| 1. |
- Hønge, Bo L., et al.
(author)
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T-cell and B-cell perturbations are similar in ART-naive HIV-1 and HIV-1/2 dually infected patients
- 2019
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In: AIDS. - 0269-9370. ; 33:7, s. 1143-1153
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Journal article (peer-reviewed)abstract
- BACKGROUND: HIV-2 may slow progression of a subsequently acquired HIV-1 infection through cross-neutralizing antibodies and polyfunctional CD8 T cells. We hypothesized that HIV-1/2 dually infected patients compared with HIV-1-infected patients had more preserved immune maturation subsets and less immune activation of T and B cells. METHODS: ART-naive patients with HIV-1 (n = 83) or HIV-1/2 dual (n = 27) infections were included in this cross-sectional study at an HIV clinic in Guinea-Bissau. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry according to T-cell maturation and activation, regulatory T-cell fraction, and B-cell maturation and activation. RESULTS: HIV-1/2 dually infected patients had lower levels of HIV-1 RNA compared with patients with HIV-1 infection, but the levels of total HIV RNA (HIV-1 and HIV-2) were similar in the two patient groups. T-cell maturation, and proportions of regulatory T cells (FoxP3+) were also similar in the two groups. HIV-1/2 dually infected patients had higher proportions of CD4 and CD8 T cells positive for the activation marker CD38, but there was no difference in other T-cell activation markers (CD28, CTLA-4, PD-1). HIV-1/2 dually infected patients also had higher proportions of IgM-only B cells and plasmablasts. CONCLUSION: HIV-1/2 was not associated with less immune perturbations than for HIV-1 infection.
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| 2. |
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| 3. |
- Jespersen, Sanne, et al.
(author)
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Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA) : A Randomized Controlled Trial
- 2018
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In: JAIDS. - 1944-7884. ; 79:3, s. 386-393
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Journal article (peer-reviewed)abstract
- BACKGROUND: Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are recommended as part of first-line treatment for HIV-1 in Africa. However, NNRTI-based regimens are more prone to resistance development than protease inhibitors (PIs) in a context in which drug interruptions are frequent. The aim of this study was to compare the efficacy and tolerability of NNRTIs with PIs in HIV-1-infected patients in Guinea-Bissau.METHODS: This open-label randomized, 2-arm superiority trial compared the use of 2 NRTIs plus either one NNRTI (efavirenz or nevirapine) or one PI (lopinavir/ritonavir) in treatment-naive HIV-1-infected adults in the Bissau HIV Cohort (ClinicalTrials.gov, NCT0019235). The primary endpoint was HIV-1 RNA <400 copies per milliliter after 12 months of treatment.RESULTS: Between May 5, 2011, and April 26, 2013, 400 patients were included in the study. In an intention-to-treat analysis, the proportions of patients with viral suppression were similar in the NNRTI [65/197 (33.0%)] and PI [68/203 (33.5%)] arms (P = 0.92). No PI resistance was detected, but high-level NNRTI resistance was seen in 17/30 (56.7%) of NNRTI vs. 3/26 (11.5%) of PI-treated patients, P < 0.01. After 1 year of follow-up, 65 patients died (16.3%) and 93 were lost to follow-up (23.3%). There was no difference in mortality (hazard ratio 0.84, 95% confidence interval: 0.51 to 1.36) or frequency of clinical adverse events between treatment arms [NNRTI: 73/197 (37.1%); and PI: 69/203 (34.0%); P = 0.52].CONCLUSIONS: In patients at an HIV clinic in Guinea-Bissau, treatment with PIs led to less development of resistance compared with NNRTIs but was not superior in terms of viral suppression, CD4 cell increment, mortality, or severe adverse events.
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| 4. |
- Al Abri, Seif, et al.
(author)
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Tools to implement the World Health Organization End TB Strategy: Addressing common challenges in high and low endemic countries
- 2020
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In: International Journal of Infectious Diseases. - : ELSEVIER SCI LTD. - 1201-9712 .- 1878-3511. ; 92, s. S60-S68
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Journal article (peer-reviewed)abstract
- 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. (C) 2020 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
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| 5. |
- Bjerregaard-Andersen, Morten, et al.
(author)
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Tuberculosis burden in an urban population: a cross sectional tuberculosis survey from Guinea Bissau
- 2010
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In: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 10
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Journal article (peer-reviewed)abstract
- Background: Little is known about the prevalence of pulmonary tuberculosis (TB) in low income countries. We conducted a cross sectional survey for pulmonary TB and TB symptoms in Bissau, Guinea-Bissau, in an urban cohort with known HIV prevalence. TB surveillance in the area is routinely based on passive case finding. Methods: Two cohorts were selected based on a previous HIV survey, but only 52.5% of those enrolled in the adult cohort had participated in the HIV survey. One cohort included all adults living in 384 randomly selected houses; in this cohort 8% (135/1687) were HIV infected. The other included individuals 50 years or older from all other houses in the study area; of these 11% (62/571) were HIV infected. Symptom screening was done through household visits using a standardised questionnaire. TB suspects were investigated with sputum smear microscopy and X-ray. Results: In the adult cohort, we found 4 cases among 2989 individuals screened, giving a total TB prevalence of 134/100,000 (95% CI 36-342/100,000). In the >50 years cohort, we found 4 cases among 571 individuals screened, giving a total prevalence of 701/100,000 (191-1784/100.000). Two of the eight detected TB cases were unknown by the TB program. Of the total TB cases five were HIV uninfected while three had unknown HIV status. The prevalence of TB symptoms was 2.1% (63/2989) and 10.3% (59/571) in the two cohorts respectively. Conclusions: In conclusion we found a moderately high prevalence of pulmonary TB and TB symptoms in the general population, higher among elderly individuals. By active case finding unknown cases were detected. Better awareness of TB and its symptoms needs to be promoted in low income settings.
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| 6. |
- Cohen, Adam, et al.
(author)
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The global prevalence of latent tuberculosis: a systematic review and meta-analysis
- 2019
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In: European Respiratory Journal. - : EUROPEAN RESPIRATORY SOC JOURNALS LTD. - 0903-1936 .- 1399-3003. ; 54:3
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Research review (peer-reviewed)abstract
- In 1999, the World Health Organization (WHO) estimated that one-third of the worlds 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-gamma 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, pamp;lt;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 worlds 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.
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| 7. |
- Dahl, Victor Naestholt, et al.
(author)
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Global trends of pulmonary infections with nontuberculous mycobacteria: a systematic review
- 2022
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In: International Journal of Infectious Diseases. - : Elsevier. - 1201-9712 .- 1878-3511. ; 125, s. 120-131
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Research review (peer-reviewed)abstract
- Objectives: To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease.Methods: A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated.Results: Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%).Conclusion: Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation.
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| 8. |
- Esbjörnsson, Joakim, et al.
(author)
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HIV-2 as a model to identify a functional HIV cure
- 2019
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In: AIDS Research and Therapy. - : Springer Science and Business Media LLC. - 1742-6405. ; 16:1
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Research review (peer-reviewed)abstract
- 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.
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| 9. |
- Gomes, Victor F., et al.
(author)
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Impact of tuberculosis exposure at home on mortality in children under 5 years of age in Guinea-Bissau
- 2011
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In: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 66:2, s. 163-167
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Journal article (peer-reviewed)abstract
- Objective To assess mortality related to exposure to tuberculosis (TB) at home among children in urban areas of Guinea-Bissau. Methods In four suburban areas included in the demographic surveillance system of the Bandim Health Project in Bissau, the mortality of children aged <5 years living with an adult with TB was compared with the mortality of children in the general population. Results Children <5 years of age exposed to an adult with intrathoracic TB had 66% higher mortality than unexposed children (HR 1.66, 95% CI 1.2 to 2.3). The risk was higher for children living in the same family as a TB case (HR 2.15, 95% CI 1.3 to 3.7) than for children living in the same house but not belonging to the same family as the TB case (HR 1.51, 95% CI 1.0 to 2.2). For children whose mother had TB, mortality was increased eightfold (HR 7.82, 95% CI 2.1 to 30). The risk of death was particularly increased from 6 months following exposure (HR 2.16, 95% CI 1.5 to 3.2) and the highest rate of excess mortality was found in children aged 3-4 years. Excess mortality was highest among children with close contact with an adult with sputum-positive pulmonary TB (HR 1.90, 95% CI 1.1 to 3.2), but contact with a sputum-negative case was also associated with increased mortality (HR 1.55, 95% CI 1.0 to 2.3). Adjusting for potential confounding factors did not change these results. The mortality among children living in the same houses 3 years earlier was not increased (HR 0.90, 95% CI 0.6 to 1.3). Conclusion Intimate family contact with a TB case represents a significant risk factor for child mortality in a low-income country.
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| 10. |
- Rudolf, Frauke, et al.
(author)
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Increasing smear positive tuberculosis detection using a clinical score - A stepped wedge multicenter trial from Africa
- 2021
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In: International Journal of Infectious Diseases. - : Elsevier Science Ltd. - 1201-9712 .- 1878-3511. ; 113, s. S55-S62
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Journal article (peer-reviewed)abstract
- Background: The Bandim TBscore is a clinical score that predicts treatment outcome in Tuberculosis (TB) patients and proved useful as an indicator of which healthcare-seeking adults to refer for sputum smear microcopy. We aimed to test in a randomized trial if the TBscore could be used to enhance the detection of smear positive (SP) TB. Methods: We carried out a stepped wedge cluster-randomized trial at six health centers in Bissau, GuineaBissau, and Gondar, Ethiopia. The primary outcome was diagnostic yield for SP TB. Secondary outcomes were successful treatment and effect on overall 12 months mortality. The study was registered at the Pan African Clinical Trials Registry (PACTR201611001838365). Results: We included 3571 adults. Overall, there was no effect of the intervention on SP PTB detected (OR 1.39 (95%CI 0.75 - 2.56). Analysis stratified by country, showed that the TBscore increased case detection in Gondar (OR 4.05 (95%CI 1.67 - 9.85)) but no effect was found in Bissau (OR 0.47 (95%CI 0.22 - 1.05)) where take-up was much lower. Overall mortality decreased during the intervention (HR 0.31 (95%CI 0.13-0.72)). Conclusion: Using the TBscore for triage before smear microscopy may improve case detection and decrease mortality if there is sufficient laboratory capacity to increase sputum smears. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
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| 11. |
- Rudolf, Frauke, et al.
(author)
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TBscore II: Refining and validating a simple clinical score for treatment monitoring of patients with pulmonary tuberculosis
- 2013
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In: Scandinavian Journal of Infectious Diseases. - : Informa Healthcare. - 0036-5548 .- 1651-1980. ; 45:11, s. 825-836
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Journal article (peer-reviewed)abstract
- Background: The TBscore, based on simple signs and symptoms, was introduced to predict unsuccessful outcome in tuberculosis patients on treatment. A recent inter-observer variation study showed profound variation in some variables. Further, some variables depend on a physician assessing them, making the score less applicable. The aim of the present study was to simplify the TBscore. Methods: Inter-observer variation assessment and exploratory factor analysis were combined to develop a simplified score, the TBscore II. To validate TBscore II we assessed the association between start score and failure (i.e. death or treatment failure), responsiveness using Cohens effect size, and the relationship between severity class at treatment start and a decrease andlt; 25% in score from the start until the end of the second treatment month and subsequent mortality. Results: We analyzed data from 1070 Guinean (2003-2012) and 432 Ethiopian (2007-2012) pulmonary tuberculosis patients. For the refined score, items with less than substantial agreement (kappa andlt;= 0.6) and/or not associated with the underlying constructs were excluded. Items kept were: cough, dyspnea, chest pain, anemia, body mass index (BMI) andlt; 18 kg/m(2), BMI andlt; 16 kg/m(2), mid upper arm circumference (MUAC) andlt; 220 mm, and MUAC andlt; 200 mm. The effect sizes for the change between the start of treatment and the 2-month follow-up were 0.51 in Guinea-Bissau and 0.68 in Ethiopia, and for the change between the start of treatment and the end of treatment were 0.68 in Guinea-Bissau and 0.74 in Ethiopia. Severity class placement at treatment start predicted failure (p andlt; 0.001 Guinea-Bissau, p = 0.208 Ethiopia). Inability to decrease at least 25% in score was associated with a higher failure rate during the remaining 4 months of treatment (p = 0.063 Guinea-Bissau, p = 0.008 Ethiopia). Conclusion: The TBscore II could be a useful monitoring tool, aiding triage at the beginning of treatment and during treatment.
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| 12. |
- Thysen, Sanne M., et al.
(author)
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Neonatal BCG vaccination and child survival in TB-exposed and TB-unexposed children : A prospective cohort study
- 2020
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In: BMJ Open. - : BMJ. - 2044-6055. ; 10:2
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Journal article (peer-reviewed)abstract
- Objectives To assess the association between neonatal BCG vaccination and mortality between 28 days and 3 years of age among tuberculosis (TB)-exposed and TB-unexposed children. Design Prospective cohort study. Setting Bandim Health Project runs an urban Health and Demographic Surveillance site in Guinea-Bissau with registration of mortality, vaccination status and TB cases. Participants Children entered the analysis when their vaccination card was inspected after 28 days of age and remained under surveillance to 3 years of age. Children residing in the same house as a TB case were classified as TB-exposed from 3 months prior to case registration to the end of follow-up. Methods Using Cox-proportional hazards models with age as underlying time scale, we compared mortality of children with and without neonatal BCG between October 2003 and September 2017. Main outcome measure HR for neonatal BCG compared with no neonatal BCG by TB-exposure status. Results Among the 39 421 children who entered the analyses, 3022 (8%) had observation time as TB-exposed. In total, 84% of children received neonatal BCG. Children with neonatal BCG had lower mortality both in TB-exposed (adjusted HR: 0.57 (0.26 to 1.27)) and in TB-unexposed children (HR: 0.57 (95% CI 0.47 to 0.69)) than children without neonatal BCG. Children exposed to TB had higher mortality than TB-unexposed children if they had not received neonatal BCG. Conclusion Neonatal BCG vaccination was associated with lower mortality among both TB-exposed and TB-unexposed children, consistent with neonatal BCG vaccination having beneficial non-specific effects. Interventions to increase timely BCG vaccination are urgently warranted.
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| 13. |
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| 14. |
- Wejse, Christian, et al.
(author)
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Serum 25-hydroxyvitamin D in a West African population of tuberculosis patients and unmatched healthy controls
- 2007
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In: American Journal of Clinical Nutrition. - 1938-3207. ; 86:5, s. 1376-1383
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Journal article (peer-reviewed)abstract
- Background: Little is known regarding vitamin D deficiency (VDD) in African populations and in tuberculosis (TB) patients. VDD has been shown to be associated with TB. Objective: We aimed to compare the degree of vitamin D insufficiency (VDI) and VDD in TB patients and healthy adult controls in a West African population. Design: An unmatched case-control study was performed at a Demographic Surveillance Site in Guinea-Bissau. Serum 25-hydroxyvitamin D-3 [25(OH)D-3] concentrations were measured in 362 TB patients and in 494 controls. Results: Hypovitammosis D [25(OH)D-3 <= 75 nmol/L] was more common in TB patients, but VDD [25(OH)D-3 <= 50 nmol/L] was more common and more severe in controls. We observed hypovitaminosis D in 467o (167/362) of the TB patients and in 39% (193/494) of the controls: the relative risk (RR) of hypovitaminosis D was 1.18 (95% Cl: 1.01. 1.38). VDD was observed in 8.5% (31/362) of the TB patients and in 13.2% (65/494) of the controls. The RR was 0.65 (95% Cl: 0.43,0.98), mainly because severe VDD [25(OH)D-3 <= 25 nmol/L] was observed in only I of 362 TB patients (0.2%) and in 24 of 494 controls (4.9%). After adjustment for background factors, hypovitaminosis D was not more frequent in TB patients than in healthy controls, but the mean serum 25(OH)D3 concentration remained lower. Conclusions: Hypovitammosis D was highly prevalent in TB patients and in healthy controls living at 12 degrees N; severe VDD was rare in TB patients. The finding indicates that the serum 25(OH)D3 concentration is associated with TB infection, but whether this role is a symptom or is causal was not established.
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| 15. |
- Wejse, Christian, et al.
(author)
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Vitamin D as Supplementary Treatment for Tuberculosis A Double-blind, Randomized, Placebo-controlled Trial
- 2009
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In: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 179:9, s. 843-850
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Journal article (peer-reviewed)abstract
- Rationale Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. Objectives: To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. Methods: We conducted a randomized, double-blind, place-bocontrolled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment. Measurements and Main Results: The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at I year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2. Conclusions: Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).
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