Active clinical trials for "Malaria"

According to the World Malaria Report, there were significant decreases in the number of P.falciparum (PF) malaria cases worldwide in the past decade. On the Thai-Myanmar border where transmission is low and seasonal and where incidence of Multi-drugs resistant P.falciparum parasites is the highest, the same trend has been observed with a clear decline in malaria episodes and the ratio of P. falciparum/P. vivax (PF/PV. Economic development, unprecedented financial support, renewed efforts in vector control, a wider use of rapid diagnosic tests (RDTs) for malaria and the deployment of artemisinin based combination treatments (ACT) are the main contributing factors to those successes against malaria. However the emergence in Cambodia and on the Thai-Myanmar border of P.falciparum isolates that exhibit resistance to artesunate is threatening those gains . This is characterized by a slow parasite clearance rate observed in patients treated with artesunate. At the same time, recent SMRU surveys along the Thai-Burmese border using a new cutting-edge technology i.e. highly sensitive quantitative Real Time PCR (RT-PCR) able to detect very low parasitaemia (10 parasites per ml), found up to a 3-5 fold increase in the prevalence of malaria compared to what is found with the usual diagnostic tools such as microscopy, RDT or even conventional PCR. It seems that a large number of asymptomatic carriers with very low parasites counts (a large potential malaria reservoir) go undetected. If confirmed, this might pose the greatest obstacle for malaria elimination in the region and containment of artemisinin resistance. The purpose of the survey is to further study and understand the epidemiology of malaria in the refugee camp population using cutting-edge technology (RT-PCR) .

The primary objective of this study is to determine to what extent provision with RUTF will promote catch up growth in children following an acute uncomplicated episode of P. falciparum malaria.

This is an open label Phase 1 study of the Ad-PfCA vaccine designed to 1) provide reagents for the development and refinement of cell-mediated immunoassays for measuring the human immune response to candidate malaria vaccines (especially protective malaria vaccines such as DNA/Ad-PfCA where better assays are needed to identify the correlates of protective immunity) and 2) to provide a repository of antigen-specific PBMCs that can be used as positive and negative controls in cell mediated immunoassays.

The emergence and spread of drug resistance is a major obstacle to combating malaria. The World Health Organization (WHO) recommends that regular efficacy monitoring should be undertaken by all malaria endemic countries that have deployed artemisinin combination therapy (ACT), to help early detection of drug resistant strains of the parasite and contain their rapid spread. Artemether-lumefantrine (AL) has been the first-line antimalarial drug against uncomplicated Plasmodium falciparum malaria in the Philippines since 2009, with primaquine as an anti-relapse drug. The objective of this study is to assess the safety and efficacy of artemether-lumefantrine for the treatment of uncomplicated P. falciparum infections in the Philippines. The study was conducted in three (3) municipalities (Bataraza, Brooke's Point, and Rizal) of Palawan. Single-arm prospective study of a 28-day follow-up was conducted from February 2017 to December 2018 according to the revised WHO 2014 drug efficacy study protocol. Study subjects were consenting individuals seeking care at the selected Rural Health Units, who were aged >6 months old to 59 years old with confirmed uncomplicated P. falciparum infections. AL was administered for 3 days according to body weight (Days 0, 1 and 2) and primaquine 0.75 mg/kg body weight single dose was given on Day 3 following the National Treatment Guidelines.

The aim of this study is to analyze the perceptions, representations and expe-riences of malaria prophylaxis in patients born in endemic areas and living in France. This analysis could lead to better understanding and communication between the medical profession and patients in malaria. It would also provide patient-specific responses to their expectations, as to their families.

The investigators propose to implement a new mobile interface that automatically reads and troubleshoots malaria rapid diagnostic test (RDT) cassettes. This device, called a Deki reader (DR), will allow the investigators to establish an extensive quality assurance program of malaria diagnosis performed by trained community health volunteers (CHVs). The study will lease 10 DRs and rotate them amongst 200 CHVs performing community-based malaria diagnosis through rapid diagnostic testing. The study setting is Bungoma East subcounty and Kiminini subcounty in Kenya. The overall goal is to measure and improve the quality of malaria diagnosis by CHVs using malaria RDTs. The investigators aim for every CHW to exceed 90% sensitivity and specificity and zero operator errors within six months. There are no appreciable risks to the CHV associated with evaluation by the DR device. The investigators' analysis will focus on descriptive statistics of RDT use and accuracy amongst all participating CHVs.

This is a phase I study that will assess the acquisition of immunity to Pf malaria over the course of 5 sequential Controlled Human Malaria Infections (CHMI) over 2-4 years, in 10 healthy adult participants. 10 subjects will initially be challenged with 5 uninfected mosquitoes (mock), followed by 5 challenges with 5 mosquitoes infected with drug sensitive, P. falciparum parasites (strain NF54) 2, 8, 14-20, 20-32, and 32-36 months later. For the final four infective CMHIs six additional immunologic malaria-naïve subjects will be enrolled and challenged as infectivity controls. If dropouts occur within the original 10 person cohort, and two or more CHMI remain, back-up replacement volunteers will be recruited to undergo successive CHMI with the core group. All volunteers (repeat CHMI subjects and infectivity controls) will be evaluated as part of an inpatient stay (or outpatient daily follow-up) to diagnose Pf malaria infection and treat with Coartem(R) (artemether/lumefantrine) or Malarone(R) (Atovaquone/proguanil). Daily observation will occur from Study Days 9-19 or until three-day directly observed therapy for P. falciparum infection is complete and two negative smears separated by a time interval >12 hours have been documented. A third negative smear >12 hours after the previous two daily smears will be documented to affirm malaria cure. Infectivity Controls enrolled as part of CHMI #5 will be treated based on concomitant us qPCR results. The repeat CHMI subjects will have additional outpatient visits days 1, 3, 5, and 7 after the challenge to obtain blood samples to monitor the development of immunity. The study is expected to last for 48 months and will include approximately 34 healthy male and female volunteers (10 active study volunteers and 18 naïve controls to confirm Pf infectivity during the 2nd -5th CHMI challenges) ages 18 to 50 years, inclusive, from the greater Baltimore community. The primary objective of this study is to determine whether protective immunity against parasite infection develops following repeat CHMI.

Based in part on the pivotal studies conducted in Mali, SMC was approved by WHO as a policy for malaria control in countries with seasonal malaria transmission such as Mali in March 2012. The goals are to identify the most effective method to deliver SMC, and to obtain more information on the long term impact of SMC on malaria immunity. Our specific aims are 1) to determine the optimal mode (fixed-point (FPD) vs door-to-door delivery (DDD); directly observed treatment (DOT) vs non-DOT (NDOT)) and frequency (3 vs 4 doses per season) of SMC delivery; 2) to compare quantitative measures of immunity in children who do and do not receive SMC. A cluster-randomized design will be sued. The target population will be children aged 3-59 months old in Ouelessebougou district, Mali. In Year 1, villages in four sub-districts will be randomized into four groups (FPD+DOT; FPD+NDOT; DDD+DOT; DDD+NDOT). The optimal mode of delivery will be selected based on the SMC coverage during the first year, and will then be implemented in villages of two additional sub-districts. Villages in these two newly selected sub-districts will be randomized in two groups. Children in the first group will received three rounds of SMC and those in the second group will receive four rounds of SMC to determine the optimal frequency of SMC based on the incidence rate of clinical malaria as measured by passive surveillance. In Year 3, children in the selected sub-districts will received SMC by the optimal delivery system determined in Years 1 -2. A survey will be conducted collect data on mortality and hospital admission and compare these outcomes in areas where SMC was implemented and areas where SMC was not implemented.

Each year, ~85.3 million pregnant women are at risk of becoming infected with Plasmodium falciparum(1). Among women in sub-Saharan Africa, most of whom have some degree of clinical immunity to malaria, malaria infection in pregnancy leads to placental malaria (PM), often without clinical symptoms in the mother. The systemic and placental changes that occur with malaria in pregnancy can adversely affect the developing fetal brain, an fetal brain injury strongly affects long-term childhood neurodevelopmental (ND) and behavior but there are no published studies to date on the impact of malaria in pregnancy on childhood ND. This study, conducted in Uganda, will address the effects of malaria in pregnancy and childhood ND and define mechanisms by which malaria may lead to ND impairment including micronutrient deficiencies. ND outcomes will be measured by the following neuropsychological and behavioral tests: Mullen Scales of Early Learning, the Color Object Association Test, the Early Childhood Vigilance Test, the Behavior Rating Scales, the Behavior Related inventory of Executive Function and the Child Behavior Checklist. These tests will be given at 12, 24, 36, and 60 months of age. This study will be nested in an ongoing Ugandan IRB approved interventional trial (PROMOTE-II) (NCT02163447). Blood sampling is being conducted in the PROMOTE-II protocol for research purposes. Some of that blood will be used to test for micronutrient deficiencies as well as other immune responses to malaria.

Microscopy remains a key indicator in drug efficacy testing performed in the context of clinical trials for monitoring existing antimalarials or in the context of regulatory clinical trials for registration of new drugs. It is one of the main diagnostic methods for malaria diagnosis in general, as in an ideal setting it can provide low-cost accurate diagnosis, determine the density of parasites in the blood, and accurately differentiate between different malaria parasite species, characteristics vital to the implementation of global plans for drug efficacy monitoring. Malaria rapid tests (RDTs), while useful for case management, do not provide information on the parasite density nor the species differentiation necessary for research and drug efficacy assessment. Microscopy therefore retains key advantages over a number of newer technologies, but its reliability is severely impeded by dependence on high technical competence of the human operators as well as availability of high quality equipment and reagents. Recent studies have demonstrated the frequent poor specificity and sensitivity associated with manual microscopy diagnostics in operational conditions , , . Advances in digital microscopy performance and affordability have now opened the door to potentially significant improvements in the performance of malaria diagnostic microscopy, overcoming serious deficiencies in current drug efficacy assessment, and more broadly in malaria diagnosis and management. Intellectual Ventures Laboratory (IVL), in collaboration with Global Good Fund (GG), has developed an initial microscope prototype to support its research into dark field imaging of unstained malaria slides. The system consists of low cost electromechanical components for scanning a standard slide, an optical train with a high numerical aperture objective, and an image capture system. Captured images are analyzed with custom image analysis software developed at GG/IVL, using algorithms that are designed for automatic malaria diagnosis, without user input. Additionally, image processing algorithms have been built around detection of Giemsa-stained malaria slides which is the current standard for malaria microscopy. Initial results show excellent potential for sensitivity and specificity which exceeds that of typical manual microscopists in the field. Based on the positive market and needs assessment in January, 2013, given by stakeholders in the malaria diagnostics community, GG/IVL are pursuing improvement and integration of this algorithm into a portable microscope platform with characteristics similar to the prototype microscope already developed at GG/IVL for dark field imaging. The prototype Autoscope was first tested in field settings in Thailand in Nov 2014 - Jan 2015 at clinics operated by the Shoklo Malaria Research Unit (SMRU). The goal of the first field evaluation was to assess the Autoscope in with respect to its diagnostic performance and also its suitability for harsh conditions typically encountered in field clinics. Further, user feedback on the design and functionality was sought. The Autoscope and the accompanying image analysis algorithms have since been further developed and a new version is now available for testing.