Seroprevalence of Burkholderia pseudomallei in East Timorese refugees: implications for healthcare in East Timor.

Melioidosis is a disease with protean clinical manifestations caused by the bacterium Burkholderia pseudomallei. It is endemic in countries surrounding the newly independent East Timor, but has yet to be isolated or demonstrated serologically in that country. One illness that can be clinically indistinguishable from melioidosis is pulmonary tuberculosis, a condition with a very high prevalence in East Timor. We used an indirect hemagglutination test (IHA) to measure antibodies to B. pseudomallei in 407 East Timorese evacuated to Darwin, Australia, in September 1999. Assuming a positive IHA titer as > or = 1:40, the overall seroprevalence rate was 17.0%, in keeping with other seroprevalence studies from the region. The IHA titres ranged up to 1:320. After adjusting for age, females were 2.5 times more likely to be seropositive than males (p = 0.0001). There was an inverse relationship between seropositivity and age. This study shows that exposure to B. pseudomallei occurs in East Timor melioidosis is also likely to occur. Due to the lack of laboratory facilities at present, it may be some time before a laboratory-confirmed case proves that melioidosis occurs. In the meantime, clinicians in East Timor should include melioidosis in the differential diagnosis of the many conditions that it may mimic.

Immune responses of a liposome/ISCOM vaccine adjuvant against streptococcal fibronectin binding protein 1 (Sfb1) in mice.

BACKGROUND & OBJECTIVES: The fibronectin binding protein Sfb1 of Streptococcus pyogenes is a well characterised antigen which induces protection against lethal challenge with group A streptococcus (GAS) when adjuvanted with cholera toxin B-subunit (CTB). As an alternative to CTB adjuvanted intranasal immunisations we investigated the immune responses generated in mice using Sfb1 incorporated in to the skin and mucosal adjuvant SAMA4. METHODS: Mice (BALB/c) were vaccinated intradermally with 100 microl of either SAMA4 (adjuvant only group) or SAMA4/Sfb1 and were boosted 7 days later. Mice vaccinated with CTB based vaccines were immunised by intranasal inoculation with a mixture containing 30 microg Sfb1 and 10 microg CTB on days 1, 3, 5 and 15. At 14 days after the last booster immunisation the immune response was characterised and mice were challenged with 10(8) CFU of S. pyogenes. RESULTS: Mice vaccinated with SAMA4/Sfb1 elicited a Sfb1-specific IgG response in the sera that was significantly higher than that seen in control mice and mice immunised with the adjuvant only (P<0.05). No significant differences were seen for specific IgA antibodies in the sera in all groups examined. Compared with non-immunised and adjuvant only immunised controls, mice immunised with the Sfb1/SAMA4 vaccine exhibited a significant increase (P<0.05) in the number of Sfb1 reactive spleen cells in lymphoproliferation assays which were three fold higher than those seen for mice vaccinated with the Sfb1/CTB vaccine. Mice vaccinated with CTB/Sfb1 had the highest level of protection (80%) as where mice vaccinated with SAMA4 and SAMA4/Sfb1 displayed no protection (20% and 40%). INTERPRETATION & CONCLUSION: These data suggest that the SAMA4 adjuvant used in this study fails to elicit protective immunity in BALB/c mice when used to adjuvant the known protective antigen Sfb1.

The 1990-1991 outbreak of melioidosis in the Northern Territory of Australia: clinical aspects.

From November 1990 to June 1991, 33 cases of acute melioidosis were diagnosed in tropical Northern Territory, Australia during an exceptionally wet monsoon. Eighteen (55%) were alcoholic, 16 (48%) diabetic and only 4 (12%, all survivors) had no risk factors. Twenty-seven (82%) were considered recent infection, with an incubation period of 3-21 days (mean 14) documented in eight cases with presumed cutaneous inoculation. Fourteen patients presented with pneumonia (4 septicemic) and of 11 others with septicemia 4 had genitourinary foci. Three of 4 with splenic abscesses required splenectomy. Three had only skin/soft tissue infection. One patient with brainstem encephalitis needed prolonged ventilation. Overall mortality was 36% (12 cases, including three relapses), despite therapy with ceftazidime and intensive care facilities. Pseudomonas pseudomallei is the commonest diagnosed cause of fatal bacteremic pneumonia at Royal Darwin Hospital and emphasis is placed on early appropriate antibiotic therapy and compliance with maintenance therapy for at least three months.

The 1990-1991 outbreak of melioidosis in the Northern Territory of Australia: epidemiology and environmental studies.

From November 1990 to June 1991 33 acute cases of melioidosis occurred in the Northern Territory, Australia; 25 cases were reported in the capital city, Darwin. We carried out an epidemiological investigation to exclude a common source outbreak, describe the risk factors for disease, and develop and institute appropriate control measures. We compared population based attack rates among various risk groups using logistic regression, and the demographic, medical and behavioral risk factors for melioidosis by a matched case-control study. Environmental Health Officers collected soil, surface water and cooling tower water specimens for Pseudomonas pseudomallei culture. The crude attack rate of melioidosis during the outbreak was 52 per 100,000. Age, gender, race, diabetes and alcohol abuse were independent risk factors for disease. The relative risk of disease in diabetic patients was 12.9 (95% CI 5.1-32.7; p < 0.001) and 6.7 in alcoholic patients (95% CI 2.9-15.2; p < 0.001). We found no significant difference between cases and controls in matched pair analysis for any of several exposure factors studied. We isolated Pseudomonas pseudomallei from 4% of soil samples and 9% of surface water samples. Our study confirms the importance of host factors in the development of melioidosis, and attempts to quantify the risk of disease during the Darwin epidemic. Pseudomonas pseudomallei is widespread in the soil of urban Darwin.