The Darwin Prospective Melioidosis Study: a 30-year prospective, observational investigation.

BACKGROUND: The global distribution of melioidosis is under considerable scrutiny, with both unmasking of endemic disease in African and Pacific nations and evidence of more recent dispersal in the Americas. Because of the high incidence of disease in tropical northern Australia, The Darwin Prospective Melioidosis Study commenced in October, 1989. We present epidemiology, clinical features, outcomes, and bacterial genomics from this 30-year study, highlighting changes in the past decade. METHODS: The present study was a prospective analysis of epidemiological, clinical, and laboratory data for all culture-confirmed melioidosis cases from the tropical Northern Territory of Australia from Oct 1, 1989, until Sept 30, 2019. Cases were identified on the basis of culture-confirmed melioidosis, a laboratory-notifiable disease in the Northern Territory of Australia. Patients who were culture-positive were included in the study. Multivariable analysis determined predictors of clinical presentations and outcome. Incidence, survival, and cluster analyses were facilitated by population and rainfall data and genotyping of Burkholderia pseudomallei, including multilocus sequence typing and whole-genome sequencing. FINDINGS: There were 1148 individuals with culture-confirmed melioidosis, of whom 133 (12%) died. Median age was 50 years (IQR 38-60), 48 (4%) study participants were children younger than 15 years of age, 721 (63%) were male individuals, and 600 (52%) Indigenous Australians. All but 186 (16%) had clinical risk factors, 513 (45%) had diabetes, and 455 (40%) hazardous alcohol use. Only three (2%) of 133 fatalities had no identified risk. Pneumonia was the most common presentation occurring in 595 (52%) patients. Bacteraemia occurred in 633 (56%) of 1135 patients, septic shock in 240 (21%) patients, and 180 (16%) patients required mechanical ventilation. Cases correlated with rainfall, with 80% of infections occurring during the wet season (November to April). Median annual incidence was 20·5 cases per 100 000 people; the highest annual incidence in Indigenous Australians was 103·6 per 100 000 in 2011-12. Over the 30 years, annual incidences increased, as did the proportion of patients with diabetes, although mortality decreased to 17 (6%) of 278 patients over the past 5 years. Genotyping of B pseudomallei confirmed case clusters linked to environmental sources and defined evolving and new sequence types. INTERPRETATION: Melioidosis is an opportunistic infection with a diverse spectrum of clinical presentations and severity. With early diagnosis, specific antimicrobial therapy, and state-of-the-art intensive care, mortality can be reduced to less than 10%. However, mortality remains much higher in the many endemic regions where health resources remain scarce. Genotyping of B pseudomallei informs evolving local and global epidemiology. FUNDING: The Australian National Health and Medical Research Council.

The role of stigma in the acceptance and disclosure of HIV among recently diagnosed men who have sex with men in Australia: A qualitative study.

BACKGROUND: Our primary study aimed to explore the experiences of men who have sex with men (MSM) recently diagnosed with HIV and their partner notification practices. Themes relating to acceptance, and disclosure of, their HIV status strongly emerged during analysis in our larger study and are reported separately here. METHOD: Fifteen MSM participated in semi-structured interviews by phone or face to face about their experience of a recent HIV diagnosis. In this paper we report on how they received and accepted the diagnosis, who they disclosed their diagnosis to and what is needed to improve support for MSM recently diagnosed with HIV. RESULTS: MSM's reactions to their HIV diagnosis ranged from shock, devastation and anger to a calm acceptance and feeling HIV would not have a significant impact on their lives. MSM who reported strong social support networks, or knew others with HIV, seemed better able to cope with and accept their diagnosis than those with fewer support networks. Due to prevailing stigma around HIV, most MSM were very selective about who they disclosed their status to, often only telling partners perceived to be at risk but no, or only few, close friends. Regardless of how well men accepted their diagnosis, most did not disclose their status to family members for fear of rejection or causing distress due to ideologies based on outdated information about HIV. CONCLUSION: The prevailing stigma around HIV can have a significant impact on MSM's acceptance of, and willingness to disclose their HIV serostatus to others, and consequently the levels of professional and social support they receive. HIV-related stigma needs to be addressed through community campaigns which better educate the wider population about the current state of HIV prognosis and treatment.

Health issues of refugees attending an infectious disease refugee health clinic in a regional Australian hospital

BACKGROUND AND OBJECTIVES: Refugees in Australia present with conditions different to those of the general population. The aim of this study was to review the reasons for referral, prevalence of conditions and treatment outcomes for refugee patients attending a specialist referral clinic in regional Victoria. METHOD: A retrospective review was undertaken of patients attending the refugee health clinic at University Hospital Geelong from January 2007 to December 2012. RESULTS: Two hundred and ninety-one refugee patients attended the clinic over the six-year period. Latent tuberculosis infection (LTBI) (54.6%), vitamin deficiencies (15.8%), hepatitis B (11%) and schistosomiasis (11%) were the most common diagnoses. Less than two-thirds of the patients completed LTBI treatment; 35.4% of patients attended all scheduled clinic appointments. DISCUSSION: LTBI, vitamin deficiencies, parasitic infections and hepatitis B were the most common diagnoses among refugees referred to the University Hospital Geelong (UHG) Refugee Health Clinic from January 2007 to December 2012. General practitioners play an important role in the care of refugees, guiding referral to specialist services when necessary and recognising the potential implications of suboptimal clinic attendance and treatment completion.

Clinical factors associated with syphilis concordance in men in sexual partnerships: a cross-sectional couples study.

BACKGROUND: Syphilis infections continue to increase among men who have sex with men (MSM) in many countries, with rates often higher among HIV-positive MSM. There is limited understanding of the risk and determinants of syphilis transmission between men. We aimed to examine the concordance of early syphilis infection between male sexual partners and clinical factors associated with transmission. METHODS: Men attending Melbourne Sexual Health Centre with their male partners, where at least one was diagnosed with early syphilis, were identified from linkage of partner records between March 2011 and April 2016. Early latent syphilis was defined as a new asymptomatic syphilis presentation of less than 2 years' duration. Associations between concordance and potential risk factors were examined using Fisher's exact test. RESULTS: Among 43 couples (86 men) identified, there were 13 couples (26 men) where both were diagnosed with early syphilis, representing a concordance rate of 30.2% (95% CI 17.2% to 46.1%). Among the 13 concordant couples, 5 men had primary syphilis (4 penile, 1 anal), 11 secondary syphilis (8 generalised rash, 3 penile, 2 anal, 1 oral lesion) and 10 early latent infections. Concordance was higher among couples where at least one partner had secondary syphilis compared with couples where neither partner had secondary syphilis (53% (9/17) vs 15% (4/26), P=0.016). Furthermore, concordance was higher among couples where one was HIV positive compared with couples where both were HIV negative (62% (5/8) vs 23% (8/35), P=0.042). CONCLUSIONS: There was an overall concordance rate of 30%. Higher concordance rates for early syphilis infection between male sexual partners were associated with HIV and secondary syphilis.

Chlamydia Infection Between Men and Women: A Cross-Sectional Study of Heterosexual Partnerships.

BACKGROUND: Studies of sexual partnerships can further our understanding of the sexual transmission of chlamydia, which is important for informing public health interventions and clinical management. The aim of this study was to ascertain among heterosexual dyads the proportion concordantly infected with chlamydia and factors associated with infection between partners. METHODS: This study was conducted at the Melbourne Sexual Health Centre between January 2006 and March 2015. Heterosexual partners attending the clinic on the same day were identified prospectively. Dyads where 1 or both individuals were diagnosed with chlamydia by a test performed on the day of joint attendance or within the prior 30 days were included. Testing was by strand displacement assay. Men and women with genital symptoms underwent clinical examination. RESULTS: Of 233 females with chlamydia, 76% (n = 178) of their male partners tested positive. Of the chlamydia-positive females with cervicitis, 91% of males were chlamydia positive. Male infection was less likely if their partner had taken azithromycin or doxycycline within 30 days (7% vs 25%; P = .039). Of 235 males with chlamydia, 77% (n = 178) of their female partners tested positive. No associations were found between male symptoms, signs, or recent antibiotic use and a positive chlamydia result in female partners. Sixty-one percent of the dyads were concordantly infected with chlamydia. CONCLUSIONS: These results underscore the high likelihood of heterosexual partners of men and women with chlamydia being infected and the importance that partners are tested and managed appropriately for chlamydia.

A Qualitative Study of Means to Improve Partner Notification After an HIV Diagnosis Among Men Who Have Sex with Men in Australia.

Improved partner notification (PN) after HIV diagnosis could help control HIV among men who have sex with men (MSM). However, there is little evidence exploring what this experience is like for Australian MSM and how achievable it is in the era of the Internet and smartphones. Fifteen of 39 invited MSM recently diagnosed with HIV undertook a semistructured interview about PN. Interviews were thematically analyzed using a combined deductive/inductive approach. Three main themes arose: fear of PN and HIV disclosure, partners' unexpected reactions, and the need for more patient support. MSM found PN difficult and uncomfortable and described fear about potential repercussions of PN; however, they felt it was the right thing to do. Regular partners were more likely to be notified, and in person, because of the availability of contact information but more notably because of a sense of moral responsibility. Men commonly had few contact details for casual partners and preferred PN strategies that allowed them to remain anonymous, largely reflecting the reasons for and ways in which they met casual partners: online or through apps and predominantly for once-off, anonymous sex. Most described unexpected positive responses from partners who were contacted personally by the men. Our study also showed that participants required professional support to carry out PN, especially with casual partners, as well as support around understanding the implications of and treatments relating to being HIV positive. PN could be improved by offering more options that allow the index patient to remain anonymous, particularly when notifying casual partners.

Increased Detection of Pharyngeal and Rectal Gonorrhea in Men Who Have Sex With Men After Transition From Culture To Nucleic Acid Amplification Testing.

BACKGROUND: This before-and-after study measured the impact of a change in testing methods from culture to nucleic acid amplification testing (NAAT) on the detection of pharyngeal and rectal gonorrhea in men who have sex with men (MSM) on a sexual health service level, including the effect on subgroups anticipated to have higher rates of gonorrhea. METHODS: In March 2015, Melbourne Sexual Health Centre changed its laboratory method for gonococcal testing from culture to NAAT using the Aptima Combo 2 and Aptima GC tests. We compared the proportion of tests positive for rectal and pharyngeal gonorrhea in MSM using culture in 2014 with those using NAAT in 2015. RESULTS: The proportion of tests positive for rectal gonorrhea by NAAT was double that obtained by culture (8% vs 3.9%; prevalence ratio [PR], 2.0; 95% confidence interval [CI], 1.8-2.4) and 5-fold for pharyngeal gonorrhea (8.3% vs 1.6%; PR, 5.2; 95% CI, 4.2-6.4). Similar increases in test positivity were observed in human immunodeficiency virus (HIV)-positive and HIV-negative men. By NAAT, test positivity for rectal gonorrhea was higher in HIV-positive compared with HIV-negative men (15.4% vs 7.3%; PR, 2.1; 95% CI, 1.7-2.6). Culture and NAAT had similar test positivity for rectal gonorrhea among men who reported contact with gonorrhea (24.9% vs 25.3%, PR 1.0, 95% CI 0.8-1.4) and men who presented with symptoms of proctitis (22.2% vs 27.9%, PR 1.3, 95% CI 0.8-2.0). CONCLUSIONS: A switch from culture to Aptima Combo 2 testing for extragenital gonorrhea in MSM increased detection and was most marked for pharyngeal infections.

Duration of gonorrhoea and chlamydia infection at the pharynx and rectum among men who have sex with men: a systematic review.

UNLABELLED: Background Chlamydia and gonorrhoea are the two most common sexually transmissible infections (STI) among men who have sex with men (MSM) worldwide. Infections at the pharynx and rectum are usually asymptomatic; however, the natural history of these infections remains unknown. The aim of this study is to estimate the duration of both infections at the extragenital sites from published epidemiological cohort studies. METHODS: English peer-reviewed articles were searched from 1 January 2000 to 12 March 2015 in three electronic databases (MEDLINE, EMBASE and Cochrane Central). The prevalence-to-incidence ratio from each study was calculated to reflect the duration of each infection. This review followed the PRISMA guidelines and was registered in PROSPERO (CRD42014007087). RESULTS: There were 2585 records identified, with 1721 abstracts and 52 full-text articles screened, resulting in four studies fulfilling the inclusion criteria. Pharyngeal gonorrhoea (114-138 days) had a shorter duration of infection than rectal gonorrhoea (346 days). In addition, chlamydia had a longer duration of infection at the pharynx (667 days) and rectum (579 days) compared with gonorrhoea infection. CONCLUSIONS: Gonorrhoea has a shorter duration of infection than chlamydia, suggesting that annual STI screening will be more effective at diagnosing chlamydia than gonorrhoea. The current STI guidelines recommend screening gonorrhoea and chlamydia at least once a year in MSM; it would only detect ~30% of incident pharyngeal gonorrhoea cases, with a mean duration of 4 months.

High prevalence of rectal gonorrhoea among men reporting contact with men with gonorrhoea: Implications for epidemiological treatment.

BACKGROUND: This study aimed to determine the prevalence of gonorrhoea and factors associated with rectal gonorrhoea among men reporting sexual contact with men with gonorrhoea. METHODS: Men who presented to Melbourne Sexual Health Centre reporting sexual contact with a male with gonorrhoea were prospectively identified between March 2011 and December 2013. These men were screened for pharyngeal and rectal gonorrhoea using culture. The prevalence of gonorrhoea among contacts was compared to that among all men who have sex with men (MSM) screened at the clinic over the same period. RESULTS: Among 363 contacts of gonorrhoea the prevalence of rectal gonorrhoea was 26.4% (95% CI: 21.8%-31.0%) compared to 3.9% (95% CI: 3.7%-4.2%) among clinic attendees (p < 0.001). The prevalence of pharyngeal gonorrhoea among contacts was 9.4% (95% CI: 6.4%-12.4%) compared to 2.1% (95% CI: 1.9%-2.4%) among clinic attendees (p < 0.001). Among contacts who reported not always using condoms during receptive anal sex with casual partners, rectal gonorrhoea was cultured in 42.4% compared with 12.7% among contacts reporting no receptive anal sex (p < 0.001) and 20.2% among those reporting always using condoms (p < 0.001). On multivariate analysis rectal gonorrhoea was associated with inconsistent condom use during receptive anal sex with casual partners (adjusted odds ratio (AOR): 4.16; 95% CI: 1.87-9.26) and a reported past history of gonorrhoea (AOR: 1.77; 95% CI: 1.01-3.14). CONCLUSIONS: The high proportion of positive cases of gonorrhoea among contacts in this study supports epidemiological treatment of MSM presenting as contacts of gonorrhoea.

Chlamydia infection in individuals reporting contact with sexual partners with chlamydia: a cross-sectional study of sexual health clinic attendees.

OBJECTIVES: We aimed to ascertain the proportion of positive, and predictive factors of chlamydia infection among females, heterosexual males and men who have sex with men (MSM) presenting to a sexual health service reporting contact with a chlamydia infected sexual partner. METHODS: A cross-sectional analysis of patients attending the Melbourne Sexual Health Centre from October 2010 to September 2013. Behavioural data obtained using computer assisted self-interview were analysed to determine factors predictive of chlamydia. RESULTS: Of the 491 female, 808 heterosexual male, and 268 MSM chlamydia contacts, the proportion diagnosed with chlamydia were 39.9% (95% CI 35.7% to 44.3%), 36.1% (95% CI 32.9% to 39.9%) and 23.5% (95% CI 18.8% to 29.0%), respectively. Female chlamydia contacts were more likely to have chlamydia if age <25 (adjusted OR (AOR) 1.86, 95% CI 1.12 to 3.10) or if they reported inconsistent condom use during vaginal sex with a regular male partner (AOR 2.5, 95% CI 1.12 to 6.14). Heterosexual male contacts were more likely to have chlamydia if age <25 (AOR 1.69, 95% CI 1.25 to 2.28) or if they had a regular female sexual partner (AOR 1.38, 95% CI 1.03 to 1.85). In MSM urethral chlamydia was diagnosed in 8.8%, rectal chlamydia in 20.2%, and 3.9% at both sites. MSM were more likely to have chlamydia if they had a regular male sexual partner (OR 2.12, 95% CI 1.18 to 3.81). CONCLUSIONS: This study of female, heterosexual male, and MSM presentations with self-reported chlamydia contact provides insight into the likelihood and predictive factors of infection. The data may inform policy and individual clinical decision making regarding presumptive treatment of chlamydia contacts.

Pre-emptive steroids for a severe oedematous Buruli ulcer lesion: a case report.

INTRODUCTION: Severe oedematous forms of Buruli ulcer (BU) often result in extensive tissue destruction, even with the institution of appropriate antibiotic treatment, leading to reconstructive surgery and long-term disability. We report a case of a patient with severe oedematous BU, which describes for the first time the pre-emptive use of prednisolone therapy commenced at the time of antibiotic initiation aimed at limiting the ongoing tissue destruction and its secondary sequelae. CASE PRESENTATION: A 91-year-old Australian-born Caucasian woman presented with a WHO category 3 oedematous BU lesion on the anterior aspect of her right ankle that she had first noticed three weeks earlier. Treatment was commenced with an antibiotic combination of rifampicin and ciprofloxacin. At the same time, pre-emptive prednisolone was commenced (a dose of 0.5mg/kg daily). Treatment resulted in rapid and significant reduction in the size of the induration associated with the lesion, and no significant increase in the size of the skin ulceration. Antibiotics were continued for 56 days and prednisolone therapy ceased 130 days after antibiotics commenced. No surgery was required. The wound healed completely after 10 months and there was no long-term limitation of movement at the ankle joint. CONCLUSIONS: Pre-emptive corticosteroid therapy may prevent further progressive tissue necrosis and the need for secondary reconstructive surgery that commonly occurs during the antibiotic treatment of severe odematous forms of BU.

Detection of Mycobacterium leprae by PCR testing of sputa from a patient with pulmonary cryptococcus coinfection in northern Australia.

A case of fever, sepsis, and chest lesions evident on a computed tomography scan of an indigenous man in northern Australia following burns to the feet is described. Sputum PCR testing revealed Mycobacterium leprae, and a fine-needle aspirate of the chest lesions demonstrated Cryptococcus coinfection.

Facilitating partner notification through an online messaging service: Let Them Know.

Let Them Know (www.letthemknow.org.au) is an Australian internet based service designed to support individuals diagnosed with an STI to notify sexual partners using anonymous or personal text messages. A review of user activity and acceptability of the website was performed. Between 17 March 2010 and 31 March 2011, of 13?024 website visits, 4863 (37%) visits resulted in a text message being sent. From 3 December 2010, of 1383 consecutive users, 963 (70%) indicated they were more likely to contact a partner because of the website. A short period of misuse was identified and controlled, and additional measures to monitor for and prevent misuse were subsequently implemented. Web-based notification systems such as the Let Them Know website can help to facilitate partner notification for individuals who may be reluctant to do this in person.

Evaluation of Electronic Medical Record (EMR) at large urban primary care sexual health centre.

OBJECTIVE: Despite substantial investment in Electronic Medical Record (EMR) systems there has been little research to evaluate them. Our aim was to evaluate changes in efficiency and quality of services after the introduction of a purpose built EMR system, and to assess its acceptability by the doctors, nurses and patients using it. METHODS: We compared a nine month period before and after the introduction of an EMR system in a large sexual health service, audited a sample of records in both periods and undertook anonymous surveys of both staff and patients. RESULTS: There were 9,752 doctor consultations (in 5,512 consulting hours) in the Paper Medical Record (PMR) period and 9,145 doctor consultations (in 5,176 consulting hours in the EMR period eligible for inclusion in the analysis. There were 5% more consultations per hour seen by doctors in the EMR period compared to the PMR period (rate ratio = 1.05; 95% confidence interval, 1.02, 1.08) after adjusting for type of consultation. The qualitative evaluation of 300 records for each period showed no difference in quality (P>0.17). A survey of clinicians demonstrated that doctors and nurses preferred the EMR system (P<0.01) and a patient survey in each period showed no difference in satisfaction of their care (97% for PMR, 95% for EMR, P = 0.61). CONCLUSION: The introduction of an integrated EMR improved efficiency while maintaining the quality of the patient record. The EMR was popular with staff and was not associated with a decline in patient satisfaction in the clinical care provided.

Immunopathogenesis and diagnosis of tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome during early antiretroviral therapy.

BACKGROUND: In many settings, the benefits of antiretroviral therapy (ART) are reduced by the high early incidence of tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). METHODS: We used tuberculin skin testing and the QuantiFERON-TB Gold In-Tube assay to investigate cellular immune responses to purified protein derivative (PPD) and region of difference 1 (RD1) antigens during the first 24 weeks of ART. RESULTS: TB-IRIS and ART-associated tuberculosis occurred in 15 of 75 (20%) and 11 of 231 (4.8%) participants at risk, respectively. Greater increases in interferon gamma (IFN-gamma) and skin test responses to PPD were seen at week 24 and 12 in participants with TB-IRIS (P< or = .04), respectively. Raw IFN-gamma responses to RD1 antigens and PPD corrected for pre-ART CD4(+) T cell counts were higher at all time points in individuals with ART-associated tuberculosis (P<.001) and were associated with areas under receiver operator characteristic curves of 0.90 for RD1 (95% confidence interval [CI], 0.78-1.00) and 0.92 for PPD (95% CI, 0.83-1.00) for the diagnosis of ART-associated tuberculosis. Pre-ART IFN-gamma responses enabled stratification of participants into groups with risks of subsequent tuberculosis of 0.7%, 9.3%, and 30.0%. CONCLUSIONS: Type 1 effector T cell responses are prominent in ART-associated tuberculosis, but additional immune defects may be more important in paradoxical TB-IRIS. IFN-gamma release assays may contribute to the prediction and diagnosis of tuberculosis during early ART.

Melioidosis epidemiology and risk factors from a prospective whole-population study in northern Australia.

OBJECTIVES: The aims of this study were to describe the epidemiology of melioidosis in tropical northern Australia and to assess the importance of defined risk factors. METHODS: The data were taken from a 14-year prospective study of 364 cases of melioidosis in the 'Top End' of the Northern Territory. A whole-population logistic regression model was used to estimate the crude and adjusted relative risk (RR) for the defined risk factors. RESULTS: The mean age of the study population was 46.8 years, 264 (72.5%) were male, 178 (49%) were aboriginal Australians and 59 (16.2%) died from melioidosis. Average annual incidence was 19.6 cases per 100 000 population, with an estimated rate of 260 cases per 100,000 diabetics per year. Using a whole-population logistic regression model, the estimated crude and adjusted RR [95% confidence intervals (CI)] for melioidosis were 6.3 (5.1-7.8) and 4.0 (3.2-5.1) for those aged > or = 45 years, 2.3 (1.8-2.9) and 2.4 (1.9-3.0) for males, 2.9 (2.3-3.5) and 3.0 (2.3-4.0) for aboriginal Australians, 21.2 (17.1-26.3) and 13.1 (9.4-18.1) for diabetics, 2.7 (2.2-3.4) and 2.1 (1.6-2.6) for those with excess alcohol consumption, 6.8 (5.4-8.6) and 4.3 (3.4-5.5) for chronic lung disease and 6.7 (4.7-9.6) and 3.2 (2.2-4.8) for chronic renal disease, respectively. CONCLUSIONS: Diabetes, excess alcohol intake, chronic renal disease and chronic lung disease are each independent risk factors for melioidosis. In tropical northern Australia, male sex, aboriginal ethnicity and age of > or = 45 years are also independent predictors for melioidosis. Impaired polymorph function may be critical in the predisposition to melioidosis.