Treatment Outcomes of Short Course Regimens for Multidrug-Resistant Tuberculosis patients in Peshawar Pakistan

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Short course regimens strategies (STR) is a new strategy for treating Multidrug-Resistant tuberculosis. The current article is an important one that informs us about the Treatment Outcomes of Short Course Regimens for Multidrug-Resistant Tuberculosis patients in Peshawar Pakistan.

What is Tuberculosis (TB)

Tuberculosis (TB) is still a major public health issue around the world. A bacterium called Mycobacterium tuberculosis causes tuberculosis, which is a fatal disease (MTB). TB is under control in a few areas of the country due to ongoing efforts, but it still exists in many regions around the globe. TB is experiencing a resurgence these days in the form of drug-resistant TB (DR-TB). Multidrug-resistant tuberculosis is the most serious form of DR-TB (MDR-TB).

Mycobacterium Tuberculosis is a causative agent of TB

What is Multidrug-Resistant Tuberculosis (MDR-TB)?

MDR-TB is a type of tuberculosis that is resistant to at least two of the most powerful medications, rifampicin (RMP) and isoniazid (INH). Today, there is an emerging public health concern. DR-TB treatment is more challenging than DS-TB treatment. Despite all possible measures to combat tuberculosis, the worldwide burden of the disease remains worrying.

Prevalence of Tuberculosis (TB)

According to the World Health Organization (WHO), approximately 480,000 people develop MDR-TB each year, with 190,000 people dying from it.

Therapy for Multidrug-resistant tuberculosis (MDR-TB)

MDR-TB therapy regimens now recommended (traditional) are complicated, lengthy (at least 20 months), expensive, and poorly tolerated, with a small global treatment success rate of 52 percent. The World Health Organization (WHO) recommends the use of directly observed therapy (DOT), in which patients take medications under the direct supervision of a health care provider, to enhance adherence to anti-TB treatment. However, in resource-scarce regions with weak health infrastructure and limited access to health care, DOT is difficult and expensive to implement. The longer duration of traditional MDR-TB regimens makes DOT implementation much more difficult. It is therefore desirable to develop strategies that reduce the length of MDR-TB treatment and the frequency of dose administration while increasing efficacy and safety profiles. The most usually proposed therapy regimens are lengthy, complex, poorly tolerated, expensive, and only somewhat effective, making it difficult to choose an effective, efficient, and acceptable treatment plan. To address this problem, the WHO and other partners attempted a variety of MDR-TB treatments.

Bangladesh regimens or short-term treatment regimens for MDR TB

Short treatment regimens, also known as Bangladesh regimens, are one of the most promising therapy types, with a high success rate when compared to traditional treatments. Following this brief treatment, other countries began STR projects in their respective countries to improve treatment outcomes. Different forms of STR type treatment have been started with different types of medications in most countries now.

MDR-TB in Pakistan

Pakistan is one of the top countries on the list, coming in fourth place out of the top 22 MDR-TB countries. According to the WHO, Pakistan has an annual incidence of around 15000 MDR-TB patients, based on 4.2 percent primary resistance and 19 percent resistance in retreatment cases.

The rising prevalence of MDR and XDR-TB in Pakistan highlights the significance of efficient DR-TB treatment programs. Extensive research is urgently needed to develop efficient MDR-TB diagnosis, treatment, and control strategies, as poor adherence to treatment protocols leads to increased resistance, which manifests as XDR-TB. To enhance treatment outcomes for MDR-TB patients, it is vital to understand the risk factors that contribute to poor treatment outcomes. As a result, STR treatment for MDR-TB was started in this country in 2017.

Short treatment therapy in Lady Reading Hospital, Peshawar Khyber Pakhtunkhwa

Pakistan’s National Tuberculosis Programme (NTP) started STR for MDRTB at various hospitals across the country. In Khyber Pakhtunkhwa, STR was originally started at the Lady Reading Hospital Peshawar at the Programmatic Management of Drug-Resistant Tuberculosis (PMDT) Unit under programmatic management. LRH is one of the oldest and most successful MDR-TB treatment centres in the world. STR treatment with a length of 4-6/11 months was first started in this centre. This study was undertaken to learn about the efficacy of this treatment. Its goal was to learn about the treatment outcome of a 4-6/11 month STR treatment at this unit.

Treatment Outcomes of Short Course Regimens for Multidrug-Resistant Tuberculosis patients in Peshawar Pakistan

Study Guidelines for Short Course Regimens for Multidrug-Resistant Tuberculosis

Patients with bacteriologically proven MDR-TB were included in this retrospective cohort institutional base study conducted at PMDT–LRH. The research lasted from December 2017 through March 2020. All study cases must agree to the study’s inclusion and exclusion criteria. All treatment is offered free of charge at this facility. Treatment is provided at the current facility under WHO and NTP Pakistan recommendations. Patients got adherence counselling, nutritional support, and compensation for transportation to and from their ambulatory sessions.

Treatment Scheme for STR Therapy at Lady Reading Hospital Peshawar

Study patients were to receive an 11-months treatment regimen, with all drugs given daily throughout. An intensive phase of a minimum duration of 4-6 months with Amikacin (AM) 10–15 mg/kg, Moxifloxacin 400 mg, Ethionamide (ETH) 15–20 mg/kg, Clofazimine 100 mg, INH (High dose) 5 mg/kg, EMB 25 mg/kg and Pyrazinamide 30–40 mg/kg was followed by a fixed-duration continuation phase of 5 months with the same drugs, but omitting INH and AM and Eto 4-6 Am, Z, E, Mfx, Eto, Cfz, INH (High Dose) / 5 Z, E, Mfx, Cfz. If two consecutive sputum smears of early morning specimens at the end of the fourth month were negative, the continuation phase commenced. The intensive phase was extended up to a maximum of 2 months if either specimen was positive, as determined by the monthly sputum smear examination result. Sputum smears, cultures, and chest radiographs (CXR) were taken at the time of enrollment and subsequently monthly throughout the intensive phase of treatment, with monthly smears and bimonthly cultures and chest radiographs during the continuation phase. Patients’ medication adherence and compliance were regularly monitored by qualified treatment supporters and therapy facilitators. On monthly follow-up visits, all patients were examined for any psychological issue and drugs for his/her therapy was provided.

Data management and analysis in the STR research project

All relevant data was double-input and entered into a Microsoft Excel sheet before being transferred to SPSS version 23 for further analysis. For analysis, percentages and cross-tabulation were applied. The final results were divided into two main categories: successful treatment outcomes and unsuccessful treatment outcomes (Died, Loss to follow-up, and failure).

Results of the STR Research Project at PMDT LRH Peshawar

This study was conducted from July 2017 to Dec 2018. In this study, only those patients were enrolled who were eligible for newly assigned 11 months short treatment of MDR-TB. All those patients who achieved outcomes at the time of this final draft were included in this study. The numbers of such patients were 109. The mean age of study cases was 19.544 with a standard deviation of ±15.947. The majority of study cases (56.0%) were females. In this study cross-tabulation of BMI with age and gender was also studied. This study also showed that the majority of study cases belonged to BMI lower than 25Kg/m, of which 2 45.8% were female gender. Similarly, cases with a BMI of more than 25Kg/m were also more female as compared to the male gender. Similarly, cases in both BMIs groups were from higher age groups having age 45 to 64 years of age. Previously treatment and its outcome along with resistance pattern also play important role in the new design of short treatment courses. Among the present study, 63 cases of the study took previous TB treatment with first-line anti-TB drugs (FLDs). Among these cases, 55.5% of patients achieved successful treatment outcomes. All study cases enrolled for treatment here in PMDT LRH completed a full course of their treatment with newly designed short treatment courses. At the time of the study, these patients achieved an outcome, and about 77.1% of these cases achieved successful treatment outcomes, and the remaining 22.9% of study cases achieved unsuccessful treatment outcomes.

Discussion of newly short treatment therapy Research

DR-TB is a severe public health concern for all health authorities. To combat this problem, accurate diagnosis and appropriate treatment of DR-TB are required. Effective DR-TB care is critical not only for curing the affected population but also for preventing the spread of resistant strains. The normal prolonged treatment of MDR-TB does not produce sufficient results, necessitating the use of another type of treatment. So, to increase adherence and good outcomes for MDR-TB patients, WHO recently suggested a new shorter treatment regimen, also known as the Bangladesh regimen, which was first implemented in Bangladesh. The length of this novel STR treatment was 4–6 months for the intensive phase and 5 months for the continuation phase. Lady Reading Hospital Peshawar’s Programmatic Management of Drug-Resistant TB Unit began treating DR-TB patients in 2008 and followed the therapy role of PMDTs in 2012. PMDT LRH is one of the country’s best treatment facilities. The treatment outcomes of the enrolled patients at this location are not poor, but they may be better. As a result, in 2017, a new STR treatment was initiated to get better results. This study was designed to determine the outcomes of the first cohort of patients who began therapy in 2017. The current study is the first of its kind in this field, involving the initial cohort of patients recruited in a new short-term therapy program at PMDT LRH in Peshawar, Pakistan. The goal of this study was to find out what happened to the initial cohort at PMDT LRH. The demographic profile of the patients in this study was similar to that of Turett et al, Khan et al, and Park et al, among others. The majority of the patients in the study were females in the economically productive age range. In the study, 84 (77.1%) of patients had a favourable outcome, which is close to the aim established by the Global Plan to End Tuberculosis. This figure is lower than the 85.0 percent achieved by a Bangladeshi study, 89.0 percent by a Cameron study, and 89.0 percent by a Niger study. On the other hand, when compared to longer WHO-recommended regimens studies, such as 49 percent in a South African study, 54.9 percent in a Shanghai study, 64 percent in New York, and 48.2 percent in a South Korean report, this result is far better. One of the most important treatment indicators of MDR-TB is treatment failure (TF) which was 0.9% in the present study which is much less than internationally reported pooled rates of 11% (10-12%) for the longer MDR-TB regimen excluding XDR-TB. If we compared the results of the present study with another study conducted in the year 2015 in the same PMDT unit. Study cases of the previous study were on longer treatment regimens (LTR) whereas study cases of the present study were on newly short treatment. The baseline treatment regimen for the previous study consists of 8 Am, Cs, Eto, Lfx, Z, PAS/16 Cs, Eto, Lfx, Z, and PAS+B6 whereas the present study with STR treatment consists of 4-6 Am, Z, E, Mfx, Eto, Cfz, INH (High Dose) / 5 Z, E, Mfx, Cfz. The duration of treatment was the first fundamental difference between the two methods of treatment, and the choice of medicines was the second. LTR contains Cycloserine, Levofloxacin, and PAS, which were not present in STR, whereas Ethambutol, Isoniazid, Cfz, and Moxifloxacin were added to STR for this purpose. Injectables Amikacin, PZA, and Ethionamide were present in both forms of treatment. Both investigations came up with some interesting results. In 2015, 74.3 percent of study cases had a successful outcome in LTR treatment, whereas 77.1 percent of research cases had a successful outcome in the current study using STR treatment. Treatment failure was 5.6 percent in the LTR group and 0.9 percent in the STR group.

Rate of Unsuccessful Outcome

The death rate in the LTR treatment was 19%, while it was 13.8 percent in the STR treatment. The rate of loss to follow-up (LTFU) in the LTR group was 1.1 percent, compared to 8.3 percent in the STR group. Looking at these results, STR appears to be superior to LTR, and if the LTFU rate in STR remains lower than in LTR, the success rate in STR might reach 90%, which is a very promising and best result, and equivalent to the findings of other international level studies. During this treatment, 9 (8.3%) of the patients were diagnosed with LTFU. Two of the nine patients are Afghan nationals who were classified as LTFU after their addresses were changed. These four patients came from far-flung places and were unable to pay for their routine visits from their hamlet to the Peshawar PMDT center. Another patient relocated from Khyber Pakhtunkhwa to the Islamabad area, and according to that patient, he received treatment in Islamabad but owing to the lack of a record, he declared himself LTFU. Two of the LTFU patients experienced serious side effects after starting these medications, thus their therapy was stopped for more than two months, and they were classified as LTFU.

It is quite possible to obtain a success rate of more than 80% if we can fix concerns like adverse drug responses, improve and frequent social support, and assist disadvantaged patients. The current PMDT unit’s good outcomes in both types of treatments are superior to many other centers in the country as well as other countries. There are a variety of conceivable explanations for this accomplishment. In the PMDT LRH, the entire treatment for each patient is managed by a programmed management system. Patients were helped in this center through ambulatory care treatment. For one month, each patient and his or her treatment supporter went to the PMDT facility for a routine checkup and medication. Sputum smears, cultures, and chest radiographs (CXR) were taken at the time of enrollment and subsequently every month throughout the intense phase of treatment, with monthly smears and biweekly cultures and chest radiographs during the continuation phase. According to national DR-TB recommendations, all patients were tested for HIV at baseline, and blood tests were performed at baseline and every month. Patients’ medication adherence and compliance were regularly monitored by qualified treatment supporters and therapy facilitators. On monthly follow-up visits, all patients were examined for any drug side effects, and suitable therapy was provided.

Individual patient home visits were scheduled for contact screening, infection control measures at home, and to establish a relationship with the regional district TB officer. Adverse effects linked with second-line medications, if any, were closely monitored and controlled, with a variety of measures including counselling, the administration of supplementary drugs, and, in rare circumstances, the permanent removal of any culprit drug from the treatment regimen as a last resort. Patients were counselled to ensure that they followed their treatment plan to the letter. The World Health Organization recently made some improvements to this STR treatment and announced changes to drug-resistant tuberculosis treatment regimens. According to this recent release, STR treatment regimens now include all oral, bedaquiline-containing regimens rather than the injectable-containing standardized shorter regimen. Treatment success rates for the all-oral bedaquiline-containing regimen were 73 percent in the key analysis on which the WHO recommendation decision was based, compared to 60 percent for the standardized shorter regimen. This new adjustment in the regimen will benefit 19 people by removing the most dreadful aspect of the DR-TB regimen: injectable medicines. Aside from treatment regimens, systematic execution of shorter regimens necessitates careful attention to side effect control and infrastructure to facilitate patient adherence. As previously said, this is the first study to be done to determine the outcomes of a new STR treatment. As a result, this study is quite important and has several advantages. One of the most significant strengths of this study was that it was conducted under PMDT, which means that the results are valid and likely to be generalizable to programs in other similar settings across the country. Second, all patients were carefully monitored and treated based on their baseline DST results to rule out any possible drug mismatch. Finally, the study was able to provide significant findings for newly developed STR treatments and their impact on MDR-TB treatment.

Conclusion of Short Course Regimens Project Study at PMDT LRH Peshawar Pakistan

The current study’s findings have several clear consequences for TB control efforts. In light of these data, it is possible to conclude that improving treatment outcomes, such as guaranteeing adherence and paying special attention to the impoverished and patients who live a long distance from the treatment facility, will help to prevent DR-TB transmission in the community. Because the main problem in establishing a successful treatment outcome is the enormous number of tablets that patients must consume every day, treatment adherence is improved by delivering a brief, highly effective treatment regimen for MDR-TB. This study also found that with experience and a motivated team, achieving the highest success rate for any form of treatment is relatively simple.