Curving Tuberculosis: Current Trends and Future Needs

Abstract

Introduction: Global Burden of Tuberculosis Mycobacterium Tuberculosis is an ancient and highly harmful successful human pathogen. Despite the advent of effective antimicrobial drugs, tuberculosis (TB) is still the most important infectious disease in humans and remains a leading cause of mortality worldwide [1, 2]. In 1993, the World Health Organization (WHO) declared TB a global public health emergency [3]. Since then, TB incidence has fallen by an average of 1.5% per year and is now 18% lower than in 2000. However, the 2015 update of the WHO Global Tuberculosis Report [2] estimated that there were still approximately 10.4 million (5.9 million men, 3.5 million women, and 1 million children) incident cases worldwide and TB was considered the underlying cause of 1.8 million deaths, 400,000 of whom were among HIV-positive individuals [4]. TB is relatively simple and inexpensive to diagnose, in most cases can be cured with well-tolerated, effective, and low-cost treatments [5, 6, 7]. It has been estimated that 37 million patients were cured between 2000 and 2013, ascribed to advanced diagnostic methods in conjunction with effective treatments [2]. However, multidrug resistant tuberculosis (MDR-TB) remains a major challenge to achieving complete disease control. The development of drug resistant TB strains is multifactorial. When TB bacteria replicate, some naturally mutate and become resistant to anti-TB drugs. TB treatment subsequent kills the non-mutated bacteria, leading to a selective survival of mutated, drug-resistant organisms. In 2015, it was estimated that approximately 580,000 individuals were carriers of rifampicin (RIF) and/or isoniazid (INH) and rifampicin-resistant (MDR) TB strains globally and that about 250,000 deaths were caused by those strains [2]. Moreover, only 25% of those cases were reported and just the 52% were successfully treated [2, 8, 9]. In 2006, extensively drug-resistant TB (XDR-TB; MDR plus resistance to any fluoroquinolone and, at least, one of the three second line injectable drug) also emerged as a more serious form of multidrug-resistant TB and a severe threat to public health, especially in countries with a high prevalence of HIV. Through 2015, XDR-TB cases have been reported in 105 countries and it is estimated 10% of cases of MDR-TB are XDR-TB [10, 11]. Diagnosing TB: Conventional Methods and Molecular Procedures WHO's global strategy for TB control prioritizes early diagnosis, which should include systematic screening of latent TB (contacts and high-risk groups) [12] and universal availability of drug susceptibility testing (DST). Unfortunately, of the 10.4 million TB cases estimated in 2015, more than 4 million remain undiagnosed and thus, continue to spread the disease [2]. Achieving global TB control requires that all of those cases be identified and effectively treated. Nowadays, TB diagnosis is still based in many countries on clinical suspicion, radiography and microbiological tests, performed by microscopic examination of sputum, a 120-year-old method. Bacilloscopy ba...

HAMLET, a Protein Complex from Human Milk, Has Bactericidal Activity and Enhances the Activity of Antibiotics against Pathogenic Streptococci

“…Classical examples are the regimen of multiple drugs in treating tuberculosis, HIV, and malaria based on the problem with antimicrobial resistance development in these organisms (10,12,(28)(29)(30). Unfortunately, resistance development in both Mycobacterium tuberculosis (10,31,32) and HIV ( 33) is still increasing. Another successful strategy used in clinics is the inclusion of beta-lactamase inhibitors, such as clavulanic acid, to improve the efficacy of beta-lactam treatment; however, strains expressing a novel class of beta-lactamases (metallo-beta-lactamases, causing resistance to carbapenems) are emerging (34).…”

“…Production and characterization of HAMLET from human milk. Human alpha-lactalbumin purified from human milk was converted into HAMLET by complexing apo-protein (treated with EDTA) with oleic acid (C 18:1 ; Sigma) on a DEAE-containing ion exchange matrix, and HAMLET complex was eluted with salt as described previously (32). The eluted HAMLET was dialyzed with water to remove salt, and the desalted protein-lipid complex was lyophilized and saved at -20°C until use.…”

Antibiotic resistance breakers: current approaches and future directions

“…While the initial treatment for M. tuberculosis infections usually consists of a combination regimen including rifampicin, ethambutol, pyrazinamide and isoniazid, streptomycin is a suitable alternative when isoniazid resistance has been established or if the patient has any tolerability issues with the initial regimen. Amikacin is a suitable second-line option when there are further issues with resistance or side effects caused by the first-line drugs (Rojano, Caminero and Hayek 2019).…”

Organoids as a Powerful Model for Respiratory Diseases

“…Nearly ten million new MTB infections have been recognized annually during the past 5 years according to a WHO TB report. Drug-resistant strains and coinfection with HIV are challenging the End TB Strategy by 2035 proposed by the WHO [64]. Animal models that have been used to investigate TB pathologies and drug screening possess several obvious faults.…”