Active clinical trials for "Malaria"

Background: Antigen-detecting rapid diagnostic tests (RDTs) for malaria provide the possibility of a parasite-based diagnosis in areas where good quality microscopy can not be achieved. P. falciparum tests targeting the histidine-rich protein (HRP2) antigen are generally more sensitive than tests targeting the Plasmodium lactate dehydrogenase (pLDH) antigen. However, as the HRP2 antigen is eliminated from the bloodstream more slowly than the pLDH antigen, HRP2-based tests can give a positive result two weeks or more after the patient has taken an effective treatment, while pLDH tests generally turn negative a few days after. The use of an RDT positive result in a routine patient care is therefore challenged by the interpretation of whether the result is due to a lasting effect of the already treated infection or to a new infection. The interpretation might also be affected by the level of malaria transmission in the area. Objective: The objective of this study is to estimate the proportion of positive tests in patients successfully treated for malaria (smear negative) at different time points in time after treatment, for three rapid diagnostic tests: SD Bioline Malaria Antigen P.f. (catalogue number: 05FK50-02-4), CareStart Malaria HRP2 (Pf) (catalogue number: G0141) and CareStart Malaria pLDH (PAN) (catalogue number: G0111). The study will be carried out in two settings with known low and high malaria transmission levels in order to provide guidance of interpretation of a RDT positive result depending on the intensity of malaria transmission. Secondary objectives will be to measure the sensitivity and specificity of the malaria rapid tests compared to smear microscopy, to estimate the median time to become negative for each of the tests and to estimate the proportion of positive tests and the median time to become negative according to the initial parasitaemia and the presence of gametocytes.

Malaria is caused by a parasite and is a health problem for mothers and fetuses (unborn infants). The Cameroonian Ministry of Health recommends that all pregnant women should take the drug sulfadoxine-pyrimethamine (also known as SP) every two months during pregnancy to avoid malaria. The purpose of this study is to find out how effective SP is in preventing pregnant Cameroonian women from getting malaria. Additional goals of this study are to see whether: SP prevents malaria parasites from causing changes in the placenta; SP prevents or helps women make a substance that keeps parasites from accumulating in the placenta; and whether SP affects the amount of protection a mother transfers to her baby. Participants will include 1,160 pregnant women, ages 15-50 years, and 216 babies born residing in Ngalii II and Ntouessong. Study procedures will include monthly blood samples from pregnant women and babies. Volunteers may participate in this study for up to 19 months.

We observed in a randomised intervention trial in Bissau that mortality due to malaria could be reduced by half by adding a small monetary incentive to the staff and strict follow-up of a standard protocol for available drugs. The Government and donors are not able to sustain such incentives. We intend to evaluate whether strict organisation of a cost recovery system and the use of part of the funds for staff incentives would improve performance of the staff and contribute to reduction of hospital and post-discharge mortality.

In areas of seasonal malaria transmission the burden of severe disease and mortality due to malaria is mainly among children under 5 years of age. Intermittent preventive treatment (IPT) with antimalarial drugs given to all children once a month during the transmission season is a promising new strategy for malaria prevention. Studies in Senegal, Ghana, Mali and The Gambia have shown this approach can be highly effective. In Senegal, seasonal IPT with sulfadoxine-pyrimethamine (SP) and one dose of artesunate resulted in a 90% reduction in incidence of clinical malaria in a recent trial in Senegal (Cisse et al., Lancet 2006). The purpose of the present project is to determine the public health impact and cost effectiveness of this intervention when it is delivered through the routine health service to communities in rural areas in Senegal. Demographic surveillance will be set up in the rural population of three districts (Mbour, Bambey and Fatick) which comprises approximately 540,000 people, including 100,000 children under 5 yrs, and is served by 54 health posts, as an expansion of the area covered by the existing DSS of Niakhar. Information about births, deaths and migrations, household characteristics such as socioeconomic status, and vaccination status of children and their use of bednets, will be recorded in 6-monthly rounds of all households. In selected areas, deaths among children under 10 years will be investigated using verbal autopsies. Over four years from September 2008 - November 2011, seasonal IPT (three monthly administrations of SP (sulfalene-pyrimethamine) plus amodiaquine during the transmission season each year to children 3-59 months of age) will be introduced gradually, in a step-wedge design, by 9 health posts in 2008, by an additional 18 posts in 2009, and another 18 in 2010 and 9 in 2011. At the end of each transmission season, a cross-sectional survey of 2400 children under 5 yrs of age, in which finger prick blood samples will be taken, will be used to estimate the prevalence of molecular markers of drug resistance to Plasmodium falciparum, the prevalence of anaemia and the nutritional status of children. Malaria incidence will be monitored by passive surveillance through health posts, health centres, and hospitals. Cost effectiveness will be assessed. Due to changes in the epidemiology of malaria in the study area, the upper age limit for inclusion was increased from 5 to 10 years old from September 2009.

Most of the neonatal deaths that occur worldwide every year are associated with low birth weight (LBW), caused by intrauterine growth restriction (IUGR) and/or preterm delivery. Accurate assessment of fetal growth and gestational age for timely identification and management of growth restriction are therefore public health priorities, especially in developing countries where 98% of all neonatal deaths occur. Every year, more than 50 million women become pregnant in malaria endemic regions. Malaria infection at any time during pregnancy reduces birthweight. However, little is known about the relationship between the timing of infection during pregnancy and the extent of the impact on birth weight. The mechanisms by which malaria causes LBW also remain unclear. Reduced placental blood flow, placental changes, red blood cell changes, severe anaemia and pro-inflammatory cytokines have all been implicated. In this proposed, longitudinal, observational, minimal risk study, which will take place in SMRU antenatal clinics on the Thai-Burmese border, the effect of malaria infection during pregnancy on fetal growth will be determined. Women will be screened before 13+6 weeks of gestation and followed with regular ultrasound examinations during pregnancy. When a woman has a malaria infection an extra ultrasound scan will be done to measure growth retardation or placental blood flow changes. Bloodsamples will be taken to detect changes in red blood cell properties and putative markers of malaria infection. For this study the maximum amount of blood taken during pregnancy is 13 cc in an uninfected woman. For each malaria episode an additional 7 cc blood will be taken. After delivery a placenta and a cord sample will be taken to detect placental changes. The investigators aim to recruit four hundred pregnant women over the course of two years. This study involves minimal risk to participants as ultrasound examination is part of routine antenatal care in many countries in the world.

The primary objective is to estimate the relative bioavailability of fixed azithromycin / chloroquine combination tablets relative to co-administered individual tablets of azithromycin and chloroquine.

Antimalarial drug resistance has reached critical levels on the Thai-Cambodian border. Many have begun advocating for concerted malaria elimination efforts in Cambodia. However, there is currently no consensus on how malaria elimination is to be achieved with the tools available. In this study, the investigators will conduct operational research with the Royal Cambodian Armed Forces (RCAF) and National Malaria Center (CNM) to quantify the relative effectiveness of the two major interventional approaches - monthly malaria prophylaxis (MMP) or focused screening and treatment (FSAT) - in a head to-head comparison. In addition, the investigators will quantify the relative contribution of a recently advocated vector intervention for military personnel - the insecticide treated uniform (ITU) - in addition to other vector control measures currently employed by the RCAF. The investigators will employ the same permethrin insecticide self-application kits currently used by the US military. The investigators will estimate the cost effectiveness of each approach and attempt to define the best way forward for malaria elimination efforts in a critically important malaria reservoir in military population (and their dependents) who reside on the Thai-Cambodian border. The aim of the study is not only to conduct research to better define the best way forward in malaria elimination efforts in the high risk military populations, but to also build capacity within the RCAF to support and lead future elimination efforts in the most difficult-to-reach mobile populations.

Plasmodium falciparum parasitaemia in pregnancy is associated with maternal anaemia, low birth-weight and increased perinatal mortality. Whilst continuous prophylaxis is difficult to implement, intermittent presumptive treatment in pregnancy (IPTp) has proved to be practical and effective. In PNG, pregnant women currently receive IPTp using sulfadoxine-pyrimethamine, however, this therapy has the potential to be compromised by parasite resistance. The aim of the present trial is to assess the safety, tolerability, pharmacokinetics and efficacy of azithromycin (AZI) plus piperaquine (PQ) given as IPTp to pregnant Papua New Guinea women. The study will comprise of two sub-studies: (i) A safety, tolerability and pharmacokinetic study of AZI-PQ in pregnancy. (ii) A safety, tolerability and preliminary efficacy study of AZI-PQ in pregnancy.

The burden of malaria is greatest in children and pregnant women in sub-Saharan Africa. Malaria is one of the most important infectious diseases in the world. Uganda reports among the highest transmission intensities in the world. Children and pregnant women are the most vulnerable populations. HIV is also reported at high rates for these populations. If malaria and HIV require treatment at the same time, there is a high risk for drug-drug interactions. This study will: Determine if the use of anti-HIV medications including lopinavir/ritonavir (LPV/r), nevirapine (NVP) and efavirenz (EFV) will affect the pharmacokinetic (PK) exposure of antimalarial medications (specifically artemether-lumefantrine, AL) during the treatment for uncomplicated malaria in HIV-infected children and pregnant women, and Evaluate the impact of age and pregnancy on the PK exposure of AL.

This is an observational safety and efficacy study on dihydroartemisinin-piperaquine in Timika, Indonesia with a 42 day follow up period.