Spatial distribution and temporal trends of tuberculosis case notifications, Uganda: a ten-year retrospective analysis (2013-2022).

BACKGROUND: Uganda has a high incidence and prevalence of tuberculosis (TB). Analysis of spatial and temporal distribution of TB is an important tool for supporting spatial decision-making, planning, and policy formulations; however, this information is not readily available in Uganda. We determined the spatial distribution and temporal trends of tuberculosis notifications in Uganda, 2013-2022. METHODS: We conducted a retrospective analysis of routinely-generated program data reported through the National TB and Leprosy Programme (NTLP) surveillance system. We abstracted data on all TB cases diagnosed from 2013 to 2022 by district and region. We drew choropleth maps for Uganda showing the TB case notification rates (CNR) per 100,000 and calculated the CNR using the cases per district as the numerator and individual district populations as the denominators. Population estimates were obtained from the 2014 National Population and Housing Census, and a national growth rate of 3% was used to estimate the annual population increase. RESULTS: Over the entire study period, 568,957 cases of TB were reported in Uganda. There was a 6% annual increase in TB CNR reported from 2013 (134/100,000) to 2022 (213/100,000) (p-value for trend p < 0.00001). Cases were reported from all 12 Ministry of Health regions during the entire period. The distribution of CNR was heterogeneous throughout the country and over time. Moroto, Napak and Kampala districts had consistently high CNR throughout the ten years. Kalangala district had lower CNR from 2013 to 2018 but high CNR from 2019 to 2022. Moroto region, in the northeast, had consistently high CNR while Mbale and Soroti regions in Eastern Uganda had the lowest CNR throughout the ten years. CONCLUSION: There was an overall increasing trend in TB CNR from 2013 to 2022. We recommend that the National TB program institutes intensified measures aided by more funding to mitigate and reverse the negative impacts of the COVID-19 pandemic on TB.

Health Screening Strategies for Artisanal and Small-Scale Miners for Tuberculosis, Human Immunodeficiency Virus and Silicosis: A Case of the USAID-Supported Kunda Nqob'iTB Project in Zimbabwe.

Artisanal and small-scale mining is characterized by excessive exposure to physical, chemical, ergonomic, psychosocial and biological hazards. There is a high burden of tuberculosis (TB), human immunodeficiency virus (HIV) infections and silicosis among artisanal and small-scale miners (ASMs). The aim of this project report is to describe lessons learned from strategies implemented to reach ASMs with screening services for TB, HIV and silicosis in Zimbabwe through the Kunda-Nqob'i TB (KNTB) project supported by the United States Agency for International Development (USAID). The intervention package for screening ASMs for TB, HIV and silicosis included service provision through two occupational health clinics at two provincial hospitals and a mobile workplace-based screening (WBS) facility at the mining sites. From 1 October 2020 to 30 September 2023, 10,668 ASMs were screened, with a high number of cases of silicosis (21%) and TB (7.4%). There was a high burden of HIV (30%) in ASMs attending the occupational health clinics. The two occupational health clinics screened 3453 ASMs, while the mobile WBS activities screened 7215 ASMs during the period. A total of 370 healthcare workers (doctors/clinical officers, nurses, environmental health technicians and district tuberculosis and Leprosy control officers) were trained on TB and the fundamental diagnostic principles of silicosis. The KNTB project has been successful in reaching out to many ASMs operating in remote and hard-to-reach mining areas. The KNTB project has brought to light the positive health-seeking behavior of ASMs operating in remote areas. The project has brought to the fore the effectiveness of multi-stakeholder engagement and collaboration in reaching out to ASMs in remote areas with health screening services. There is a high burden of TB, HIV and silicosis in ASMs. Screening for TB, HIV and silicosis using workplace-based screening and occupational health clinics is an effective strategy and should be rolled out to all areas with high artisanal and small-scale mining activity.

Undernotification and underreporting of tuberculosis in Zambia: a national data quality assessment.

BACKGROUND: Despite national implementation of several high impact interventions and innovations to bolster tuberculosis (TB) detection and improve quality of TB services in Zambia, notifications have been declining since 2004. A countrywide data quality assessment (DQA) of Zambia's National TB and Leprosy Programme (NTLP) was undertaken to quantify the degree to which undernotification and underreporting of TB notifications may be occurring. METHODS: The NTLP conducted a retrospective DQA of health facilities in high burden districts in all ten Zambian provinces. Multiple routine programmatic data sources were triangulated through a multi-step verification process to enumerate the total number of unique TB patients diagnosed between 1st January and 31st August 2019; both bacteriologically confirmed and clinically diagnosed TB patients were included. Undernotification was defined as the number of TB patients identified through the DQA that were not documented in facility treatment registers, while underreporting was defined as the number of notified TB cases not reported to the NTLP. RESULTS: Overall, 265 health facilities across 55 districts were assessed from which 28,402 TB patients were identified; 94.5% of TB patients were ≥ 15 years old, 65.1% were male, 52.0% were HIV-positive, and 89.6% were a new/relapse case. Among all TB cases, 32.8% (95%CI: 32.2-33.3) were unnotified. Undernotification was associated with age ≥ 15 years old (adjusted prevalence odds ratio [aPOR] = 2.4 [95%CI: 2.0-2.9]), HIV-positive status (aPOR = 1.6 [95%CI: 1.5-1.8]), being a new/relapse TB case (aPOR = 17.5 [95%CI: 13.4-22.8]), being a clinically diagnosed TB case (aPOR = 4.2 [95%CI:3.8-4.6]), and being diagnosed at a hospital (range, aPOR = 1.5 [95%CI: 1.3-1.6] to 2.6 [95%CI: 2.3-2.9]). There was substantial heterogeneity in the proportion of unnotified TB cases by province (range, 18.2% to 43.6%). In a sub-analysis among 22,199 TB patients with further data available, 55.9% (95%CI: 55.2-56.6) were notified and reported to the NTLP, 32.8% (95%CI: 32.2-33.4) were unnotified, and 11.3% (95%CI: 10.9-11.7) went unreported to the NTLP. CONCLUSIONS: The findings from Zambia's first countrywide TB programme DQA demonstrate substantial undernotification and underreporting of TB cases across all provinces. This underscores the urgent need to implement a robust and integrated data management system to facilitate timely registration and reporting of all TB patients who are diagnosed and treated.

Histoplasmosis masquerading as tuberculosis: A report of three cases in immunocompetent children.

The most common cause of granulomatous lymphadenitis in countries like ours is mycobactrium tuberculosis followed by atypical mycobacterial infection, fungal infections, parasitic infection, cat scratch disease, lymphogranuloma venereum (inguinal lymphadenopathy), and leprosy Here, we present three cases of lymphadenopathy due to histoplasmosis in immunocompetent children. Two of them presented with fever, lymphadenopathy, initially diagnosed as granulomatous lymphadenitis consistent with tuberculosis on FNAC and were put on antitubercular drugs. However, their condition gradually became worse. As the patients continued to deteriorate, subsequent lymph node biopsies were done and diagnosed as histoplasmosis. Third case presented with acute loss of vision with hepatosplenomegaly and lymphadenopathy. Initially considered as acute leukemia, but eventually established as histoplasmosis. Histoplasmosis should be considered as one of the possible causes of granulomatous lymphadenitis in children.

A simple assay to quantify mycobacterial lipid antigen-specific T cell receptors in human tissues and blood.

T cell receptors (TCRs) encode the history of antigenic challenge within an individual and have the potential to serve as molecular markers of infection. In addition to peptide antigens bound to highly polymorphic MHC molecules, T cells have also evolved to recognize bacterial lipids when bound to non-polymorphic CD1 molecules. One such subset, germline-encoded, mycolyl lipid-reactive (GEM) T cells, recognizes mycobacterial cell wall lipids and expresses a conserved TCR-ɑ chain that is shared among genetically unrelated individuals. We developed a quantitative PCR assay to determine expression of the GEM TCR-ɑ nucleotide sequence in human tissues and blood. This assay was validated on plasmids and T cell lines. We tested blood samples from South African subjects with or without tuberculin reactivity or with active tuberculosis disease. We were able to detect GEM TCR-ɑ above the limit of detection in 92% of donors but found no difference in GEM TCR-ɑ expression among the three groups after normalizing for total TCR-ɑ expression. In a cohort of leprosy patients from Nepal, we successfully detected GEM TCR-ɑ in 100% of skin biopsies with histologically confirmed tuberculoid and lepromatous leprosy. Thus, GEM T cells constitute part of the T cell repertoire in the skin. However, GEM TCR-ɑ expression was not different between leprosy patients and control subjects after normalization. Further, these results reveal the feasibility of developing a simple, field deployable molecular diagnostic based on mycobacterial lipid antigen-specific TCR sequences that are readily detectable in human tissues and blood independent of genetic background.

Tuberculosis treatment within differentiated service delivery models in global HIV/TB programming.

INTRODUCTION: Providing more convenient and patient-centred options for service delivery is a priority within global HIV programmes. These efforts improve patient satisfaction and retention and free up time for providers to focus on new HIV diagnoses or severe illness. Recently, the coronavirus disease 2019 (COVID-19) pandemic precipitated expanded eligibility criteria for these differentiated service delivery (DSD) models to decongest clinics and protect patients and healthcare workers. This has resulted in dramatic scale-up of DSD for antiretroviral therapy, cotrimoxazole and tuberculosis (TB) preventive treatment. While TB treatment among people living with HIV (PLHIV) has traditionally involved frequent, facility-based management, TB treatment can also be adapted within DSD models. Such adaptations could include electronic tools to ensure appropriate clinical management, treatment support, adherence counselling and adverse event (AE) monitoring. In this commentary, we outline considerations for DSD of TB treatment among PLHIV, building on best practices from global DSD model implementation for HIV service delivery. DISCUSSION: In operationalizing TB treatment in DSD models, we consider the following: what activity is being done, when or how often it takes place, where it takes place, by whom and for whom. We discuss considerations for various programme elements including TB screening and diagnosis; medication dispensing; patient education, counselling and support; clinical management and monitoring; and reporting and recording. General approaches include multi-month dispensing for TB medications during intensive and continuation phases of treatment and standardized virtual adherence and AE monitoring. Lastly, we provide operational examples of TB treatment delivery through DSD models, including a conceptual model and an early implementation experience from Zambia. CONCLUSIONS: COVID-19 has catalysed the rapid expansion of differentiated patient-centred service delivery for PLHIV. Expanding DSD models to include TB treatment can capitalize on existing platforms, while providing high-quality, routine treatment, follow-up and patient education and empowerment.

Economic evaluation of patient costs associated with tuberculosis diagnosis and care in Solomon Islands.

BACKGROUND: Tuberculosis (TB) care can be costly for patients and their families. The End TB Strategy includes a target that zero TB affected households should experience catastrophic costs associated with TB care. Costs are catastrophic when a patient spends 20% or more of their annual household income on their TB diagnosis and care. In Solomon Islands the costs of TB care are unknown. The aim of this study was to determine the costs of TB diagnosis and care, the types of costs and the proportion of patients with catastrophic costs. METHODS: This was a nationally representative cross-sectional survey of TB patients carried out between 2017 and 2019. Patients were recruited from health care facilities, from all ten provinces in Solomon Islands. During an interview they were asked about the costs of TB diagnosis and care. These data were analysed using descriptive statistics to describe the costs overall and the proportions of different types of costs. The proportion of patients with catastrophic costs was calculated and a multivariate logistic regression was undertaken to determine factors associated with catastrophic costs. RESULTS: One hundred and eighty-three TB patients participated in the survey. They spent a mean of 716 USD (inter quartile range: 348-1217 USD) on their TB diagnosis and care. Overall, 62.1% of costs were attributable to non-medical costs, while income loss and medical costs comprised 28.5 and 9.4%, respectively. Overall, 19.7% (n = 36) of patients used savings, borrowed money, or sold assets as a financial coping mechanism. Three patients (1.6%) had health insurance. A total of 92.3% (95% CI: 88.5-96.2) experienced catastrophic costs, using the output approach. Being in the first, second or third poorest wealth quintile was significantly associated with catastrophic costs (adjusted odds ratio: 67.3, 95% CI: 15.86-489.74%, p <  0.001). CONCLUSION: The costs of TB care are catastrophic for almost all patients in Solomon Islands. The provision of TB specific social and financial protection measures from the National TB and Leprosy Programme may be needed in the short term to ameliorate these costs. In the longer term, advancement of universal health coverage and other social and financial protection measures should be pursued.

Association of PTPN22-C1858T Polymorphism With Susceptibility to Mycobacterium tuberculosis and Mycobacterium leprae Infection: A Meta-Analysis.

It was previously published that single-nucleotide polymorphism rs2476601 (PTPN22 [protein tyrosine phosphatase non-receptor type 22]-C1858T) might be related to increased sensibility to Mycobacterium tuberculosis and M. leprae infection. However, the results were inconclusive despite a high degree of similarity between both parameters. Herein, we carried out this meta-analysis to systematically summarize and articulate the correlation between PTPN22-C1858T polymorphism and mycobacterial infection. The susceptibility of PTPN22-C1858T carriers with autoimmune conditions receiving immunosuppressive therapy to M. tuberculosis and M. leprae infection was determined. A systematic retrieval of studies on relevance of PTPN22-C1858T polymorphism to susceptibility of M. tuberculosis or M. leprae infection was performed in Chinese National Knowledge Infrastructure, PubMed and Embase databases. We regarded Odds ratios (ORs) and 95% confidence intervals (CIs) as the determined effect size. Finally, four and two case-control studies on tuberculosis and leprosy, respectively, were included. In all genetic models, without indicated association between PTPN22-C1858T polymorphism and tuberculosis's susceptibility. [C versus T: OR = 0.22 (95% CI: 0.09-0.50, PH = 0.887); CT versus CC: OR = 0.21 (95% CI: 0.09-0.49, PH = 0.889); TT+CT versus CC: OR = 0.21 (95% CI: 0.09-0.49, PH = 0.889)]. A significantly increased risk of leprosy was perceived in patients with the PTPN22-C1858T polymorphism [C versus T: OR = 2.82 (95% CI: 1.02-7.81, PH = 0.108)]. While the PTPN22-C1858T polymorphism is irrelevant to higher susceptibility to the infection of M. tuberculosis in Caucasians and Asians, it is relevant to increased susceptibility to the infection of M. leprae. However, the results of M. leprae are supposed to interpreted with prudence owing to the limited quantity of studies and heterogeneity. Further well-designed studies with sufficient populations are required to verify our conclusions.

Treatment outcomes of drug susceptible Tuberculosis in private health facilities in Lagos, South-West Nigeria.

BACKGROUND: The Lagos State Tuberculosis, Buruli Ulcer, and Leprosy Control Program (LSTBLCP) started engaging private hospitals under the Public-Private Mix (PPM) Program in 2008. The study aimed to evaluate the trend and predictors of successful Tuberculosis (TB) treatment outcomes of patients managed across these private health facilities between 2010-2016 in Lagos, Nigeria. METHODS: Retrospective review of TB treatment register and treatment cards of patients commenced on TB treatment between January 2010 and December 2016 in 36 private health facilities engaged by the LSTBLCP. Between December 2016 and February 2017, data were collected and entered into Microsoft Excel by trained data entry clerks. The analysis was done using SPSS software. Independent predictors of successful treatment outcomes were determined using multivariate analysis at the statistical significance of p<0.05 and 95% confidence interval. RESULTS: A total of 1660 records of TB patients were reviewed. 1535 (92.47%) commenced treatment, while 1337 (87.10%) of all records had documented treatment outcomes. Of the 1337 patients with outcomes, 1044 (78.09%) had a successful treatment outcome, and 293 (21.91%) had an unsuccessful outcome. Majority were male, 980 (59.04%), Human Immunodeficiency Virus (HIV) negative status, 1295 (80.24%), diagnosed with smear, 1141 (73.14%), treated in private not-for-profit (PNFP) hospital, 1097 (66.08%), treated for TB between 2014-2016 (18.96%-19.52%). In multivariate analysis, age>20years (aOR = 0.26, p = 0.001), receiving TB treatment in 2013 (aOR = 0.39, p = 0.001), having genexpert for TB diagnosis (aOR = 0.26, p = 0.031) and being HIV positive (aOR = 0.37, p = 0.001) significantly reduced likelihood of successful treatment outcome. The site of TB, being on ART or CPT, were confounding determinants of successful treatment outcomes as they became non-significant at the multivariate analysis level. CONCLUSION: Treatment outcome among Lagos private hospitals was low compared with NTBLCP and World Health Organization (WHO) target. We urge the government and TB stakeholders to strengthen the PPM interventions to improve adherence, particularly among People Living with HIV (PLHIV) and older TB patients. Hence, promotion of early care-seeking, improving diagnostic and case holding efficiencies of health facilities, and TB/HIV collaborative interventions can reduce the risk of an unsuccessful outcome.

Coexistence of mycobacterial infections - Mycobacterium tuberculosis and Mycobacterium leprae - in Sri Lanka: a case series.

BACKGROUND: Leprosy is one of the oldest mycobacterial infections and tuberculosis is the most common mycobacterial infection with a higher degree of infectivity than leprosy. Although both diseases are prevalent in clusters in developing countries, simultaneous occurrence of them in an individual is a rare entity, even in an endemic setting. CASE PRESENTATION: We describe six cases of tuberculosis and leprosy coinfection: a 57-year-old Sinhalese woman, a 47-year-old Tamil woman, a 72-year-old Tamil man, a 59-year-old Sinhalese man, a 54-year-old Sinhalese man, and a 50-year-old Sinhalese man. In this case series, five patients had lepromatous leprosy and the majority of patients were men. Three patients were detected to have tuberculosis at the outset of treatment of leprosy, while two developed tuberculosis later and one had extrapulmonary tuberculosis 5 years before the diagnosis of leprosy. The latter developed pulmonary tuberculosis as a reactivation while on treatment for leprosy. A majority of our patients with pulmonary tuberculosis had positive Mantoux test, high erythrocyte sedimentation rate, radiological evidence, and acid-fast bacilli in sputum. Human immunodeficiency virus and diabetes were detected in one patient. One patient had rifampicin-resistant tuberculosis, while she was on monthly rifampicin therapy for leprosy. CONCLUSION: An immunocompromised status, such as human immunodeficiency virus infection, diabetes, and immunosuppressive drugs, are risk factors for tuberculosis infection. The use of steroids in the treatment of leprosy may increase the susceptibility to develop tuberculosis. Development of rifampicin resistance secondary to monthly rifampicin in leprosy is a major concern in treating patients coinfected with tuberculosis. Despite the paucity of reports of coinfection, it is advisable to screen for tuberculosis in patients with leprosy, especially if there are respiratory or constitutional symptoms, high erythrocyte sedimentation rate, and abnormal chest X-ray. The fact is that positive Mantoux and QuantiFERON Gold tests and presence of acid-fast bacilli in sputum are misleading, chest X-ray evidence of active tuberculosis and positive tuberculosis cultures are important diagnostic clues for active tuberculosis infection in a patient with leprosy. This is important to avoid monthly rifampicin in patients with suspected coinfections, which may lead to development of drug resistance to tuberculosis treatment. Whether prolonged steroid therapy in leprosy is a risk factor for development of tuberculosis is still controversial.

The Many Hosts of Mycobacteria 8 (MHM8): A conference report.

Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycobacteria include leprosy, tuberculosis (TB), nontuberculous mycobacteria (NTM) infections and Buruli Ulcer. To better understand and treat mycobacterial disease, clinicians, veterinarians and scientists use a range of discipline-specific approaches to conduct basic and applied research, including conducting epidemiological surveys, patient studies, wildlife sampling, animal models, genetic studies and computational simulations. To foster the exchange of knowledge and collaboration across disciplines, the Many Hosts of Mycobacteria (MHM) conference series brings together clinical, veterinary and basic scientists who are dedicated to advancing mycobacterial disease research. Started in 2007, the MHM series recently held its 8th conference at the Albert Einstein College of Medicine (Bronx, NY). Here, we review the diseases discussed at MHM8 and summarize the presentations on research advances in leprosy, NTM and Buruli Ulcer, human and animal TB, mycobacterial disease comorbidities, mycobacterial genetics and 'omics, and animal models. A mouse models workshop, which was held immediately after MHM8, is also summarized. In addition to being a resource for those who were unable to attend MHM8, we anticipate this review will provide a benchmark to gauge the progress of future research concerning mycobacteria and their many hosts.

Community health care workers in pursuit of TB: Discourses and dilemmas.

Community-led tuberculosis (TB) active case finding is widely promoted, heavily funded, but many efforts fail to meet expectations. The underlying reasons why TB symptom screening programs underperform are poorly understood. This study examines Nigerian stakeholders' insights to characterize the mechanisms, enabling structures and influences that lead programs to succeed or fail. Eight focus group discussions were held with Community Health Workers (CWs) from four models of community-based TB screening and referral. In-depth interviews were conducted with 2 State TB program managers, 8 Community based organizations (CBOs), and 6 state TB and Leprosy Local Government supervisors. Transcripts were coded using Framework Analysis to assess how divergent understandings of CWs' roles, expectations, as well as design, political and structural factors contributed to the observed underperformance. Altruism, religious faith, passion, and commitment to the health and well-being of their communities were reasons CWs gave for starting TB symptom screening and referral. Yet politicized or donor-driven CWs' selection processes at times yielded implementers without a firm grounding in TB or the social, cultural, and physical terrain. CWs encountered suspicion, stigma, and hostility in both health facilities and communities. As the interface between the TB program and communities, CWs often bore the brunt of frustrations with inadequate TB services and CBO/iNGO collaboration. Some CWs expended their own social and financial capital to cover gaps in the active case finding (ACF) programs and public health services or curtailed their screening activities. Effective community-led TB active case finding is challenging to design, implement and sustain. Contrary to conventional wisdom, CWs did not experience it as inherently empowering. Sustainable, supportive models that combine meaningful engagement for communities with effective program stewardship and governance are needed. Crucially effective and successful implementation of community-based TB screening and referral requires a functional public health system to which to refer.

Cytological diagnosis in a clinically unsuspected case of disseminated BCGosis: A case report.

Bacille Calmette-Guerin (BCG) vaccine is administered worldwide to neonates and considered safe. Serious complications like disseminated BCGosis are extremely rare occurrences (<1 per million vaccinations). A 6 months male was brought to paediatric outpatient department with fever and swelling over the dorsum of the left hand for 5 days. On examination, he was febrile and had hepatosplenomegaly. X-ray of the hand showed lytic lesions in the first and second metacarpals. Provisional clinical diagnosis included Langerhans cell histiocytosis, congenital syphilis, and haematological malignancy. Fine Needle Aspiration Cytology (FNAC) was done from the swelling and showed diffuse sheets of histiocytes with both intracellular and extracellular rod-shaped unstained structures along with inflammatory cells. These ghost images stained positive with ZN stain. A cytological diagnosis of atypical mycobacteria vs leprosy was made. Child was revisited and found to have an active BCG scar. Further investigations showed low serum IgM and positive AFB culture. These bacilli were confirmed by GenoType MTBDR plus test as Mycobacterium bovis. Despite Antitubercular therapy, the patient succumbed to death. This case highlights the variable clinical presentation of BCGosis. Its occurrence may unmask any underlying immunodeficiency. If unfamiliar with the above cytological features and in absence of routinely performed special stains, the cytopathologist may miss these notorious organisms and treat such cases like suppurative lesions. To conclude, an early and definitive diagnosis of BCGosis can be established on FNAC which would ensure timely management and better outcome in this highly lethal entity.

The National Tuberculosis Control Programme of Liberia Laboratory Programme Performance.

Background: Tuberculosis (TB) is a major public health problem in Liberia. Little is known about the TB laboratory performance of Liberia and the challenges after the 14 years of civil war which ended in 2003. The purpose of the study was to evaluate the TB laboratory performance of Liberia. Methods: A cross-sectional study was conducted from 2014 to 2015. The study was conducted using quantitative data of TB case findings, sputum microscopy proficiency testing, and on-site assessment of sputum microscopy laboratories in Liberia. 80 laboratories participated in the proficiency testing. Besides, four years' (2012-2015) TB case finding data obtained from the National Leprosy and Tuberculosis Control Programme (NLTCP) were used to complement the study. The data were analysed using descriptive statistics. Results: From the 80 TB sputum microscopy testing laboratories participating in proficiency testing, only 20 (25%) scored acceptable performance. 46 (58%) TB microscopy laboratories reported quantification errors for the proficiency panel slide 6 which was 3+. The national TB smear-positive cases notified were 4342 in 2012 but decreased to 3820 and 2448 in 2013 and 2014, respectively. The TB smear case detection rate showed an increase from 68% in 2010 to 78% in 2011 and a decrease to 60%, 57%, and 42% in 2012, 2013, and 2014, respectively. Conclusion: Between 2010 and 2013, the NLTCP succeeded in increasing the number of TB sputum microscopy laboratories. At most of the TB microscopy sites, the TB laboratory quality system was not implemented. The NLTCP of Liberia should develop strategies to overcome its challenges in TB laboratory testing.

Infect and Inject: How Mycobacterium tuberculosis Exploits Its Major Virulence-Associated Type VII Secretion System, ESX-1.

Mycobacterium tuberculosis is an ancient master of the art of causing human disease. One important weapon within its fully loaded arsenal is the type VII secretion system. M. tuberculosis has five of them: ESAT-6 secretion systems (ESX) 1 to 5. ESX-1 has long been recognized as a major cause of attenuation of the FDA-licensed vaccine Mycobacterium bovis BCG, but its importance in disease progression and transmission has recently been elucidated in more detail. This review summarizes the recent advances in (i) the understanding of the ESX-1 structure and components, (ii) our knowledge of ESX-1's role in hijacking macrophage function to set a path for infection and dissemination, and (iii) the development of interventions that utilize ESX-1 for diagnosis, drug interventions, host-directed therapies, and vaccines.

A case of febrile ulceronecrotic Mucha-Habermann disease with comorbidities.

Febrile ulceronecrotic Mucha-Habermann disease is a very rare and severe variant of pityriasis lichenoides et varioliformis acuta. Adult cases are difficult to diagnose as in the early course they can mimic erythema multiforme or lymphomatoid papulosis. We report a case of a 38-year-old woman who presented with 90% body surface area involvement, fever, diarrhea, malaise and associated comorbidities. She was treated with systemic steroids and methotrexate but suffered a fatal outcome. So far, a total of 65 cases are reported in the literature.

Intervention Packages for Early Visceral Leishmaniasis Case Detection and Sandfly Control in Bangladesh: A Comparative Analysis.

We compared the efficacy of three intervention packages for active case detection (ACD) of visceral leishmaniasis (VL)/post-kala-azar dermal leishmaniasis (PKDL) combined with sandfly control around an index case. The packages were 1) no kala-azar transmission activity involving indoor residual spraying (IRS) with deltamethrin, peri-domestic deployment of larvicide with temephos, and house-to-house search for cases; 2) fever camp (FC) plus durable wall lining (DWL) with deltamethrin; and 3) FC plus insecticide (deltamethrin) impregnated bed-nets (ITN) around an index case. Fever camp includes 1-day campaign at the village level to screen and diagnose VL, PKDL, leprosy, malaria, and tuberculosis among residents with chronic fever or skin disease. Efficacy was measured through yield of new cases, vector density reduction, and mortality at 1, 3, 6, 9, and 12 months following intervention. Fever camp + DWL was the most efficacious intervention package with 0.5 case detected per intervention, 79% reduction in vector density (incidence rate ratio [IRR] = 0.21, P = 0.010), and 95.1% (95% confidence interval: 93.4%, 96.8%) sandfly mortality at 12 months. No kala-azar transmission activity was efficacious for vector control (74% vector reduction, IRR = 0.26, P < 0.0001 at 9 months; and 84% sandfly mortality at 3 months), but not for case detection (0 case per intervention). Fever camp + ITN was efficacious in detection of VL/PKDL cases (0.43 case per intervention), but its efficacy for vector control was inconsistent. We recommend index case-based FC for ACD combined with DWL or IRS plus larvicide for sandfly control during the consolidation and maintenance phases of the VL elimination program of the Indian subcontinent.

Under-reporting of tuberculosis in Praia, Cape Verde, from 2006 to 2012.

SETTING: According to World Health Organization (WHO) estimates, the under-reporting rate for tuberculosis (TB) in Cape Verde between 2006 and 2012 was 49%. However, the WHO recognises the challenges associated with this estimation process and recommends implementing other methods, such as record linkage, to combat TB under-reporting. OBJECTIVES: To estimate and analyse under-reporting of cases by TB surveillance health units and to evaluate TB cases retrieved from other TB diagnostic sources in Praia, Cape Verde, from 2006 to 2012. DESIGN: This cross-sectional study evaluated under-reporting using the following data: 1) the under-reporting index from TB reporting health units (RHUs), where the number of validated TB cases from RHUs was compared with data from the National Programme for the Fight against Tuberculosis and Leprosy (NPFTL); and 2) the under-reporting index among overall data sources, or a comparison of the number of all validated TB cases from all sources with NPFTL data. RESULTS: The TB under-reporting rate was 40% in Praia during the study period, and results were influenced by laboratory findings. CONCLUSION: The TB under-reporting rate was very similar to the rate estimated by the WHO. TB surveillance must be improved to reduce under-reporting.