Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cryptococcal Study Group.

A prospective population-based study was conducted in Australia and New Zealand during 1994-1997 to elucidate the epidemiology of cryptococcosis due to Cryptococcus neoformans var. neoformans (CNVN) and C. neoformans var. gattii (CNVG) and to relate clinical manifestations to host immune status and cryptococcal variety. The mean annual incidence per 10(6) population was 6.6 in Australia and 2.2 in New Zealand. Of 312 episodes, CNVN caused 265 (85%; 98% of the episodes in immunocompromised hosts) and CNVG caused 47 (15%; 44% of the episodes in immunocompetent hosts). The incidence of AIDS-associated cases in Australia declined annually (P<.001). Aborigines in rural or semirural locations (P<.001) and immunocompetent males (P<.001) were at increased risk of CNVG infection. Cryptococcomas in lung or brain were more common in immunocompetent hosts (P< or =.03) in whom there was an association only between lung cryptococcomas and CNVG. An AIDS-associated genetic profile of CNVN serotype A was confirmed by random amplification of polymorphic DNA analysis. Resistance to antifungal drugs was uncommon. The epidemiology of CNVN infection has changed substantially. Clinical manifestations of disease are influenced more strongly by host immune status than by cryptococcal variety.

Alatrofloxacin-induced seizures during slow intravenous infusion.

OBJECTIVE: To report a case of seizures associated with slow infusion (1-2 h) of alatrofloxacin, the prodrug of trovafloxacin. CASE SUMMARY: A 37-year-old Asian man was admitted to the hospital for a distal pancreatectomy and drainage of a pseudocyst. Postoperative complications developed, which included peritonitis and pneumonia, requiring intensive care admission. Cultures from peritoneal drainage fluid and sputum isolated Klebsiella pneumoniae and Pseudomonas aeruginosa, respectively. He was treated with multiple courses of antibiotics, including intravenous gentamicin, metronidazole, vancomycin, meropenem, and ceftazidime. After three weeks, the patient still had sepsis and began therapy with alatrofloxacin in addition to ceftazidime and vancomycin. Alatrofloxacin infusion was administered according to product information instructions. Fifteen minutes after the first dose was started, the patient developed generalized clonus. On rechallenge, infusing at half the initial rate, the seizure recurred; consequently, the infusion was discontinued and replaced with intravenous ciprofloxacin and metronidazole. The patient remained seizure free thereafter. DISCUSSION: Fluoroquinolones have been implicated in central nervous system adverse effects, including seizures, which have been reported with other fluoroquinolones but not with alatrofloxacin or trovafloxacin. In these reports, the patients often had preexisting risk factors such as increased age and electrolyte imbalances. The only apparent predisposition in this patient was mild hyponatremia. CONCLUSIONS: Alatrofloxacin may cause seizures even during slow infusion. This case highlights the need for caution when commencing parenteral fluoroquinolone therapy, particularly with a new agent.

Tuberculosis infection and homelessness in Melbourne, Australia, 1995-1996.

OBJECTIVE: To describe tuberculosis infection among persons experiencing homelessness in inner Melbourne, Australia. DESIGN: Homeless people were surveyed during late 1995 and early 1996. In stage one of the study 284 homeless people from crisis and long-term accommodation sites were recruited by means of stratified, systematic, random sampling. In stage two a convenience sample of 100 homeless people from squats and the streets were recruited. Participants completed a questionnaire and Mantoux testing was performed. RESULTS: A past history of tuberculosis was reported by 3%. Thirty-seven per cent had a Mantoux > or =10 mm; 21% > or =15 mm; and 11% > or =20 mm. A Mantoux > or =15 mm was independently associated with being aged > or =40 years, coming from the accommodated sample, overseas birth, and a past history of tuberculosis. Using logistic regression modelling, a Mantoux > or =15 mm was predicted by being aged > or =40 years, overseas birth, and past history of tuberculosis. CONCLUSION: Mantoux test results suggest that this group of homeless people had a high prevalence of infection with the tubercle bacillus. Many aspects of the physical and social circumstances of homeless people predispose to reactivation and have the potential to enhance rapid spread should latent infection become active disease.

Serum antibody response to Cryptococcus neoformans in cats, dogs and koalas with and without active infection.

Anti-cryptococcal antibodies were measured in normal cats, dogs, horses and koalas, and cats, dogs and koalas with cryptococcosis using an enzyme immunoassay. Antibody levels were expressed as absorbance readings. Over 80% of cats and dogs with cryptococcal infection had elevated antibody levels at the time of diagnosis, during or after successful therapy. Antibody levels in these patients either remained elevated or declined slowly after treatment. For cats, anti-cryptococcal antibody levels were higher in C. neoformans var. gattii than var. neoformans infections, and lower in mild than in moderate or severe infections. The persistence of increased anti-cryptococcal antibody levels in over half of the feline and canine cases following active infection suggested the use of antibody determinations as a seroepidemiologic marker of previous infection. Consequently, antibody measurements from 'normal' animals indicated a prevalence of previous cryptococcal infection of 10% in cats and dogs, compared with 3% in horses and 5% in koalas. Preliminary studies of young animals suggested that anti-cryptococcal antibody levels were substantially lower in the young cats but not the young dogs surveyed, compared with their mature counterparts. The cut-offs used in the present work may thus be erroneously high, with a corresponding underestimation of the prevalence of inapparent cryptococcosis.

Fatal disseminated infection by Scedosporium prolificans during induction therapy for acute leukemia: a case report and literature review.

We report a case of fatal disseminated fungal infection by Scedosporium prolificans which occurred in a patient with acute leukemia during induction chemotherapy. Rapid clinical deterioration despite high-dose empirical amphotericin B highlights both the pathogenicity of this fungus in immunocompromised hosts and its resistance to standard antifungal therapy.

A methodology for sampling and accessing homeless individuals in Melbourne, 1995-96.

A methodology for sampling homeless populations in inner Melbourne was developed to study their health status and prevalence of tuberculosis. This paper describes the design, development and implementation of the project. The results of health status and tuberculosis analysis are published elsewhere. Involvement and interaction with local service providers and agencies to homeless people was central to the project throughout. A definitional construct of homelessness was developed, drawn from local and overseas literature and contemporary local experience. The study's aim was to obtain a representative sample of homeless individuals in various levels of accommodation and a convenience sample of those who were unaccommodated (streets and parks). A comprehensive sampling frame of accommodation options was constructed from available databases, and systematic sampling applied to produce a sample of 396 beds, from which 284 participants were enrolled. Convenience sampling of unaccommodated homeless individuals produced 100 participants. All agreed to undergo a comprehensive questionnaire, blood and Mantoux testing, the latter being completed successfully in 94%. Commonsense, cultural sensitivity and a non-threatening approach were critical to the success of the project and the security of the field workers. The methods described attempt to address recognised difficulties of sampling from homeless populations and should be reproducible both in the future and elsewhere. Potential for selection bias remains the main threat to validity, which the described methodology combined with adequate resources should help to address.

Health indicators and risks among people experiencing homelessness in Melbourne, 1995-1996.

During the study's first stage, 284 homeless people from crisis and long-term accommodation sites were surveyed using stratified, systematic sampling. The second stage involved a survey of a convenience sample of 100 homeless people from squats and the streets. Participants completed a questionnaire, Mantoux testing was performed and blood taken for gamma-interferon assay, liver and renal function tests. The group's health status was poor, with 72% experiencing medical conditions in the preceding two years and 77% symptoms in the month prior to interview. Bronchitis, asthma and gastroenteritis were the most commonly reported conditions; productive and persistent coughing, shortness of breath and wheezing the commonest symptoms. Twenty-one per cent had Mantoux reactions 15 mm or greater, 28% a raised GGT and 19% a raised ALT. Seventy-seven per cent smoked, 74% were current drinkers, 28% had injected drugs at some time in their lives and 14% were regularly injecting drugs. Forty-four per cent had experienced mental illness, 49% of whom reported depression and 15% schizophrenia. Homeless people in Melbourne have poor health status and engage in behaviours that place their health at risk. The high number of respiratory and gastro-intestinal complaints, the high level of cigarette smoking and injecting drug use (IDU) and the proportion likely to be infected with Mycobacterium tuberculosis (MTb) are all issues with important health consequences. Participants recruited from the street had significantly poorer health and engaged in more risk behaviours than those from accommodation sites; those from the accommodated sample were more likely to be infected with Mtb.

Serological evidence for infection with Campylobacter jejuni/coli in patients with multifocal motor neuropathy.

Campylobacter jejuni/coli (CJC) infection has been implicated in the immunopathogenesis of Guillain-Barré syndrome (GBS), acute motor axonal neuropathy (AMAN), and Miller Fisher syndrome (MFS). However, its role in chronic immune mediated neuropathies such as multifocal motor neuropathy (MMN) or chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is less clear. Anti-ganglioside antibodies are associated with chronic motor neuropathies such as MMN and IgM anti-GM1, and IgM anti-asialo GM1 antibodies have been shown to cross-react with CJC lipopolysaccharides. Molecular mimicry between CJC and IgG anti-GM1 antibodies has also been suggested. Therefore we have performed a retrospective assessment of anti-CJC-specific IgG, IgM, and IgA antibodies in a cohort of seven patients with clinical and electrophysiologically definite MMN. The control group consisted of 140 healthy blood donors with no history of enteric illnesses. We found elevated titres of anti-CJC-specific IgG in 5 of 7 patients, IgM in 3 of 7 and IgA in 1 of 7. At least 1 anti-CJC antibody was elevated in 6 of 7 patients, and 3 patients had elevations of both IgG and IgM antibodies. Three patients had significantly elevated titres of anti-ganglioside antibodies without a clear relationship to the anti-CJC titres. Therefore antibodies specific for CJC were found more frequently than expected in patients with MMN. Prior or ongoing infection with CJC may play a role in the actiopathogenesis of MMN.

Time to initiation of anti-tuberculosis treatment.

SETTING: Fairfield Hospital, Victoria, Australia. OBJECTIVE: To examine delay in initiation of treatment for tuberculosis (TB). DESIGN: Delay in the initiation of treatment for 142 notified TB patients was examined by a retrospective record review. Particular attention was given to the periods between (1) onset of symptoms and initiation of treatment, and (2) determination of sputum positivity and initiation of treatment. An expert panel nominated 30 days and 3 days as 'acceptable' periods for (1) and (2), respectively. RESULTS: Only 31% of patients commenced treatment within 30 days of onset of symptoms. This was so for both sputum smear-positive and negative cases, and was not significantly related to the site of infection, referral source, age, gender or ethnicity of the patient. Of patients with smear-positive pulmonary TB, 86% received treatment within 3 days of this result being demonstrated. Those with a delay of greater than 3 days were all investigated by private doctors through private laboratories. CONCLUSION: There are appreciable delays in initiation of treatment for TB. Measures to combat these unacceptable delays are discussed.

Serum antibody response to active infection with Cryptococcus neoformans and its varieties in immunocompetent subjects.

Using a class-specific enzyme immunoassay IgG and IgA anticryptococcal antibody was measured in 400 serum specimens at 1 week to 11.7 years after diagnosis from 43 immunocompetent subjects with confirmed active cryptococcosis. The prevalence of IgG was 86% at diagnosis, rose to 100% by 2 weeks and remained high thereafter. IgA prevalence was 71% at diagnosis, rose to 75% at 2 weeks and then fell over 2 years. IgG and IgA prevalence in paediatric controls was 5% and 0%, respectively. Mean antibody levels showed the same pattern and neither levels nor prevalence were influenced by age, sex or site of infection. Patients with the variety gattii infection had a greater antibody response than those with the variety neoformans which was significant for IgA. Specific anticryptococcal antibody was regularly present in conjunction with cryptococcal antigen at diagnosis. IgG persists but IgA falls over 1-2 years. The assay described may be a useful tool to study the antibody response and seroepidemiology of infection with C. neoformans.

Clinical management of fungal infections.

Fungal infections require clinical and microbiological diagnosis for optimal therapy. Superficial mycoses often respond to topical agents but newer, less toxic drugs are available for systemic treatment when required. For invasive mycoses, amphotericin B remains the gold standard, with triozoles as the preferred oral agents.

A review of antifungal agents.

A vigorous approach to the management of fungal related diseases has been precipitated by a number of issues; HIV/AIDS being one of the most prominent. In line with this there have been a number of new developments that all practitioners should know about. This article reviews the appropriate use of all agents currently available for antifungal treatments. The second part of this article (appearing in the June issue) will look at the clinical applications of these treatment options.

Viral haemorrhagic fevers: current status, future threats.

In developing countries, the major outbreaks of viral haemorrhagic fevers such as Marburg, Ebola and Lassa fever viruses have been nosocomially spread. The high mortality and absence of specific treatment have had a devastating effect. Epidemics of this highly contagious disease remain a constant threat to Australia and, as a result, carefully planned laboratory and public health strategies and clinical infection control measures have been instituted for the management of suspected cases.

Clinical and host differences between infections with the two varieties of Cryptococcus neoformans.

A population-based register of cases of cryptococcosis in patients treated in Victoria, Australia, over a 10-year period was established for studying the epidemiologic and clinical features of infection with Cryptococcus neoformans and its two varieties, gattii and neoformans. One hundred thirty-three cases of cryptococcosis were entered on the register; the incidence was 3.0 cases per 1 million population per year, a rate that increased to 5.0 cases per 1 million population per year over the decade as a result of the AIDS epidemic. There was a distinct association between immune status and C. neoformans variety: all C. neoformans variety gattii infections occurred in healthy hosts and 90% of C. neoformans variety neoformans infections occurred in immunosuppressed hosts. Meningitis was the commonest manifestation, with focal CNS and pulmonary lesions occurring primarily in healthy hosts with C. neoformans variety gattii infection; isolation of C. neoformans from blood and urine was associated with immunosuppression and C. neoformans variety neoformans infection. The mortality among patients with C. neoformans variety neoformans infection was high, while none of those patients with C. neoformans variety gattii died but often had neurological sequelae that required surgery and prolonged therapy. These findings appear to be related to variety-specific interactions between host and parasite and warrant further epidemiologic and immunologic study.