BackgroundTo determine if infectious disease events in HIV-infected patients treated with highly active antiretroviral therapy (HAART) are a consequence of the restoration of pathogen-speci®c immune responses, a single-centre retrospective study of all HIV-infected patients commencing HAART prior to 1 July 1997 was undertaken to determine the incidence, characteristics and time of onset of disease episodes in HAART responders (decrease in plasma HIV RNA of > 1 log 10 copies/mL). MethodsBaseline and post-therapy changes in CD4 T-cell counts and HIV RNA were compared in patients with and without disease and delayed-type hypersensitivity responses to mycobacterial antigens were measured in selected patients. ResultsThirty-three of 132 HAART responders (25%) exhibited one or more disease episodes after HAART, related to a pre-existent or subclinical infection by an opportunistic pathogen. Disease episodes were most often related to infections by mycobacteria or herpesviruses but hepatitis C virus (HCV), molluscum contagiosum virus and human papilloma virus were also implicated. They were most common in patients with a baseline CD4 T-cell count of < 50/uL and occurred most often during the ®rst 2 months of therapy and when CD4 T-cell counts were increasing. Mycobacteria-and HCV-related diseases were associated with restoration of pathogen-speci®c immune responses. ConclusionsWe conclude that improved immune function in immunode®cient patients treated with HAART may restore pathogen-speci®c immune responses and cause in¯ammation in tissues infected by those pathogens. Key words: HAART, HIV, immune restorationReceived: 4 June 1999, accepted 13 September 1999 IntroductionWhile the immediate aim of using antiretroviral therapy is suppression of HIV replication, the ultimate aim is restoration or maintenance of protective HIV-speci®c and pathogen-speci®c immune responses. Treatment of immunode®cient patients with highly active antiretroviral therapy (HAART) appears to restore pathogen-speci®c immune responses resulting in prevention or regression of diseases caused by opportunistic pathogens [1]. However, in some patients suppression of HIV replication by antiretroviral therapy and the resultant increase in blood CD4 T-cells is associated with in¯ammation in tissues infected by those pathogens. Thus, disease related to subclinical or pre-existent infections by Mycobacterium avium complex (MAC) [2±4], M. tuberculosis (MTB) [5,6], Bacille Calmette±Guerin (BCG) [7], cytomegalovirus (CMV) [8±10], hepatitis B virus (HBV) [11,12], hepatitis C virus (HCV) [13] immunological response to HAART. Many of these disease episodes were associated with the presence of a pathogenspeci®c immune response and/or more exaggerated inammatory response than is usually present in patients with opportunistic infections. It has therefore been argued that the disease results from the effects of a restored immune response against the pathogen [2±7,10,11,13,14]. However, Michelet et al. have argued that`opportunistic infections' in patients treated...

Hepatitis in HCV-HIV-coinfected patients following treatment with potent antiretroviral therapy may reflect restoration of anti-HCV immune responses rather than increased HCV replication or a hepatotoxic effect of antiretroviral therapy.

Barmah Forest virus (BFV) and Ross River virus (RRV) are mosquito-borne viruses with similar vectors and environmental requirements. They cause diseases characterised by arthralgia, arthritis and myalgia, often accompanied by fever and rash. Arthritis is more common and more prominent in RRV disease and rash is more common and florid with BFV infection, although the diseases cannot be reliably distinguished by their clinical symptoms. Diagnosis is based on serological tests and a definite diagnosis of recent infection requires the demonstration of rising titres of IgG. Arthralgia, myalgia and lethargy may continue for at least six months in up to half of patients with RRV, but in only about 10% of patients with BFV. Both diseases are managed symptomatically. (MJA 1998; 169: 159-163)

Objective:To demonstrate that nosocomial transmission of vancomycin-resistant enterococci (VRE) can be terminated and endemicity prevented despite widespread dissemination of an epidemic strain in a large tertiary-care referral hospital.Interventions:Two months after the index case was detected in the intensive care unit, 68 patients became either infected or colonized with an epidemic strain of vanB vancomycin-resistantEnterococcus faeciumdespite standard infection control procedures. The following additional interventions were then introduced to control the outbreak: (1) formation of a VRE executive group; (2) rapid laboratory identification (30 to 48 hours) using culture and polymerase chain reaction detection ofvanA andvanBresistance genes; (3) mass screening of all hospitalized patients with isolation of carriers and cohorting of contacts; (4) environmental screening and increased cleaning; (5) electronic flagging of medical records of contacts; and (6) antibiotic restrictions (third-generation cephalosporins and vancomycin).Results:A total of 19,658 patient and 24,396 environmental swabs were processed between July and December 2001. One hundred sixty-nine patients in 23 wards were colonized with a single strain of vanB vancomycin-resistantE. faecium.Introducing additional control measures rapidly brought the outbreak under control. Hospital-wide screening found 39 previously unidentified colonized patients, with only 7 more nonsegregat-ed patients being detected in the next 2 months. The outbreak was terminated within 3 months at a cost of $2.7 million (Australian dollars).Conclusion:Despite widespread dissemination of VRE in a large acute care facility, eradication was achievable by a well-resourced, coordinated, multifaceted approach and was in accordance with good clinical governance.

A real-time PCR assay previously developed for use on the Roche LightCycler platform was investigated as an alternative to culture for the direct detection of vancomycin-resistant enterococci (VRE) in clinical specimens. PCR primers and fluorescence resonance energy transfer hybridization probes specific for the vanA and vanB genes were combined in a multiplex real-time PCR assay performed directly with fecal material obtained by rectal swabbing and with enrichment broth samples. DNA was prepared from the rectal swabs and enrichment broths with a commercially available DNA preparation column designed specifically for use with fecal specimens. One hundred eighty duplicate rectal swabs were obtained from 42 patients who were previously found to be positive for VRE and who were being monitored for carriage of VRE. Direct and enrichment broth cultures were performed with one swab, while PCR was performed with the other swab as well as any corresponding presumptive positive enrichment broth. In total, 100 specimens from 30 patients remained positive for VRE by at least one method. The multiplex real-time PCR was positive for 88 enrichment broths of rectal swabs from 27 patients but for only 45 rectal swabs from 15 patients. Direct culture was positive for VRE for only 43 specimens from 11 patients, while enrichment broth culture was positive for VRE for 75 specimens from 22 patients. Inhibition studies for the multiplex real-time PCR assay, performed by spiking the DNA extracts from 50 negative rectal swabs and the corresponding enrichment broths with between 1 and 10 CFU of a VanB Enterococcus faecium strain, detected inhibition rates of 55.1 and 10%, respectively. PCR performed directly with enrichment broths was found to be significantly more sensitive than enrichment broth culture (P < 0.025). Negative samples were identified significantly earlier by PCR than by culture alone.