Post Doc, Resident, Aarhus University/Clinical Institute
Improving case-finding of Tuberculosis in low-ressource settings using a clinical score.
Introduction: Tuberculosis (TB) remains one of the world’s deadliest diseases, with approximate 10 million people developing TB, 1.4 million deaths due to it and an estimated 3 million TB cases remaining undiagnosed in 2015. Sputum smear microscopy is still the main diagnostic tool in most high-burden areas, despite recently developed new and improved methods, such as the GenXpert MTB/Rif. It is well established that more men than women are diagnosed with Tuberculosis, but the reason for this is unknown. While care seeking studies from Asia have shown that fewer women seek help for signs and symptoms suggesting TB disease, the picture from Africa is more diverse. We have previously shown that more women seek help for TB disease-like signs and symptoms, but more men are diagnosed with the disease. Methods: In a group of diagnosed TB patients we assessed time with symptoms before diagnosis, method of diagnosis and health care seeking behavior. Further, disease severity at time of diagnosis was assessed using the Bandim TBscore.
Results: We included 1006 TB patients diagnosed from 2004-2017. Of those 36% (n=363) were female and the mean age was 35 years. HIV- coinfection was more prevalent among women than men (34% vs 21%, p<0.001) with no differences in regards to HIV-type. Time to diagnosis was significantly longer for women compared to men (108 days vs 96 days, p=0.002). Further, more men (51% vs 39%) were diagnosed at the first consultation and only 2% of them had to seek help more than three times to get diagnosed compared to 7% among the females. In the care seeking process. Compared to men women had a higher TBscore at the time of diagnosis than men (5.8 vs. 5.2, p<0.001) and of the 363 women in the cohort, fewer (66%) were smear positive than among the males (79%) (p=0.002) while the smear grade among smear positive patients was equally distributed (p=0.149).
Discussion and Conclusion: While more women than men seek help for symptoms and signs suggesting TB less are diagnosed with the disease. This may, partly, be due to a higher rate of HIV co-infection among women complicating the diagnostic work-up. It may also reflect the womens inability to produce sufficient sputum samples which prevents them to be diagnosed by the most used diagnostic tool; sputum smear microscopy. In conclusion, women have a longer way to diagnosis and therefore are sicker when starting TB treatment.
Abstract: The Bandim Health Project study area in Bissau, Guinea-Bissau.To assess the potential usefulness of predictors (elsewhere applied) and clinical scores (TBscore and TBscore II) based on signs and symptoms typical of tuberculosis (TB) in case finding.Observational prospective cohort study of patients with signs and symptoms suggestive of pulmonary TB (PTB) from 2010 to 2012.We included 1089 PTB suspects with a mean age of 34 years (95%CI 33-35); human immunodeficiency virus (HIV) prevalence was 15.1%. PTB was diagnosed in 107 suspects (76.4% sputum smear-positive, 25.2% HIV-infected). Cough > 2 weeks had the highest diagnostic ability (area under the receiver operating characteristic curve [AUC] 0.66, 95%CI 0.62-0.71), while TBscore < 3 best excluded PTB (negative likelihood ratio [LR-] 0.3) when HIV status was not known. TBscore II ≥ 3 had the highest diagnostic ability in HIV-infected PTB suspects (AUC 0.62, 95%CI 0.53-0.72), while the absence of self-reported weight loss best excluded PTB (LR- 0.2). Cough > 2 weeks as a trigger for smear microscopy missed 32.1% of smear-positive PTB cases.Case finding could be improved by screening symptomatic adults for cough and/or weight loss using TBscore II as the trigger for smear microscopy. To suspect PTB only in patients with cough > 2 weeks (non-HIV-infected) or with current cough, fever, weight loss or night sweats (HIV-infected) was not effective in patients whose HIV status was unknown at first visit.
Pub.: 29 Mar '14, Pinned: 25 Jun '17
Abstract: A suburban area of Bissau, the capital of Guinea-Bissau; the study was conducted among presumptive pulmonary tuberculosis (prePTB) patients seeking medical care for signs and symptoms suggestive of PTB.To determine if a clinical TB score and a biomarker suPAR (soluble urokinase plasminogen activator receptor) have separate and composite ability to predict PTB diagnosis and mortality in prePTB patients.Observational prospective follow-up study conducted from August 2010 to August 2012.We included 1011 prePTB patients (mean age 34 years, 95%CI 33-35); 55% (n = 559) were female and 161 (16%) had human immunodeficiency virus (HIV) infection. Of all included patients, 10% (n = 101) were diagnosed with PTB. Mortality during follow-up was 5% (n = 48), with a mean survival time of 158 days (95%CI 27-289) in prePTB patients diagnosed with PTB vs. 144 days (95%CI 109-178) in those not diagnosed with PTB (P = 0.774). After adjusting for HIV status and age, the best separate predictor was suPAR 5 ng/ml, with a hazard ratio (HR) of 4.6 (95%CI 2.1-9.9) for mortality and 6.7 (95%CI 4.0-11.2) for TB diagnosis. All patients who died had a TBscore II + suPAR 7; the HR of the composite score for subsequent PTB diagnosis was 33.0 (95%CI 4.6-236.6).The proposed composite score of suPAR + TBscore II 7 can improve TB case finding and clinical monitoring.
Pub.: 06 Feb '17, Pinned: 25 Jun '17
Abstract: We aimed to model the incidence of infection with Mycobacterium tuberculosis among adults using data on infection incidence in children, disease prevalence in adults, and social contact patterns. We conducted a cross-sectional face-to-face survey of adults in 2011, enumerating "close" (shared conversation) and "casual" (shared indoor space) social contacts in 16 Zambian communities and 8 South African communities. We modeled the incidence of M. tuberculosis infection in all age groups using these contact patterns, as well as the observed incidence of M. tuberculosis infection in children and the prevalence of tuberculosis disease in adults. A total of 3,528 adults participated in the study. The reported rates of close and casual contact were 4.9 per adult per day (95% confidence interval: 4.6, 5.2) and 10.4 per adult per day (95% confidence interval: 9.3, 11.6), respectively. Rates of close contact were higher for adults in larger households and rural areas. There was preferential mixing of close contacts within age groups and within sexes. The estimated incidence of M. tuberculosis infection in adults was 1.5-6 times higher (2.5%-10% per year) than that in children. More than 50% of infections in men, women, and children were estimated to be due to contact with adult men. We conclude that estimates of infection incidence based on surveys in children might underestimate incidence in adults. Most infections may be due to contact with adult men. Treatment and control of tuberculosis in men is critical to protecting men, women, and children from tuberculosis.
Pub.: 10 Dec '15, Pinned: 25 Jun '17
Abstract: Unacceptable levels of Mycobacterium tuberculosis transmission are noted in high burden settings and a renewed focus on reducing person-to-person transmission in these communities is needed. We review recent developments in the understanding of airborne transmission. We outline approaches to measure transmission in populations and trials and describe the Wells-Riley equation, which is used to estimate transmission risk in indoor spaces. Present research priorities include the identification of effective strategies for tuberculosis infection control, improved understanding of where transmission occurs and the transmissibility of drug-resistant strains, and estimates of the effect of HIV and antiretroviral therapy on transmission dynamics. When research is planned and interventions are designed to interrupt transmission, resource constraints that are common in high burden settings-including shortages of health-care workers-must be considered.
Pub.: 13 Feb '16, Pinned: 25 Jun '17
Abstract: Tuberculosis (TB) case notification rates are usually higher in men than in women, but notification data are insufficient to measure sex differences in disease burden. This review set out to systematically investigate whether sex ratios in case notifications reflect differences in disease prevalence and to identify gaps in access to and/or utilisation of diagnostic services.In accordance with the published protocol (CRD42015022163), TB prevalence surveys in nationally representative and sub-national adult populations (age ≥ 15 y) in low- and middle-income countries published between 1 January 1993 and 15 March 2016 were identified through searches of PubMed, Embase, Global Health, and the Cochrane Database of Systematic Reviews; review of abstracts; and correspondence with the World Health Organization. Random-effects meta-analyses examined male-to-female (M:F) ratios in TB prevalence and prevalence-to-notification (P:N) ratios for smear-positive TB. Meta-regression was done to identify factors associated with higher M:F ratios in prevalence and higher P:N ratios. Eighty-three publications describing 88 surveys with over 3.1 million participants in 28 countries were identified (36 surveys in Africa, three in the Americas, four in the Eastern Mediterranean, 28 in South-East Asia and 17 in the Western Pacific). Fifty-six surveys reported in 53 publications were included in quantitative analyses. Overall random-effects weighted M:F prevalence ratios were 2.21 (95% CI 1.92-2.54; 56 surveys) for bacteriologically positive TB and 2.51 (95% CI 2.07-3.04; 40 surveys) for smear-positive TB. M:F prevalence ratios were highest in South-East Asia and in surveys that did not require self-report of signs/symptoms in initial screening procedures. The summary random-effects weighted M:F ratio for P:N ratios was 1.55 (95% CI 1.25-1.91; 34 surveys). We intended to stratify the analyses by age, HIV status, and rural or urban setting; however, few studies reported such data.TB prevalence is significantly higher among men than women in low- and middle-income countries, with strong evidence that men are disadvantaged in seeking and/or accessing TB care in many settings. Global strategies and national TB programmes should recognise men as an underserved high-risk group and improve men's access to diagnostic and screening services to reduce the overall burden of TB more effectively and ensure gender equity in TB care.
Pub.: 07 Sep '16, Pinned: 25 Jun '17
Abstract: Mycobacterium tuberculosis is a facultative intracellular pathogen that thrives inside host macrophages. A key trait of M. tuberculosis is to exploit and manipulate metal cation trafficking inside infected macrophages to ensure survival and replication inside the phagosome. Here, we describe the recent fascinating discoveries that the mammalian immune system responds to infections with M. tuberculosis by overloading the phagosome with copper and zinc, two metals which are essential nutrients in small quantities but are toxic in excess. M. tuberculosis has developed multi-faceted resistance mechanisms to protect itself from metal toxicity including control of uptake, sequestration inside the cell, oxidation, and efflux. The host response to infections combines this metal poisoning strategy with nutritional immunity mechanisms that deprive M. tuberculosis from metals such as iron and manganese to prevent bacterial replication. Both immune mechanisms rely on the translocation of metal transporter proteins to the phagosomal membrane during the maturation process of the phagosome. This review summarizes these recent findings and discusses how metal-targeted approaches might complement existing TB chemotherapeutic regimens with novel anti-infective therapies.
Pub.: 24 Feb '15, Pinned: 25 Jun '17