Microscopic<i>Plasmodium falciparum</i>Gametocytemia and Infectivity to Mosquitoes in Cambodia

Lin, Jessica T.; Ubalee, Ratawan; Lon, Chanthap; Balasubramanian, Sujata; Kuntawunginn, Worachet; Rahman, Rifat; Saingam, Piyaporn; Heng, Thay Kheang; Vy, Dav; Savoeun, San,; Nuom, Sarath; Hana, Burkly,; Chanarat, Nitima; Chanudom, Ponsa,; Levitz, Lauren; Parobek, Christian M.; Chuor, Char Meng; Sok, Somethy; Spring, Michele; Lanteri, Charlotte; Gosi, Panita; Meshnick, Steven R.; Saunders, David

doi:10.1093/infdis/jiv599

Cited by 48 publications

(57 citation statements)

References 14 publications

(25 reference statements)

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“…Counterintuitively, the proportion of submicroscopic infections on a global scale is inversely correlated to transmission intensity, i.e., the proportion is highest at low endemicity [2, 3, 11, 21]. Asymptomatic carriers to a sizeable extent contribute to malaria transmission, also in low endemicity settings [2, 3, 7], even though the magnitude of this impact is not well established [39]. In the present study, more than 90% of Plasmodium infected children attending school were considered asymptomatic based on the absence of fever.…”

Section: Discussionmentioning

confidence: 99%

Asymptomatic only at first sight: malaria infection among schoolchildren in highland Rwanda

Sifft

Geus

Mukampunga

et al. 2016

Malar J

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Background Plasmodium infection and malaria in school children are increasingly recognized as a relevant public health problem, but data on actual prevalence and health consequences are insufficient. The present study from highland southern Rwanda aimed at estimating infection prevalence among children attending school, at identifying associated factors and at assessing the clinical consequences of these infections.MethodsIn a survey including 12 schools in the Huye district of Rwanda, 1089 children aged 6–10 years were clinically and anthropometrically examined, malaria parasites were diagnosed by microscopy and PCR, haemoglobin concentrations were measured, and socio-economic and behavioural parameters as well as medical histories were obtained.ResultsUpon examination, the vast majority of children was asymptomatic (fever 2.7%). Plasmodium infection was detected in 22.4% (Plasmodium falciparum, 18.8%); 41% of these were submicroscopic. Independent predictors of infection included low altitude, higher age, preceding antimalarial treatment, and absence of electricity or a bicycle in the household. Plasmodium infection was associated with anaemia (mean haemoglobin difference of −1.2 g/dL; 95% CI, −0.8 to −1.5 g/dL), fever, underweight, clinically assessed malnutrition and histories of fever, tiredness, weakness, poor appetite, abdominal pain, and vomiting. With the exception of underweight, these conditions were also increased at submicroscopic infection.ConclusionMalaria infection is frequent among children attending school in southern highland Rwanda. Although seemingly asymptomatic in the vast majority of cases, infection is associated with a number of non-specific symptoms in the children´s histories, in addition to the impact on anaemia. This argues for improved malaria surveillance and control activities among school children.

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Section: Discussionmentioning

confidence: 99%

Asymptomatic only at first sight: malaria infection among schoolchildren in highland Rwanda

Sifft

Geus

Mukampunga

et al. 2016

Malar J

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“…Molecular detection of gametocytes at baseline, day 7, and day 14 was carried out using reverse-transcriptase PCR (RT-PCR) of Pfs25 [16–18]. This assay has a reported detection limit of 1–2 gametocytes/μL when applied to blood spots [16].…”

Section: Methodsmentioning

confidence: 99%

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

Lin

Lon²,

Spring

et al. 2017

PLoS ONE

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BackgroundSingle 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.MethodsCambodian 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.ResultsPrior 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.ConclusionsIn 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.

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“…6 Though infections detected by microscopy and RDT are likely responsible for the majority of transmission, further studies are needed to assess the impact of subpatent infections on the transmission reservoir. 7,8 In the context of vaccine trials, these low-level, subpatent parasitemias may confound estimates of transmission intensity used to study vaccine efficacy.To evaluate the impact of subpatent parasitemias on parasite prevalence estimates, we collected dried blood spots from all participants during the final year of the 3-year MTI study in Lilongwe, Malawi, to allow for nucleic acid detection of parasitemia. Using clinical data and a spatial database to evaluate ecological factors that may influence transmission, we attempted to identify risk factors for subpatent parasitemia.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Estimation of Plasmodium falciparum Transmission Intensity in Lilongwe, Malawi, by Microscopy, Rapid Diagnostic Testing, and Nucleic Acid Detection

Parr

Belson

Patel

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Estimates of malaria transmission intensity (MTI) typically rely upon microscopy or rapid diagnostic testing (RDT). However, these methods are less sensitive than nucleic acid amplification techniques and may underestimate parasite prevalence. We compared microscopy, RDT, and polymerase chain reaction (PCR) for the diagnosis of Plasmodium falciparum parasitemia as part of an MTI study of 800 children and adults conducted in Lilongwe, Malawi. PCR detected more cases of parasitemia than microscopy or RDT. Age less than 5 years predicted parasitemia detected by PCR alone (adjusted odds ratio = 1.61, 95% confidence interval = 1.09-2.38, Wald P = 0.02). In addition, we identified one P. falciparum parasite with a false-negative RDT result due to a suspected deletion of the histidinerich protein 2 (hrp2) gene and used a novel, ultrasensitive PCR assay to detect low-level parasitemia missed by traditional PCR. Molecular methods should be considered for use in future transmission studies as a supplement to RDT or microscopy.Plasmodium falciparum infects hundreds of millions of individuals and kills 600,000 persons every year.1 A recently completed phase three trial of the RTS,S/ASO1 malaria vaccine demonstrated moderate and varying efficacy in different transmission settings.2 Study sites conducted annual malaria transmission intensity (MTI) studies during the trial using microscopy and rapid diagnostic test (RDT) parasite prevalence as a surrogate for transmission intensity.Both microscopy and RDT are known to produce negative results in Africa when parasitemia levels are beneath their limits of detection, 50 and 200 parasites/μL blood, respectively. [3][4][5] Infections not detected by microscopy or RDT, often referred to as subpatent infections, can often be detected by nucleic acid detection methods. 6 Though infections detected by microscopy and RDT are likely responsible for the majority of transmission, further studies are needed to assess the impact of subpatent infections on the transmission reservoir. 7,8 In the context of vaccine trials, these low-level, subpatent parasitemias may confound estimates of transmission intensity used to study vaccine efficacy.To evaluate the impact of subpatent parasitemias on parasite prevalence estimates, we collected dried blood spots from all participants during the final year of the 3-year MTI study in Lilongwe, Malawi, to allow for nucleic acid detection of parasitemia. Using clinical data and a spatial database to evaluate ecological factors that may influence transmission, we attempted to identify risk factors for subpatent parasitemia. We also investigated the impact of other factors on discordances between polymerase chain reaction (PCR) and other assays (RDT and microscopy) including 1) nonfalciparum parasitemia, 2) the occurrence of histidine-rich protein 2 (hrp2) gene deletions on false-negative RDTs, and 3) low-level parasitemia detectable by ultrasensitive PCR targeting high copy number genes. 9 This work adds to the growing literature concerning the rela...

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MicroscopicPlasmodium falciparumGametocytemia and Infectivity to Mosquitoes in Cambodia

Cited by 48 publications

References 14 publications

Asymptomatic only at first sight: malaria infection among schoolchildren in highland Rwanda

Asymptomatic only at first sight: malaria infection among schoolchildren in highland Rwanda

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

Estimation of Plasmodium falciparum Transmission Intensity in Lilongwe, Malawi, by Microscopy, Rapid Diagnostic Testing, and Nucleic Acid Detection

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