Anthony Allworth

Fatal encephalitis due to novel paramyxovirus transmitted from horses

BACKGROUND In September, 1994, an outbreak of severe respiratory disease affected 18 horses, their trainer, and a stablehand in Queensland, Australia. Fourteen horses and one human being died. A novel virus was isolated from those affected and named equine morbillivirus (EMV). We report a case of encephalitis caused by this virus. FINDINGS A 35-year-old man from Queensland had a brief aseptic meningitic illness in August, 1994, shortly after caring for two horses that died from EMV infection and then assisting at their necropsies. He then suffered severe encephalitis 13 months later, characterised by uncontrolled focal and generalised epileptic activity. Rising titres of neutralising antibodies to EMV in the patients serum at the time of the second illness suggested an anamnestic response. Distinctive cortical changes were shown on magnetic resonance neuroimaging and histopathological examination of the brain at necropsy. Immunohistochemistry and electronmicroscopy of brain tissue revealed pathology characteristic of the earlier cases of EMV infection. PCR on cerebrospinal fluid taken during the second illness, brain tissue, and serum retained from the original illness resulted in an amplified product identical to that previously described from EMV. INTERPRETATION The results of serology, PCR, electronmicroscopy, and immunohistochemistry strongly suggest that EMV was the cause of this patients encephalitis, and that exposure to the virus occurred 3 months before the fatal illness.

HIV combination therapy: partial immune restitution unmasking latent cryptococcal infection

Objective:To describe two cases of cryptococcal meningitis and one re-exacerbation of Cryptococcus-associated meningitis occurring in temporal association with commencement of highly active antiretroviral therapy (HAART) in patients with advanced HIV infection (CD4 cells < 50 × 106/l), which suggests that partial immune restitution can facilitate development of clinically apparent meningitis in response to Cryptococcus or its antigen. Design:All HIV-infected patients with culture-proven cryptococcal meningitis diagnosed at a tertiary referral centre specialist infectious diseases unit from 1 January 1996 to 31 December 1996 were reviewed to examine the clinical and immunological parameters prior to and after commencing antiretroviral therapy. Results:Three patients were diagnosed with clinically apparent meningitis within 7–39 days of changing or altering antiretroviral combination therapy consisting of zidovudine or stavudine, in combination with lamivudine and saquinavir. All patients had CD4 cell counts below 50 × 106/l at initiation of therapy. Following institution of HAART, evidence of immune restitution was suggested by the following: (i) significant increases (3.7–14-fold) in numbers of CD4 cells (all three patients), (ii) significantly reduced (> 2–4 log10 reduction) HIV viral loads (two out of three patients), and (iii) prominent inflammatory changes in cerebrospinal fluid (white blood cells > 10 × 106/l) at diagnosis (two out of three patients). Conclusions:Our report suggests that in patients with advanced HIV infection, partial immune restitution induced by HAART can precipitate onset of clinically apparent meningitis in those patients with latent cryptococcal central nervous system infection or with residual cryptococcal antigen present in the cerebrospinal fluid.

Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant

Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.

Ethanol lock therapy to treat tunnelled central venous catheter-associated blood stream infections: Results from a prospective trial

In order to assess the efficacy of 70% ethanol locks in addition to antibiotic therapy to treat tunnelled central venous catheter-associated bloodstream infections, a pilot study of 19 patients was performed prospectively using ethanol locks for 5 d in addition to antibiotic therapy to treat tunnelled central venous catheter-associated bacteraemia. 12 patients had mono-microbial infections and 7 had polymicrobial isolates. 17 of 19 patients completed ethanol lock therapy. 15 of 17 patients completing ethanol lock therapy had no recurrence of the original organism and retained their catheter for a median of 36 and an average of 47 d following initiation of ethanol lock therapy. These results demonstrate the safety and potential efficacy of this technique against a broad range of potentially virulent organisms. The intervention was acceptable to both staff and patients with no significant side-effects. These preliminary results from our prospective pilot study suggest that ethanol lock therapy is safe and easily integrated into clinical practice, and may have utility in treating central venous catheter-associated infections, avoiding removal of catheters in patients requiring long-term venous access.

Successful treatment of post-influenza pseudomembranous necrotising bronchial aspergillosis with liposomal amphotericin, inhaled amphotericin B, gamma interferon and GM-CSF

A case of aspergillus tracheobronchitis following influenza A infection in an immunocompetent 35 year old woman is described that required prolonged mechanical ventilation for airways obstruction. Treatment included liposomal amphotericin, inhaled amphotericin, gamma interferon and GM-CSF. Liposomal amphotericin therapy was associated with reversible hepatosplenomegaly. Inhaled corticosteroids with continued antifungal therapy were used for the management of severe recurrent airway obstruction. After a prolonged course of treatment she survived with fixed airways obstruction unresponsive to corticosteroids.

Histoplasmosis in Australia: Report of 16 Cases and Literature Review

We describe 16 previously unreported patients with histoplasmosis from Queensland and northern New South Wales, Australia, and review all previous Australian reports, providing 63 cases in total to study (17 cases of acute pulmonary histoplasmosis, 2 cases of chronic pulmonary disease, and 44 cases of systemic disease, including 17 cases of single-organ infection and 27 instances of disseminated disease). All acute pulmonary disease was acquired in Australia, with 52% of systemic disease definitely autochthonous. Most cases of single-organ disease occurred in immunocompetent patients (76%), and were oropharyngeal (53%) in location. Forty-one percent of disseminated disease occurred in patients with human immunodeficiency virus (HIV). Patients with HIV had high rates of systemic symptoms, pancytopenia, fungemia, and hepatosplenomegaly. Oropharyngeal and adrenal involvement as well as systemic symptoms were prominent in immunocompetent patients with disseminated disease, with 6 of 7 cases of adrenal involvement leading to Addison disease. Most systemic disease was diagnosed by culture of Histoplasma capsulatum. Where serology was assessed in cases other than acute pulmonary disease, it was positive in only 32%. Prognosis for patients with single-organ disease was excellent. Disseminated disease was associated with recurrence in 30% and death in 37%. The results of this study confirm several previously known patterns of disease but also provide new insights into this rare but endemic condition in Australia. Abbreviation: HIV = human immunodeficiency virus.

Three Cases of Q Fever Osteomyelitis in Children and a Review of the Literature

Q fever is a common zoonosis worldwide. Awareness of the disease and newer diagnostic modalities have resulted in increasing recognition of unusual manifestations. We report 3 cases of Q fever osteomyelitis in children and review the literature on 11 other reported cases. The cases demonstrate that Coxiella burnetii can cause granulomatous osteomyelitis that presents without systemic symptoms and frequently results in a chronic, relapsing, multifocal clinical course. Optimal selection and duration of antimicrobial therapy and methods of monitoring therapy are currently uncertain.

gamma delta T cells: Their immunobiology and role in malaria infections

The status of research on gamma delta T cells is reviewed. Recent research shows that gamma delta T cells may see antigens in an immunoglobulin-like manner and that non-peptidic substance can be antigens for these cells. Considerable advances have been made in defining the immunobiology of gamma delta T cells, with evidence for sentinel, protective and immunoregulatory roles. Research on gamma delta T cells in malaria infections suggests that gamma delta T cells are mediators of protective immunity, most probably through the production of Th1 cytokines such as TNF alpha, TNF delta and IFN gamma and that excessive production of such cytokines may contribute to pathology. Our data on the features of the peripheral blood gamma delta T cells response in humans infected with Plasmodium falciparum show that there is considerable variation between individuals in the relative expansion of gamma delta T lymphocytes following primary or secondary infection. They confirm that activation of gamma delta T cells occurs during P. falciparum infection and that activated cells can persist for many weeks after treatment. The possibility that gamma delta T cells have an immunoregulatory function in malaria infections is proposed.

Control of an Outbreak of Carbapenem- Resistant Acinetobacter baumannii in Australia after Introduction of Environmental Cleaning with a Commercial Oxidizing Disinfectant

In the midst of an outbreak, carbapenem-resistant Acinetobacter baumannii was grown from samples of multiple environmental sites in an intensive care unit. A commercial oxidizing disinfectant (potassium peroxomonosulphate 50%, sodium alkyl benzene sulphonate 15%, and sulphamic acid 5%) was introduced throughout the intensive care unit, and its use coincided with cessation of the outbreak.

Human trichostrongyliasis in Queensland

&NA; Trichostrongylus infection, an uncommonly reported zoonosis in Australia, is common in parts of the world where there is close human contact with herbivorous animals. We report 5 cases diagnosed in our laboratory since 1992. Over this period the laboratory has conducted over 46,000 parasitological examinations on feces. All 5 cases were investigated for fecal parasites following detection of a blood eosinophilia. Two of the 5 cases complained of mild abdominal discomfort and diarrhea. It is likely that all obtained their infection following ingestion of contaminated unwashed vegetables which had been fertilized with animal manure. Four of the cases acquired their infection in Queensland and the fifth may have become infected in rural Victoria. All were treated with pyrantel embonate with resolution of the eosinophilia. Follow up fecal specimens showed no parasites. Patients were instructed on the mode of transmission and advised to thoroughly wash any uncooked vegetables prior to ingestion. In our cases, goats and horses were possibly implicated. No published reports of Trichostrongylus spp. in humans in Australia have occurred since the 1930s and it may be more common in Australia than is recognized. The infection may be missed because patients are asymptomatic or have mild gastrointestinal symptoms or only a blood eosinophilia. Trichostronglyus eggs may also be mistaken for hookworm eggs. It is important therefore to distinguish these infections from hookworm infection as the modes of transmission, management and advice regarding prevention differ.