Incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infection in European hospitals: the COMBACTE-NET ARTHR-IS multi-centre study.

BACKGROUND: The aim of this study was to estimate the incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infections (SA-PJI) after primary hip and knee arthroplasty in European centres. METHODS: This study was conducted in patients who underwent primary hip and knee arthroplasty in 19 European hospitals between 2014 and 2016. The global incidence of PJI and SA-PJI was calculated. The associated disease burden was measured indirectly as infection-related mortality plus loss of function. For healthcare utilization, number and duration of hospitalizations, number and type of surgical procedures, duration of antibiotic treatments, and number of outpatient visits were collected. Subgroup and regression analyses were used to evaluate the impact of SA-PJI on healthcare utilization, controlling for confounding variables. RESULTS: The incidence of PJI caused by any micro-organism was 1.41%, and 0.40% for SA-PJI. Among SA-PJI, 20.7% were due to MRSA with substantial regional differences, and were more frequent in partial hip arthroplasty (PHA). Related deaths and loss of function occurred in 7.0% and 10.2% of SA-PJI cases, respectively, and were higher in patients with PHA. Compared with patients without PJI, patients with SA-PJI had a mean of 1.4 more readmissions, 25.1 more days of hospitalization, underwent 1.8 more surgical procedures, and had 5.4 more outpatient visits, controlling for confounding variables. Healthcare utilization was higher in patients who failed surgical treatment of SA-PJI. CONCLUSIONS: This study confirmed that the SA-PJI burden is high, especially in PHA, and provided a solid basis for planning interventions to prevent SA-PJI.

HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact.

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33-57%] and 61% genotypes 2/3 [95%CI 47-76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence.

Review article: 2014 UK consensus guidelines - hepatitis C management and direct-acting anti-viral therapy.

BACKGROUND: Therapeutic options for the management of hepatitis C virus (HCV) infection have evolved rapidly over the past two decades, with a consequent improvement in cure rates. Novel therapeutic agents are an area of great interest in the research community, with a number of these agents showing promise in the clinical setting. AIMS: To assess and present the available evidence for the use of novel therapeutic agents for the treatment of HCV, updating previous guidelines. METHODS: All Phase 2 and 3 studies, as well as abstract presentations from international Hepatology meetings were identified and reviewed for suitable inclusion, based on studies of new therapies in HCV. Treatment-naïve and experienced individuals, as well as cirrhotic and co-infected individuals were included. RESULTS: Sofosbuvir, simeprevir and faldaprevir, along with pegylated interferon and ribavirin, have a role in the treatment of chronic HCV infection. The precise regimens are largely dependent on the patient characteristics, patient and physician preferences, and cost implication. CONCLUSIONS: Therapies for chronic HCV have evolved dramatically in recent years. Interferon-free regimens are now possible without compromise in the rate of sustained viral response. The decision as to which regimen is most appropriate is multifactorial, and based on efficacy, safety and cost.

Opinions of general medical registrars on HIV teaching and their competence in HIV-related clinical issues.

More HIV-positive patients are living longer and presenting to non-infection specialties with non-HIV-related issues (eg diabetes, heart disease). National recommendations advise routinely offering HIV testing to all new registrants to primary care and all general medical admissions where community prevalence exceeds 2:1000. It is, therefore, imperative that all physicians are educated and competent in HIV infection, counselling and testing. This study aimed to establish regional medical registrars' opinions on teaching provision, and confidence in, HIV medicine. The results indicated a lack of confidence in HIV medicine and, in those without postgraduate rotations in HIV medicine or infectious diseases, a perception that HIV and infection-related teaching provision is inadequate.

Risk of septic arthritis in patients with rheumatoid arthritis and the effect of anti-TNF therapy: results from the British Society for Rheumatology Biologics Register.

OBJECTIVES: To evaluate the risk of septic arthritis (SA) in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. METHODS: Using data from the British Society for Rheumatology Biologics Register, a prospective observational study, the authors compared the risk of SA between 11 881 anti-TNF-treated and 3673 non-biological disease-modifying antirheumatic drug (nbDMARD)-treated patients. RESULTS: 199 patients had at least one episode of SA (anti-TNF: 179, nbDMARD: 20). Incidence rates were: anti-TNF 4.2/1000 patient years (pyrs) follow-up (95% CI 3.6 to 4.8), nbDMARD 1.8/1000 pyrs (95% CI 1.1 to 2.7). The adjusted HR for SA in the anti-TNF cohort was 2.3 (95% CI 1.2 to 4.4). The risk did not differ significantly between the three agents: adalimumab, etanercept and infliximab. The risk was highest in the early months of therapy. The patterns of reported organisms differed in the anti-TNF cohort. Prior joint replacement surgery was a risk factor for SA in all patients. The rate of postoperative joint infection (within 90 days of surgery) was 0.7%. This risk was not significantly influenced by anti-TNF therapy. CONCLUSIONS: Anti-TNF therapy use in RA is associated with a doubling in the risk of SA. Physicians and surgeons assessing the RA patient should be aware of this potentially life-threatening complication.

Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR).

BACKGROUND: The risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) is thought to be increased following anti-tumour necrosis factor (anti-TNF) therapy, with a proposed differential risk between the anti-TNF drugs etanercept (ETA), infliximab (INF) and adalimumab (ADA). OBJECTIVE: To compare directly the risk between drugs, to explore time to event, site of infection and the role of ethnicity. METHODS: Data from the British Society for Rheumatology Biologics Register (BSRBR), a national prospective observational study, were used to compare TB rates in 10 712 anti-TNF treated patients (3913 ETA, 3295 INF, 3504 ADA) and 3232 patients with active RA treated with traditional disease-modifying antirheumatic drugs. RESULTS: To April 2008, 40 cases of TB were reported, all in the anti-TNF cohort. The rate of TB was higher for the monoclonal antibodies ADA (144 events/100,000 person-years) and INF (136/100,000 person-years) than for ETA (39/100,000 person-years). After adjustment, the incidence rate ratio compared with ETA-treated patients was 3.1 (95% CI 1.0 to 9.5) for INF and 4.2 (1.4 to 12.4) for ADA. The median time to event was lowest for INF (5.5 months) compared with ETA (13.4 months) and ADA (18.5 months). 13/40 cases occurred after stopping treatment. 25/40 (62%) cases were extrapulmonary, of which 11 were disseminated. Patients of non-white ethnicity had a sixfold increased risk of TB compared with white patients treated with anti-TNF therapy. CONCLUSION: The rate of TB in patients with RA treated with anti-TNF therapy was three- to fourfold higher in patients receiving INF and ADA than in those receiving ETA.

Falciparum malaria as a cause of fever in adult travellers returning to the United Kingdom: observational study of risk by geographical area.

BACKGROUND: The probability that a returned traveller with a history of fever has malaria is likely to vary by geographical area, but this has not been quantified in travellers. AIM: To collect data on prevalence of malaria in outpatients returning with a fever or history of fever from malaria-endemic countries, at the point of presentation for a malaria test. DESIGN: Observational retrospective study. Consecutive patients presenting to an unselected 'walk-in' clinic for returned travellers. RESULTS: Of 2867 patients meeting inclusion criteria, 337 (11.8%) had malaria, 89.5% originating in sub-Saharan Africa. Of travellers returning from sub-Saharan Africa excluding South Africa with fever/history of fever, 291/1497 had malaria (19.4%, 95% CI 17-21%). A high proportion was visiting friends and relatives. In those from other areas the proportions were: 16/707 (2.3%, 95% CI 1.5-3.8) from Indian subcontinent/Southeast Asia; 2/143 (1.4%) from Southern America; 4/129 (3.1%) from South Africa; 1/44 (2.3%) from North Africa; and 8/41 (19.5%) from Oceania. Compared to other malaria-endemic regions, African travel gave an adjusted odds ratio of 7.8 (95% CI 5.4-11.2, P < 0.0001). Only 45.1% of malaria cases had a fever (> or =37.5 degrees C) at the time of presentation. Only 3% of all diagnoses of malaria had no history of fever. In 28% of cases parasite count increased in the initial 24 h of antimalarial treatment. CONCLUSION: The likelihood that a patient with fever returning from Africa has malaria is high (around 1 in 5), and is significantly lower from other areas. Absence of fever at presentation does not exclude malaria.

Prevalence and associations of vitamin D deficiency in foreign-born persons with tuberculosis in London.

OBJECTIVES: The incidence of tuberculosis (TB) is high amongst foreign-born persons resident in developed countries. Vitamin D is important in the host defence against TB in vitro and deficiency may be an acquired risk factor for this disease. We aimed to determine the incidence and associations of vitamin D deficiency in TB patients diagnosed at an infectious diseases unit in London, UK. METHODS: Case-note analysis of 210 unselected patients diagnosed with TB who had plasma vitamin D (25(OH)D3) levels routinely measured. Prevalence of 25(OH)D3 deficiency and its relationship to ethnic origin, religion, site of TB, sex, age, duration in the UK, month of 25(OH)D3 estimation and TB diagnosis were determined. RESULTS: Of 210 patients 76% were 25(OH)D3 deficient and 56% had undetectable levels. 70/82 Indian, 24/28 East African Asian, 29/34 Somali, 14/19 Pakistani and Afghani, 16/22 Sri Lankan and 2/6 other African patients were deficient (with 58, 17, 23, 9, 6 and 1 having undetectable levels, respectively). Only 0/6 white Europeans and 1/8 Chinese/South East Asians had low plasma 25(OH)D3 levels. Muslims, Hindus and Sikhs all had equivalent rates of deficiency though Hindus were more likely to have undetectable levels (odds ratio 1.87, 95% CI 1.27-2.76). There was no significant association between 25(OH)D3 level and site of TB or duration of residence in the UK. There was no apparent seasonal variation in either TB diagnosis or 25(OH)D3 level. CONCLUSIONS: 25(OH)D3 deficiency commonly associates with TB among all ethnic groups apart from white Europeans, and Chinese/South East Asians. Our data support a lack of sunlight exposure and potentially a vegetarian diet as contributors to this deficiency.

Human immunodeficiency virus type 1-related pulmonary Mycobacterium xenopi infection: a need to treat?

We report treatment decisions and outcomes for 20 patients who were infected with human immunodeficiency virus type 1 (HIV-1) and were receiving highly active antiretroviral therapy (HAART) who had respiratory symptoms and from whom Mycobacterium xenopi was isolated. All patients also had coexisting pulmonary pathologic conditions. The median blood T cell CD4 count was 37 cells/microL (range, 2-480 cells/microL). Fifteen of 20 patients received no antimycobacterial therapy and remain healthy after a median of approximately 4 years of follow-up, and 2 patients required treatment specifically for M. xenopi infection, both showing clinical improvement. We conclude that pulmonary M. xenopi isolation in HIV-1 patients receiving HAART does not usually require specific treatment.

M. tuberculosis: immunology and vaccination.

Tuberculosis is increasing. Current treatment regimens require at least 6 months, because latent or stationary phase organisms are difficult to kill. Such regimens do not achieve full compliance, and "directly observed therapy short course" (DOTS) is having less impact than expected. This worrying situation is aggravated by coinfection with human immunodeficiency virus (HIV), and by the increase in drug-resistant strains. We need new insights that lead to more rapid therapies and immunotherapies, and more reliable vaccines. Recent insights have come from: understanding of the relationship between Mycobacterium tuberculosis and macrophages; the multiple T cell types that recognise mycobacterial peptides, lipids and glycolipids; the critical role of interferon-gamma (IFNgamma) and interleukin-12 (IL-12) in human mycobacterial infection revealed by genetically defective children; quantitation of the presence and importance of Th2 lymphocyte activation in human tuberculosis; the role of local conversion of inactive cortisone to active cortisol in the lesions; the recognition that some effective prophylactic vaccines also work as immumotherapeutics whereas others do not. In the longer term the recent sequencing of the M. tuberculosis genome will lead to further advances. In the short term, effective immunotherapy remains the most accessible breakthrough in the management of tuberculosis. The types of practical advance that will result from sequencing the genome are discussed speculatively, but cannot yet be predicted with certainty.

A study of maternal mortality at the University Teaching Hospital, Lusaka, Zambia: the emergence of tuberculosis as a major non-obstetric cause of maternal death.

SETTING: The Department of Obstetrics and Gynaecology, University Teaching Hospital, Lusaka, Zambia. OBJECTIVES: To ascertain 1) the non-obstetric causes of maternal mortality, 2) the importance of tuberculosis as a cause of maternal deaths, and 3) the trends in the aetiology of non-obstetric causes of maternal deaths during the past decade in the light of the human immunodeficiency virus epidemic. DESIGN: A 2-year retrospective study of the aetiology of all maternal deaths occurring at the University Teaching Hospital (UTH), Lusaka, Zambia between 1 January 1996 and 31 December 1997. Comparison of these data with available data published between 1974 and 1989. RESULTS: There were 251 maternal deaths recorded during the study period. Of these, 106 (42%) were due to direct (obstetric) causes and 145 (58%) were due to indirect (non-obstetric) causes. Malaria (30%), tuberculosis (25%) and unspecified chronic respiratory tract infections (22%) accounted for 77% of non-obstetric causes of maternal deaths and 44% of all causes of maternal deaths. The diagnosis of AIDS was closely linked with that of tuberculosis (92% of cases), and unspecified chronic respiratory illnesses (97%), but not with malaria (37%). The maternal mortality ratio for UTH was calculated at 921 per 100,000 live births, a significant increase from the 118 noted in 1982 and 667 in 1989. CONCLUSIONS: Despite improved obstetric services, the maternal mortality ratios at UTH, Lusaka, have increased eight-fold over the past two decades. This dramatic increase is mainly due to non-obstetric causes of death. Malaria and AIDS-associated tuberculosis and unspecified 'chronic respiratory illnesses' are now major causes of maternal death in Zambia. Greater emphasis is urgently required on early detection, accurate diagnosis, treatment and prevention of malaria and tuberculosis in pregnancy. Further definition of chronic 'unspecified' respiratory illnesses is also required.

HIV-1 seroprevalence in Zambian patients with acute diarrhea: a community-based study.

The seroprevalence of HIV-1 in sub-Saharan African patients with diarrhea in the community remains largely unknown. We present the findings of a 2-month study that we undertook to ascertain the seroprevalence of HIV-1 in Zambian patients presenting with acute diarrhea in a community-based health center. A total of 256 patients with diarrhea and 140 apparently healthy controls was seen. Of the patients with diarrhea, 161 were < 16 years old and 95 were adults. Most children with diarrhea were < 6 years old (147 of 161; 91%). Overall, 81 of 256 (32%) patients with diarrhea were HIV-1-seropositive. When results from children < 18 months old and possibly having maternal anti-HIV-1 antibodies were excluded, 64 of 172 (37%) patients with diarrhea were HIV-seropositive. Rates of HIV-1 seropositivity for patients with diarrhea were significantly higher than were rates for diarrhea-free controls (p < .001 for both the total population; odds ratio [OR], 95% confidence interval [CI], 1.42 < 2.48 < 4.35) and population > 18 months old (OR, 95% CI, 1.54 < 2.90 < 5.49). Among children between 18 months and 5 years old, 14 of 63 (22%) were HIV-1-seropositive compared with 8 of 62 (13%) without diarrhea (p > .05, not significant). Moreover, 49 of 95 (52%) adults with acute diarrhea were HIV-1-seropositive compared with 10 of 44 (23%) healthy adult controls (p < .003; OR, 95% CI, 1.51 < 3.62 < 8.87). No significant differences were found in HIV-1 seroprevalence rates between males and females in all age groups. These data show a close association between acute diarrhea and HIV seropositivity in Zambian adults in the community.

PIP: Chronic diarrhea is a common clinical presentation of HIV infection worldwide and a major cause of mortality in cohorts of HIV-infected African children. Findings are presented from a study of HIV-1 seroprevalence among Zambian patients presenting to George Health Center, a community-based health center northwest of center Lusaka, with acute diarrhea during March-April 1994. 256 patients with diarrhea and 140 apparently healthy controls participated in the study. Of the patients with diarrhea, 161 were under 16 years old and 95 were adults. 147 (91%) of the children with diarrhea were under age 6 years. Overall, 81 of the 256 (32%) patients with diarrhea were HIV-1-seropositive. Excluding results from infants under age 18 months who may have had maternal anti-HIV-1 antibodies, 64 of 172 (37%) patients with diarrhea were HIV-seropositive. Among children aged 18 months to 5 years, 14 of 63 (22%) were HIV-1-seropositive compared with 8 of 62 (13%) without diarrhea. 49 of 95 adults with acute diarrhea were HIV-1-seropositive compared with 10 of 44 healthy adult controls. No significant differences were found in HIV-1 seroprevalence rates between males and females in all age groups. These data point to a close association between acute diarrhea and HIV seropositivity in this research setting.