Prospective Observational Study of Incidence and Preventable Burden of Childhood Tuberculosis, Kenya.
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ABSTRACT:
SUBMITTER: Brent AJ
PROVIDER: S-EPMC5823335 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In 2015, the World Health Organization (WHO) declared tuberculosis (TB) to be responsible for more deaths than any other single infectious disease. The burden of TB among children has frequently been dismissed as relatively low with resulting deaths contributing very little to global under-five all-cause mortality, although without rigorous estimates of these statistics, the burden of childhood TB was, in reality, unknown. Recent work in the area has resulted in a WHO estimate of 1 million new cases of childhood TB in 2014 resulting in 136,000 deaths. Around 3% of these cases likely have multidrug-resistant TB and at least 40,000 are in HIV-infected children. TB is now thought to be a major or contributory cause of many deaths in children under five years old, despite not being recorded as such, and is likely in the top ten causes of global mortality in this age group. In particular, recent work has shown that TB is an under-lying cause of a substantial proportion of pneumonia deaths in TB-endemic countries. Childhood TB should be given higher priority: we need to identify children at greatest risk of TB disease and death and make more use of tools such as active case-finding and preventive therapy. TB is a preventable and treatable disease from which no child should die.
| S-EPMC5166554 | biostudies-other
Project description:IntroductionAlthough vaccines provide a cost-effective solution to vaccine-preventable diseases (VPDs), the disease burden of VPDs is still very high in most parts of the world.MethodsA population-based observational study was conducted in Shandong province, China, from 2013 to 2017, giving an insight into the epidemiological characteristics and disease burden of seven VPDs. The incidence trend was estimated using the Poisson regression model. The disease burden was calculated using the disability-adjusted life years (DALYs).ResultsMost VPDs included in the China's National Immunization Program had higher incidence density (ID) in inland cities. The ID of mumps decreased significantly, while herpes zoster increased (both P < 0.05). The top three causes of the disease burden as assessed with DALYs included tuberculosis, herpes zoster, and hepatitis B, with the rates of 72.21, 59.99, and 52.10 DALYs/100 000, respectively. The disease burden of influenza and herpes zoster were relatively high in people aged > 50 years, while highest DALYs of hepatitis B were found in young adults.ConclusionInequalities in the vaccine coverage by geography, socio-economic status, and targeted population contribute to the increasing incidence and high burden of VPDs and call for renewed and sustained immunization strategies in China.
| S-EPMC8867126 | biostudies-literature
Project description:New diagnoses of tuberculosis (TB) present important opportunities to detect and treat HIV. Rates of HIV and TB in Indonesia's easternmost Papua Province exceed national figures, but data on co-infection rates and outcomes are lacking. We aimed to measure TB-HIV co-infection rates, examine longitudinal trends, compare management with World Health Organisation (WHO) recommendations, and document progress and outcome.Adults with newly-diagnosed smear-positive pulmonary TB managed at the Timika TB clinic, Papua Province, were offered voluntary counselling and testing for HIV in accordance with Indonesian National Guidelines, using a point-of-care antibody test. Positive tests were confirmed with 2 further rapid tests. Study participants were assessed using clinical, bacteriological, functional and radiological measures and followed up for 6 months.Of 162 participants, HIV status was determined in 138 (85.2%), of whom 18 (13.0%) were HIV+. Indigenous Papuans were significantly more likely to be HIV+ than Non-Papuans (Odds Ratio [OR] 4.42, 95% confidence interval [CI] 1.38-14.23). HIV prevalence among people with TB was significantly higher than during a 2003-4 survey at the same TB clinic, and substantially higher than the Indonesian national estimate of 3%. Compared with HIV- study participants, those with TB-HIV co-infection had significantly lower exercise tolerance (median difference in 6-minute walk test: 25 m, p = 0.04), haemoglobin (mean difference: 1.3 g/dL, p = 0.002), and likelihood of cavitary disease (OR 0.35, 95% CI 0.12-1.01), and increased occurrence of pleural effusion (OR 3.60, 95% CI 1.70-7.58), higher rates of hospitalisation or death (OR 11.80, 95% CI 1.82-76.43), but no difference in the likelihood of successful 6-month treatment outcome. Adherence to WHO guidelines was limited by the absence of integration of TB and HIV services, specifically, with no on-site ART prescriber available. Only six people had CD4+ T-cell counts recorded, 11 were prescribed co-trimoxazole and 4 received ART before, during or after TB treatment, despite ART being indicated in 14 according to 2006 WHO guidelines.TB-HIV co-infection in southern Papua, Indonesia, is a serious emerging problem especially among the Indigenous population, and has risen rapidly in the last 5 years. Major efforts are required to incorporate new WHO recommendations on TB-HIV management into national guidelines, and support their implementation in community settings.
| S-EPMC3022835 | biostudies-literature
Project description:BackgroundBlood transcriptional signatures are candidates for non-sputum triage or confirmatory tests of tuberculosis. Prospective head-to-head comparisons of their diagnostic accuracy in real-world settings are necessary to assess their clinical use. We aimed to compare the diagnostic accuracy of candidate transcriptional signatures identified by systematic review, in a setting with a high burden of tuberculosis and HIV.MethodsWe did a prospective observational study nested within a diagnostic accuracy study of sputum Xpert MTB/RIF (Xpert) and Xpert MTB/RIF Ultra (Ultra) tests for pulmonary tuberculosis. We recruited consecutive symptomatic adults aged 18 years or older self-presenting to a tuberculosis clinic in Cape Town, South Africa. Participants provided blood for RNA sequencing, and sputum samples for liquid culture and molecular testing using Xpert and Ultra. We assessed the diagnostic accuracy of candidate blood transcriptional signatures for active tuberculosis (including those intended to distinguish active tuberculosis from other diseases) identified by systematic review, compared with culture or Xpert MTB/RIF positivity as the standard reference. In our primary analysis, patients with tuberculosis were defined as those with either a positive liquid culture or Xpert result. Patients with missing blood RNA or sputum results were excluded. Our primary objective was to benchmark the diagnostic accuracy of candidate transcriptional signatures against the WHO target product profile (TPP) for a tuberculosis triage test.FindingsBetween Feb 12, 2016, and July 18, 2017, we obtained paired sputum and RNA sequencing data from 181 participants, 54 (30%) of whom had confirmed pulmonary tuberculosis. Of 27 eligible signatures identified by systematic review, four achieved the highest diagnostic accuracy with similar area under the receiver operating characteristic curves (Sweeney3: 90·6% [95% CI 85·6-95·6]; Kaforou25: 86·9% [80·9-92·9]; Roe3: 86·9% [80·3-93·5]; and BATF2: 86·8% [80·6-93·1]), independent of age, sex, HIV status, previous tuberculosis, or sputum smear result. At test thresholds that gave 70% specificity (the minimum WHO TPP specificity for a triage test), these four signatures achieved sensitivities between 83·3% (95% CI 71·3-91·0) and 90·7% (80·1-96·0). No signature met the optimum criteria, of 95% sensitivity and 80% specificity proposed by WHO for a triage test, or the minimum criteria (of 65% sensitivity and 98% specificity) for a confirmatory test, but all four correctly identified Ultra-positive, culture-negative patients.InterpretationSelected blood transcriptional signatures met the minimum WHO benchmarks for a tuberculosis triage test but not for a confirmatory test. Further development of the signatures is warranted to investigate their possible effects on clinical and health economic outcomes as part of a triage strategy, or when used as add-on confirmatory test in conjunction with the highly sensitive Ultra test for Mycobacterium tuberculosis DNA.FundingRoyal Society Newton Advanced Fellowship, Wellcome Trust, National Institute of Health Research, and UK Medical Research Council.
| S-EPMC7113842 | biostudies-literature
Project description:Childhood TB diagnosis is challenging. Studies in adults suggest Microscopic Observation Drug Susceptibility (MODS) culture or the Xpert MTB/RIF assay might be used to expand bacteriological diagnosis. However data from children are more limited. We prospectively compared MODS and Xpert MTB/RIF with standard microscopy and culture using the BD MGIT 960 system among 1442 Kenyan children with suspected TB. 97 specimens from 54 children were TB culture-positive: 91 (94%) by MGIT and 74 (76%) by MODS (p = 0.002). 72 (74%) culture-positive and 7 culture-negative specimens were Xpert MTB/RIF positive. Xpert MTB/RIF specificity was 100% (99.7-100%) among 1164 specimens from 892 children in whom TB was excluded, strongly suggesting all Xpert MTB/RIF positives are true positives. The sensitivity of MGIT, MODS and Xpert MTB/RIF was 88%, 71% and 76%, respectively, among all 104 true positive (culture and/or Xpert MTB/RIF positive) specimens. MGIT, MODS and Xpert MTB/RIF on the initial specimen identified 40/51 (78%), 33/51 (65%) and 33/51 (65%) culture-confirmed pulmonary TB cases, respectively; Xpert MTB/RIF detected 5 additional culture-negative cases. The high sensitivity and very high specificity of the Xpert MTB/RIF assay supports its inclusion in the reference standard for bacteriological diagnosis of childhood TB in research and clinical practice.
| S-EPMC5603584 | biostudies-literature
Project description:The purpose of this study was to estimate the burden of osteoporotic fractures beyond the hospitalization period covering up to the first year after the fracture. This was a prospective, 12-month, observational study including patients aged ?65 years hospitalized due to a first low-trauma hip fracture, in six Spanish regions. Health resource utilization (HRU), quality of life (QoL) and autonomy were collected and total costs calculated. Four hundred and eighty seven patients (mean ± SD age 83 ± 7 years, 77 % women) were included. Twenty-two percent of patients reported a prior non-hip low-trauma fracture, 16 % were receiving osteoporotic treatment at baseline, and 3 % had densitometry performed (1.8 % T-score ?-2.5). Sixteen percent of patients died (women 14 %; men 25 %; p = 0.0011) during the first year. Mean hospital stay was 11.8 ± 7.9 days and 95.1 % of patients underwent surgery. Other relevant HRUs were: outpatient visits in 78 % of patients (mean 9.2 ± 9.7); walking aids, 58.7 %; rehabilitation facilities, 35.5 % (28.7 ± 41.2 sessions); and formal and informal home care, 22.2 % (49.6 ± 72.2 days) and 53.4 % (77.1 ± 101.0 h), respectively. Mean direct cost was €9690 (95 % confidence interval: 9184-10,197) in women and €9019 (8079-9958) in men. Main cost drivers were: first hospitalization episode (women €7067 [73 %]; men €7196 [80 %]); outpatient visits (€1323 [14 %]; €997 [11 %]); and home care (€905 [9 %]; €767 [9 %]). QoL and autonomy showed a marked decrease during hospitalization, not entirely recovered at 12 months (p < 0.05 vs. baseline for EQ-5D, Harris hip score and modified Barthel index). In a Spanish setting, osteoporotic hip fractures incur a high societal and economic cost, mainly due to the first hospitalization HRU, but also due to subsequent outpatient visits and home care.
| S-EPMC5214753 | biostudies-other
Project description:ObjectivesTo characterize the types and magnitude of psychosocial burden present in caregivers who have a child with sickle cell disease (SCD) in Kenya and to identify predictors of caregiver psychosocial burden, including disease severity and financial hardship.MethodsPrimary caregivers (N = 103) of children aged 1-10 years diagnosed with SCD completed surveys assessing multiple domains of caregiver quality of life (QOL), adjustment to child illness, mental health, and financial hardship. Descriptive statistics characterize psychosocial burden, and linear models assess associations.ResultsOn indicators of QOL, caregivers report multiple difficulties across most domains, including daily activities and physical, social, cognitive, and emotional well-being. Daily activities emerged as most burdensome. On indicators of parental adjustment to chronic illness, guilt and worry emerged as the greatest concern, followed by long-term uncertainty and unresolved sorrow and anger; relative to these, they reported higher levels of emotional resources. Financial hardship was high, as caregivers reported moderate to major financial losses due to the time spent caring for their child. General linear model analyses revealed that level of financial hardship was a significant predictor of all negative psychosocial outcomes.ConclusionsResults document that Kenyan caregivers of children with SCD experience difficulties across multiple domains of functioning and that financial difficulties are likely associated with psychosocial burden. Results can guide intervention development for caregivers of children with SCD in low-resource, global contexts.
| S-EPMC7825476 | biostudies-literature
Project description:INTRODUCTION:Tuberculosis (TB) continues to be an important public health problem throughout much of the world. Drug treatment is the only effective treatment method, but adverse drug events (ADEs) and adverse drug reactions (ADRs) can affect medication adherence. As the number of drug-resistant TB patients and the number of anti-TB drugs have increased, it is necessary to explore the risk factors for ADEs/ADRs to reduce their occurrence. This study aims to build a home-based anti-TB treatment cohort and to recognise the incidences, prognosis and risk factors of anti-TB drug-induced ADEs/ADRs in real-world experiences. METHODS AND ANALYSIS:This study is a multicentre, prospective observational cohort study. The study population will consist of 3200 newly diagnosed TB patients between January 2019 and December 2020. After initiating the anti-TB treatment, all patients will be followed up until finishing treatment unless they withdraw, and we will record personal drug use and signs and/or symptoms of discomfort. Patients will receive scheduled laboratory tests in designated hospitals every 2 weeks during the first 2 months, and the residual blood sample after conducting the laboratory tests will be preserved. The ADEs/ADRs will be placed into eight categories: liver dysfunction, gastrointestinal reactions, drug allergy, arthralgia or muscle pain, nervous system disorders, haematological system disorders, renal impairment and others. ETHICS AND DISSEMINATION:This study protocol has been approved by the ethics committees of Nanjing Medical University. All patients will give written informed consent before enrollment. The findings of the study will be published in peer-reviewed journals and will be presented at national and international conferences.
| S-EPMC6475199 | biostudies-other
Project description:BackgroundTuberculosis (TB) stigma remains a barrier to early diagnosis and treatment completion. Increased understanding of stigma is necessary for improved interventions to minimise TB stigma and its effects. The purpose of this study is to quantitatively measure TB stigma and to explore qualitatively its manifestation among TB patients in a rural Kenyan community.MethodsThis hospital based study using explanatory sequential mixed methods approach was conducted in 2016. In the quantitative part of the study, a questionnaire containing socio-demographic characteristics and scales measuring perceived TB stigma and experienced TB stigma, was administered to 208 adult pulmonary TB patients receiving treatment in West Pokot County. Respondents with high stigma were purposively selected to take part in in-depth interviews and focus group discussions. The qualitative data were collected through 15 in-depth interviews and 6 focus group discussions with TB patients. Descriptive and bivariate analysis was done for the quantitative data while the thematic analysis was done for qualitative data.ResultsThe internal consistency reliability coefficients were satisfactory with Cronbach alphas of 0.87 and 0.86 for the 11-item and 12-item stigma measurement scale. The investigation revealed that TB stigma was high. The key drivers of TB stigma were the association of TB with HIV/AIDS and the fear of TB transmission. TB stigma was exemplified through patients being isolated by others, self-isolation, fear to disclose TB diagnosis, association of TB with human immunodeficiency virus (HIV) and lack of social support. Being a woman was significantly associated with high levels of both experienced stigma (p = 0.007) and perceived stigma (p = 0.005) while age, marital status, occupation and the patient's religion were not.ConclusionThere is a need to implement stigma reduction interventions in order to improve TB program outcomes.
| S-EPMC7561176 | biostudies-literature
Project description:Controversial data have been reported on the prognostic value of C-X-C motif chemokine receptor 4 (CXCR4) in chronic lymphocytic leukemia (CLL). This prospective, single-center, observational study aimed to evaluate the role of CXCR4 in the pathophysiology of CLL and its prognostic role. A total of 158 patients of CLL were enrolled, and CXCR4 expression on CLL cells was detected by flow cytometry (FCM) at initial diagnosis. The patients were divided into 2 groups according to the CXCR4 mean fluorescence intensity (MFI) median. Also, four patient specimens from the CXCR4low and CXCR4high groups were selected for whole transcriptome sequencing. The progression-free survival (PFS) of CLL patients in the CXCR4high group was significantly shorter than the CXCR4low group, with a median follow-up time of 27 months (log-rank P < 0.001). Moreover, CXCR4 overexpression (MFI > 3376) was an independent marker of poor PFS in CLL patients (P < 0.001). Analysis of whole transcriptome sequencing results revealed that CXCR4 plays an important role in the migration of CLL. Collectively, CXCR4 expression levels on leukemia cells can be detected rapidly by FCM. CXCR4 overexpression was significantly associated with poorer prognosis in CLL patients within a shorter follow-up time.
2024-01-26 | GSE254015 | GEO