Active clinical trials for "Malaria, Falciparum"

This project aims to disentangle the role of host immune resistance and disease tolerance in afebrile malaria infections, with the goal of guiding context-adapted tactics to target this hidden reservoir, as well as to develop new approaches to clear malaria infection and reduce its severity through host-directed therapies.

In areas of the Sahel sub-region of Africa with intense seasonal malaria transmission, seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SP+AQ) has become the standard-of-care for the prevention of malaria in children. Despite the scale-up of SMC across West Africa, the malaria burden remains high. Reasons for this are not well understood, however, it is hypothesized that children eligible for SMC who get malaria may be underdosed or may have not received SP+AQ. Moreover, there are major concerns that the continued use of the SMC strategy may increase selection of AQ and/or SP-resistant Plasmodium falciparum parasites. The overall objective of this observational study are to understand the factors driving malaria among children eligible to receive SMC and whether circulating levels of sulfadoxine (SDX), pyrimethamine (PYR), and AQ are associated with risks of malaria and antimalarial drug resistance.

An antimalarial drug efficacy trial was conducted for artemether-lumefantrine (AL) and chloroquine (CQ) in the three (3) municipalities (Bataraza, Brookes and Rizal) of Palawan. Study subjects are febrile individuals between > 6 months old and 59 years old with confirmed uncomplicated P. falciparum or P. vivax infections. Patients with P. falciparum was treated with Artemether-lumefantrine administered 3 days (Days 0, 1 and 2) according to body weight. Primaquine at 0.75 mg base/kg body weight single dose was given on Day 3. For Plasmodium vivax patients chloroquine were administered according to body weight at a total dose of 25 mg/kg over 3 days (10 mg/kg on Day 0; 10 mg/kg on Day 1 and 5 mg/kg on Day 2), and primaquine following the National Treatment Guidelines. During the period that this report covers, 84 and 75 patients met the inclusion criteria for Pf and Pv respectively. Clinical and parasitological parameters were monitored over a 28-day follow-up period for both drugs. The presence of only 1 Late Clinical Failure (LCF) of P. falciparum parasitemia out of 84 enrolled patients and 2 Late Parasitological Failure (LPF) of P. vivax patients out of 75 enrolled patients within the 28 days follow up suggest that both drugs are still efficacious.

Background: In high-transmission settings, up to 70% of school-aged children harbour malaria parasites which is mostly asymptomatic, thus, from an epidemiological point of view, they contribute significantly as reservoir to onward malaria transmission to others. In endemic areas, malaria accounts for around 50% of the mortality, 13-50% of all school absenteeism, and causes anaemia in approximately 85 million school-aged children of sub Saharan Africa that also impairs the cognitive development of children. Intermittent preventive treatment (IPT) of pregnant women as well as seasonal malaria chemoprevention in children under the age of five have been implemented in several sub-Saharan countries and have proven to be very effective. However, none of these IPT strategies is targeting school children. A clinical trial is being conducted to expand the IPT by testing effectiveness and safety of two antimalarial drugs Dihydroartemisinin-piperaquine (DP) and Artesunate-amodiaquine (ASAQ) in preventing malaria related morbidity in school aged children (IPTsc) living in high endemic areas. Methods: A randomized, open label, controlled trial will enrol 1602 school children aged 5-15 years, who will receive either DP or ASAQ or control (no drug ), using a "balanced block design" with the "standard of care" arm as reference. The interventional treatments are given every 4 months 3 rounds for the first year. A second non-interventional year will assess possible rebound effects. All study-arms receive bed nets, early diagnosis and care for malaria, and praziquantel and albendazole as mass treatment for helminthiasis. The primary endpoint are change from baseline in mean haemoglobin concentration at months 12 and 20 of follow-up and clinical malaria incidence from month 0 till months 12 and 20 of follow up. Adverse events will be monitored throughout the study. Mixed design methods will be used to assess the acceptability, cost-effectiveness and feasibility of this IPTsc as part of a more comprehensive school children health package. Discussion: The national school health programme (NSHP), Tanzania, combines schistosomiasis and soil transmitted helminthes (STH) control package under national schistosomiasis and STH control programme (NSSCP). Malaria intervention using IPTsc strategy may be integrated in NSHP with the same platform as NSSCP, however, there is limited systematic evidence to assess the operational feasibility of this approach. School aged children are a reachable target population in any endemic malaria setting. The suggested strategy will provide effective protection against malaria, hasten either the elimination process and/or diminish the reservoir and burden.

In Afghanistan, studies over the past 15 years have shown a high degree of Plasmodium falciparum resistance to chloroquine (80%) and more recently an increasing degree of resistance to sulfadoxine-pyrimethamine monotherapy (12%). In 2003 the high failure rate of chloroquine against falciparum malaria led the national malaria treatment programme to switch its recommended first line drug treatment for uncomplicated Plasmodium falciparum malaria to artemisinin-based combination therapy (ACT) in the form of Artesunate/Sulfadoxine-Pyrimethamine (AS+SP). Second line drug treatment is oral quinine (7 days). The aim of this study is to conduct ongoing monitoring of the efficacy of the new combination against P. falciparum in a group of sentinel sites in Afghanistan.

The safety and efficacy of Intermittent Preventive Treatment for malaria and anaemia control in Infants (IPTi) have already been documented in Southern Tanzania, affording an opportunity to gain operational experience in developing a strategy for the longer-term implementation of IPTi. Working in conjunction with national and district-based health authorities, a strategy will be developed to make IPTi available through routine health services and an effectiveness evaluation conducted. This will be based on the comparison of process and outcome indicators in areas with and without IPTi. Information on safety will be consolidated and the effect of IPTi on the rate of development of drug resistance explored. The acceptability and costs of implementing IPTi will be monitored and combined with assessments of effectiveness (in terms of morbidity and mortality) to assess the cost-effectiveness of IPTi.

In the EHMI-8 study (CMO 2006/207) the investigators induced sterile protection against P. falciparum challenge in healthy Dutch volunteers by repeated exposure to infected mosquitoes whilst under chloroquine prophylaxis. The surprisingly efficient induction of protection in this study strongly supports the development of whole parasite vaccines and is therefore an important finding to malaria vaccine development. In this study (EHMI8B) the investigators would like to explore the longevity of the protective immune response and simultaneously further characterise immune mechanisms responsible for protection by re-exposing EHMI-8 volunteers to infected mosquito bites.

This study will attempt to find out what effect mosquito insecticides have on the transmission of malaria in The Gambia. Eight hundred healthy men and women, aged 18 to 40 years, living in selected villages east of Farafenni town in The Gambia, West Africa will be screened for parasites. About 552 of these people are expected to be free of malaria and will form the study group. These people will participate in the study for 7 months and will be checked for the malaria-causing parasite every two weeks by finger prick blood sample.

The newly introduced antimalarial drug artemether-lumefantrine is currently recommended as second line antimalarial in Sudan. Recurrent infection after treatment with this drug has been associated with selection of certain genes in the malaria parasite. However there is no information on this association in Sudan.This study is going to look into the genetics of resistance to artemether-lumefantrine.

Artemether-lumefantrine has been used as a first-line treatment for uncomplicated Plasmodium falciparum infection since 2009 in the Philippines. The 28 day therapeutic efficacy study was conducted between February 2015 and December 2015, in accordance with WHO guidelines in the three (3) municipalities (Bataraza, Brookes and Rizal) of Palawan. Attempt was made to include Panglima-Sugala, Tawi-Tawi; however, due to the decline in the number of malaria cases, no evaluable subject was enrolled. The study subjects were febrile individuals between > 6 months old and 59 years old with confirmed uncomplicated P. falciparum. They were treated with artemether-lumefantrine (20 mg and 120 mg, respectively) administered 3 days (Days 0, 1 and 2) according to body weight. Primaquine (0.75 mg base/kg body weight single dose) was given on Day 3. Outcomes were classified as early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF) and adequate clinical and parasitological response (ACPR).