Tuberculosis (TB) continues to be a global challenge. Reducing the duration of TB treatment for drug-sensitive TB (DSTB) has direct and distinct advantages. We ventured into the aspect of utilizing linezolid as a pivotal drug in shortening therapy in DSTB. Linezolid has gained prominence as it is faring well in resistant TB management. Only a few studies use the strategy of Linezolid in DS-TB but it seems a lucrative approach, the bactericidal effects have been reported favourably in the studies. There have been concerns about the potential adverse drug effects of Linezolid reported but clinical trials have demonstrated safety and tolerability when administered for shorter periods. If the safety and efficacy of giving Linezolid for a shorter period along with standard drugs for DSTB is established it could lead to newer avenues using Linezolid for shortening the duration of treatment for DSTB as an alternative to treat DSTB.

Drug-resistant tuberculosis (TB) can be considered the man-made result of interrupted, erratic or inadequate TB therapy. As reported in WHO data, resistant Mycobacterium tuberculosis (Mtb) strains continue to constitute a public health crisis. Mtb is naturally able to survive host defence mechanisms and to resist most antibiotics currently available. Prolonged treatment regimens using the available first-line drugs give rise to poor patient compliance and a rapid evolution of strains resistant to rifampicin only or to both rifampicin and isoniazid (multi drug-resistant, MDR-TB). The accumulation of mutations may give rise to extensively drug-resistant strains (XDR-TB), i.e. strains with resistance also to fluoroquinolones and to the injectable aminoglycoside, which represent the second-line drugs. Direct lung delivery of anti-tubercular drugs, as an adjunct to conventional routes, provides high concentrations within the lungs, which are the intended target site of drug delivery, representing an interesting strategy to prevent or reduce the development of drug-resistant strains. The purpose of this paper is to describe and critically analyse the most recent and advanced results in the formulation development of WHO second-line drug inhalation products, with particular focus on dry powder formulation. Although some of these formulations have been developed for other lung infectious diseases (Pseudomonas aeruginosa, nontuberculous mycobacteria), they could be valuable to treat MDR-TB and XDR-TB.

New evidence and knowledge about the clinical management of drug-resistant tuberculosis (TB) in the last 3 years, makes it necessary to update the recent guideline published by SEPAR in 2017, mainly in relation to new diagnostic methods, drug classification, and regimens of treatment recommended to treat patients with isoniazid-resistance TB, rifampicin resistance TB and multidrug-resistant TB. With respect to tuberculosis diagnosis, we recommend the use of rapid molecular assays that also help to detect mutations associated with resistance. In relation to the treatment of multidrug-resistant TB we prioritize effective all-oral shorter treatment regimens including bedaquiline, a fluoroquinolone (levofloxacin or moxifloxacin), bedaquiline and linezolid, instead of the previously recommended short-course treatment with aminoglycosides and other less effective and more toxic drugs. The design of these regimens (initial schedule and changes in the regimen if necessary) should be made in accordance with drug-resistant TB experts; the treatment should be the responsibility of personnel with experience in the treatment of TB and in TB units guaranteeing the follow-up of the treatment and the management of drugs adverse effects.

BACKGROUND: Drug resistant tuberculosis is a major public health problem in Morocco and worldwide. Treatment outcome of drug resistant tuberculosis is poor and requires a long period of treatment with many toxic and expensive antituberculosis drugs. The aim of this study is to evaluate treatment outcomes of drug resistant tuberculosis and to determine predictors of poor treatment outcomes in a large region of Morocco.
METHODS: It is a multi-centric observational cohort study conducted from January 01, 2014 to January 01, 2016. A questionnaire was established to collect data from clinical charts of patients with confirmed resistant TB. The study was carried out in all the 11 centers located in the Rabat-Salé-Kénitra region of Morocco where drug resistant tuberculosis is treated. Treatment outcomes were reported and the definitions and classifications of these outcomes were defined according to the WHO guidelines. Univariate and multivariate logistic regression were conducted to determine factors associated with poor drug resistant tuberculosis treatment outcomes in Morocco.
RESULTS: In our study, 101 patients were treated for drug resistant tuberculosis between January 01, 2014 and January 01, 2016. Patients\' age ranged from 9.5 to70 years; 72patients (71.3%) were male and 80 patients (79.2%) were living in urban areas. Thirty two patients were smokers, 74 patients had multidrug-resistant tuberculosis, 25 patients had rifampicin resistance and 2 patients had isoniazid resistance. Treatment outcomes of tuberculosis patients were as follows: 45 patients were cured (44.5%), 9 completed treatment (8.9%), 5 patients died before completing the treatment, 35 patients were lost to follow up (34.6%) and 7 patients had treatment failure. In the multivariate analysis, being a smoker is an independent risk factor for poor treatment outcomes, (p-value = 0.015, OR = 4.355, IC [1.327-14.292]).
CONCLUSIONS: Treatment success outcomes occurred in more than half of the cases, which is lower than the World Health Organization target of at least a 75% success rate. A significant number of patients abandoned their treatment before its completion. These dropouts are a serious public health hazard that needs to be addressed urgently.

New-onset clinical or radiological symptoms in a patient with tuberculosis pose diagnostic treatment challenges, which can be due to treatment failure, disease relapse, or paradoxical response. We describe an adolescent case of recurrent paradoxical response complicating tuberculous meningitis. The first paradoxical tuberculosis presented as chest wall abscess, which was complicated by uniocular, gradually progressive, painless loss of vision after 6 months.

Tuberculosis (TB) is a serious major health concern that has existed from millennia. According to annual WHO report 2016, it is considered as world\'s ninth highest killer disease by single infectious agent, ranking above HIV/AIDS. To worsen the scenario the development of multi-drug resistant tuberculosis (MDR-TB) and extremely drug-resistant tuberculosis (XDR-TB) have significantly reduced the success rate of TB treatment. Several efforts are being made to handle pharmacodynamic resistance (MDR and XDR-TB) involving designing of new inhibitors, targeting mutated target or by multi-targeting agents. However, the issue of pharmacokinetic resistance in TB is not being addressed appropriately till date. Pharmacokinetic mode of resistance involves an intrinsic mechanism of bacterial drug resistance via expression of various enzymes and efflux pumps that are responsible for the loss of activity of the therapeutic agents. Mycobacterium tuberculosis is also intrinsically resistant to various approved agents via pharmacokinetic mechanism of resistance. Several bacterial enzymes are encoded that either degrade or modifies the drugs and renders them ineffective. Targeting such inactivating bacterial enzymes provides a novel approach to make the current therapy effective and combat the problem of resistance. This review provides an insight into different bacterial enzymes which are responsible for pharmacokinetic drug resistance in TB. The structure attributes and mechanism of catalysis employed by these enzymes to inactivate drug have also been discussed which may provide basis for developing novel therapeutic agents for resistant TB.

Paragonimiasis, human lung fluke disease, is a foodborne anthropozoonosis caused by the trematodes assigned to Paragonimus and is regarded by the World Health Organization as a Neglected Tropical Disease (NTD). The life cycle of this medically important parasite centres on a complex freshwater biological community that includes two intermediate hosts: a mollusc and a decapod, usually a brachyuran. Although there is a perception that the biology, symptoms, diagnosis and treatment of Paragonimus is well understood, in reality, this is not the case, especially in Africa. Much remains unknown concerning the life-cycle of the parasite, its transmission, the current epidemiology of the disease, diagnosis and the effectiveness of treatment. Furthermore, cases of paragonimiasis may be misdiagnosed as resistant tuberculosis (TB) because of the similar pulmonary symptoms and no remission after anti TB therapy. The endemic foci of human paragonimiasis in Africa have been reported mainly in the forest zones of Upper Guinea (Liberia, Guinea and Ivory Coast) and Lower Guinea (Nigeria, Cameroon, Equatorial Guinea and Gabon). Despite the perceived medical importance of paragonimiasis, relatively little attention has been paid to this NTD since its discovery in Africa in the 1960s. This review focuses on the current understanding of the life cycle and transmission of Paragonimus in Africa, discusses its diagnosis and public health importance and highlights many outstanding gaps in the knowledge that still exist for this NTD.

Tuberculosis caused by resistant M. tuberculosis strains poses a serious threat as it requires prolonged and costly treatment and has high mortality rate. In order to investigate resistance to antituberculous drugs in Croatia, we analysed all resistant M. tuberculosis strains isolated from patients\' samples in period 2010-2014 (1 strain per patient). Out of 2384 M. tuberculosis strains, we identified 88 (3.69 %) resistant strains. The analysis included resistance patterns, resistance conferring mutations and, according to MIRU-VNTR analysis, clustering and global lineages distribution. Relatively high number of strains was monoresistant, especially to isoniazid, while there were only six multiresistant strains. Among 59 strains with any pattern that includes resistance to isoniazid, a total of 22 (37.29 %) had resistance conferring mutation in katG gene (S315T), 23 (38.98 %) in inhA promoter region (C-15T) and 14 (23.73 %) had none of these mutations. The observed clustering rate of resistant strains was 28.41 %, and the most common global lineage was Euro-American (75 %).

BACKGROUND: In the light of the 2010 World Health Organization estimation of 650 000 cases of multidrug-resistant tuberculosis (MDR-TB) globally, the need to develop, implement and scale up MDR-TB treatment programs is clear. The need is greatest and urgent in resource-poor countries, such as Kenya, with a high TB burden and an anticipated rise in reported cases of MDR-TB with increasing access to drug susceptibility testing.
OBJECTIVE: To describe the set-up of a community-based program, early clinical outcomes, challenges and possible solutions.
METHODS: The Moi Teaching and Referral Hospital (Moi Hospital) catchment areas: Western and North Rift Provinces, Kenya.
METHODS: Program description and retrospective chart review.
RESULTS: An MDR-TB team established a community-based program with either home-based DOT or local facility-based DOT. Following referral, the team instituted a home visit, identified and hired a DOT worker, trained family and local health care professionals in MDR-TB care and initiated community-based MDR-TB treatment. In the first 24 months, 14 patients were referred, 5 died prior to initiation of treatment and one had extensively drug-resistant TB. Among eight patients who initiated community-based DOT, 87% underwent culture conversion by 6 months, and 75% were cured with no relapse after a median follow-up of 15.5 months. Multiple challenges were experienced, including system delays, stigma and limited funding.
CONCLUSIONS: Despite multiple challenges, our model of an MDR-TB team that establishes a community-based treatment system encircling diagnosed cases of MDR-TB is feasible, with acceptable treatment outcomes.
La nécessité d’élaborer, de mettre en œuvre et d’étendre des programmes de la tuberculose multirésistante (TB-MDR) est évidente vu l’estimation en 2010 de l’Organisation Mondiale de la Santé concernant les 650 000 cas mondiaux de TB-MDR. La nécessité est la plus marquée et la plus urgente dans des pays à ressources li-mitées comme le Kenya, où le fardeau de la tuberculose (TB) est élevé et où l’on s’attend à un accroissement des cas déclarés de TB-MDR en raison de l’accessibilité croissante aux tests de sensibilité aux médicaments.
Décrire la mise en route d’un programme basé sur la collectivité, les résultats cliniques précoces, les défis et les solutions possibles.
Zone de recrutement du Moi Teaching and Referral Hospital (Moi Hospital) : Provinces de l’Ouest et du Nord Rift au Kenya.
Description du programme et révision rétrospective des dossiers.
Une équipe TB-MDR a élaboré un programme basé sur la collectivité comportant soit un traitement directement observé (DOT) basé sur la maison, soit un DOT basé sur les services locaux. Après référence, l’équipe a institué une visite domiciliaire, identifié et payé un travailleur DOT, formé la famille ainsi que les professionnels locaux de soins de santé au sujet des soins de la TB-MDR et mis en route le traitement de la TB-MDR basé sur la collectivité. Au cours des 24 premiers mois, 14 patients ont été référés. Le décès est survenu chez cinq d’entre eux avant la mise en route du traitement ; un de ceux-ci souffrait d’une TB ultrarésistante. Chez huit patients qui ont commencé le DOT basé sur la collectivité, la négativation des cultures est survenue dans les 6 mois chez 87% et la guérison a été obtenue sans rechute dans 75% des cas après un suivi médian de 15,5 mois. On a rencontré de nombreux défis, comportant les délais du système, la stigmatisation et les limitations de financement.
En dépit de défis multiples, notre modèle d’une équipe TB-MDR qui met en route un système de traitement basé sur la collectivité pour soutenir les cas diagnostiqués de TB-MDR est réalisable et obtient des résultats acceptables de traitement.
A la luz del cálculo de la Organización Mundial de la Salud de 650 000 casos de tuberculosis multidrogorresistente (TB-MDR) en el mundo, es clara la necesidad de formular, aplicar y ampliar los programas de tratamiento de esta enfermedad. Esta obligación es mayor y más apremiante en los países con escasos recursos como Kenia, donde existe una alta carga de morbilidad por TB, un incremento anticipado de los casos notificados de TB-MDR y un aumento progresivo del acceso a las pruebas de sensibilidad a los medicamentos.
Describir la puesta en marcha de un programa comunitario, definir sus desenlaces clínicos iniciales, las dificultades encontradas y proponer las soluciones posibles.
La zona de influencia del hospital universitario y de referencia Moi (Moi Hospital): las provincias del norte y del oeste del Valle del Rift en Kenia.
Se llevó a cabo una descripción del programa y un examen retrospectivo de los expedientes clínicos.
Un equipo experto en TB-MDR estableció un programa comunitario basado en la administración domiciliaria o en un centro local del tratamiento directamente observado (DOT). Tras la remisión de los pacientes, el equipo programó una visita domiciliaria, escogió y contrató a un agente DOT, capacitó a las familias y a los profesionales sanitarios locales en la atención de la TB-MDR e inició la administración del tratamiento comunitario. Durante los primeros 24 meses se remitieron 14 pacientes. Cinco pacientes fallecieron antes de comenzar el tratamiento; de los ocho pacientes que iniciaron el tratamiento DOT comunitario, el 87% alcanzó la conversión del cultivo a los 6 meses y el 75% logró la curación, sin recaída, tras un seguimiento con una mediana de 15,5 meses. Se presentaron muchos obstáculos, entre ellos los retrasos debidos al sistema, la estigmatización y la insuficiencia del financiamiento.
Pese a las múltiples dificultades, el modelo propuesto de un equipo que establezca el sistema de tratamiento comunitario de pacientes con diagnóstico de TB-MDR es factible y ofrece desenlaces clínicos aceptables.

Tuberculosis (TB) in a major health problem in the world. WHO and its partners especially, the stop TB partnership launched numerous strategies against TB especially in the 1990. Strategy DOTS (directly observed therapy short course) was launched in 1995. One main key was the direct supervision of drug intake by patients. Progress was achieved but it was insufficient. A new strategy called \"Stop TB Strategy 2006-2015\" was launched in 2006 in the context of Millennium Development Goals (MDG) elaborated by United Nations. The common goals were to halt and start to reverse the incidence of TB, reduce the prevalence and death rate by 50% compared to their level in 1990 by 2015 to eliminate TB as a public health problem by 2050. The end of 2010 marks the mid-point of the Global Plan and is an obvious time to update it and take into account actual progress with a focus on the 2015 to reach goals. So an updated Global Plan to stop TB 2011-2015, was launched. Expected progress and targets were defined for 2015, in diagnosis and treatment, in co-infection TB/HIV, in drug-resistant TB and achievements expected in new tests for diagnosis, new medications, new vaccines and new regimens with shorter duration of treatment. WHO and partners have started discussions to define the new post 2015 strategy to TB control and elimination. Risk factors (diabetes, malnutrition, tobacco smoke…) and socioeconomic factors, which are associated with TB, should be included in the new strategy to eliminate TB in 2050.