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Identification of peptide mimotopes of Trypanosoma brucei gambiense variant surface glycoproteins
No full textBACKGROUND: The current antibody detection tests for the diagnosis of gambiense human African trypanosomiasis (HAT) are based on native variant surface glycoproteins (VSGs) of Trypanosoma brucei (T.b.) gambiense. These native VSGs are difficult to produce, and contain non-specific epitopes that may cause cross-reactions. We aimed to identify mimotopic peptides for epitopes of T.b. gambiense VSGs that, when produced synthetically, can replace the native proteins in antibody detection tests. METHODOLOGY/PRINCIPAL FINDINGS: PhD.-12 and PhD.-C7C phage display peptide libraries were screened with mouse monoclonal antibodies against the predominant VSGs LiTat 1.3 and LiTat 1.5 of T.b. gambiense. Thirty seven different peptide sequences corresponding to a linear LiTat 1.5 VSG epitope and 17 sequences corresponding to a discontinuous LiTat 1.3 VSG epitope were identified. Seventeen of 22 synthetic peptides inhibited the binding of their homologous monoclonal to VSG LiTat 1.5 or LiTat 1.3. Binding of these monoclonal antibodies to respectively six and three synthetic mimotopic peptides of LiTat 1.5 and LiTat 1.3 was significantly inhibited by HAT sera (p<0.05). CONCLUSIONS/SIGNIFICANCE: We successfully identified peptides that mimic epitopes on the native trypanosomal VSGs LiTat 1.5 and LiTat 1.3. These mimotopes might have potential for the diagnosis of human African trypanosomiasis but require further evaluation and testing with a large panel of HAT positive and negative sera
Post-mortem examination and laboratory-based analysis for the diagnosis of bovine tuberculosis among dairy cattle in Ecuador
No full textVeterinary inspection in slaughterhouses allows for the detection of macroscopic lesions reminiscent of bovine tuberculosis, but the presence of Mycobacterium bovis must be confirmed by laboratory methods. This study aimed at comparing the performances of the standard diagnostic tools used to identify M. bovis in tissue specimens sampled from suspicious animals. During a two years period, 1390 cattle were inspected at the Machachi abattoir in the Mejia canton - Ecuador. A total of 33 animals with granulomatous lesions were detected, representing 2.33% (16/687) and 2.42% (17/703) animals examined in 2007 and 2008, respectively. Ninety-four tissue specimens were sampled and screened for the presence of mycobacteria. Acid-fast bacilli were identified in one third of the suspicious cattle (11/33) and suggestive microscopic lesions in 27.3% (9/33) of the samples examined by direct microscopy and histopathology, respectively. Culturing on Stonebrink medium and 16S-rRNA-based polymerase chain reaction (PCR) yielded 36.4% (12/33) and 27.3% (9/33) of positives, respectively. Compared to culture, other diagnostic procedures displayed a lower sensitivity, with 56.5% for PCR, and 43.5% for direct microscopy and histopathology; however, the specificity was higher (94.4% for PCR and microscopy, and 97.2% for histopathology). We conclude that reliable post-mortem laboratory testing either requires the combination of a set of available diagnostic tools or necessitates the development of improved new-generation tools with better sensitivity and specificity characteristics
High affinity nanobodies against the Trypanosome brucei VSG are potent trypanolytic agents that block endocytosis
No full textThe African trypanosome Trypanosoma brucei, which persists within the bloodstream of the mammalian host, has evolved potent mechanisms for immune evasion. Specifically, antigenic variation of the variant-specific surface glycoprotein (VSG) and a highly active endocytosis and recycling of the surface coat efficiently delay killing mediated by anti-VSG antibodies. Consequently, conventional VSG-specific intact immunoglobulins are non-trypanocidal in the absence of complement. In sharp contrast, monovalent antigen-binding fragments, including 15 kDa nanobodies (Nb) derived from camelid heavy-chain antibodies (HCAbs) recognizing variant-specific VSG epitopes, efficiently lyse trypanosomes both in vitro and in vivo. This Nb-mediated lysis is preceded by very rapid immobilisation of the parasites, massive enlargement of the flagellar pocket and major blockade of endocytosis. This is accompanied by severe metabolic perturbations reflected by reduced intracellular ATP-levels and loss of mitochondrial membrane potential, culminating in cell death. Modification of anti-VSG Nbs through site-directed mutagenesis and by reconstitution into HCAbs, combined with unveiling of trypanolytic activity from intact immunoglobulins by papain proteolysis, demonstrates that the trypanolytic activity of Nbs and Fabs requires low molecular weight, monovalency and high affinity. We propose that the generation of low molecular weight VSG-specific trypanolytic nanobodies that impede endocytosis offers a new opportunity for developing novel trypanosomiasis therapeutics. In addition, these data suggest that the antigen-binding domain of an anti-microbial antibody harbours biological functionality that is latent in the intact immunoglobulin and is revealed only upon release of the antigen-binding fragment
Risk factors of active tuberculosis in people living with HIV/AIDS in southwest Ethiopia: a case control study
No full textEstimating the number of women with female genital mutilation in Belgium
No full textObjective To estimate the number of women with female genital mutilation (FGM) living in Belgium, the number of girls at risk, and the target population of medical and social services (MSSs) concerned. Methods Data about prevalence of FGM from the most recently published Demographic and Health Surveys and Multiple Indicator Cluster Surveys were applied to females living in Belgium who migrated from countries where excision or infibulation are being practised, and to their daughters. Results Amongst the 22,840 women and girls living in Belgium who are from a country concerned, 6,260 have 'most probably already undergone a FGM' (women born in the country of origin), and 1,975 are 'at risk' (second generation born in Belgium). The target population of MSSs comprises 1,190 girls less than five years old attending well-baby clinics, 1,690 girls aged 5-19 years attending preventive school health centres, 4,905 women 20-49 years old and 450 women over 50 years of age attending reproductive health services. The population of women concerned is unequally dispersed in Belgium and reflects the distribution of migrant settlement in the different provinces. Conclusion FGM in Belgium requires a more concerted approach in terms of prevention, and medical and social care. Accurate information about the distribution of women concerned should permit better planning of competent services
Streptomycin resistance and lineage specific polymorphisms in Mycobacterium tuberculosis gidB gene
No full textMutations related to streptomycin-resistance in the rpsL and rrs genes are well known and can explain about 70% of this phenotypic resistance. Recently, the gidB gene was found to be associated with low level streptomycin-resistance in Mycobacterium tuberculosis. Mutations in gidB have been reported with high frequency, and this gene appears to be very polymorphic, with frameshift and point mutations occurring in streptomycin-susceptible and streptomycin-resistant strains. In this study, mutations in gidB appeared in 27% of streptomycin-resistant strains that contained no mutations in the rpsL or rrs genes and were associated with low-level streptomycin-resistance. However, the association of certain mutations in gidB with streptomycin-resistance needs to be further investigated as we also found mutations in gidB in streptomycin-susceptible strains. This occurred only when the strain was resistant to rifampicin and isoniazid. Two specific mutations appear very frequently in this and other studies in streptomycin-susceptible and resistant strains, these mutations were not considered as related to streptomycin-resistance, but as a polymorphism. We stratified the strains according to the different phylogenetic lineages and showed that the gidB(16) polymorphism (16G allele) was exclusively present in the Latin American Mediterranean genotype, while the gidB(92) polymorphism (92C allele) was associated with the Beijing lineage in another population. In the sample studied, the two characterized single nucleotide polymorphisms could distinguish LAM and Beijing lineages from the other lineages
Prevention of mother-to-child transmission of HIV and the health-related Millennium Development Goals: time for a public health approach [viewpoint]
No full textVirulence in Trypanosoma congolense Savannah subgroup. A comparison between strains and transmission cycles
No full textTrypanosoma congolense strains have been shown to differ in their virulence both between subgroups and within the Savannah subgroup between strains. This review revisits these findings and complements them with information on the virulence of T. congolense Savannah subgroup strains isolated from cattle (domestic transmission cycle) in different geographical areas and of strains isolated in protected areas where trypanotolerant wildlife species are the reservoir of the trypanosomes (sylvatic transmission cycle). The virulence of a total of 62 T. congolense Savannah subgroup strains (50 domestic and 12 sylvatic), determined using a standard protocol in mice, was compared. Virulence varied substantially between strains with, depending on the strain, the median survival time of infected mice varying from 5 to more than sixty days. The proportion of highly virulent strains (median survival time < 10 days) was significantly (P = 0.005) higher in strains from the sylvatic transmission cycle. The analysis highlights repercussions of the domestication of the trypanosomiasis transmission cycle that may have to be taken in consideration in the development of trypanosomiasis control strategies
Monitoring of the intra-dermal tuberculosis skin test performed by Belgian field practitioners
No full textThe present study aimed to monitor skin test practices as performed by veterinarian field practitioners in Belgium. For this purpose, an anonymous postal questionnaire was elaborated and dispatched to veterinarians involved in bovine tuberculosis detection. The questionnaire included items focusing on the skin test performance. International experts in the field of bovine tuberculosis were asked to fill the questionnaire and a scoring scale was built as follows: 0='ideal' answer, 1=acceptable answer, whereas 2=unacceptable answer. Furthermore, experts were asked to rank the questionnaire's items according to their possible impact on the risk of not detecting reactors. A global score was further calculated for each participant and a comparison of practices was carried out between the two regions of the country, i.e. Wallonia and Flanders. Significant differences were observed between both regions, a harmonization at the country level is thus essential. No veterinarian summed a null score, corresponding to the ideal skin test procedure, which suggests that skin-testing is far from being performed correctly. Field practitioners need to be sensitized to the importance of correctly performing the test. The authors recommend the questionnaire is suitable for application in other countries or regions
High prevalence of Taenia solium cysticerosis in a village community of Bas-Congo, Democratic Republic of Congo
No full textCysticercosis results from tissue infection with the larval stage of the pig tapeworm Taenia solium. Infection of the brain may cause neurocysticercosis, the most frequent cause of acquired epilepsy in developing countries. Information on human cysticercosis in the Democratic Republic of Congo (DRC) is scarce and outdated. We believe this is the first reported study on human cysticercosis and epilepsy in a village community of DRC. The proportion of villagers seropositive by ELISA for T. solium circulating antigen was 21.6%, the highest figure reported to date. The adjusted prevalence of active epilepsy in the community was 12.7 in 1,000