Risk factors for Plasmodium falciparum and Plasmodium vivax gametocyte carriage in Papua New Guinean children with uncomplicated malaria

Karl, Stephan; Laman, Moses; Moore, Brioni R.; Benjamin, John; Salib, Mary; Lorry, Lina; Maripal, Samuel; Siba, Peter; Robinson, Leanne J.; Müeller, Ivo; Davis, Timothy

doi:10.1016/j.actatropica.2016.04.002

Cited by 12 publications

(11 citation statements)

References 43 publications

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“…Additionally, all the RT-PCR gametocyte positives in our study were also positive by Pfs16 -based RT-LAMP, justifying our use of RT-LAMP in the association studies. Consistent with findings elsewhere, young age, anemia [15–17] and fever [11,14,16,18,46,47] were identified as potential risk factors for both all stage and mature gametocyte carriage in the study area. In contrast to a previous study in Senegal [11] wherein various parasite density and the ABO blood groups (O and B) were identified as predictors of gametocyte positivity by light microscopy, we observed no such association with both all stage and mature gametocyte carriage based on molecular detection of the early gametocytogenesis Pfs16 marker or the mature gametocyte marker Pfs25 (cf Table 3).…”

Section: Discussionsupporting

confidence: 89%

“…Risk factors for mature gametocyte carriage in P . falciparum infected patients include patient age [10–12], gender [13], asexual parasite densities, [13–15], blood hemoglobin levels [15–17], infection duration [13], presence of a fever [5,11,14,16,18,19], as well as patient’s blood group [11,15]. Blood levels of Plasmodium gametocytes may also depend on the gametocytogenic potential of the infecting clones and the ability of the host environment to either promote or block gametocyte production in vivo [6,20].…”

Section: Introductionmentioning

confidence: 99%

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Demographical, hematological and serological risk factors for Plasmodium falciparum gametocyte carriage in a high stable transmission zone in Cameroon

et al. 2019

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Presence of mature gametocyte forms of malaria parasites in peripheral blood is a key requirement for malaria transmission. Yet, studies conducted in most malaria transmission zones report the absence of gametocyte in the majority of patients. We therefore sought to determine the risk factors of both all-stage and mature gametocyte carriage in an area with high stable transmission of Plasmodium falciparum in Cameroon. Gametocyte positivity was determined using three complementary methods: thick blood smear microscopy, RT-PCR and RT-LAMP, whereas exposure to the infection was assessed by enzyme-linked immunosorbent assay. Of 361 malaria endemic residents randomly included in the study (mean age: 28±23 years, age range: 2–100 years, male/female sex ratio: 1.1), 87.8% were diagnosed with P . falciparum infection, of whom 45.7% presented with fever (axillary body temperature ≥37.5°C). Mature gametocyte positivity was 1.9% by thick blood smear microscopy and 8.9% by RT-PCR targeting the mature gametocyte transcript, Pfs25 . The gametocyte positivity rate was 24.1% and 36.3% by RT-PCR or RT-LAMP, respectively, when targeting the sexual stage marker, Pfs16 . Multivariate analyses revealed anemia as a common independent risk factor for both mature and all-stage gametocyte carriage, whereas fever and low anti-gametocyte antibody levels were independently associated with all-stage gametocyte carriage only. Taken together, the data suggest important differences in risk factors of gametocyte carriage depending on stage analyzed, with anemia, fever and low antiplasmodial plasma antibody levels representing the major contributing risk factors.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Demographical, hematological and serological risk factors for Plasmodium falciparum gametocyte carriage in a high stable transmission zone in Cameroon

et al. 2019

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“…Conversely, other studies on P . vivax epidemiology have reported that prevalence of sexual stage infections decreases with age [10,15,19,20,23]. On one hand, individuals aged >15 years included here worked mainly in agriculture, forestry and fishing activities, what can increase their exposure to Anopheles darlingi bites during daytime.…”

Section: Discussionmentioning

confidence: 99%

“…Low haemoglobin levels and fever have also been linked with P . vivax gametocyte presence [15,23], although equally high rates of gametocytes were reported in symptomatic and asymptomatic infections in Brazil [21,26]. …”

Section: Introductionmentioning

confidence: 99%

Predominance of asymptomatic and sub-microscopic infections characterizes the Plasmodium gametocyte reservoir in the Peruvian Amazon

et al. 2017

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Malaria transmission requires that Anopheles mosquitoes ingest Plasmodium gametocyte stages circulating in the human bloodstream. In the context of malaria elimination, understanding the epidemiology of gametocytes relative to all Plasmodium infections and the contribution of asymptomatic and sub-microscopic parasite carriers to the gametocyte reservoir is necessary, especially in low endemic settings with predominance of P.vivax. A 13-month longitudinal study was conducted in two communities (n = 1935 individuals) of Loreto Department, Peru, with five active screenings for Plasmodium infections and gametocyte stages by quantitative real-time PCR (qPCR) and reverse transcription (RT)-qPCR, respectively. Parasite prevalence by qPCR was 7.2% for P.vivax (n = 520/7235; range by survey 6.0%-8.1%) and 3.2% for P.falciparum (n = 235/7235; range by survey 0.4%-7.7%). Sub-microscopic infections accounted for 73.5% of P.vivax (range by survey 60%-89%) and almost the totality of P.falciparum cases. Gametocytes were found in 28.4% P.vivax infections (range by survey 18.7%-34.1%), with a peak of 61.5% in one community at the start of the transmission season. About 59.8% of all P.vivax gametocyte carriers were asymptomatic and 31.9% were sub-microscopic. Age patterns for gametocyte prevalence paralleled asexual stage infections and peaked among >15–25 year old individuals. Asexual parasite density was found to be the strongest predictor for P.vivax gametocyte presence in longitudinal multivariate analysis (odds ratio 2.33 [95% confidence interval 1.96, 2.78]; P<0.001). Despite significant differences in seasonality patterns and P.vivax prevalence found at the local scale, sub-microscopic and asymptomatic infections predominate and contribute significantly to the gametocyte reservoir in different communities of the Peruvian Amazon. Control and elimination campaigns need sensitive tools to detect all infections that escape routine malaria surveillance, which may contribute to maintain transmission in the region.

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“…In addition, a Pf co-infection reduced Pv gametocyte densities by half. A study in 0.5 to 5 year old PNG children with uncomplicated malaria confirmed that Pv gametocytaemia in Pf/Pv mixed infections was reduced compared to Pv single infections [ 41 ]. Moreover, a community study in PNG showed a lower proportion of Pf gametocyte carriers in Pf / Pv mixed infections compared to Pf single-species infections [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum

et al. 2017

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BackgroundPrimaquine (PQ) is the only currently licensed antimalarial that prevents Plasmodium vivax (Pv) relapses. It also clears mature P. falciparum (Pf) gametocytes, thereby reducing post-treatment transmission. Randomized PQ treatment in a treatment-to-reinfection cohort in Papua New Guinean children permitted the study of Pv and Pf gametocyte carriage after radical cure and to investigate the contribution of Pv relapses.MethodsChildren received radical cure with Chloroquine, Artemether-Lumefantrine plus either PQ or placebo. Blood samples were subsequently collected in 2-to 4-weekly intervals over 8 months. Gametocytes were detected by quantitative reverse transcription-PCR targeting pvs25 and pfs25.ResultsPQ treatment reduced the incidence of Pv gametocytes by 73%, which was comparable to the effect of PQ on incidence of blood-stage infections. 92% of Pv and 79% of Pf gametocyte-positive infections were asymptomatic. Pv and to a lesser extent Pf gametocyte positivity and density were associated with high blood-stage parasite densities. Multivariate analysis revealed that the odds of gametocytes were significantly reduced in mixed-species infections compared to single-species infections for both species (ORPv = 0.39 [95% CI 0.25–0.62], ORPf = 0.33 [95% CI 0.18–0.60], p<0.001). No difference between the PQ and placebo treatment arms was observed in density of Pv gametocytes or in the proportion of Pv infections that carried gametocytes. First infections after blood-stage and placebo treatment, likely caused by a relapsing hypnozoite, were equally likely to carry gametocytes than first infections after PQ treatment, likely caused by an infective mosquito bite.ConclusionPv relapses and new infections are associated with similar levels of gametocytaemia. Relapses thus contribute considerably to the Pv reservoir highlighting the importance of effective anti-hypnozoite treatment for efficient control of Pv.Trial registrationClinicalTrials.gov NCT02143934

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Risk factors for Plasmodium falciparum and Plasmodium vivax gametocyte carriage in Papua New Guinean children with uncomplicated malaria

Cited by 12 publications

References 43 publications

Demographical, hematological and serological risk factors for Plasmodium falciparum gametocyte carriage in a high stable transmission zone in Cameroon

Demographical, hematological and serological risk factors for Plasmodium falciparum gametocyte carriage in a high stable transmission zone in Cameroon

Predominance of asymptomatic and sub-microscopic infections characterizes the Plasmodium gametocyte reservoir in the Peruvian Amazon

Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum

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