Single dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission in Cambodia: An open-label randomized trial

Autor: Soklyda Chann, David L. Saunders, Worachet Kuntawunginn, Rifat Rahman, Michele D. Spring, Steven R. Meshnick, Mengchuor Char, Kheangheng Thay, Mali Ittiverakul, Panita Gosi, Charlotte A. Lanteri, Sujata Balasubramanian, Somethy Sok, Ratawan Ubalee, Mok My, Chanthap Lon, Jessica T. Lin
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Primaquine
Drug Resistance
lcsh:Medicine
Artificial Gene Amplification and Extension
Drug resistance
Disease Vectors
Gametocytes
Mosquitoes
Biochemistry
Polymerase Chain Reaction
0302 clinical medicine
Animal Cells
Medicine and Health Sciences
Malaria
Falciparum

Artemisinin
lcsh:Science
Glucose-6-Phosphate Dehydrogenase Deficiency
Multidisciplinary
Drugs
Anemia
Hematology
Artemisinins
3. Good health
Insects
Drug Combinations
Infectious Diseases
Female
Cellular Types
Research Article
medicine.drug
Adult
medicine.medical_specialty
Arthropoda
Adolescent
Combination therapy
Plasmodium falciparum
030231 tropical medicine
030106 microbiology
Biology
Research and Analysis Methods
Antimalarials
03 medical and health sciences
Internal medicine
Parasite Groups
Anopheles
parasitic diseases
Parasitic Diseases
medicine
Gametocyte
Animals
Humans
Hemoglobin
Molecular Biology Techniques
Molecular Biology
Pharmacology
Dose-Response Relationship
Drug

lcsh:R
Organisms
Oocysts
Hemolytic Anemia
Biology and Life Sciences
Proteins
Cell Biology
Reverse Transcriptase-Polymerase Chain Reaction
Tropical Diseases
medicine.disease
biology.organism_classification
Invertebrates
Virology
Insect Vectors
Malaria
Species Interactions
Germ Cells
Parasitology
lcsh:Q
Apicomplexa
Glucose-6-phosphate dehydrogenase deficiency
Zdroj: PLoS ONE, Vol 12, Iss 6, p e0168702 (2017)
PLoS ONE
ISSN: 1932-6203
Popis: Background Single low dose primaquine (SLD PQ, 0.25mg/kg) is recommended in combination with artemisinin-based combination therapy (ACT) as a gametocytocide to prevent Plasmodium falciparum transmission in areas threatened by artemisinin resistance. To date, no randomized controlled trials have measured primaquine’s effect on infectiousness to Anopheline mosquitoes in Southeast Asia. Methods Cambodian adults with uncomplicated falciparum malaria were randomized to receive a single 45mg dose of primaquine (equivalent to three SLD PQ) or no primaquine after the third dose of dihydroartemisin-piperaquine (DHP) therapy. A membrane-feeding assay measured infectiousness to Anopheles dirus on days 0, 3, 7, and 14 of blood-stage therapy. Gametocytemia was evaluated by microscopy and reverse-transcriptase PCR. Results Prior to trial halt for poor DHP treatment efficacy, 101 participants were randomized and 50 received primaquine. Overall microscopic gametocyte prevalence was low (9%), but gametocytemic subjects given primaquine were gametocyte-free by day 14, and significantly less likely to harbor gametocytes by day 7 compared to those treated with DHP-alone, who remained gametocytemic for a median of two weeks. Only one infectious subject was randomized to the primaquine group, precluding assessment of transmission-blocking efficacy. However, he showed a two-fold reduction in oocyst density of infected mosquitoes less than 24 hours after primaquine dosing. In the DHP-alone group, four subjects remained infectious through day 14, infecting roughly the same number of mosquitoes pre and post-treatment. Overall, microscopic gametocytemia was an excellent predictor of infectiousness, and performed better than submicroscopic gametocytemia post-treatment, with none of 474 mosquitoes infected post-treatment arising from submicroscopic gametocytes. Conclusions In a setting of established ACT resistance, a single dose of 45mg primaquine added to DHP rapidly and significantly reduced gametocytemia, while DHP-alone failed to reduce gametocytemia and prevent malaria transmission to mosquitoes. Continued efforts to make single dose primaquine widely available are needed to help achieve malaria elimination.
Databáze: OpenAIRE
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