RESUMEN
BACKGROUND: The role of ribonucleases in tuberculosis among people with human immunodeficiency virus (HIV; PWH) is unknown. We explored ribonuclease activity in plasma from PWH with and without tuberculosis. METHODS: Participants were identified from a cohort of treatment-naive PWH in Ethiopia who had been classified for tuberculosis disease (HIV positive [HIV+]/tuberculosis positive [tuberculosis+] or HIV+/tuberculosis negative [tuberculosis-]). Ribonuclease activity in plasma was investigated by quantification of synthetic spike-in RNAs using sequencing and quantitative polymerase chain reaction and by a specific ribonuclease activity assay. Quantification of ribonuclease 1, 2, 3, 6, 7, and T2 proteins was performed by enzyme-linked immunosorbent assay. Ribonuclease activity and protein concentrations were correlated with markers of tuberculosis and HIV disease severity and with concentrations of inflammatory mediators. RESULTS: Ribonuclease activity was significantly higher in plasma of HIV+/tuberculosis+ (n = 51) compared with HIV+/tuberculosis- (n = 78), causing reduced stability of synthetic spike-in RNAs. Concentrations of ribonucleases 2, 3, and T2 were also significantly increased in HIV+/tuberculosis+ compared with HIV+/tuberculosis-. Ribonuclease activity was correlated with HIV viral load, and inversely correlated with CD4 cell count, mid-upper arm circumference, and body mass index. Moreover, ribonuclease activity was correlated with concentrations of interleukin 27, procalcitonin and the kynurenine-tryptophan ratio. CONCLUSIONS: PWH with tuberculosis disease have elevated plasma ribonuclease activity, which is also associated with HIV disease severity and systemic inflammation.
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Infecciones por VIH , Ribonucleasas , Tuberculosis , Humanos , Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , Adulto , Masculino , Femenino , Tuberculosis/sangre , Ribonucleasas/sangre , Ribonucleasas/metabolismo , Etiopía/epidemiología , Persona de Mediana Edad , Biomarcadores/sangre , Estudios de Cohortes , Coinfección/sangre , Adulto JovenRESUMEN
BACKGROUND: Tuberculosis (TB) disease has been associated with pregnancy complications. However, the potential impact of TB infection (TBI) on pregnancy outcome is unknown. To investigate this, we conducted a register-based study in immigrant women screened with QuantiFERON assays for TBI in antenatal care in Sweden. METHODS: Women with history of immigration from TB-endemic countries were eligible for inclusion if national identification numbers and available QuantiFERON results obtained during pregnancy from 2014 to 2018 were available. QuantiFERON results were linked to data on maternal characteristics and pregnancy outcomes from the national Pregnancy and Patient Registers. TBI was defined as nil-corrected QuantiFERON result ≥0.35 IU/mL, in the absence of TB disease. Pregnancies in women with TB disease or human immunodeficiency virus were excluded, as were multiplex pregnancies, pregnancies resulting in miscarriage, and pregnancies occurring >10 years after immigration. Odds of defined adverse pregnancy outcomes were compared by maternal TBI status using mixed effects logistic regression with adjustment for maternal age and region of origin. RESULTS: In total, 7408 women with 12 443 pregnancies were included. In multivariable analysis, stillbirth (adjusted odds ratio [AOR], 1.90; 95% confidence interval [CI], 1.13-3.21; P = .016), severe preeclampsia (AOR, 1.62; 95% CI, 1.03-2.56; P = .036), low birthweight (<2500 g; AOR, 1.38; 95% CI, 1.01-1.88; P = .041), and emergency cesarean section (AOR, 1.28; 95% CI, 1.02-1.63; P = .033) were significantly associated with TBI. CONCLUSIONS: Among immigrant women seeking antenatal care in Sweden, TBI was independently associated with adverse pregnancy outcomes. Further studies are needed to corroborate these findings and to explore mechanisms involved.
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Tuberculosis Latente , Tuberculosis , Embarazo , Femenino , Humanos , Resultado del Embarazo , Atención Prenatal , Suecia/epidemiología , Cesárea , Mortinato , Tuberculosis/diagnóstico , Tuberculosis/epidemiologíaRESUMEN
BACKGROUND: It is unclear whether low-level viremia (LLV), defined as repeatedly detectable viral load (VL) of <200 copies/mL, and/or transient viremic episodes (blips) during antiretroviral therapy (ART), predict future virologic failure. We investigated the association between LLV, blips, and virologic failure (VF) in a multicenter European cohort. METHODS: People with HIV-1 who started ART in 2005 or later were identified from the EuResist Integrated Database. We analyzed the incidence of VF (≥200 copies/mL) depending on viremia exposure, starting 12 months after ART initiation (grouped as suppression [≤50 copies/mL], blips [isolated VL of 51-999 copies/mL], and LLV [repeated VLs of 51-199 copies/mL]) using Cox proportional hazard models adjusted for age, sex, injecting drug use, pre-ART VL, CD4 count, HIV-1 subtype, type of ART, and treatment experience. We queried the database for drug-resistance mutations (DRM) related to episodes of LLV and VF and compared those with baseline resistance data. RESULTS: During 81 837 person-years of follow-up, we observed 1424 events of VF in 22 523 participants. Both blips (adjusted subhazard ratio [aHR], 1.7; 95% confidence interval [CI], 1.3-2.2) and LLV (aHR, 2.2; 95% CI, 1.6-3.0) were associated with VF, compared with virologic suppression. These associations remained statistically significant in subanalyses restricted to people with VL <200 copies/mL and those starting ART 2014 or later. Among people with LLV and genotype data available within 90 days following LLV, 49/140 (35%) had at least 1 DRM. CONCLUSIONS: Both blips and LLV during ART are associated with increased risk of subsequent VF.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Fármacos Anti-VIH/uso terapéutico , Viremia/epidemiología , Insuficiencia del Tratamiento , Infecciones por VIH/tratamiento farmacológico , Terapia Antirretroviral Altamente Activa , Carga ViralRESUMEN
OBJECTIVE: The role of HIV exposure in determining growth among HIV-uninfected children is debated. We determined whether intrauterine HIV exposure influences linear growth in a cohort of Ethiopian children followed up to 18 months of age in public health facilities in Adama city, Ethiopia. METHODS: Participants were offspring of pregnant women enrolled in a prospective cohort study that included screening for HIV infection during antenatal care. Growth patterns of HIV-exposed and uninfected (HEU) and HIV-unexposed (HU) children were compared up to 18 months of age, with length-for-age z-score (LAZ) and proportion with stunting as primary outcomes. Multivariable linear and logistic regression models were constructed to investigate the associations between HIV exposure and linear growth, controlling for socio-demographic factors and breastfeeding status. RESULTS: Of 1705 included infants (164 HEU), 1276 remained in follow-up at 18 months. Among HIV-positive mothers, 132 (80.5%) were receiving antiretroviral therapy at enrolment. At the 18-month visit, mean LAZ was -1.08 among HEU children and -0.74 among HU children (p = 0.052). Proportions of HEU and HU children with stunting at the 18-month visit were 27.8% and 18.7%, respectively (p = 0.010). In multivariable models, HIV exposure was associated with lower LAZ at all follow-up visits, and with stunting at the 18-month visit (adjusted odds ratio 2.29, 95% confidence interval 1.40-3.71). HIV exposure was not associated with weight-related growth outcomes. CONCLUSIONS: HEU children in Ethiopia had inferior linear growth compared with HU children, implying that intrauterine HIV exposure impacts early childhood growth in this setting.
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Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Niño , Preescolar , Etiopía/epidemiología , Femenino , Trastornos del Crecimiento/complicaciones , Trastornos del Crecimiento/etiología , Infecciones por VIH/complicaciones , Humanos , Lactante , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Estudios ProspectivosRESUMEN
BACKGROUND: The impact of low levels of human immunodeficiency virus (HIV) RNA (low-level viremia [LLV]) during combination antiretroviral therapy (cART) on clinical outcomes is unclear. We explored the associations between LLV and all-cause mortality, AIDS, and serious non-AIDS events (SNAEs). METHODS: We grouped individuals starting cART 1996-2017 (identified from the Swedish InfCare HIV register) as virologic suppression (VS; <50 copies/mL), LLV (repeated viral load, 50-999 copies/mL), and nonsuppressed viremia (NSV; ≥1000 copies/mL). Separately, LLV was subdivided into 50-199 and 200-999 copies/mL (reflecting different definitions of virologic failure). Proportional-hazard models (including sex, age, pre-ART CD4 count and viral load, country of birth, injection drug use, treatment experience and interruptions, and an interaction term between viremia and time) were fitted for the study outcomes. RESULTS: A total of 6956 participants were followed for a median of 5.7 years. At the end of follow-up, 60% were categorized as VS, 9% as LLV, and 31% as NSV. Compared with VS, LLV was associated with increased mortality (adjusted hazard ratio [aHR], 2.2; 95% confidence interval [CI], 1.3-3.6). This association was also observed for LLV 50-199 copies/mL (aHR, 2.2; 95% CI, 1.3-3.8), but was not statistically significant for LLV 200-999 copies/mL (aHR, 2.1; 95% CI, .96-4.7). LLV 50-999 copies/mL was not linked to increased risk of AIDS or SNAEs, but in subanalysis, LLV 200-999 copies/mL was associated with SNAEs (aHR, 2.0; 95% CI, 1.2-3.6). CONCLUSIONS: In this population-based cohort, LLV during cART was associated with adverse clinical outcomes.
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Síndrome de Inmunodeficiencia Adquirida , Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Humanos , Suecia/epidemiología , Carga Viral , Viremia/tratamiento farmacológico , Viremia/epidemiologíaRESUMEN
BACKGROUND: Knowledge on tuberculosis (TB) infection epidemiology in women of reproductive age living in TB-endemic areas is limited. We used a composite definition of TB infection in a cohort of pregnant women recruited in an Ethiopian city as a model for TB exposure patterns, and to identify factors associated with TB infection. METHODS: Women seeking antenatal care at public health facilities underwent structured interviews, physical examination, and QuantiFERON-TB Gold-Plus (QFT) testing. Women with symptoms compatible with TB disease, and all human immunodeficiency virus (HIV)-positive women, were investigated for active TB by sputum bacteriological testing. TB infection (TB+) was defined as either positive QFT (≥ 0.35 IU/mL), self-reported previous active TB, or current active TB. Associations between TB infection and clinical, demographic, and socioeconomic characteristics were tested in multiple logistic regression analysis. RESULTS: Among 1834 participants, 679 (37.0%) met criteria for TB+ (80 [4.4%] previous active TB, 5 [0.3%] current active TB, and 594 [32.4%] QFT-positive without previous or current active TB). Age (annual adjusted odds ratio [AOR], 1.069 [95% confidence interval {CI}, 1.045-1.093]) and HIV infection (AOR, 1.43 [95% CI, 1.033-1.988]) were independently associated with TB+. The relationship with increasing age was only observed in HIV-negative women, and translated to an estimated annual risk of TB infection of 2.1% in HIV-negative women. CONCLUSIONS: TB infection in women of reproductive age in Ethiopia was independently associated with HIV infection and increasing age, suggesting exposure to contagious TB and continuous acquisition of TB infection in this population.
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Infecciones por VIH , Tuberculosis , Estudios Transversales , Etiopía/epidemiología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Ensayos de Liberación de Interferón gamma , Embarazo , Atención Prenatal , Prueba de Tuberculina , Tuberculosis/diagnóstico , Tuberculosis/epidemiologíaRESUMEN
BACKGROUND: Acute retroviral syndrome (ARS) is associated with human immunodeficiency virus type 1 (HIV-1) subtype and disease progression, but the underlying immunopathological pathways are poorly understood. We aimed to elucidate associations between innate immune responses during hyperacute HIV-1 infection (hAHI) and ARS. METHODS: Plasma samples obtained from volunteers (≥18.0 years) before and during hAHI, defined as HIV-1 antibody negative and RNA or p24 antigen positive, from Kenya, Rwanda, Uganda, Zambia, and Sweden were analyzed. Forty soluble innate immune markers were measured using multiplexed assays. Immune responses were differentiated into volunteers with stronger and comparatively weaker responses using principal component analysis. Presence or absence of ARS was defined based on 11 symptoms using latent class analysis. Logistic regression was used to determine associations between immune responses and ARS. RESULTS: Of 55 volunteers, 31 (56%) had ARS. Volunteers with stronger immune responses (nâ =â 36 [65%]) had increased odds of ARS which was independent of HIV-1 subtype, age, and risk group (adjusted odds ratio, 7.1 [95% confidence interval {CI}: 1.7-28.8], Pâ =â .003). Interferon gamma-induced protein (IP)-10 was 14-fold higher during hAHI, elevated in 7 of the 11 symptoms and independently associated with ARS. IP-10 threshold >466.0 pg/mL differentiated stronger immune responses with a sensitivity of 84.2% (95% CI: 60.4-96.6) and specificity of 100.0% (95% CI]: 90.3-100.0). CONCLUSIONS: A stronger innate immune response during hAHI was associated with ARS. Plasma IP-10 may be a candidate biomarker of stronger innate immunity. Our findings provide further insights on innate immune responses in regulating ARS and may inform the design of vaccine candidates harnessing innate immunity.
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Síndrome Retroviral Agudo , Infecciones por VIH , VIH-1 , Quimiocina CXCL10 , Humanos , Inmunidad InnataRESUMEN
Pregnancy may influence cellular immune responses to Mycobacterium tuberculosis. We investigated M. tuberculosis-specific interferon-γ responses in women followed longitudinally during pregnancy and postpartum. Interferon-γ levels (stimulated by M. tuberculosis antigens [TB1 and TB2] and mitogen included in the QuantiFERON-TB Gold Plus assay) were measured in blood from pregnant HIV-negative women identified from a prospective cohort at Ethiopian antenatal care clinics. Longitudinal comparisons included women without active tuberculosis (TB) with M. tuberculosis-triggered interferon-γ responses of ≥ 0.20 IU/ml, sampled on two and/or three occasions (1st/2nd trimester, 3rd trimester, and 9 months postpartum). Among 2,093 women in the source cohort, 363 met inclusion criteria for longitudinal comparisons of M. tuberculosis-stimulated interferon-γ responses. Median M. tuberculosis-triggered interferon-γ concentrations were higher at 3rd than those at the 1st/2nd trimester (in 38 women with samples available from these time points; TB1: 2.8 versus 1.6 IU/ml, P = 0.005; TB2: 3.3 versus 2.8 IU/ml, P = 0.03) and postpartum (in 49 women with samples available from these time points; TB1: 3.1 versus 2.2 IU/ml, P = 0.01; TB2: 3.1 versus 2.3 IU/ml, P = 0.03). In contrast, mitogen-stimulated interferon-γ levels were lower at 3rd than those at 1st/2nd trimester (in 32 women with samples available from these time points: 21.0 versus 34.9 IU/ml, P = 0.02). Results were similar in 22 women sampled on all 3 occasions. In HIV-negative women, M. tuberculosis-stimulated interferon-γ responses were higher during the 3rd trimester than those at earlier stages of pregnancy and postpartum, despite decreased mitogen-triggered responses. These findings suggest increased M. tuberculosis-specific cellular responses due to dynamic changes of latent TB infection during pregnancy.
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Infecciones por VIH , Tuberculosis Latente , Mycobacterium tuberculosis , Femenino , Humanos , Interferón gamma , Ensayos de Liberación de Interferón gamma , Tuberculosis Latente/diagnóstico , Periodo Posparto , Embarazo , Estudios ProspectivosRESUMEN
BACKGROUND AND AIMS: Hepatitis delta virus (HDV) infection is associated with fast progression to liver cirrhosis and liver complications. Previous studies have, however, been mainly from tertiary care centers, with risk for referral bias toward patients with worse outcomes. Furthermore, the impact of HDV viremia per se on liver-related outcomes is not really known outside the human immunodeficiency virus co-infection setting. We have therefore evaluated the long-term impact of HDV viremia on liver-related outcomes in a nationwide cohort of patients with hepatitis B and D co-infection, cared for at secondary care centers in Sweden. APPROACH AND RESULTS: In total, 337 patients with anti-HDV positivity, including 233 patients with HDV RNA viremia and 91 without HDV viremia at baseline, were retrospectively studied, with a mean follow-up of 6.5 years (range, 0.5-33.1). The long-term risks for liver-related events (i.e., hepatocellular carcinoma [HCC], hepatic decompensation, or liver-related death/transplantation) were assessed, using Cox regression analysis. The risk for liver-related events and HCC was 3.8-fold and 2.6-fold higher, respectively, in patients with HDV viremia compared with those without viremia, although the latter was not statistically significant. Among patients with HDV viremia with no baseline cirrhosis, the cumulative risk of being free of liver cirrhosis or liver-related events was 81.9% and 64.0% after 5 and 10 years of follow-up, respectively. This corresponds to an incidence rate of 0.04 cases per person-year. CONCLUSIONS: HDV RNA viremia is associated with a 3.8-fold higher risk for liver-related outcomes. The prognosis was rather poor for patients with HDV viremia without cirrhosis at baseline, but it was nevertheless more benign than previous estimates from tertiary centers. Our findings may be of importance when making decisions about treatment and evaluating potential outcomes of upcoming antivirals against HDV.
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Carcinoma Hepatocelular/etiología , Hepatitis D/complicaciones , Cirrosis Hepática/etiología , Neoplasias Hepáticas/etiología , Viremia/complicaciones , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Atención Secundaria de SaludRESUMEN
OBJECTIVES: Absence of a functional interferon-λ 4 (IFN-λ4) gene (IFNL4) predicts spontaneous resolution of acute hepatitis C virus (HCV) infections in regions with a predominance of genotype 1, whereas variants of the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) entailing reduced activity associate with increased sustained virologic response rates following some therapeutic regimens. This study aimed at investigating the impact of IFNL4 on acute HCV genotype 2 or 3 infections, and whether ITPase activity influenced outcome. MATERIALS AND METHODS: Two hundred and seven people who injected drugs (PWID) with documented anti-HCV seroconversion, and 57 PWID with reinfection with HCV were analyzed regarding IFNL4 (rs368234815 and rs12979860) and ITPA (rs1127354 and rs7270101), and longitudinally followed regarding HCV RNA. RESULTS: The spontaneous clearance of HCV infection in anti-HCV seronegative PWID was enhanced when IFN-λ4 was absent (44% vs. 20% for IFNL4 TT/TTrs1368234815 and ΔGrs1368234815 respectively, p < .001; OR 3.2) across genotypes 1-3. The proportion lacking IFN-λ4 was further increased following resolution of repeated re-exposure to HCV (74% among re-infected participants who had cleared at least two documented HCV infections). ITPA genetic variants did not independently impact on the outcome, but among males lacking IFN-λ4, reduced ITPase activity markedly augmented the likelihood of resolution (65% vs. 29% for <100% and 100% ITPase activity, p = .006). CONCLUSIONS: Absence of IFN-λ4 entails an enhanced likelihood of spontaneous resolution both following primary acute infection and repeated re-exposure to HCV across genotypes 1-3. Among men lacking IFN-λ4, reduced ITPase activity improved outcome.
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Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Genotipo , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/genética , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Interferones/uso terapéutico , Interleucinas/genética , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
This study explored factors associated with interest in taking PrEP among men who have sex with men (MSM) attending HIV testing venues in Sweden. Data from 658 HIV-negative respondents, surveyed by a questionnaire at six sites, were analyzed descriptively and by univariable and multivariable logistic regression. A total of 453 (68.8%) of the respondents expressed interest in taking PrEP. Reporting self-perceived risk of HIV acquisition as moderate or high, reporting ≥ 5 partners for condomless anal intercourse during the past year, and reporting hard drug use during the past year were independently associated with interest in taking PrEP. However, an aggregated variable of self-reported rectal gonorrhea, rectal chlamydia, or syphilis infection during the past year was not associated with interest in taking PrEP. Overall, Swedish MSM were well-informed regarding PrEP, and interest in taking PrEP was positively associated with sexual risk indicators.
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Homosexualidad Masculina/estadística & datos numéricos , Profilaxis Pre-Exposición/métodos , Adulto , Infecciones por VIH/prevención & control , Humanos , Masculino , Factores de Riesgo , SueciaRESUMEN
OBJECTIVES: Restricted capacity for viral load (VL) testing is a major obstacle for antiretroviral therapy (ART) programmes in high-burden regions. Algorithms for targeted VL testing could help allocate laboratory resources rationally. We validated the performance of the Viral Load Testing Criteria (VLTC), an algorithm with satisfactory performance in derivation (sensitivity 91%, specificity 43%). METHODS: HIV-positive adults who had been receiving first-line ART for ≥12 months at three Ethiopian public ART clinics were included. Healthcare providers collected data on variables of the VLTC: current CD4 count, mid-upper arm circumference (MUAC) and self-reported treatment interruption. VL testing was performed in parallel. Performance of the algorithm for identification of patients with VL ≥ 1000 copies/ml was evaluated. RESULTS: Of 562 patients (female 62%, median ART duration 92 months), 33 (6%) had VL ≥ 1000 copies/ml. Sensitivity for the VLTC was 85% (95% CI, 68-95), specificity 60% (95% CI, 55-64), positive predictive value 12% (95% CI, 10-14) and negative predictive value 98% (95% CI, 97-99). Use of the algorithm would reduce the number of VL tests required by 57%. Misclassification occurred in 5/33 (15%) of subjects with VL ≥ 1000 copies/ml. CONCLUSION: In validation, the VLTC performed similarly well as derivation. Use of the VLTC may be considered for targeted VL testing for ART monitoring in high-burden regions.
OBJECTIFS: La capacité restreinte de mesure de la charge virale (CV) constitue un obstacle majeur pour les programmes de traitement antirétroviral (ART) dans les régions à prévalence élevée. Des algorithmes pour des tests ciblés de la CV pourraient aider à allouer les ressources de laboratoire de manière rationnelle. Nous avons validé la performance des critères de mesure de la charge virale (VLTC), un algorithme dont la performance de dérivation est satisfaisante (sensibilité de 91%, spécificité de 43%). MÉTHODES: Des adultes VIH positifs qui recevaient un ART de première ligne depuis au moins 12 mois dans trois cliniques ART publiques éthiopiennes ont été inclus. Les prestataires de soins de santé ont collecté des données sur les variables des VLTC: nombre actuel de CD4, périmètre brachial et interruption de traitement auto-déclarée. La mesure de la CV a été réalisée en parallèle. La performance de l'algorithme pour l'identification des patients avec une CV≥1000 copies/mL a été évaluée. RÉSULTATS: Sur 562 patients (femmes 62%, durée médiane de l'ART 92 mois), 33 (6%) avaient une CV ≥1000 copies/mL. La sensibilité des VLTC était de 85% (IC95%: 68-95), sa spécificité de 60% (IC95%: 55-64), sa valeur prédictive positive de 12% (IC95%: 10-14) et sa valeur prédictive négative de 98% (IC95%: 97-99). L'utilisation de l'algorithme réduirait le nombre de tests de CV requis de 57%. Une mauvaise classification est survenue chez 5/33 (15%) des sujets avec CV ≥1000 copies/ml. CONCLUSION: En validation, les VLTC ont obtenu une performance aussi bonne comme dérivation. L'utilisation des VLTC peut être envisagée pour des mesures ciblées de la CV dans le suivi des ART dans les régions à forte charge de morbidité.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Carga Viral , Adulto , Algoritmos , Etiopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Injection drug users (IDUs) are at increased risk of various medical conditions, including bacterial skin and soft tissue infections (SSTIs). SSTIs, which are painful and can lead to life-threatening complications, are common but scarcely studied. OBJECTIVES: To investigate life time, past 12 month and past 30-day prevalence for SSTI related to injection drug use, in IDUs at Malmö syringe exchange program (Malmö SEP). To investigate factors associated with having ever had an SSTI. METHODS: IDUs were recruited from Malmö SEP (N = 80). They participated in a survey with questions about demographics, drug use, and experience of SSTIs. Factors independently associated with self-reported SSTI ever were assessed using logistic regression analysis. RESULTS: The lifetime reported prevalence of SSTI was 58%, past 12 months 30%, and past 30 days 14%. Factors independently associated with SSTI ever were age (adjusted odds ratio [AOR] = 1.09; 95% confidence interval [CI] = 1.01-1.18), female sex (AOR = 6.75; 95% CI = 1.40-32.47), having ever injected prescribed drugs (AOR = 52.15; 95% CI = 5.17-525.67), and having ever injected in the neck (AOR = 8.08; 95% CI = 1.16-56.08). CONCLUSIONS/IMPORTANCE: SSTI is common among IDUs in Malmö. Women and those injecting in the neck or injecting prescribed drugs (crushed tablets/liquids), are more likely to have had an SSTI.
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Consumidores de Drogas/estadística & datos numéricos , Programas de Intercambio de Agujas , Enfermedades Cutáneas Bacterianas/epidemiología , Infecciones de los Tejidos Blandos/epidemiología , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto , Trastornos Relacionados con Anfetaminas/epidemiología , Buprenorfina , Combinación Buprenorfina y Naloxona , Femenino , Dependencia de Heroína/epidemiología , Personas con Mala Vivienda/estadística & datos numéricos , Vivienda/estadística & datos numéricos , Humanos , Modelos Logísticos , Masculino , Metadona , Metilfenidato , Persona de Mediana Edad , Cuello , Oportunidad Relativa , Trastornos Relacionados con Opioides/epidemiología , Medicamentos bajo Prescripción , Prevalencia , Factores Sexuales , Encuestas y Cuestionarios , Suecia/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: To assess the diagnostic performance of urine lipoarabinomannan (LAM) detection for TB screening in HIV-positive adults in Ethiopia. METHODS: Testing for LAM was performed using the Determine TB-LAM lateral flow assay on urine samples from participants in a prospective cohort with baseline bacteriological categorisation for active TB in sputum. Characteristics of TB patients with regard to LAM status were determined. Participants were followed for 6 months to evaluate survival, retention in care and incident TB. RESULTS: Positive LAM results were found in 78/757 participants. Among 128 subjects with definite (confirmed by culture and/or Xpert MTB/RIF) TB, 33 were LAM-positive (25.8%); the respective figure for clinically diagnosed cases was 2/20 (10%). Five of the remaining 43 LAM-positive individuals had died during the 6-month follow-up period, whereas 38 remained in care without clinical signs of TB. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 25.8%, 92.9%, 42.3% and 86.0%, respectively. Among TB patients, LAM positivity was associated with higher WHO clinical stage, lower body mass index (BMI), CD4 cell and haemoglobin levels, and with increased mortality. A combination algorithm of urine LAM testing and sputum smear microscopy detected 49 (38.2%) of definite TB cases; among those with CD4 count ≤100 cells/mm3 , this proportion was 66.7%. CONCLUSIONS: The performance of urine LAM testing for TB detection was poor in this population. However, this was improved among subjects with CD4 count ≤100 cells/mm3 . In combination with sputum microscopy urine, LAM could be considered for targeted TB screening in this subgroup.
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BACKGROUND: The proportion of Mycoplasma pneumoniae isolates carrying point mutations in the 23S region of the genome associated with macrolide resistance has increased. We evaluated the probability of developing M. pneumoniae macrolide resistance mutations during macrolide treatment. METHODS: M. pneumoniae strains from initial and follow-up oropharyngeal samples from 38 Swedish patients were tested for 23S rRNA mutations by amplifying and pyrosequencing the gene target region. The duration of symptoms and of M. pneumoniae carriage were recorded in cases with and without the macrolide resistance mutation. RESULTS: Macrolide resistance mutations were absent in all baseline strains. Twenty-two patients were prescribed macrolides; the longest M. pneumoniae carriage time in these patients was 7 months and the longest symptomatic period was 7.5 months. Macrolide resistance was detected after macrolide treatment in 1 patient (carriage time 3.5 months and symptomatic period 7.5 months). CONCLUSIONS: M. pneumoniae may develop macrolide resistance during macrolide treatment. A long duration of M. pneumoniae carriage and symptoms is common in patients regardless of the presence of resistance.
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Antibacterianos/administración & dosificación , Macrólidos/administración & dosificación , Mycoplasma pneumoniae/efectos de los fármacos , Neumonía por Mycoplasma/microbiología , Adolescente , Adulto , Anciano , Antibacterianos/efectos adversos , Niño , Preescolar , Farmacorresistencia Bacteriana , Femenino , Humanos , Macrólidos/efectos adversos , Masculino , Persona de Mediana Edad , Mycoplasma pneumoniae/genética , Neumonía por Mycoplasma/tratamiento farmacológico , Neumonía por Mycoplasma/epidemiología , Suecia/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Opiate substitution therapy (OST) reduces the risk of death from directly drug-related causes in heroin users, allowing other chronic health problems to emerge. People who inject drugs (PWID) are exposed to hepatitis C virus (HCV), with an associated risk of chronic liver disease. We investigated HCV prevalence and liver-related morbidity in a cohort of OST recipients, and analyzed factors associated with significant hepatic fibrosis. METHODS: All patients registered on 1 April 2008 in 4 clinics providing OST in the 3 largest cities in Sweden were eligible for inclusion. HCV viremic subjects were evaluated for fibrosis stage by liver biopsy, transient elastometry (TE), and/or a biochemical fibrosis index (Göteborg University Cirrhosis Index; GUCI). Factors associated with severity of fibrosis were determined by logistic regression analysis. RESULTS: Out of 524 eligible patients, 277 consented to enrolment. Two hundred and thirty-six subjects (88%) were anti-HCV-positive, and 162 of these were viremic (69%). Significant liver fibrosis (defined as Ishak stages F3-F6, TE value ≥ 8.85 kPa, or GUCI > 0.33) was found in 69 out of 103 (67%) tested viremic patients, and was associated with alcohol intake (p = 0.03), higher body mass index (BMI; p = 0.04), and the presence of anti-HBc antibodies (indicating exposure to hepatitis B virus (HBV); p = 0.02). CONCLUSIONS: Significant liver fibrosis was detected in two-thirds of HCV viremic OST recipients in this cohort, and was associated with alcohol use, high BMI, and exposure to HBV. These findings indicate that the management of HCV and associated risk factors should be emphasized in Swedish OST programs.
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Hepatitis C Crónica/patología , Cirrosis Hepática/virología , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/virología , Adulto , Femenino , Hepatitis C Crónica/epidemiología , Humanos , Cirrosis Hepática/epidemiología , Masculino , Persona de Mediana Edad , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/epidemiología , Suecia/epidemiología , Adulto JovenRESUMEN
Background: Pregnancy has been associated with elevated incidence of tuberculosis (TB) disease. Since 2014, people living in Sweden with origin in TB-endemic countries have been offered screening for TB infection in antenatal care (ANC) using Quantiferon-TB assays. We assessed factors associated with TB infection in this population and determined the incidence of TB disease during pregnancy and postpartum periods with regard to ANC Quantiferon-TB results. Methods: Quantiferon-TB results obtained during ANC in Sweden, 2014-2018, were linked to data from national registers (Pregnancy Register, Patient Register and Tuberculosis Register). Factors associated with TB infection (defined as Quantiferon-TB ≥0.35â IU/mL) were identified using logistic regression analysis. Incidence of TB disease was determined with regard to pregnancy, postpartum and subsequent periods, and ANC Quantiferon-TB results. Results: Among 7638 screened individuals, 1424 (18.6%) had TB infection. Tuberculosis infection was independently associated with higher age at immigration (adjusted odds ratio, 1.04 [95% confidence interval, 1.03-1.05]; P < .001), and was more common among people originating from Africa compared to other world regions (845/3088 [27.4%] vs 579/4550 [12.7%]; P < .001). In total, 16 participants were diagnosed with TB disease (10 during pregnancy, 4 at <6 months after delivery, 2 at >6 months after delivery); among these, all diagnosed during pregnancy/postpartum had positive ANC Quantiferon-TB results (constituting 14/1424 [1%] of people with TB infection). Conclusions: Among pregnant people screened in Swedish ANC, TB infection was associated with higher age and African origin. All cases of TB disease reported in persons with TB infection at ANC screening occurred during pregnancy or postpartum.
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Background: Despite reported tuberculosis (TB) treatment success rate of 86%, TB remains a leading cause of death in Ethiopia. We investigated patient and provider-specific factors associated with unfavorable treatment outcomes in Ethiopian health facilities providing TB care. Methods: Data on characteristics and treatment outcomes of patients registered for TB treatment at 15 public health facilities (4 hospitals and 11 health centres) were collected from clinic registers. Proportions of unfavorable outcomes (defined as deaths, loss-to-follow-up [LTFU] and treatment failure), were compared across facilities using multivariable logistic regression, with separate analyses for death and LTFU. Results: Among 3359 patients (53.5 % male, median age 28 years, 19.6 % HIV-positive), 296 (8.8 %) had unfavorable treatment outcome. Proportions of unfavorable outcomes across facilities ranged from 2.0 % to 21.1 % (median 8.3 %). Median proportions of death and LTFU among facilities were 3.3 % (range 0-10.9 %) and 2.6 % (range 0.6 %-19.2 %), respectively. Three facilities had significantly higher rates of LTFU, whereas two facilities had higher rates of death. The two facilities with full-time TB-nurses had higher proportions of successful outcomes (95.2 % vs 90.1 %, adjusted odds ratio 2.27, p < 0.0001). Conclusion: Substantial variability of TB treatment outcomes was observed across the assessed health facilities providing TB care, independently of age and HIV co-infection, reflecting possible differences in service structure and related quality of care.
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BACKGROUND: Targeted viral load (VL) testing has been proposed for antiretroviral treatment (ART) monitoring in resource-limited settings. In this study, we have investigated the performance of the host biomarker galectin-9 (Gal-9), alone and in combination with interferon-γ-inducible protein 10 (IP-10), in identifying individuals at increased likelihood of viremia during ART. SETTING: Cohort of HIV-positive adults receiving ART at Ethiopian health centers. METHODS: We included participants with detectable viremia (VL ≥150 copies/mL) 12 months after starting ART and sex-matched nonviremic controls. Performance to identify individuals with VL ≥1000 copies/mL was determined for Gal-9 and the Gal-9/IP-10 combination, respectively, using receiver operating characteristic (ROC) analysis. RESULTS: Among 191 participants (50.3% women), 46 (24.1%) had VL ≥1000 copies/mL, 23 (12.0%) had 150-999 copies/mL, and 122 (63.9%) had <150 copies/mL. Gal-9 and VL were positively correlated (r s = 0.451, P < 0.001). Sensitivity and specificity for Gal-9 to identify individuals with VL ≥1000 copies/mL were 91.3% (95% CI: 79.2-97.6) and 54.5% (95% CI: 46.0-62.8), respectively. The area under the ROC curve for Gal-9 was 0.810 (95% CI: 0.745-0.875), which was similar to that of the combination of Gal-9 and IP-10 [0.849 (95% CI: 0.792-0.905)]. Assuming 10% prevalence of VL ≥1000 copies/mL, using Gal-9 for targeted VL testing instead of universal VL testing would reduce the number of VL tests from 10 to 5 to identify 1 viremic individual, with misclassification of 1 in 10 viremic individuals. CONCLUSIONS: Gal-9 is a potential screening marker for targeted VL monitoring in ART recipients. Further studies are needed to determine optimal threshold levels.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Adulto , Femenino , Masculino , Infecciones por VIH/tratamiento farmacológico , Quimiocina CXCL10 , Configuración de Recursos Limitados , Viremia/tratamiento farmacológico , Antirretrovirales/uso terapéutico , Carga Viral , Fármacos Anti-VIH/uso terapéuticoRESUMEN
BACKGROUND: Injecting drug use (IDU) may lead to exposure to a range of carcinogenic agents. We investigated the risk and distribution of cancers among individuals with a history of IDU in Sweden. MATERIAL AND METHODS: The cancer incidence in a cohort of longitudinally followed participants in a needle exchange program (NEP), recruited between 1987 and 2007, was compared to that in the Swedish general population, matching for age group and gender. Baseline demographic and drug use data were collected and longitudinal testing of serological markers for HIV, hepatitis B and C virus was performed during NEP participation. Standardized incidence ratios (SIR) for types of cancer found in the study cohort were calculated, using data from the Swedish National Cancer Registry for reference. RESULTS: The mean follow-up time for the 3255 participants was 11.8 years, constituting 38 419 person years at risk. The mean age at end of follow-up was 42.7 years, and 75% of participants were men. Seventy-eight cases of cancer were observed (SIR 1.1 [95% CI = 0.9-1.4]). The SIR was significantly increased for five cancer types among men; primary liver, laryngeal, lung, oropharyngeal and non-melanoma skin cancer (respective SIR 12.8 [95% CI = 4.2-30.0], 9.2 [95% CI = 1.9-26.8], 3.2 [95% CI = 1.5-6.1], 7.3 [95% CI = 1.5-21.2], and 3.5 [95% CI = 1.1-8.2]), and for cancers of endocrine organs among women (5.3 [95% CI = 1.7-12.4]). CONCLUSION: Although the standardized overall cancer incidence in this relatively young IDU cohort was similar to that in the general population, the risk of specific types of cancer was significantly increased, suggesting that IDU confers elevated risks for certain malignancies. These findings prompt further studies to investigate causative factors and suggest the need for surveillance among persons with a history of IDU.