BACKGROUND: Adolescents have poorer outcomes across the HIV cascade compared to adults. We aimed to assess progress in HIV case-finding, antiretroviral treatment (ART), viral load coverage (VLC), and viral load suppression (VLS) among adolescents enrolled in the U.S. President's Emergency Plan for AIDS Relief (PEPFAR)-supported programs over a three-year period that included the beginning of the COVID-19 pandemic. METHODS: We analyzed PEPFAR program data in 28 countries/regions for adolescents 10-19 years between year 1 (October 2017-September 2018), year 2 (October 2018-September 2019), and year 3 (October 2019-September 2020). We calculated the number and percent change for HIV tests, HIV-positive tests, and total number on ART. Calculated indicators included positivity, percent of positives newly initiated on ART (ART linkage), VLC (percent of ART patients on ART for ≥6 months with a documented viral load result within the past 12 months), and VLS (percent of viral load tests with <1000 copies/mL). RESULTS: Between Years 1 and 3, the number of HIV tests conducted decreased by 44.2%, with a 29.1% decrease in the number of positive tests. Positivity increased from 1.3% to 1.6%. The number of adolescents receiving ART increased by 10.4%. Additionally, ART linkage increased (77.8% to 86.7%) as did VLC (69.4% to 79.4%) and VLS (72.8% to 81.5%). CONCLUSIONS: Our findings demonstrate PEPFAR's success in increasing the adolescent treatment cohort. We identified ongoing gaps in adolescent case-finding, linkage, VLC, and VLS that could be addressed with a strategic mix of testing strategies, optimal ART regimens, and adolescent-focused service delivery models.

BACKGROUND: With countries moving towards reaching the UNAIDS 90-90-90 goal to achieve HIV epidemic control, there are going to be an unprecedented number of persons who will need to be tested, treated, and regularly monitored for viral suppression. However, most of the countries with the greatest burden of HIV/AIDS experience regular stock outages which could be detrimental to reaching these targets. ART and other commodities such as HIV test kits and laboratory supplies need to be readily and consistently available to achieve these targets. The main objective was to improve access to HIV/AIDS related commodities and strengthening institutional capacity for the management of HIV/AIDS logistics services through the MAUL procurement and supply chain strengthening project (PSSP) that rolled out four interventions on mentorship and support supervision, stock level monitoring, spatial visualization of stock indicators using GIS, and using WhatsApp to submit order reports as photo images. METHODS: Medical Access Uganda Limited, a private-not-for-profit supply chain management company in Uganda, implemented these interventions as part of a procurement and supply chain strengthening project (PSSP). These interventions were evaluated using performance monitoring indicators from 2011-2016. We tested for the significance in the change in scores of performance monitoring indicators using the test for difference in proportions. Health facilities were scored on 6 categories and accredited as bronze, silver or gold based on their total scores. Kaplan-Meier estimates were computed for time to silver, and gold ranking and univariate and multivariate Cox proportional hazards models were computed for time to gold ranking. RESULTS: We observed a significant reduction in reported stock-outs from 46 to 4% (p < 0.001) in the analysis period. Accurate stock card inventory rose from 79 to 91% (p < 0.001); adequate stock levels rose from 54 to 71% (p = 0.002) and stock reporting rates from 91 to 100% (p < 0.001). The stock order fill rate improved from a high of 93% to 97% (p = 0.375). Patient load (medium vs low adjusted hazard ratio (aHR): 2.19, p = 0.026; high vs low aHR: 2.97, p = 0.034) and number of support supervision visits (6-10 aHR: 3.33, p = 0.024; > 10 aHR: 5.78, p = 0.003) were associated with better stock management ranking scores. CONCLUSIONS: Improvements in supply chain management in countries committed to achieving the 90-90-90 goals are crucial to achieving HIV epidemic control. Health system strengthening and mentorship investments in Uganda were feasible and are essential for sustainable disease control efforts.

Fostering a "balanced" gut microbiome through the administration of beneficial microbes that can competitively exclude pathogens has gained a lot of attention and use in human and animal medicine. However, little is known about how microbes affect the horizontal gene transfer of antimicrobial resistance (AMR). To shed more light on this question, we challenged neonatal broiler chicks raised on reused broiler chicken litter-a complex environment made up of decomposing pine shavings, feces, uric acid, feathers, and feed-with Salmonella enterica serovar Heidelberg (S. Heidelberg), a model pathogen. Neonatal chicks challenged with S. Heidelberg and raised on reused litter were more resistant to S. Heidelberg cecal colonization than chicks grown on fresh litter. Furthermore, chicks grown on reused litter were at a lower risk of colonization with S. Heidelberg strains that encoded AMR on IncI1 plasmids. We used 16S rRNA gene sequencing and shotgun metagenomics to show that the major difference between chicks grown on fresh litter and those grown on reused litter was the microbiome harbored in the litter and ceca. The microbiome of reused litter samples was more uniform and enriched in functional pathways related to the biosynthesis of organic and antimicrobial molecules than that in fresh litter samples. We found that Escherichia coli was the main reservoir of plasmids encoding AMR and that the IncI1 plasmid was maintained at a significantly lower copy per cell in reused litter compared to fresh litter. These findings support the notion that commensal bacteria play an integral role in the horizontal transfer of plasmids encoding AMR to pathogens like Salmonella. IMPORTANCE Antimicrobial resistance spread is a worldwide health challenge, stemming in large part from the ability of microorganisms to share their genetic material through horizontal gene transfer. To address this issue, many countries and international organizations have adopted a One Health approach to curtail the proliferation of antimicrobial-resistant bacteria. This includes the removal and reduction of antibiotics used in food animal production and the development of alternatives to antibiotics. However, there is still a significant knowledge gap in our understanding of how resistance spreads in the absence of antibiotic selection and the role commensal bacteria play in reducing antibiotic resistance transfer. In this study, we show that commensal bacteria play a key role in reducing the horizontal gene transfer of antibiotic resistance to Salmonella, provide the identity of the bacterial species that potentially perform this function in broiler chickens, and also postulate the mechanism involved.

BACKGROUND: To assess the effect of a combination strategy for prevention of human immunodeficiency virus (HIV) on the incidence of HIV infection, we analyzed the association between the incidence of HIV and the scale-up of antiretroviral therapy (ART) and medical male circumcision in Rakai, Uganda. Changes in population-level viral-load suppression and sexual behaviors were also examined. METHODS: Between 1999 and 2016, data were collected from 30 communities with the use of 12 surveys in the Rakai Community Cohort Study, an open, population-based cohort of persons 15 to 49 years of age. We assessed trends in the incidence of HIV on the basis of observed seroconversion data, participant-reported use of ART, participant-reported male circumcision, viral-load suppression, and sexual behaviors. RESULTS: In total, 33,937 study participants contributed 103,011 person-visits. A total of 17,870 persons who were initially HIV-negative were followed for 94,427 person-years; among these persons, 931 seroconversions were observed. ART was introduced in 2004, and by 2016, ART coverage was 69% (72% among women vs. 61% among men, P<0.001). HIV viral-load suppression among all HIV-positive persons increased from 42% in 2009 to 75% by 2016 (P<0.001). Male circumcision coverage increased from 15% in 1999 to 59% by 2016 (P<0.001). The percentage of adolescents 15 to 19 years of age who reported never having initiated sex (i.e., delayed sexual debut) increased from 30% in 1999 to 55% in 2016 (P<0.001). By 2016, the mean incidence of HIV infection had declined by 42% relative to the period before 2006 (i.e., before the scale-up of the combination strategy for HIV prevention) - from 1.17 cases per 100 person-years to 0.66 cases per 100 person-years (adjusted incidence rate ratio, 0.58; 95% confidence interval [CI], 0.45 to 0.76); declines were greater among men (adjusted incidence rate ratio, 0.46; 95% CI, 0.29 to 0.73) than among women (adjusted incidence rate ratio, 0.68; 95% CI, 0.50 to 0.94). CONCLUSIONS: In this longitudinal study, the incidence of HIV infection declined significantly with the scale-up of a combination strategy for HIV prevention, which provides empirical evidence that interventions for HIV prevention can have a population-level effect. However, additional efforts are needed to overcome disparities according to sex and to achieve greater reductions in the incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

On March 9, 2016, a male butcher from Kabale District, Uganda, aged 45 years, reported to the Kabale Regional Referral Hospital with fever, fatigue, and headache associated with black tarry stools and bleeding from the nose. One day later, a student aged 16 years from a different sub-county in Kabale District developed similar symptoms and was admitted to the same hospital. The student also had a history of contact with livestock. Blood specimens collected from both patients were sent for testing for Marburg virus disease, Ebola virus disease, Rift Valley fever (RVF), and Crimean Congo Hemorrhagic fever at the Uganda Virus Research Institute, as part of the viral hemorrhagic fevers surveillance program. The Uganda Virus Research Institute serves as the national viral hemorrhagic fever reference laboratory and hosts the national surveillance program for viral hemorrhagic fevers, in collaboration with the CDC Viral Special Pathogens Branch and the Uganda Ministry of Health.

BACKGROUND: With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS: We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS: Between 1990 and 2013, global viral hepatitis deaths increased from 0.89 million (95% uncertainty interval [UI] 0.86-0.94) to 1.45 million (1.38-1.54); YLLs from 31.0 million (29.6-32.6) to 41.6 million (39.1-44.7); YLDs from 0.65 million (0.45-0.89) to 0.87 million (0.61-1.18); and DALYs from 31.7 million (30.2-33.3) to 42.5 million (39.9-45.6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION: Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING: Bill & Melinda Gates Foundation.

Acute febrile illness (AFI) is associated with substantial morbidity and mortality worldwide yet an etiologic agent is often not identified. Convalescent serology is impractical, blood culture is slow, and many pathogens are fastidious or impossible to cultivate. We developed a real-time PCR based TaqMan Array Card (TAC) that can test six to eight samples within 2.5 hours from sample to results and simultaneously detect 26 AFI associated organisms, including 15 viruses (Chikungunya, Crimean-Congo hemorrhagic fever virus, Dengue, Ebola virus, Bundibugyo virus, Sudan virus, Hantaviruses (HTN and SEO), Hepatitis E, Marburg, Nipah virus, O'nyong-nyong virus, Rift Valley fever virus, West Nile virus, Yellow fever virus), eight bacteria (Bartonella spp., Brucella spp., Coxiella burnetii, Leptospira spp., Rickettsia spp., Salmonella enterica and Salmonella enterica serovar Typhi, Yersinia pestis), and three protozoa (Leishmania spp., Plasmodium spp., Trypanosoma brucei). Two extrinsic controls (Phocine Herpesvirus 1 and bacteriophage MS2) were included to assure extraction and amplification efficiency. Analytical validation was performed on spiked specimens for linearity, intra-assay precision, inter-assay precision, limit of detection, and specificity. The performance of the card on clinical specimens was evaluated with 1,050 blood samples by comparison to the individual real-time PCR assays, and TAC exhibited overall 88% (278/315, 95% confidence interval 84% to 92%) sensitivity and 99% (5261/5326, 98% to 99%) specificity. This TaqMan Array Card can be used in field settings as a rapid screen for outbreak investigation or pathogen surveillance, including Ebola virus.

Medical students have limited exposure to field epidemiology, even though will assume public health roles after graduation. We established a 10-week elective in field epidemiology during medical school. Students attended one-week didactic sessions on epidemiology, and nine weeks in field placement sites. We administered pre- and post-tests to evaluate the training. We enrolled 34 students in 2011 and 2012. In 2011, we enrolled five of 24 applicants from a class of 280 medical students. In 2012, we enrolled 18 of 81 applicants from a class of 360 students; plus 11 who participated in the didactic sessions only. Among the 34 students who completed the didactic sessions, 74% were male, and their median age was 24 years (range: 22-26). The median pre-test score was 64% (range: 47-88%) and the median post-test score was 82% (range: 72-100%). Successful completion of the field projects was 100%. Six (30%) students were not aware of public health as a career option before this elective, 56% rated the field experience as outstanding, and 100% reported it increased their understanding of epidemiology. Implementing an elective in field epidemiology within the medical training is a highly acceptable strategy to increase awareness for public health among medical students.

BACKGROUND: As the WHO verified that China reached the target of 1% prevalence of chronic hepatitis B infection among children targeted by universal hepatitis B immunization of newborns, the country considered new options for hepatitis B prevention and control. We reviewed hepatitis B surveillance in the broader context of viral hepatitis surveillance to propose recommendations to improve the system. METHODS: We described surveillance for viral hepatitis in China with a specific focus on hepatitis B. We assessed critical attributes of the system, including data quality, predictive positive value and usefulness. RESULTS: While remarkable progress in hepatitis B immunization of infants and children has likely almost eliminated transmission in younger age groups, reported rates of hepatitis B increased steadily in China between 1990 and 2008, probably because of a failure to distinguish acute from chronic infections. Elements that prevented a clearer separation between acute and chronic cases included (1) missed opportunity to report cases accurately among clinicians, (2) low availability and use of tests to detect IgM against the hepatitis B core antigen (IgM anti-HBc) and (3) lack of systems to sort, manage and analyze surveillance data. CONCLUSIONS: To improve hepatitis B surveillance, China may consider (1) training clinicians to diagnose acute cases and to use IgM anti-HBc to confirm them, (2) improving access and use of validated IgM anti-HBc tests and (3) developing data management and analysis techniques that sort out acute from chronic cases.

In efforts to inform public health decision makers, the Global Burden of Diseases, Injuries, and Risk Factors 2010 (GBD2010) Study aims to estimate the burden of disease using available parameters. This study was conducted to collect and analyze available prevalence data to be used for estimating the hepatitis C virus (HCV) burden of disease. In this systematic review, antibody to HCV (anti-HCV) seroprevalence data from 232 articles were pooled to estimate age-specific seroprevalence curves in 1990 and 2005, and to produce age-standardized prevalence estimates for each of 21 GBD regions using a model-based meta-analysis. This review finds that globally the prevalence and number of people with anti-HCV has increased from 2.3% (95% uncertainty interval [UI]: 2.1%-2.5%) to 2.8% (95% UI: 2.6%-3.1%) and >122 million to >185 million between 1990 and 2005. Central and East Asia and North Africa/Middle East are estimated to have high prevalence (>3.5%); South and Southeast Asia, sub-Saharan Africa, Andean, Central, and Southern Latin America, Caribbean, Oceania, Australasia, and Central, Eastern, and Western Europe have moderate prevalence (1.5%-3.5%); whereas Asia Pacific, Tropical Latin America, and North America have low prevalence (<1.5%). CONCLUSION: The high prevalence of global HCV infection necessitates renewed efforts in primary prevention, including vaccine development, as well as new approaches to secondary and tertiary prevention to reduce the burden of chronic liver disease and to improve survival for those who already have evidence of liver disease. (HEPATOLOGY 2013).

BACKGROUND: Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS: We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS: In 2010, the three leading risk factors for global disease burden were high blood pressure (7.0% [95% uncertainty interval 6.2-7.7] of global DALYs), tobacco smoking including second-hand smoke (6.3% [5.5-7.0]), and alcohol use (5.5% [5.0-5.9]). In 1990, the leading risks were childhood underweight (7.9% [6.8-9.4]), household air pollution from solid fuels (HAP; 7.0% [5.6-8.3]), and tobacco smoking including second-hand smoke (6.1% [5.4-6.8]). Dietary risk factors and physical inactivity collectively accounted for 10.0% (95% UI 9.2-10.8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0.9% (0.4-1.6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION: Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS: We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS: Global DALYs remained stable from 1990 (2.503 billion) to 2010 (2.490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION: Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). METHODS: Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. FINDINGS: Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350,000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0.37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. INTERPRETATION: Rates of YLDs per 100,000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. FUNDING: Bill & Melinda Gates Foundation.

OBJECTIVE: Chronic hepatitis B virus infection is one of the most serious infections and a major risk factor for deaths from cirrhosis and liver cancer. We estimate age-, sex- and region-specific prevalence of chronic HBV infection and calculate the absolute number of persons being chronically infected. METHODS: A systematic review of the literature for studies reporting HBV infection was conducted and worldwide HBsAg seroprevalence data was collected over a 27-year period (1980-2007). Based on observed data, age-specific prevalence and endemicity were estimated on a global level and for all world regions for 1990 and 2005 using an empirical Bayesian hierarchical model. FINDINGS: From 1990 to 2005, the prevalence of chronic HBV infection decreased in most regions. This was particularly evident in Central sub-Saharan Africa, Tropical and Central Latin America, South East Asia and Central Europe. Despite this decrease in prevalence, the absolute number of HBsAg positive persons increased from 223 million in 1990 to 240 million in 2005. Age-specific prevalence varied by geographical region with highest endemicity levels in sub-Saharan Africa and prevalence below 2% in regions such as Tropical and Central Latin America, North America and Western Europe. Asian regions showed distinct prevalence patterns with lower intermediate prevalence in South Asia, but up to 8.6% HBsAg prevalence in East Asia. Strong declines were seen in South East Asian children. CONCLUSION: Declines in HBV infection prevalence may be related to expanded immunization. The increasing overall number of individuals being chronically infected with HBV, and the widespread global differences in HBV prevalence call for targeted approaches to tackle HBV-related mortality and morbidity. HBV infection prevalence data are needed at country and sub-national level to estimate disease burden and guide health and vaccine policy.

INTRODUCTION: Surveillance for health outcomes is critical for rapid responses and timely prevention of disaster-related illnesses and injuries after a disaster-causing event. The Disaster Surveillance Workgroup (DSWG) of the US Centers for Disease Control and Prevention developed a standardized, single-page, morbidity surveillance form, called the Natural Disaster Morbidity Surveillance Individual Form (Morbidity Surveillance Form), to describe the distribution of injuries and illnesses, detect outbreaks, and guide timely interventions during a disaster. PROBLEM: Traditional data sources can be used during a disaster; however, supplemental active surveillance may be required because traditional systems often are disrupted, and many persons will seek care outside of typical acute care settings. Generally, these alternative settings lack health surveillance and reporting protocols. The need for standardized data collection was demonstrated during Hurricane Katrina, as the multiple surveillance instruments that were developed and deployed led to varied and uncoordinated data collection methods, analyses, and morbidity data reporting. Active, post-event surveillance of affected populations is critical for rapid responses to minimize and prevent morbidity and mortality, allocate resources, and target public health messaging. METHODS: The CDC and the Georgia Department of Public Health (GDPH) conducted a study to evaluate a Morbidity Surveillance Form to determine its ability to capture clinical presentations. The form was completed for each patient evaluated in an emergency department (ED) during triage from 01 August, 2007 through 07 August, 2007. Data from the form were compared with the ED discharge diagnoses from electronic medical records, and kappa statistics were calculated to assess agreement. RESULTS: Nine hundred forty-nine patients were evaluated, 41% were male and 57% were Caucasian. According to the forms, the most common reasons for seeking treatment were acute illness, other (29%); pain (12%); and gastrointestinal illness (8%). The frequency of agreement between discharge diagnoses and the form ranged from 3 to 100%. Kappa values ranged from 0.23-1.0, with nine of the 12 categories having very good or good agreement. CONCLUSION: With modifications to increase sensitivity for capturing certain clinical presentations, the Morbidity Surveillance Form can be a useful tool for capturing data needed to guide public health interventions during a disaster. A validated collection instrument for a post-disaster event facilitates rapid and standardized comparison and aggregation of data across multiple jurisdictions, thus, improving the coordination, timeliness, and accuracy of public health responses. The DSWG revised the Morbidity Surveillance Form based on information from this study.

Most of the estimated 350 million people with chronic hepatitis B virus (HBV) infection live in resource-constrained settings. Up to 25% of those persons will die prematurely of hepatocellular carcinoma (HCC) or cirrhosis. Universal hepatitis B immunization programmes that target infants will have an impact on HBV-related deaths several decades after their introduction. Antiviral agents active against HBV are available; treatment of HBV infection in those who need it has been shown to reduce the risk of HCC and death. It is estimated that 20-30% of persons with HBV infection could benefit from treatment. However, drugs active against HBV are not widely available or utilized in persons infected with HBV. Currently recommended antiviral agents used for treatment of human immunodeficiency virus (HIV) infection do not adequately suppress HBV, which is of great concern for the estimated 10% of the HIV-infected persons in Africa who are co-infected with HBV. Progressive liver disease has been shown to occur in co-infected persons whose HBV infection is not suppressed. In view of these concerns, an informal World Health Organization consultation of experts concluded that: chronic HBV is a major public health problem in emerging nations; all HIV-infected persons should be screened for HBV infection; HIV/HBV co-infected persons should be treated with therapies active against both viruses and that reduce the risk of resistance; standards for the management of chronic HBV infection should be adapted to resource-constrained settings. In addition, a research agendum was developed focusing on issues related to prevention and treatment of chronic HBV in resource-constrained settings.

OBJECTIVE: To identify risk factors for polymicrobial bloodstream infections (BSIs) in pediatric bone marrow transplant (BMT) outpatients attending a newly constructed clinic affiliated with a children's hospital. METHODS: All 30 outpatients treated at a new BMT clinic during September 10-21, 2007, were enrolled in a cohort study. The investigation included interviews, medical records review, observations, and bacterial culture and molecular typing of patient and environmental isolates. Data were analyzed using exact conditional logistic regression. RESULTS: Thirteen patients experienced BSIs caused by 16 different, predominantly gram-negative organisms. Presence of a tunneled catheter (odds ratio [OR], 19.9 [95% confidence interval {CI}, 2.4-infinity), catheter access (OR, 13.7 [95% CI, 1.8-infinity]), and flushing of a catheter with predrawn saline (OR, 12.9 [95% CI, 1.0-766.0]) were independently associated with BSI. The odds of experiencing a BSI increased by a factor of 16.8 with each additional injection of predrawn saline (95% CI, 1.8-827.0). Although no environmental source of pathogens was identified, interviews revealed breaches in recommended infection prevention practice and medication handling. Saline flush solutions were predrawn, and multiple doses were obtained from single-dose preservative-free vials to avoid delays in patient care. CONCLUSION: We speculate that infection prevention challenges in the new clinic, combined with successive needle punctures of vials, facilitated extrinsic contamination and transmission of healthcare-associated pathogens. We recommend that preservative-free single-use vials not be punctured more than once. Use of single-use prefilled saline syringes might prevent multiuse of single-use saline vials. Storage of saline outside a medication supply system might be advisable. Before opening new clinic facilities, hospitals should consider conducting a mock patient flow exercise to identify infection control challenges.

BACKGROUND: Homeless persons are at higher risk for morbidity and mortality from both chronic and episodic illness than the general population. Few data are available on the prevalence of these conditions and uptake of vaccination for prevention. METHODS: In March 2007, we administered a cross-sectional survey to a convenience sample of homeless persons in Atlanta. RESULTS: Approximately half (46.2%) of the survey participants reported at least one chronic medical condition. Acute respiratory symptoms within the previous 30 days were reported by up to 57.7% of survey participants. Receipt of influenza vaccination was reported by 31.9% of survey participants, receipt of pneumococcal vaccine by 18.7%. Vaccination rates varied by age and risk group. DISCUSSION: The survey demonstrated high rates of morbidity in this population. Influenza and pneumococcal vaccination rates were suboptimal. Culturally appropriate interventions must be developed to prevent respiratory and other diseases in this important group.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has rapidly emerged in the USA as a cause of severe infections in previously healthy persons without traditional risk factors. We describe the epidemiology of severe CA-MRSA disease in the state of Georgia, USA and analyse the risk of death associated with three different clinical syndromes of CA-MRSA disease - pneumonia, invasive disease, and skin and soft-tissue infections (SSTIs). A total of 1670 cases of severe CA-MRSA disease were reported during 2005-2007. The case-fatality rate was 3.4%; sex and race of fatal and non-fatal cases did not differ significantly. While CA-MRSA pneumonia and invasive disease were less common than SSTIs, they were about 15 times more likely to result in death [risk ratio 16.69, 95% confidence interval (CI) 10.28-27.07 and 13.98, 95% CI 7.74-25.27, respectively]. When controlling for age and the presence of other clinical syndromes the odds of death in patients manifesting specific severe CA-MRSA syndromes was highest in those with pneumonia (odds ratio 11.34). Possible risk factors for severe CA-MRSA SSTI and pneumonia included the draining of lesions without medical assistance and an antecedent influenza-like illness.