Tuberculous osteomyelitis of the mandibular condyle: A rare case report and review of the literature

Tuberculosis (TB) is a chronic infectious granulomatous disease caused by the air-borne bacillus Mycobacterium tuberculosis and less frequently by other bacteria in the M. tuberculosis complex (Mycobacterium Bovis and Mycobacterium africanum). Tuberculous osteomyelitis of the condyle may present atypical clinical findings akin to temporomandibular joint arthritis or middle ear infections. A detailed clinical and radiographic examination aided by a histopathological and a microbiological diagnostic workup is the key to timely detection and administration of appropriate therapeutic regimens. A high degree of clinical suspicion is thus advocated in patients with such atypical presentations. We, hereby, are presenting a rare case of tuberculous osteomyelitis in a 15-year-old female child.

ATENÇÃO FARMACÊUTICA NO TRATAMENTO DE TUBERCULOSE

A Tuberculose (TB) Peste branca ou como é popularmente conhecida, a tuberculose surgiu no continente africano há pelo menos 70.000 anos, acompanhou humanos na evolução e processo de expansão pelo planeta, mesmo hoje em dia considerada uma ameaça para à saúde. A TB é uma doença infecciosa crônica granulomatosa causada por bactérias do grupo das microbactérias. É importante ressaltar que existem microbactérias que podem causar tuberculose e outras que não podem. As principais causadoras são, da mais importante para a menos: tubercle bacillus, Mycobacterium bovis e Mycobacterium africanum. É considerada a doença mais infecciosa e mortal do mundo, responsável por mais de 04 mil mortes diárias no mundo todo, de acordo com a Organização Mundial da Saúde (OMS). Embora afete outros órgãos e / ou sistemas, é uma doença infecciosa e contagiosa que atinge principalmente os pulmões. As formas extrapulmonares que afetam outros órgãos além dos pulmões são mais comuns entre as pessoas com HIV, especialmente aquelas com sistema imunológico enfraquecido. No Brasil, a doença é um grave problema de saúde pública com profundas raízes sociais. A epidemia de HIV e a existência de bacilos resistentes a medicamentos complicaram a situação. Todos os anos, são notificados cerca de 70.000 novos casos e cerca de 4.500 mortes por tuberculose.

Rapid and Visual Differentiation of Mycobacterium tuberculosis From the Mycobacterium tuberculosis Complex Using Multiplex Loop-Mediated Isothermal Amplification Coupled With a Nanoparticle-Based Lateral Flow Biosensor

Tuberculosis (TB) is a chronic infectious disease mainly caused by Mycobacterium tuberculosis (MTB), but other members of the Mycobacterium tuberculosis complex (MTBC), especially Mycobacterium bovis (pyrazinamide-resistant organisms), may also be involved. Thus, the ability to rapidly detect and identify MTB from other MTBC members (e.g., M. bovis, Mycobacterium microti, Mycobacterium africanum) is essential for the prevention and treatment of TB. A novel diagnostic method for the rapid detection and differentiation of MTB, which employs multiplex loop-mediated isothermal amplification (mLAMP) combined with a nanoparticle-based lateral flow biosensor (LFB), was established (mLAMP-LFB). Two sets of specific primers that target the IS6110 and mtp40 genes were designed according to the principle of LAMP. Various pathogens were used to optimize and evaluate the mLAMP-LFB assay. The optimal conditions for mLAMP-LFB were determined to be 66°C and 40 min, and the amplicons were directly verified by observing the test lines on the biosensor. The LAMP assay limit of detection (LoD) was 125 fg per vessel for the pure genomic DNA of MTB and 4.8 × 103 CFU/ml for the sputum samples, and the analytical specificity was 100%. In addition, the whole process, including the clinical specimen processing (35 min), isothermal amplification (40 min), and result confirmation (1–2 min), could be completed in approximately 80 min. Thus, mLAMP-LFB is a rapid, reliable, and sensitive method that is able to detect representative members of MTBC and simultaneously differentiate MTB from other MTBC members, and it can be used as a potential screening tool for TB in clinical, field, and basic laboratory settings.

Import and transmission of Mycobacterium orygis and Mycobacterium africanum, Norway

Background The aim of the current study was to improve our understanding of the origins and transmission of Mycobacterium africanum (MAF) in Norway. Methods Whole-genome sequences (WGS) were generated for all (n = 29) available clinical isolates received at the Norwegian National Reference Laboratory for Mycobacteria (NRL) and identified as MAF in Norway, in the period 2010–2020. Phylogenetic analyses were performed. Results The analyses indicated several imports of MAF lineage 6 from both East and West African countries, whereas MAF lineage 5 was restricted to patients with West African connections. We also find evidence for transmission of MAF in Norway. Finally, our analyses revealed that a group of isolates from patients originating in South Asia, identified as MAF by means of a commercial line-probe assay, in fact belonged to Mycobacterium orygis. Conclusions Most MAF cases in Norway are the result of import, but transmission is occurring within Norway.

Analysis of Mycobacterium africanum in the last 17 years in Aragon identifies a specific location of IS6110 in Lineage 6

The purpose of this study was to increase our knowledge about Mycobacterium africanum and report the incidence and characteristics of tuberculosis (TB) due to their lineages in Aragon, Spain, over the period 2003–2019. The study includes all the cases in our region, where all the M. tuberculosis complex isolates are systematically characterised. We detected 31 cases of M. africanum among 2598 cases of TB in the period studied. TB caused by M. africanum is rare (1.19%) in our population, and it affects mainly men of economically productive age coming from West African countries. Among the isolates, Lineage (L) 6 was more frequent than L5. The genotyping of these strains identified five clusters and 13 strains with a unique pattern. The isolates’ characterisation identified a copy of IS6110 within the moaX gene, which turned out to be specific for L6. It will allow the differentiation of this lineage from the rest of MTBC with a simple PCR reaction. It remains to be established whether this polymorphism may limit M. africanum transmission. Furthermore, a mutation in the mutT2 promoter was found as specific for L6 strains, which could be related to the high variability found for L6 compared to L5.

Isolation and Molecular Characterization of Mycobacterium Africanum from the Sputum of Butchers in a Municipal Abattoir in

Tuberculosis (TB) caused by the Mycobacterium tuberculosis complex (MTC) remains a major public health concern due to its high rate of person to person transfer as well as a high level of morbidity and mortality. The risk factors for transmission of zoonotic TB to humans are close physical contact with cattle, consumption of unpasteurised milk and milk products and unhealthy meat processing by butchers are common in developing countries like Nigeria. However, the circulating MTC among the occupationally exposed are unknown therefore the need to determine the prevalence of tuberculosis and to characterize the mycobacterial species in them. A crosssectional study was conducted among butchers, cattle traders and herders in Bodija Municipal Abattoir, Akinyele International Cattle Market and some herds respectively. Using systematic random sampling, 93 sputum samples were collected and analyzed by culture, Mycobacterium Genus Typing as well as Deletion Typing (Multiplex Polymerase Chain Reaction (PCR)). Of the 93 sputa collected, two (2.2%) were positive for mycobacteria by culture which were confirmed to be Mycobacterium africanum by molecular characterization. These bacilli were isolated from two butchers; one of which had the habit of eating raw meat and cherish ‘wara’ (a local soft cheese made from milk). The isolation of M. africanum from butchers in this study raises public health concern on the contamination of the meat processed as well as highlights its importance in the epidemiology of tuberculosis in Nigeria.

Phylogenomics of Mycobacterium africanum reveals a new lineage and a complex evolutionary history

Human tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC). The MTBC comprises several human-adapted lineages known as M. tuberculosis sensu stricto, as well as two lineages (L5 and L6) traditionally referred to as Mycobacterium africanum . Strains of L5 and L6 are largely limited to West Africa for reasons unknown, and little is known of their genomic diversity, phylogeography and evolution. Here, we analysed the genomes of 350 L5 and 320 L6 strains, isolated from patients from 21 African countries, plus 5 related genomes that had not been classified into any of the known MTBC lineages. Our population genomic and phylogeographical analyses showed that the unclassified genomes belonged to a new group that we propose to name MTBC lineage 9 (L9). While the most likely ancestral distribution of L9 was predicted to be East Africa, the most likely ancestral distribution for both L5 and L6 was the Eastern part of West Africa. Moreover, we found important differences between L5 and L6 strains with respect to their phylogeographical substructure and genetic diversity. Finally, we could not confirm the previous association of drug-resistance markers with lineage and sublineages. Instead, our results indicate that the association of drug resistance with lineage is most likely driven by sample bias or geography. In conclusion, our study sheds new light onto the genomic diversity and evolutionary history of M. africanum , and highlights the need to consider the particularities of each MTBC lineage for understanding the ecology and epidemiology of TB in Africa and globally.

Import and Transmission of Mycobacterium Orygis and Mycobacterium Africanum, Norway

Background : The aim of the current study was to improve our understanding of the origins and transmission of Mycobacterium africanum (MAF) in Norway.Methods : Whole-genome sequences (WGS) were generated for all (n=29) available clinical isolates identified as in Norway in the period 2010 – 2020. Phylogenetic analyses were performed.Results : The analyses indicated multiple imports of MAF lineage 6 from both East and West African countries, whereas MAF lineage 5 was restricted to patients with West African connections. We also find evidence for transmission of MAF in Norway. Finally, our analyses revealed that a group of isolates from patients originating in South Asia, identified as MAF by means of a commercial line-probe assay, in fact belonged to Mycobacterium orygis.Conclusions : Most MAF cases in Norway are the result of import, but transmission is occurring in immigrant communities.

Culturomics Discloses Anti-Tubercular Enterococci Exclusive of Pulmonary Tuberculosis: A Preliminary Report

Mycobacterium tuberculosis causes pulmonary tuberculosis, a deadly infection of which the clinical expression and prognosis are not fully understood at the individual level, apart from genetic susceptibility traits. We investigated whether individual gut microbiota may correlate with pulmonary tuberculosis status. Culturomics investigations of gut microbiota in two pulmonary tuberculosis patients and two controls in Burkina Faso found 60 different bacterial species in patients and 97 in controls, including 45 in common. Further analysis of the results at the individual level indicated seven bacteria, including Enterococcus mundtii and Enterococcus casseliflavus, which were exclusively cultured in controls. Blind quantitative PCR-based exploration of faeces samples in two cohorts in Burkina Faso and in France confirmed a nonsignificant association of E. mundtii and E. casseliflavus with controls. Further in vitro explorations found four E. mundtii and E. casseliflavus strains inhibiting the growth of M. tuberculosis strains representative of four different lineages as well as Mycobacterium africanum, Mycobacterium canettii, and Mycobacterium bovis, in an inoculum-dependent manner. Heat-killed E. mundtii or E. casseliflavus were ineffective. These unprecedented observations of direct interactions between gut E. mundtii and E. casseliflavus with M. tuberculosis complex mycobacteria suggest that gut microbiota may modulate the expression of pulmonary tuberculosis.

Pan-Genome Analysis of Mycobacterium Africanum: Insights to Dynamics and Evolution.

Background: Mycobacterium tuberculosis complex (MTBC) consists of seven major lineages with three of them reported to circulate within West Africa: lineage 5 (West African 1) and lineage 6 (West African 2) which are geographically restricted to West Africa and lineage 4 (Euro-American lineage) which is found globally. It is unclear why the West African lineages are not found elsewhere; some hypotheses suggest that it could either be harboured by an animal reservoir which is restricted to West Africa, or strain preference for hosts of West African ethnicity, or inability to compete with other lineages in other locations.We tested the hypothesis that M. africanum West African 2 (lineage 6) might have emigrated out of West Africa but was outcompeted by more virulent modern strains of M. tuberculosis (MTB).Whole genome sequences of M. tuberculosis from Nigeria (n=21), South Africa (n=24) and M. africanum West African 2 from Mali (n=22) were retrieved, and a pan-genome analysis was performed after fully annotating these genomes. Results: The outcome of this analysis shows that Lineages 2, 4 and 6 all have a close pan-genome. We also see a correlation in numbers of some multiple copy core genes and amino acid substitution with lineage specificity that may have contributed to geographical distribution of these lineages.Conclusions: The findings in this study provides a perspective to one of the hypotheses that M. africanum West African 2 might find it difficult to compete against the more modern lineages outside West Africa hence its localization to the geographical region.