Whole-blood culture-derived cytokine combinations for the diagnosis of tuberculosis.

Introduction: The diagnosis of tuberculosis (TB) disease and TB infection (TBI) remains a challenge, and there is a need for non-invasive and blood-based methods to differentiate TB from conditions mimicking TB (CMTB), TBI, and healthy controls (HC). We aimed to determine whether combination of cytokines and established biomarkers could discriminate between 1) TB and CMTB 2) TB and TBI 3) TBI and HC. Methods: We used hemoglobin, total white blood cell count, neutrophils, monocytes, C-reactive protein, and ten Meso Scale Discovery analyzed cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon (IFN)-É£, and tumor necrosis factor (TNF)-α) in TruCulture whole blood tubes stimulated by lipopolysaccharides (LPS), zymosan (ZYM), anti-CD3/28 (CD3), and unstimulated (Null) to develop three index tests able to differentiate TB from CMTB and TBI, and TBI from HC. Results: In 52 persons with CMTB (n=9), TB (n=23), TBI (n=10), and HC (n=10), a combination of cytokines (LPS-IFN-É£, ZYM-IFN-É£, ZYM-TNF-α, ZYM-IL-1ß, LPS-IL-4, and ZYM-IL-6) and neutrophil count could differentiate TB from CMTB with a sensitivity of 52.2% (95% CI: 30.9%-73.4%) and a specificity of 100 % (66.4%-100%). Null- IFN-É£, Null-IL-8, CD3-IL-6, CD3-IL-8, CD3-IL-13, and ZYM IL-1b discriminated TB from TBI with a sensitivity of 73.9% (56.5% - 91.3%) and a specificity of 100% (69.2-100). Cytokines and established biomarkers failed to differentiate TBI from HC with ≥ 98% specificity. Discussion: Selected cytokines may serve as blood-based add-on tests to detect TB in a low-endemic setting, although these results need to be validated.

Screening for latent tuberculosis in migrants-status quo and future challenges.

OBJECTIVES: To review the evidence that migrants from tuberculosis (TB) high-incidence countries migrating to TB low-incidence countries significantly contribute to active TB cases in the counties of destination, primarily through reactivation of latent TB. METHODS: This is a narrative review. The different screening programs in the countries of destination are reviewed either based on screening and preventive treatment of latent TB pre or more commonly - post arrival. RESULTS: Screening can be performed using interferon-gamma release assays (IGRA) or tuberculin skin tests (TST). Preventive treatment of latent TB is using either monotherapy with isoniazid, or in combination with rifampicin or rifapentine. We discuss the ethical issues of preventive treatment in asymptomatic individuals and how these are addressed in different screening programs. CONCLUSION: Screening migrants from TB high endemic countries to TB low endemic countries is beneficial. There is a lack of standardization and agreement on screening protocols, follow up and treatment.

Mortality, risk factors, and causes of death among people with tuberculosis in Denmark, 1990-2018.

OBJECTIVES: This study aimed to analyze mortality, risk factors, and causes of death among people with tuberculosis (TB). METHODS: This is a population-based cohort study with patients with TB ≥18 years notified from 1990 to 2018 in Denmark, compared with sex- and age-matched controls. Mortality was assessed in Kaplan-Meier models and risk factors for death were estimated in Cox proportional hazards models. RESULTS: Overall mortality was twofold higher among people with TB compared with controls up to 15 years after TB diagnosis (hazard ratio [HR]: 2.18, 95% confidence interval [CI]: 2.06-2.29, P <0.0001). Danes with TB were three times more likely to die than migrants (adjusted HR: 3.13, 95% CI: 2.84-3.45, P <0.0001). Risk factors for death included living alone, being unemployed, having low income, and comorbidities such as mental illness with substance abuse, lung diseases, hepatitis, and HIV. TB was the most common cause of death (21%), followed by chronic obstructive pulmonary disease (7%), lung cancer (6%), alcoholic liver disease (5%), and mental illness with substance abuse (4%). CONCLUSION: People with TB had substantially inferior survival up to 15 years after TB diagnosis, in particular, socially disadvantaged Danes with TB with specific comorbidities. This may reflect unmet needs for enhanced treatment of other medical/social conditions during TB treatment.

Mycobacterium marinum: A Challenging Cause of Protracted Tenosynovitis.

Mycobacterium marinum infections are rare, and they can be difficult to diagnose and treat. This may lead to further spread of the infection and complications, such as tenosynovitis, pyomyositis, and osteomyelitis. A 40-year-old previously healthy man presented with tenosynovitis of the extensor tendons on the second phalanx of his right hand. He was initially treated with steroid injections without any effect. Followingly, ulceration and an abscess developed on the dorsal site of the hand. At this point, it came to the physician's knowledge that the patient had been cleaning an aquarium before onset of symptoms. After progression to massive tenosynovitis, the patient was admitted and underwent multiple surgical debridements. Briefly, after the first surgery, an interferon-γ release assay was positive, and treatment for M. marinum with rifampicin and azithromycin was initiated after eight months of symptoms. Later, a surgical biopsy showed acid-fast bacilli, and a polymerase chain reaction confirmed the diagnosis of M. marinum. In this case story, we highlight the difficulties of diagnosing and managing this complicated infection, describe the considerable morbidity associated with it, and suggest that local tissue concentrations could be useful to improve clinical outcomes, as these concentrations are potentially suboptimal.

Tobacco smoking impact on tuberculosis treatment outcome: an observational study from West Africa.

OBJECTIVE: Both tuberculosis (TB) and tobacco smoking are preventable health hazards. Few studies have examined the relationship between TB and tobacco smoking in an African setting, where the two health burdens collide heavily. This study aimed to describe the severity of TB disease and treatment outcomes among smokers with TB compared with nonsmokers with TB in Guinea-Bissau. METHODS: We conducted a prospective follow-up study between 2003-2017 in Guinea-Bissau, enrolling adult patients with TB classified as nonsmokers or smokers. Disease severity was assessed using the Bandim TBscore. Multivariate logistic and Cox proportional hazard regressions were used to analyse treatment outcomes. RESULTS: Of 1780 included patients, 385 were smokers who had smoked for a median 10 years (interquartile range [IQR] 5-20). No difference in disease severity at the time of diagnosis was observed. Smokers were not significantly more prone to a nonsuccessful treatment outcome, although a trend was seen (adjusted odds ratio [OR] 1.24, 95% confidence interval [CI] 0.91-1.70), and smokers tended to be more often lost to follow-up, but this also was not a significant finding (adjusted hazard ratio [HR] 2.09, 95% CI 0.89-4.94). CONCLUSION: In a TB high-endemic setting with few tobacco smokers, smoking was not associated with disease severity or worse outcome, possibly because of socioeconomic confounders.

The cascade of care in tuberculosis infection screening and management in newly arrived refugees in Aarhus, Denmark.

BACKGROUND: Screening for tuberculosis (TB) disease and infection is often a part of health screening programs offered to refugees, but the yield of screening varies and losses along the steps from screening to treatment completion was reported. METHODS: A retrospective cohort study was performed investigating a newly arrived refugee population offered a systematic refugee health assessment in Aarhus, Denmark. Data was collected on screening, referral, diagnosis and treatment for TB disease and infection. RESULTS: Among both adults and children IGRA positivity was associated with origin in a high TB incidence country and increasing age. The number needed to screen (NNS) to find one case of TB infection was 7 among adult refugees and 19 among children, while NNS for TB disease was 266 and 164 respectively. The proportion of the eligible population with a valid result was 78.1% for adults and 71.3% for children, while 43.1% and 50% of adults and children with presumed TB infection completed preventive treatment. DISCUSSION: Screening for TB disease and infection among refugees in Aarhus had a high yield in terms of diagnosis, however significant losses were seen during screening, follow-up and preventive treatment completion.

Active case-finding of tuberculosis in general populations and at-risk groups: a systematic review and meta-analysis.

BACKGROUND: The World Health Organization (WHO) recommends active case-finding (ACF) of tuberculosis (TB) in certain high-risk groups; however, more evidence is needed to elucidate the scope of ACF beyond the current recommendations. In this study we aimed to systematically review yields (the prevalence of active TB) of studies on ACF in general populations and at-risk groups. METHODS: A literature search in PubMed, Embase and the Cochrane Central Library (CENTRAL) was performed for studies concluded after 31 December 1999 and published before 1 September 2020. Screening yields were estimated and yield/prevalence ratios (ratio between yield of study and WHO estimated prevalence of TB) were calculated to assess which groups might especially benefit from ACF. Finally, risk of bias was assessed and heterogeneity was investigated using meta-regression and sensitivity analyses. RESULTS: We included 197 studies, with a total of 12 372 530 screened and 53 158 cases found. Yields were high among drug users, close contacts, the poor and marginalised, people living with HIV, and prison inmates across incidence strata, and estimated yield/prevalence ratios in screenings of general populations tended to be >1 with an overall ratio of 1.4 and ranging between 1.0 and 1.5. Sensitivity analyses suggested that inclusion of studies at high risk of bias contributed to underestimation of yields. CONCLUSION: Despite many studies using insensitive screening methods, these results suggest that more at-risk groups should be considered for inclusion in future screening recommendations and that screening of general populations may outperform current case-finding practices, providing evidence for extending ACF beyond the current recommendations.

High yield from repeated testing for tuberculosis among high-risk citizens in Denmark.

BACKGROUND: Screening for TB (tuberculosis) among socially marginalized citizens has been implemented in many urban areas in countries with a low incidence of TB, including Denmark. This study aims to describe the findings of the screening programs for TB and latent tuberculosis (LTBI) used in the western part of Denmark in the period 2014-2019. METHODS: Data was collected retrospectively on test results from interferon-gamma release assays (IGRA), spot sputum tests and chest X-rays performed as part of TB and LTBI screening among 1024 socially marginalized citizens in urban areas of western Denmark in 2014-2019. RESULTS: The overall TB incidence was 2148/100.000 and number needed to screen to find one TB case was 39. The incidence of LTBI in the group screened using IGRA was 17.500/100.000. TB incidence when using spot sputum test was 2.5, while TB incidence when using IGRA as the primary screening test was 2.7. In total, 38.9% of TB diagnoses were obtained after the second or third round of screening. CONCLUSION: We demonstrated a high incidence of TB and LTBI among socially marginalized citizens in Denmark. Screening with spot sputum testing and IGRA generated comparable results in diagnosing TB in this setting.

Using BCG vaccine to enhance non-specific protection of health care workers during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial in Denmark.

OBJECTIVES: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism.The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. HYPOTHESIS: BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months. TRIAL DESIGN: Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study. PARTICIPANTS: The trial will recruit 1,500 HCW at Danish hospitals.To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week.A potential subject who meets any of the following criteria will be excluded from participation in this study: Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species Previous confirmed COVID-19 Fever (>38 C) within the past 24 hours Suspicion of active viral or bacterial infection Pregnancy Breastfeeding Vaccination with other live attenuated vaccine within the last 4 weeks Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1) b) subjects with solid organ transplantation c) subjects with bone marrow transplantation d) subjects under chemotherapy e) subjects with primary immunodeficiency f) subjects under treatment with any anti-cytokine therapy within the last year g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months h) Active solid or non-solid malignancy or lymphoma within the prior two years Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place. MAIN OUTCOMES: Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation.Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation.Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1.Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference.The physicians administering the treatment are not blinded.Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group.Trial Status: Current protocol version 5.1, from July 6, 2020.Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020. TRIAL REGISTRATION: The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291.Full protocol: The full protocol is attached as an additional file, accessible from the Trialswebsite (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Tools to implement the World Health Organization End TB Strategy: Addressing common challenges in high and low endemic countries.

AIM: The purpose of this viewpoint is to summarize the advantages and constraints of the tools and strategies available for reducing the annual incidence of tuberculosis (TB) by implementing the World Health Organization (WHO) End TB Strategy and the linked WHO TB Elimination Framework, with special reference to Oman. METHODS: The case-study was built based on the presentations and discussions at an international workshop on TB elimination in low incidence countries organized by the Ministry of Health, Oman, which took place from September 5 to September 7, 2019, and supported by the WHO and European Society of Clinical Microbiology and Infectious Diseases (ESCMID). RESULTS: Existing tools were reviewed, including the screening of migrants for latent TB infection (LTBI) with interferon-gamma release assays, clinical examination for active pulmonary TB (APTB) including chest X-rays, organization of laboratory services, and the existing centres for mandatory health examination of pre-arrival or arriving migrants, including examination for APTB. The need for public-private partnerships to handle the burden of screening arriving migrants for active TB was discussed at length and different models for financing were reviewed. CONCLUSIONS: In a country with a high proportion of migrants from high endemic countries, screening for LTBI is of high priority. Molecular typing and the development of public-private partnerships are needed.

A clinical score has utility in tuberculosis case-finding among patients with HIV: A feasibility study from Bissau.

BACKGROUND: Clinical scores are promising case-finding tools for tuberculosis (TB) among HIV-infected patients. The Bandim TBscore has been shown to increase the diagnostic yield among patients with presumed TB in general, but has not previously been tested among newly diagnosed HIV patients at high risk of TB. METHODS: HIV-infected patients were included in this cross-sectional study. A pre-post-intervention study design was used to assess the outcome of a change in practice, i.e. the application of a clinical score (TBscore) consisting of 13 signs and symptoms to assess the need for further TB diagnostics. Patients with a TBscore ≥2 were evaluated using smear microscopy and Xpert MTB/RIF. A TB diagnosis was made based on microbiology or clinical evaluation. The sensitivity and specificity of the TBscore were compared with those of World Health Organization symptoms. RESULTS: The TB prevalence among newly enrolled HIV-infected patients during the study period was 13.4% (22/164). Using the TBscore and a diagnostic algorithm, it was possible to increase the proportion of patients started on TB treatment from 2.7% (10/367) the year before the study to 10.4% (17/164) during the study period. Five patients diagnosed with TB were not started on TB treatment as they were lost to follow-up or died. With a cut-off value of 2, the TBscore had a sensitivity, specificity, positive predictive value, and negative predictive value of 95.5% (21/22), 36.9% (41/111), 23.1% (22/118), and 97.6% (41/42), respectively. CONCLUSION: The TBscore is useful for standardized TB screening among HIV-infected individuals and may be a valuable tool to prioritize patients at high risk of TB.

Soluble Macrophage Mannose Receptor (sCD206/sMR) as a Biomarker in Human Immunodeficiency Virus Infection.

Macrophages play important roles during human immunodeficiency virus (HIV) infection, reflected by changes in macrophage-activation biomarker soluble CD163 (sCD163). Here, we present data on the novel macrophage-activation biomarker soluble mannose receptor/CD206 (sCD206) in HIV infection. We investigated sCD206 blood levels at baseline and follow-up with/without antiretroviral therapy (ART), in 212 patients with HIV type 1 (HIV-1), HIV type 2 (HIV-2), or dual infection. At baseline, there was no difference in sCD206 level between HIV types, and sCD206 was unchanged at follow-up without ART. However, in contrast to sCD163, sCD206 levels decreased significantly for both HIV-1 and HIV-2, but not for HIV-1/2 patients, during ART. Further investigations are needed to establish sCD206 as a biomarker in HIV infection.

Increased mortality among HIV infected patients with cryptococcal antigenemia in Guinea-Bissau.

Cryptococcal antigenemia may precede development of cryptococcal meningitis and death among patients with advanced HIV infection. Among 200 retrospectively and randomly selected ART-naïve patients with CD4 counts < 100 cells/µl from Guinea-Bissau, 20 (10%) had a positive cryptococcal antigen test. Self-reported headache and fever were predictors of a positive test, while cryptococcal antigenemia was a strong predictor of death within the first year of follow-up, MRR 2.22 (95% CI: 1.15-4.30). Screening for cryptococcal antigenemia should be implemented for patients with advanced HIV in Guinea-Bissau. Pre-emptive anti-fungal therapy should be initiated prior to ART-initiation if the screening is positive.

Comorbidities, mortality and causes of death among patients with tuberculosis in Denmark 1998-2010: a nationwide, register-based case-control study.

OBJECTIVE: To evaluate the impact of comorbidities, age and clinical presentation of TB on mortality among Danish patients with TB. METHODS: Danish patients with an ICD-10 (International Statistical Classification of Diseases and Related Health Problems 10th Revision) diagnosis of TB in 1998-2010 were identified in the National Patient Registry and matched with controls (1:4) on age, gender, civil status and geography. Comorbid diagnoses up to 3 years before and after TB diagnosis or enrolment as control as well as survival data were obtained from national databases RESULTS: We included 8433 cases and 33 707 controls. Respiratory diseases were the most common comorbidities among cases (12.4% of cases, 3.8% of controls (p<0.001)). Overall HR of death was 2.45 (2.31; 2.59). Relative mortality was especially increased among younger adults (HR 8.70 (95% CI 5.53 to 13.69) among the 30 to 39-year-olds). While overall mortality increased with Deyo-Charlson comorbidity (DCC) score, relative mortality among cases was highest in the low-DCC group. Additionally, male gender, low income and central nervous system TB were risk factors for death among TB cases. The most common cause of death in both groups was non-lung cancers, among TB cases followed by COPD, TB and lung cancer, all being significantly more common among TB cases. CONCLUSION: In Denmark, TB carries substantial mortality. Among those who die, 12% are reported to die from TB. A high relative mortality among younger adults underscores the importance of continually targeting high-risk TB groups in low-incidence countries.

Medical treatment for urogenital tuberculosis (UGTB).

Urogenital tuberculosis (UGTB) should in general be treated as pulmonary TB with a four-drug regimen of Isoniazid, Rifampicin, Ethambutol and Pyrazinamide for a total of 6 months, Ethambutol and Pyrazinamide only the first two months. Some patients may need longer treatment (cavitary disease, kidney abscess/malfunction, HIV co-infection). Treatment of multi-drug resistant tuberculosis (MDR-TB) requires use of long-term intravenous treatment with aminoglycosides and other drugs with considerable toxicity for 18-24 months. Complications such as urinary tract obstruction may occur and should be treated with corticosteroids or surgery.

Anemia and growth retardation associated with Schistosoma haematobium infection in Mali: a possible subtle impact of a neglected tropical disease.

Background: The aim of this cross-sectional study was to investigate a possible association of Schistosoma haematobium with child growth development and describe a plausible schistosomiasis-related anemia in children and adults in a highly schistosomiasis endemic area of Mali. Methods: Urine, feces and blood samples from 399 participants of both sexes (2-40 years of age) were analyzed and supplemented by anthropometric measurements. Results: S. haematobium prevalence was 79.8%, S. mansoni 13.2% and Plasmodium falciparum 80.2%. S. haematobium infection intensity as five categories was significantly associated with anemia; i.e., odds of having anemia in the highest and the next highest category was 3.25 (95% CL 1.61-6.55; p<0.01) and 2.45 (95% CL 1.28-4.70; p<0.01), respectively, of that in the three lower categories combined after adjusting for age group and gender and the interaction between the two factors. Anemia was most pronounced in the 2-5 year olds males (55.5%, n=98). P. falciparum infection was not significantly associated with anemia. Stunting (body mass index [BMI] for age z-score<-2.00) was observed in 2.6% (2/78) of the 2-5 years olds and in 7.7% (14/182) in the 6-19 years age group. Lower BMI-z-scores (as continuous variable) were associated with anemia (p<0.05) while high intensity of S. haematobium infection was not significant when adjusting for age group and anemia. Participants with malaria infection had lower z-scores (as continuous variables) of weight and height for age. Lower height for age z-scores were also associated with anemia. Conclusions: S. haematobium infection is likely to impact on child growth and possibly also anemia in all age groups and advocates for inclusion of whole populations into future control programes.

Development of an epitope panel for consistent identification of antigen-specific T-cells in humans.

We aimed to establish a panel of MHC-peptide multimers suitable as a positive control in the detection of HLA A*0201 restricted antigen specific T cells (ASTC) by flow cytometry. MHC Dextramers were loaded with HLA A*0201 binding peptides from viral antigens and melanoma targets identified from a literature search and in silico prediction. Peripheral blood mononuclear cells (PBMC) from healthy donors were analysed with the MHC Dextramers using flow cytometry. The best performing epitopes were tested on PBMC from patients undergoing testing for Mycobacterium tuberculosis infection to assess the coverage of this epitope panel. Of 21 candidate epitopes, ASTC could be detected against 12 (57·1%) in at least one of 18 healthy blood donors. Reactivity to two or more epitopes was seen in 17 of the 18 donors (94·4%). We selected the six best-performing epitopes and demonstrated a positive response in 42 (97·7%) of 43 patient samples (healthy, latent and active M. tuberculosis infection). The selected panel of six antigenic epitopes sufficed as a positive control in the detection of ASTC in HLA A*0201. Performance was robust in different stages of latent and active M. tuberculosis infection, indicating reliability also during infection.

Systematic health screening of refugees after resettlement in recipient countries: a scoping review.

CONTEXT: Health screening of refugees after settlement in a recipient country is an important tool to find and treat diseases. Currently, there are no available reviews on refugee health screening after resettlement. METHODS: A systematic literature search was conducted using the online Medical Literature Analysis and Retrieval System ('MEDLINE') database. Data extraction and synthesis were performed according to the PRISMA statement. RESULTS: The search retrieved 342 articles. Relevance screening was conducted on all abstracts/titles. The final 53 studies included only original scientific articles on health screening of refugees conducted after settlement in another country. The 53 studies were all from North America, Australia/New Zealand and Europe. Because of differences in country policies, the screenings were conducted differently in the various locations. The studies demonstrated great variation in who was targeted for screening and how screening was conducted. The disease most frequently screened for was tuberculosis; this was done in approximately half of the studies. Few studies included screening for mental health and non-infectious diseases like diabetes and hypertension. CONCLUSION: Health screening of refugees after resettlement is conducted according to varying local policies and there are vast differences in which health conditions are covered in the screening and whom the screening is available to.

Noma in an HIV infected patient in Guinea-Bissau: a case report.

BACKGROUND: Noma is a multifactorial and multibacterial opportunistic infection that initially causes necrotic gingivitis but rapidly spreads to the nearby orofacial tissue resulting in sloughing and severe deformation of the facial structures. The majority of cases are seen in young children under the age of 6 years. Noma is strongly associated with poverty, malnutrition and immunosuppression, and is often preceded by severe systemic infections such as measles and malaria. Only few cases of noma infection in adults have been described. CASE REPORT: We present here a case report with a 32-year-old Guinean woman who was diagnosed with noma infection and on that occasion discovered that she was HIV-1 seropositive. After treatment with amoxicillin/clavulanic acid and metronidazole for her noma infection the woman was transferred to the national hospital where antiretroviral treatment was initiated. CONCLUSION: Noma is an opportunistic infection and immunodeficiencies such as HIV should always be suspected when presenting in an adult patient.

Latent tuberculosis infection is prevalent among socially marginalised citizens in Aarhus, Denmark.

INTRODUCTION: Even in low-incidence countries, tuberculosis (TB) is common among socially marginalised people. Latent tuberculosis infection (LTBI) comprises a reservoir for future disease, and screening for LTBI and TB in these groups aids in the prevention and early detection of TB. METHODS: We performed a screening for LTBI with interferon gamma release assay (IGRA) testing, and TB screening with sputum smear examination at four shelters and four additional locations in a Danish urban area. Additionally, shelter volunteers were offered examination. RESULTS: A total of 145 subjects were tested; 124 with sputum smear and 100 with IGRA. Overall, 13 (13%) had LTBI, and one (0.8%) had smear-negative, culture-positive, non-cavitating TB. Among 107 socially marginalised citizens, persons of Greenlandic origin had significantly more LTBI (40.0%) than Danish subjects (9.1%) (odds ratio (OR) = 6.67 (range: 1.55-28.63)), and other ethnicities had an intermediate prevalence of LTBI (18.2%) (OR versus Danish subjects = 2.22 (range: 0.35-14.06)). A total of 38 shelter volunteers were also included; IGRA was performed in 30 of those and one (3.33%) had LTBI. CONCLUSIONS: Our results confirm that a screening approach may reveal early cases of active TB. LTBI is common among the socially marginalised people, but varies substantially with ethnic origin. FUNDING: T-spot.TB kits were provided by Oxford Immunotec. TRIAL REGISTRATION: not relevant.