Multidrug-resistant tuberculosis in Australia, 1998-2012.

OBJECTIVE: To describe the epidemiology and outcomes of multidrug-resistant tuberculosis (MDR-TB) diagnosed in Australia between 1998 and 2012. DESIGN: A retrospective review was undertaken involving all patients with laboratory-confirmed MDR-TB notified in Australia between 1998 and 2012 inclusive. Demographic, clinical and laboratory features are described. Clinical outcomes were defined according to World Health Organization definitions of treatment success (cure and treatment completion), treatment failure, death, loss to follow-up (including transfer out), or not evaluated at treatment completion. RESULTS: A total of 244 cases of MDR-TB were diagnosed in Australia during the study period, representing 1.4% of all TB cases notified. The majority were born outside Australia, including one third in Papua New Guinea. Of those with treatment outcome data available, treatment success was demonstrated in 81%. Treatment success was positively associated with use of a second-line injectable agent. Those born in Papua New Guinea were less likely to achieve treatment success. CONCLUSION: MDR-TB is uncommon in Australia. The large number of cases born in Papua New Guinea, and the poorer outcomes in this cohort, represent challenges with cross-border management of MDR-TB in the Torres Strait. Australia has an ongoing role in the prevention and management of MDR-TB locally and in the region.

Cell-mediated immune response to Leishmania chagasi experimental infection of BALB/c immunosuppressed mice

Leishmaniasis, a zoonosis of worldwide distribution, presents a significant impact on immunosupressed patients. This study aimed to evaluate Leishmania chagasi infection in BALB/c mice immunosuppressed with dexamethasone. Spleen cells stimulated or not with L. chagasi were cultured for cytokine quantification (IFN-gama, IL-2, IL-4 and IL-10) by sandwich ELISA. Parasite loads in the spleen and liver were determined by means of culture microtitration. Immunosuppressed groups showed statistically lower spleen weight and CD4-cell percentage in blood on the day of infection and produced Th1 and Th2 cytokines on other days of the study. The other infected groups, weather immunosupressed or not, also produced Th1 and Th2 cytokines. Parasite loads in the spleen and liver were not statistically different among the groups. It was concluded that L. chagasi infection was not affected by dexamethasone-induced immunosuppression, probably due the reversible effect of the treatment.

Tuberculosis in east timorese refugees: implications for health care needs in East Timor.

SETTING: East Timorese refugees evacuated to Darwin, Australia, September 1999. OBJECTIVE: Presentation of the process and results of tuberculosis (TB) screening in a previously unscreened refugee population. DESIGN: Screening for TB by clinical examination (all persons) and chest X-ray (CXR) (persons over 12 years of age and those of any age with respiratory symptoms) and sputum microscopy and mycobacterial culture (abnormal CXR). RESULTS: Seventy-six patients were diagnosed with TB (38 culture-positive for Mycobacterium tuberculosis, including 11 sputum smear-positive). Of 89 positive mycobacterial cultures, 51 were non-tuberculous mycobacteria (NTM). Of the M. tuberculosis isolates, 82.2% were fully sensitive, 17.2% were resistant to isoniazid and 8.6% were resistant to isoniazid and streptomycin. Fifty-three consecutively diagnosed patients with TB were HIV-negative. The TB burden in this population was very high (point prevalence of 542/100,000 for smear-positive and 2,060/100,000 for culture-positive cases). Rates of culture for NTM were also high. Information from this study assisted the implementation of a National TB Control Programme for East Timor in February 2000. CONCLUSION: The challenges for public health authorities in East Timor to provide a successful TB control programme are enormous. The apparently low prevalence of drug resistance and HIV co-infection in the population is encouraging.

Invasive pneumococcal disease in the Northern Territory of Australia, 1994-1998.

OBJECTIVE: To examine the epidemiology of invasive pneumococcal disease (IPD) in the Northern Territory of Australia as a basis for optimising vaccination and healthcare provision. DESIGN: Prospective laboratory surveillance, with information collected from hospital and clinic records. SETTING: Northern Territory (NT) and rural communities in north-west South Australia served by an NT hospital, 1994-1998 (NT population is 27% Indigenous). MAIN OUTCOME MEASURES: IPD incidence and mortality, risk factors, clinical presentation and disease-causing serotypes in Indigenous and non-Indigenous people. RESULTS: 425 cases of IPD were detected, with 77% in Indigenous people. IPD incidence was highest in Indigenous children aged < 2 years (1534 per 100,000 in central Australia), but about 100 per 100,000 in non-Indigenous children < 2 years and all Indigenous age groups aged > or = 15 years. Mean ages of those with disease were 39 years in Indigenous people and 48 years in non-Indigenous people (P = 0.006) and, of those who died, 41 and 53 years, respectively (P = 0.04). IPD risk factors were present in 72% of Indigenous and 55% of non-Indigenous patients aged > or = 2 years. Serotype results for 363 isolates showed that the 23-valent vaccine covered 68% and 85% of isolates from Indigenous and non-Indigenous people aged > or = 2 years, respectively, while the proposed seven-, nine- and 11-valent conjugate vaccines covered 58%, 66% and 67% of isolates, respectively, from Indigenous children aged < 2 years and 72% each of those from non-Indigenous children. Case-fatality rates were 10% in both Indigenous and non-Indigenous people. CONCLUSION: These data support the recent change in NT vaccination policy which extended funding for the 23-valent vaccine to all Indigenous people aged > or = 15 years and all Indigenous children in central Australia aged 2-5 years. The high rates of IPD in both Indigenous and non-Indigenous children mandate action to make conjugate vaccine available as soon as possible.

Nontuberculous mycobacterial disease in northern Australia: a case series and review of the literature.

We performed a retrospective/prospective review of all cases of disease due to nontuberculous mycobacteria (NTM) reported in the Northern Territory, Australia, during the period 1989-1997. Fifty-eight cases were reported, with an average yearly incidence of 3.9 cases per 100,000 persons. The number increased significantly for the second half of the study period (39 vs. 19 cases; P<.02). The yearly incidence of pulmonary Mycobacterium avium/Mycobacterium intracellulare complex (MAC) disease not associated with human immunodeficiency virus (HIV) infection was 2.1 cases per 100,000 population. MAC was the most common isolate (78%) and pulmonary disease the most frequent clinical presentation (62%). Disease due to NTM or MAC was not found more commonly in rural areas. Significant risks for non-HIV-associated pulmonary MAC disease included male sex (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.0-4.5) and age >50 years (OR, 26.5; 95% CI, 10.9-67.3), but aboriginal people appeared underrepresented (OR, 0.77; 95% CI, 0.30-1.87). Mycobacterium tuberculosis was almost 5 times more likely than NTM to be the cause of non-HIV-associated mycobacterial pulmonary disease (153 vs. 32 cases; OR, 4.79; 95% CI, 3.22-7.14). Mycobacterial lymphadenitis in aboriginal children was more likely to be tuberculous than nontuberculous (OR, 6.5; 95% CI, 1.4-41.7), but not in nonaboriginal children (OR, 1.0). With treatment, 66% of the cases of non-HIV-associated pulmonary MAC disease had favorable outcomes, and 7% of patients had progressive fatal disease. Outcomes of therapy for lymphadenitis and skin/soft-tissue disease were excellent, but those of HIV-associated disseminated MAC disease were poor.

Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature.

In a prospective study of melioidosis in northern Australia, 252 cases were found over 10 years. Of these, 46% were bacteremic, and 49 (19%) patients died. Despite administration of ceftazidime or carbapenems, mortality was 86% (43 of 50 patients) among those with septic shock. Pneumonia accounted for 127 presentations (50%) and genitourinary infections for 37 (15%), with 35 men (18%) having prostatic abscesses. Other presentations included skin abscesses (32 patients; 13%), osteomyelitis and/or septic arthritis (9; 4%), soft tissue abscesses (10; 4%), and encephalomyelitis (10; 4%). Risk factors included diabetes (37%), excessive alcohol intake (39%), chronic lung disease (27%), chronic renal disease (10%), and consumption of kava (8%). Only 1 death occurred among the 51 patients (20%) with no risk factors (relative risk, 0.08; 95% confidence interval, 0.01-0.58). Intensive therapy with ceftazidime or carbapenems, followed by at least 3 months of eradication therapy with trimethoprim-sulfamethoxazole, was associated with decreased mortality. Strategies are needed to decrease the high mortality with melioidosis septic shock. Preliminary data on granulocyte colony-stimulating factor therapy are very encouraging.

Universal hepatitis B vaccination: hospital factors influencing first-dose uptake for neonates in Darwin.

A universal neonatal hepatitis B vaccination program was introduced in the Northern Territory in 1990. We compared live births with vaccine usage to determine the uptake of the first dose of hepatitis B vaccine under this new policy and to identify hospital factors that influenced this rate. Attitudes and vaccine administration practices were determined through interviews, using standard questions with midwifery and paediatric nursing staff at both hospitals. Hepatitis B vaccines dispensed at Hospital A indicated a 96 per cent coverage of neonates in 1993 and 93 per cent in 1994. Vaccination at Hospital B indicated 71 per cent coverage in 1993 and 77 per cent in 1994. Differences in vaccine uptake appeared to be influenced by the use of standing drug orders, the nursing staff's attitudes and knowledge, and misinformation among health professionals. Education programs for health professionals and parents need to be established before the introduction of a universal hepatitis B vaccination policy for it to be well accepted. Standing orders for hepatitis B vaccine in postnatal wards allow nursing staff to promote it and thus maximise coverage rates.

Aborigines and tuberculosis: why they are at risk.

Aborigines have higher rates of Mycobacterium tuberculosis than the rest of the community. There are insufficient contemporary data to assess how much risk tuberculosis poses to the Aboriginal community. Tuberculosis is of particular concern because of its interaction with human immuno-deficiency virus (HIV). We aimed to ascertain the available data about tuberculosis in Australian Aborigines: to determine morbidity and mortality of tuberculosis in Australian Aborigines, to ascertain the extent of known risk factors for tuberculosis in Australian Aborigines and to consider the public health implications of our findings. Sparse evidence suggests that Aborigines have higher rates of infection and of clinical tuberculosis than non-Aboriginal Australians, along with a high prevalence of known risk factors for tuberculosis. However, there is a paucity of data about specific risk factors and tuberculosis in Aborigines. In addition, Aborigines have a high prevalence of risk factors for HIV infection. The existence of concurrent risk factors for tuberculosis and HIV, in a population that already has a high rate of infection with tuberculosis is cause for grave concern. Tuberculosis control is centred on correct and rapid diagnosis and appropriate treatment, as well as efficient contact tracing. These are the most important strategies for control of tuberculosis among Aborigines, and are especially important when there is concurrence of other risk factors. Appropriate preventive therapy for infected people should also be considered.

Should aboriginals in the "top end" of the Northern Territory be vaccinated against hepatitis A?

OBJECTIVE: To determine the level of immunity to hepatitis A virus infection in rural Australian Aboriginal populations in the "Top End" of the Northern Territory. METHODS: A total of 344 sera, for which details of donors' age, sex and domicile were available, were collected and tested for hepatitis A total antibody in a delinked seroprevalence study. RESULTS: Overall, 337/344 samples (97.97%) tested positive for hepatitis A total antibodies--18/20 samples (90%) in the 1-5 year age group; 85/88 (96.6%) in the 6-10 year age group; 98/98 (100%) in the 11-15 year age group; 32/33 (97.0%) in the 16-20 year age group and 104/105 (99%) in the older than 20 year age group. CONCLUSION: Hepatitis A is hyperendemic in the rural Aboriginal communities studied and the virus is acquired predominantly in the first five years of life. Symptomatic hepatitis A infection is uncommon in this population. We suggest that hepatitis A vaccination for rural Aboriginal children is not indicated as it would not reduce clinical disease rates and may produce a cohort whose immunity could decrease over the following 10 years. Although vaccination is appropriate for non-immune individuals working in remote communities, emphasis must be placed on the inequities in health infrastructure and education underlying the high transmission rates in Aboriginal children.

Tuberculosis in the tropics.

Until recently tuberculosis was considered a well controlled disease, at least in developed countries. In developing countries, more than seven million people are affected by active tuberculosis. This situation is exacerbated by poor infrastructure to support tuberculosis control measures and the interaction between tuberculosis and infection with the human immunodeficiency virus. The three major strategies for controlling tuberculosis remain BCG vaccination in children, appropriate preventive therapy and, most importantly, reducing the sources of infection through case finding and curative treatment. Research and resources to improve on these strategies should be given high priority by the international health community.

PIP: Tuberculosis (TB) has long been under control in developed countries. Recently, however, the stability of this comfortable position has begun to erode. More than 7 million people are affected by active TB in developing countries where poor infrastructure thwarts control efforts and TB interacts with HIV infection. The 3 major strategies for controlling TB remain BCG vaccination in children, preventive therapy, and reducing the sources of infection through case identification and curative treatment. The international health community should confer high priority to research and resources upon improving these strategies. TB is highly prevalent in the tropics not because it is a tropical disease, but because it is an opportunistic disease of poverty, overcrowding, and malnutrition which are seen in higher incidence in tropical countries with relatively newly exposed populations and countries where health infrastructure is hindered by economic disadvantage and political instability. Sections review global trends; the size of the problem; tuberculosis in tropical Australia; tuberculosis and HIV infection; the current status of TB prevention; and the current status of case control.

Focal neurological signs in cerebral malaria accounted for by preceding neurological damage.

In 1987 at Port Moresby General Hospital, Papua New Guinea, two out of 103 adults with a final diagnosis of cerebral malaria had focal neurological signs noted on admission. In both cases the focal signs could be explained by documented prior neurological disease with residual focal damage. Focal neurological signs in patients presenting with malaria should prompt careful investigation to exclude other active neurological disease. Where no additional diagnosis is evident a history of past neurological damage may become apparent to explain the focal nature of the malaria presentation.