three preventive strategies for the control of malaria during pregnancy in low-transmission settings. The study is located in Kabale district, a highland area in SW Uganda. Women attending antenatal care are randomised to receive either: intermittent preventive treatment with sulfadoxine-pyrimethamine (IPT-SP) an insecticide treated net (ITN), or intermittent preventive treatment with SP and an ITN. It is hypothesized that when combined with IPT-SP, the additional impact of ITNs by reducing exposure may be greatest where the intensity of transmission is low. In addition to the main individually-randomised trial, outcome data was subsequently also gathered on pregnant women whose houses where sprayed with indoor residual insecticides (IRS) as part of a non-randomised district-wide control programme to compare the impact of IRS with the three intervention arms. The study aims to identify the most effective intervention strategies suited to areas characterised by low and unstable transmission. Research findings should be applicable to other hypoendemic areas of the East African highlands.

Official Title
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The Efficacy and Cost-effectiveness of Malaria Prevention in Pregnancy in an Area of Low and Unstable Transmission in Kabale, Uganda: Use of Intermittent Preventive Treatment and Insecticide-treated Nets.

Conditions
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Malaria, Falciparum

Intervention / Treatment
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* Drug: Intermittent preventive treatment:sulphadoxine-pyrimethamine
* Device: Insecticide-treated mosquito bed net


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women whose pregnancies are at <27 weeks gestation at first antenatal booking Permanent resident in study area Informed consent Exclusion Criteria: Late presentation: pregnancies more than 26 weeks gestation at first antenatal booking Severe anaemia (Hb<70g/L) on enrolment Previous reaction to a sulfa-drug (e.g. sulphadoxine-pyrimethamine, septrin) History of severe skin reaction to any drug Current (or history) of severe disease (e.g. hepatitis, jaundice, TB, AIDS) Withdrawal Criteria: Withdrawal of consent Women developing severe anaemia (Hb<70g/L)during pregnancy
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Drug: Intermittent preventive treatment:sulphadoxine-pyrimethamine | Drug: Intermittent preventive treatment:sulphadoxine-pyrimethamine<br>* Two doses given twice during pregnancy (once in the second trimester, and once in the third trimester). Oral medication in tablet form: single daily dose given on each occasion<br>|
| Active Comparator: 2<br>Device: Insecticide-treated mosquito bed net | Device: Insecticide-treated mosquito bed net<br>* Insecticide-treated mosquito bed net<br>|
| Active Comparator: 3<br>Combination of Drug + Device: Drug: Intermittent preventive treatment:sulphadoxine-pyrimethamine Device: Insecticide-treated mosquito bed net | Drug: Intermittent preventive treatment:sulphadoxine-pyrimethamine<br>* Two doses given twice during pregnancy (once in the second trimester, and once in the third trimester). Oral medication in tablet form: single daily dose given on each occasion<br>Device: Insecticide-treated mosquito bed net<br>* Insecticide-treated mosquito bed net<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean birthweight |  | April 2004-Jan 2007 | 
| prevalence of low birthweight |  | April 2004 - Jan 2007 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maternal anaemia - mean Hb at gestational age 36 weeks, prevalence of Hb<100g/L at gestational age 36 weeks |  | Feb 2003 - Jan 2007 | 
| spontaneous abortions |  | Feb 2003 - Jan 2007 | 
| stillbirths |  | April 2003-Jan 2007 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malaria, pregnancy, intermittent preventive treatment, insecticide-treated nets