Active clinical trials for "Malaria"

The study is designed to establish infectivity of Plasmodium falciparum sporozoites (PfSPZ) via intravenous (IV) administration in three groups with different malaria immunity-status: Adults with a history of lifelong malaria exposure without sickle cell trait (HbAA) Adults with a history of lifelong malaria exposure with sickle cell trait (HbAS) Adults without previous malaria episodes without sickle cell trait (HbAA) Initially a dose of 3,200 PfSPZ will be given and the time until thick blood smear positivity after challenge will be assessed. If in any of the groups with a history of lifelong malaria exposure, 50% or less of individuals become thick blood smear positive during the 28 days post injection of PfSPZ Challenge, the dose will be increased 4-fold to 12,800 PfSPZ in this group.

Malaria is one of the major infectious diseases in the world with a tremendous impact on the quality of life significantly contributing to the ongoing poverty in endemic countries. It causes almost one million deaths per year, the majority of which are children under the age of five. The malaria parasite enters the human body through the skin, by the bite of an infected mosquito. Subsequently, it invades the liver and develops and multiplies inside the hepatocytes. After a week, the hepatocytes burst open and the parasites are released in the blood stream, causing the clinical phase of the disease. As a unique opportunity to study malaria immunology and efficacy of immunisation strategies, a protocol has been developed in the past to conduct experimental human malaria infections (EHMIs). EHMIs generally involve small groups of malaria-naïve volunteers infected via the bites of P. falciparum infected laboratory-reared Anopheline mosquitoes. Although potentially serious or even lethal, P. falciparum malaria can be radically cured at the earliest stages of blood infection where risks of complications are virtually absent. The investigators have shown previously that healthy human volunteers can be protected from a malaria mosquito (sporozoite) challenge by immunization with sporozoites (by mosquito bites) under chloroquine prophylaxis (CPS immunization). However, it is unknown how many mosquito bites are necessary to confer protection. Moreover, as all volunteers were protected in this study, no correlates of protection could be established. For future development of vaccines and understanding of protective immunity to malaria, it is important to investigate the lowest dose of CPS immunization that confers 100% protection and to find correlates of protection. Therefore, the present study aims to make the CPS immunization protocol more sensitive by lowering the number of infected mosquito bites, in order to study the underlying mechanisms of protection.

Plasmodium falciparum isolates display a wide genetic diversity with possibly different properties to induce immune responses. These properties could directly influence the ability to induce protective efficacy. Since 1998 an experimental human malaria infection model at the Radboud University Nijmegen Medical Center (RUNMC) has been very successful in answering questions with regards to immunological mechanisms of human Pf infection. To date only the NF54 strain of Pf has been deployed in this Nijmegen model. However, investigation of heterologous Pf challenge is not only highly informative for our basic understanding of induction of immune responses but also provides an essential model for protective capacity testing in the clinical development of candidate malaria vaccines. Recently, the parasite culture laboratory of the RUNMC has been able to overcome technical hurdles to produce infectious mosquitoes of two genetically different isolates from different geographical regions to increase the portfolio for Phase IIa trials. These isolates, PfA and PfB will be compared with the NF54 strain for parasitic, immunological and clinical features in humans.

Design: Single-centre, controlled study in adults with uncomplicated falciparum malaria in the Nouna Health District, north-western Burkina Faso Phase: Phase II Objectives: The primary objective of this trial is to study the efficacy of different methylene blue regimens given to adults with uncomplicated falciparum malaria in an African area of high malaria transmission intensity. Population: Male adults with uncomplicated malaria from Nouna town. Sample size: N= 60 (n=20 for each group; three different dosing regimens of MB). Treatment: The participants in the three different MB regimens will receive orally twice daily 390 mg MB (total daily dose 780mg) over 7,5 or 3 days respectively. Treatment with the five (three) day regimen will only start after all patients of the seven (five) days regimen have been followed up until day 3. Endpoints: The primary endpoint is the adequate clinical and parasitological response (ACPR) rate on day 28. Secondary endpoints are the number of adverse events (AE) after drug intake until day 28, clinical and parasitological failure rates on day 14 and 28, changes in haemoglobin/haematocrit until day 28, and fever and parasite clearance time.

This is a prospective, single arm, single intervention safety and immunogenicity study in 6 healthy, malaria-naive adults, conducted to demonstrate the successful implementation of the well-established malaria challenge model at the Seattle Biomedical Research Institute (Seattle BioMed).

This study will examine safety of single doses of GSK369796 in healthy subjects, along with some test to examine how quickly GSK369796 gets in your blood, and how long it takes your body to get rid of it.

In Malawi, the standard of care to prevent malaria during pregnancy at the time of the study was a two dose sulfadoxine-pyrimethamine intermittent protective treatment (SP IPT) regimen administered in the second and third trimester of pregnancy. In this investigation, this two dose strategy was compared to a monthly SP regimen. The objective for the study was to determine the efficacy of the different regimens for HIV positive and HIV negative women in the prevention of placental malaria.

The work will be conducted in six health posts in the regions of Matam (Kanel and Ranérou districts) and Louga (Linguère district), that were selected in 2014 on the basis of the malaria incidence rate, the heterogeneity of transmission between villages in the health post catchment areas, their proximity, and the availability of historical data from before 2014. Malaria elimination strategies were already implemented in the same health posts in 2014 and are still ongoing, thus this protocol aims to strengthen these activities. Seven health posts with similar characteristics but with a slightly lower incidence rate were chosen as controls. It will be implemented in all villages in the six intervention health posts and it will consist of investigating all passively detected cases (index cases) and conducting focal test and focal drug administration (FT/FDA) with dihydroartemisinin-piperaquine (DHAP) in all index case and neighboring households with a positive RDT. All household members in households with a positive RDT will be treated, regardless of their RDT results. Impact of the enhanced Step D on malaria incidence and prevalence will be evaluated using before-after comparison and compared to the change in the control health posts and the operational aspects will be assessed for subsequent scale up.

In the past decade, massive scale-up of insecticide-treated nets (ITN) and indoor residual spraying (IRS), together with the introduction of artemisinin-combination treatments, have led to substantial reductions in malaria prevalence and incidence in African highlands. However, rising insecticide resistance and increased outdoor transmission have greatly hampered the effectiveness of ITN and IRS because the current indoor-based interventions do not target the outdoor-biting mosquitoes. Therefore, new supplemental interventions that can tackle outdoor transmission and pyrethroid insecticide resistance are urgently needed. The central objective of this study is to determine the efficacy and cost-effectiveness of EPA-approved long-lasting microbial larvicides in reducing malaria transmission and clinical malaria incidence in western Kenya highlands.

The purpose of this study is to assess whether twice-daily text message reminders over a six-month period to health workers in Malawi about diagnosis and treatment of malaria, pneumonia, and diarrhea improve case management of these diseases.