Converging Human and Malaria Vector Diagnostics with Data Management towards an Integrated Holistic One Health Approach

Abstract

Monitoring malaria prevalence in humans, as well as vector populations, for the presence of Plasmodium, is an integral component of effective malaria control, and eventually, elimination. In the field of human diagnostics, a major challenge is the ability to define, precisely, the causative agent of fever, thereby differentiating among several candidate (also non-malaria) febrile diseases. This requires genetic-based pathogen identification and multiplexed analysis, which, in combination, are hardly provided by the current gold standard diagnostic tools. In the field of vectors, an essential component of control programs is the detection of Plasmodium species within its mosquito vectors, particularly in the salivary glands, where the infective sporozoites reside. In addition, the identification of species composition and insecticide resistance alleles within vector populations is a primary task in routine monitoring activities, aiming to support control efforts. In this context, the use of converging diagnostics is highly desirable for providing comprehensive information, including differential fever diagnosis in humans, and mosquito species composition, infection status, and resistance to insecticides of vectors. Nevertheless, the two fields of human diagnostics and vector control are rarely combined, both at the diagnostic and at the data management end, resulting in fragmented data and mis- or non-communication between various stakeholders. To this direction, molecular technologies, their integration in automated platforms, and the co-assessment of data from multiple diagnostic sources through information and communication technologies are possible pathways towards a unified human vector approach.

Detection and Monitoring of Insecticide Resistance Mutations in Anopheles gambiae: Individual vs. Pooled Specimens

“…A novel method with no requirement for dissection and post-PCR processing was recently developed for the detection of Plasmodium falciparum infective mosquitoes [ 23 ]; with high sensitivity, it can detect infective-stage specific parasite transcripts in samples containing a mix of infective with non-infected mosquitoes at a 1:100 ratio. The feasibility of analysing mosquito pools, maintained in RNA later (Invitrogen, ) solutions, sets the basis for the development of more holistic and automated approaches to vector population monitoring [ 24 ], as the same biological material e.g. a mosquito pool, can be used both for DNA-markers, such as target site mutations and species identification, as well as for RNA-markers (transcript levels of major detoxification genes, infective-stage plasmodium transcripts).…”

VectorDisk: A Microfluidic Platform Integrating Diagnostic Markers for Evidence-Based Mosquito Control

“…A comprehensive review of candidate analytical methods and platforms has been published by Vontas et al [16]. The fact that the LabDisk platform has been shown to successfully detect tropical infections on human samples (malaria, dengue, chikungunya) [26,54,55], in combination with the current demonstration of compatibility with analysis of multiple vector-related assays, paves the way for a One Health approach of combined human/vector diagnostics [22]. Overall, the NA Study was performed by using the same disk design and fluidic operations, as well as the same lyopellet as the Vector Study, by only exchanging the primer/probes in the reaction chambers, and by slightly modifying the PCR protocol.…”

“…Three levels of information are crucial for vector surveillance and control: (i) mosquito species identity is essential for differentiating vector from non-vector species (e.g., out of 476 Anopheles species, only 70 are capable of transmitting malaria) [17]; (ii) pathogen detection in the case of malaria vectors, the determination of the Plasmodium species (P. falciparum, P. vivax, P. ovale, or P. malariae), whether the parasites are present in their infective stage [18,19], and-in the case of vectors of viral diseases-the determination of arbovirus species (e.g., West Nile virus, dengue virus); and (iii) the potential involvement of an insecticide resistance mechanism, including target site mutations (DNA) and expression levels of metabolic detoxification genes (RNA) [20,21]. Despite various methods that have been developed in the past to address one or more of these characteristics [22], there is no universal tool to collect all necessary information at once; the individual protocols can be very tedious and can involve manual steps such as the dissection of salivary glands [23], or require the analytical skills to perform microscopic identification through morphological examination.…”

Fully automated point-of-care differential diagnosis of acute febrile illness

“…It was shown in this work that in total 14 FeverDisks were true positive for malaria at both test sites, and the P spp assays were always concordant with the Pf assay. Thus, the FeverDisk platform could support comprehensive data acquisition for vector-borne pathogens ( Plasmodium , DENV, CHIKV, ZIKV) [ 57 , 58 ].…”