Resistant Forms Of Tuberculosis Research Articles

�˲Ͳ�Ͳ, �����̲�Ͳ �� �������ò�Ͳ ���������Ҳ ������������ ������ �� ˲�������� �Ҳ�ʲ��� �� ղ���ò���� ˲��������

Tuberculosis (TB) remains a global medical problem and is one of the leading causes of death from infectious diseases worldwide. One of the main factors preventing successful control of the infection is the progressive increase in cases of drug-resistant TB. In order to increase the effectiveness of treatment of patients with resistant forms of TB, more and more attention is paid to a complex approach in the treatment of such patients, using surgical methods of treatment. The aim of the work is to determine and compare the clinical and pathological characteristics of pulmonary tuberculosis with different grade of drug resistance to antituberculosis drugs and additional surgical treatment. Materials and methods. This was a cohort retrospective study, which enrolled 49 patients with different clinical forms of pulmonary TB and defined antituberculosis drug resistance profile (MDR-TB or pre-XDR-TB groups according to the the results of drug susceptibility test). The 1-st group included MDR-TB cases (n=25) and the 2-nd group � pre-XDR-TB cases (n=24). The 1-st group consisted of 15 men and 10 women, 2nd group � 10men and 14 women, respectively. The mean age of patients in both groups was approximately the same: 32.2�2.3 years in grouo 1, and 30.6�1.8 years in group 2. Surgery was performed after completion of a standardized 6-month or individualized chemotherapy. Clinical-morphological forms of pulmonary TB were determined based on a comprehensive analysis of the results of chest X-ray, macroscopic examination of the operative material and histological examination of the affected tissue. Morphological signs determined the activity of a specific inflammatory process during histological examination. Results. The clinical-morphological forms of pulmonary TB were established in both groups based on radiological and pathomorphological examination data and a comparative analysis between the groups was carried out. Fibro-caseous TB was diagnosed almost three times more often in the group with pre-XDR-TB by chest X-ray examination. Single or multiple tuberculomas, on the contrary, were 2 times more common in the MDR-TB group. Regardless of the resistance profile, the most common surgical intervention was a resection of a segment or several segments of the lung (77.5 % of cases). The forms of pulmonary tuberculosis established by means of radiological and morphological examination were compared. In MDR-TB group, complete coincidence of diagnosis occurred in 19 out of 25 cases (76.0 %). In pre-XDR-TB group, complete agreement of radiological and morphological diagnosis observed in 11 out of 24 cases (45.8 %). Moreover, the diagnosis of tuberculoma in both groups most often coincided. In cases with pre-XDR-TB, tuberculosis mycobacteria were detected by the cultural method in the operative material almost 2 times more often. In both groups, morphological signs of high or moderate activity of specific inflammation were observed in 70�80 % of cases. Conclusions. In cases of MDR-TB, progression of specific inflammation persisted in 32 %, and in cases of pre-XDR-TB � in 21 %, respectively. Stabilization of the process before surgical treatment was established in almost half of the cases of both MDR-TB (48.0 %) and pre-XDR-TB (50.0 %) groups. Only in 20-29 % of cases was the regression of a specific process was registared. Regardless of the drug-resistant profile, different forms of pulmonary TB were presented in both study groups. Thus, just a complex of clinical and morphological examinations makes can objectively determine the form of pulmonary tuberculosis and the grade of morphological activity of specific inflammation at the time of surgical intervention. Key words: drug-resistant pulmonary tuberculosis, clinical-morphological forms, surgical treatment, histological examination.

RESTRICTED PROTEOLIS AND OXIDIZING MODIFICATION OF PROTEINS IN HEPATOCYATES OF PATIENTS WITH DIABETES AND TUBERCULOSIS

Objective: The objective of the work is to investigate the oxidative modification of proteins and limited proteolysis in hepatocytes in patients with diabetes and pulmonary tuberculosis. Design and method: A prospective pathomorphological study of 60 cases of death of patients who died of various causes, in which in the final clinical and pathologoanatomical diagnosis as the main disease appeared pulmonary tuberculosis. Depending on clinical forms and variants of tuberculosis, the main group was divided into three subgroups. Results: An important role in the pathogenesis of the formation of both diabetes mellitus and tuberculosis play an impairment of immune homeostasis, especially in patients with expressive symptoms of exacerbation of the disease and prolonged relapse. Oxidative stress leads to an increase in the production of active forms of oxygen and as a consequence - oxidation modification of proteins (OMB): their aggregation and fragmentation, which is accompanied by irreversible changes in the physical, chemical and biological properties of the protein molecule. Taking into account the different functional activity of hepatocytes of different zones of the acinus (according to Rappoport) according to their own research, the R / B coefficient (specific coloration on acid and main proteins for Michel Calvo) and average values of relative units of optical density of a specific color on the free amino group of proteins for A. Yasuma and T. Ichikava were determined separately in the hepatocytes of the first, second and third zones and established the linear nature of the increase in the intensity of the oxidative modification of proteins and limited proteolysis from the 1st to the 3rd zone (from peripartal to centrolobular branches of acinus) in patients with resistant forms of tuberculosis. Conclusions: Diabetes mellitus in patients with lung tuberculosis leads to increased processes of free radical oxidation of proteins with characteristic effects - increased proteolysis and oxidation of amino groups of proteins – in hepatocytes of the liver.

Unraveling Major Proteins of Mycobacterium tuberculosis Envelope

Abstract: Although treatable, resistant form of tuberculosis (TB) has posed a major impediment to the effective TB control programme. As the Mycobacterium tuberculosis cell envelope is closely associated with its virulence and resistance, it is very important to understand the cell envelope for better treatment of causative pathogens. Cell membrane plays a crucial role in imparting various cell functions. Proteins being the functional moiety, it is impossible to characterize the functional properties based on genetic analysis alone. Proteomic based research has indicated mycobacterial envelope as a good source of antigens/proteins. Envelope/membrane and associated proteins have an anticipated role in biological processes, which could be of vital importance to the microbe, and hence could qualify as drug targets. This review provides an overview of the prominent and biologically important cell envelope and highlights the different functions offered by the proteins associated with it. Selective targeting of the mycobacterial envelope offers an untapped opportunity to address the problems associated with the current drug regimen and also will lead to the development of more potent and safer drugs against all forms of tuberculous infections.

Experience of primary thoracoplastics in the treatment of resistant tuberculosis of the lungs

Objective — to present the own results of the use of extrapleural thoracoplasty (ET) for the treatment of resistant pulmonary tuberculosis.
 Materials and methods. A retrospective analysis of the results of the use of extraleural thoracoplasty (EPTP) in patients with multidrug-resistant pulmonary tuberculosis and tuberculosis with extensively drug resistance, operated in the NIFP clinic of NAMNS in the period from 01.01.2004 to 01.07.2022 was conducted. Patients were divided into two clinical groups: the main — 28 patients who underwent a modified EPTP technique, and the control group — 13 patients who underwent EPTP according to the traditional Bogush technique. When evaluating the results of surgical treatment, each group was divided into subgroups according to the resistance profile of Mycobacterium tuberculosis: A — patients with multidrug-resistant pulmonary tuberculosis, B — patients with tuberculosis with extensively drug resistance. Male patients predominated in both groups. The age range of patients is from 21 to 44 years. The groups did not differ statistically significantly in terms of mean age. Operative treatment was more often performed on the right side. The duration of the period from the onset of the disease to the operation varied from 16 to 60 months (main group — (24.6 ± 1.1) months, control group — (22.8 ± 2.6) months).
 Results and discussion. Extrapleural thoracoplasty (EPTP) is a rather traumatic surgical intervention with a significant cosmetic defect and certain functional losses. Recently, such operations are performed less often, thanks to the development of new schemes of anti-tuberculosis therapy, and the associated better outcome of treatment of patients with resistant forms of tuberculosis. But if there are indications, the use of EPTP makes it possible to achieve results unattainable when using only conservative treatment. When performing EPTP, a complex of preoperative preparation measures, operational and technical features of the modified EPTP technique, measures to prevent postoperative complications and recurrences of TV was developed, which allowed to improve the results of surgical treatment in patients of the main group compared to the control group by 12.9 and 11.8 % and reduce the level of postoperative mortality.
 Conclusions. Performing EPTP, in the presence of widespread forms of tuberculosis, when it is not possible to perform resection interventions, is the method of choice, which allows improving the effectiveness of treatment of this category of patients.

ИЗУЧЕНИЕ РЕЗИСТЕНТНОСТИ К ПРОТИВОТУБЕРКУЛЕЗНЫМ СРЕДСТВАМ У БОЛЬНЫХ, НАХОДЯЩИХСЯ НА СТАЦИОНАРНОМ ЛЕЧЕНИИ В ОТДЕЛЕНИИ РЕЗИСТЕТНЫХ ФОРМ ТУБЕРКУЛЕЗА ЛЕГКИХ

A comparative study of resistance to anti-tuberculosis drugs in patients with newly diagnosed pulmonary tuberculosis and in patients with chronic forms of tuberculosis who were treated in an anti-tuberculosis hospital was carried out. We examined 142 patients treated in the department of resistant forms of tuberculosis. A complete bacteriological study of sputum for Mycobacterium tuberculosis was carried out with the determination of sensitivity to anti-tuberculosis drugs during the cultivation of microorganisms on a liquid nutrient medium in a system with automated registration of bacterial growth and on a dense nutrient medium of Lowenstein-Jensen using the method of absolute concentrations. Methods of PCR analysis were also used. According to the anamnesis, two groups of patients were formed: 82 patients with newly diagnosed tuberculosis and 60 patients with a chronic course of the disease or with a relapse of the disease. According to the age structure, patients under the age of 50 prevailed in both groups. At the same time, in the first group there was a significant number of patients aged 18-29 years - 20.7%. In the second group, the number of patients aged 18-29 years was significantly less - 5%. Despite the fact that all patients were assigned to the category of multidrug-resistant pathogen and were treated in the unit of resistant forms of tuberculosis, it was important to assess the level of Mycobacterium tuberculosis resistance separately for patients in each of the selected groups. The largest differences between groups were found in the assessment of second-line drug resistance. Patients of the second group showed high resistance to fluoroquinolones - 30% and amikacin - 41.6%. In patients with newly diagnosed pulmonary tuberculosis (first group), resistance to fluoroquinolones was 9.7%, and to amikacin - 17.1%. Capreomycin was the most effective in both groups. The resistance of the causative agent of tuberculosis in patients of the first group was 4.9%, in the second - 11.6%.

PARTICULAR QUALITIES OF THE PROTEOLYTIC SYSTEM IN PATIENTS WITH TUBERCULOSIS DEPENDING ON THE SENSITIVITY OF THE PATHOGEN

The aim: Studying the features of the proteolytic system in patients with tuberculosis depending on the sensitivity of the pathogen. Materials and methods: In the course of the research we studied the level of elastase in the blood of 111 patients. The first group consisted of 66 (59.5%) people with pulmonary tuberculosis (39 were sensitive to antibacterial drugs, 27 were resistant). The second group included 13 (11.7%) patients with tuberculous pleurisy. The third group consisted of 32 (28.8%) patients with dual localization of the process (pulmonary tuberculosis and pleural tuberculosis). Results: The level of neutrophil elastase in patients with tuberculous pleurisy (253.2 nmol / min • ml) was 2.2 times higher than in patients with sensitive pulmonary tuberculosis (110.1 nmol / min • ml) and higher than in patients with resistant pulmonary tuberculosis 3.0 times. In combined pulmonary and pleural tuberculosis (third group) the level of elastase was 1.6 times higher than in pulmonary tuberculosis (176.9 nmol / min • ml)) (p <0.01), but lower than in pleurisy in 1, 4 times. In sensitive combined tuberculosis (lungs and pleura) the level of NE was 1.5 times higher than in patients of subgroup 1a (p <0.01) and 1.4 times lower than in patients with tuberculous pleurisy (p <0.01 ). Conclusions: The highest level of elastase in tuberculous pleurisy can be explained by its increased production, contributes to increased "permeability" of the pleural sheets and the accumulation of pleural effusion. In resistant forms of tuberculosis, the immune response in the form of the activity of the proteolytic system, which is lower than in sensitive forms, can be explained by the exhaustion of the immune system under the influence of aggressive tuberculosis. The above can be associated with both the weakening of the patient's body and the aggressiveness of the pathogen.

Exploring the Potential Inhibition of Candidate Drug Molecules for Clinical Investigation Based on their Docking or Crystallographic Analyses against M. tuberculosis Enzyme Targets.

Tuberculosis (TB) is a devastating disease responsible for millions of humans' deaths worldwide. It is caused by a mycobacterial organism, the tubercle bacillus or Mycobacterium tuberculosis. Although TB can be treated, cured and can be prevented if patients take prescribed medicines, scientists have never come close to wiping it out due to a sharp rise in the incidence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) mycobacterium strains. Due to long regimen treatment and emergence of MDR and XDR-TB, it is urgent to re-engineer and reposition old drugs for developing new antimycobacterial entities with novel mechanisms of action to achieve effective TB control even against the resistant forms of TB. To combat the dreadful MDR and XDR-TB, potential targets are being extensively searched for the last couple of years for the design and discovery of active potential antitubercular chemotherapeutics. To explore the disease virulence, potential new tubercular target enzymes such as InhA, MmpL3, ATP synthase, DprE1, QcrB and MenA have been taken into consideration in the present study and the structure-based design of the corresponding target inhibitors which are under clinical investigation has been attempted to identify structural features for the discovery of new chemical entities (NCEs) having specificity towards MDR and XDR Mycobacterium tuberculosis (M. tuberculosis).

Solution NMR Studies of CYP121 of Mycobacterium tuberculosis; Evidence that Ligand Binding is Bi‐modal

Mycobacterium tuberculosis (Mtb) is the causative pathogen in the development of tuberculosis (TB). The rise of multi‐drug resistant forms of TB, combined with the fact that one third of the world’s population are carriers of latent TB, underscores the need for the development of novel anti‐TB agents. A current drug target is the cytochrome P450 (CYP) 121 of Mtb; an essential enzyme that mediates an unusual phenol coupling reaction of the dipeptide di‐cyclotyrosine (cYY). Our current understanding of atomic level active site/inhibitor interactions in CYP121 stems primarily from co‐crystallization of drug fragments or cYY with the enzyme. However, these studies result in protein structures that reflect the same unchanging conformation, thus resulting in a gap in our understanding of dynamic active site/ligand interactions that would otherwise help inform specificity in the design of novel CYP121 inhibitors.In this preliminary work, we’ve begun to address this gap by adapting CYP121 for analysis by solution NMR. The enzyme produces a well‐dispersed, resolvable 1H‐15N HSQC spectrum. We have acquired 2D spectra of the enzyme while bound to a variety of azoles representing a range of ligand sizes and chemistry. We report that, while ligands with a similar overall structure (econazole and miconazole) produce similar perturbations of the NMR spectra, other ligands with distinct overall structures (ketoconazole and fluconazole) produce chemical shift perturbations that are unexpectedly similar to each other, yet can be categorized separately from other ligand‐induced changes. These preliminary studies suggest that ligand binding in CYP121 is partially bi‐modal, indicative of a structure that retains a semi‐rigid backbone in solution. This work lays the foundation for understanding CYP121 dynamics that will be a critical component of future drug design of novel anti‐TB agents.Support or Funding InformationResearch supported by start‐up funds at SUNY BuffaloA backbone amide resonance of CYP121 in response to azole bindingFigure 1

Limited proteolysis and oxidative modification of proteins in the hepatocytes of patients with resistant forms of tuberculosis

Abstract The aim of this paper was to evaluate the oxidative modification of proteins and limited proteolysis in the hepatocytes of patients with resistant forms of pulmonary tuberculosis (TB). Material and method: This is a prospective pathomorphological study of 60 patients with confirmed pulmonary TB (clinically and anatomopathologically) deaths from various causes. To evaluate the intensity of free radical processes in hepatocytes, we used a methodology developed by Davydenko IS, 2003. Histological sections were stained with bromphenol blue by Michel-Calvo. Results: When comparing the digital data indicated in our study, it is evident that changes in proteins properties in average tendencies run virtually identically in the hepatocytes of different zones of the comparison group. Thus, the difference is unlikely (p &gt; 0.05) when comparing red/blue ratio (specific staining of acid and basic proteins by Michel-Calvo) in the hepatocytes of zones I, II and III of the comparison group. A similar trend is observed in the analysis of average values of the optical density of a specific colouration on the free amino group of proteins by A. Yasuma and T. Ichikava. The analysis of all parameters showed a linear increase in the intensity of oxidative protein modification and limited proteolysis from zone I to III (from the periportal to the centrolobular parts of the acinus) in all subgroups of the main group according to the acinus zone (by Rappoport). Conclusions: Pulmonary TB leads to increased processes of free radical oxidation of proteins with characteristic effects – increased proteolysis and oxidation of amino groups of proteins – in the hepatocytes of the liver.

Features of lethal cases in patients with TB/HIV co-infection depending on the resistance to antituberculosis agents in the conditions of the antituberculosis dispensary

Purpose of the study. Analyze lethal cases in patients with the TB/HIV co-infection depending in resistance to anti-TB drugs in the conditions of the antituberculosis dispensary.&#x0D; Materials and methods. Retrospective analysis was conducted 80 histories and autopsy reports of patients with TB /HIV infection who died in the MI «Zaporizhzhya Regional Anti Tuberculosis Clinical Dispensary» from 2012–2017.&#x0D; Results. In patients with chemoresistant forms, disseminated tuberculosis was in 36 patients (90%), infiltrative tuberculosis was noted in 2 cases, focal and fibrosis and cavernous – one person each. In the disseminated processes, in addition to the lungs, intranuclear lymph nodes were more often affected – 19 (47,5%), meningoencephalitis – 9 (22,5%), pleurisy –&#x0D; 9 (22,5%), retroperitoneal lymphnodes 2 (5,0%), peripheral lymphnodes – 2 (5,0%), lesions of the spleen – 2 (5,0%), kidneys – 2 (5,0), intestine – 1 (2,5%). In patients with susceptible tuberculosis, pulmonary and extrapulmonary lymph nodes are found in 36 (90.0%), only extrapulmonary – 4 (10,0%). These were pulmonary disseminated processes, including miliary forms. In addition to the lungs, intrathoracic lymph nodes were more often affected in 16 patients (40,0%), in 14 (35,0%) cases there was TB meningoencephalitis, Objective mesenteric lymphnodes – 4 (10,0%), spleen – 3 (7,5%), kidneys – 3 (7,5%), liver – 3 (7,5%), brain tuberculoma –1(2,5%).&#x0D; Conclusions. Inconducting a comparative analysis of clinical and pathoanatomical diagnoses in patients with susceptible tuberculosis there was only one case in which a patient with brain tuberculoma had not been diagnosed with purulentnecrotizing pneumonia of the upper lobe of the right lung. In patients with resistant forms of tuberculosis in all cases there was a coincidence of diagnoses. The main secondary diagnosis was cryptococcal meningoencephalitis – 8 (20,0%), oncopathology – 2 (5,0%).

The prevalence of chronic pancreatitis in patients with the first diagnosed pulmonary tuberculosis

Despite the reduction in the incidence of tuberculosis, the side effects of antimycobacterial drugs limit the conduction of a complete chemotherapy. They often develop upon comorbid pancreatic lesion.&#x0D; Analysis has shown that chronic pancreatitis is observed in 22.2% of cases. It is found that lesions of the pancreas occur 1.7 times more often in patients with resistant forms of tuberculosis than in patients with more sensitive forms.&#x0D; Lack of proper attention to comorbidity from hepato-pancreatic-biliary system leads to the development of adverse reactions to tuberculosis treatment, which in the future may lead to a temporary cancellation of antituberculous drugs, development of drug resistance and ineffective treatment.&#x0D;

Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis.

Given the ability of M. tuberculosis to survive as an intracellular pathogen and its propensity to develop resistance to the existing antituberculosis drugs, its treatment requires new approaches. Here the antimycobacterial properties of verapamil, thioridazine, chlorpromazine, flupenthixol and haloperidol were investigated against a panel of drug resistant M. tuberculosis strains, both in vitro and on human-infected macrophages. These compounds are efflux inhibitors that share among them the characteristic of being ion channel blockers. In vitro, all compounds exhibited synergistic inhibitory activities when combined with isoniazid and rifampicin, and were able to inhibit active efflux, demonstrating their role as efflux inhibitors. Gene expression analysis showed that M. tuberculosis efflux genes were overexpressed in response to antibiotic exposure, in vitro and within macrophages, irrespective of their resistance pattern. These compounds displayed a rapid and high killing activity against M. tuberculosis, associated with a decrease in intracellular ATP levels demonstrating that the bactericidal action of the ion channel blockers against M. tuberculosis clinical strains is associated with their interference with energy metabolism. The compounds led to a decrease in the intracellular mycobacterial load by increasing phagosome acidification and activating lysosomal hydrolases. The results presented in this study enable us to propose the following mechanism of action for these compounds: a) in the bacteria, the compounds generate a cascade of events involving the inhibition of the respiratory chain complexes and energy production for efflux activity. Indirectly, this reduce the resistance level to antituberculosis drugs potentiating their activity; b) on the host cell, the treatment with the ion channel blockers increases phagosome acidification and induces the expression of phagosomal hydrolases, leading to bacterial growth restriction irrespective of their resistance pattern. This work highlights the potential value ion channel blockers as adjuvants of tuberculosis chemotherapy, in particular for the development of new therapeutic strategies, with strong potential for treatment shortening against drug susceptible and resistant forms of tuberculosis. Medicinal chemistry studies are now needed to improve the properties of these compounds, increasing their M. tuberculosis efflux-inhibition and killing-enhancement activity and reduce their toxicity for humans, therefore optimizing their potential for clinical usage.

Directly Observed Treatment Strategy Still a Challenge in Tuberculosis Control: The South African Plight

The challenges in the management of tuberculosis (TB) are clearly manifested by the escalating numbers of not only the ordinary tuberculosis but also the drug resistant forms of TB, namely MDR-(Multi-Drug Resistance) and XDR-TB (Extreme Drug Resistance-Tuberculosis). The management of tuberculosis in SA and the whole world has been ranked as a priority due to its impact on health and economy. The effectiveness of Directly Observed Treatment Strategy (DOTS) as a strategy for the control of TB and its treatment is affected by a variety of socioeconomic issues around the world and particularly in the developing countries. This study was conducted to highlight the challenges faced by the country in the control tuberculosis even in the implementation of the directly observed treatment strategy.

Tuberculosis in children perinatally exposed to HIV in the current epidemiological TB context

Method During 01.01.2011 -01.07.2014 in the Immunocompromised Children Department from the National Institute for Infectious Diseases “Prof. Dr. Matei Bals” we analyzed the dynamical evolution of 214 perinatally HIV exposed children, aged 0-4 years. Lack of vaccination due to prematurity and the degree of immunosuppression in maternity contributed considerably to the increased incidence of TB in the family’s epidemiological context (at least one family member is diagnosed with tuberculosis). A troubling aspect is that these children come from families with resistant forms of tuberculosis (TB MDR) due to their parents’ poor adherence to treatment, mainly those pertaining to the 1989-1993 HIV cohort in Romania.

Spectinamides: a challenge, a proof, and a suggestion

New drugs and shorter regimens are needed to fight resistant forms of tuberculosis. Screening of chemical libraries for mining hit compounds is the common approach to find new antituberculars. A new medicinal chemistry and biology directed research rational has recently been successfully described by Lee and coworkers in Nature Medicine.

Tuberculosis of the spine 2011 update

Tuberculosis of the spine has been the most common extra-pulmonary manifestation. There is however a growing emergence of the resistant forms of tuberculosis in the recent years with its management problems. The accountability of emerging drug resistance rests on the managing health care clinician. This is increasingly a man made issue. With increasing awareness and appropriate laboratory facilities a methodical approach can successfully treat this growing menace. This present article reviews the recent updates in the management of this common problem.

P160 Treating TB patients with no entitlement to social support—welcome to the social jungle

BackgroundIn the UK, TB medication is free but access to additional resources necessary for treatment completion is conditional. Patients with no recourse to public funds (NRPF), including undocumented and some...

Using a decision support systems computer simulation model to examine HIV and tuberculosis: the Russian Federation

The aim of this paper is to describe the development and use of a computer simulation model that can be used as a Decision Support System (DSS) to tackle the critical public health issues of HIV and HIV-related tuberculosis in the Russian Federation. This country has recently witnessed an explosion of HIV infections and a worrying spread of the Multi-Drug Resistant form of Tuberculosis (MDRTB). The conclusions drawn are that a high population coverage with Highly Active Anti-Retroviral Treatment (HAART) (75% or higher), allied with high MDRTB cure rates, reduces cumulative deaths by 60%, with limited impact below this level. This research offers a simulation model that can be applied as a DSS by public health officials to inform policy making. By doing so, ways of controlling the spread of HIV and MDRTB and reduce mortality from these serious public health threats is provided.