Childhood hepatitis C virus infection: An Australian national surveillance study of incident cases over five years

NHMRC: Enabling Grant No: 402784ARC Linkage Project Grant(LP110200277

High Prevalence of Tuberculosis and Serious Bloodstream Infections in Ambulatory Individuals Presenting for Antiretroviral Therapy in Malawi

Background Tuberculosis (TB) and serious bloodstream infections (BSI) may contribute to the high early mortality observed among patients qualifying for antiretroviral therapy (ART) with unexplained weight loss, chronic fever or chronic diarrhea. Methods and Findings A prospective cohort study determined the prevalence of undiagnosed TB or BSI among ambulatory HIV-infected adults with unexplained weight loss and/or chronic fever, or diarrhea in two routine program settings in Malawi. Subjects with positive expectorated sputum smears for AFB were excluded. Investigations Bacterial and mycobacterial blood cultures, cryptococcal antigen test (CrAg), induced sputum (IS) for TB microscopy and solid culture, full blood count and CD4 lymphocyte count. Among 469 subjects, 52 (11%) had microbiological evidence of TB; 50 (11%) had a positive (non-TB) blood culture and/or positive CrAg. Sixty-five additional TB cases were diagnosed on clinical and radiological grounds. Nontyphoidal Salmonellae (NTS) were the most common blood culture pathogens (29 cases; 6% of participants and 52% of bloodstream isolates). Multivariate analysis of baseline clinical and hematological characteristics found significant independent associations between oral candidiasis or lymphadenopathy and TB, marked CD4 lymphopenia and NTS infection, and severe anemia and either infection, but low positive likelihood ratios (<2 for all combinations). Conclusions We observed a high prevalence of TB and serious BSI, particularly NTS, in a program cohort of chronically ill HIV-infected outpatients. Baseline clinical and hematological characteristics were inadequate predictors of infection. HIV clinics need better rapid screening tools for TB and BSI. Clinical trials to evaluate empiric TB or NTS treatment are required in similar populations

Hepatitis B and hepatitis C virus in an antenatal population : an epidemiological study

Although Australian epidemiology of HBV and HCV has been well described for populations groups at higher risk, but the information available for groups generally considered to be lower risk is much more limited. An understanding of the prevalence of these infections and their risk factors in antenatal women is important to guide testing policy and practice. A study was therefore conducted of the epidemiology of hepatitis B and hepatitis C infection in women. In addition, women were asked about their experience with antenatal testing. A total of 516 women participated in the survey, of these 479 (95%) women had been tested for HCV antibodies .The prevalence of HCV antibodies was 4% overall, and 2% among women who were unaware of their HCV status prior to their antenatal test. A history of injecting drug use and residing with a HCV positive person were significantly associated with HCV infection in multivariate analyses. HBV testing was conducted in 468 (99.6%) of women, and the overall prevalence was 2%. Risk factors identified were birthplace in countries of South East Asia. Women were asked about their perception of antenatal testing and pre-test information. Nearly a third (143, 30.5%) of women who had been tested for HCV infection either said that they did not know whether they had been tested, or said that they had declined testing. The corresponding proportion for HBV infection was 28.8% (135). Over 65% and 66% of women said that had not received any information about testing for HCV and HBV respectively. The finding that virtually all antenatal women were being tested for HCV was in contrast to government and non-government organisation policies of selective screening in place during the study period. Of concern was the substantial proportion of women who were tested despite reporting that they had declined their clinicians offer to test for HCV and HBV, and the large number of women who reported an absence of pre-test information. Women who said they had received information reported the delivery and quality of information varied according to the antenatal clinician group, but perceived the overall quality as poor

Prevalence and correlates of perceived infertility in Ghana

Perceived infertility is an understudied phenomenon in low‐ and middle‐income countries, where biomedical infertility can have severe consequences, particularly for women. We conducted a nationally representative survey of Ghanaian women, estimated the prevalence of and reasons for perceived infertility, and assessed factors associated with higher levels of perceived infertility using a partial proportional odds model. Among 4,070 women, 13 percent believed they were “very likely” to have difficulty getting pregnant when they wanted to, 21 percent believed this was “somewhat likely,” and 66 percent believed this was “not at all likely.” Reasons for perceived infertility varied by whether the respondent was currently seeking pregnancy. In multivariable analysis, several factors were associated with higher levels of perceived infertility, while unexpectedly, women who reported ever using contraception were less likely to report perceived infertility. Acknowledging the need to address infertility globally and understanding the role of perceived infertility are important components in supporting people\u27s ability to decide whether and when to have children

Interference competition between coyotes and raccoons: a test of the mesopredator release hypothesis

Some predator species appear to conform to the mesopredator release hypothesis (MRH), in which larger predators help limit populations of smaller predators. This hypothesis has been used to explain the possible relationship between coyotes, mesopredators, and resultant cascades involving nonpredators. However, relationships between coyotes and noncanid mesopredators are poorly understood, and predictions from the MRH have rarely been rigorously tested. We monitored sympatric raccoon and coyote populations to assess 2 predictions derived from the MRH: coyote predation is an important cause of mortality in raccoon populations or raccoons avoid areas used by coyotes. Between March 2000 and September 2001, we recorded 3553 locations for 27 radio-collared raccoons and 1393 locations for 13 coyotes captured on the Max McGraw Wildlife Foundation in Illinois, USA. No raccoon mortality from coyote predation was observed during the study, and raccoon survival was >0.7 each season. All raccoon 95% home ranges exhibited overlap with 95% coyote home ranges in each season. The mean proportion of raccoon locations within 95% coyote home ranges did not vary by sex but did vary by season. Raccoon overlap of coyote core areas varied considerably among individuals within seasons, ranging from 0% to 83%. However, 45% of raccoons had <10% overlap with coyote core areas, whereas only 14% of raccoons exhibited >50% overlap. Mean overlap with core areas did not vary by season or sex. For those raccoons with home ranges overlapping coyote core areas, mean proportion of observed raccoon locations within coyote core areas was generally greater than the mean proportion of random locations. Scent-station experiments failed to document raccoon avoidance of specific sites that had been marked with coyote urine. We did not find support for a mortality prediction or avoidance prediction to support MRH with regard to raccoons and coyotes. These results suggest that relationships among mammalian predators may not be simply dictated by body size, particularly for species outside the Canidae. Copyright 2007.Canis latrans; coyote; habitat use; mesopredator release; predation risk; Procyon lotor; raccoon; survival

Odanacatib for the treatment of postmenopausal osteoporosis : Results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study

Background Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42–0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40–0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66–0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95–1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90–1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02–1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58–1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98–1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02–1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10–1·71; p=0·0051). Interpretation Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis