To investigate the distribution of Mycobacterium tuberculosis genotypes across Africa.
The SITVIT2 global repository and PUBMED were searched for spoligotype and published genotype data respectively, ...of M. tuberculosis from Africa. M. tuberculosis lineages in Africa were described and compared across regions and with those from 7 European and 6 South-Asian countries. Further analysis of the major lineages and sub-lineages using Principal Component analysis (PCA) and hierarchical cluster analysis were done to describe clustering by geographical regions. Evolutionary relationships were assessed using phylogenetic tree analysis.
A total of 14727 isolates from 35 African countries were included in the analysis and of these 13607 were assigned to one of 10 major lineages, whilst 1120 were unknown. There were differences in geographical distribution of major lineages and their sub-lineages with regional clustering. Southern African countries were grouped based on high prevalence of LAM11-ZWE strains; strains which have an origin in Portugal. The grouping of North African countries was due to the high percentage of LAM9 strains, which have an origin in the Eastern Mediterranean region. East African countries were grouped based on Central Asian (CAS) and East-African Indian (EAI) strain lineage possibly reflecting historic sea trade with Asia, while West African Countries were grouped based on Cameroon lineage of unknown origin. A high percentage of the Haarlem lineage isolates were observed in the Central African Republic, Guinea, Gambia and Tunisia, however, a mixed distribution prevented close clustering.
This study highlighted that the TB epidemic in Africa is driven by regional epidemics characterized by genetically distinct lineages of M. tuberculosis. M. tuberculosis in these regions may have been introduced from either Europe or Asia and has spread through pastoralism, mining and war. The vast array of genotypes and their associated phenotypes should be considered when designing future vaccines, diagnostics and anti-TB drugs.
This study focuses on identifying variations in selected CYP genes related to treatment responses in patients with HIV in African populations by investigating variant characteristics and effects in ...African cohorts.
Cytochrome P450 (CYP) 2A6, 2B6, and Uridine 5'-diphospho-glucuronosyltransferase (UGT) 2B7 allele frequencies were studied using public-domain datasets obtained from the 1000 Genomes Phase 3 project, the African Genome Variation Project (AGVP), and the South African Human Genome Programme (SAHGP).
Variant annotations were performed using self-identified ethnicities to conduct allele frequency analysis in a population-stratification-sensitive manner. The NCBI DB-SNP database was used to identify documented variants and standard frequencies, and the E! Ensembl Variant Effect Predictor tool was used to perform the prediction of possible deleterious variants.
A total of 4468 variants were identified across 3676 individuals following pre-filtering. Seventy-one variants were identified at an allelic frequency (1% or more in at least one population), which were predicted to be linked to existing disease associations and, in some cases, linked to drug metabolisms. This list was further studied to identify 23 alleles with disease considerations found at significantly different frequencies in one or more populations.
This study describes allele frequencies observed in African populations at significantly different frequencies relative to at least one other reference population and identifies a subset of variants of clinical interest. Despite the inclusion of mixed sequence coverage datasets, the variants identified pose notable avenues for future inquiries. A subset of variants of clinical interest with statistically significant inter-population frequency differences was identified for further inspection, which provides evidence of an African population-specific variant frequency profile. This study highlights the need for additional research and African genetics data given the presence of this unique frequency profile to better facilitate the genetic pre-screening of patients as a standard of practice in HIV care, particularly on the African continent where HIV is highly prevalent.
•Young alpacas were vaccinated with Barbervax® in a randomized, blinded challenge trial.•Alpacas were experimentally inoculated with Haemonchus contortus.•Vaccinated alpacas demonstrated titers to ...Haemonchus contortus H-gal-GP hidden antigens.•Barbervax® was found to be safe in this group of alpacas.
Haemonchosis in camelids remains a challenging disease to treat, and prevention has become increasingly problematic due to widespread anthelmintic resistance. Barbervax®is an adjuvanted vaccine containing natural H-11, H-gal-GP antigens obtained from Haemonchus contortus adults via a proprietary process and solubilized in Quil A. This vaccine is approved for use in Australia, after demonstrating its safety and efficacy in sheep and goats. There are no published studies evaluating Barbervax in other ruminants/pseudoruminants such as camelids which can be parasitized with H. contortus. The vaccine utilizes a mixture of the parasite gut mucosal membrane enzymes including H-gal-GP and H11, involved in digesting a blood meal from the host. This study monitored the safety profile of the Barbervax® vaccine in a group of adolescent alpacas. Although designed into the original study of vaccine efficacy, the experimental infection with viable H. contortus third stage larvae could not be completed due to lack of detectable significant variation of infection following experimental challenge. Twelve alpacas (158 + 15 days) were randomized to vaccination with Barbervax® or no treatment. Three doses of Barbervax® were administered at 3 week intervals and investigators involved in animal monitoring and sample collection were blinded to the groupings. Clinical pathologic parameters were evaluated 7 days before vaccination, and 1 and 2 months post-vaccination. Daily clinical observations were made and specific observations regarding the injection site and rectal temperatures were monitored in each alpaca twice daily for 1 week following vaccination. Fecal egg counts, packed cell volume, and total protein were monitored following challenge with 1500 H. contortus larvae on days 42, 46, and 50. An increase in rectal temperature for a duration of 2 days (range 2–4 days) was observed post-vaccination. Vaccinated alpacas were lethargic for 2-3 days following vaccination; however, they maintained an appetite and no visible or palpable injection site reactions were observed. Following the first vaccination, all animals maintained normal clinical pathologic parameters throughout the study period. The vaccinated animals did develop titers to the H. contortus antigen as measured by ELISA. In conclusion, the Barbervax® vaccine demonstrated safety in this small group of young, healthy alpacas, but additional studies are required to evaluate the efficacy of the vaccine under field conditions in protecting alpacas against infection with H. contortus.
The purpose of this study was to determine the frequency of vertical transmission of Mycoplasma haemolamae from dam to cria, whether colostral transmission of M. haemolamae occurs and provide ...preliminary data on colostral M. haemolamae specific antibody from pregnant alpacas on a farm with known prevalence of infection. M. haemolamae specific PCR was performed on blood and colostrum from pregnant alpacas and their cria (n=52 pairs). Indirect fluorescent antibody testing was performed on a subset (n=43) of the colostrum samples. Total immunoglobulin concentrations of colostrum and cria sera and M. haemolamae specific IgG (prior to and after ingesting colostrum) were determined by turbidometric immunoassay and indirect fluorescence antibody testing respectively. Sixteen of 52 dams (30.7%) pre-partum and one of 52 cria post-partum (1.9%; prior to ingesting colostrum) were PCR positive for M. haemolamae, while 36/52 dams (69%) and 51/52 cria (98%) tested negative for M. haemolamae by PCR. All 43 colostrum samples and 52 of 52 post-colostrum cria blood samples (100%) were negative by PCR. The dam giving birth to the M. haemolamae PCR positive cria was PCR negative. Statistically, it was no more likely for a PCR positive dam to give birth to a M. haemolamae, PCR positive cria (prior to colostrum ingestion) than a PCR negative dam (p=0.3077). M. haemolamae specific IgG was present in 22 of 43 (51%) of colostrum samples at a 1:10 dilution and 14 of 22 (64%) at a 1:100 dilution. There was no relationship between the PCR status of the dam and whether or not M. haemolamae specific antibodies were present in colostrum. Among the animals tested, in utero transmission of M. haemolamae was rare (1/52 pre-colostral alpaca cria), and all colostrum samples were negative for M. haemolamae by PCR. These data indicate that colostrum from positive dams is unlikely to harbor this parasite and therefore does not serve as a source of infection to newborn cria. Colostrum derived from both PCR positive and negative dams contained M. haemolamae specific antibodies. Our findings suggest that M. haemolamae specific antibodies may play a role in immunity to this hemoparasite; however, challenge studies are necessary to fully evaluate the role of M. haemolamae specific antibodies. Furthermore, antibody prevalence and detectable titers may provide different estimates than those available from current PCR based prevalence studies. Our findings also suggest that M. haemolamae isolates from geographically distinct regions do not differ significantly from each other.
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