Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation

Clinical significance of molecular techniques for HPV detection in liquid-based cytology specimens (ThinPrep Pap-test)

Purpose. This prospective accuracy study aimed to assess the diagnostic accuracy of NASBA and Flow Cytometry for E6&7-HPV-mRNA detection as a primary screening test compared to cytology in the triage of severe CIN lesions. Methods. 1116 women referred for a routine Pap test were recruited. Residual material of pap-smears was tested by NASBA and by flow cytometry for E6&7-mRNA expression. The accuracy indices of both techniques and of NASBA-HPV-16 were assessed for detection of CIN2+ lesions and compared to cytology. Results. Increased lesion severity was associated with increased positivity rates of both NASBA and flow (p<0.001). A positive correlation between NASBA and flow cytometry was identified when these methods were examined with the Phi coefficient (value 0.473). Both tests exhibited higher specificity rates than cytology (87.7% and 78.8% vs 63.6% for CIN2+ lesions). However, their sensitivity rates did not exceed those of cytology (75.3% and 78.3% vs 87.6%). Conclusions. NASBA and flow cytometry exhibited increased specificity for the triage of CIN2+ lesions. However, their relatively lower sensitivity and higher positivity rates compared to cytology do not make them ideal for a primary screening. The role of mRNA detection in the screening for severe cervical lesions remains to be clarified.Σκοπός. Η εκτίμηση της διαγνωστικής ακρίβειας του NASBA και της κυτταρομετρίας ροής για την ανίχνευση του mRNA για τις πρωτεΐνες E6&7 του HPV ως πρωτοβάθμιας μεθόδου πληθυσμιακού ελέγχου σε σύγκριση με την κυτταρολογία. Μέθοδοι. Συλλέχθηκαν 1116 δείγματα από Pap test ρουτίνας. Το δείγμα αναλύθηκε με NASBA και κυτταρομετρία ροής για έκφραση του E6&7-mRNA. Έγινε σύγκριση μεταξύ της κυτταρολογίας και των δεικτών ακρίβειας των δύο τεχνικών, καθώς και του NASBA-HPV-16 για την ανίχνευση CIN2+ βλαβών. Αποτελέσματα. Αυξημένη βαρύτητα βλάβης συσχετίστηκε με αυξημένα ποσοστά θετικών αποτελεσμάτων τόσο για το NASBA όσο και για την κυτταρομετρία ροής (p<0.001). Θετική συσχέτιση βρέθηκε μεταξύ των 2 τεχνικών όταν αυτές εξετάστηκαν με το Phi coefficient (τιμή: 0.473). Αμφότερες οι τεχνικές επέδειξαν υψηλότερη ειδικότητα από την κυτταρολογία (87.7% και 78.8% προς 63.6% για CIN2+ βλάβες). Εντούτοις, η ευαισθησία τους δεν ξεπέρασε αυτήν της κυτταρολογίας (75.3% και 78.3% προς 87.6% αντίστοιχα). Συμπεράσματα. Το NASBA και η κυτταρομετρία ροής επέδειξαν υψηλότερη ειδικότητα στην ανίχνευση CIN2+ βλαβών. Όμως, η σχετικά χαμηλότερη ευαισθησία τους σε σχέση με την κυτταρολογία τις καθιστά ανεπαρκείς ως πρωτοβάθμια εξέταση πληθυσμιακού ελέγχου