Using BCG Vaccine to Enhance Nonspecific Protection of Health Care Workers During the COVID-19 Pandemic: A Randomized Controlled Trial.

BACKGROUND: The BCG (Bacillus Calmette-Guérin) vaccine can induce nonspecific protection against unrelated infections. We aimed to test the effect of BCG on absenteeism and health of Danish health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A single-blinded randomized controlled trial included 1221 HCWs from 9 Danish hospitals. Participants were randomized 1:1 to standard dose BCG or placebo. Primary outcome was days of unplanned absenteeism. Main secondary outcomes were incidence of COVID-19, all-cause hospitalization, and infectious disease episodes. RESULTS: There was no significant effect of BCG on unplanned absenteeism. Mean number of days absent per 1000 workdays was 20 in the BCG group and 17 in the placebo group (risk ratio, 1.23; 95% credibility interval, 0.98-1.53). BCG had no effect on incidence of COVID-19 or all-cause hospitalization overall. In secondary analyses BCG revaccination was associated with higher COVID-19 incidence (hazard ratio [HR], 2.47; 95% confidence interval [CI], 1.07-5.71), but also reduced risk of hospitalization (HR, 0.28; 95% CI, .09-.86). The incidence of infectious disease episodes was similar between randomization groups (HR, 1.09; 95% CI, .96-1.24). CONCLUSIONS: In this relatively healthy cohort of HCWs, there was no overall effect of BCG on any of the study outcomes. CLINICAL TRIALS REGISTRATION: NCT0437329 and EU Clinical Trials Register (EudraCT number 2020-001888-90).

Drug-Resistant Tuberculosis, Georgia, Kazakhstan, Kyrgyzstan, Moldova, and Ukraine, 2017-2022.

In 2021, the World Health Organization recommended new extensively drug-resistant (XDR) and pre-XDR tuberculosis (TB) definitions. In a recent cohort of TB patients in Eastern Europe, we show that XDR TB as currently defined is associated with exceptionally poor treatment outcomes, considerably worse than for the former definition (31% vs. 54% treatment success).

SARS-CoV-2 vaccine immunogenicity for people living with HIV: A systematic review and meta-analysis.

BACKGROUND: Previous publications on the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with HIV (PLWH) have reported inconsistent results. Additionally, a meta-analysis investigating the immunogenicity in PLWH after the third SARS-CoV-2 vaccine dose is lacking. In this article we aim to provide a systematic review and a meta-analysis studying the immunogenicity of SARS-CoV-2 vaccines in PLWH and to identify potential drivers for antibody response in PLWH. METHODS: We used three databases (PubMed, Embase and Web of Science) to conduct our review. Studies with information on numbers of PLWH producing immunoglobulin G (IgG) antibodies or neutralizing antibodies were included. RESULTS: The meta-analysis included 59 studies and illustrated a pooled serological response of 87.09% in the 10 343 PLWH after they received a SARS-CoV-2 vaccine. High CD4 T-cell counts and low viral load indicated that the study populations had HIV that was well treated, despite varying in location. The pooled effect increased to 91.62% for 8053 PLWH when excluding studies that used inactivated vaccines (BBIBP-CorV and CoronaVac). For the third vaccine dose, the pooled effect was 92.35% for 1974 PLWH. Additionally, weighted linear regression models demonstrated weak relationships between CD4 T-cell count, percentages of people with undetectable HIV load, and age compared with the percentages of PLWH producing a serological response. However, more research is needed to determine the effect of those factors on SARS-CoV-2 vaccine immunogenicity in PLWH. CONCLUSION: SARS-CoV-2 vaccines show a favourable effect on immunogenicity in PLWH. However, the results are not ideal. This meta-analysis suggests that a third SARS-CoV-2 vaccine dose and good HIV treatment procedures are vital to induce a good immunogenicity in PLWH.

Prevalence estimates of tuberculosis infection in adults in Denmark: a retrospective nationwide register-based cross-sectional study, 2010 to 2018.

BackgroundTuberculosis (TB) elimination requires identifying and treating persons with TB infection (TBI).AimWe estimate the prevalence of positive interferon gamma release assay (IGRA) tests (including TB) and TBI (excluding TB) in Denmark based on TBI screening data from patients with inflammatory bowel disease (IBD) or inflammatory rheumatic disease (IRD).MethodsUsing nationwide Danish registries, we included all patients with IBD or IRD with an IGRA test performed between 2010 and 2018. We estimated the prevalence of TBI and positive IGRA with 95% confidence intervals (CI) in adolescents and adults aged 15-64 years after sample weighting adjusting for distortions in the sample from the background population of Denmark for sex, age group and TB incidence rates (IR) in country of birth.ResultsIn 13,574 patients with IBD or IRD, 12,892 IGRA tests (95.0%) were negative, 461 (3.4%) were positive and 221 (1.6%) were indeterminate, resulting in a weighted TBI prevalence of 3.2% (95% CI: 2.9-3.5) and weighted positive IGRA prevalence of 3.8% (95% CI: 3.5-4.2) among adults aged 15-64 years in the background population of Denmark. Unweighted TBI prevalence increased with age and birthplace in countries with a TB IR higher than 10/100,000 population.ConclusionEstimated TBI prevalence is low in Denmark. We estimate that 200,000 persons have TBI and thus are at risk of developing TB. Screening for TBI and preventive treatment, especially in persons born in high TB incidence countries or immunosuppressed, are crucial to reduce the risk of and eliminate TB.

The association between common mental disorders and tuberculosis: a case-control study from Guinea-Bissau.

OBJECTIVE: The aim of the study was to explore the association between tuberculosis (TB) and common mental disorders (CMD), in an area with high prevalence of TB. METHODS: We performed a case-control study of TB patients and unmatched healthy controls, from a demographic surveillance site in Guinea-Bissau. Screening for CMD was performed once for controls and at inclusion and follow-up for TB patients. Kessler 10 (K-10) and a brief version of Hopkins Symptom Checklist 25 (SCL-8d) were used as screening instruments. RESULTS: 571 controls were interviewed and 416 interviews were performed for 215 TB cases. Estimated CMD prevalence at the time of diagnosis of TB was 33.6 % (SCL-8d) and 46.2 % (K-10), compared with 6.8 % (SCL-8d) and 6.7 % (K-10) among controls; adjusted OR 7.18 (95 % CI 4.07 to 12.67) and 14.52 (95 % CI 8.15 to 25.84), respectively. No significant difference in CMD prevalence rates was observed between TB patients, after 6 months of treatment, and controls. CONCLUSION: Psychological distress and common mental disorders were more prevalent among TB patients at the time of diagnosis compared with the background population, but after completion of TB treatment no increased prevalence of psychological distress was found.

Efficacy and Tolerability of Concomitant Use of Bedaquiline and Delamanid for Multidrug- and Extensively Drug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis.

The introduction of two novel drugs, bedaquiline and delamanid, has given hope for better and shorter treatments of drug-resistant tuberculosis. A systematic review was conducted to evaluate the efficacy and safety of concomitant bedaquiline and delamanid administration. Pooled estimates of World Health Organization-defined favorable treatment outcome and significant QTc-interval prolongation (QTc ≥500 ms or ≥60 ms increase from baseline) were calculated using a random-effects model. Thirteen studies including a total of 1031 individuals with multidrug-resistant/rifampicin-resistant tuberculosis who received bedaquiline and delamanid were included. The pooled estimate of favorable treatment outcome was 73.1% (95% confidence interval [CI]: 64.3-81.8%). Sputum culture conversion at 6 months ranged from 61% to 95%. Overall, the pooled proportion of QTc-prolongation was 7.8% (95% CI: 4.1-11.6%) and few cardiac events were reported (0.8%; n = 6/798). Rates of sputum culture conversion and favorable treatment outcome were high in patients treated concomitantly with bedaquiline and delamanid, and the treatment seemed tolerable with low rates of clinically significant cardiac toxicity.

Incidence of pulmonary tuberculosis in suburban Bissau, Guinea-Bissau between 2004 and 2020: a prospective cohort study.

OBJECTIVES: Previous studies have found declining incidence of tuberculosis (TB) in Bissau, Guinea-Bissau. This study aimed to report incidence rates of TB for the period 2004-2020, stratifying by sex, smear-status, and HIV-status, as well as describe developments in TB case fatality rate and diagnostic delay. DESIGN AND METHODS: Data from the Bandim Health Project HDSS and the TB registry from Jan 1st, 2004 to Dec 31st, 2020 were used. Incidence rates were calculated for each year and for smear-positive, smear-negative, HIV-positive, HIV-negative, and unknown HIV-status. Incidence rate ratio and test for trend were done using a one-step Newton approximation to the log-linear Poisson regression coefficient. RESULTS: Overall TB incidence declined only slightly over the period from 294 per 100,000 in 2004 to 273 in 2020. TB/HIV coinfection declined from 108 in 2004 to 14 in 2020, as did incidence among females and smear-negative cases. CONCLUSIONS: Incidence of PTB in Bissau, Guinea-Bissau is declining slowly, if at all. TB incidence among females, smear-negative TB, TB case fatality rate, and TB/HIV coinfection and diagnostic delay are declining.

Is being a refugee associated with increased 30-day mortality after visiting the emergency department? A register-based cohort study using Danish data.

AIM: Refugees face many challenges that could lead to disparity in quality of care from the health-care system compared with native Danes. These challenges could be language barriers, cultural differences, mental health co-morbidities and socio-economic status (SES). The aim of this study was to compare the 30-day mortality of refugees and native Danes after visiting the emergency department (ED) at Aarhus University Hospital, Denmark. METHODS: In this register-based cohort study linking clinical and socio-demographic data, we included all visits to a major Danish ED from 1 January 2016 to 31 December 2018. According to the predefined analysis plan, we present non-parametric Kaplan-Meier plots and propensity score-weighted analysis. RESULTS: We included 29,257 eligible unique patients of whom 631 were refugees. In the 30-day time period after discharge from the ED, 11 deaths occurred in the group of refugees, resulting in a Kaplan-Meier estimate of 1.8% (95% confidence interval (CI) 0.7-2.8), and 1638 deaths occurred in the group of Danes, resulting in a Kaplan-Meier estimate of 5.9% (95% CI 5.6-6.1). The adjusted 30-day mortality risk difference was 1.6 percentage points (95% CI -2.0 to -1.2 percentage points) lower for refugees compared to native Danes. The 30-day mortality risk difference decreased from approximately 4 to 1.6 percentage points in the adjusted analysis. Thus, there were 16 fewer deaths among refugees within 30 days per 1000 discharged from the ED compared with native Danes when adjusting for age, sex, SES and co-morbidities. CONCLUSIONS: This study shows that refugees had a lower 30-day mortality after visiting the ED compared with native Danes.

Interaction between host genes and Mycobacterium tuberculosis lineage can affect tuberculosis severity: Evidence for coevolution?

Genetic studies of both the human host and Mycobacterium tuberculosis (MTB) demonstrate independent association with tuberculosis (TB) risk. However, neither explains a large portion of disease risk or severity. Based on studies in other infectious diseases and animal models of TB, we hypothesized that the genomes of the two interact to modulate risk of developing active TB or increasing the severity of disease, when present. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which there were 3 MTB lineages of which L4-Ugandan (L4.6) is the most recent. TB severity, measured using the Bandim TBscore, was modeled as a function of host SNP genotype, MTB lineage, and their interaction, within two independent cohorts of TB cases, N = 113 and 121. No association was found between lineage and severity, but association between multiple polymorphisms in IL12B and TBscore was replicated in two independent cohorts (most significant rs3212227, combined p = 0.0006), supporting previous associations of IL12B with TB susceptibility. We also observed significant interaction between a single nucleotide polymorphism (SNP) in SLC11A1 and the L4-Ugandan lineage in both cohorts (rs17235409, meta p = 0.0002). Interestingly, the presence of the L4-Uganda lineage in the presence of the ancestral human allele associated with more severe disease. These findings demonstrate that IL12B is associated with severity of TB in addition to susceptibility, and that the association between TB severity and human genetics can be due to an interaction between genes in the two species, consistent with host-pathogen coevolution in TB.

Rolling Circle Enhanced Detection of Specific Restriction Endonuclease Activities in Crude Cell Extracts.

Restriction endonucleases are expressed in all bacteria investigated so far and play an essential role for the bacterial defense against viral infections. Besides their important biological role, restriction endonucleases are of great use for different biotechnological purposes and are indispensable for many cloning and sequencing procedures. Methods for specific detection of restriction endonuclease activities can therefore find broad use for many purposes. In the current study, we demonstrate proof-of-concept for a new principle for the detection of restriction endonuclease activities. The method is based on rolling circle amplification of circular DNA products that can only be formed upon restriction digestion of specially designed DNA substrates. By combining the activity of the target restriction endonuclease with the highly specific Cre recombinase to generate DNA circles, we demonstrate specific detection of selected restriction endonuclease activities even in crude cell extracts. This is, to our knowledge, the first example of a sensor system that allows activity measurements of restriction endonucleases in crude samples. The presented sensor system may prove valuable for future characterization of bacteria species or strains based on their expression of restriction endonucleases as well as for quantification of restriction endonuclease activities directly in extracts from recombinant cells.

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.

Life expectancy of HIV-infected patients followed at the largest hospital in Guinea-Bissau is one-fourth of life expectancy of the background population.

PURPOSE: To estimate the life expectancy (LE) of HIV-infected patients in the West African country Guinea-Bissau and compare it with the background population. METHODS: Using data from the largest HIV outpatient clinic at the Hospital Nacional Simão Mendes in the capital Bissau, a retrospective observational cohort study was performed. The study included patients attending the clinic between June 2005 and January 2018. A total of 8958 HIV-infected patients were included. In the analysis of the background population, a total of 109,191 people were included. LE incorporating loss to follow-up (LTFU) was estimated via Kaplan-Meier estimators using observational data on adult HIV-infected patients and background population. RESULTS: The LE of 20-year-old HIV-infected patients was 9.8 years (95% CI 8.3-11.5), corresponding to 22.3% (95% CI 18.5-26.7%) of the LE of the background population. (LE for 20-year-olds in the background population was 44.0 years [95% CI 43.0-44.9].) Patients diagnosed with CD4 cell counts below 200 cells/µL had a LE of 5.7 years (95% CI 3.6-8.2). No increase in LE with later calendar period of diagnosis was observed. CONCLUSIONS: LE was shown to be markedly lower among HIV-infected patients compared with the background population. While other settings have shown marked improvements in prognosis of HIV-infected patients in recent years, no improvement in Bissau was observed over time (9.8 years (95% CI 7.6-12.2) and 9.9 years (95% CI 7.6-12.1) for the periods 2005-2010 and 2014-2016, respectively).

Pregnancy complications among refugee women: A systematic review.

INTRODUCTION: Pregnancy is a time of increased vulnerability for women. Women of refugee background may be further challenged in pregnancy due to a complex series of physical, psychological and social factors. Previous studies show ambiguous results, with some showing increased the risk of prenatal complications in refugees compared with their native counterparts, whereas other studies report the opposite. With the current steep rise in the number of refugees and displaced persons worldwide, research is important to understand whether pregnancy disparities between this population and their native counterparts exist, and the causes. This systematic literature review aims to find out whether refugee women have a higher prevalence of adverse pregnancy outcomes and prenatal infections compared with native women. MATERIAL AND METHODS: We conducted a literature search in the databases PubMed and Embase, supplemented with screening of reference lists and citations for relevant literature. We included studies published in English reporting risk of preeclampsia, spontaneous abortion and stillbirths, preterm birth, preterm prelabor rupture of membranes (PPROM) and adverse prenatal infectious diseases in women of refugee status. PROSPERO registration CRD42020205628. RESULTS: We identified 19 articles eligible for inclusion: 12 were cross-sectional, six were cohort studies and one was a case-control study. The most frequently reported outcome in the literature was preterm birth (reported in 16 of the studies) and preeclampsia (reported in 11 of the studies). Refugees had increased risk of stillbirth (reported relative risk ranging from 1.20 to 2.24) and spontaneous abortion (reported relative risk ranging from 1.56 to 1.58), when compared with native women and a decreased risk of preeclampsia (reported relative risk ranging from 0.65 to 0.81). CONCLUSIONS: The small number of articles eligible for inclusion in the review highlights the lack of research and knowledge on refugee health during pregnancy. Further research is required to understand and reduce disparities in pregnancy outcomes between refugee and non-refugee women.

Hepatitis B and C in the adult population of Bissau, Guinea-Bissau: a cross-sectional survey.

OBJECTIVE: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are prevalent in West Africa. To address the WHO 2030 goals of a 90% reduction in incidence and a 65% reduction in mortality for both infections, we assessed the prevalence of HBV and HCV from surveys in the general population. METHODS: Participants in this cross-sectional survey were included from randomly selected houses in a demographic surveillance site in Bissau, Guinea-Bissau. Participants were interviewed and had a blood sample drawn for viral analyses (HBsAg, anti-HBs, anti-HBc, anti-HCV and HCV RNA). Risk factors of HBV and HCV infection were determined by binomial regression adjusted for sex and age. RESULTS: A total of 2715 participants were included in this study. The overall HBsAg prevalence was 18.7% (95% CI: 17.3-20.2%). HBsAg was associated with male sex (adjusted risk ratio (aRR): 1.64), and prevalence decreased with age >34 years. HBV exposure was found in 91.9% of participants. Although 72.6% of individuals without sexual debut had been exposed to HBV, ever engaging in a sexual relationship was associated with higher risk of HBV exposure (aRR 1.18). The anti-HCV prevalence was 0.5% (95% CI: 0.3-0.9%), and 78.6% of those had detectable HCV RNA. Risk factors for anti-HCV sero-positivity were age above 55 (aRR 10.60), a history of blood transfusion (aRR 5.07) and being in a polygamous marriage (aRR 3.52). CONCLUSION: In Guinea-Bissau initiatives to implement treatment and widespread testing are needed to reach the WHO 2030 goals.

OBJECTIF: Le virus de l'hépatite B (VHB) et le virus de l'hépatite C (VHC) sont répandus en Afrique de l'Ouest. Pour atteindre les objectifs de 2030 de l'OMS d'une réduction de 90% de l'incidence et de 65% de la mortalité pour les deux infections, nous avons évalué la prévalence du VHB et du VHC à partir d'enquêtes dans la population générale. MÉTHODES: Les participants inclus dans cette enquête transversale provenaient de foyers sélectionnés au hasard dans un site de surveillance démographique à Bissau, en Guinée-Bissau. Les participants ont été interrogés et ont subi un prélèvement d'échantillon de sang pour des analyses virales (HBsAg, anti-HBs, anti-HBc, anti-HCV et ARN du HCV). Les facteurs de risque d'infection par le VHB et le VHC ont été déterminés par la régression binomiale ajustée en fonction du sexe et de l'âge. RÉSULTATS: 2.715 participants ont été inclus dans cette étude. La prévalence globale de l'HBsAg était de 18,7% (IC95%: 17,3-20,2%). L'HBsAg était associé au sexe masculin (rapport de risque ajusté (aRR): 1,64), et la prévalence diminuait avec l'âge >34 ans. Une exposition au VHB a été observée chez 91,9% des participants. Bien que 72,6% des personnes sans début d'activité sexuelle aient été exposées au VHB, le fait de s'engager dans des relations sexuelles était associé à un risque plus élevé d'exposition au VHB (aRR: 1,18). La prévalence d'anti-VHC était de 0,5% (IC95%: 0,3-0,9%) et 78,6% d'entre eux avaient de l'ARN du VHC détectable. Les facteurs de risque de séropositivité anti-VHC étaient l'âge de plus de 55 ans (aRR: 10,60), les antécédents de transfusion sanguine (aRR: 5,07) et le fait d'être dans un mariage polygame (aRR: 3,52). CONCLUSION: En Guinée-Bissau, des initiatives pour mettre en œuvre un traitement et des tests généralisés sont nécessaires pour atteindre les objectifs de l'OMS 2030.

Acceptance and Feasibility of Partner Notification to HIV Infected Individuals in Guinea-Bissau.

As partner notification (PN) has shown effective in increasing the number of partners of HIV infected patients being tested we aimed to evaluate the feasibility of implementing PN in the West-African country Guinea-Bissau. Patients enrolled were offered the choice of three different PN methods. Acceptance, successful referrals and HIV status of partners were evaluated. Of 697 patients offered PN, 495 (71.0%) accepted and listed 547 partners. At end of follow-up 118 (21.5%) partners had been tested of which 44 (37.3%) were HIV infected. HIV infected partners had a higher median CD4 count at diagnosis compared with index patients; 401 cells/mm3 versus 240 cells/mm3, p < 0.001. The results indicate that implementation of PN is feasible, effective in identifying HIV infected partners and enables initiation of earlier treatment, yet there are major barriers to bringing partners in for testing which should be addressed in order to exploit the full potential of PN.

Review of tuberculosis treatment outcome reporting system in Denmark, a retrospective study cohort study from 2009 through 2014.

BACKGROUND: In Denmark, reporting of tuberculosis (TB) treatment outcome is voluntary and data incomplete. In the European Centre for Disease Prevention and Control most recent report presenting data from 2017, only 53.9% of Danish pulmonary TB cases had a reported outcome. Monitoring of TB treatment outcome is not feasible based on such limited results. In this retrospective study from 2009 to 2014, we present complete treatment outcome data and describe characteristics of cases lost to follow up. METHODS: All cases notified from 2009 through 2014 were reviewed. Hospital records were examined, and TB treatment outcome was categorized according to the World Health Organization's (WHO) definitions. RESULTS: A total of 2131 TB cases were included. Treatment outcome was reported to the Surveillance Unit in 1803 (84.6%) cases, of which 468 (26.0%) were reclassified. For pulmonary TB, 339 (28.9%) cases were reclassified between cured and treatment completed. Overall, the proportion of cases who achieved successful treatment outcome increased from 1488 (70.4%) to 1748 (81.8%). CONCLUSION: A high number of cases were reclassified during the review process. Increased focus on correct treatment outcome reporting is necessary in Denmark. A more comprehensive and exhaustive categorization of TB treatment outcome could be beneficial, especially for cases where collection of sputum or tissue towards the end of treatment is challenging.

The global prevalence of latent tuberculosis: a systematic review and meta-analysis.

In 1999, the World Health Organization (WHO) estimated that one-third of the world's population had latent tuberculosis infection (LTBI), which was recently updated to one-fourth. However, this is still based on controversial assumptions in combination with tuberculin skin test (TST) surveys. Interferon-γ release assays (IGRAs) with a higher specificity than TST have since been widely implemented, but never used to estimate the global LTBI prevalence.We conducted a systematic review and meta-analysis of LTBI estimates based on both IGRA and TST results published between 2005 and 2018. Regional and global estimates of LTBI prevalence were calculated. Stratification was performed for low, intermediate and high TB incidence countries and a pooled estimate for each area was calculated using a random effects model.Among 3280 studies screened, we included 88 studies from 36 countries with 41 IGRA (n=67 167) and 67 TST estimates (n=284 644). The global prevalence of LTBI was 24.8% (95% CI 19.7-30.0%) and 21.2% (95% CI 17.9-24.4%), based on IGRA and a 10-mm TST cut-off, respectively. The prevalence estimates correlated well to WHO incidence rates (Rs=0.70, p<0.001).In the first study of the global prevalence of LTBI derived from both IGRA and TST surveys, we found that one-fourth of the world's population is infected. This is of relevance, as both tests, although imperfect, are used to identify individuals eligible for preventive therapy. Enhanced efforts are needed targeting the large pool of latently infected individuals, as this constitutes an enormous source of potential active tuberculosis.

Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data.

BACKGROUND: Randomised controlled trials of adjunctive vitamin D in pulmonary tuberculosis (TB) treatment have yielded conflicting results. Individual participant data meta-analysis could identify factors explaining this variation. METHODS: We meta-analysed individual participant data from randomised controlled trials of vitamin D in patients receiving antimicrobial therapy for pulmonary TB. Primary outcome was time to sputum culture conversion. Secondary outcomes were time to sputum smear conversion, mean 8-week weight and incidence of adverse events. Pre-specified subgroup analyses were done according to baseline vitamin D status, age, sex, drug susceptibility, HIV status, extent of disease and vitamin D receptor genotype. RESULTS: Individual participant data were obtained for 1850 participants in eight studies. Vitamin D did not influence time to sputum culture conversion overall (adjusted HR 1.06, 95% CI 0.91-1.23), but it did accelerate sputum culture conversion in participants with multidrug-resistant pulmonary TB (adjusted HR 13.44, 95% CI 2.96-60.90); no such effect was seen in those whose isolate was sensitive to rifampicin and/or isoniazid (adjusted HR 1.02, 95% CI 0.88-1.19; p-value for interaction=0.02). Vitamin D accelerated sputum smear conversion overall (adjusted HR 1.15, 95% CI 1.01-1.31), but did not influence other secondary outcomes. CONCLUSIONS: Vitamin D did not influence time to sputum culture conversion overall, but it accelerated sputum culture conversion in patients with multidrug-resistant pulmonary TB.

Delays in the Diagnosis and Treatment of Tuberculous Lymphadenitis in Low-Incidence Countries: A Systematic Review.

Early detection and treatment of tuberculosis (TB) is essential to achieve the goals appointed in the WHO End TB Strategy. Tuberculous lymphadenitis (TBLA) is the most common manifestation of extrapulmonary TB, but the diagnosis can be challenging in low-incidence countries due to sparse and inconsistent clinical features, resulting in delay. We aimed to summarize and discuss the current literature on patient delay, health care delay, and total delay (i.e., time to first health care contact, diagnosis, and treatment) in patients with TBLA in TB low-incidence countries. A systematic review using PubMed was conducted, searching for studies set in TB low-incidence countries (defined as <20 per 100,000 citizens) that reported on health care seeking behaviour, patient delay, health care delay, and/or total delay. Studies were categorized by type of delay and compared. We identified 11 heterogeneous studies with highly variable observations. Mean patient delay varied from 55 to 154 days (range, 14-1,461), mean health care delay from 44 to 94 days (range, 7-224) and median total delay from 77.5 to 122 days (range, 0-2,820). Evidently, more comprehensive insights into the diagnostic pathway and delay in TBLA patients are warranted.

HIV-2 as a model to identify a functional HIV cure.

Two HIV virus types exist: HIV-1 is pandemic and aggressive, whereas HIV-2 is confined mainly to West Africa and less pathogenic. Despite the fact that it has been almost 40 years since the discovery of AIDS, there is still no cure or vaccine against HIV. Consequently, the concepts of functional vaccines and cures that aim to limit HIV disease progression and spread by persistent control of viral replication without life-long treatment have been suggested as more feasible options to control the HIV pandemic. To identify virus-host mechanisms that could be targeted for functional cure development, researchers have focused on a small fraction of HIV-1 infected individuals that control their infection spontaneously, so-called elite controllers. However, these efforts have not been able to unravel the key mechanisms of the infection control. This is partly due to lack in statistical power since only 0.15% of HIV-1 infected individuals are natural elite controllers. The proportion of long-term viral control is larger in HIV-2 infection compared with HIV-1 infection. We therefore present the idea of using HIV-2 as a model for finding a functional cure against HIV. Understanding the key differences between HIV-1 and HIV-2 infections, and the cross-reactive effects in HIV-1/HIV-2 dual-infection could provide novel insights in developing functional HIV cures and vaccines.