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The WHO recommends preventive treatment for all pediatric contacts of a confirmed TB case, but coverage remains low in many high TB burden countries. We aimed to assess the coverage and adherence of the isoniazid preventive therapy (IPT) program among children under 5 years of age with household exposure to an adult pulmonary TB case in a rural district of Southern Mozambique. The estimated IPT coverage was 11.7%. A longer distance to the health center and lower age of the children hindered IPT initiation. Among patients who started IPT, 12/18 (69.9%) were adherent to the 6-month treatment.
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Infecciones por VIH , Tuberculosis Pulmonar , Adulto , Niño , Humanos , Preescolar , Isoniazida/uso terapéutico , Antituberculosos/uso terapéutico , Mozambique/epidemiología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/prevención & control , Instituciones de Salud , Infecciones por VIH/tratamiento farmacológicoRESUMEN
AIMS: We present a field evaluation of the diagnostic accuracy of Xpert MTB/RIF ("Xpert") and Xpert MTB/RIF Ultra ("Ultra") using two cohorts in a high tuberculosis/HIV burden setting in Southern Mozambique. METHODS: Single respiratory specimens from symptomatic adults accessing healthcare services (passive case finding (PCF) cohort) and from household and community close contacts (active case finding (ACF) cohort) were tested by smear microscopy, culture, Xpert and Ultra. Liquid and solid culture served as a composite reference standard. We explored the impact of trace results on specificity via their recategorisation to negative (in all and just among those previously treated individuals). RESULTS: 1419 and 252 participants were enrolled in the PCF and ACF cohorts, respectively. For the PCF cohort, Ultra showed higher sensitivity than Xpert overall (0.95 (95% CI 0.90-0.98) versus 0.88 (96% CI 0.82-0.93); p<0.001) and among smear-negative patients (0.84 (96% CI 0.71-0.93) versus 0.63 (96% CI 0.48-0.76)). Ultra's specificity was lower than Xpert's (0.96 (96% CI 0.95-0.97) versus 0.98 (96% CI 0.97-0.99); p=0.008). For ACF, sensitivities were the same (0.67 (95% CI 0.22-0.96) for both tests), although Ultra detected a higher number of microbiologically confirmed samples than Xpert (4.7% (12 out of 252) versus 2.7% (seven out of 252)). Conditional recategorisation of trace results among previously treated participants maintained differences in specificity in the PCF cohort. CONCLUSION: These results add evidence on the improved sensitivity of Ultra and support its use in different case finding scenarios.
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Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Adulto , Pruebas Diagnósticas de Rutina , Humanos , Sensibilidad y Especificidad , Esputo , Tuberculosis Pulmonar/diagnósticoAsunto(s)
Paraplejía/etiología , Tuberculosis Ganglionar/microbiología , Tuberculosis de la Columna Vertebral/diagnóstico por imagen , Absceso/microbiología , Antituberculosos/administración & dosificación , Antituberculosos/uso terapéutico , Preescolar , Humanos , Masculino , Mycobacterium tuberculosis/aislamiento & purificación , Cuello/microbiología , Cuello/patología , Paraplejía/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Tuberculosis Ganglionar/patología , Tuberculosis de la Columna Vertebral/tratamiento farmacológico , Tuberculosis de la Columna Vertebral/microbiología , Tuberculosis de la Columna Vertebral/patologíaRESUMEN
Prompt diagnosis is critical for tuberculosis (TB) control, as it enables early treatment which in turn, reduces transmission and improves treatment outcomes. We investigated the impact on TB diagnosis of introducing Xpert Ultra as the frontline diagnostic test, combined with an innovative active-case finding (ACF) strategy (based on Xpert Ultra semi-quantitative results and spatial parameters), in a semi-rural district of Southern Mozambique. From January-December 2018 we recruited incident TB-cases (index cases, ICs) and their household contacts (HCs). Recruitment of close community contacts (CCs) depended on IC´s Xpert Ultra results, and the population density of their area. TB-contacts, either symptomatic or people living with HIV, were asked to provide a spot sputum for lab-testing. Trends on TB case notification were compared to the previous years and to those of two districts in the south of the Maputo province (control area), using an interrupted time series analysis with and without control (CITS/ITS). A total of 1010 TB ICs (37.1% laboratory-confirmed) were recruited; 3165 HCs and 4730 CCs were screened for TB. Eighty-nine additional TB cases were identified through the ACF intervention (52.8% laboratory-confirmed). The intervention increased by 8.2% all forms of TB cases detected in 2018. Xpert Ultra trace positive results accounted for a high proportion of laboratory confirmations in the ACF cohort (51.1% vs 13.7% of those passively diagnosed). The Number Needed to Screen to find a TB case differed widely among HCs (55) and CCs (153). During the intervention period, a reversal of the previous negative trend in lab-confirmed case notifications was observed in the district. However, the CITS model did not show any statistically significant difference compared to the control area. Paediatric population benefited the most from the ACF strategy and HCs screening seemed an effective intervention to find microbiological confirmed cases in early stages of the disease.
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BACKGROUND: Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens. METHODS: We undertook a prospective diagnostic accuracy study in Eswatini, Mozambique, and Tanzania from Sept 21, 2020, to Feb 2, 2023, to compare the diagnostic accuracy for tuberculosis of a novel stool qPCR test with the current diagnostic standard for Mycobacterium tuberculosis DNA detection from sputum and stool, Xpert-MTB/RIF Ultra (Xpert Ultra). Sputum, stool, and urine samples were provided by a cohort of participants, aged 10 years or older, diagnosed with tuberculosis. Participants with tuberculosis (cases) were enrolled within 72 h of treatment initiation for tuberculosis diagnosed clinically or following laboratory confirmation. Participants without tuberculosis (controls) consisted of household contacts of the cases who did not develop tuberculosis during a 6-month follow-up. The performance was compared with a robust composite microbiological reference standard (CMRS). FINDINGS: The cohort of adolescents and adults (n=408) included 268 participants with confirmed or clinical tuberculosis (cases), 147 (55%) of whom were living with HIV, and 140 participants (controls) without tuberculosis. The sensitivity of the novel stool qPCR was 93·7% (95% CI 87·4-97·4) compared with participants with detectable growth on M tuberculosis culture, and 88·1% (81·3-93·0) compared with sputum Xpert Ultra. The stool qPCR had an equivalent sensitivity as sputum Xpert Ultra (94·8%, 89·1-98·1) compared with culture. Compared with the CMRS, the sensitivity of the stool qPCR was higher than the current standard for tuberculosis diagnostics on stool, Xpert Ultra (80·4%, 73·4-86·2 vs 73·5%, 66·0-80·1; p=0·025 on paired comparison). The qPCR also identified 17-21% additional tuberculosis cases compared to sputum Xpert Ultra or sputum culture. In controls without tuberculosis, the specificity of the stool qPCR was 96·9% (92·2-99·1). INTERPRETATION: In this study, a novel qPCR for the diagnosis of tuberculosis from stool specimens had a higher accuracy in adolescents and adults than the current diagnostic PCR gold standard on stool, Xpert-MTB/RIF Ultra, and equivalent sensitivity to Xpert-MTB/RIF Ultra on sputum. FUNDING: National Institutes of Health (NIH) Allergy and Infectious Diseases, and NIH Fogarty International Center.
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Heces , Mycobacterium tuberculosis , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Esputo , Tuberculosis , Humanos , Adolescente , Heces/microbiología , Heces/química , Adulto , Estudios Prospectivos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Femenino , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adulto Joven , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Tuberculosis/orina , Esputo/microbiología , Persona de Mediana Edad , Niño , Tanzanía/epidemiología , ADN Bacteriano/análisis , Mozambique/epidemiologíaRESUMEN
In several low-income countries, the transport of sputa could take up to one week to reach the laboratories, resulting in increased contamination rates and a loss of growth. The aim of this study was to evaluate the effect of the OMNIgene-SPUTUM in preserving Mycobacterium tuberculosis on sputum samples simulating three hypothetical scenarios for conservation and/or decontamination: (1) sputum was mixed with OMN and conserved at room temperature for five days and then processed for culture (OMN); (2) sputum cultures followed the routine standing operating procedure at day 0 (STD); and (3) sputum samples were kept at room temperature for five days and mixed with the standard decontamination reagent (SDT5) and then processed for culture. The positivity rate based on smear microscopy was 36.4%, 29.1%, and 27.3% for STD, STD5, and OMN, respectively. The proportion of positive results by liquid culture (MGIT) was 39.1% (43/110) for STD, 26.4% (29/110) for STD5, and 20.0% for OMN (22/110). The overall concordance of liquid culture results was 51.8% (57/110): 37.3% (41/110) for negative results, 11.8% (13/110) for MTBC growth, and 2.7% (3/110) for contaminated results. The OMN arm showed better performance in solid culture than in liquid culture, with a notable reduction in contaminated results.
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Strengthening tuberculosis diagnosis is an international priority and the advocacy for multi-disease testing devices raises the possibility of improving laboratory efficiency. However, the advantages of centralized platforms might not translate into real improvements under operational conditions. This study aimed to evaluate the field use of the Abbott RealTime MTB (RT-MTB) and Xpert MTB/RIF assays, in a large cohort of HIV-positive and TB presumptive cases in Southern Mozambique. Over a 6-month period, 255 HIV-positive TB presumptive cases were consecutively recruited in the high TB/HIV burden district of Manhiça. The diagnostic performance of both assays was evaluated against two different reference standards: a microbiological gold standard (MGS) and a composite reference standard (CRS). Results from the primary analysis (MGS) showed improved sensitivity (Se) and reduced specificity (Sp) for the Abbott RT-MTB assay compared to the Xpert MTB/RIF (RT-MTB Se: 0.92 (95% CI: 0.75;0.99) vs Xpert Se: 0.73 (95% CI: 0.52;0.88) p value = 0.06; RT-MTB Sp: 0.80 (0.72;0.86) vs Xpert Sp: 0.96 (0.92;0.99) p value < 0.001). The lower specificity may be due to cross-reactivity with non-tuberculous mycobacteria (NTMs), the detection of non-viable MTBC, or the identification of true TB cases missed by the gold standard.
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Infecciones por VIH/complicaciones , Mycobacterium tuberculosis/aislamiento & purificación , Juego de Reactivos para Diagnóstico , Tuberculosis/diagnóstico , Adulto , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Farmacorresistencia Bacteriana/genética , Femenino , Infecciones por VIH/inmunología , Humanos , Isoniazida/farmacología , Isoniazida/uso terapéutico , Masculino , Mozambique , Mycobacterium tuberculosis/genética , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa/instrumentación , Rifampin/farmacología , Rifampin/uso terapéutico , Sensibilidad y Especificidad , Tuberculosis/tratamiento farmacológico , Tuberculosis/inmunología , Tuberculosis/microbiología , Adulto JovenRESUMEN
INTRODUCTION: AIDS-mortality remains unacceptably high in sub-Saharan Africa, largely driven by advanced HIV disease (AHD). We nested a study in an existing tuberculosis (TB) contact-tracing intervention (Xpatial-TB). The aim was to assess the burden of AHD among high-risk people living with HIV (PLHIV) identified and to evaluate the provision of the WHO-recommended package of care to this population. METHODS: All PLHIV ≥14 years old identified between June and December 2018 in Manhiça District by Xpatial-TB were offered to participate in the study if ART naïve or had suboptimal ART adherence. Consenting individuals were screened for AHD. Patients with AHD (CD4 < 200 cells/µL or WHO stage 3 or 4) were offered a package of interventions in a single visit, including testing for cryptococcal antigen (CrAg) and TB-lipoarabinomannan (TB-LAM), prophylaxis and treatment for opportunistic infections, adherence support or accelerated ART initiation. We collected information on follow-up visits carried out under routine programmatic conditions for six months. RESULTS: A total of 2881 adults were identified in the Xpatial TB-contact intervention. Overall, 23% (673/2881) were HIV positive, including 351 TB index (64.2%) and 322 TB contacts (13.8%). Overall, 159/673 PLHIV (24%) were ART naïve or had suboptimal ART adherence, of whom 155 (97%, 124 TB index and 31 TB-contacts) consented to the study and were screened for AHD. Seventy percent of TB index-patients (87/124) and 16% of TB contacts (5/31) had CD4 < 200 cells/µL. Four (13%) of the TB contacts had TB, giving an overall AHD prevalence among TB contacts of 29% (9/31). Serum-CrAg was positive in 4.6% (4/87) of TB-index patients and in zero TB contacts. All ART naïve TB contacts without TB initiated ART within 48 hours of HIV diagnosis. Among TB cases, ART timing was tailored to the presence of TB and cryptococcosis. Six-month mortality was 21% among TB-index cases and zero in TB contacts. CONCLUSIONS: A TB contact-tracing outreach intervention identified undiagnosed HIV and AHD in TB patients and their contacts, undiagnosed cryptococcosis among TB patients, and resulted in an adequate provision of the WHO-recommended package of care in this rural Mozambican population. Same-day and accelerated ART initiation was feasible and safe in this population including among those with AHD.
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Infecciones por VIH , Tuberculosis , Adolescente , Adulto , Trazado de Contacto , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Mozambique/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Organización Mundial de la SaludRESUMEN
Tuberculosis (TB) misdiagnosis remains a public health concern, especially among people living with HIV (PLHIV), given the high mortality associated with missed TB diagnoses. The main objective of this study was to describe the all-cause mortality, TB incidence rates and their associated risk factors in a cohort of PLHIV with presumptive TB in whom TB was initially ruled out. We retrospectively followed a cohort of PLHIV with presumptive TB over a 2 year-period in a rural district in Southern Mozambique. During the study period 382 PLHIV were followed-up. Mortality rate was 6.8/100 person-years (PYs) (95% CI 5.2-9.2) and TB incidence rate was 5.4/100 PYs (95% CI 3.9-7.5). Thirty-six percent of deaths and 43% of TB incident cases occurred in the first 12 months of the follow up. Mortality and TB incidence rates in the 2-year period after TB was initially ruled out was very high. The TB diagnostic work-up and linkage to HIV care should be strengthened to decrease TB burden and all-cause mortality among PLHIV with presumptive TB.
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Coinfección/mortalidad , Infecciones por VIH/mortalidad , VIH/aislamiento & purificación , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/mortalidad , Adulto , Coinfección/epidemiología , Coinfección/virología , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mozambique/epidemiología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Tuberculosis/epidemiología , Tuberculosis/virologíaRESUMEN
Traditionally, smear microscopy has been used as a point-of-care measure of bacillary burden in tuberculosis patients to inform infection control and contact tracing. Xpert MTB/RIF has the potential to replace smear. However, data to support the use of its quantitative output [cycle threshold (CT)] as an alternate point-of-care measure of bacillary burden are limited. This study assessed the correlation (Spearman's) between CT, smear, culture time-to-positivity (TTP), and clinical factors in patients with Xpert-positive sputum from Mozambique (n = 238) and South Africa (n = 462). Mean CT and smear grade correlated well (ρ0.72); compared to TTP and smear (ρ0.61); and mean CT and TTP (ρ0.50). In multivariate analyses, lower CT (higher bacillary load) was associated with negative HIV serostatus and low BMI. A smear positivity rule-out (95% sensitivity) CT cut-off of 28.0 was identified, with 54.1% specificity, 2.07 positive likelihood ratio, 0.09 negative likelihood ratio and 79.0% correctly classified. Cut-offs were higher for HIV positive compared to HIV negative individuals for any set sensitivity level. This study suggests Xpert CT values correlate well with smear, both in HIV positive and negative individuals, and that CT cut-offs might be broadly applicable to multiple settings. Studies to directly assess the association of CT with infectiousness are needed.
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Coinfección/epidemiología , Infecciones por VIH/epidemiología , Mycobacterium tuberculosis/patogenicidad , Tuberculosis Pulmonar/epidemiología , Adulto , África Austral/epidemiología , Coinfección/diagnóstico , Coinfección/microbiología , Coinfección/virología , Femenino , VIH/genética , VIH/patogenicidad , Infecciones por VIH/microbiología , Infecciones por VIH/patología , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Mozambique/epidemiología , Mycobacterium tuberculosis/aislamiento & purificación , Sistemas de Atención de Punto , Esputo/microbiología , Esputo/virología , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/patología , Tuberculosis Pulmonar/virologíaRESUMEN
Simple effective tools to monitor the long treatment of tuberculosis (TB) are lacking. Easily measured host derived biomarkers have been identified but need to be validated in larger studies and different population groups. Here we investigate the early response in IP-10 levels (between day 0 and day 7 of TB therapy) to identify bacteriological status at diagnosis among 127 HIV-infected patients starting TB treatment. All participants were then classified as responding or not responding to treatment blindly using a previously described IP-10 kinetic algorithm. There were 77 bacteriologically confirmed cases and 41 Xpert MTB/RIF® and culture negative cases. Most participants had a measurable decline in IP-10 during the first 7 days of therapy. Bacteriologically confirmed cases were more likely to have high IP-10 levels at D0 and had a steeper decline than clinically diagnosed cases (mean decline difference 2231 pg/dl, 95% CI: 897-3566, p = 0.0013). Bacteriologically confirmed cases were more likely to have a measurable decline in IP-10 at day 7 than clinically diagnosed cases (48/77 (62.3%) vs 13/41 (31.7%), p < 0.001). This study confirms the association between a decrease in IP-10 levels during the first week of treatment and a bacteriological confirmation at diagnosis in a large cohort of HIV positive patients.
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Quimiocina CXCL10/sangre , Infecciones por VIH/complicaciones , Seropositividad para VIH/complicaciones , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Adolescente , Adulto , Algoritmos , Antibióticos Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana/fisiología , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Encuestas y Cuestionarios , Resultado del Tratamiento , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto JovenRESUMEN
El suicidio adolescente es un problema a nivel mundial que ha impulsado diversos esfuerzos de prevención, siendo relevante poder detectar a tiempo el riesgo a edades tempranas. A pesar de que existen diversos instrumentos para este propósito, sobre todo en adultos, en Chile no existe uno validado en población menor a 15 años de edad, donde se ha visto un aumento progresivo del riesgo durante los últimos años. Este estudio es una validación de la escala de suicidalidad OKASHA en población de 10 a 14 años. El instrumento presentó buenas propiedades psicométricas, tanto en la predicción de intentos reales de suicidio como en su correlación con otros predictores de riesgo descritos en la literatura. Debido a su buen poder predictivo, fácil administración y poco tiempo requerido, el instrumento resulta idóneo para ser utilizado en contextos como la atención primaria de salud o en la comunidad, donde la detección oportuna del riesgo y la adecuada derivación son de vital importancia, especialmente en una población donde dicho riesgo ha sido muchas veces invisibilizado y por ende no abordado hasta cometerse el acto propiamente tal.
Adolescent suicide is a worldwide problem that has triggered diverse prevention efforts. Detecting the risk as quickly as possible at an early age is highly relevant. Although there are various instruments that exist for this very purpose, mostly for adults, there is no validated instrument for those under 15 years of age. Incidentally, in the past couple of years this same age group has had an increased risk in this area. This study is a validation of the suicidal scale "OKASHA" for the population between 10 and 14 years old. The instrument presented good psychometric properties in both the prediction of real suicidal attempts and in its correlation with other risk predictors taken from literature. Due to its good predictive ability, easy administration, and the little time that is required, the instrument is ideal for being used in contexts such as in primary healthcare. It can also be used in the community, where detecting risk and referral in a timely fashion are of vital importance, especially in a population where such risk has been made invisible and for this reason, has not been detected until the final act has been accomplished.
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Humanos , Masculino , Femenino , Niño , Adolescente , Suicidio , Encuestas y Cuestionarios , Ideación Suicida , Psicometría , Chile , Valor Predictivo de las Pruebas , Curva ROCAsunto(s)
Juego de Reactivos para Diagnóstico , Tuberculosis/diagnóstico , Antibióticos Antituberculosos/uso terapéutico , Proteínas Bacterianas/genética , ARN Polimerasas Dirigidas por ADN/genética , Reacciones Falso Positivas , Humanos , Mycobacterium tuberculosis/genética , Rifampin/uso terapéutico , Sensibilidad y Especificidad , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Pulmonar/diagnósticoRESUMEN
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