Addressing Plasmodium vivax: From Control to Elimination

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: closed (15 July 2021) | Viewed by 22073

Special Issue Editors


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Guest Editor
Global and Tropical Health Divisions, Menzies School of Health Research and Charles Darwin University, Darwin, Australia
Interests: vivax malaria; malaria; clinical trials; epidemiology; drug resistance; translational research
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, WA, Australia
2. Medical School, University of Western Australia, Crawley, WA, Australia
Interests: malaria; clinical trials; antimalarial pharmacology; pharmacokinetics; maternal and infant health

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Guest Editor
International Center for Diarrheal Diseases, Dhaka, Bangladesh
Interests: malaria; drug resistance; clinical trials; G6PD; medical entomology

Special Issue Information

Dear Colleagues,

The recently launched global technical strategy for malaria elimination aims to achieve a 90% reduction in global malaria mortality by 2030, with the Asia-Pacific region committing to elimination by 2030. Achieving this ambitious milestone requires innovative and broad-ranging malaria control strategies. Over the last decades, the global incidence of malaria has decreased substantially, but this decline has been far greater for Plasmodium falciparum than for P. vivax. Because of the important biological differences, P. vivax has proven to be a far more difficult parasite to eliminate. Unlike P. falciparum, P. vivax can form dormant liver stages (hypnozoites), which can reactivate weeks to months after an acute infection (relapse), posing unique challenges for treatment, control, and elimination. Additionally, a radical cure of P. vivax is further complicated by the limited pharmaceutical options for an effective cure, and the widespread prevalence of G6PD deficiency in vivax endemic regions.

For this Special Issue of Pathogens, we invite authors to submit original research, review articles, short notes, or communications related to all aspects of P. vivax treatment, control, and elimination including diagnostics. We look forward to your contribution.

Dr. Kamala Ley-Thriemer
Dr. Brioni Moore
Dr. Mohammad Shafiul Alam
Guest Editors

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Keywords

  • P. vivax
  • Radical cure
  • Malaria
  • Malaria elimination
  • Vivax malaria
  • G6PD deficiency
  • Diagnostic tools

Published Papers (9 papers)

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16 pages, 5582 KiB  
Article
Dry Post Wintertime Mass Surveillance Unearths a Huge Burden of P. vivax, and Mixed Infection with P. vivax P. falciparum, a Threat to Malaria Elimination, in Dhalai, Tripura, India
by Ipsita Pal Bhowmick, Tulika Nirmolia, Apoorva Pandey, Sarala K. Subbarao, Aatreyee Nath, Susmita Senapati, Debabrata Tripathy, Rocky Pebam, Suman Nag, Rajashree Roy, Dipanjan Dasgupta, Jayanta Debnath, Kongkona Gogoi, Karuna Gogoi, Lakhyajit Borah, Rajdeep Chanda, Arup Borgohain, Chelapro Mog, Ujjwal Sarkar, Phiroz Gogoi, Bishal Debnath, Jyotish Debbarma, Dibya Ranjan Bhattacharya, Pyare Lal Joshi, Harpreet Kaur and Kanwar Narainadd Show full author list remove Hide full author list
Pathogens 2021, 10(10), 1259; https://doi.org/10.3390/pathogens10101259 - 29 Sep 2021
Cited by 8 | Viewed by 2879
Abstract
With India aiming to achieve malaria elimination by 2030, several strategies have been put in place. With that aim, mass surveillance is now being conducted in some malaria-endemic pockets. As dry season mass surveillance has been shown to have its importance in targeting [...] Read more.
With India aiming to achieve malaria elimination by 2030, several strategies have been put in place. With that aim, mass surveillance is now being conducted in some malaria-endemic pockets. As dry season mass surveillance has been shown to have its importance in targeting the reservoir, a study was undertaken to assess the parasite load by a sensitive molecular method during one of the mass surveys conducted in the dry winter period. It was executed in two malaria-endemic villages of Dhalai District, Tripura, in northeast India, also reported as P. falciparum predominated area. The present study found an enormous burden of Rapid Diagnostic Test negative malaria cases with P. vivax along with P. vivax and P. falciparum mixed infections during the mass surveillance from febrile and afebrile cases in dry winter months (February 2021–March 2021). Of the total 150 samples tested, 72 (48%) were positive and 78 (52%) negative for malaria by PCR. Out of the 72 positives, 6 (8.33%) were P. falciparum, 40 (55.55%) P. vivax, and 26 (36.11%) mixed infections. Out of 78 malaria negative samples, 6 (7.7%) were with symptoms, while among the total malaria positive, 72 cases 7 (9.8%) were with symptoms, and 65 (90.2%) were asymptomatic. Out of 114 samples tested by both microscopy and PCR, 42 samples turned out to be submicroscopic with 4 P. falciparum, 23 P. vivax, and 15 mixed infections. Although all P. vivax submicroscopic infections were asymptomatic, three P. falciparum cases were found to be febrile. Evidence of malaria transmission was also found in the vectors in the winter month. The study ascertained the use of molecular diagnostic techniques in detecting the actual burden of malaria, especially of P. vivax, in mass surveys. As Jhum cultivators in Tripura are at high risk, screening for the malarial reservoirs in pre-Jhum months can help with malaria control and elimination. Full article
(This article belongs to the Special Issue Addressing Plasmodium vivax: From Control to Elimination)
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18 pages, 2153 KiB  
Article
Plasmodium vivax Genetic Diversity in Panama: Challenges for Malaria Elimination in Mesoamerica
by Ana María Santamaría, Vanessa Vásquez, Chystrie Rigg, Franklyn Samudio, Dianik Moreno, Luis Romero, Azael Saldaña, Luis Fernando Chaves and José Eduardo Calzada
Pathogens 2021, 10(8), 989; https://doi.org/10.3390/pathogens10080989 - 05 Aug 2021
Cited by 3 | Viewed by 2465
Abstract
Panama and all nations within the Mesoamerican region have committed to eliminate malaria within this decade. With more than 90% of the malaria cases in this region caused by Plasmodium vivax, an efficient national/regional elimination plan must include a comprehensive study of [...] Read more.
Panama and all nations within the Mesoamerican region have committed to eliminate malaria within this decade. With more than 90% of the malaria cases in this region caused by Plasmodium vivax, an efficient national/regional elimination plan must include a comprehensive study of this parasite’s genetic diversity. Here, we retrospectively analyzed P. vivax genetic diversity in autochthonous and imported field isolates collected in different endemic regions in Panama from 2007 to 2020, using highly polymorphic markers (csp, msp-1, and msp-3α). We did the analysis using molecular techniques that are cost-effective for malaria molecular surveillance within Mesoamerica. Thus, we used molecular analyses that are feasible for malaria molecular surveillance within the region, and that can provide useful information for policy and decision making about malaria elimination. We also evaluated if haplotypes established by combining the genotypes found in these genes were associated with relevant epidemiological variables and showed structure across the transmission foci that have been observed in Panama. Ten different haplotypes were identified, some of them strongly associated with geographical origin, age, and collection year. Phylogenetic analysis of csp (central repeat domain) revealed that both major variant types (vk210 and vk247) were circulating in Panama. Variant vk247 was restricted to the eastern endemic regions, while vk210 was predominant (77.3%) and widespread, displaying higher diversity (14 alleles) and geographically biased alleles. The regional implications of these molecular findings for the control of P. vivax malaria to achieve elimination across Mesoamerica are discussed. Full article
(This article belongs to the Special Issue Addressing Plasmodium vivax: From Control to Elimination)
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23 pages, 3164 KiB  
Article
PvMSP8 as a Novel Plasmodium vivax Malaria Sero-Marker for the Peruvian Amazon
by Elizabeth Villasis, Katherine Garro, Angel Rosas-Aguirre, Pamela Rodriguez, Jason Rosado, Anthony Gave, Mitchel Guzman-Guzman, Paulo Manrique, Michael White, Niko Speybroeck, Joseph Michael Vinetz, Katherine Torres and Dionicia Gamboa
Pathogens 2021, 10(3), 282; https://doi.org/10.3390/pathogens10030282 - 02 Mar 2021
Cited by 5 | Viewed by 2602
Abstract
The measurement of recent malaria exposure can support malaria control efforts. This study evaluated serological responses to an in-house Plasmodium vivax Merozoite Surface Protein 8 (PvMSP8) expressed in a Baculovirus system as sero-marker of recent exposure to P. vivax (Pv) in the Peruvian [...] Read more.
The measurement of recent malaria exposure can support malaria control efforts. This study evaluated serological responses to an in-house Plasmodium vivax Merozoite Surface Protein 8 (PvMSP8) expressed in a Baculovirus system as sero-marker of recent exposure to P. vivax (Pv) in the Peruvian Amazon. In a first evaluation, IgGs against PvMSP8 and PvMSP10 proteins were measured by Luminex in a cohort of 422 Amazonian individuals with known history of Pv exposure (monthly data of infection status by qPCR and/or microscopy over five months). Both serological responses were able to discriminate between exposed and non-exposed individuals in a good manner, with slightly higher performance of anti-PvMSP10 IgGs (area under the curve AUC = 0.78 [95% CI = 0.72–0.83]) than anti-PvMSP8 IgGs (AUC = 0.72 [95% CI = 0.67–0.78]) (p = 0.01). In a second evaluation, the analysis by ELISA of 1251 plasma samples, collected during a population-based cross-sectional survey, confirmed the good performance of anti-PvMSP8 IgGs for discriminating between individuals with Pv infection at the time of survey and/or with antecedent of Pv in the past month (AUC = 0.79 [95% CI = 0.74–0.83]). Anti-PvMSP8 IgG antibodies can be considered as a good biomarker of recent Pv exposure in low-moderate transmission settings of the Peruvian Amazon. Full article
(This article belongs to the Special Issue Addressing Plasmodium vivax: From Control to Elimination)
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20 pages, 939 KiB  
Article
Diagnostic Practices and Treatment for P. vivax in the InterEthnic Therapeutic Encounter of South-Central Vietnam: A Mixed-Methods Study
by Thuan Thi Nguyen, Xa Xuan Nguyen, Maya Ronse, Quynh Truc Nguyen, Phuc Quang Ho, Duong Thanh Tran, Rene Gerrets, Kamala Thriemer, Benedikt Ley, Jutta Marfurt, Ric N. Price, Koen Peeters Grietens and Charlotte Gryseels
Pathogens 2021, 10(1), 26; https://doi.org/10.3390/pathogens10010026 - 31 Dec 2020
Cited by 4 | Viewed by 3245
Abstract
Malaria elimination in the Greater Mekong Sub-Region is challenged by a rising proportion of malaria attributable to P. vivax. Primaquine (PQ) is effective in eliminating the parasite’s dormant liver stages and can prevent relapsing infections, but it induces severe haemolysis in patients with [...] Read more.
Malaria elimination in the Greater Mekong Sub-Region is challenged by a rising proportion of malaria attributable to P. vivax. Primaquine (PQ) is effective in eliminating the parasite’s dormant liver stages and can prevent relapsing infections, but it induces severe haemolysis in patients with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, highlighting the importance of testing enzyme activity prior to treatment. A mixed-method study was conducted in south-central Vietnam to explore the factors that affect acceptability of G6PD testing, treatment-seeking behaviors, and adherence to current regimens. The majority of respondents (75.7%) were unaware of the different parasite species and rather differentiated malaria by perceived severity. People sought a diagnosis if suspected of malaria fever but not if they perceived their fevers as mild. Most respondents agreed to take prescribed medication to treat asymptomatic infection (94.1%) and to continue medication even if they felt better (91.5%). Health professionals did not have G6PD diagnostic tools nor the means to prescribe PQ safely. Adherence to treatment was linked to trust in public providers, who were perceived to make therapeutic decisions in the interest of the patient. Greater focus on providing acceptable ways of assessing G6PD deficiency will be needed to ensure the timely elimination of malaria in Vietnam. Full article
(This article belongs to the Special Issue Addressing Plasmodium vivax: From Control to Elimination)
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9 pages, 1436 KiB  
Article
An Ultra-Sensitive Technique: Using Pv-mtCOX1 qPCR to Detect Early Recurrences of Plasmodium vivax in Patients in the Brazilian Amazon
by Laila R. A. Barbosa, Emanuelle L. da Silva, Anne C. G. de Almeida, Yanka E. A. R. Salazar, André M. Siqueira, Maria das Graças Costa Alecrim, José Luiz Fernandes Vieira, Quique Bassat, Marcus V. G. de Lacerda, Wuelton M. Monteiro and Gisely C. Melo
Pathogens 2021, 10(1), 19; https://doi.org/10.3390/pathogens10010019 - 30 Dec 2020
Viewed by 1737
Abstract
Background: Early recurrence of Plasmodium vivax is a challenge for malaria control in the field, particularly because this species is associated with lower parasitemia, which hinders diagnosis and monitoring through blood smear testing. Early recurrences, defined as the persistence of parasites in the [...] Read more.
Background: Early recurrence of Plasmodium vivax is a challenge for malaria control in the field, particularly because this species is associated with lower parasitemia, which hinders diagnosis and monitoring through blood smear testing. Early recurrences, defined as the persistence of parasites in the peripheral blood despite adequate drug dosages, may arise from resistance to chloroquine. The objective of the study was to estimate early recurrence of P. vivax in the Brazilian Amazon by using a highly-sensitive detection method, in this case, PCR. Methods: An ultra-sensitive qPCR that targeted mitochondrial DNA was used to compare a standard qPCR that targeted 18S rDNA to detect early recurrence of P. vivax in very low densities in samples from patients treated with chloroquine. Results: Out of a total of 312 cases, 29 samples (9.3%) were characterized as recurrences, from which 3.2% (10/312) were only detected through ultra-sensitive qPCR testing. Conclusions: Studies that report the detection of P. vivax early recurrences using light microscopy may severely underestimate their true incidence. Full article
(This article belongs to the Special Issue Addressing Plasmodium vivax: From Control to Elimination)
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18 pages, 458 KiB  
Article
Precarity at the Margins of Malaria Control in the Chittagong Hill Tracts in Bangladesh: A Mixed-Methods Study
by Mohammad Abdul Matin, Nandini D. P. Sarkar, Ching Swe Phru, Benedikt Ley, Kamala Thriemer, Ric N. Price, Koen Peeters Grietens, Wasif Ali Khan, Mohammad Shafiul Alam and Charlotte Gryseels
Pathogens 2020, 9(10), 840; https://doi.org/10.3390/pathogens9100840 - 14 Oct 2020
Cited by 6 | Viewed by 2859
Abstract
Bangladesh has achieved significant progress towards malaria elimination, although health service delivery for malaria remains challenging in remote forested areas such as the Chittagong Hill Tracts (CHT). The aim of this study was to investigate perceptions of malaria and its treatment among the [...] Read more.
Bangladesh has achieved significant progress towards malaria elimination, although health service delivery for malaria remains challenging in remote forested areas such as the Chittagong Hill Tracts (CHT). The aim of this study was to investigate perceptions of malaria and its treatment among the local population to inform contextualized strategies for rolling out radical cure for P. vivax in Bangladesh. The study comprised two sequential strands whereby the preliminary results of a qualitative strand informed the development of a structured survey questionnaire used in the quantitative strand. Results show that ethnic minority populations in the CHT live in precarious socio-economic conditions which increase their exposure to infectious diseases, and that febrile patients often self-treat, including home remedies and pharmaceuticals, before attending a healthcare facility. Perceived low quality of care and lack of communication between Bengali health providers and ethnic minority patients also affects access to public healthcare. Malaria is viewed as a condition that affects vulnerable people weakened by agricultural work and taking away blood is perceived to increase such vulnerability. Healthcare providers that initiate and sustain a dialogue about these issues with ethnic minority patients may foster the trust that is needed for local malaria elimination efforts. Full article
(This article belongs to the Special Issue Addressing Plasmodium vivax: From Control to Elimination)
13 pages, 300 KiB  
Article
Molecular Detection of Antimalarial Drug Resistance in Plasmodium vivax from Returned Travellers to NSW, Australia during 2008–2018
by Chaturong Noisang, Wieland Meyer, Nongyao Sawangjaroen, John Ellis and Rogan Lee
Pathogens 2020, 9(2), 101; https://doi.org/10.3390/pathogens9020101 - 05 Feb 2020
Cited by 7 | Viewed by 3108
Abstract
To monitor drug resistance in Plasmodium vivax, a multidrug resistance 1 (Pvmdr1) gene and a putative transporter protein (Pvcrt-o) gene were used as molecular markers for chloroquine resistance. The biomarkers, the dihydrofolate reductase (Pvdhfr) gene and [...] Read more.
To monitor drug resistance in Plasmodium vivax, a multidrug resistance 1 (Pvmdr1) gene and a putative transporter protein (Pvcrt-o) gene were used as molecular markers for chloroquine resistance. The biomarkers, the dihydrofolate reductase (Pvdhfr) gene and the dihydropteroate synthetase (Pvdhps) gene, were also used for the detection of resistance to sulphadoxine-pyrimethamine (SP); this drug is often accidentally used to treat P. vivax infections. Clinical blood samples (n = 120) were collected from patients who had been to one of eight malaria-endemic countries and diagnosed with P. vivax infection. The chloroquine resistance marker, the Pvmdr1 gene, showed F976:L1076 mutations and L1076 mutation. A K10 insertion in the Pvcrt-o gene was also found among the samples successfully sequenced. A combination of L/I57:R58:M61:T117 mutations in the Pvdhfr gene and G383:G553 mutations in the Pvdhps gene were also observed. Mutations found in these genes indicate that drug resistance is present in these eight countries. Whether or not countries are using chloroquine to treat P. vivax, there appears to be an increase in mutation numbers in resistance gene markers. The detected changes in mutation rates of these genes do suggest that there is still a trend towards increasing P. vivax resistance to chloroquine. The presence of the mutations associated with SP resistance indicates that P. vivax has had exposure to SP and this may be a consequence of either misdiagnosis or coinfections with P. falciparum in the past. Full article
(This article belongs to the Special Issue Addressing Plasmodium vivax: From Control to Elimination)

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3 pages, 208 KiB  
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Reply to Deora et al. Multiplexing for Plasmodium spp.? Think Again! Comment on “Bhowmick et al. Dry Post Wintertime Mass Surveillance Unearths a Huge Burden of P. vivax, and Mixed Infection with P. vivax P. falciparum, a Threat to Malaria Elimination, in Dhalai, Tripura, India. Pathogens 2021, 10, 1259”
by Ipsita Pal-Bhowmick, Tulika Nirmolia, Apoorva Pandey, Sarala K. Subbarao, Aatreyee Nath, Susmita Senapati, Debabrata Tripathy, Rocky Pebam, Suman Nag, Rajashree Roy, Dipanjan Dasgupta, Jayanta Debnath, Kongkona Gogoi, Karuna Gogoi, Lakhyajit Borah, Rajdeep Chanda, Arup Borgohain, Chelapro Mog, Ujjwal Sarkar, Phiroz Gogoi, Bishal Debnath, Jyotish Debbarma, Dibya Ranjan Bhattacharya, Pyare Lal Joshi, Harpreet Kaur and Kanwar Narainadd Show full author list remove Hide full author list
Pathogens 2022, 11(8), 832; https://doi.org/10.3390/pathogens11080832 - 26 Jul 2022
Viewed by 1090
Abstract
We thank Deora et al. [...] Full article
(This article belongs to the Special Issue Addressing Plasmodium vivax: From Control to Elimination)
2 pages, 178 KiB  
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Multiplexing for Plasmodium spp.? Think Again! Comment on Bhowmick et al. Dry Post Wintertime Mass Surveillance Unearths a Huge Burden of P. vivax, and Mixed Infection with P. vivax P. falciparum, a Threat to Malaria Elimination, in Dhalai, Tripura, India. Pathogens 2021, 10, 1259
by Nimita Deora, Sonalika Kar and Abhinav Sinha
Pathogens 2022, 11(7), 737; https://doi.org/10.3390/pathogens11070737 - 29 Jun 2022
Cited by 1 | Viewed by 957
Abstract
The study by Bhowmick et al. [...] Full article
(This article belongs to the Special Issue Addressing Plasmodium vivax: From Control to Elimination)
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