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Malaria Journal
Published in: Malaria Journal 1/2023

Open Access 01-12-2023 | Malaria | Research

Gametocyte prevalence and risk factors of P. falciparum malaria patients admitted at the Hospital for Tropical Diseases, Thailand: a 20-year retrospective study

Authors: Panita Looareesuwan, Srivicha Krudsood, Saranath Lawpoolsri, Noppadon Tangpukdee, Wasin Matsee, Wang Nguitragool, Polrat Wilairatana

Published in: Malaria Journal | Issue 1/2023

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Abstract

Background

The incidence of malaria in Thailand has dramatically declined over the past two decades, and the goal is to eliminate malaria by 2025. Despite significant progress, one of the key challenges to malaria elimination are undetected gametocyte carriers. Human migration adds complexity to the malaria situation, as it not only sustains local transmission but also poses the risk of spreading drug-resistant parasites. Currently, no study has assessed the prevalence of gametocytes across multiple years in Plasmodium falciparum malaria patients in Thailand, and the risk factors for gametocyte carriage have not been fully explored.

Methods

Medical records of all P. falciparum malaria patients admitted from January 1, 2001 to December 31, 2020 at the Hospital for Tropical Diseases, Thailand, were retrospectively examined and a total of 1962 records were included for analysis. Both P. falciparum parasites and gametocytes were diagnosed by microscopy. A regression model was used to evaluate predictors of gametocyte carriage.

Results

The study demonstrated gametocyte prevalence in low malaria transmission areas. Nine risk factors for gametocyte carriage were identified: age between 15 and 24 years [adjusted odds ratio (aOR) = 1.96, 95% confidence interval (CI) 1.18−3.26], Karen ethnicity (aOR = 2.59, 95% CI 1.56−4.29), preadmission duration of fever > 7 days (aOR = 5.40, 95% CI 3.92−7.41), fever on admission (> 37.5 °C) (aOR = 0.61, 95% CI 0.48−0.77), haemoglobin ≤ 8 g/dL (aOR = 3.32, 95% CI 2.06−5.33), asexual parasite density > 5000−25,000/µL (aOR = 0.71, 95% CI 0.52−0.98), asexual parasite density > 25,000−100,000/µL (aOR = 0.74, 95% CI 0.53−1.03), asexual parasite density > 100,000/µL (aOR = 0.51, 95% CI 0.36−0.72), platelet count ≤ 100,000/µL (aOR = 0.65, 95% CI 0.50−0.85, clinical features of severe malaria (aOR = 2.33, 95% CI 1.76−3.10) and dry season (aOR = 1.41, 95% CI 1.10−1.80). An increasing incidence of imported transnational malaria cases was observed over the past two decades.

Conclusions

This is the first study to determine the prevalence of gametocytes among patients with symptomatic P. falciparum malaria, identify the risk factors for gametocyte carriage, and potential gametocyte carriers in Thailand. Blocking transmission is one of the key strategies for eliminating malaria in these areas. The results might provide important information for targeting gametocyte carriers and improving the allocation of resources for malaria control in Thailand. This study supports the already nationally recommended use of a single dose of primaquine in symptomatic P. falciparum malaria patients to clear gametocytes.

Graphical Abstract

Appendix
Available only for authorised users
Literature
1.
WHO. Strategy for malaria elimination in the Greater Mekong Subregion : 2015–2030. Regional Office for the Western Pacific; World Health Organization; 2015.
2.
Nguitragool W, Karl S, White M, Koepfli C, Felger I, Singhasivanon P, et al. Highly heterogeneous residual malaria risk in western Thailand. Int J Parasitol. 2019;49:455–62.PubMedPubMedCentral
3.
Kaewpitoon N, Loyd RA, Kaewpitoon SJ, Rujirakul R. Malaria risk areas in Thailand border. J Med Assoc Thai. 2015;98(Suppl 4):S17-21.PubMed
4.
Nguitragool W, Mueller I, Kumpitak C, Saeseu T, Bantuchai S, Yorsaeng R, et al. Very high carriage of gametocytes in asymptomatic low-density Plasmodium falciparum and P. vivax infections in western Thailand. Parasit Vectors. 2017;10:512.PubMedPubMedCentral
5.
6.
Wangdi K, Gatton ML, Kelly GC, Clements ACA. Cross-border malaria: a major obstacle for malaria elimination. Adv Parasitol. 2015;89:79–107.PubMed
7.
Franco-Paredes C, Santos-Preciado JI. Problem pathogens: prevention of malaria in travellers. Lancet Infect Dis. 2006;6:139–49.PubMed
8.
Sriwichai P, Karl S, Samung Y, Kiattibutr K, Sirichaisinthop J, Mueller I, et al. Imported Plasmodium falciparum and locally transmitted Plasmodium vivax: cross-border malaria transmission scenario in northwestern Thailand. Malar J. 2017;16:258.PubMedPubMedCentral
9.
Kritsiriwuthinan K, Ngrenngarmlert W. Asymptomatic malaria infections among foreign migrant workers in Thailand. Asian Pac J Trop Med. 2011;4:560–3.PubMed
10.
Kritsiriwuthinan K, Ngrenngarmlert W. Molecular screening of Plasmodium infections among migrant workers in Thailand. J Vector Borne Dis. 2011;48:214–8.PubMed
11.
Mita T, Tanabe K. Evolution of Plasmodium falciparum drug resistance: implications for the development and containment of artemisinin resistance. Jpn J Infect Dis. 2012;65:465–75.PubMed
12.
Ecker A, Lehane AM, Clain J, Fidock DA. PfCRT and its role in antimalarial drug resistance. Trends Parasitol. 2012;28:504–14.PubMedPubMedCentral
13.
Balikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana S-I, Yamauchi M, et al. Evidence of artemisinin-resistant malaria in Africa. N Engl J Med. 2021;385:1163–71.PubMed
14.
Uwimana A, Umulisa N, Venkatesan M, Svigel SS, Zhou Z, Munyaneza T, et al. Association of Plasmodium falciparum kelch13 R561H genotypes with delayed parasite clearance in Rwanda: an open-label, single-arm, multicentre, therapeutic efficacy study. Lancet Infect Dis. 2021;21:1120–8.PubMedPubMedCentral
15.
Bousema T, Drakeley C. Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination. Clin Microbiol Rev. 2011;24:377–410.PubMedPubMedCentral
16.
Usui M, Williamson KC. Stressed out about Plasmodium falciparum gametocytogenesis. Front Cell Infect Microbiol. 2021;11:790067.PubMedPubMedCentral
17.
Bousema T, Okell L, Shekalaghe S, Griffin JT, Omar S, Sawa P, et al. Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs. Malar J. 2010;9:136.PubMedPubMedCentral
18.
Andagalu B, Mativo J, Kamau E, Ogutu B. Longitudinal study on Plasmodium falciparum gametocyte carriage following artemether-lumefantrine administration in a cohort of children aged 12–47 months living in Western Kenya, a high transmission area. Malar J. 2014;13:265.PubMedPubMedCentral
19.
Piyaphanee W, Krudsood S, Tangpukdee N, Thanachartwet W, Silachamroon U, Phophak N, et al. Emergence and clearance of gametocytes in uncomplicated Plasmodium falciparum malaria. Am J Trop Med Hyg. 2006;74:432–5.PubMed
20.
Coleman RE, Kumpitak C, Ponlawat A, Maneechai N, Phunkitchar V, Rachapaew N, et al. Infectivity of asymptomatic Plasmodium -infected human populations to Anopheles dirus mosquitoes in Western Thailand. J Med Entomol. 2004;41:201–8.PubMed
21.
Grange L, Loucoubar C, Telle O, Tall A, Faye J, Sokhna C, et al. Risk Factors for Plasmodium falciparum gametocyte positivity in a longitudinal cohort. PLoS ONE. 2015;10:e0123102.PubMedPubMedCentral
22.
Muthui MK, Mogeni P, Mwai K, Nyundo C, Macharia A, Williams TN, et al. Gametocyte carriage in an era of changing malaria epidemiology: a 19-year analysis of a malaria longitudinal cohort. Wellcome Open Res. 2019;4:66.PubMedPubMedCentral
23.
Adomako-Ankomah Y, Chenoweth MS, Tocker AM, Doumbia S, Konate D, Doumbouya M, et al. Host age and Plasmodium falciparum multiclonality are associated with gametocyte prevalence: a 1-year prospective cohort study. Malar J. 2017;16:473.PubMedPubMedCentral
24.
Koepfli C, Robinson LJ, Rarau P, Salib M, Sambale N, Wampfler R, et al. Blood-stage parasitaemia and age determine Plasmodium falciparum and P. vivax gametocytaemia in Papua New Guinea. PLoS ONE. 2015;10:e0126747.PubMedPubMedCentral
25.
Akim NI, Kingo T, Drakeley C, Senkoro K, Sauerwein RW, Simon B. Dynamics of P. falciparum gametocytemia in symptomatic patients in an area of intense perennial transmission in Tanzania. Am J Trop Med Hyg. 2000;63:199–203.PubMed
26.
WWARN Gametocyte Study Group. Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy: a systematic review and meta-analysis of individual patient data. BMC Med. 2016;14:79.PubMedCentral
27.
Ouédraogo AL, Bousema T, de Vlas SJ, Cuzin-Ouattara N, Verhave J-P, Drakeley C, et al. The plasticity of Plasmodium falciparum gametocytaemia in relation to age in Burkina Faso. Malar J. 2010;9:281.PubMedPubMedCentral
28.
Sowunmi A, Fateye BA, Adedeji AA, Fehintola FA, Happi TC. Risk factors for gametocyte carriage in uncomplicated falciparum malaria in children. Parasitol. 2004;129:255–62.
29.
Lawaly YR, Sakuntabhai A, Marrama L, Konate L, Phimpraphi W, Sokhna C, et al. Heritability of the human infectious reservoir of malaria parasites. PLoS ONE. 2010;5:e11358.PubMedPubMedCentral
30.
White NJ, Chongsuphajaisiddhi T, Nosten F, van Vugt M, Price R, ter Kuile F, et al. Risk factors for gametocyte carriage in uncomplicated falciparum malaria. Am J Trop Med Hyg. 1999;60:1019–23.PubMed
31.
Sondo P, Bihoun B, Tahita MC, Derra K, Rouamba T, Nakanabo Diallo S, et al. Plasmodium falciparum gametocyte carriage in symptomatic patients shows significant association with genetically diverse infections, anaemia, and asexual stage density. Malar J. 2021;20:31.PubMedPubMedCentral
32.
Nacher M, Singhasivanon P, Silachamroon U, Treeprasertsuk S, Tosukhowong T, Vannaphan S, et al. Decreased hemoglobin concentrations, hyperparasitemia, and severe malaria are associated with increased Plasmodium falciparum gametocyte carriage. J Parasitol. 2002;88:97–101.PubMed
33.
Essangui E, Eboumbou Moukoko CE, Nguedia N, Tchokwansi M, Banlanjo U, Maloba F, et al. Demographical, hematological and serological risk factors for Plasmodium falciparum gametocyte carriage in a high stable transmission zone in Cameroon. PLoS ONE. 2019;14:e0216133.PubMedPubMedCentral
34.
Gbotosho GO, Sowunmi A, Okuboyejo TM, Happi CT, Michael OS, Folarin OA, et al. Plasmodium falciparum gametocyte carriage, emergence, clearance and population sex ratios in anaemic and non-anaemic malarious children. Mem Inst Oswaldo Cruz. 2011;106:562–9.PubMed
35.
Touray AO, Mobegi VA, Wamunyokoli F, Butungi H, Herren JK. Prevalence of asymptomatic P. falciparum gametocyte carriage among school children in Mbita, Western Kenya and assessment of the association between gametocyte density, multiplicity of infection and mosquito infection prevalence. Wellcome Open Res. 2021;5:259.PubMedPubMedCentral
36.
Okebe J, Bousema T, Affara M, Di Tanna GL, Dabira E, Gaye A, et al. The gametocytocidal efficacy of different single doses of primaquine with dihydroartemisinin-piperaquine in asymptomatic parasite carriers in The Gambia: a randomized controlled trial. EBioMedicine. 2016;13:348–55.PubMedPubMedCentral
37.
Gonçalves BP, Tiono AB, Ouédraogo A, Guelbéogo WM, Bradley J, Nebie I, et al. Single low dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission after artemether-lumefantrine in children with asymptomatic infection: a randomised, double-blind, placebo-controlled trial. BMC Med. 2016;14:40.PubMedPubMedCentral
38.
Lin JT, Lon C, Spring MD, Sok S, Chann S, Ittiverakul M, et al. Single dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission in Cambodia: an open-label randomized trial. PLoS ONE. 2017;12:e0168702.PubMedPubMedCentral
39.
Dicko A, Roh ME, Diawara H, Mahamar A, Soumare HM, Lanke K, et al. Efficacy and safety of primaquine and methylene blue for prevention of Plasmodium falciparum transmission in Mali: a phase 2, single-blind, randomised controlled trial. Lancet Infect Dis. 2018;18:627–39.PubMedPubMedCentral
40.
Mwaiswelo RO, Ngasala B, Msolo D, Kweka E, Mmbando BP, Mårtensson A. A single low dose of primaquine is safe and sufficient to reduce transmission of Plasmodium falciparum gametocytes regardless of cytochrome P450 2D6 enzyme activity in Bagamoyo district, Tanzania. Malar J. 2022;21:84.PubMedPubMedCentral
41.
42.
43.
44.
45.
46.
WHO. Meeting report of the evidence review group on border malaria. Geneva: World Health Organization; 2018.
47.
Mercado CEG, Lawpoolsri S, Sudathip P, Kaewkungwal J, Khamsiriwatchara A, Pan-ngum W, et al. Spatiotemporal epidemiology, environmental correlates, and demography of malaria in Tak Province, Thailand (2012–2015). Malar J. 2019;18:240.PubMedPubMedCentral
48.
Carrara VI, Lwin KM, Phyo AP, Ashley E, Wiladphaingern J, Sriprawat K, et al. Malaria burden and artemisinin resistance in the mobile and migrant population on the Thai-Myanmar border, 1999–2011: an observational study. PLoS Med. 2013;10:e1001398.PubMedPubMedCentral
49.
Oyibo W, Latham V, Oladipo O, Ntadom G, Uhomoibhi P, Ogbulafor N, et al. Malaria parasite density and detailed qualitative microscopy enhances large-scale profiling of infection endemicity in Nigeria. Sci Rep. 2023;13:1599.PubMedPubMedCentral
50.
51.
Parker DM, Landier J, Von Seidlein L, Dondorp A, White L, Hanboonkunupakarn B, et al. Limitations of malaria reactive case detection in an area of low and unstable transmission on the Myanmar–Thailand border. Malar J. 2016;15:571.PubMedPubMedCentral
52.
O’Flaherty K, Chan J-A, Cutts JC, Zaloumis SG, Ashley EA, Phyo AP, et al. Anti-gametocyte antigen humoral immunity and gametocytemia during treatment of uncomplicated falciparum multi-national study. Front Cell Infect Microbiol. 2022;12:804470.PubMedPubMedCentral
53.
Shekalaghe SA, Teun Bousema J, Kunei KK, Lushino P, Masokoto A, Wolters LR, et al. Submicroscopic Plasmodium falciparum gametocyte carriage is common in an area of low and seasonal transmission in Tanzania: submicroscopic gametocytes at low endemicity. Trop Med Int Health. 2007;12:547–53.PubMed
54.
Parker DM, Matthews SA, Yan G, Zhou G, Lee M-C, Sirichaisinthop J, et al. Microgeography and molecular epidemiology of malaria at the Thailand–Myanmar border in the malaria pre-elimination phase. Malar J. 2015;14:198.PubMedPubMedCentral
55.
Sturrock HJW, Roberts KW, Wegbreit J, Ohrt C, Gosling RD. Tackling imported malaria: an elimination endgame. Am J Trop Med and Hyg. 2015;93:139–44.
56.
57.
Schneweis S, Maier WA, Seitz HM. Haemolysis of infected erythrocytes ? A trigger for formation of Plasmodium falciparum gametocytes? Parasitol Res. 1991;77:458–60.PubMed
58.
Farid R, Dixon MW, Tilley L, McCarthy JS. Initiation of gametocytogenesis at very low parasite density in Plasmodium falciparum infection. J Infect Dis. 2017;215:1167–74.PubMedPubMedCentral
59.
Nacher M, Silachamroon U, Singhasivanon P, Wilairatana P, Phumratanaprapin W, Fontanet A, et al. Risk factors for Plasmodium vivax gametocyte carriage in Thailand. Am J Trop Med Hyg. 2004;71:693–5.PubMed
60.
Babiker HA, Schneider P, Reece SE. Gametocytes: insights gained during a decade of molecular monitoring. Trends Parasitol. 2008;24:525–30.PubMedPubMedCentral
61.
62.
Bancone G, Chowwiwat N, Somsakchaicharoen R, Poodpanya L, Moo PK, Gornsawun G, et al. Single low dose primaquine (0.25 mg/kg) does not cause clinically significant haemolysis in G6PD deficient subjects. PLoS ONE. 2016;11:e0151898.PubMedPubMedCentral
63.
Dysoley L, Kim S, Lopes S, Khim N, Bjorges S, Top S, et al. The tolerability of single low dose primaquine in glucose-6-phosphate deficient and normal falciparum-infected Cambodians. BMC Infect Dis. 2019;19:250.PubMedPubMedCentral
64.
Sattabongkot J, Suansomjit C, Nguitragool W, Sirichaisinthop J, Warit S, Tiensuwan M, et al. Prevalence of asymptomatic Plasmodium infections with sub-microscopic parasite densities in the northwestern border of Thailand: a potential threat to malaria elimination. Malar J. 2018;17:329.PubMedPubMedCentral
65.
Shimizu S, Chotirat S, Dokkulab N, Hongchad I, Khowsroy K, Kiattibutr K, et al. Malaria cross-sectional surveys identified asymptomatic infections of Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi in Surat Thani, a southern province of Thailand. J Infect Dis. 2020;96:445–51.
66.
Alemayehu A. Biology and epidemiology of Plasmodium falciparum and Plasmodium vivax gametocyte carriage: implication for malaria control and elimination. Parasite Epidemiol Control. 2023;21:e00295.PubMedPubMedCentral
67.
Vantaux A, Samreth R, Piv E, Khim N, Kim S, Berne L, et al. Contribution to malaria transmission of symptomatic and asymptomatic parasite carriers in Cambodia. J Infect Dis. 2018;217:1561–8.PubMed
68.
Tadesse FG, Slater HC, Chali W, Teelen K, Lanke K, Belachew M, et al. The relative contribution of symptomatic and asymptomatic Plasmodium vivax and Plasmodium falciparum infections to the infectious reservoir in a low-endemic setting in Ethiopia. Clin Infect Dis. 2018;66:1883–91.PubMed
69.
Liu Y, Sturrock HJW, Yang H, Gosling RD, Cao J. The challenge of imported malaria to eliminating countries. Lancet Infect Dis. 2017;17:141.PubMed
Metadata
Title
Gametocyte prevalence and risk factors of P. falciparum malaria patients admitted at the Hospital for Tropical Diseases, Thailand: a 20-year retrospective study
Authors
Panita Looareesuwan
Srivicha Krudsood
Saranath Lawpoolsri
Noppadon Tangpukdee
Wasin Matsee
Wang Nguitragool
Polrat Wilairatana
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2023
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-023-04728-7

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