Baseline and end-of-treatment host serum biomarkers predict relapse in adults with pulmonary tuberculosis.

Background: There is a need for new tools for monitoring of the response to TB treatment. Such tools may allow for tailored treatment regimens, and stratify patients initiating TB treatment into different risk groups. We evaluated combinations between previously published host biomarkers and new candidates, as tools for monitoring TB treatment response, and prediction of relapse.

Point-of-care C-reactive protein and Xpert MTB/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: a prospective, cross-sectional, diagnostic accuracy study.

Background: Tuberculosis, a major cause of death in people living with HIV, remains challenging to diagnose. Diagnostic accuracy data are scarce for promising triage and confirmatory tests such as C-reactive protein (CRP), sputum and urine Xpert MTB/RIF Ultra (Xpert Ultra), and urine Determine TB LAM Ag (a lateral flow lipoarabinomannan [LF-LAM] test), without symptom selection. We evaluated novel triage and confirmatory tests in ambulatory people with HIV initiating antiretroviral therapy (ART).

"Spotting" infection in leopards () - novel application of diagnostic tools.

Background: () is the causative agent of animal tuberculosis (TB) which poses a threat to many of South Africa's most iconic wildlife species, including leopards (). Due to limited tests for wildlife, the development of accurate ante-mortem tests for TB diagnosis in African big cat populations is urgently required. The aim of this study was to evaluate currently available immunological assays for their ability to detect infection in leopards.

Point-of-care C-reactive protein and Xpert MTB/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: a prospective diagnostic accuracy study.

Background: Tuberculosis (TB), a major cause of death in people living with HIV (PLHIV), remains challenging to diagnose. Diagnostic accuracy data are lacking for promising triage tests, such as C-reactive protein (CRP), and confirmatory tests, such as sputum and urine Xpert MTB/RIF Ultra (Ultra), and urine LAM, without prior symptom selection.

Methods: 897 PLHIV initiating antiretroviral therapy were consecutively recruited in settings with high TB incidence, irrespective of symptoms.

Comparison of interferon gamma release assay and gene expression assay for the detection of infection in African lions ().

() infection has been identified in both domestic and wild animals and may threaten the conservation of vulnerable species including African lions (). There is a need to develop accurate ante-mortem tools for detection of infection in African big cat populations for wildlife management and disease surveillance. The aim of this study was to compare the performances of two immunological assays, the QuantiFERON-TB Gold Plus (QFT) Mabtech Cat interferon gamma release assay (IGRA) and QFT gene expression assay (GEA), which have both shown diagnostic potential for detection in African lions.

African wild dogs (Lycaon pictus) from the Kruger National Park, South Africa are currently not inbred but have low genomic diversity.

African wild dogs (Lycaon pictus) have undergone severe population reductions and are listed as endangered on the International Union for Conservation of Nature Red List. Small, isolated populations have the potential to suffer from threats to their genetic diversity that may impact species viability and future survival. This study provides the first set of population-wide genomic data to address conservation concerns for this endangered species.

Adaptation and Diagnostic Potential of a Commercial Cat Interferon Gamma Release Assay for the Detection of Infection in African Lions ().

() infection in wildlife, including lions (), has implications for individual and population health. Tools for the detection of infected lions are needed for diagnosis and disease surveillance. This study aimed to evaluate the Mabtech Cat interferon gamma (IFN-γ) ELISA kit for detection of native lion IFN-γ in whole blood samples stimulated using the QuantiFERON TB Gold Plus (QFT) platform as a potential diagnostic assay.

Deciphering Genetic Susceptibility to Tuberculous Meningitis.

Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis (TB) that arises when a caseating meningeal granuloma discharges its contents into the subarachnoid space. It accounts for ~1% of all disease caused by and the age of peak incidence is from 2-4 years. The exact pathogenesis of TBM is still not fully understood and the mechanism(s) by which the bacilli initially invade the blood-brain-barrier are still to be elucidated.

CYTOKINE-RELEASE ASSAY FOR THE DETECTION OF INFECTION IN CHEETAH ().

The lack of species-specific assays for the diagnosis of infectious diseases, such as bovine tuberculosis, poses a threat to the management of wildlife populations, especially for vulnerable species such as cheetah (). The aim of this study was to identify and develop a cell-mediated immunological cytokine-release assay that could distinguish between -infected and uninfected cheetahs using commercially available feline cytokine ELISA and domestic cat () recombinant proteins. Antibodies against domestic cat cytokines, tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interferon gamma (IFN-γ), were screened for cross-reactivity with plasma cytokines from cheetah whole blood stimulated using QuantiFERON-TB Gold Plus (QFT) tubes.

Local Ancestry Adjusted Allelic Association Analysis Robustly Captures Tuberculosis Susceptibility Loci.

Pulmonary tuberculosis (TB), caused by , is a complex disease. The risk of developing active TB is in part determined by host genetic factors. Most genetic studies investigating TB susceptibility fail to replicate association signals particularly across diverse populations.

Improved detection of and in African wildlife samples using cationic peptide decontamination and mycobacterial culture supplementation.

In South Africa, mycobacterial culture is regarded as the gold standard for the detection of complex (MTBC) infection in wildlife even though it is regarded as "imperfect." We compared a novel decontamination and mycobacterial culture technique (TiKa) to the conventional mycobacterium growth indicator tube (MGIT) system using known amounts of bacilli and clinical samples from MTBC-infected African buffaloes (), white rhinoceros (), and African elephants (). Use of the TiKa-KiC decontamination agent on samples spiked with 10,000 to 10 colony forming units (cfu) of (SB0121) and (H37Rv) had no effect on isolate recovery in culture.

1,3-Diarylpyrazolyl-acylsulfonamides as Potent Anti-tuberculosis Agents Targeting Cell Wall Biosynthesis in .

Phenotypic whole cell high-throughput screening of a ∼150,000 diverse set of compounds against (Mtb) in cholesterol-containing media identified 1,3-diarylpyrazolyl-acylsulfonamide as a moderately active hit. Structure-activity relationship (SAR) studies demonstrated a clear scope to improve whole cell potency to MIC values of <0.5 μM, and a plausible pharmacophore model was developed to describe the chemical space of active compounds.

Complex evolutionary history of felid anelloviruses.

Anellovirus infections are highly prevalent in mammals, however, prior to this study only a handful of anellovirus genomes had been identified in members of the Felidae family. Here we characterise anelloviruses in pumas (Puma concolor), bobcats (Lynx rufus), Canada lynx (Lynx canadensis), caracals (Caracal caracal) and domestic cats (Felis catus). The complete anellovirus genomes (n = 220) recovered from 149 individuals were diverse.

Anaerobe-enriched gut microbiota predicts pro-inflammatory responses in pulmonary tuberculosis.

Background: The relationship between tuberculosis (TB), one of the leading infectious causes of death worldwide, and the microbiome, which is critical for health, is poorly understood.

Methods: To identify potential microbiome-host interactions, profiling of the oral, sputum and stool microbiota [n = 58 cases, n = 47 culture-negative symptomatic controls (SCs)] and whole blood transcriptome were done in pre-treatment presumptive pulmonary TB patients. This was a cross-sectional study.

Diagnostic accuracy of the FluoroType MTB and MTBDR VER 2.0 assays for the centralized high-throughput detection of Mycobacterium tuberculosis complex DNA and isoniazid and rifampicin resistance.

Objectives: To evaluate the accuracy of two new molecular diagnostic tests for the detection of drug-resistant tuberculosis, the FluoroType MTB and MTBDR VER 2.0 assays, in combination with manual and automated DNA extraction methods.

Methods: Sputa from 360 Xpert Ultra Mycobacterium tuberculosis complex (MTBC)-positive patients and 250 Xpert Ultra MTBC-negative patients were tested.

Shedding of Mycobacterium bovis in respiratory secretions of free-ranging wild dogs (Lycaon pictus): Implications for intraspecies transmission.

It has recently been discovered that Mycobacterium bovis (M. bovis) causes disease in the endangered African wild dog (Lycaon pictus) in areas endemic for bovine tuberculosis (bTB), including the Kruger National Park (KNP). However, information on M.

A multi-phenotype genome-wide association study of clades causing tuberculosis in a Ghanaian- and South African cohort.

Despite decades of research and advancements in diagnostics and treatment, tuberculosis remains a major public health concern. New computational methods are needed to interrogate the intersection of host- and bacterial genomes. Paired host genotype datum and infecting bacterial isolate information were analysed for associations using a multinomial logistic regression framework implemented in SNPTest.

Novel molecular transport medium used in combination with Xpert MTB/RIF ultra provides rapid detection of Mycobacterium bovis in African buffaloes.

Mycobacterium bovis is the causative agent of bovine tuberculosis (bTB) in wildlife. Confirmation of M. bovis infection relies on mycobacterial culture, which is time-consuming.

High diversity, inbreeding and a dynamic Pleistocene demographic history revealed by African buffalo genomes.

Genomes retain records of demographic changes and evolutionary forces that shape species and populations. Remnant populations of African buffalo (Syncerus caffer) in South Africa, with varied histories, provide an opportunity to investigate signatures left in their genomes by past events, both recent and ancient. Here, we produce 40 low coverage (7.

Mycobacterium bovis Infection in Free-Ranging African Elephants.

Mycobacterium bovis infection in wildlife species occurs worldwide. However, few cases of M. bovis infection in captive elephants have been reported.

Review of Diagnostic Tests for Detection of Infection in South African Wildlife.

Wildlife tuberculosis is a major economic and conservation concern globally. Bovine tuberculosis (bTB), caused by (), is the most common form of wildlife tuberculosis. In South Africa, to date, infection has been detected in 24 mammalian wildlife species.

Development of a cytokine gene expression assay for the relative quantification of the African elephant (Loxodonta africana) cell-mediated immune responses.

Immunological assays are the basis for many diagnostic tests for infectious diseases in animals and humans. Application in wildlife species, including the African elephant (Loxodonta africana), is limited however due to lack of information on immune responses. Since many immunoassays require both identified biomarkers of immune activation as well as species-specific reagents, it is crucial to have knowledge of basic immunological responses in the species of interest.

Optimisation of the tuberculin skin test for detection of Mycobacterium bovis in African buffaloes (Syncerus caffer).

Effective screening methods are critical for preventing the spread of bovine tuberculosis (bTB) among livestock and wildlife species. The tuberculin skin test (TST) remains the primary test for bTB globally, although performance is suboptimal. African buffaloes (Syncerus caffer) are a maintenance host of Mycobacterium bovis in South Africa, tested using the single intradermal tuberculin test (SITT) or comparative test (SICTT).

Diagnosis of Mycobacterium bovis infection in free-ranging common hippopotamus (Hippopotamus amphibius).

Bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. bovis) infection, is a multi-host disease which negatively affects the wildlife industry, with adverse consequences for conservation, ecotourism, and game/wildlife sales. Although interspecies transmission has been reported between some wildlife hosts, the risk of spread in complex ecosystems is largely unknown.