Background Haematopoietic stem cells expressing the CD34 surface marker have been posited as a niche for Mycobacterium tuberculosis complex bacilli during latent tuberculosis infection. Our aim was to determine whether M tuberculosis complex DNA is detectable in CD34-positive peripheral blood mononuclear cells (PBMCs) isolated from asymptomatic adults living in a setting with a high tuberculosis burden.Methods We did a cross-sectional study in Ethiopia between Nov 22, 2017, and Jan 10, 2019. Digital PCR (dPCR) was used to determine whether M tuberculosis complex DNA was detectable in PBMCs isolated from 100 mL blood taken from asymptomatic adults with HIV infection or a history of recent household or occupational exposure to an index case of human or bovine tuberculosis. Participants were recruited from HIV clinics, tuberculosis clinics, and cattle farms in and around Addis Ababa. A nested prospective study was done in a subset of HIV-infected individuals to evaluate whether administration of isoniazid preventive therapy was effective in clearing M tuberculosis complex DNA from PBMCs. Follow-up was done between July 20, 2018, and Feb 13, 2019. QuantiFERON-TB Gold assays were also done on all baseline and follow-up samples. Findings Valid dPCR data (ie, droplet counts >10 000 per well) were available for paired CD34-positive and CD34-negative PBMC fractions from 197 (70%) of 284 participants who contributed data to cross-sectional analyses. M tuberculosis complex DNA was detected in PBMCs of 156 of 197 participants with valid dPCR data (79%, 95% CI 74-85). It was more commonly present in CD34-positive than in CD34-negative fractions (154 [73%] of 197 vs 46 [23%] of 197; p<0•0001). Prevalence of dPCR-detected M tuberculosis complex DNA did not differ between QuantiFERONnegative and QuantiFERON-positive participants (77 [78%] of 99 vs 79 [81%] of 98; p=0•73), but it was higher in HIV-infected than in HIV-uninfected participants (67 [89%] of 75 vs 89 [73%] of 122, p=0•0065). By contrast, the proportion of QuantiFERON-positive participants was lower in HIV-infected than in HIV-uninfected participants (25 [33%] of 75 vs 73 [60%] of 122; p<0•0001). Administration of isoniazid preventive therapy reduced the prevalence of dPCR-detected M tuberculosis complex DNA from 41 (95%) of 43 HIV-infected individuals at baseline to 23 (53%) of 43 after treatment (p<0•0001), but it did not affect the prevalence of QuantiFERON positivity (17 [40%] of 43 at baseline vs 13 [30%] of 43 after treatment; p=0•13). Interpretation We report a novel molecular microbiological biomarker of latent tuberculosis infection with properties that are distinct from those of a commercial interferon-γ release assay. Our findings implicate the bone marrow as a niche for M tuberculosis in latently infected individuals. Detection of M tuberculosis complex DNA in PBMCs has potential applications in the diagnosis of latent tuberculosis infection, in monitoring response to preventive therapy, and as an outcome measure in clinical trials of interventions to prev...
Bovine tuberculosis (bTB) continues to be one of the most widely distributed chronic infectious diseases of zoonotic importance, which causes a significant economic loss in animal production. A cross-sectional study was conducted to estimate the prevalence of bTB and its associated risk factors and type the Mycobacterium bovis isolated in central Ethiopia. A total of 65 dairy farms and 654 cattle were tested for bTB using a single intradermal comparative cervical tuberculin (SICCT) test. Data on farm management, animal-related characteristics, and the owner's knowledge of the zoonotic importance of bTB were collected using a structured questionnaire. In addition, a total of 16 animals from different farms were identified for postmortem examination. Lowenstein Jensen (LJ) culture was also conducted, and spoligotyping was used to type the M. bovis strains isolated. Chi-square test and logistic regression models were used to analyze the herd- and animal-level risk factors. Herd- and animal-level prevalence rates of bTB were 58.5% (95% CI: 46.2%−69.2%) and 39.3% (95% CI: 35.5%−43.5%), respectively. At the herd level, poor farm management was the predictor for bTB positivity (p < 0.05). Animal breed, poor BCS, farm type, and poor farm management conditions were significant predictors of bTB positivity (p < 0.05) at an individual animal level. All animals identified for postmortem examination were found to have gross TB-like lesions. A total of 14 M. bovis strains were identified from 12 animals that were positive for LJ culture. The strain with the largest number of clusters (five isolates) was SB1176, followed by SB0134 (three isolates), SB0192 (two isolates), and SB2233 (two isolates), and two new strains, each consisting of only one isolate. The majority (58.5%) of the respondents did not know the zoonotic importance of bTB. The result of this study showed a high prevalence of bTB in the Addis Ababa milkshed and a low level of consciousness of the owners on its transmission to humans. Therefore, the launching of acceptable control measures of bTB and the creation of public awareness about its zoonotic transmission and prevention measures are required.
Context Kniphofia (Asphodelaceae) is found mainly in South Africa and Tropical Africa. Malaria, hepatitis B, blood purifier, cancer, eczema, and female infertility have all been traditionally treated using this genus. Objective The current review provides a complete and up-to-date compilation of documented traditional medicinal uses, phytochemicals, and pharmacological activities of the genus. Method Relevant literature was collected by searching the major electronic scientific databases including PubMed, Science Direct, Web of Science, and Google Scholar using appropriate keywords ethnomedicinal studies, phytochemical investigations, and pharmacological activities of Kniphofia species. The search strategy included all articles with descriptors that were available until November 30, 2021. Only published works in English were used for this study. The data were collected using textual descriptions of the studies, tabulation, grouping, and figures. Result At present, more than 40 compounds have been isolated from different parts of Kniphofia species. The major compounds isolated from the Kniphofia species are monomeric anthraquinones and dimeric anthraquinones. Pharmacologically the extracts and isolated compounds showed antioxidant, antimalarial, antiproliferative, anti-HIV-1, anti-leukotriene, and cytotoxic activity. The genus afforded exemplary drug leads such as knipholone and knipholone anthrone with anti-HIV-1, antimalarial and cytotoxicity activity. Conclusions Kniphofia species have traditionally been used to treat a variety of diseases. Pharmacological actions of phytochemicals were shown to be promising. Despite this, considering the genus's inclusion on the red data list of South Africa, it deserves more attention. In order to find novel drug candidates, more studies on promising crude extracts and compounds are needed.
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