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Addressing the challenges of declining malaria transmission in the Amazon on the way to elimination: non-malarial fevers and low parasitaemias

English title Addressing the challenges of declining malaria transmission in the Amazon on the way to elimination: non-malarial fevers and low parasitaemias
Applicant Felger Ingrid
Number 164182
Funding scheme Bilateral programmes
Research institution Abt. öff. Gesundheitswesen und Epidemiologie Schweizerisches Tropen- und Public Health-Institut
Institution of higher education University of Basel - BS
Main discipline Infectious Diseases
Start/End 01.05.2016 - 31.07.2019
Approved amount 249'780.00
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All Disciplines (2)

Discipline
Infectious Diseases
Tropical Medicine

Keywords (4)

molecular epidemiology; aetiology of fever; sub-microscopic Plasmodium vivax infection; malaria elimination

Lay Summary (German)

Lead
Dieses Forschungsprojekt untersucht wie die Behandlung von Malaria und anderen Fiebererkrankungen in Brasilien optimiert werden können und wie wichtig symptomfreie Parasitenträger für die Übertragung der Malaria sind. Beide Forschungsziele spielen für das Design zukünftiger Malaria-Bekämpfungsstrategien eine zentrale Rolle.
Lay summary

Plasmodium vivax ist der häufigste Malaria-Erreger in Brasilien. Dieser einzellige Parasit wird durch Moskitos übertragen und befällt menschliche Erythrozyten, was meist bei Kleinkindern zu Fieberanfällen führt. P. vivax stellt ein grosses Gesundheitsproblem im Amazonasgebiet dar, obwohl die Übertragung des Parasiten dank intensiver Malaria-Kontrollprogramme stetig sinkt. In Folge nimmt der Anteil der Malaria an Fiebererkrankungen relativ zu anderen Infektionskrankheiten ab. Andere Erreger werden in ländlichen Gesundheitszentren, die bisher allein auf Malaria-Diagnose spezialisiert waren, jedoch nur schwer erkannt. Daher müssen neue klinische Vorschriften und Diagnosemöglichkeiten für verschiedene Erreger für eine patientennahe und dezentrale Gesundheitsversorgung entwickelt und erprobt werden.

Für die Planung gezielter Massnahmen zur Malaria-Eliminierung in Brasilien ist eine entscheidende Frage derzeit noch ungelöst: Wie viel tragen Infektion, die keine Symptome hervorrufen und somit unbemerkt und unbehandelt bleiben, zur allgemeinen Malaria-Übertragung im Land bei? Dieses Projekt untersucht daher, ob und wie viele P. vivax-infizierte Blutproben von symptomfreien Patienten Moskitos infizieren können. Diese Information ist entscheidend dafür, wie sensitiv ein diagnostischer Test für Malaria sein muss und liefert eine wichtige Entscheidungsgrundlage zur Entwicklung von Malaria-Kontrollstrategien um die Weiterübertragung auf den Moskito zu blockieren.

Direct link to Lay Summary Last update: 14.01.2016

Responsible applicant and co-applicants

Employees

Project partner

Publications

Collaboration

Group / person Country
Types of collaboration
Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University Thailand (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
FIOCRUZ - Fundaçao do Medicine Tropical, Manaus Brazil (South America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Papua New Guinea Institute of Medical Research PapuaNew Guinea (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Walter and Eliza Hall Institute Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
7th International Conference on Plasmodium vivax Research (ICPvR) Talk given at a conference Lessons learnt through ultra-sensitive detection of asexual and sexual parasites in population-based studies 26.06.2019 Paris, France Siqueira Andre Machado; Felger Ingrid;
67th ASTMH Annual meeting 2018 (American Society of Tropical Medicine and Hygiene) Talk given at a conference How relevant is ultra-sensitive malaria diagnostics for malaria elimination? 28.10.2018 New Orleans, United States of America Siqueira Andre Machado; Hofmann Natalie; Felger Ingrid;
XV Reunião Nacional de Pes-quisa em Malaria (Annual Brazilian Malaria Conference) Talk given at a conference How to improve surveillance in low-transmission context? Como melhorar a vigilância em contexto de baixa transmissão? 03.09.2018 Recife, Brazil Felger Ingrid; Siqueira Andre Machado;
14th International Congress of Parasitology (ICOPA) Talk given at a conference Innovative molecular diagnostics for deeper understanding of malaria epidemiology and public health applications 19.08.2018 Daegu, Korean Republic (South Korea) Hofmann Natalie; Felger Ingrid;
The 66th Annual meeting 2017 of the American Society of Tropical Medicine and Hygiene Poster Maximized diagnostic sensitivity reveals unexpected reservoir for malaria transmission 05.11.2017 Baltimore, United States of America Felger Ingrid; Hofmann Natalie;
EMBO at Basel Life Poster Maximized diagnostic sensitivity reveals unexpected reservoir of malaria infections 10.09.2017 Basel, Switzerland Felger Ingrid; Hofmann Natalie;
Joint annual meeting 2017 of the Swiss Societies for Microbiology SSM/Infectious Diseases SSI/Hospital Hygiene SSHH/Tropical Medicine and Parasitology SSTMP/Tropical and Travel Medicine SSTTM Poster Uncovering the extent of sub-microscopic malaria infections using ultra-sensitive diagnostics 30.08.2017 Basel, Switzerland Felger Ingrid; Hofmann Natalie;
Joint annual meeting 2017 of the Swiss Societies for Microbiology SSM/Infectious Diseases SSI/Hospital Hygiene SSHH/Tropical Medicine and Parasitology SSTMP/Tropical and Travel Medicine SSTTM Poster Evaluation of Loop-mediated isothermal amplification (LAMP) for malaria diagnosis at the Point-of-Care 30.08.2017 Basel, Switzerland Felger Ingrid;
6th International Conference on Plasmodium vivax Research Talk given at a conference Limitations of nucleic acid amplification tests for diagnosis of P. vivax in community surveys and possible solutions 14.06.2017 Manaos, Brazil Felger Ingrid;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved


Communication with the public

Communication Title Media Place Year

Associated projects

Number Title Start Funding scheme
134889 Molecular tools for monitoring the impact of intensified malaria control on malaria epidemiology 01.04.2011 Project funding (Div. I-III)
159580 Epidemiology of ultra-low density malaria infections and their relevance for control and elimination 01.05.2015 Project funding (Div. I-III)

Abstract

The malaria parasite Plasmodium vivax remains a major public health problem in Brazil despite many efforts towards its control and elimination. One of the outstanding problems currently is to provide precise, robust and reliable tools for parasite diagnostics in rural and resource limited settings. While cases of high parasite density can be detected by microscopy and rapid diagnostics tests, many asymptomatic infections often escape detection by the tests currently available. These sub-patent infections are increasingly acknowledged as a previously neglected reservoir for onwards transmission. In parallel, with reduced transmission intensity, the proportion of individuals seeking healthcare for acute febrile illness not caused by malaria will increase. This is not being addressed adequately in the rural Amazon region, where health systems are precarious and the only health diagnostic tool provided at most health posts is for malaria infection. Previous research performed in the region have already pointed to the great diversity of infectious agents causing acute fever, from arbovirus to bacteria, at the same time that studies have shown the usefulness of clinical algorithms for the improvement of management of febrile cases.Addressing these two major issues is of great importance for the enhancement of public health actions and healthcare provided in the Amazon region. Both implications of declining malaria transmission deserve to be further investigated.Aims: Two lines of research will address present shortfalls in the clinical and laboratory-based diagnosis of malaria. The proposal aims to:(i) investigate the aetiology of acute febrile illness (AFS) amongst children seeking for healthcare at peri-urban and rural health centres in the Amazon region with the focus of generating clinical and laboratorial algorithms for case management and referral to secondary and tertiary centres. (ii) gain knowledge on the prevalence of very low density asymptomatic malaria infections that are below the detection limit of standard diagnosis in the field (microscopy, rapid diagnostic tests) and investigate the relevance of low density infections for onward transmission. Methods (i) Previous research performed at the Swiss TPH and other groups on the aetiology of fever in malaria-endemic regions in Africa and Asia will guide the development of a research protocol to characterize the aetiology of AFS in the Amazon region.(ii) Ultra-sensitive molecular methods will be applied for the diagnosis of P. falciparum and P. vivax. Archived samples from a cross sectional survey in which the Brazilian PI participated in the Amazonas region as well as currently collected samples from response surveillance (indicator cases and individual from the same household and neighbouring houses up to 2.5 km distance) will be analysed by highly sensitive quantitative PCR and reverse transcription PCR. (iii) Membrane and direct blood feeding assays performed with blood samples from sub-microscopic but qPCR-positive household contacts will be conducted in Manaus using Anopheles aquasalis colonies at the laboratory of collaborator M. Lacerda, with the aim to assess the infectivity of low density infections and their potential for transmission. Expected outcomes-A description of the fever-related syndromes and associated causes amongst patients seeking health care in the Amazon. As malaria transmission intensity decreases, a higher proportion of febrile cases not caused by Plasmodium sp. has to be expected. Some of these fevers are potentially severe, e.g. arbovirus infections such as dengue or bacterial diseases causing sepsis. By describing its epidemiology, the clinical aspects and the referral behaviour, we will be able to provide health authorities with valuable information that can assist on the design of better health care strategies to alleviate the suffering of these populations.-The development of recommendations for clinical management and referral to secondary and tertiary hospital centres to be applied in rural and peri-urban areas of the Amazon region. -A strategy to precisely and reliably estimate P. falciparum and P. vivax prevalence in index communities to inform or monitor malaria control programmes. This measure includes for the first time also very low density infections that remain undetected not only by the routinely used methods, microscopic and rapid diagnostic tests, but also by standard molecular detection. Such enhanced diagnostic sensitivity provides essential knowledge for the design of transmission reducing interventions.-Knowledge about infectivity of low density infections. A precise description of the human infective reservoir for onwards transmission is urgently needed to guide malaria control strategies. -A strategy for quality assurance in malaria diagnosis. Molecular diagnostics facilities in FIUCRUZ Rio and Manaus will quality control a subset of diagnostic tests performed during this study. The routine standard tests (Microscopy, Rapid Diagnostic Test, basic PCR) will be compared to quantitative molecular detection and highly sensitive molecular assays. Based on this pilot project the feasibility for a wider dissemination of Quality Assurance strategies will be explored.
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