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

PLoS Medicine ◽  
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.

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

2014 ◽  
Vol 13 (1) ◽  
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

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

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.

scholarly journals Natural infections with different Plasmodium species induce antibodies reactive to a chimeric Plasmodium vivax recombinant protein

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jessica N. McCaffery ◽  
Balwan Singh ◽  
Douglas Nace ◽  
Alberto Moreno ◽  
Venkatachalam Udhayakumar ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Malaria Elimination ◽  
Malaria Incidence ◽  
Binding Capacity ◽  
Specific Antigen ◽  
Plasmodium Species ◽  
Population Level ◽  
Antibody Detection ◽  
Plasma Samples ◽  
High Responders

Abstract Background As malaria incidence and transmission in a region decreases, it becomes increasingly difficult to identify areas of active transmission. Improved methods for identifying and monitoring foci of active malaria transmission are needed in areas of low parasite prevalence in order to achieve malaria elimination. Serological assays can provide population-level infection history to inform elimination campaigns. Methods A bead-based multiplex antibody detection assay was used to evaluate a chimeric Plasmodium vivax MSP1 protein (PvRMC-MSP1), designed to be broadly immunogenic for use in vaccine studies, to act as a pan-malaria serological tool based on its ability to capture IgG in plasma samples obtained from naturally exposed individuals. Samples from 236 US travellers with PCR confirmed infection status from all four major Plasmodium species infecting humans, Plasmodium falciparum (n = 181), Plasmodium vivax (n = 38), Plasmodium malariae (n = 4), and Plasmodium ovale (n = 13) were tested for IgG capture using PvRMC-MSP1 as well as the four recombinant MSP1-19 kD isoforms representative of these Plasmodium species. Results Regardless of infecting Plasmodium species, a large proportion of plasma samples from infected US travellers provided a high assay signal to the PvRMC-MSP1 chimeric protein, with 115 high responders out of 236 samples assessed (48.7%). When grouped by active infection, 38.7% P. falciparum-, 92.1% of P. vivax-, 75.0% P. malariae-, and 53.4% of P. ovale-infected individuals displayed high assay signals in response to PvRMC-MSP1. It was also determined that plasma from P. vivax-infected individuals produced increased assay signals in response to the PvRMC-MSP1 chimera as compared to the recombinant PvMSP1 for 89.5% (34 out of 38) of individuals. PvRMC-MSP1 also showed improved ability to capture IgG antibodies from P. falciparum-infected individuals when compared to the capture by recombinant PvMSP1, with high assay signals observed for 38.7% of P. falciparum-infected travellers in response to PvRMC-MSP1 IgG capture compared to just 1.1% who were high responders to capture by the recombinant PvMSP1 protein. Conclusions These results support further study of designed antigens as an approach for increasing sensitivity or broadening binding capacity to improve existing serological tools for determining population-level exposure to Plasmodium species. Including both broad-reacting and Plasmodium species-specific antigen-coated beads in an assay panel could provide a nuanced view of population-level exposure histories, an extensive IgG profile, and detailed seroestimates. A more sensitive serological tool for detection of P. vivax exposure would aid malaria elimination campaigns in co-endemic areas and regions where P. vivax is the dominant parasite.

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

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.

scholarly journals Modeling the Heterogeneity of Dengue Transmission in a City

2018 ◽  
Vol 15 (6) ◽  
pp. 1128 ◽  
Author(s):  
Lingcai Kong ◽  
Jinfeng Wang ◽  
Zhongjie Li ◽  
Shengjie Lai ◽  
Qiyong Liu ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Negative Binomial ◽  
Influence Factors ◽  
Population Level ◽  
Transmission Dynamics ◽  
Extended Model ◽  
Vector Borne Diseases ◽  
Small Peak ◽  
High Level ◽  
The Impact

Dengue fever is one of the most important vector-borne diseases in the world, and modeling its transmission dynamics allows for determining the key influence factors and helps to perform interventions. The heterogeneity of mosquito bites of humans during the spread of dengue virus is an important factor that should be considered when modeling the dynamics. However, traditional models generally assumed homogeneous mixing between humans and vectors, which is inconsistent with reality. In this study, we proposed a compartmental model with negative binomial distribution transmission terms to model this heterogeneity at the population level. By including the aquatic stage of mosquitoes and incorporating the impacts of the environment and climate factors, an extended model was used to simulate the 2014 dengue outbreak in Guangzhou, China, and to simulate the spread of dengue in different scenarios. The results showed that a high level of heterogeneity can result in a small peak size in an outbreak. As the level of heterogeneity decreases, the transmission dynamics approximate the dynamics predicted by the corresponding homogeneous mixing model. The simulation results from different scenarios showed that performing interventions early and decreasing the carrying capacity for mosquitoes are necessary for preventing and controlling dengue epidemics. This study contributes to a better understanding of the impact of heterogeneity during the spread of dengue virus.

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

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.

scholarly journals The use of ultrasensitive quantitative-PCR to assess the impact of primaquine on asymptomatic relapse of Plasmodium vivax infections: a randomized, controlled trial in Lao PDR

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Koukeo Phommasone ◽  
Frank van Leth ◽  
Mallika Imwong ◽  
Gisela Henriques ◽  
Tiengkham Pongvongsa ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Quantitative Pcr ◽  
Cumulative Incidence ◽  
Controlled Trial ◽  
Lao Pdr ◽  
Radical Cure ◽  
Directly Observed Therapy ◽  
Exact Test ◽  
The Impact

Abstract Background Trials to assess the efficacy of the radical cure of Plasmodium vivax malaria with 8-aminoquinolines require that most post-treatment relapses are identified, but there is no consensus on the optimal duration of follow-up in either symptomatic or asymptomatic vivax malaria. The efficacy of a 14-day course of primaquine on the cumulative incidence of recurrent asymptomatic P. vivax infections detected by ultrasensitive quantitative PCR (uPCR) as a primary endpoint was assessed. Methods A randomized, placebo-controlled, single-blind trial was conducted in four villages of the Lao PDR during 2016–2018 nested in a larger project evaluating mass drug administrations (MDA) with dihydroartemisinin-piperaquine (DP) and a single low-dose primaquine to clear Plasmodium falciparum infections. In the nested sub-study, eligible participants with mono- or mixed P. vivax infections detected by uPCR were randomized to receive either 14 days of primaquine (0.5 mg/kg/day) or placebo during the last round of MDA (round 3) through directly observed therapy. Participants were checked monthly for 12 months for parasitaemia using uPCR. The primary outcome was cumulative incidence of participants with at least one recurrent episode of P. vivax infection. Results 20 G6PD-normal participants were randomized in each arm. 5 (29%) of 20 participants in the placebo arm experienced asymptomatic, recurrent P. vivax infections, resulting in a cumulative incidence at month 12 of 29%. None of the 20 participants in the intervention arm had recurrent infections (p = 0.047 Fisher’s exact test). Participants with recurrent P. vivax infections were found to be parasitaemic for between one and five sequential monthly tests. The median time to recurrence of P. vivax parasitaemia was 178 days (range 62–243 days). Conclusions A 14-day course of primaquine in addition to a DP-MDA was safe, well-tolerated, and prevented recurrent asymptomatic P. vivax infections. Long follow-up for up to 12 months is required to capture all recurrences following the treatment of asymptomatic vivax infection. To eliminate all malarias in settings where P. vivax is endemic, a full-course of an 8-aminoquinolines should be added to MDA to eliminate all malarias. Trial registration This study was registered with ClinicalTrials.gov under NCT02802813 on 16th June 2016. https://clinicaltrials.gov/ct2/show/NCT02802813

Use of Nutrition Information and Understanding of “Percent Daily Value” on Nutrition Facts Tables: Evaluating the Impact of a National Public Education Campaign among Youth and Young Adults in Canada

2019 ◽  
Vol 80 (4) ◽  
pp. 200-204 ◽  
Author(s):  
Brittany Cormier ◽  
Lana Vanderlee ◽  
David Hammond
Keyword(s):  
Population Level ◽  
Correct Recall ◽  
Nutrition Information ◽  
Education Campaign ◽  
Knowledge Based ◽  
Public Education Campaign ◽  
Youth And Young Adults ◽  
Campaign Message ◽  
Health Canada ◽  
The Impact

Purpose: In 2010, Health Canada implemented a national campaign to improve understanding of “percent daily value” (%DV) in Nutrition Facts Tables (NFTs). This study examined sources of nutrition information and knowledge of %DV information communicated in the campaign. Methods: Respondents aged 16–30 years completed the Canada Food Study in 2016 (n = 2665). Measures included sources of nutrition information, NFT use, and %DV knowledge based on the campaign message (“5% DV or less is a little; 15% DV or more is a lot”). A logistic regression examined correlates of providing “correct” responses to %DV questions related to the campaign messaging. Results: Overall, 7.2% (n = 191) respondents correctly indicated that 5% is “a little”, and 4.3% (n = 115) correctly indicated 15% DV was “a lot”. Only 4.0% (n = 107) correctly answered both. Correct recall of %DV amounts was not associated with number of information sources reported, but was greater among those who were female, were younger, and reported greater NFT understanding and serving size information use (P < 0.05 for all). Conclusions: Results show low awareness of messaging from the Nutrition Facts Education Campaign among young Canadians. Such a mass media campaign may be insufficient on its own to enhance population-level understanding of %DV.

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