PANIC PAthogen’s NIChe: a new approach for infectious diseases control
Duration Post- doc : 2016-2017
FUNDING : ANR
ABSTRACT : During the last century, WHO have led public health interventions that resulted in spectacular achievements such as the worldwide eradication of smallpox and the elimination of malaria from the Western world. However, besides major successes achieved in control of infectious diseases, most elimination/control programs remain frustrating in many tropical countries where specific biological and socio-economical features have prevented implementation of disease control over broad spatial and temporal scales. Emblematic examples include malaria, dengue, yellow fever, measles and HIV. There is consequently an urgent need to develop affordable and sustainable disease control strategies that can target the core of infectious disease transmission in highly endemic areas. Although on the one hand most pathogens are resistant to elimination, on the other hand, paradoxically, human activities are major drivers of the current high rate of extinction among higher organisms through alteration of their ecology and evolution, i.e., their « niche ». During the last decades, the accumulation of ecological and evolutionary studies focused on infectious diseases has shown that the niche of a pathogen holds more dimensions than just the immune system targeted by vaccination and treatment. Indeed, it comprises various intra- and inter- host levels at very different spatial and temporal scales. This project aims to shift from disease control to reverse conservation biology of pathogens in order to devise new public health strategies. Our objective is a qualitative understanding of the “niche” of two different pathogens at a fine spatial scale, Plasmodium falciparum in Bobo- Dioulasso (Burkina-Faso) and dengue virus in Kâmpóng Cham (Cambodia), through a transdisciplinary approach mixing ecology of infectious diseases, public health and health economics to carefully tailor mathematical models able to demonstrate how public health strategies could be improved for these diseases control in these areas and potentially drive the pathogens to local extinction. Such public health tools could be thus extended to other areas of interest and other
Figure : Spatial and temporal opportunities for pathogen control. From Roche et al (in revision)
PROJECT MALARIA IN BOBO-DIOULASSO
Malaria in Bobo-Dioulasso (Burkina-Faso). Malaria is a vector-borne disease caused by Plasmodium parasites and transmitted by female Anopheles mosquitoes. Transmission of the disease is consequently largely impacted by the ecology of the mosquito vector populations (e.g. lifespan, hostbiting preference, etc…). According to the World Malaria Report 2012, there were 219 million cases of malaria worldwide and an estimated 660 000 deaths in 2009. In terms of public health measures, the World Health Organization (WHO) launched a campaign for global malaria eradication after the Second World War. Despite elimination in many developed countries, Plasmodium falciparum is still endemic in developing countries where transmission is mitigated through vector control. Prophylactic
treatments also exist, but are rarely used by local populations. Bobo-Dioulasso is located in a high-endemicity area with a seasonal malaria transmission and several vector species with contrasting biology incriminated. By comparing old  and more recentdata , an increase of the entomological inoculation rate (EIR) can be observed in Bobo- Dioulasso. This could represent a change in the malaria transmission related to the climatic evolution and resilience activities: dwellers develop market gardening all year long as the city is crossed by permanent river (Houet river) to improve their socio-economic conditions. That offers numerous and permanent productive breeding sites favorable to culicids. Malaria diagnostic is increasingly realized through the use of Rapid Diagnostic Tests (RDTs) that target HRP2, aldolase and LDH proteins of P. falciparum. Once infection and the malaria attack are confirmed, patients are treated with Artemisinin derivatives (ACTs) used in combination with other molecules. Few data are available about chloroquine/ACT resistance in Bobo-Dioulasso. Nevertheless recent monitoring of P. falciparum sensitivity to artemisinin derivatives and its partner drugs reported that these treatments remained globally efficacious in Bobo-Dioulasso except for one first line drug,
lumefanthrine. Despite the other drugs remain efficient, a high decrease of efficacy was observed within the chloroquine (CQ) resistant isolates compared to the CQ-sensitive one. But genotypes were not characterized nor the polymorphism which should occur within these strains. Here, we aim to complete these preliminary results by genotyping the main resistant mutations observed in Plasmodium isolates from Bobo-Dioulasso (Tinto et al, unpublished). Vector control against Anopheles mosquitoes is chiefly done through the use of Long Lasting Impregnated Nets (LLINs, impregnated with pyrethroid insecticides) and Indoor Residual Spraying (IRS) using pyrethroids, carbamates or organophosphorous insecticides (and DDT under some restriction) to control the adult mosquito population.
Objectives: The overall aim of this Task is to provide updated data on the geographic and temporal dynamics of malaria transmission in the city of Bobo-Dioulasso, Burkina Faso. The project will build upon data recently collected within the frame of the SANTINELLES project and extend sampling area in order to provide the most extensive and up-to-date dataset on malaria vector bionomics, transmission dynamics and pathogen circulation in Bobo-Dioulasso that will further contribute biological material for investigation
conducted under Tasks 3 and 4 as well as be used for Task 6.
Sub task 1: Entomological surveys. This task will rely on the project SANTINELLES (ANR; 2012-2015, PI: Gérard Salem, IRD) that aims to study major health determinants in African populations. Mosquitoes will be collected in sites not covered by the SANTINELLES project, especially in the districts surrounding river Houet (Dioulassoba, Koko and Kodeni), where water can be found all year round. Host-seeking female mosquitoes will be collected through longitudinal human landing catches during two consecutive days per month for two years in the three districts. Collections will be conducted for 48 hours, in order to
document the full array of mosquito biting activity. Mosquitoes will be collected both indoors and outdoors, according to routine protocols in use at IRSS . Mosquitoes will also be collected at rest within selected human dwellings in the morning, after insecticide spraying. Specimens will be identified to species using morphological keys and molecular protocols. Detection of Plasmodium parasites within the vectors will be done by qPCR on whole mosquitoes DNA extracts . In each site, we will assess vector species omposition to incriminate epidemiologically important mosquito species/populations and quantify
their relative contribution to local malaria transmission. In the meantime, we will also document adult females’ behavior (i.e., preferred feeding and resting habits, feeding time, etc.). The dynamics of the mosquito populations will also be monitored at the larval stage, though the follow-up of some breeding sites phenology over one year. Mosquito immature stages (i.e. larvae and pupa) will be collected and identified to species. Surveillance will be increased during the dry season (November-May) in order to identify and characterize mosquitoes’ dry-season refugia within the city. All data will be geo-localized.
Sub task 2: Vector resistance to insecticides. The susceptibility of the major mosquito species/populations identified above will be assessed following WHO-recommended procedures . Mosquitoes will be collected as larvae in the different districts of Bobo-Dioulasso. They will be reared to adults in the IRSS facilities and tested against the main classes of insecticides used in public health including pyrethroids, carbamates and organophasphates . We will also explore susceptibility to IGRs (insect growth regulator) using similar protocols because these molecules have shown great promises for mosquito control in the context of emerging insecticide resistance. Bio-assays results will provide a phenotypic quantification of the resistance ratio of the different mosquito populations sampled within the city of Bobo-
Dioulasso, therefore complementing data already available from more rural neighboring areas .
Sub task 3: Parasitological surveys. A wealth of parasitological data is already available through the running SANTINELLES project and the recently successfully completed TransMalariaBlock project (EUFP7, 2008-2012, PI: Dr Georges K Christophides), both hosted by IRD/MIVEGEC and IRSS. We will conduct additional sampling for Plasmodium detection in the human population of Bobo-Dioulasso through active screening in the district population using microscopy and rapid diagnostic test (RDT). The sampling size is expected to cover at least 300 persons per district, including children less than 15 years old, pregnant women and adults. Blood samples will be collected on filter paper for parasitological investigations.