Data-driven identification of previously unrecognized communities with alarming levels of tuberculosis infection in the Democratic Republic of Congo.

When access to diagnosis and treatment of tuberculosis is disrupted by poverty or unequal access to health services, marginalized communities not only endorse the burden of preventable deaths, but also suffer from the dramatic consequences of a disease which impacts one's ability to access education and minimal financial incomes. Unfortunately, these pockets are often left unrecognized in the flow of data collected National tuberculosis reports, as localized hotspots are diluted in aggregated reports focusing on notified cases. Such system is therefore profoundly inadequate for identifying these marginalized groups, which urgently require adapted interventions. We computed an estimated incidence-rate map for the South-Kivu province of the Democratic Republic of Congo, a province of 6.3 million inhabitants, leveraging available data including notified incidence, level of access to health care and exposition to identifiable risk factors. These estimations were validated in a prospective multi-centric study. We could demonstrate that combining different sources of openly-available data allows to precisely identify pockets of the population which endorses the biggest part of the burden of disease. We could precisely identify areas with a predicted annual incidence of > 1%, a value three times higher than the national estimates. While hosting only 2.5% of the total population, we estimated that these areas were responsible for 23.5% of the actual tuberculosis cases of the province. The bacteriological results obtained from systematic screenings strongly correlated with the estimated incidence (r=0.86), and much less with the incidence reported from epidemiological reports (r=0.77), highlighting the inadequacy of these reports when used alone to guide disease control programs.

Costs of TB services in India (No 1)

BACKGROUND: There is a dearth of economic analysis required to support increased investment in TB in India. This study estimates the costs of TB services from a health systems´ perspective to facilitate the efficient allocation of resources by India´s National Tuberculosis Elimination Programme.METHODS: Data were collected from a multi-stage, stratified random sample of 20 facilities delivering TB services in two purposively selected states in India as per Global Health Cost Consortium standards and using Value TB Data Collection Tool. Unit costs were estimated using the top-down (TD) and bottom-up (BU) methodology and are reported in 2018 US dollars.RESULTS: Cost of delivering 50 types of TB services and four interventions varied according to costing method. Key services included sputum smear microscopy, Xpert® MTB/RIF and X-ray with an average BU costs of respectively US$2.45, US$17.36 and US$2.85. Average BU cost for bacille Calmette-Guérin vaccination, passive case-finding, TB prevention in children under 5 years using isoniazid and first-line drug treatment in new pulmonary and extrapulmonary TB cases was respectively US$0.76, US$1.62, US$2.41, US$103 and US$98.CONCLUSION: The unit cost of TB services and outputs are now available to support investment decisions, as diagnosis algorithms are reviewed and prevention or treatment for TB are expanded or updated in India.

Active Case Finding for Tuberculosis in India: A Syntheses of Activities and Outcomes Reported by the National Tuberculosis Elimination Programme

India launched a national community-based active TB case finding (ACF) campaign in 2017 as part of the strategic plan of the National Tuberculosis Elimination Programme (NTEP). This review evaluated the outcomes for the components of the ACF campaign against the NTEP’s minimum indicators and elicited the challenges faced in implementation. We supplemented data from completed pretested data proformas returned by ACF programme managers from nine states and two union territories (for 2017–2019) and five implementing partner agencies (2013–2020), with summary national data on the state-wise ACF outcomes for 2018–2020 published in annual reports by the NTEP. The data revealed variations in the strategies used to map and screen vulnerable populations and the diagnostic algorithms used across the states and union territories. National data were unavailable to assess whether the NTEP indicators for the minimum proportions identified with presumptive TB among those screened (5%), those with presumptive TB undergoing diagnostic tests (>95%), the minimum sputum smear positivity rate (2% to 3%), those with negative sputum smears tested with chest X-rays or CBNAAT (>95%) and those diagnosed through ACF initiated on anti-TB treatment (>95%) were fulfilled. Only 30% (10/33) of the states in 2018, 23% (7/31) in 2019 and 21% (7/34) in 2020 met the NTEP expectation that 5% of those tested through ACF would be diagnosed with TB (all forms). The number needed to screen to diagnose one person with TB (NNS) was not included among the NTEP’s programme indicators. This rough indicator of the efficiency of ACF varied considerably across the states and union territories. The median NNS in 2018 was 2080 (interquartile range or IQR 517–4068). In 2019, the NNS was 2468 (IQR 1050–7924), and in 2020, the NNS was 906 (IQR 108–6550). The data consistently revealed that the states that tested a greater proportion of those screened during ACF and used chest X-rays or CBNAAT (or both) to diagnose TB had a higher diagnostic yield with a lower NNS. Many implementation challenges, related to health systems, healthcare provision and difficulties experienced by patients, were elicited. We suggest a series of strategic interventions addressing the implementation challenges and the six gaps identified in ACF outcomes and the expected indicators that could potentially improve the efficacy and effectiveness of community-based ACF in India.

Trends in incidence and mortality of tuberculosis in India over past three decades: a joinpoint and age–period–cohort analysis

Background Tuberculosis, as a communicable disease, is an ongoing global epidemic that accounts for high burden of global mortality and morbidity. Globally, with an estimated 10 million new cases and around 1.4 million deaths, TB has emerged as one of the top 10 causes of morbidity and mortality in 2019. Worst hit 8 countries account for two thirds of the new TB cases in 2019, with India leading the count. Despite India's engagement in various TB control activities since its first recognition through the resolution passed in the All-India Sanitary Conference in 1912 and launch of first National Tuberculosis Control Programme in 1962, it has remained a major public health challenge to overcome. To accelerate progress towards the goal of ending TB by 2025, 5 years ahead of the global SDG target, it is imperative to outline the incidence and mortality trends of tuberculosis in India. This study aims to provide deep insights into the recent trends of TB incidence and mortality in India from 1990 to 2019. Methods This is an observational study based on the most recent data from the Global Burden of Disease (GBD) Study 2019. We extracted numbers, age-specific and age-standardized incidence and mortality rates of Tuberculosis for the period 1990–2019 from the Global Health Data Exchange. The average annual percent change (AAPC) along with 95% Confidence Interval (CI) in incidence and mortality were derived by joinpoint regression analysis; the net age, period, and cohort effects on the incidence and mortality rates were estimated by using Age–Period–Cohort model. Results During the study period, age-standardized incidence and mortality rates of TB in India declines from 390.22 to 223.01 and from 121.72 to 36.11 per 100,000 population respectively. The Joinpoint regression analysis showed a significant decreasing pattern in incidence rates in India between 1990 and 2019 for both male and female; but larger decline was observed in case of females (AAPC: − 2.21; 95% CI: − 2.29 to − 2.12; p < 0.001) as compared to males (AAPC: − 1.63; 95% CI: − 1.71 to − 1.54; p < 0.001). Similar pattern was observed for mortality where the declining trend was sharper for females (AAPC: − 4.35; 95% CI: − 5.12 to − 3.57; p < 0.001) as compared to males (AAPC: − 3.88; 95% CI: − 4.63 to − 3.11; p < 0.001). For age-specific rates, incidence and mortality rates of TB decreased for both male and female across all ages during this period. The age effect showed that both incidence and mortality significantly increased with advancing age; period effect showed that both incidence and mortality decreased with advancing time period; cohort effect on TB incidence and mortality also decreased from earlier birth cohorts to more recent birth cohorts. Conclusion Mortality and Incidence of TB decreased across all age groups for both male and female over the period 1990–2019. The incidence as well as mortality was higher among males as compared to females. The net age effect showed an unfavourable trend while the net period effect and cohort effect presented a favourable trend. Aging was likely to drive a continued increase in the mortality of TB. Though the incidence and mortality of tuberculosis significantly decreased from 1990 to 2019, the annual rate of reduction is not sufficient enough to achieve the aim of India’s National Strategic plan 2017–2025. Approximately six decades since the launch of the National Tuberculosis Control Programme, TB still remains a major public health problem in India. Government needs to strengthen four strategic pillars “Detect–Treat–Prevent–Build” (DTPB) in order to achieve TB free India as envisaged in the National Tuberculosis Elimination Programme (2020).

Addressing constraints to informal providers’ involvement in tuberculosis control: a qualitative study of patent medicine dealers and tuberculosis programme managers

Background A major constraint to tuberculosis control is low case finding with under-reporting to national authorities. Evidence shows that Patent Medicine Dealers are first port of call for most people with symptoms of tuberculosis, yet there is poor referral of such clients to tuberculosis treatment facilities for further evaluation. This study investigated constraints to involvement of Patent Medicine Dealers in tuberculosis control. Methods This was a cross-sectional qualitative study among Patent Medicine Dealers and Tuberculosis Control Programme Managers in Ebonyi State Nigeria. Sixty-four Patent Medicine Dealers and five Tuberculosis Control Programme Managers were interviewed using Focus Group Discussion and In-Depth Interview respectively. Data was collected with electronic audio-recording device and analyzed using thematic approach. Results There are some knowledge gaps about tuberculosis signs, symptoms, free-treatment policy and mode of operation of care service among Patent Medicine Dealers. Patent Medicine Dealers and Tuberculosis Control Programme Managers are willing to collaborate in tuberculosis control effort but constant demand for incentives by Patent Medicine Dealers and inability of National Tuberculosis Control Programme to keep up with such demands are obvious constraints. Conclusions Knowledge gaps in tuberculosis, its control, constant demand for incentives by Patent Medicine Dealers and inability of National Tuberculosis Control Programme to satisfy such demands are constraints to involvement of Patent Medicine Dealers in tuberculosis control. More robust engagement of Patent Medicine Dealers in tuberculosis control with clear job description through tuberculosis education and provision of incentives to support them are recommended policy approaches to improve linkage of clients to tuberculosis treatment facilities.

Genetic Diversity of Non-Tuberculous Mycobacteria among Symptomatic TB negative Patients in Kenya

Non-Tuberculous Mycobacteria (NTM) transmission to humans occurs through inhalation of dust particles or vaporized water containing NTM leading to pulmonary manifestations. NTM infections are often misdiagnosed for tuberculosis (TB) due to their similar clinical and radiological manifestations. We, therefore, performed a species-level identification of NTM in symptomatic TB negative patients through sequencing of the hsp65 gene. We conducted a cross-sectional study at the National Tuberculosis Reference Laboratory in the period between January to November 2020. One hundred and sixty-six mycobacterial culture-positive samples that tested negative for TB using capilia underwent Polymerase Chain Reaction targeting the hsp65 gene. Isolates showing a band with gel electrophoresis at 441 bp position were sequenced using Sanger technology. Geneious software was used to analyze the obtained sequences, and the National Center for Biotechnology Information gene database identified NTM species for each isolate. A phylogenetic tree was constructed from the DNA sequences and evolutionary distances computed using the general time-reversible method. Pearson chi-square was used to determine the association between NTM infection and participants characteristics. Our study identified 43 different NTM species. The dominant NTM belonged to Mycobacterium avium complex 37 (31%). Slow-growing NTM were the majority at 86 (71%) while rapid-growing NTM were 36 (29%). A significant association (p<0.05) was observed for regions and age, while patient type had a week likelihood of NTM infection. Our study characterized the diversity of NTM in Kenya for the first time and showed a high diversity of NTM species.

Adhesiolysis and Decortication for Reccurent Hydropneumothorax Associated with Pleural Tuberculosis

Introduction: Pleural tuberculosis is a pleural infection of tuberculosis caused by Mycobacterium tuberculosis which commonly manifests as hydropneumothorax. Initial treatment with anti-tuberculosis drugs is aimed to prevent progression of the disease and relieve patient’s symptoms. Indication of adhesiolysis and decortication is to remove layer of fibrous tissue and allow the lung to reexpand. Case: A 60 year old woman with shortness of breath, cough, and right-sided chest pain. She had a history of treatment with first-line anti-tubercular drugs for a year stop in September 2016. She was identified with recurrent right-sided hydropneumothorax by chest imaging and thorax CT-scan. Adhesiolysis and decortication were performed on her. Two months later she was diagnosed again with recurrent right-sided hydropneumothorax. VATS (Video-Assisted Thoracoscopic Surgery) revealed fistula involving inferior lobe of the lung. Then, she was treated with second-line anti tuberculosis drugs. After four times reccurent hydropneumothorax, patient showed significant improvement in clinical condition, radiology finding, and lung function test after she finished the tuberculosis treatment. Discussion: Definitive diagnosis of pleural tuberculosis is by the finding of mycobacterium tuberculosis in pleural biopsy, or Mtb culture, and it was difficult to perform. In this case pleural fluid analysis revealed that cause of recurrent right-sided hydropneumothorax was tuberculosis infection. Summary: A 60 year old woman with four times reccurent right-sided hydropneumothorax, and the pleural fluid analysis suggested it was tuberculosis infection. Providing anti-tuberculosis medication based on clinically diagnosed tuberculosis based on flowchart of tuberculosis diagnosis from national tuberculosis programmed are essential to prevent progression of the disease.

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).

Treatment success using novel and adapted treatment regimens in registered DR-TB children in Dushanbe, Tajikistan, 2013-2019

Introduction: Approximately 3% of all pediatric TB cases develop MDR-TB, with only 3–4% of such children receiving MDR-TB treatment. In Tajikistan, children as a proportion of all DR-TB in the country increased from 4.3 to 7.5% during 2013-2018. Despite limited evidence on the use of new anti-TB drugs in children, WHO has updated its guidelines for DR-TB treatment for children, and Tajikistan did so in 2013 and 2017. Novel and adapted regimens included individual regimens for RR/MDR, XDR (with and without Bedaquiline and Delamanid) and short treatment regimens with and without injectables. It is important to document the outcomes of the treatment regimens. Therefore, the aim of this study was to describe characteristics of children receiving different treatment regimens for DR-TB, the culture conversion and treatment outcomes. Methodology: Cohort study of children enrolled in DR-TB treatment by the National Tuberculosis Program in Dushanbe, Tajikistan, January 2013 to July 2019. Results: The study included 60 DR-TB children. The male to female ratio was 1:2 and mean age 13.6 years. Median time to culture conversion was 66 days [IQR:31-103; Range:2-232]. In children with treatment outcomes (N = 58), 93% had favorable outcomes. There were four children (7%) with unfavorable treatment outcomes, all of whom were female 15-17 years, on standard (RR/MDR) treatment during 2013-2015. Favorable outcomes by DR-TB type were 91%, 90%, and 100% in RR/MDR, PreXDR, and XDR-TB patients, respectively. Conclusions: All children enrolled after the introduction of modified guidelines for novel and adapted regimens for DR-TB showed positive TB treatment outcomes.

The Co-management of Tuberculosis-diabetes Co-morbidities in Indonesia Under the National Tuberculosis Control Program: Results From a Retrospective Cohort Study From 2017-2019

Background: Indonesia suffers from a high burden of tuberculosis (TB) and diabetes (DM). The government initiated national TB-DM co-management activities under the National TB Control Program in 2017. This study investigates the detection and treatment outcomes of TB-DM in Jakarta after implementing these activities, and identifies the main factors associated with these outcomes. Methods: A retrospective cohort study was conducted using TB registry data in two districts of Jakarta, East Jakarta (low-income) and South Jakarta (high-income). A 5-step cascade analysis was used: diagnosed TB patients; TB patients tested for DM; diagnosed TB-DM patients; and patients received and completed TB treatment/cured. We conducted descriptive analyses to understand the characteristics of TB and TB-DM patients, and used a two-level mixed-effect logistic regression to explore factors associated with having a DM test and completing TB treatment/being cured. Results: Over the study period (2017-2019) 50.8% of the new pulmonary TB patients aged over 15 were tested for DM. The percentage increased from 41.7% in 2017-2018 to 60.1% in 2019. Of the TB patients tested for DM, 20.8% were diagnosed with DM. Over 90% of the detected TB-DM patients received standard TB treatment, 86.3% of whom completed treatment/were cured. Patients in East Jakarta were more likely to be tested for DM and to complete standard TB treatment/be cured than patients in South Jakarta (P<0.001). Bacteriologically positive TB patients were more likely to be tested for DM (OR=1.37, 95% CI 1.17,1.60). Patients diagnosed in sub-district level healthcare centers had a higher likelihood of being tested for DM than those in government and private hospitals (P<0.05). Receiving DM treatment was associated with a higher likelihood of completing TB treatment/being cured (OR=1.82, 95% CI 1.20, 2.77).Conclusions: TB-DM case detection significantly improved in 2019 after introducing TB-DM co-management activities in Jakarta, while gaps in TB-DM co-management existed between bacteriologically positive and clinically diagnosed TB patients, and across different types of health facilities. Collaboration between TB and DM departments should be strengthened, and more resources need to be mobilized to further improve the co-management of TB-DM in Indonesia.