Prospective surveillance study to detect antimalarial drug resistance, gene deletions of diagnostic relevance and genetic diversity of Plasmodium falciparum in Mozambique: protocol

Abstract

Introduction: Genomic data constitute a valuable adjunct to routine surveillance that can guide programmatic decisions to reduce the burden of infectious diseases. However, genomic capacities remain low in Africa. This study aims to operationalise a functional malaria molecular surveillance system in Mozambique for guiding malaria control and elimination.

Methods and analyses: This prospective surveillance study seeks to generate Plasmodium falciparum genetic data to (1) monitor molecular markers of drug resistance and deletions in rapid diagnostic test targets; (2) characterise transmission sources in low transmission settings and (3) quantify transmission levels and the effectiveness of antimalarial interventions. The study will take place across 19 districts in nine provinces (Maputo city, Maputo, Gaza, Inhambane, Niassa, Manica, Nampula, Zambézia and Sofala) which span a range of transmission strata, geographies and malaria intervention types. Dried blood spot samples and rapid diagnostic tests will be collected across the study districts in 2022 and 2023 through a combination of dense (all malaria clinical cases) and targeted (a selection of malaria clinical cases) sampling. Pregnant women attending their first antenatal care visit will also be included to assess their value for molecular surveillance. We will use a multiplex amplicon-based next-generation sequencing approach targeting informative single nucleotide polymorphisms, gene deletions and microhaplotypes. Genetic data will be incorporated into epidemiological and transmission models to identify the most informative relationship between genetic features, sources of malaria transmission and programmatic effectiveness of new malaria interventions. Strategic genomic information will be ultimately integrated into the national malaria information and surveillance system to improve the use of the genetic information for programmatic decision-making.

Ethics and dissemination: The protocol was reviewed and approved by the institutional (CISM) and national ethics committees of Mozambique (Comité Nacional de Bioética para Saúde) and Spain (Hospital Clinic of Barcelona). Project results will be presented to all stakeholders and published in open-access journals.

Trial registration number: NCT05306067.

Keywords: Epidemiology; Genetics; MOLECULAR BIOLOGY; Molecular diagnostics; PARASITOLOGY; Public health.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1

Malaria genomic use cases and National Malaria Control Programme (NMCP) decisions. The letter on the left (A–D) expresses the level of action described in the WHO Technical consultation on the role of parasite and anopheline genetics in malaria surveillance. (A) Immediate action; (B) medium-term action; (C) long-term action. Arrows in colour at the right express the research required for action in the medium-term and long-term (grey, not essential for action; green, immediate evidence; yellow, medium-term evidence). ANC, antenatal care clinics; IPT, intermittent preventive treatment; MDA, mass drug administration; rfMDA, reactive focal MDA; SMC, seasonal malaria chemoprevention.

Figure 2

Low and medium-to-high transmission study districts targeted in the protocol. ANC, antental care clinics.

Figure 3

Modelling approaches for malaria genomics. Overview of the components of a joint malaria epidemiology-genetic model, that builds on the capabilities of two models previously developed at the Institute of Disease Modelling (a malaria genetic model calibrated to a longitudinal genetic study in Senegal and a disease transmission model calibrated with the Magude data).