Background: Drugs that kill or inhibit sexual stages of Plasmodium such as Primaqiune (PQ) could potentially amplify or synergize the impact of first line antimalarials by blocking transmission to mosquitoes. This stu...Background: Drugs that kill or inhibit sexual stages of Plasmodium such as Primaqiune (PQ) could potentially amplify or synergize the impact of first line antimalarials by blocking transmission to mosquitoes. This study examined the effect of Primaquine on gametocyte carriage in the case management of uncomplicated falciparum malaria with artemisinin-based combination therapy (ACT) with the overall purpose of possibly recommending it as an adjunct drug for malaria control. Methods: A total of 181 patients with uncomplicated falciparum malaria, normal glucose-6-phosphate dehydrogenase (G6PD) enzyme levels, and haemoglobin levels ≥ 8 g/dL completed this two-arm randomized blinded clinical trial to test the efficacy of a single dose PQ (0.75 mg/kg) on falciparum gametocytaemia. 88 subjects were assigned to a standard 3-day course of Dihydroartemisinin-Piperaquine (DHP) alone (n = 88) while 93 others had DHP combined with a single dose of PQ on day 3 (n = 93). A 28-day follow-up schedule carried out in the outpatient clinic of a Primary health facility in Vom, Plateau State Nigeria where study participants were seen on days 1, 3, 7 and then weekly to assess the presence of asexual parasites and gametocytes by microscopy. A Kaplan-Meier analysis was employed to determine the survival function of gametocytes on day 3. The data was analyzed using Epi info version 7.1.5. Results: With a gametocyte prevalence of 27.1%, gametocyte carriage rate was lower in the PQ group due to higher probability of clearing gametocytes (Breslow test χ2 = 8.306, df = 1, p = 0.004) and significantly less likely to harbor gametocytes by day 7 when compared to the DHP-alone group (χ2 = 6.218, df = 1, p = 0.013). Conclusion: Addition of single-dose 0.75 mg/kg PQ was associated with reduced gametocyte carriage as a result of faster gametocyte clearance and lower incidence of gametocyte development in DHP-treated patients. PQ as gametocytocidal drug may be useful in combination with artemisinin-based combination therapy (ACT) regimen to clear gametocytes and thereby interrupt malaria transmission to mosquito vector more effectively than ACT alone.展开更多
Background Understanding Plasmodium sexual differentiation is crucial for blocking transmission.This study identified risk factors for gametocyte carriage and gametocytemia in P.vivax and P.falciparum to inform malari...Background Understanding Plasmodium sexual differentiation is crucial for blocking transmission.This study identified risk factors for gametocyte carriage and gametocytemia in P.vivax and P.falciparum to inform malaria elimination strategies at the China-Myanmar border.Methods Gametocytes and asexual parasites were microscopically detected on thick smears collected from 2011 to 2020 in Laiza Township,Kachin State,Myanmar.Mono-/polyclonality were detected by genotyping at Pvmsp3α/βfor P.vivax,and Pfmsp1/2 for P.falciparum.Kulldorff’s retrospective time scan statistics tested for likely clusters of gametocyte-positive cases over time.Chi-square or Fisher’s exact tests compared proportions of gametocyte-positive cases in categorical variables.Generalized linear models assessed risk factors(year,season,demographics,clinical/parasitological features)for gametocyte carriage(logistic regression for a binomial outcome)and gametocytemia(Gaussian regression for continuous outcome),respectively.Results During 2011-2020,8240 patients had P.vivax infections,with 7249 testing positive for gametocytes.Among 510 P.falciparum cases,56 tested positive for gametocytes.A significant cluster of P.vivax gametocyte carriage occurred from May 2015 to August 2017(P=0.001).For P.vivax,dry season,previous malaria history,fever,and parasite density were associated with gametocyte carriage.Gametocyte density increased with asexual parasite density(P<0.001)but was lower during the rainy season and in those with a history of malaria infection(P<0.001).Over time,gametocytes carriage proportion increased while density decreased(P<0.001).For P.falciparum,younger age and previous malaria history were associated with gametocyte carriage,and density was higher in the dry season(P=0.0115).Polyclonal P.vivax infections had higher gametocyte densities than monoclonal infections(P<0.0001)and P.falciparum gametocyte density tended to increase with multiplicity of infection.Conclusions Younger age,prior malaria infection,travel,and polyclonal infections correlate with higher P.vivax gametocyte prevalence.Gametocyte carriage peakes during the dry season,highlighting the need for seasonal strategies to support malaria elimination.These findings enhance understanding of risk factors for the transmissible stage of the two main human Plasmodium species in the Greater Mekong Subregion border areas.展开更多
文摘Background: Drugs that kill or inhibit sexual stages of Plasmodium such as Primaqiune (PQ) could potentially amplify or synergize the impact of first line antimalarials by blocking transmission to mosquitoes. This study examined the effect of Primaquine on gametocyte carriage in the case management of uncomplicated falciparum malaria with artemisinin-based combination therapy (ACT) with the overall purpose of possibly recommending it as an adjunct drug for malaria control. Methods: A total of 181 patients with uncomplicated falciparum malaria, normal glucose-6-phosphate dehydrogenase (G6PD) enzyme levels, and haemoglobin levels ≥ 8 g/dL completed this two-arm randomized blinded clinical trial to test the efficacy of a single dose PQ (0.75 mg/kg) on falciparum gametocytaemia. 88 subjects were assigned to a standard 3-day course of Dihydroartemisinin-Piperaquine (DHP) alone (n = 88) while 93 others had DHP combined with a single dose of PQ on day 3 (n = 93). A 28-day follow-up schedule carried out in the outpatient clinic of a Primary health facility in Vom, Plateau State Nigeria where study participants were seen on days 1, 3, 7 and then weekly to assess the presence of asexual parasites and gametocytes by microscopy. A Kaplan-Meier analysis was employed to determine the survival function of gametocytes on day 3. The data was analyzed using Epi info version 7.1.5. Results: With a gametocyte prevalence of 27.1%, gametocyte carriage rate was lower in the PQ group due to higher probability of clearing gametocytes (Breslow test χ2 = 8.306, df = 1, p = 0.004) and significantly less likely to harbor gametocytes by day 7 when compared to the DHP-alone group (χ2 = 6.218, df = 1, p = 0.013). Conclusion: Addition of single-dose 0.75 mg/kg PQ was associated with reduced gametocyte carriage as a result of faster gametocyte clearance and lower incidence of gametocyte development in DHP-treated patients. PQ as gametocytocidal drug may be useful in combination with artemisinin-based combination therapy (ACT) regimen to clear gametocytes and thereby interrupt malaria transmission to mosquito vector more effectively than ACT alone.
基金supported by a grant(U19AI089672)from the National Institute of Allergy and Infectious Diseases,National Institutes of Health,USA.
文摘Background Understanding Plasmodium sexual differentiation is crucial for blocking transmission.This study identified risk factors for gametocyte carriage and gametocytemia in P.vivax and P.falciparum to inform malaria elimination strategies at the China-Myanmar border.Methods Gametocytes and asexual parasites were microscopically detected on thick smears collected from 2011 to 2020 in Laiza Township,Kachin State,Myanmar.Mono-/polyclonality were detected by genotyping at Pvmsp3α/βfor P.vivax,and Pfmsp1/2 for P.falciparum.Kulldorff’s retrospective time scan statistics tested for likely clusters of gametocyte-positive cases over time.Chi-square or Fisher’s exact tests compared proportions of gametocyte-positive cases in categorical variables.Generalized linear models assessed risk factors(year,season,demographics,clinical/parasitological features)for gametocyte carriage(logistic regression for a binomial outcome)and gametocytemia(Gaussian regression for continuous outcome),respectively.Results During 2011-2020,8240 patients had P.vivax infections,with 7249 testing positive for gametocytes.Among 510 P.falciparum cases,56 tested positive for gametocytes.A significant cluster of P.vivax gametocyte carriage occurred from May 2015 to August 2017(P=0.001).For P.vivax,dry season,previous malaria history,fever,and parasite density were associated with gametocyte carriage.Gametocyte density increased with asexual parasite density(P<0.001)but was lower during the rainy season and in those with a history of malaria infection(P<0.001).Over time,gametocytes carriage proportion increased while density decreased(P<0.001).For P.falciparum,younger age and previous malaria history were associated with gametocyte carriage,and density was higher in the dry season(P=0.0115).Polyclonal P.vivax infections had higher gametocyte densities than monoclonal infections(P<0.0001)and P.falciparum gametocyte density tended to increase with multiplicity of infection.Conclusions Younger age,prior malaria infection,travel,and polyclonal infections correlate with higher P.vivax gametocyte prevalence.Gametocyte carriage peakes during the dry season,highlighting the need for seasonal strategies to support malaria elimination.These findings enhance understanding of risk factors for the transmissible stage of the two main human Plasmodium species in the Greater Mekong Subregion border areas.
