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Microbiology & Humanities Sciences

Team 11: Jean-François Trape, DREC IRD

 

Team composition

 

  1. Jean-François TRAPE, DR CE
  2. Jean-François MOLEZ, CR1 IRD
  3. Oleg MEDIANNIKOV, CR2
  4. Cheikh SOKHNA, IR2

 

Details of implementation

 

The program is based on six platforms of medical and demographic monitoring inSenegaland a regional network inWest Africa. Four of the platforms of medical and demographic monitoring are more particularly adapted to the studies on broad scale and measurements of impact on mortality: - The Demographic System of Follow-up (SSD) of Bambey/Mbour/Fatick, operational since September 2008, includes 602.000 people divided into 756 villages. It includes 54 stations of health. Financed within the framework of a convention with the Bill and Melinda Gates Foundation, the University of Dakar and the London School of Hygiene and Tropical Medicine (“Evaluation at a large scale of an intermittent preventive medication against malaria”), it currently constitutes the greatest system of demographic and medical monitoring in Africa. - The platforms of Niakhar (35 000 inhabitants) in theSahelzone, Mlomp (8 000 inhabitants) in Guinean zone and Bandafassi (10 000 inhabitants) in Soudanian zone supplement the monitoring. These platforms belong to the international network INDEPHT. That of Niakhar, created and managed by the IRD since 1962, constitutes the oldest demographic monitoring system in Africa. The management of the platforms of Mlomp and Bandafassi associates the IRD and the INED. Since 2008, the management of the databases, the organization of the demographic follow-up and that of the causes of death in Niakhar, Mlomp and Bandafassi are entirely ensured by the URMITE. It is the follow-up of the malaria in the populations of Niakhar, Mlomp and Bandafassi which had enabled us to reveal the catastrophic impact of the emergence of resistance to chloroquine on the mortality of malaria in Africa. This work was determining in the decisions to abandon chloroquine and to finance in 2004 by the Global Fund the use of combinations containing artemisinim everywhere inAfrica. The platforms of Dielmo and Ndiop are more particularly adapted to the studies on the morbidity and the comprehension of the implicated biological mechanisms. They include 700 people who are the object of a clinical and epidemiologic monitoring daily. Since the beginning of the project in 1990, their management associates the IRD and the Pasteur Institute of Dakar. A convention was signed in 2004 with the Ministry for the Health of Senegal and is regularly renewed since. Conceived for the study of malaria, the protocol continued since 20 years has shown that it was also adapted to the study of other pathologies emergent or ignored like borrelioses, rickettsioses, Q Fever and Whipple’s disease. Set up in 2003 for our research on borrelioses, an African Regional Network supplements the monitoring. The work coordinated by the Dakar team of URMITE currently associates teams of 15 countries (Senegal, Mauritania, Mali, Guinea, Liberia, Burkina-Faso, Niger, Chad, Cameroun, Togo, Benin, Ivory Coast, Morocco, Algeria, Tunisia). Since 2009, researches on the borrelioses are associated on investigations on rickettsioses, bartonelloses and Q Fever.

 

Research studies in progress or planned:

 

Malaria

 

Evaluation of the impact of the administration of seasonal intermittent preventive treatment to the children of less than 10 years delivered through health services with community participation in Sahel

The intermittent preventive treatment (IPT) is a type of preventive treatment that has already showed its effectiveness in the fight against malaria. The previous studies conducted in 2002-2004, we showed that it was possible to reduce the malaria morbidity by 86% in Sahel zone by administrating to the children of the combination the antimalarial agents three times with an month interval during the seasonal peak of transmission (Cisse and Al, Lancet 2006). Our objective is to evaluate this strategy when it is applied to large scales under the control of the responsible medical attendant in village dispensary and via a definite number of matriarchs in each village with the administration of the drugs. The protocol of research entitled “Large scale Preventive implementation off Intermittent Treatment in Children Delivered through Health Services with Community Participation in the Sahel” with collaboration of our partners of the UCAD, London School and the Ministry for the was set up in 2008.

The project is in the course of implementation in the zones of responsibility of 54 dispensaries (stations of health), all localised in the districts of Fatick, Mbour or Bambey in Senegal. For the data-gathering in the field, 187 investigators, 18 supervisors and 2 coordinators were recruited. An important utility was set up to manage the tools for data acquisition. The workshop proceeds regularly to “return-ground” where confrontation is made with the persons in charge of the investigations to correct the errors met. The errors are documented and filed to keep traceability in the data processing. To coordinate work, a data processing specialist set up an Access database with an Visual BASIC interface. The data are then transferred on SQL Server (set up of an Intranet controlled by Windows 2008 Server, which requires an authentification with any user before entering the system). This is supervised by the data processing technician, two supervisors and 10 operators. The files are preserved and arranged by area and station of health. Finally a statistician is charged to analyze the data.

The 602.000 registered persons are divided in 49.567 households with a single identifier by household. The mothers of 208.156 children of less than 10 years received an individual chart with the name, the code and the age of their children included in the project. This chart is used for the recording of any intervention of health carried out on the children (administration of preventive medication, consultations, hospitalizations, vaccinations etc.). The proportion of children receiving a complete treatment was of 92% the 1st year and 93% the 2nd year. The number of deaths at the time of the demographic passage into 2009 was 1.870 and a number of birth was 13.635. The evaluation of the impact of the intervention on the morbidity, mortality and the prevalence of malaria at the time of the first year of the project is in the progress.

Identification, measurement and analysis of the epidemiologic determinants of the human resistance to malaria.

Project begun in 1990 in two villages, Dielmo and Ndiop. The individual background, clinical and epidemiologic data of 700 villagers are continuously surveyed daily by the specialists of Institute of the research for the development (IRD) and the Pasteur Institute of Dakar. These data describe the heterogeneity of the individual response to the infection and the disease, help to identify the innate or acquired biological and epidemiologic determinants, and to quantify and model their importance. Both the data and collected specimens are regularly analysed in order to, from one side, to develop the anti-malaria vaccine and, on the other hand, to define new therapeutic and preventive strategies. More than one hundred articles have been published during 15 years of the project. Up to date, no equal long-termed project on malaria research exists.

 

Malaria and other mortality causes: enteric infection, pneumopathies, infectious cancers

 

Evaluation of the impact of the replacement of chloroquine by association artesunate-amodiaquine for the treatment of malaria in Senegal on the rates and causes of death.

This project has begun in 2006 at the time of the installation of association artesunate-amodiaquine by the Ministry of Health for the treatment of malaria in all dispensaries of Senegal. We showed that the emergence of resistance to chloroquine had caused in the years 1990 an increase of malaria-associated mortality from 250% up to 600%. Chloroquine has been replaced by artesunate-amodiaquine combination and the impact of the new drugs on morbidity, mortality, the transmission and the chimiosensibility of malaria in  Mlomp, Dielmo, Ndiop, Niakhar and Bandafassi regions were surveyed. At the same time, other child and overall mortality were surveyed.

In our works (JF. Trape et al. Reaching Millenium Development Goal 4 – Senegal – submitted; three communications in 2009 on MIM conference) we show that morbidity, mortality and prevalence of malaria crumbled in Senegal since the introduction of the therapeutic combinations. The analysis data collected in the zone of Niakhar (Figures 1 and 2) also showed decreasing of infanto-juvenile mortality (198 per thousand into 2000,55 per thousand in 2008). This decrease was even more important than that one of the isolated mortality due to malaria (15,0 per thousand on average during the period 1995-1999, 2,2 per thousand in 2008). At the absence of any other specific treatment it suggests that the malaria plays the major role in a great number of deaths of childhood.

The analysis of mortality data also shows that cancers of probable infectious origin may also constitute an important cause of mortality in the adults of Niakhar, Mlomp and Bandafassi. 

During next four years we propose to follow up the evolution of mortality rates and death causes in each observatory and to continue to analyze their importance. In addition to the traditional infectious causes (malaria, enteric infections, pneumopathies), specific survey studies should be perform regarding to cancers of possible infectious origin.

 

Biodiversity of emergent pathogens

 

Study of the tick-borne relapsing fever in Africa

This project was initiated in 2003. The tick-borne relapsing fever is the second (after malaria) cause febrile disease in rural Senegal. Its incidence is high in all the age groups. In Dielmo village, every year from 5% to 25% of the inhabitants become infected without developing a protective immunity afterwards. Three species of Ornithodoros soft ticks are classical vectors of relapsing fever in Africa. The analysis of sequenced tick genes shows that the conventional classification should be re-examined. The same situation is in the taxonomy of Borrelia spp., new species may still be discovered. Our objective is to specify the geographical distribution of the disease, to deep the knowledge of its epidemiology and to characterize the genetic structures of pathogens and the vectors. The diagnostic tests and treatment of tick-borne relapsing fever also have to be significantly improved. Intrinsic mechanisms of natural history of the relapsing fever including the relationships to the climate and the other environmental factors are to be studied.

Beginning from 2006 we extended our research network to North Africa (Figure 3), the futher expanding to the East Africa and Middle East are proposed and planned. Currently, the studies performed in 16 African countries show that there are at least eight distinct genetic entities in the complex Ornithodoros erraticus/O. sonrai soft ticks. At least six of these possible new species are able to transmit of the relapsing fever. In Senegal, the data collected during the period of 2006-2009 confirm very high level of incidence of this disease in rural area (on average 11% annually in the overall population).

 

Other bacterial diseases

The URMITE in Marseilles developed techniques based on broad-spectrum PCR targeting the 16S rRNA sequence followed by sequencing as well as specific real-time quantitative PCR (qPCR) which make it possible simultaneously to detect a great number of bacteria (in particular Rickettsia, Coxiella, Bartonella, Anaplasma, spirochetes…) in blood specimens from patients and in ectoparasitic arthropods. We began in 2008 the systematic exploration of the fevers non linked to malaria among inhabitants from Dielmo and Ndiop. In parallel, we began the systematic collection of the ectoparasites from the inhabitants, the cattle, the pets and the wildlife, in particular mammals, reptiles and birds: (1) in the various medical and demographic platforms of monitoring in Senegal, in order to be able to connect the newly detected pathogens to the clinical, biological and epidemiologic data collected in parallel; (2) in various sites of other countries of West Africa selected on geographical and bio-ecological criteria. The first results from Dielmo and Ndiop show that 25% of the fevers non linked to malaria are due to one of the five following infectious diseases: Whipple’s disease, borrelioses, rickettsioses caused by Rickettsia felis and R. africae, Q fever. In the case of Whipple’s disease, we also observed a very high rate of carriage in the stools from children (44%) and we detected for the first time this bacterium in the blood specimens from patients during a feverish episode. These results lead us to propose for these next years the continuation of the researches in progress and the extension of the systematic exploration of the fevers by molecular biology in five areas of Senegal that represent the various eco-epidemiologic situations of the country and in five other areas of West Africa.

 

Influenza

The Dakar-team of the URMITE began in Niakhar in March2009, incollaboration with PATH, the CDC of Atlanta and the Institute Pasteur of Dakar, the evaluation among 8.000 children from 6 months to 10 years-old of a new inactivated trivalent vaccine against the influenza. The main aim of this study is to evaluate if the trivalent anti-flu vaccine (VGT), when it is used massively, can confer an elevated level of protection to the immunized people by limiting the transmission of the virus and also indirectly protect the not vaccinated population. The duration of the project is 3 years, with two distinct annual vaccination campaigns, between February and May. In July 2009, 7.839 out of the 8.000 awaited children were vaccinated by 15 teams of vaccination from the IRD (15 nurses, 15 community relays, 35 investigators) under the control of 7 teams of supervision. This project comprises the active monitoring by the IRD of the feverish episodes. In the current context of flu epidemic H1N1, this project has a very particular importance. The first cases of influenza H1N1 occurred in January 2010 but the epidemic remained weak and it stopped as of March. In addition to the influenza, whose research in laboratory will be to make by the Pasteur Institute of Dakar, it is expected that the URMITE performs inMarseillesandDakarthe systematic detection of other viral and bacterial pathogens. The passive monitoring of the influenza is carried out on the level of the three medical stations which serve the 30 villages of the area of demographic monitoring (SSD) of Niakhar.

 


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