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Murine models for Trypanosoma brucei gambiense disease progression; from silent to chronic infections and early brain tropism
No full textBACKGROUND: Human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense remains highly prevalent in west and central Africa and is lethal if left untreated. The major problem is that the disease often evolves toward chronic or asymptomatic forms with low and fluctuating parasitaemia producing apparently aparasitaemic serological suspects who remain untreated because of the toxicity of the chemotherapy. Whether the different types of infections are due to host or parasite factors has been difficult to address, since T. b. gambiense isolated from patients is often not infectious in rodents thus limiting the variety of isolates. METHODOLOGY/PRINCIPAL FINDINGS: T. b. gambiense parasites were outgrown directly from the cerebrospinal fluid of infected patients by in vitro culture and analyzed for their molecular polymorphisms. Experimental murine infections showed that these isolates could be clustered into three groups with different characteristics regarding their in vivo infection properties, immune response and capacity for brain invasion. The first isolate induced a classical chronic infection with a fluctuating blood parasitaemia, an invasion of the central nervous system (CNS), a trypanosome specific-antibody response and death of the animals within 6-8 months. The second group induced a sub-chronic infection resulting in a single wave of parasitaemia after infection, followed by a low parasitaemia with no parasites detected by microscope observations of blood but detected by PCR, and the presence of a specific antibody response. The third isolate induced a silent infection characterised by the absence of microscopically detectable parasites throughout, but infection was detectable by PCR during the whole course of infection. Additionally, specific antibodies were barely detectable when mice were infected with a low number of this group of parasites. In both sub-chronic and chronic infections, most of the mice survived more than one year without major clinical symptoms despite an early dissemination and growth of the parasites in different organs including the CNS, as demonstrated by bioluminescent imaging. CONCLUSIONS/SIGNIFICANCE: Whereas trypanosome characterisation assigned all these isolates to the homogeneous Group I of T. b. gambiense, they clearly induce very different infections in mice thus mimicking the broad clinical diversity observed in HAT due to T. b. gambiense. Therefore, these murine models will be very useful for the understanding of different aspects of the physiopathology of HAT and for the development of new diagnostic tools and drugs
Bidirectional introgressive hybridization between a cattle and human schistosome species
No full textSchistosomiasis is a disease of great medical and veterinary importance in tropical and subtropical regions, caused by parasitic flatworms of the genus Schistosoma (subclass Digenea). Following major water development schemes in the 1980s, schistosomiasis has become an important parasitic disease of children living in the Senegal River Basin (SRB). During molecular parasitological surveys, nuclear and mitochondrial markers revealed unexpected natural interactions between a bovine and human Schistosoma species: S. bovis and S. haematobium, respectively. Hybrid schistosomes recovered from the urine and faeces of children and the intermediate snail hosts of both parental species, Bulinus truncatus and B. globosus, presented a nuclear ITS rRNA sequence identical to S. haematobium, while the partial mitochondrial cox1 sequence was identified as S. bovis. Molecular data suggest that the hybrids are not 1st generation and are a result of parental and/or hybrid backcrosses, indicating a stable hybrid zone. Larval stages with the reverse genetic profile were also found and are suggested to be F1 progeny. The data provide indisputable evidence for the occurrence of bidirectional introgressive hybridization between a bovine and a human Schistosoma species. Hybrid species have been found infecting B. truncatus, a snail species that is now very abundant throughout the SRB. The recent increase in urinary schistosomiasis in the villages along the SRB could therefore be a direct effect of the increased transmission through B. truncatus. Hybridization between schistosomes under laboratory conditions has been shown to result in heterosis (higher fecundity, faster maturation time, wider intermediate host spectrum), having important implications on disease prevalence, pathology and treatment. If this new hybrid exhibits the same hybrid vigour, it could develop into an emerging pathogen, necessitating further control strategies in zones where both parental species overlap
Clinical and molecular evicence for a case of Buruli Ulcer (Mycobacterium ulcerans infection) in Kenya
No full textMycobacterium ulcerans infection is an emerging disease that causes indolent, necrotizing skin lesions known as Buruli ulcer (BU) and occasional contiguous or metastatic bone lesions. Buruli ulcer is named after Buruli County in Uganda (east Africa), where an epidemic occurred in the 1960s. Today, BU is most common in central and west Africa. We describe clinical and molecular evidence for a case of BU in Kenya
Emotional support and gender in people living with HIV: effects on psychological well-being
No full textCurrent research indicates that emotional support is strongly associated with physical and psychological adjustment in persons living with HIV/AIDS. While gender-differences in health and health behaviors of HIV positive patients are well studied, less is known about how men and women living with HIV/AIDS may differentially perceive and integrate support into their lives, and how it subsequently affects their psychological well-being. This cross-sectional study examines how emotional support received from partners and family/friends and gender explains psychological well-being (i.e., stress, depression, anxiety) in a sample of 409 partnered European HIV positive individuals. We hypothesized that gender would modify the associations between support and psychological well-being such that men would benefit more from partner support whereas women would benefit more from family/friend support. Results revealed that regardless of the source of support, men's well-being was more positively influenced by support than was women's well-being. Women's difficulties in receiving emotional support may have deleterious effects on their psychological well-being
Strongyloidiasis; the most neglected of the neglected tropical diseases?
No full textSoil-transmitted helminths of the genus Strongyloides (S. fuelleborni and the more prevalent S. stercoralis) are currently believed to infect an estimated 30-100 million people worldwide. The health consequences of S. stercoralis infections range from asymptomatic light infections to chronic symptomatic strongyloidiasis. Uncontrolled multiplication of the parasite (hyperinfection) and potentially life-threatening dissemination of larvae to all internal organs is found among individuals with compromised immune system functions. This paper provides an overview of the current state of the art in relation to diagnostic methods for detecting the infection, the morbidity caused by the infection and the recommended treatment. It further discusses some of the reasons why this infection is so neglected and the consequence of this for the estimated global prevalence. The paper finally points to the gaps in our knowledge and future research needs related to this infection. As Strongyloides infections have the potential to develop into severe disease in certain population subgroups, untreated infections could cause serious problems in the community. Therefore, we need to carefully investigate this parasite in order to develop and implement effective control programmes
The invariant surface glycoprotein ISG75: a target for vaccination and diagnosis of trypanosomiasis
No full textParticipación y empoderamiento en la atención primaria en salud: desde Alma Ata hasta la era de la globalización
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The availability of drugs for rich and poor people in developing countries [reflection and reaction]
No full textSelective antileishmania activity of 13,28-Epoxy-oleanane and related triterpene saponins from the plant families Myrsinaceae, Primulaceae, Aceraceae and Icacinaceae
No full textMaesa saponins with the 13,28-epoxy-oleanane triterpene core skeleton were described recently to possess strong and selective in vitro and in vivo antileishmania activity. In the absence of direct chemical derivatization possibilities, a structure-based literature search was carried out to explore a structure-activity relationship. Crude alcohol extracts from several plant species of Myrsinaceae, Primulaceae, Aceraceae and Icacinaceae were evaluated for in vitro activity against Leishmania infantum intracellular amastigotes and cytotoxicity on MRC-5(SV2) cells, while the saponin content was evaluated qualitatively by TLC. A clear correlation was found between the presence of close analogue 13,28-epoxy-oleanane triterpene saponins and potent and selective antileishmania activity. This was most striking in Maesa species, except for M. macrosepala. Interesting activities were also found in extracts that did not exactly match the TLC characteristics of the Maesa saponin references, as was the case for Ardisia angusta, A. amherstiana, A. caudata, A. gigantifolia, A. roseiflora, Myrsine affinis, Acer brevipes and A. laurinum var. petelotii. This study indicates that the 13,28-epoxy-oleanane triterpene moiety is essential for selective antileishmania potential and that several other plant species could still be explored for antileishmania drug discovery