Advertisement

Topics

Severe Malaria and Anti-malarial Drug Resistance in Cambodia

2014-08-27 03:43:59 | BioPortfolio

Summary

This study, conducted by the National Center for Malaria Control of Cambodia's Ministry of Health, the Guangzhou University of Traditional Chinese Medicine in the People's Republic of China, and the U.S. National Institutes of Health, will explore why some people with mild malaria progress to a severe form of the disease and why some malaria parasites are resistant to treatment.

Malaria is caused by a parasite that is transmitted to humans through a mosquito bite. It can cause fever, aches, and weakness. Left untreated, it can cause severe illness and even death. Malaria can be cured when it is treated with effective medicine, but some malaria parasites are resistant to medicine.

Children and adults with malaria symptoms and parasites in their blood will be recruited for this study from the Pursat Regional Health Center in Cambodia and the Thai-Cambodian border area within Pursat Province.

Participants are hospitalized for 4 to 6 days at the Pursat Regional Health Center. A small blood sample is collected for genetic study and to look for substances in the blood, such as certain proteins, that may help protect against severe malaria. Patients are then treated with two doses of Artequick(Registered Trademark) (artemisinin-piperaquine), the first dose upon arrival at the hospital and the second the next day. (Participants who are pregnant will be treated with either quinine or artesunate-mefloquine instead of Artequick.)

Patients undergo fingersticks several times during their hospital stay to collect a small drop of blood to monitor parasite counts. They are discharged from the hospital when their symptoms resolve and parasites can no longer be detected in their blood. After discharge, patients return to the clinic once a week for 3 weeks for a blood test to monitor for parasites, as some parasites may be slightly resistant to the medication. Patients in whom symptoms or parasites reappear undergo treatment with artesunate and mefloquine.

...

Description

Hemoglobin E (HbE) is distinguished from normal HbA by a single amino acid mutation (beta26: Glu to Lys). High allele frequencies in some areas of Cambodia are believed to have been naturally selected by life-threatening manifestations of malaria. Few epidemiological studies support this hypothesis, however, and in vitro studies have not clearly defined a mechanism of protection. The prevalence of drug-resistant malaria is alarmingly high along the Thai-Cambodian border, such that chloroquine, quinine, or mefloquine can no longer effect acceptable cure rates. Recently, prolonged parasite clearance times after artemisinin treatment have been documented in Battambang and Pailin provinces in Cambodia. Combinations of artemisinins and other drugs (e.g., mefioquine, piperaquine) are now used as standard first-line treatments for P. falciparum malaria in Southeast Asia. Further decreases in the effectiveness of these drugs would constitute a disaster, making some cases of malaria essentially untreatable. The molecular basis for parasite resistance to these antimalarials has not been firmly established. The main aims of this study are to (1) determine whether HbE protects against severe P. falciparum malaria, (2) identify genetic determinants associated with parasite resistance to antimalarial drugs, and (3) determine whether HbE and other erythrocyte polymorphisms influence parasite clearance times after artemisinin treatment. To meet these aims, we are conducting an unmatched case-control study comparing the prevalence of HbE in patients with severe and uncomplicated P. falciparum malaria. Cambodians who complain of fever and/or symptoms of malaria are recruited from Pursat Regional Health Center and surrounding districts within Pursat Province. Patients with uncomplicated malaria are treated with weight-based doses of artesunate given orally each day for 3 days, followed by weight-based doses of mefloquine given orally each day for 2 days. Patients with severe malaria will be treated with artemisinin compounds given parenterally for 5 consecutive days, followed by artesunate plus mefioquine treatment, as above. We will also collect parasitized blood samples from malaria patients prior to antimalarial drug administration. These parasites will be tested in short-term in vitro culture experiments to determine their susceptibility to antimalarial drugs. Genome-wide typing of drug-sensitive and drug-resistant P. falciparum isolates (using microsatellite and single nucleotide polymorphism markers) and genetic association studies will be used to identify genes that determine parasite responses to various antimalarial drugs.

Study Design

N/A

Conditions

Severe Malaria

Location

Pursat Regional Health Center
Pursat
Cambodia

Status

Recruiting

Source

National Institutes of Health Clinical Center (CC)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:43:59-0400

Clinical Trials [593 Associated Clinical Trials listed on BioPortfolio]

Study of Factors Involved in Resistance to Severe Malaria

This study will examine whether resistance to severe malaria is associated with weakening of a specific immune response (TLR-mediated pro-inflammatory cytokine response). Some children wit...

Rosiglitazone Adjunctive Therapy for Severe Malaria in Children

Even with optimal anti-malaria therapy and supportive care, severe and cerebral malaria are associated with a 10-30% mortality rate and neurocognitive deficits in up to 33% of survivors. A...

Azithromycin Combination Therapy for Malaria

The goal of this study is to develop a safe, well tolerated, and highly efficacious azithromycin combination treatment for uncomplicated falciparum malaria. Azithromycin is a drug that has...

Study of SAR97276A in the Treatment of Uncomplicated and Severe Malaria in Adults and Children.

The objective of the study is to assess the efficacy and safety of SAR97276A in severe malaria in pediatric patients. Before treating pediatric patients with severe malaria, the efficacy ...

Evaluation of Volume Status, Haemodynamics and Microcirculatory Flow in Adult Patients With Severe Falciparum Malaria

acidosis, acute renal failure and acute pulmonary oedema are common, and frequently fatal, manifestations of severe P. falciparum malaria. The course of all three might be ameliorated by o...

PubMed Articles [4923 Associated PubMed Articles listed on BioPortfolio]

Seroepidemiology of helminths and the association with severe malaria among infants and young children in Tanzania.

The disease burden of Wuchereria bancrofti and Plasmodium falciparum malaria is high, particularly in Africa, and co-infection is common. However, the effects of filarial infection on the risk of seve...

Clinical, laboratorial and immunological aspects of severe malaria in children from Guinea-Bissau.

Malaria is a parasitic disease of which Plasmodium falciparum causes the most severe form of the disease. The immune response against Plasmodium spp. is complex and remains unclear. The present report...

Urinalysis as a diagnostic tool in severe malaria.

Malaria accounts for a significant morbidity and mortality rate around the world, especially in communities with limited access to healthcare. Some clinical signs in urine, like haematuria, coluria an...

Acetaminophen as a Renoprotective Adjunctive Treatment in Patients with Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial.

Acute kidney injury independently predicts mortality in falciparum malaria. It is not known whether acetaminophen's capacity to inhibit plasma hemoglobin-mediated oxidation is renoprotective in severe...

Neuropsychological Benefits of Computerized Cognitive Rehabilitation Training in Ugandan Children Surviving Severe Malaria: A Randomized Controlled Trial.

Computerized cognitive rehabilitation training (CCRT) may be beneficial for alleviating persisting neurocognitive deficits in Ugandan severe malaria survivors. We completed a randomized controlled tri...

Medical and Biotech [MESH] Definitions

Malaria caused by PLASMODIUM VIVAX. This form of malaria is less severe than MALARIA, FALCIPARUM, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day.

Vaccines made from antigens arising from any of the four strains of Plasmodium which cause malaria in humans, or from P. berghei which causes malaria in rodents.

A protozoan parasite that causes vivax malaria (MALARIA, VIVAX). This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions.

Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.

A protozoan parasite that occurs naturally in the macaque. It is similar to PLASMODIUM VIVAX and produces a type of malaria similar to vivax malaria (MALARIA, VIVAX). This species has been found to give rise to both natural and experimental human infections.

More From BioPortfolio on "Severe Malaria and Anti-malarial Drug Resistance in Cambodia"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Infectious-diseases
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...


Searches Linking to this Trial