Efficacy and safety of short course chemotherapy regimens in older children and adolescents with multiple and extensive drug resistant respiratory tuberculosis

The objective of the study: to evaluate the efficacy and safety of short course chemotherapy regimens for multiple/extensive drug resistant tuberculosis of the respiratory system (MDR/XDR) in older children and adolescents.Subjects and Methods. A cohort prospective controlled study (2017 to 2019) included 23 patients from 13 to 17 years old with various clinical forms of respiratory tuberculosis with multiple/extensive drug resistance.Results. In 22 out of 23 cases, the following chemotherapy regimen was used: 6 months - the intensive phase / 6 months - the continuation phase, in one patient – 3 months of the intensive phase / 9 months of the continuation phase. In 15 out of 23 cases, the chemotherapy regimens in the intensive phase, taking into account the MBT drug sensitivity test, consisted of 5 drugs, in 8 cases – of 4 drugs. During the continuation phase, all patients received 3 drugs. Of the 23 patients, 8 patients used bedaquiline in short course chemotherapy regimens: 2 – 1 course, 6 – 2 courses.Conclusion. The possibility of reducing the main course of chemotherapy for MDR/XDR TB in children and adolescents to 12 months instead of 18-24 months has been proved.

Sputum Smears Conversion in Daily Versus Intermittent Treatment Regimen in New Sputum Smear Positive Pulmonary Tuberculosis Patients - A Retrospective Study

BACKGROUND Sputum smear conversion is the negative conversion of the sputum smear at the end of the second month of treatment regimen under the National Tuberculosis Elimination Program (NTEP). When the acid-fast bacillus (AFB) smear comes negative at the end of an intensive phase, the treatment regimen can shift to the continuation phase that indicates bacillary load is a minimum. Although some authors consider the conversion of cultures when the AFB smear is negative, two potent drugs in the continuation phase are sufficient to kill the remaining bacilli. The drug that can kill bacteria in the first 2 days of treatment is called early bactericidal activity (EBA). This can be assessed by the percentage of negative conversion of cultures at the end of the intensive phase of the treatment regimen. EBA is very essential because it reduces the transmission in the community and chances of patient death. When the purpose is to kill as many bacilli as possible in the first few days and weeks of treatment, it is very important to include bactericidal drugs in the treatment regimen so that it reduces the chances of patient death and infectiousness and the negative conversion of the cultures after 2-month treatment regimen is an indication of the bactericidal capacity of the drug. The purpose of this study was to compare sputum smear conversion in daily versus intermittent treatment regimens in diagnosed cases of new sputum smear-positive pulmonary tuberculosis patients. METHODS This retrospective observational study was carried out in the Department of Respiratory medicine and nodal drug resistance tuberculosis centre (DR-TB) at the Government medical college and hospital, Akola. In this study, a total of 120 new patients were taken. 60 patients were given daily and intermittent regimens respectively under NTEP. RESULTS Out of 120 patients, 56 (93.33 %) patients in intermittent and 53 (88.33 %) patients in daily regimen were sputum smear-negative at the end of 2nd month (intensive phase) and at the end of 6th month (continuation phase). 1 patient (1.6 %) remained sputum smear-positive after the intensive phase. That patient was given 1 month of extension of anti-tuberculosis treatment (AKT) in the intensive phase and the patient became sputum negative after 1 month of extension. CONCLUSIONS It was concluded in this study, daily regimens and intermittent regimens were equally effective in negative conversion of the sputum smear at the end of the intensive phase and the end of the continuation phase. Negative conversion of the sputum smear is quite important because the bacillary load will be so low at the end of 2nd month that reduces the chances of patient death and transmission in the community. KEY WORDS Pulmonary Tuberculosis (PTB), Drug-Resistant TB (DR-TB), National Tuberculosis Programme (NTP), Revised National TB Control Program (RNTCP), Intensive Phase (IP), continuation Phase (CP), National Tuberculosis Elimination Program (NTEP).

INFLUENCE OF EARLY TERMINATION OF TREATMENT OF PATIENTS WITH TUBERCULOSIS ON ITS EFFECTIVENESS

The effectiveness of a course of chemotherapy largely depends on the continuity and duration. An ineffective outcome of a course of chemotherapy, in addition to objective reasons, also has an additional factor that strengthens it – a break in treatment or its early termination. The aim of the work is to study the effectiveness of treatment of patients with pulmonary tuberculosis with preserved drug sensitivity of the pathogen with early termination of the course of chemotherapy. Materials and methods: A retrospective analysis of the outcomes of a course of chemotherapy of tuberculosis patients who prematurely interrupted treatment, registered for 1-2-3 chemotherapy regimens in the Perm Region, was carried out. Results: Interruptions in treatment or its early termination were present in 7.8% of patients registered for treatment with 1-2-3 chemotherapy regimens. At the stage of inpatient treatment, there is a separation from treatment in 3.5% of patients receiving treatment in the intensive phase of 1-2-3 chemotherapy regimens. Separation from treatment at the outpatient stage is noted in 7.9% of patients receiving treatment in the continuation phase of 1-2-3 chemotherapy regimens, these terms are insufficient for a full course of chemotherapy.. An additional unfavorable factor of intermittent treatment is the formation of secondary drug resistance of Mycobacterium tuberculosis. The ineffectiveness of the course of chemotherapy leads to an increase in the number of patients with tuberculosis and the tension of the epidemic situation. Conclusions: In the treatment of patients with drug-sensitive tuberculosis in the Perm Region, treatment is interrupted more often at the outpatient stage than at the inpatient stage (p=0.03), which requires further study of the reasons for preventing early termination of treatment. It was found that the termination of treatment prematurely in all patients led to the ineffectiveness of CT. Social factors (lack of income, unfavorable living conditions and distance from drug dispensaries, staffing of qualified medical personnel) can affect the adherence and effectiveness of treatment.

Paradoxical immune reconstitution inflammatory syndrome in neurotuberculosis

Tuberculosis (TB) remains the most common infection in developing countries and India contributes the maximum number of cases to the global burden. Primary healthcare physicians across the country face major challenges in diagnosis and treatment of childhood TB. In this context, clinical cases of paradoxical responses to antitubercular therapy seem to be under-reported. We report a case of tubercular meningitis in an adolescent girl who belonged to a remote village. She developed a paradoxical immune response to TB while on anti-TB treatment (ATT). She presented with raised intracranial tension and neurological deficits during the continuation phase of ATT after stopping corticosteroids. The ring-enhancing lesions of tuberculomas in the brain and spine characterised the diagnosis of paradoxical response to TB. Brain biopsy suggested necrotising granulomatous disease and was negative for S100 and CD1a marker, ruling out active TB. Retreatment with a prolonged course of steroids and ATT resulted in the clinical and radiological recovery, though some motor and visual deficits persisted. Clinical risk factors and socioeconomic factors also contributed to the present state of the child.

Adherence to TB treatment remains low during continuation phase among adult patients in Northwest Ethiopia

Background Patients’ failure to adhere to TB treatment was a major challenge that leads to poor treatment outcomes. In Ethiopia, TB treatment success was low as compared with the global threshold. Despite various studies done in TB treatment adherence, little was known specifically in continuation phase where TB treatment is mainly patient-centered. This study aimed to determine adherence to TB treatment and its determinants among adult patients during continuation phase. Methods We deployed a facility-based cross-sectional study design supplemented with qualitative data to explore perspectives of focal healthcare providers. The study population was all adult (≥18 years) TB patients enrolled in the continuation phase and focal healthcare workers in TB clinics. The study included 307 TB patients from 22 health facilities and nine TB focal healthcare providers purposively selected as key-informant. A short (11 questions) version Adherence to Refill and Medication Scale (ARMS) was used for measuring adherence. Data was collected using an interviewer-administered questionnaire and in-depth interview for qualitative data. Binary logistic regression was applied to identify factors associated with patient adherence. We followed a thematic analysis for the qualitative data. The audio data was transcribed, coded and categorized into themes using OpenCode software. Results Among 307 participants, 64.2% (95% CI (58.6–69.4%) were adherent to TB treatment during continuation phase. A multi-variable analysis shown that secondary education (AOR = 4.138, 95% CI; 1.594–10.74); good provider-patient relationship (AOR = 1.863, 95% CI; 1.014–3.423); good knowledge on TB treatment (AOR = 1.845, 95% CI; 1.012–3.362) and middle family wealth (AOR = 2.646, 95% CI; 1.360–5.148) were significantly associated with adherence to TB treatment. The majority (58%) of patients mentioned forgetfulness, and followed by 17.3% of them traveling away from home without pills as major reasons for non-adherence to TB treatment. Conclusions The study indicated that patients’ adherence to TB treatment remains low during continuation phase. The patient’s education level, knowledge, family wealth, and provider-patient relationship were found positively associated with patient adherence. Forgetfulness, traveling away, and feeling sick were major reasons for non-adherence to TB treatment. Interventional studies are needed on those factors to improve patient adherence to TB treatment during continuation phase.

Case Report: Delayed treatment of tuberculosis of the elbow joint

Extrapulmonary tuberculosis (TB) is known to occur in the musculoskeletal system, including the elbow joints. These cases are rarely found because the signs and symptoms are not specific to extrapulmonary TB or other diseases. We report a case of a 24-year-old male, who complained about pain in his left elbow and noticed swelling. Initially, he complained about pain all over his left arm, after several reflexology massages to alleviate his toothache. However, instead of seeking medical treatment, he visited a traditional massage therapist every week without improvement in his left arm pain for almost one year. Examination showed skin perforation with discharge. He also had fever during the first few days when the elbow became swollen. Weight loss and a decreased appetite were also noticed by the patient. The patient went to the orthopedic department and underwent surgery. Radiological examination indicated bone erosion on the left humerus and radius, while posteroanterior chest X-ray did not show any abnormality. Histopathological examinations from biopsy and fluid aspiration showed granulomas and datia Langhans cells. Mycobacterium tuberculosis was found on acid-fast bacteria smear and culture. The patient was administered multidrug tuberculosis therapy, which consisted of two months of an intensive phase and seven months of a continuation phase, in accordance with the World Health Organization’s guidelines for extrapulmonary tuberculosis treatment. He has currently undergone the continuation phase of the treatment and his condition has improved. Early detection of tuberculosis of the elbow can prevent damage to joint structure and impairment of joint function.

Effect of a phone reminder system on patient-centered tuberculosis treatment adherence among adults in Northwest Ethiopia: a randomised controlled trial

ObjectivesThis study aimed to evaluate the effect of the phone reminder system on patient-centred TB treatment adherence during continuation phase, where patients are responsible for taking medication at home.MethodsWe conducted a two-arm randomised controlled trial on adult patients with TB during the continuation phase. In the intervention arm, patients received routine care plus phone-based weekly pill refilling and daily medication reminders. In the control arm, participants received only routine care. A covariate adaptive randomisation technique was used to balance covariates during allocation. The primary outcome was adherence to patient-centred TB treatment, and secondary outcomes included provider–patient relationship and treatment outcomes. We applied per-protocol and intention-to-treat analysis techniques.ResultsWe randomised 306 patients to intervention (n=152) and control (n=154) groups. Adherence to patient-centred TB treatment was 79% (110/139) in intervention and 66.4% (95/143) in control groups, with relative risk (RR) (95% lower CI) (RR=1.632 (1.162 to ∞); p=0.018, one tailed). Good provider–patient relationship was 73.3% (102/139) in intervention group and 52.4% (75/143) in control group, p=0.0001. TB treatment success was 89.5% (136/152) in intervention group and 85.1% (131/154) in control group, p=0.1238.ConclusionsMobile phone-based weekly refilling with daily medication reminder system improved adherence to patient-centred TB treatment and provider–patient relationship; however, there was no significant effect on treatment success.Trial registration numberPan African Clinical Trials Registry (PACTR201901552202539).

Child sexual abuse material on the darknet: a script analysis of how offenders operate

The development of online technologies in recent decades has facilitated the distribution and consumption of child sexual abuse material (CSAM) over the internet, which also led to the emergence of CSAM on the darknet—the segment of the internet hidden from the general public. Using data obtained from interviews with online investigators, this study uses crime script analysis to reconstruct step-by-step how offenders operate on the darknet. The findings highlight the three phases of the script: (1) the crime set-up phase, (2) the crime completion phase, and (3) the crime continuation phase. Scripting is a practical method of developing concrete ways to address this problem. The implications of using crime scripts to fight CSAM are discussed.

Hospitalizations and Treatment Outcomes in Patients with Urogenital Tuberculosis in Tashkent, Uzbekistan, 2016–2018

Despite the global shift to ambulatory tuberculosis (TB) care, hospitalizations remain common in Uzbekistan. This study examined the duration and determinants of hospitalizations among adult patients (≥18 years) with urogenital TB (UGTB) treated with first-line anti-TB drugs during 2016–2018 in Tashkent, Uzbekistan. This was a cohort study based on the analysis of health records. Of 142 included patients, 77 (54%) were males, the mean (±standard deviation) age was 40 ± 16 years, and 68 (48%) were laboratory-confirmed. A total of 136 (96%) patients were hospitalized during the intensive phase, and 12 (8%) had hospital admissions during the continuation phase of treatment. The median length of stay (LOS) during treatment was 56 days (Interquartile range: 56–58 days). LOS was associated with history of migration (adjusted incidence rate ratio (aIRR): 0.46, 95% confidence interval (CI): 0.32–0.69, p < 0.001); UGTB-related surgery (aIRR: 1.18, 95% CI: 1.01–1.38, p = 0.045); and hepatitis B comorbidity (aIRR: 3.18, 95% CI: 1.98–5.39, p < 0.001). The treatment success was 94% and it was not associated with the LOS. Hospitalization was almost universal among patients with UGTB in Uzbekistan. Future research should focus on finding out what proportion of hospitalizations were not clinically justified and could have been avoided.

Treatment Compliance of Multidrug Resistant Tuberculosis in Uzbekistan: Does Practice Follow Policy?

Compliance with treatment guidelines is essential to achieve successful outcomes in tuberculosis patients. Thus, we assessed if multidrug-resistant tuberculosis treatment practices from 2012–2018 in Uzbekistan were compliant with national guidelines in terms of regimens prescribed, weight-based drug dosages used, and documentation of treatment changes (such as prolongation of intensive phase, change of drugs, and their reasons) in the treatment card and Consilium form. A total of 1481 patients were included. Of them, only 25% received standardized regimens as per guidelines and the remaining received individualized regimens. There was an increasing trend in using standardized regimens from 2% in 2012 to 44% in 2018. Compliance to recommended weight-based drug dosages was observed in 85% of the patients during the intensive phase and 84% in the continuation phase—ranged 71–91% over the years. Prolongation of the intensive phase was done in 42% of patients. The treatment was changed in 44% of patients during the intensive phase and 34% of patients during the continuation phase. The documentation of treatment changes was suboptimal (42–75%) during the initial years (2012–2014); however, it improved significantly during later years (86–100%). Future research should explore reasons for non-compliance so that the quality of patient care can be improved.