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Estimating transition rates for epidemiological models of endemic Plasmodium vivax malaria

English title Estimating transition rates for epidemiological models of endemic Plasmodium vivax malaria
Applicant Smith Thomas
Number 125316
Funding scheme Project funding (Div. I-III)
Research institution Swiss Tropical and Public Health Institute
Institution of higher education University of Basel - BS
Main discipline Methods of Epidemiology and Preventive Medicine
Start/End 01.04.2009 - 30.09.2012
Approved amount 443'975.00
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Keywords (5)

malaria; epidemiology; Plasmodium vivax; dynamics; Papua New Guinea

Lay Summary (English)

Lead
Lay summary
Four species of malaria parasites infect humans. Until recently, the focus has fallen largely on Plasmodium falciparum, which places a huge burden of disease across Africa. Attention is now also turning to Plasmodium vivax due to a growing awareness that it too can cause severe and fatal disease. P. vivax has the widest geographical spread, including Asia, the Middle East, Central and South America and the Western Pacific, totaling an estimated 70 million cases per year. Effective control strategies are urgently needed. Planners are hampered by the lack of information on the likely consequences of different interventions. Where data are lacking, mathematical models can be used to provide a 'best guess'. To provide valid predictions, the building blocks of the models must be correct. Basic measures of P. vivax infections are required, such as the duration of infections, relapse and clearance rates, the rate of new infections, infectivity to mosquitoes, and the relationship between clinical symptoms and parasite densities in the blood.P. vivax infection dynamics are difficult to study because people living in endemic areas may harbour several different infections at the same time, the density of parasites in the blood may transiently lie below the limit of detection, and because the parasites can lie dormant in liver cells for long periods and then relapse. Different infections can only be distinguished by high resolution genotyping which allows the characterization of the number of different infections and their diversity. Genotyping of samples from study participants taken repeatedly over time is underway for studies from Papua New Guinea. Statistical methods to analyse this data are not well developed. We propose to develop analyses, fitting models of the dynamics of infections to both the genotyping data and other sources, to estimate the above quantities. We expect that the estimates will be useful for both modelling and for P. vivax epidemiology.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
The Incidence and Differential Seasonal Patterns of Plasmodium vivax Primary Infections and Relapses in a Cohort of Children in Papua New Guinea
Ross A et al (2016), The Incidence and Differential Seasonal Patterns of Plasmodium vivax Primary Infections and Relapses in a Cohort of Children in Papua New Guinea, in PloS Neglected Tropical Diseases, 10(5), e0004582.
Asymptomatic Plasmodium falciparum infections may not be shortened by acquired immunity
Bretscher Michael T, Maire Nicolas, Felger Ingrid, Owusu-Agyei Seth, Smith Tom (2015), Asymptomatic Plasmodium falciparum infections may not be shortened by acquired immunity, in Malaria Journal, 14(1), 294.
A High Force of Plasmodium vivax Blood-Stage Infection Drives the Rapid Acquisition of Immunity in Papua New Guinean Children
Koepfli Cristian, Colborn Katherine L, Kiniboro Benson, Lin Enmoore, Speed Terence P, Siba Peter, Felger Ingrid, Mueller Ivo (2013), A High Force of Plasmodium vivax Blood-Stage Infection Drives the Rapid Acquisition of Immunity in Papua New Guinean Children, in PLoS Neglected Tropical Diseases, 7(9), e2403.
A Large Plasmodium vivax Reservoir and Little Population Structure in the South Pacific
Koepfli Cristian, Timinao Lincoln, Antao Tiago, Barry Alyssa, Siba Peter, Mueller Ivo, Felger Ingrid (2013), A Large Plasmodium vivax Reservoir and Little Population Structure in the South Pacific, in PLoS ONE, 8(6), e66041.
Estimating the burden of malaria infections in blood samples from high-resolution genotyping data
Ross Amanda, Koepfli Cristian, Li Xiaohong, Schoepflin Sonja, Siba Peter, Mueller Ivo, Felger Ingrid, Smith Thomas (2012), Estimating the burden of malaria infections in blood samples from high-resolution genotyping data, in PLoS ONE, 7(8), e42496-e42496.
How much remains detected? Probability of molecular detection of human Plasmodia in the field
Koepfli Cristian, Schoepflin Sonja, Bretscher Michael, Lin Enmoore, Kiniboro Benson, Zimmerman Peter, Smith Thomas, Mueller Ivo, Felger Ingrid (2011), How much remains detected? Probability of molecular detection of human Plasmodia in the field, in PLoS ONE, 6, e19019-e19019.
The distribution of Plasmodium falciparum infection durations
Bretscher Michael, Maire Nicolas, Chitnis Nakul, Felger Ingrid, Owusu-Agyei Seth, Smith Thomas (2011), The distribution of Plasmodium falciparum infection durations, in Epidemics, 3, 109-118.
Detectability of Plasmodium falciparum clones
Bretscher Michael, Valsangiacomo Frederica, Owusu-Agyei Seth, Penny Melissa, Felger Ingrid, Smith Thomas (2010), Detectability of Plasmodium falciparum clones, in Malaria Journal, 9, 234-234.
A novel approach for measuring the burden of uncomplicated Plasmodium falciparum malaria: application to data from Zambia
Crowell Valerie, Yukich Joshua, Briet Olivier, Ross Amanda, Smith Thomas, A novel approach for measuring the burden of uncomplicated Plasmodium falciparum malaria: application to data from Zambia, in PLoS ONE.
Multiplicity and diversity of P vivax infections in a highly endemic region in Papua New Guinea
Koepfli Cristian, Ross Amanda, Kiniboro Benson, Smith Thomas, Zimmerman Peter, Siba Peter, Mueller Ivo, Felger Ingrid, Multiplicity and diversity of P vivax infections in a highly endemic region in Papua New Guinea, in PLoS Negl Trop Dis, 5(12), e1424.

Collaboration

Group / person Country
Types of collaboration
Molecular parasitology group, Swiss Tropical Institute Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Papua New Guinea Institute of Medical Research PapuaNew Guinea (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Centers for Disease Control United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
BG Medicine (Xiaohong Li) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Walter and Eliza Hall Institute Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel

Associated projects

Number Title Start Funding scheme
52984 Epidemiological interactions between heterologous human malaria parasites. 01.04.1998 Project funding (Div. I-III)
163473 Movement rates of African malaria vectors and their implications in models of vector control interventions 01.01.2016 Project funding (Div. I-III)
105994 Predicting efficacy and cost-effectiveness of malaria control interventions in Africa using dynamic models 01.10.2004 Project funding (Div. I-III)
105994 Predicting efficacy and cost-effectiveness of malaria control interventions in Africa using dynamic models 01.10.2004 Project funding (Div. I-III)
112196 Fitness costs of antimalarial drug resistance 01.05.2006 Project funding (Div. I-III)

Abstract

BackgroundPlasmodium vivax is a protozoan parasite, one of four species that account for nearly all human malaria infections. Plasmodium vivax and Plasmodium falciparum together account for the vast majority of human malaria infections worldwide. Until recently, P. vivax has been the focus of relatively little research partly because it causes less severe disease than P. falciparum [2]. However it is increasingly recognized that P. vivax can cause severe and even fatal disease With growing awareness of the burden of P. vivax on affected populations, control of P. vivax infections and morbidity is once again seen as a priority for areas where the disease is endemic. The recent call from the Bill and Melinda Gates Foundation for malaria eradication has further highlighted the neglect of P. vivax since malaria eradication necessarily entails the elimination of both species.Mathematical models of Plasmodium vivax dynamics in humans are hampered by the lack of information on basic parameters describing infections and disease in endemic areas. Existing compartmental models of P. vivax population dynamics are unsuitable for predicting the impact of interventions.Aims and methods We have identified five processes that need to be quantified in any adequate general model of P. vivax dynamics, (i) the force of infection of the liver, (ii) the release of merozoites from the liver, (iii) the clearance of blood stage infections, (iv) pathogenesis, and (v) infectivity to Anopheles mosquitoes. We now propose a project to use both literature review and statistical analyses, (a) to obtain field-based estimates of the corresponding transition probabilites and rates; (b) to examine, where possible, what are the main factors modifying and determining these probabilities and rates; (c) to examine, in particular, how these rates and probabilities vary with age, and/or exposure to P. vivax.These analyses require longitudinal field studies to study infection dynamics over time. We will take advantage of such datasets from Papua New Guinea (PNG). P. vivax is endemic in PNG, and the north coast (Madang and East Sepik provinces) include some of the highest rates of P. vivax transmission in the world [3]. A number of intensive studies of P. vivax epidemiology are currently in progress and the data is made available via a strong existing collaboration between the Swiss Tropical Institute (STI) and the Papua New Guinea Institute of Medical Research (PNGIMR). The research proposed now is additional to the primary analyses covered by existing support of these field studies, but is covered by the existing research approvals and consent obtained for these studies. Infection dynamics of P. vivax in endemic areas are difficult to study because of the challenge of distinguishing persisting infections from new ones, because parasite densities are often transiently below the limit of detection and because of relapses. In high endemicity populations many hosts harbour multiple clones of P. vivax [1] and new or relapsing infections can only be distinguished from persisting ones by high resolution genotyping. Extensive genotyping (collected for characterising infection multiplicity and parasite diversity) is already planned for some of the PNG P. vivax studies. To estimate rates of infection, relapse, and clearance of blood stage infections in the PNG data we will therefore extend hidden Markov models and/or immigration-death models developed to analyse longitudinal genotyping data for P. falciparum [4;5]. Where necessary we will supplement these data with additional genotyping.Reference List1. Bruce MC, Galinski MR, Barnwell JW, Donnelly CA, Walmsley M, Alpers MP, Walliker D, Day KP: Genetic diversity and dynamics of plasmodium falciparum and P. vivax populations in multiply infected children with asymptomatic malaria infections in Papua New Guinea. Parasitology 121 ( Pt 3):257-272, 20002. Herrera S, Corradin G, Arevalo-Herrera M: A update on the search for a Plasmodium vivax vaccine. Trends Parasitol 23:122-128, 20073. Muller I, Bockarie M, Alpers MP, Smith T: The epidemiology of malaria in Papua New Guinea. Trends Parasitol 19:253-259, 20034. Sama W, Owusu-Agyei S, Felger I, Vounatsou P, Smith T: An immigration-death model to estimate the duration of malaria infection when detectability of the parasite is imperfect. Stat.Med. 24:3269-3288, 20055. Smith T, Vounatsou P: Estimation of infection and recovery rates for highly polymorphic parasites when detectability is imperfect, using hidden Markov models. Stat.Med. 22:1709-1724, 2003
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