Active clinical trials for "Malaria"

Malaria is responsible for over 2 million deaths each year. The development of an efficient vaccine would present by far the best solution for solving this disastrous situation. Liver-Stage-Antigen-3 (LSA-3) is an antigen that is mainly exhibited by Plasmodium falciparum sporozoites and liver-stage parasites. It is characterized by its remarkable antigenicity in humans with a wide range and a variety of B and T-lymphocyte epitopes, by its extremely high immunogenicity and by an excellent protective efficacy against sporozoite challenge in animal models. Therefore, PfLSA-3-rec is a promising candidate vaccine against P. falciparum in humans The aim is to screen two different formulations of the recombinant malaria vaccine PfLSA-3-rec, one adjuvated with aluminium hydroxide and one with Montanide Isa 720, by assessing the safety and immunogenicity (phase I) profile of each formulation in humans, as well as its protective efficacy following a sporozoite challenge (phase IIa).

In malaria-endemic areas, young children have an especially high risk of malaria morbidity and mortality. Malaria is estimated to cause up to 2 million deaths and 500 million clinical episodes in Africa alone. The bulk of disease in Africa and severe disease and deaths globally is due to P. falciparum. However, P. vivax is also responsible for a substantial disease burden in endemic regions outside Africa, where P. vivax may account for more than half of all malaria cases. Efforts to reduce this unacceptably high disease burden are hampered by the limited availability of affordable interventions. Following the cessation of large-scale vector control in highly endemic areas, malaria control efforts have centred on early diagnosis and treatment of clinical cases and reducing exposure through the use of insecticide-treated nets (ITNs). While ITNs have been shown to significantly reduce the burden of malaria additional effective interventions are urgently needed. Several trials have shown that chemoprophylaxis given to children at weekly or fortnightly intervals reduces morbidity from malaria in a number of different settings and populations. An alternative approach has been to use intermittent preventive therapy (IPT) involving the administration of a full therapeutic dose of antimalarials at regular intervals. This is logistically easier to deliver, and is less costly, and may reduce problems of promoting drug resistance associated with regular chemoprophylaxis. Intermittent administration of sulphadoxine-pyrimethamine (SP) during antenatal clinic visits was shown to be highly effective in reducing malaria and anaemia in pregnant women and improving infant birth weights. IPT in pregnancy (IPTp) is now recommended by WHO for endemic regions of Africa.

The purpose of this study is to determine whether 2 investigational malaria vaccines are safe as well as protective against malaria in adults living in the United States

This study examines two new malaria vaccines (FP9-PP and MVA-PP) in healthy human volunteers to determine their safety and ability to induce a measurable immune response against malaria.

There is clear evidence diagnosis of malaria in much of Africa is sub-optimal and this has a negative impact on patient care. Many of those treated for malaria do not have it. Rapid diagnostic tests (RDTs) are dipsticks which diagnose malaria rapidly and accurately. The main objective of this trial is to determine by means of a randomised trial the impact of introducing RDTs into a standard outpatient setting in Tanzania has on the appropriate prescription of antimalarials. Other objectives are: To compare at high, moderate and low P.falciparum transmission intensity the sensitivity and specificity of malaria diagnosis using hospital slide results and RDTs, using research quality slides as the reference. To estimate the specificity of clinical diagnosis of malaria at high, moderate and low transmission intensity of P. falciparum. To compare the proportion of cases reported as slide-negative who are treated for malaria with the proportion of RDT-negative cases treated for malaria. To evaluate the cost effectiveness of introducing RDTs compared to current diagnostic practice in facilities with microscopic diagnosis of malaria at different levels of transmission of P.falciparum.

Intermittent preventive treatment for malaria in children (IPTc) is a promising new approach to malaria control. Preliminary studies of IPTc in Senegal and Mali indicate that this approach can be very effective. Although the results of these studies suggest that IPTc with sulphadoxine-pyrimethamine (SP) plus artesunate (AS) or SP alone is an efficacious and safe intervention for reducing the burden of malaria and anaemia in children in high transmission areas with short transmission periods, there is no data from areas with long transmission periods. This study aims to evaluate the effectiveness of IPTc in reducing anaemia and malaria in an area with up to 6 months of transmission in Ghana. Two thousand two hundred forty children aged 3-59 months will be randomly allocated to four groups (560 per arm) to receive amodiaquine plus artesunate (AQ+AS), given at two different intervals (monthly or bimonthly), SP or placebo. The children will also be followed to determine if there is any rebound in the incidence of severe malaria and anaemia in the year following IPTc.

There is conflicting evidence regarding the influence of HIV infection on the success of malaria prevention in pregnancy and effect on pregnancy outcome. The purpose of the proposed study is to assess the impact of HIV infection on the effectiveness of malaria prevention during pregnancy. This will be carried out by comparing two intermittent preventive treatments (IPTs) with sulfadoxine/pyrimethamine (SP) plus 300 mg weekly chloroquine with two doses IPT plus a weekly chloroquine placebo. The emphasis will be on assessing the effect of chloroquine on HIV viral load and malaria morbidity and foetal outcome. The study will be a randomised double-blind placebo-controlled trial with two arms, involving pregnant women attending antenatal classes (ANCs) at health units, enrolled early in their second trimester at 3 health units of the Mbarara district and Kampala. All pregnant women presenting for antenatal care, irrespective of parity, who consent to participate will be enrolled. Women with severe systemic disease or symptoms of AIDS will be excluded from the study data analysis. Women will be screened for HIV status and their HIV viral loads will be measured at enrolment. Parasitaemia will be assessed at enrolment; at the beginning of the third trimester; and at delivery. Haemoglobin will be measured at the same time points. The main outcome variables to be assessed will be maternal peripheral parasitaemia; placental parasitaemia; maternal clinical malaria; congenital parasitaemia; and maternal and neonatal haemoglobin, birth weight and viral load at enrolment and before nevirapine administration to the HIV positive mothers at birth. Anthropological pre-studies to assess the quality of ANC services and healthcare seeking practices of pregnant women in the study area will be carried out. Focus group discussions (FGD) with pregnant women and mothers of neonates; in-depth interviews with relevant health workers; and illness narratives from pregnant women will be used to collect data. The anthropological study results will assist in appropriately planning for the trial to enhance compliance to the intervention. The data collection is planned to commence in August 2003 and is expected to end in October 2005. Twelve months will be spent on the write-up phase.

In countries of the Sahel and sub-Sahel, malaria transmission is highly seasonal with nearly all infections occurring during a few months of the year. However, mortality and morbidity from malaria may be high during this period, especially in young children who are the group most at risk. Intermittent preventative treatment (IPT) is a new approach to the prevention of malaria in this situation. IPT involves the administration of an anti-malarial to children at risk for malaria at fixed times, even if they are not infected. To investigate how effective this approach might be in Senegal, a trial has been undertaken in which 1136 children aged 6 weeks to 59 months were given a single dose of sulfadoxine pyrimethamine and artesunate on three occasions during a three-month rainy season and the incidence of clinical malaria in these children was compared with that in a group of children who received placebo. Additional observations were made on the incidence of side effects in children in the two groups and on the impact of IPT in children (IPTc) on markers of drug resistance in children whose blood films were positive for Plasmodium falciparum.

The aim of the study is to determine the tolerability and safety of ATV-PG + AQ, ATV-PG + AQ placebo, ATV-PG placebo + AQ, and ATV-PG placebo + AQ placebo administered once daily for 3 days to healthy adult male and female subjects.This study in healthy adults is the first step towards establishing the tolerability and safety of the approved doses of ATV-PG and AQ when co-administered. If considered acceptable based on the findings of this study, the tolerability, safety and PE will subsequently be assessed, within the target geographical areas.

An open label, partially blinded clinical trial in which healthy volunteers will be administered experimental malaria vaccines. There will be seven experimental groups of volunteers, of which five receive vaccination with the novel malaria vaccine candidate, R21, in combination with the vaccine adjuvant, Matrix M. The study will assess the safety & immune responses to vaccination, and the efficacy of the vaccine.