Peer-led active tuberculosis case-finding among people living with HIV: lessons from Nepal.

PROBLEM: People living with a human immunodeficiency virus (HIV) infection have a high risk of tuberculosis and should undergo regular screening. However, they can be difficult to reach because they are stigmatized and discriminated against. APPROACH: In Nepal, the nongovernmental organization Naya Goreto implemented a peer-led tuberculosis screening project in which people living with HIV volunteered to contact others in this high-risk population. Volunteers took part in a short training course, after which they attempted to contact people living with HIV through existing networks and self-help groups. Tuberculosis screening and testing were carried out in accordance with national guidelines. LOCAL SETTING: In Nepal, the prevalence of HIV infection is 0.3% in the general population but is much higher, at 6%, in people in Kathmandu who inject drugs. To date, the health system has not been able to implement systematic tuberculosis screening in people living with HIV. RELEVANT CHANGES: Between May 2014 and mid-September 2015, 30 volunteers screened 6642 people in 10 districts, 5430 (82%) of whom were living with HIV. Of the 6642, 6046 (91%) were tested for tuberculosis and 287 (4.3%) were diagnosed with the disease, 240 of whom were HIV-positive. Of those with tuberculosis, 270 (94%) initiated treatment. LESSONS LEARNT: Using peers to contact people living with HIV for tuberculosis screening resulted in a high participation rate and the identification of a considerable number of HIV-positive tuberculosis patients. Follow-up during treatment was difficult in this highly mobile group and needs more attention in future interventions.

An easy tool to assess ventilation in health facilities as part of air-borne transmission prevention: a cross-sectional survey from Uganda.

BACKGROUND: No guidelines exist on assessing ventilation through air changes per hour (ACH) using a vaneometer. The objective of the study was to evaluate the position and frequency for measuring air velocity using a vaneometer to assess ventilation with ACH; and to assess influence of ambient temperature and weather on ACH. METHODS: Cross-sectional survey in six urban health facilities in Kampala, Uganda. Measurements consisted of taking air velocity on nine separate moments in five positions in each opening of the TB clinic, laboratory, outpatient consultation and outpatient waiting room using a vaneometer. We assessed in addition the ventilation with the "20% rule", and compared this estimation with the ventilation in ACH assessed using the vaneometer. RESULTS: A total of 189 measurements showed no influence on air velocity of the position and moment of the measurement. No significant influence existed of ambient temperature and a small but significant influence of sunny weather. Ventilation was adequate in 17/24 (71%) of all measurements. Using the "20% rule", ventilation was adequate in 50% of rooms assessed. Agreement between both methods existed in 13/23 (56%) of the rooms assessed. CONCLUSION: Most rooms had adequate ventilation when assessed using a vaneometer for measuring air velocity. A single vaneometer measurement of air velocity is adequate to assess ventilation in this setting. These findings provide practical input for clear guidelines on assessing ventilation using a vaneometer. Assessing ventilation with a vaneometer differs substantially from applying the "20% rule".

Tuberculosis retreatment 'others' in comparison with classical retreatment cases; a retrospective cohort review.

BACKGROUND: Many of the countries in sub-Saharan Africa are still largely dependent on microscopy as the mainstay for diagnosis of tuberculosis (TB) including patients with previous history of TB treatment. The available guidance in management of TB retreatment cases is focused on bacteriologically confirmed TB retreatment cases leaving out those classified as retreatment 'others'. Retreatment 'others' refer to all TB cases who were previously treated but with unknown outcome of that previous treatment or who have returned to treatment with bacteriologically negative pulmonary or extra-pulmonary TB. This study was conducted in 11 regional referral hospitals (RRHs) serving high burden TB districts in Uganda to determine the profile and treatment success of TB retreatment 'others' in comparison with the classical retreatment cases. METHODS: A retrospective cohort review of routinely collected National TB and Leprosy Program (NTLP) facility data from 1 January to 31 December 2010. This study uses the term classical retreatment cases to refer to a combined group of bacteriologically confirmed relapse, return after failure and return after loss to follow-up cases as a distinct group from retreatment 'others'. Distribution of categorical characteristics were compared using Chi-squared test for difference between proportions. The log likelihood ratio test was used to assess the independent contribution of type of retreatment, human immunodeficiency virus (HIV) status, age group and sex to the models. RESULTS: Of the 6244 TB cases registered at the study sites, 733 (11.7%) were retreatment cases. Retreatment 'others' constituted 45.5% of retreatment cases. Co-infection with HIV was higher among retreatment 'others' (70.9%) than classical retreatment cases (53.5%). Treatment was successful in 410 (56.2%) retreatment cases. Retreatment 'others' were associated with reduced odds of success (AOR = 0.44, 95% CI 0.22,0.88) compared to classical cases. Lost to follow up was the commonest adverse outcome (38% of adverse outcomes) in all retreatment cases. Type of retreatment case, HIV status, and age were independently associated with treatment success. CONCLUSION: TB retreatment 'others' constitute a significant proportion of retreatment cases, with higher HIV prevalence and worse treatment success. There is need to review the diagnosis and management of retreatment 'others'.

Results from early programmatic implementation of Xpert MTB/RIF testing in nine countries.

BACKGROUND: The Xpert MTB/RIF assay has garnered significant interest as a sensitive and rapid diagnostic tool to improve detection of sensitive and drug resistant tuberculosis. However, most existing literature has described the performance of MTB/RIF testing only in study conditions; little information is available on its use in routine case finding. TB REACH is a multi-country initiative focusing on innovative ways to improve case notification. METHODS: We selected a convenience sample of nine TB REACH projects for inclusion to cover a range of implementers, regions and approaches. Standard quarterly reports and machine data from the first 12 months of MTB/RIF implementation in each project were utilized to analyze patient yields, rifampicin resistance, and failed tests. Data was collected from September 2011 to March 2013. A questionnaire was implemented and semi-structured interviews with project staff were conducted to gather information on user experiences and challenges. RESULTS: All projects used MTB/RIF testing for people with suspected TB, as opposed to testing for drug resistance among already diagnosed patients. The projects placed 65 machines (196 modules) in a variety of facilities and employed numerous case-finding strategies and testing algorithms. The projects consumed 47,973 MTB/RIF tests. Of valid tests, 7,195 (16.8%) were positive for MTB. A total of 982 rifampicin resistant results were found (13.6% of positive tests). Of all tests conducted, 10.6% failed. The need for continuous power supply was noted by all projects and most used locally procured solutions. There was considerable heterogeneity in how results were reported and recorded, reflecting the lack of standardized guidance in some countries. CONCLUSIONS: The findings of this study begin to fill the gaps among guidelines, research findings, and real-world implementation of MTB/RIF testing. Testing with Xpert MTB/RIF detected a large number of people with TB that routine services failed to detect. The study demonstrates the versatility and impact of the technology, but also outlines various surmountable barriers to implementation. The study is not representative of all early implementer experiences with MTB/RIF testing but rather provides an overview of the shared issues as well as the many different approaches to programmatic MTB/RIF implementation.

Implementing a chest X-ray artificial intelligence tool to enhance tuberculosis screening in India: Lessons learned.

Artificial Intelligence (AI) based chest X-ray (CXR) screening for tuberculosis (TB) is becoming increasingly popular. Still, deploying such AI tools can be challenging due to multiple real-life barriers like software installation, workflow integration, network connectivity constraints, limited human resources available to interpret findings, etc. To understand these challenges, PATH implemented a TB REACH active case-finding program in a resource-limited setting of Nagpur in India, where an AI software device (qXR) intended for TB screening using CXR images was used. Eight private CXR laboratories that fulfilled prerequisites for AI software installation were engaged for this program. Key lessons about operational feasibility and accessibility, along with the strategies adopted to overcome these challenges, were learned during this program. This program also helped to screen 10,481 presumptive TB individuals using informal providers based on clinical history. Among them, 2,303 individuals were flagged as presumptive for TB by a radiologist or by AI based on their CXR interpretation. Approximately 15.8% increase in overall TB yield could be attributed to the presence of AI alone because these additional cases were not deemed presumptive for TB by radiologists, but AI was able to identify them. Successful implementation of AI tools like qXR in resource-limited settings in India will require solving real-life implementation challenges for seamless deployment and workflow integration.

The effect of tuberculosis and antiretroviral treatment on CD4+ cell count response in HIV-positive tuberculosis patients in Mozambique.

BACKGROUND: Tuberculosis (TB) presents a serious problem in Mozambique. HIV prevalence among TB patients is estimated at 47%. A delay in having their first CD4+ cell count could lead to a missed opportunity for ART initiation due to a CD4+ cell increase above the cut-off caused by TB treatment. The objective is to describe CD4+ cell response during TB treatment and quantify the effect of TB treatment and ART on this response. METHODS: All new HIV + adult TB cases in 2007 from three TB clinics in Mozambique were included. Data on TB diagnosis and treatment and HIV parameters were collected. A general mixed model was used for CD4+ cell count response. RESULTS: 338 HIV + patients were notified and 252 (75%) were included in the analysis. Using TB medication was not independently associated with the CD4+ count response (19 cells/mm3; 95% CI: -40 to 79; p = 0.529). ART-use was associated with statistically significantly higher CD4+ cells compared to no ART-use (81 cells/mm3; 95% confidence interval (CI): 12 to 151; p = 0.022). CONCLUSION: In this study, no independent effect of TB treatment on CD4+ cell count was found. HIV-infected TB patients on ART had a significantly higher CD4+ cell count than those not receiving ART. CD4+ cell counts for patients not on ART at TB treatment start, remained below the cut off for initiating ART during the first three months of TB treatment; therefore some delay in getting the first CD4+ cell count would not lead to missing the opportunity to start ART.

Can Patient Navigators Help Potential TB Patients Navigate the Diagnostic and Treatment Pathways? An Implementation Research from India.

Navigating the Indian health system is a challenge for people with tuberculosis (TB) symptoms. The onus of organizing care is on the patient and their families alone. Factors like gender discrimination and opportunity costs further aggravate this. As a result, people may not complete the diagnostic and treatment pathway even though they experience poor health. Navigators can aid in the pathway's completion. We implemented two projects in India-a public sector intervention in Bihar, with a population of 1.02 million, and a private sector intervention in Andhra Pradesh (AP), with a population of 8.45 million. Accredited Social Health Activists (ASHAs) of the public health system in Bihar and local field officers in AP facilitated the patients' navigation through the health system. In Bihar, ASHAs accompanied community-identified presumptive TB patients to the nearest primary health center, assisted them through the diagnostic process, and supported the patients throughout the TB treatment. In AP, the field officers liaised with the private physicians, accompanied presumptive patients through the diagnosis, counseled and started treatment, and followed-up with the patients during the treatment. Both projects recorded case-based data for all of the patients, and used the yield and historical TB notifications to evaluate the intervention's effect. Between July 2017 and December 2018, Bihar confirmed 1650 patients, which represented an increase of 94% in public notifications compared to the baseline. About 97% of them started treatment. During the same period in AP, private notifications increased by 147% compared to the baseline, and all 5765 patients started treatment. Patient navigators support the patients in the diagnostic and treatment pathways, and improve their health system experience. This novel approach of involving navigators in TB projects can improve the completion of the care cascade and reduce the loss to follow-up at various stages.

Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans.

Animal experiments have shown that nonhuman primates, cats, ferrets, hamsters, rabbits, and bats can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, SARS-CoV-2 RNA has been detected in felids, mink, and dogs in the field. Here, we describe an in-depth investigation using whole-genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced by humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period, several weeks before detection. Despite enhanced biosecurity, early warning surveillance, and immediate culling of animals in affected farms, transmission occurred between mink farms in three large transmission clusters with unknown modes of transmission. Of the tested mink farm residents, employees, and/or individuals with whom they had been in contact, 68% had evidence of SARS-CoV-2 infection. Individuals for which whole genomes were available were shown to have been infected with strains with an animal sequence signature, providing evidence of animal-to-human transmission of SARS-CoV-2 within mink farms.

Prediagnostic loss to follow-up in an active case finding tuberculosis programme: a mixed-methods study from rural Bihar, India.

OBJECTIVE: To quantify the prediagnostic loss to follow-up (PDLFU) in an active case finding tuberculosis (TB) programme and identify the barriers and enablers in undergoing diagnostic evaluation. DESIGN: Explanatory mixed-methods design. SETTING: A rural population of 1.02 million in the Samastipur district of Bihar, India. PARTICIPANTS: Based on their knowledge of health status of families, community health workers or CHWs (called accredited social health activist or locally) and informal providers referred people to the programme. The field coordinators (FCs) in the programme screened the referrals for TB symptoms to identify presumptive TB cases. CHWs accompanied the presumptive TB patients to free diagnostic evaluation, and a transport allowance was given to the patients. Thereafter, CHWs initiated and supported the treatment of confirmed cases. We included 13 395 community referrals received between January and December 2018. To understand the reasons of the PDLFU, we conducted in-depth interviews with patients who were evaluated (n=3), patients who were not evaluated (n=4) and focus group discussions with the CHWs (n=2) and FCs (n=1). OUTCOME MEASURES: Proportion and characteristics of PDLFU and association of demographic and symptom characteristics with diagnostic evaluation. RESULTS: A total of 11 146 presumptive TB cases were identified between January and December 2018, out of which 4912 (44.1%) underwent diagnostic evaluation. In addition to the free TB services in the public sector, the key enablers were CHW accompaniment and support. The major barriers identified were misinformation and stigma, deficient family and health provider support, transport challenges and poor services in the public health system. CONCLUSION: Finding the missing cases will require patient-centric diagnostic services and urgent reform in the health system. A community-oriented intervention focusing on stigma, misinformation and patient support will be critical to its success.

The TB REACH Initiative: Supporting TB Elimination Efforts in the Asia-Pacific.

After many years of TB 'control' and incremental progress, the TB community is talking about ending the disease, yet this will only be possible with a shift in the way we approach the TB response. While the Asia-Pacific region has the highest TB burden worldwide, it also has the opportunity to lead the quest to end TB by embracing the four areas laid out in this series: using data to target hotspots, initiating active case finding, provisioning preventive TB treatment, and employing a biosocial approach. The Stop TB Partnership's TB REACH initiative provides a platform to support partners in the development, evaluation and scale-up of new and innovative technologies and approaches to advance TB programs. We present several approaches TB REACH is taking to support its partners in the Asia-Pacific and globally to advance our collective response to end TB.

Active Case Finding of Tuberculosis: Randomized Evaluation of Simple and Infotainment Chest Camps.

BACKGROUND: In Pakistan, many tuberculosis (TB) cases are not reported to the national surveillance system. An active case finding strategy in the form of conventional (simple) or innovative (infotainment) chest camps can contribute to diagnosing these missed cases. OBJECTIVE: To compare the yield in terms of TB patients detected at a simple chest camp (SCC) versus an infotainment chest camp (ICC) in rural areas. METHODS: A cluster randomized controlled trial with 2 parallel arms was conducted in 4 districts of Pakistan from June 2012 to May 2013. Rural neighborhoods (n = 318) were randomly allocated in a ratio of 1:3 to receive either SCC or ICC. Incidence of TB (all forms and sputum smear positive [SS+]) and number needed to screen (NNS) to diagnose 1 TB case were calculated. Cluster analysis was done according to intention to treat and risk ratio (RR), and 95% confidence intervals (CIs) were calculated. FINDINGS: A total of 3086 participants were tested at the SCC and 9029 at the ICC, of whom 38.5% were female. Mean age was 37.4 ± 15.9 years. Incidences of previously undiagnosed TB (all forms) for SCC and ICC were 23.6 (95% CI 20.04-27.4) and 22.1 (95% CI 20.3-24.1) per 100,000 population (P = .42), SS+ TB 22.5 (95% CI 19.3-26.1) and 21.6 (95% CI 19.8-23.6) (P = .67), respectively. NNS to diagnose 1 TB case were 260 (95% CI 234.3-289.6) and 258 (95% CI 233.3-287.9) for SCC and ICC, respectively (P = .9). RRs for all forms of TB and SS+ TB in SCC compared to ICC were 0.94 (95% CI 0.73-1.19) and 0.95 (95% CI 0.74-1.22) and P values were .58 and .71, respectively. CONCLUSIONS: Both types of chest camps are equally effective in active case finding of previously undiagnosed TB cases in rural areas in 2 provinces in Pakistan.

Healthcare workers' challenges in the implementation of tuberculosis infection prevention and control measures in Mozambique.

OBJECTIVE: Healthcare Workers (HCWs) have a higher frequency of TB exposure than the general population and have therefore an occupational TB risk that infection prevention and control (IPC) measures aim to reduce. HCWs are crucial in the implementation of these measures. The objective of the study was to investigate Mozambican HCWs' perceptions of their occupational TB risk and the measures they report using to reduce this risk. In addition, we explored the challenges HCWs encounter while using these TBIPC measures. METHODS: Focus group discussion. Analysis according content method. PARTICIPANTS: Four categories of HCWs: auxiliary workers, medical (doctors and clinical officers), nurses and TB program staff. RESULTS: HCWs are aware of their occupational TB risk and use various measures to reduce their risk of infection. HCWs find it challenging to employ measures that minimize such risks and a lack of clear guidelines contributes to these challenges. HCWs' and patient behavior further complicate the use of TBIPC measures. CONCLUSION: HCWs in Mozambique perceive a high occupational risk of TB infection. They report several challenges using measures to reduce this risk such as shortage of material, lack of clear guidelines, insufficient motivation and inadequate training. Robust training with motivational approaches, alongside supervision and support for HCWs could improve implementation of TBIPC measures. Healthcare management should address the areas for improvement that are beyond the individual HCW's control.

A pragmatic approach to measuring, monitoring and evaluating interventions for improved tuberculosis case detection.

The inability to detect all individuals with active tuberculosis has led to a growing interest in new approaches to improve case detection. Policy makers and program staff face important challenges measuring effectiveness of newly introduced interventions and reviewing feasibility of scaling-up successful approaches. While robust research will continue to be needed to document impact and influence policy, it may not always be feasible for all interventions and programmatic evidence is also critical to understand what can be expected in routine settings. The effects of interventions on early and improved tuberculosis detection can be documented through well-designed program evaluations. We present a pragmatic framework for evaluating and measuring the effect of improved case detection strategies using systematically collected intervention data in combination with routine tuberculosis notification data applying historical and contemporary controls. Standardized process evaluation and systematic documentation of program implementation design, cost and context will contribute to explaining observed levels of success and may help to identify conditions needed for success. Findings can then guide decisions on scale-up and replication in different target populations and settings.

Are routine tuberculosis programme data suitable to report on antiretroviral therapy use of HIV-infected tuberculosis patients?

BACKGROUND: Antiretroviral therapy (ART) is lifesaving for HIV-infected tuberculosis (TB) patients. ART-use by these patients lag behind compared to HIV-testing and co-trimoxazole preventive therapy. TB programmes provide the data on ART-use by HIV-infected TB patients, however often the HIV services provide the ART. We evaluated whether the data on ART-use in the TB register were complete and correct. The timing of ART initiation was evaluated to assess whether reporting on ART-use could have happened with the TB case finding reporting. We collected data on TB treatment, HIV testing and ART for adult TB cases in 2007 from three TB clinics in Manica Province, Mozambique. These data on use of ART from TB registers were compared with those from the HIV services. FINDINGS: Of 628 patients included, 504 (81%) were tested and of these 356 (71%) were HIV-infected. Of the co-infected patients, 81% registered with the HIV services in the same facility. The TB register was correct on ART-use in 73% of co-infected cases and complete in 74%. Information on ART-use could have been reported with the TB case finding reports in 56% of co-infected patients. CONCLUSION: The TB register is reasonably correct and complete on ART-use. However, the HIV patient record seems a much better source to provide this information. Reporting on ART-use at the end of the quarter in which TB treatment starts provides the programme with timely but incomplete information. A more complete but less timely picture is available after a year.