Serologic Markers in Relation to Parasite Exposure History Help to Estimate Transmission Dynamics of Plasmodium vivax

Often regarded as “benign,”Plasmodium vivaxinfections lay in the shadows of the much more virulentP. falciparuminfections. However, about 1.98 billion people are at risk of both parasites worldwide, stressing the need to understand the epidemiology ofPlasmodium vivax, particularly under the scope of decreasingP. falciparumprevalence and ecological interactions between both species. Two epidemiological observations put the dynamics of both species into perspective: (1) ACT campaigns have had a greater impact onP. falciparumprevalence. (2) Complete clinical immunity is attained at younger ages forP. vivax, under similar infection rates. We systematically compared two mathematical models of transmission for both Plasmodium species. Simulations suggest that an ACT therapy combined with a hypnozoite killing drug would eliminate both species. However,P. vivaxelimination is predicted to be unstable. Differences in age profiles of clinical malaria can be explained solely byP. vivax's ability to relapse, which accelerates the acquisition of clinical immunity and serves as an immunity boosting mechanism.P. vivaxtransmission can subsist in areas of low mosquito abundance and is robust to drug administration initiatives due to relapse, making it an inconvenient and cumbersome, yet less lethal alternative toP. falciparum.

Download Full-text

Population structure and spatio-temporal transmission dynamics of Plasmodium vivax after radical cure treatment in a rural village of the Peruvian Amazon

Malaria Journal ◽

10.1186/1475-2875-13-8 ◽

2014 ◽

Vol 13 (1) ◽

Cited By ~ 20

Author(s):

Christopher Delgado-Ratto ◽

Veronica E Soto-Calle ◽

Peter Van den Eede ◽

Dionicia Gamboa ◽

Angel Rosas ◽

...

Keyword(s):

Population Structure ◽

Plasmodium Vivax ◽

Transmission Dynamics ◽

Radical Cure ◽

Peruvian Amazon ◽

Rural Village ◽

Spatio Temporal

Download Full-text

Evolution of Plasmodium vivax populations in border areas of the Greater Mekong Subregion during malaria elimination

10.21203/rs.2.22640/v1 ◽

2020 ◽

Author(s):

Yuling Li ◽

Yubing Hu ◽

Yan Zhao ◽

Qinghui Wang ◽

Huguette Gaelle Ngassa Mbenda ◽

...

Keyword(s):

Genetic Diversity ◽

Plasmodium Vivax ◽

Malaria Elimination ◽

Scale Up ◽

Transmission Dynamics ◽

Clinical Samples ◽

Effective Population ◽

Border Areas ◽

Greater Mekong Subregion ◽

International Border

Abstract Background: Countries within the Greater Mekong Subregion (GMS) of Southeast Asia have committed to eliminating malaria by 2030. Although malaria situation has greatly improved, Plasmodium vivax remains at international border regions. Therefore, to gain a better understanding of transmission dynamics, knowledge on the evolution of P. vivax populations after the scale-up of control interventions will guide more effective targeted control efforts. Methods: We investigated genetic diversity and population structures in 206 longitudinally collected P. vivax clinical samples in two international border areas at the China-Myanmar border (CMB, n=50 in 2004 and n=52 in 2016) and western Thailand border (n=50 in 2012 and n=54 in 2015). Parasites were genotyped using 10 microsatellite markers. Results: Despite intensified control efforts, genetic diversity in the four populations remained high (HE = 0.66-0.86). The proportions of polyclonal infections showed substantial decreases to 23.7 and 30.7% in the CMB and western Thailand, respectively, with corresponding decreases in the multiplicity of infection. Consistent with the shrinking map of malaria transmission in the GMS over time, there were also increases in multilocus linkage disequilibrium, suggesting of more fragmented and increasingly inbred parasite populations. There were considerable genetic differentiation and subdivision with the four tested populations. Various degrees of clustering were evident between the older parasite samples collected in 2004 at the CMB with the 2016 CMB and 2012 Thailand populations, suggesting some of these parasites had shared ancestry. In contrast, the 2015 Thailand population was genetically distinctive, which may reflect a process of population replacement. The moderately large effective population sizes and proportions of polyclonal infections highlight the necessity of further coordinated and integrated control efforts on both sides of the borders in the pursuit of malaria elimination. Conclusions: With enhanced control efforts on malaria elimination, P. vivax population in the GMS has fragmented into a limited number of clustered foci, but the presence of large P. vivax reservoirs still sustains genetic diversity and transmission. These findings provide new insights into P. vivax transmission dynamics and population structure in this area.

Download Full-text

Evolution of Plasmodium vivax populations in border areas of the Greater Mekong Subregion during malaria elimination

10.21203/rs.2.19786/v1 ◽

2019 ◽

Author(s):

Yuling Li ◽

Yubing Hu ◽

Yan Zhao ◽

Qinghui Wang ◽

Huguette Gaelle Ngassa Mbenda ◽

...

Keyword(s):

Genetic Diversity ◽

Plasmodium Vivax ◽

Malaria Elimination ◽

Scale Up ◽

Transmission Dynamics ◽

Clinical Samples ◽

Effective Population ◽

Border Areas ◽

Greater Mekong Subregion ◽

International Border

Abstract BackgroundCountries within the Greater Mekong Subregion (GMS) of Southeast Asia have committed to eliminating malaria by 2030. Although malaria situation has greatly improved, Plasmodium vivax remains at international border regions. Therefore, to gain a better understanding of transmission dynamics, knowledge on the evolution of P. vivax populations after the scale-up of control interventions will guide more effective targeted control efforts. MethodsWe investigated genetic diversity and population structures in 206 longitudinally collected P. vivax clinical samples in two international border areas at the China-Myanmar border (CMB, n=50 in 2004 and n=52 in 2016) and western Thailand border (n=50 in 2012 and n=54 in 2015). Parasites were genotyped using 10 microsatellite markers. ResultsDespite intensified control efforts, genetic diversity in the four populations remained high (HE = 0.66-0.86). The proportions of polyclonal infections showed substantial decreases to 23.7 and 30.7% in the CMB and western Thailand, respectively, with corresponding decreases in the multiplicity of infection. Consistent with the shrinking map of malaria transmission in the GMS over time, there were also increases in multilocus linkage disequilibrium, suggesting of more fragmented and increasingly inbred parasite populations. There were considerable genetic differentiation and subdivision with the four tested populations. Various degrees of clustering were evident between the older parasite samples collected in 2004 at the CMB with the 2016 CMB and 2012 Thailand populations, suggesting some of these parasites had shared ancestry. In contrast, the 2015 Thailand population was genetically distinctive, which may reflect a process of population replacement. The moderately large effective population sizes and proportions of polyclonal infections highlight the necessity of further coordinated and integrated control efforts on both sides of the borders in the pursuit of malaria elimination. ConclusionsWith enhanced control efforts on malaria elimination, P. vivax population in the GMS has fragmented into a limited number of clustered foci, but the presence of large P. vivax reservoirs still sustains genetic diversity and transmission. These findings provide new insights into P. vivax transmission dynamics and population structure in this area.

Download Full-text

Estimated impact of tafenoquine for Plasmodium vivax control and elimination in Brazil: A modelling study

PLoS Medicine ◽

10.1371/journal.pmed.1003535 ◽

2021 ◽

Vol 18 (4) ◽

pp. e1003535

Author(s):

Narimane Nekkab ◽

Raquel Lana ◽

Marcus Lacerda ◽

Thomas Obadia ◽

André Siqueira ◽

...

Keyword(s):

Case Management ◽

Plasmodium Vivax ◽

Malaria Elimination ◽

Population Level ◽

Transmission Dynamics ◽

Radical Cure ◽

Treatment Pathways ◽

The Impact ◽

Modelling Study ◽

Clinical Cases

Background Despite recent intensification of control measures, Plasmodium vivax poses a major challenge for malaria elimination efforts. Liver-stage hypnozoite parasites that cause relapsing infections can be cleared with primaquine; however, poor treatment adherence undermines drug effectiveness. Tafenoquine, a new single-dose treatment, offers an alternative option for preventing relapses and reducing transmission. In 2018, over 237,000 cases of malaria were reported to the Brazilian health system, of which 91.5% were due to P. vivax. Methods and findings We evaluated the impact of introducing tafenoquine into case management practices on population-level transmission dynamics using a mathematical model of P. vivax transmission. The model was calibrated to reflect the transmission dynamics of P. vivax endemic settings in Brazil in 2018, informed by nationwide malaria case reporting data. Parameters for treatment pathways with chloroquine, primaquine, and tafenoquine with glucose-6-phosphate dehydrogenase deficiency (G6PDd) testing were informed by clinical trial data and the literature. We assumed 71.3% efficacy for primaquine and tafenoquine, a 66.7% adherence rate to the 7-day primaquine regimen, a mean 5.5% G6PDd prevalence, and 8.1% low metaboliser prevalence. The introduction of tafenoquine is predicted to improve effective hypnozoite clearance among P. vivax cases and reduce population-level transmission over time, with heterogeneous levels of impact across different transmission settings. According to the model, while achieving elimination in only few settings in Brazil, tafenoquine rollout in 2021 is estimated to improve the mean effective radical cure rate from 42% (95% uncertainty interval [UI] 41%–44%) to 62% (95% UI 54%–68%) among clinical cases, leading to a predicted 38% (95% UI 7%–99%) reduction in transmission and over 214,000 cumulative averted cases between 2021 and 2025. Higher impact is predicted in settings with low transmission, low pre-existing primaquine adherence, and a high proportion of cases in working-aged males. High-transmission settings with a high proportion of cases in children would benefit from a safe high-efficacy tafenoquine dose for children. Our methodological limitations include not accounting for the role of imported cases from outside the transmission setting, relying on reported clinical cases as a measurement of community-level transmission, and implementing treatment efficacy as a binary condition. Conclusions In our modelling study, we predicted that, provided there is concurrent rollout of G6PDd diagnostics, tafenoquine has the potential to reduce P. vivax transmission by improving effective radical cure through increased adherence and increased protection from new infections. While tafenoquine alone may not be sufficient for P. vivax elimination, its introduction will improve case management, prevent a substantial number of cases, and bring countries closer to achieving malaria elimination goals.

Download Full-text

Contrasting Transmission Dynamics of Co-endemic Plasmodium vivax and P. falciparum: Implications for Malaria Control and Elimination

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0003739 ◽

2015 ◽

Vol 9 (5) ◽

pp. e0003739 ◽

Cited By ~ 45

Author(s):

Rintis Noviyanti ◽

Farah Coutrier ◽

Retno A. S. Utami ◽

Hidayat Trimarsanto ◽

Yusrifar K. Tirta ◽

...

Keyword(s):

Plasmodium Vivax ◽

Malaria Control ◽

Transmission Dynamics

Download Full-text

Transmission dynamics of a trematode parasite: exposure, acquired resistance and parasite aggregation

Parasitology Research ◽

10.1007/s00436-003-1035-y ◽

2004 ◽

Vol 92 (3) ◽

pp. 183-188 ◽

Cited By ~ 34

Author(s):

Anssi Karvonen ◽

Peter J. Hudson ◽

Otto Sepp�l� ◽

E. Tellervo Valtonen

Keyword(s):

Acquired Resistance ◽

Transmission Dynamics ◽

Trematode Parasite ◽

Parasite Aggregation ◽

Parasite Exposure

Download Full-text

Dynamics of Plasmodium vivax populations in border areas of the Greater Mekong Sub-region during malaria elimination

10.21203/rs.2.22640/v2 ◽

2020 ◽

Author(s):

Yuling Li ◽

Yubing Hu ◽

Yan Zhao ◽

Qinghui Wang ◽

Huguette Gaelle Ngassa Mbenda ◽

...

Keyword(s):

Genetic Diversity ◽

Genetic Differentiation ◽

Plasmodium Vivax ◽

Malaria Elimination ◽

Malaria Incidence ◽

Scale Up ◽

Transmission Dynamics ◽

Clinical Samples ◽

Border Areas ◽

International Border

Abstract Background Countries within the Greater Mekong Sub-region (GMS) of Southeast Asia have committed to eliminating malaria by 2030. Although the malaria situation has greatly improved, malaria transmission remains at international border regions. In some areas, Plasmodium vivax has become the predominant parasite. To gain a better understanding of transmission dynamics, knowledge on the changes of P. vivax populations after the scale-up of control interventions will guide more effective targeted control efforts. Methods This study investigated genetic diversity and population structures in 206 P. vivax clinical samples collected at two time points in two international border areas: the China-Myanmar border (CMB) (n=50 in 2004 and n=52 in 2016) and Thailand-Myanmar border (TMB) (n=50 in 2012 and n=54 in 2015). Parasites were genotyped using 10 microsatellite markers. Results Despite intensified control efforts, genetic diversity remained high ( H E = 0.66-0.86) and was not significantly different among the four populations ( P >0.05). Specifically, H E slightly decreased from 0.76 in 2004 to 0.66 in 2016 at the CMB and increased from 0.80 in 2012 to 0.86 in 2015 at the TMB. The proportions of polyclonal infections varied significantly among the four populations ( P < 0.05), and showed substantial decreases from 48.0% in 2004 to 23.7 at the CMB and from 40.0% in 2012 to 30.7% in 2015 at the TMB, with corresponding decreases in the multiplicity of infection. Consistent with the continuous decline of malaria incidence in the GMS over time, there were also increases in multilocus linkage disequilibrium, suggesting more fragmented and increasingly inbred parasite populations. There were considerable genetic differentiation and sub-division among the four tested populations. Temporal genetic differentiation was observed at each site ( F ST = 0.081 at the CMB and F ST = 0.133 at the TMB). Various degrees of clustering were evident between the older parasite samples collected in 2004 at the CMB with the 2016 CMB and 2012 TMB populations, suggesting some of these parasites had shared ancestry. In contrast, the 2015 TMB population was genetically distinctive, which may reflect a process of population replacement. Whereas the effective population size ( N e ) at the CMB showed a decrease from 4979 in 2004 to 3052 in 2016 with the infinite allele model, the N e at the TMB experienced an increase from 6289 to 10259. Conclusions With enhanced control efforts on malaria, P. vivax at the TMB and CMB showed considerable spatial and temporal differentiation, but the presence of large P. vivax reservoirs still sustained genetic diversity and transmission. These findings provide new insights into P. vivax transmission dynamics and population structure in these border areas of the GMS. Coordinated and integrated control efforts on both sides of international borders are essential to reach the goal of regional malaria elimination.

Download Full-text