Active clinical trials for "Malaria"

This study will investigate the safety and immunogenicity of 2 candidate malaria vaccines administered according to 3 different vaccination schedules in 5 to 17 months old Ghanaian children. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

The purpose of this study is to investigate the impact of rapid diagnostic tests (RDTs) in the context of a newly implemented malaria case management guidelines using artemisinin-based combination therapy on the malaria prescribing practices of health care workers in Kenya.

BCG vaccine is given at or shortly after birth in many developing countries to prevent tuberculosis. In Guinea Bissau, it has been shown that its protective effect against death is greater than would be expected from its effect against tuberculosis. This observation suggests that BCG may enhance the ability of the immune system of young children to make a protective response to other infections, including malaria. There is some evidence to support this hypothesis as BCG protects against malaria in experimental animals. Because BCG is a recommended vaccine, a randomised controlled trial of BCG at birth would not be ethically justifiable. However, it is not known whether re-vaccination with BCG in the second year of life might provide some added benefit and a large study to determine this is under way in Guinea Bissau. This study examined the effect of re-vaccination with BCG on the incidence of clinical malaria. If re-vaccination with BCG at 19 months of age is found to protect against malaria this would support the hypothesis that one of the ways that BCG at birth provides protection to young children is through an effect on malaria.

Animal and human studies have shown that the prime-boost immunization strategy using malaria antigens expressed in plasmid or viral vectors induces strong cellular immune responses. An immunization regimen with the malaria vaccines DNA ME-TRAP followed by MVA ME-TRAP induced strong T cell responses in adults in the United Kingdom (UK) and in the Gambia but did not provide significant clinical protection against infection. The investigators assessed two new vaccines which utilize a similar immunization strategy but a different malaria antigen, a circumsporozoite (CS) protein. The entire CS protein was expressed either in a modified vaccinia virus Ankara (MVA) CS, or an attenuated fowlpox virus strain (FP9) CS.

In areas of stable transmission, pregnant women, especially during the first and second pregnancies, have an increased susceptibility to Plasmodium falciparum malaria, malaria-related anaemia and an increased risk of having low birthweight babies. Intermittent Preventive Treatment in pregnancy(IPTp) with sulphadoxine-pyrimethamine has been shown to be effective in reducing the effects of malaria in pregnancy. This has mainly been in areas of perennial transmission and there is a need to study this effect in intense seasonal transmission settings. The emergence and spread of resistance to SP is likely to undermine its useful lifespan and it is important that other antimalarials that are safe and effective are identified for use in IPTp. The options are however limited. Amodiaquine has been shown to be effective in treatment of clinical cases of malaria, even in areas where chloroquine resistance is prevalent, and its combination with SP has been associated with favourable results. Both are affordable. However, there is limited data on their use in pregnancy. This study aims to assess the efficacy of SP in an area of intense seasonal transmission, and evaluate the safety and efficacy of amodiaquine and a combination of sulphadoxine-pyrimethamine and amodiaquine as possible alternatives to SP for use as IPTp.

A recent study has shown that the administration of a single dose of sulfadoxine/pyrimethamine plus artesunate to Senegalese children on three occasions during a short malaria transmission season reduced the incidence of clinical attacks of malaria by 86%. However, use of this drug regimen led to the selection of parasites with molecular markers of resistance to pyrimethamine and sulfadoxine. Therefore, a trial of three alternative regimens has been undertaken to see if these are as effective and safe as the drug combination used in the initial study but less likely to select for drug resistance.

It has now been demonstrated clearly that in Western Cambodia parasitological responses to artesunate and artemether containing treatment regimens for uncomplicated falciparum malaria are slower than elsewhere in the world. Median parasite clearance time (PCT) in patients treated with artesunate 4 mg/kg/day was 78 hours and with 2 mg/kg/day 82 hours, compared to 54 and 48 hours, respectively, in Western Thailand; at 72hours peripheral blood parasitaemia was still detectable in 55% of patients in Western Cambodia, compared to 7.5% in Western Thailand. Although occasional poor responses to artesunate have been described previously the current reports suggest a consistent problem. These antimalarials are central to current treatment strategies, and so spread of parasites with reduced artemisinin susceptibility outside this area would be a disaster. A recent consensus meeting Pnomh Penh agreed that this should indeed be termed resistance, and represented a major threat to malaria control. Radical containment measures would be needed. This study aims to address whether a semi-synthetic or fully synthetic peroxide antimalarial would be more effective than artesunate and could therefore be used in Cambodia as part of the elimination strategy. Artemisone is a semisynthetic derivative of dihydroartemisinin, which importantly changes its tertiary structure. This drug has also shown promising efficacy for the treatment of uncomplicated falciparum malaria in phase II trials in Thailand and seems to be at least as efficacious as artesunate. No significant toxicity has been reported for artemisone and it is very well tolerated. If sensitivity for artemisone has remained intact in Western Cambodia, this will have important implications for the strategies available for containment of the threatening problem of artesunate resistance in Western Cambodia. It will also have important implications for further development of these drugs for the use in artemisinin combination therapies (ACTs).

Insecticide-impregnated bed nets and curtains (ITN) have been shown to be effective against malaria. However, given that most ITN studies were of limited length, researchers have postulated the hypothesis that in areas of intense malaria transmission and due to possible interactions with immunity development, ITN interventions may cause no effect at all or even a long-term increase in malaria morbidity and mortality. The overall objective of the trial is to analyse the long-term effects of ITN on child morbidity and mortality in an area of intense malaria transmission. The specific objective is to analyse if there is a difference in the rates of malaria morbidity and mortality as well as in all-cause mortality in children being protected with ITNs from birth compared to children protected with ITNs from age 6 months onwards. The study is conducted in the Nouna Health District, in Burkina Faso, and specifically in a sub-portion of the District under demographic surveillance since 1999. The sub-portion of the District under demographic surveillance includes a total population of 70 000 individuals, distributed in 42 villages and in the town of Nouna. The region is a dry Savannah characterised by high levels of malaria transmission. The study design entails a prospective community-based trial, with newborn children being identified at the village level and then individually randomised to receive either intervention A or intervention B. Intervention A is defined as ITN protection from age 0 to 59 months (i.e. protection from birth). Intervention B is defined as ITN protection from age 6 to 59 months (i.e. protection from 6 months onwards). Enrollment in the study cohort in continued until the sample size is reached (n = 2 600, 1 300 group A and 1 300 group B). Detailed data on morbidity is collected through means of a prospective follow up on a sub-sample of 420 children from 6 sentinel villages (210 from group A and 210 from group B). These 420 children are visited daily by field workers who measure their temperature. In case of fever, field workers take a blood sample through finger prick to be analysed for malaria parasitaemia. Treatment free of charge is organised for all children in this subsample. In addition, these children are visited twice a year for the collection of clinical (malaria episodes, anaemia) and parasitological (rates of malaria parasitaemia, parasite density) parameters. Data collection on this subsample of children is meant to last from June 2000 to December 2003. For study purposes, falciparum malaria is defined as 37.5 C or more plus at least 5 000 parasites per micro-litre. All-cause mortality in the overall study sample (2 600 children) are ascertained through means of a demographic surveillance system (DSS), which regularly monitors deaths (as well as births and migration) in the region. The causes of death are identified through means of verbal autopsy. All children enrolled in the study are followed up through means of the DSS from birth up to 5 years of age. The primary study outcome will be the five-year all-cause mortality in the total number of children enrolled in the study (2 600). Secondary outcomes will be the study of malaria-specific mortality, clinical parameters, and parasitological parameters in a sub-sample of the study cohort (420).

This study is an investigation to compare the efficacy of two different intermittent sulfadoxine/pyrimethamine (SP) treatment regimens and intermittent sulfadoxine/pyrimethamine (SP) + artesunate (SP/AS) treatment of HIV negative and positive mothers in clearing placental parasitemia at delivery. If intermittent protective SP/AS treatment is equally efficacious and safe as intermittent protective SP, such a regimen could be adapted for programmatic use as a potentially more durable alternative to SP monotherapy in areas of increasing SP resistance.

Malaria and anaemia are major causes of morbidity and mortality in children in sub-Saharan Africa. Administration of three courses of sulfadoxine/pyrimethamine (SP) as intermittent preventive treatment (IPTi) to infants when they receive EPI vaccines reduced the incidence of malaria and anaemia in infants in an area with low SP resistance, low transmission pressure and high bednet use. However, it is not clear whether this observation can be generalised to areas with high transmission and high SP resistance. The mechanism of the protective effect of IPTi is unclear. There is an urgent need to identify other anti-malarial drugs that could be used for IPTi instead of SP. This study objectives are: Identification of a drug that could be used safely and effectively for IPTi instead of SP in areas, such as north eastern Tanzania, where there is a high level of resistance to SP and amodiaquine. Determination of whether a short acting antimalarial drug (Lapdap) is as effective as a long acting drug (mefloquine) when used for IPTi. Investigation of the effect of the intensity of transmission on the requirements for a long or short acting drug for IPTi. Assessment of the effect of IPTi on the development of clinical immunity in children in low and high transmission areas. A randomised trial with four treatment regimes is proposed which will be conducted in two different transmission settings. The four treatment regimens are as follows: (1) placebo; (2) mefloquine; (3) Lapdap; (4) SP. All medications will be given at the time of immunisation with DPT/polio 2, DPT/polio 3, and measles vaccines. The study will involve 1280 infants in a high endemic area and 2440 infants in a low endemic area, in Tanzania.The primary outcome is the incidence of clinical malaria.