Plant-derived recombinant F1, V, and F1-V fusion antigens of Yersinia pestis activate human cells of the innate and adaptive immune system

Plague is still endemic in different regions of the world. Current vaccines raise concern for their side effects and limited protection, highlighting the need for an efficacious and rapidly producible vaccine. F1 and V antigens of Yersinia pestis, and F1-V fusion protein produced in Nicotiana benthamiana administered to guinea pigs resulted in immunity and protection against an aerosol challenge of virulent h pestis. We examined the effects of plant-derived F1, V, and F1-V on human cells of the innate immunity. F1, V, and F1-V proteins engaged TLR2 signalling and activated IL-6 and CXCL-8 production by monocytes, without affecting the expression of TNF-alpha, IL-12, IL-10, IL-1 beta, and CXCL10. Native F1 antigen and recombinant plant-derived F1 (rF1) and rF1-V all induced similar specific T-cell responses, as shown by their recognition by T-cells from subjects who recovered from E pestis infection. Native F1 and rF1 were equally well recognized by serum antibodies of Y. pestis-primed donors, whereas serological reactivity to rF1-V hybrid was lower, and that to rV was virtually absent. In conclusion, plant-derived F1, V, and F1-V antigens are weakly reactogenic for human monocytes and elicit cell-mediated and humoral responses similar to those raised by Y pestis infection

Seroprevalence of malaria in inhabitants of the urban zone of Antananarivo, Madagascar

BACKGROUND: Antananarivo, the capital of Madagascar, is located at an altitude of over 1,200 m. The environment at this altitude is not particularly favourable to malaria transmission, but malaria nonetheless remains a major public health problem. The aim of this study was to evaluate exposure to malaria in the urban population of Antananarivo, by measuring the specific seroprevalence of Plasmodium falciparum. METHODS: Serological studies specific for P. falciparum were carried out with an indirect fluorescent antibody test (IFAT). In a representative population of Antananarivo, 1,059 healthy volunteers were interviewed and serum samples were taken. RESULTS: The seroprevalence of IgG+IgA+IgM was 56.1% and that of IgM was 5.9%. The major risk factor associated with a positive IgG+IgA+IgM IFAT was travel outside Antananarivo, whether in the central highlands or on the coast. The abundance of rice fields in certain urban districts was not associated with a higher seroprevalence. CONCLUSION: Malaria transmission levels are low in Antananarivo, but seroprevalence is high. Humans come into contact with the parasite primarily when travelling outside the city. Further studies are required to identify indigenous risk factors and intra-city variations more clearly

Hepatitis C Virus Infection May Lead to Slower Emergence of P. falciparum in Blood

International audienceBACKGROUND: Areas endemic for Plasmodium falciparum, hepatitis B virus (HBV) and hepatitis C virus (HCV) overlap in many parts of sub-Saharan Africa. HBV and HCV infections develop in the liver, where takes place the first development stage of P. falciparum before its further spread in blood. The complex mechanisms involved in the development of hepatitis may potentially influence the development of the liver stage of malaria parasites. Understanding the molecular mechanisms of these interactions could provide new pathophysiological insights for treatment strategies in Malaria. METHODOLOGY: We studied a cohort of 319 individuals living in a village where the three infections are prevalent. The patients were initially given a curative antimalarial treatment and were then monitored for the emergence of asexual P. falciparum forms in blood, fortnightly for one year, by microscopy and polymerase chain reaction. PRINCIPAL FINDINGS: At inclusion, 65 (20.4%) subjects had detectable malaria parasites in blood, 36 (11.3%) were HBV chronic carriers, and 61 (18.9%) were HCV chronic carriers. During follow-up, asexual P. falciparum forms were detected in the blood of 203 patients. The median time to P. falciparum emergence in blood was respectively 140 and 120 days in HBV- and HBV+ individuals, and 135 and 224 days in HCV- and HCV+ individuals. HCV carriage was associated with delayed emergence of asexual P. falciparum forms in blood relative to patients without HCV infection. CONCLUSIONS: This pilot study represents first tentative evidence of a potential epidemiological interaction between HBV, HCV and P. falciparum infections. Age is an important confounding factor in this setting however multivariate analysis points to an interaction between P. falciparum and HCV at the hepatic level with a slower emergence of P. falciparum in HCV chronic carriers. More in depth analysis are necessary to unravel the basis of hepatic interactions between these two pathogens, which could help in identifying new therapeutic approaches against malaria

Space-time clustering of childhood malaria at the household level: a dynamic cohort in a Mali village

BACKGROUND: Spatial and temporal heterogeneities in the risk of malaria have led the WHO to recommend fine-scale stratification of the epidemiological situation, making it possible to set up actions and clinical or basic researches targeting high-risk zones. Before initiating such studies it is necessary to define local patterns of malaria transmission and infection (in time and in space) in order to facilitate selection of the appropriate study population and the intervention allocation. The aim of this study was to identify, spatially and temporally, high-risk zones of malaria, at the household level (resolution of 1 to 3 m). METHODS: This study took place in a Malian village with hyperendemic seasonal transmission as part of Mali-Tulane Tropical Medicine Research Center (NIAID/NIH). The study design was a dynamic cohort (22 surveys, from June 1996 to June 2001) on about 1300 children (<12 years) distributed between 173 households localized by GPS. We used the computed parasitological data to analyzed levels of Plasmodium falciparum, P. malariae and P. ovale infection and P. falciparum gametocyte carriage by means of time series and Kulldorff's scan statistic for space-time cluster detection. RESULTS: The time series analysis determined that malaria parasitemia (primarily P. falciparum) was persistently present throughout the population with the expected seasonal variability pattern and a downward temporal trend. We identified six high-risk clusters of P. falciparum infection, some of which persisted despite an overall tendency towards a decrease in risk. The first high-risk cluster of P. falciparum infection (rate ratio = 14.161) was detected from September 1996 to October 1996, in the north of the village. CONCLUSION: This study showed that, although infection proportions tended to decrease, high-risk zones persisted in the village particularly near temporal backwaters. Analysis of this heterogeneity at the household scale by GIS methods lead to target preventive actions more accurately on the high-risk zones identified. This mapping of malaria risk makes it possible to orient control programs, treating the high-risk zones identified as a matter of priority, and to improve the planning of intervention trials or research studies on malaria

Atelier paludisme : an international malaria training course held in Madagascar - art. no. 80

The Atelier Paludisme (Malaria Workshop) is an international training course organized by the Institut Pasteur de Madagascar, which has been held annually for the past five years. The course was designed for both young and experienced researchers, as well as for healthcare professionals, mostly from malaria-endemic countries. Its objective is to provide participants with a broad knowledge of all features of malaria, to improve their skills in project management, to break geographical isolation by using the Internet as a source of documentary information. This six-week course makes use of concepts of andragogy and problem-based learning, i.e. a relationship between participants and tutors, which promotes a process of exchange rather than the simple transmission of knowledge, where participants have to search actively for information. This approach to training, combined with the wide background and experience of those involved, creates positive dynamics and enables participants to acquire new skills, develop their critical and analytical abilities. This paper describes the course and the lessons learned from its evaluation

Anthropophilic mosquitoes and malaria transmission in the eastern foothills of the central highlands of Madagascar

Malaria remains a major public health problem in Madagascar as it is the first cause of morbidity in health care facilities Its transmission remains poorly documented An entomological study was carried out over 1 year (October 2003-September 2004) in Saharevo a village located at an altitude of 900 m on the eastern edge of the Malagasy central highlands Mosquitoes were sampled weekly upon landing on human volunteers and in various resting-places Out of 5515 mosquitoes collected on humans 3219 (58 4%) were anophelines Eleven anopheline species were represented among which Anopheles funestus Anopheles gambiae Anopheles arabiensis and Anopheles mascarensis Out of 677 mosquitoes collected in bedrooms by pyrethrum spray catches and in Muirhead-Thomson pits 656 (96 9%) were anopheline belonging to these four latter species The proportion of mosquitoes that fed on human varied according to the resting-places and the mosquito species 86% of An funestus resting in bedrooms fed on humans whereas only 16% of An funestus and 0% of An mascarensis resting in pits fed on humans The proportion of anopheline mosquitoes infected with human Plasmodium was measured by circumsporozoite protein-ELISA 10/633 An funestus (1 58%) 1/211 An gambiae s l (048%) and 2/268 An mascarensis (075%) The annual entomological inoculation rate (number of bites of infected anophelines per adult) was estimated at 2 78 The transmission was mainly due to An funestus and only observed in the second half of the rainy season from February to May These results are discussed in the context of the current malaria vector control policy in Madagascar (C) 2010 Elsevier B V All rights reserve