Latent Tuberculosis: Challenges in Diagnosis and Treatment, Perspectives, and the Crucial Role of Biomarkers.

Tuberculosis (TB) is the major cause of morbidity and mortality globally, which is caused by a single infectious agent Mycobacterium tuberculosis. For years, many TB control programmes are established for effective diagnosis and treatment of active TB cases, but these approaches alone are insufficient for TB eradication. This review aims to discourse on the crucial management of latent tuberculosis infection. This review will first summarize the current status, and methods for diagnosing latent tuberculosis then describes the challenges involved in the diagnosis and treatment of latent tuberculosis, and finally encounters the purpose of biomarkers as predicting tool in latent tuberculosis.

Cutaneous Manifestations of Mycobacterium tuberculosis: A Literature Review.

Tuberculosis is an ancient disease that humanity struggled with for centuries and continues to struggle with. The bacteria Mycobacterium tuberculosis often infects the lungs through respiratory transmission and manifests itself through various symptoms, including cutaneous infections. Cutaneous tuberculosis (CTB) comprises about 1% to 1.5% of all extrapulmonary manifestations and is often accompanied by polymorphous lesions, including papules, nodules, plaques, ulcers, gummas, and verrucous lesions. CTB is most commonly observed in low-income, HIV, and immunosuppressed populations, similar to intrapulmonary manifestations. The main pathogen for CTB is M. tuberculosis but less commonly with M. bovis and BCG vaccine, and the modes of transmission are largely classified into exogenous and endogenous CTB. Current treatment options for CTB include oral therapy of antibiotic medications such as rifampicin, streptomycin, ethambutol, isoniazid, and pyrazinamide, which is occasionally combined with surgical intervention.

Neutralization function affected by single amino acid replacement in the HIV-1 antibody targets.

The viral envelope glycoproteins are essential for entry into their host cells and studied extensively for designing vaccines. We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). The glycosylation occurring on the 50th residue (Asparagine) contained in the target (NWFNIT) can mask itself to be inaccessible for these neutralizing antibodies. The glycosylation rate of the epitopes which are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 were predicited in silico. We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). It is evident that the glycosylation by a mannose that masks these targets is possible only when the 50th amino-acid is N (Asparagine, Asn) which is not possible when N is mutated to D (Aspartatic acid, Asp). The additive advantage for the retrovirus is its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model. So the glycan shields varying in their intensity and patterns have to be essentially studied to understand the viral escape strategies that will give a way forward towards a successful vaccine that can elicit a neutralizing antibody response to confer protection.