The epidemiology and clinical features of rickettsial diseases in North Queensland, Australia: Implications for patient identification and management.

BACKGROUND: Rickettsial infections are a common cause of hospitalization in tropical settings, although early diagnosis is challenging in the rural locations where these infections are usually seen. METHODS: This retrospective, clinical audit of microbiologically-confirmed cases of scrub typhus or spotted fever group (SFG) rickettsial infection between 1997 and 2016 was performed a tertiary referral hospital in tropical Australia. Clinical, laboratory and radiological findings at presentation were correlated with the patients' subsequent clinical course. RESULTS: There were 135 locally-acquired cases (95 scrub typhus, 37 SFG, 3 undifferentiated). There were nine hospitalizations during the first 5 years of the study period and 81 in the last 5 years (p for trend = 0.003). Eighteen (13%) of the 135 cases required ICU admission, all of whom were adults. A greater proportion of patients with SFG infection required ICU support (8/37 (22%) compared with 10/95 (11%) scrub typhus cases), although this difference did not reach statistical significance (p = 0.10). Three (8%) of the 37 patients with SFG infection had severe disease (1 died, 2 developed permanent disability) versus 0/95 scrub typhus patients (p = 0.02). Adults with a high admission qSOFA score (≥2) had an odds ratio (OR) of 19 (95% CI:4.8-74.5) for subsequent ICU admission (p<0.001); adults with a high NEWS2 score (≥7) had an OR of 14.3 (95% CI:4.5-45.32) for ICU admission (p<0.001). A patient's respiratory rate at presentation had strong prognostic utility: if an adult had an admission respiratory rate <22 breaths/minute, the negative predictive value for subsequent ICU admission was 95% (95% CI 88-99). CONCLUSIONS: In the well-resourced Australian health system outcomes are excellent, but the local burden of rickettsial disease appears to be increasing and the clinical phenotype of SFG infections may be more severe than previously believed. Simple, clinical assessment on admission has prognostic utility and may be used to guide management.

Case Report: Endemic Amebiasis in Australia: Implications for Residents, Travelers, and Clinicians.

Entamoeba histolytica is considered endemic in Australia; however, cases are rare, occurring almost exclusively in high-risk individuals. We describe a series of locally acquired, complicated cases in low-risk individuals from Far North Queensland in whom the diagnosis was delayed. Amebiasis may pose a greater local threat than is currently recognized.

Implications of male circumcision for women in Papua New Guinea: a transformational grounded theory study.

BACKGROUND: Male circumcision reduces the risk of female-to-male transmission of human immunodeficiency virus (HIV) and is being explored for HIV prevention in Papua New Guinea (PNG). PNG has a concentrated HIV epidemic which is largely heterosexually transmitted. There are a diverse range of male circumcision and penile modification practices across PNG. Exploring the implications of male circumcision for women in PNG is important to inform evidence-based health policy that will result in positive, intended consequences. METHODS: The transformational grounded theory study incorporated participatory action research and decolonizing methodologies. In Phase One, an existing data set from a male circumcision study of 861 male and 519 female participants was theoretically sampled and analyzed for women's understanding and experience of male circumcision. In Phase Two of the study, primary data were co-generated with 64 women in seven interpretive focus group discussions and 11 semi-structured interviews to develop a theoretical model of the processes used by women to manage the outcomes of male circumcision. In Phase Three participants assisted to refine the developing transformational grounded theory and identify actions required to improve health. RESULTS: Many women know a lot about male circumcision and penile modification and the consequences for themselves, their families and communities. Their ability to act on this knowledge is determined by numerous social, cultural and economic factors. A transformational grounded theory was developed with connecting categories of: Women Know a Lot, Increasing Knowledge; Increasing Options; and Acting on Choices. Properties and dimensions of each category are represented in the model, along with the intervening condition of Safety. The condition of Safety contextualises the overarching lived realty for women in PNG, enables the inclusion of men in the transformational grounded theory model, and helps to explain relationships between men and women. The theory presents the core category as Power of Choice. CONCLUSIONS: This transformational grounded theory provides a means to explore how women experience male circumcision and penile modification in PNG, including for HIV prevention. Women who have had opportunities for education have a greater range of choices and an increased opportunity to act upon these choices. However, women can only exercise their power of choice in the context of safety. The concept of Peace drawn from the Social Determinants of Health is applied in order to extend the explanatory power of the transformational grounded theory. This study shows that women's ambivalence about male circumcision is often related to lack of safety, a consequence of gender inequality in PNG.

Efficacy of a trivalent influenza vaccine against seasonal strains and against 2009 pandemic H1N1: A randomized, placebo-controlled trial.

BACKGROUND: Before pandemic H1N1 vaccines were available, the potential benefit of existing seasonal trivalent inactivated influenza vaccines (IIV3s) against influenza due to the 2009 pandemic H1N1 influenza strain was investigated, with conflicting results. This study assessed the efficacy of seasonal IIV3s against influenza due to 2008 and 2009 seasonal influenza strains and against the 2009 pandemic H1N1 strain. METHODS: This observer-blind, randomized, placebo-controlled study enrolled adults aged 18-64years during 2008 and 2009 in Australia and New Zealand. Participants were randomized 2:1 to receive IIV3 or placebo. The primary objective was to demonstrate the efficacy of IIV3 against laboratory-confirmed influenza. Participants reporting an influenza-like illness during the period from 14days after vaccination until 30 November of each study year were tested for influenza by real-time reverse transcription polymerase chain reaction. RESULTS: Over a study period of 2years, 15,044 participants were enrolled (mean age±standard deviation: 35.5±14.7years; 54.4% female). Vaccine efficacy of the 2008 and 2009 IIV3s against influenza due to any strain was 42% (95% confidence interval [CI]: 30%, 52%), whereas vaccine efficacy against influenza due to the vaccine-matched strains was 60% (95% CI: 44%, 72%). Vaccine efficacy of the 2009 IIV3 against influenza due to the 2009 pandemic H1N1 strain was 38% (95% CI: 19%, 53%). No vaccine-related deaths or serious adverse events were reported. Solicited local and systemic adverse events were more frequent in IIV3 recipients than placebo recipients (local: IIV3 74.6% vs placebo 20.4%, p<0.001; systemic: IIV3 46.6% vs placebo 39.1%, p<0.001). CONCLUSIONS: The 2008 and 2009 IIV3s were efficacious against influenza due to seasonal influenza strains and the 2009 IIV3 demonstrated moderate efficacy against influenza due to the 2009 pandemic H1N1 strain. Funded by CSL Limited, ClinicalTrials.gov identifier NCT00562484.

Weighing up the costs of seeking health care for dengue symptoms: a grounded theory study of backpackers' decision-making processes.

Dengue fever, a mosquito-borne virus, is an ongoing public health issue in North Queensland. Importation of dengue fever by travellers visiting or returning to Australia can lead to epidemics. The mosquito can acquire the virus in the symptomatic viraemic phase, so timely recognition of cases is important to prevent epidemics. There is a gap in the literature about backpackers' knowledge of dengue fever and the decision-making process they use when considering utilising the Australian health-care system. This study uses grounded theory methods to construct a theory that explains the process backpackers use when seeking health care. Fifty semi-structured interviews with backpackers, hostel receptionists, travel agents and pharmacists were analysed, resulting in identification of a core category: 'weighing up the costs of seeking health care'. This core category has three subcategories: 'self-assessment of health status', 'wait-and-see' and 'seek direction'. Findings from this study identified key areas where health promotion material and increased access to health-care professionals could reduce the risk of backpackers spreading dengue fever.

Prevalence of patients with acute febrile illnesses and positive dengue NS1 tests in a tertiary hospital in Papua New Guinea.

Because the prevalence of dengue fever in urban settings in Papua New Guinea is unknown, we investigated the presence of dengue using the NS1 antigen test in an outpatient-based prospective observational study at Port Moresby General Hospital. Of 140 patients with acute febrile illnesses, dengue fever was diagnosed in 14.9% (20 of 134; 95% confidence interval [95% CI] = 9.6-22.4). Malaria (2 of 137; 1.5%; 95% CI = 0.3-5.7), chikungunya (3 of 140; 2.1%; 95% CI = 0.6-6.6), and bacterial bloodstream infections (0 of 80; 0%; 95% CI = 0-5.7) were uncommon. Dengue fever should no longer be considered rare in Papua New Guinea.

An inactivated Ross River virus vaccine is well tolerated and immunogenic in an adult population in a randomized phase 3 trial.

Ross River virus (RRV) is endemic in Australia and several South Pacific Islands. More than 90,000 cases of RRV disease, which is characterized by debilitating polyarthritis, were reported in Australia in the last 20 years. There is no vaccine available to prevent RRV disease. A phase 3 study was undertaken at 17 sites in Australia to investigate the safety and immunogenicity of an inactivated whole-virus Vero cell culture-derived RRV vaccine in 1,755 healthy younger adults aged 16 to 59 years and 209 healthy older adults aged ≥60 years. Participants received a 2.5-µg dose of Al(OH)(3)-adjuvanted RRV vaccine, with a second and third dose after 3 weeks and 6 months, respectively. Vaccine-induced RRV-specific neutralizing and total IgG antibody titers were measured after each immunization. Vaccine safety was monitored over the entire study period. The vaccine was safe and well-tolerated after each vaccination. No cases of arthritis resembling RRV disease were reported. The most frequently reported systemic reactions were headache, fatigue, and malaise; the most frequently reported injection site reactions were tenderness and pain. After the third immunization, 91.5% of the younger age group and 76.0% of the older age group achieved neutralizing antibody titers of ≥1:10; 89.1% of the younger age group and 70.9% of the older age group achieved enzyme-linked immunosorbent assay (ELISA) titers of ≥11 PanBio units. A whole-virus Vero cell culture-derived RRV vaccine is well tolerated in an adult population and induces antibody titers associated with protection from RRV disease in the majority of individuals. (This study is registered at www.clinicaltrials.gov under registration no. NCT01242670.).

Mycoplasma genitalium and its resistance to azithromycin in incarcerated men from Far North Queensland.

This study examined the prevalence of Mycoplasma genitalium in incarcerated men from Far North Queensland as well as the prevalence of macrolide resistance in identified isolates. Overall, eight out of 140 [5.71% (95% CI 1.82-9.60)] urine samples tested positive and two out of eight (25%) samples carried a mutation in the 23S rRNA gene associated with macrolide resistance.

Male Circumcision and HIV Transmission; What Do We Know?

Male circumcision (MC) has been shown to be protective against heterosexual HIV transmission and is being explored in some parts of the world as a means of combating the epidemic. The World Health Organization (WHO) recommends that MC be considered as an important component of HIV prevention in high prevalence settings. We review evidence that demonstrates that the inner foreskin is likely to be the main portal of entry for the HIV virus in males. Whether removal of the inner foreskin accounts for all the protection afforded by circumcision is yet to be established. The proposed mechanisms of protection range from inherent immunohistological factors of foreskin such as difference in thickness of keratin layer and density of target cells for HIV between inner and outer foreskin to physiological mechanisms that follow male circumcision such as drying of secretions underneath foreskin after sexual intercourse, loss of microbiome that attract target cells to the genital mucosa and lack of priming the genital mucosa with less abundant sexual transmitted infections among circumcised men. The aim of this review is to give an updated account on the mechanisms proposed so far on the demonstrated 50-70% protection from HIV transmission through heterosexual intercourse, by male circumcision.

Acute undifferentiated fever in Asia: a review of the literature.

Acute undifferentiated fever (AUF) is a temporary febrile illness accompanied by non-specific symptoms. Previous studies in Asia have primarily focused on delineating specific agent(s) causing AUF. None were designed to assess the frequency of undiagnosed cases. This study aimed to review the case definition, laboratory investigations, etiologies and proportion of undiagnosed episodes of AUF. We reviewed nine studies, each employing different case definitions and diagnostic tools. Malaria, dengue, leptospirosis and rickettsial illnesses were frequently identified as the etiologies of AUF and the frequencies of undiagnosed cases ranged from 8% to 80%. An international consensus definition is required to compare the occurrence of AUF in different geographical sites, particularly if this condition were to be used as an indicator for the emergence or re-emergence of infectious agents. Use of general diagnostic tools for infectious diseases might reduce the proportion of undiagnosed AUF cases.

Women and HIV in a moderate prevalence setting: an integrative review.

BACKGROUND: Almost 32,000 people are living with human immunodeficiency virus (HIV) in Papua New Guinea (PNG). The primary route of transmission in this moderate prevalence setting is through heterosexual sex. Thus a gendered understanding of HIV is required to inform HIV prevention, treatment and care options. The aim of this review is to investigate understandings specifically about women and HIV in PNG and to identify gaps in the literature to inform future HIV research. METHODS: An integrative review of literature about women, HIV and PNG was conducted using a systematic search of online databases, including book chapters and grey literature. Prior to inclusion, literature was assessed using inclusion and exclusion criteria, and the Critical Appraisal Skills Programme (CASP) appraisal tool. Selected articles, book chapters and reports were coded and a constant comparative method of analysis used to construct a series of themes. RESULTS: The 26 articles, book chapters and reports included in the review were predominantly descriptive, original research (23/26 pieces of literature). Six themes were identified in the literature: economic, social and cultural factors (including mobility); gender issues (including violence against women); knowledge about HIV (including perception of risk of HIV); religious beliefs about HIV; women perceived as responsible for HIV transmission; and prevention of HIV. Literature about women and HIV in PNG is predominantly focussed upon women who sell sex, women as mothers or young women. Women are usually represented as either victims of HIV or responsible for transmitting HIV. Anthropological and social research has described the economic, social and cultural context along with the lived experience of HIV in PNG, but there is limited operations research or implementation research available. CONCLUSIONS: The literature reviewed has highlighted the importance of a gendered analysis of HIV prevention, care and treatment in PNG. There is an opportunity for operations, implementation and health systems research about HIV in PNG to shift research from description to action.

Implications of dengue outbreaks for blood supply, Australia.

Dengue outbreaks have increased in size and frequency in Australia, and transfusion-transmitted dengue poses a risk to transfusion safety. Using whole blood samples collected during the large 2008-2009 dengue epidemic, we estimated the risk for a dengue-infectious blood donation as ≈1 in 7,146 (range 2,218-50,021).

Antifungal therapy and management of complications of cryptococcosis due to Cryptococcus gattii.

BACKGROUND: We describe antifungal therapy and management of complications due to Cryptococcus gattii infection in 86 Australian patients followed for at least 12 months. METHODS: Patient data from culture-confirmed cases (2000-2007) were recorded at diagnosis, 6 weeks, 6 months, and 12 months. Clinical, laboratory, and treatment variables associated with raised intracranial pressure (ICP) and immune reconstitution inflammatory syndrome (IRIS) were determined. RESULTS: Seven of 10 patients with lung infection received amphotericin B (AMB) induction therapy (6 with 5-flucytosine [5-FC] for a median of 2 weeks); median duration of therapy including azole eradication therapy was 41 weeks, with a complete/partial clinical response in 78%. For neurologic disease, 88% of patients received AMB, 78% with 5-FC, for a median of 6 weeks. The median total course was 18 months. Nine patients receiving fluconazole induction therapy were reinduced with AMB plus 5-FC for clinical failure. Raised ICP (31 patients) was associated with initial abnormal neurology, and neurologic sequelae and/or death at 12 months (both P = .02); cerebrospinal fluid drains/shunts were placed in 58% of patients and in 64% of 22 patients with hydrocephalus. IRIS developed 2-12 months after starting antifungals in 8 patients, who presented with new/enlarging brain lesions. Risk factors included female sex, brain involvement at presentation, and higher median CD4 counts (all P < .05); corticosteroids reduced cryptococcoma-associated edema. CONCLUSIONS: Induction AMB plus 5-FC is indicated for C. gattii neurologic cryptococcosis (6 weeks) and when localized to lung (2 weeks). Shunting was often required to control raised ICP. IRIS presents with cerebral manifestations.

No evidence of prolonged Hendra virus shedding by 2 patients, Australia.

To better understand the natural history of Hendra virus infection and its tendency to relapse, 2 humans infected with this virus were monitored after acute infection. Virus was not detected in blood samples when patients were followed-up at 2 and 6 years. Thus, no evidence was found for prolonged virus shedding.

Clinical manifestations of Cryptococcus gattii infection: determinants of neurological sequelae and death.

BACKGROUND: Longer-term morbidity and outcomes of Cryptococcus gattii infection are not described. We analyzed clinical, microbiological, and outcome data in Australian patients followed for 12 months, to identify prognostic determinants. METHODS: Culture-confirmed C. gattii cases from 2000 to 2007 were retrospectively evaluated. Clinical, microbiological, radiological, and outcome data were recorded at diagnosis and at 6 weeks, 6 months, and 12 months. Clinical and laboratory variables associated with mortality and with death and/or neurological sequelae were determined. RESULTS: Annual C. gattii infection incidence was 0.61 per 10(6) population. Sixty-two of 86 (72%) patients had no immunocompromise; 6 of 24 immunocompromised hosts had idiopathic CD4 lymphopenia, and 1 had human immunodeficiency virus/AIDS. Clinical and microbiological characteristics of infection were similar in immunocompromised and healthy hosts. Isolated lung, combined lung and central nervous system (CNS), and CNS only disease was reported in 12%, 51% and 34% of the cases, respectively. Complications in CNS disease included raised intracranial pressure (42%), hydrocephalus (30%), neurological deficits (27%; 6% developed during therapy) and immune reconstitutionlike syndrome (11%). Geometric mean serum cryptococcal antigen (CRAG) titers in CNS disease were 563.9 (vs 149.3 in isolated lung infection). Patient immunocompromise was associated with increased mortality risk. An initial cerebrospinal fluid CRAG titer of ≥256 predicted death and/or neurological sequelae (P = .05). CONCLUSIONS: Neurological C. gattii disease predominates in the Australian endemic setting. Lumbar puncture and cerebral imaging, especially if serum CRAG titers are ≥512, are essential. Long-term follow up is required to detect late neurological complications. Immune system evaluation is important because host immunocompromise is associated with reduced survival.

Who brings dengue into North Queensland? A descriptive, exploratory study.

OBJECTIVE: To describe the demographics, patterns of assessment and treatment of people visiting a regional emergency department with potential diagnoses of malaria or dengue fever. DESIGN: To identify potential dengue fever cases, we used an indicator of recent overseas travel and fever that is a request for malaria testing. A chart audit of 301 medical records of people between 2008 and 2010 was conducted to describe patient characteristics, diagnostic tests performed and treatment. SETTING: A regional hospital located in the wet tropics. RESULTS: Malaria testing was most often performed on Australian citizens (64.1%), medical evacuees (20.3%) and tourists (18.6%). Overall, 49.8% of patients tested for malaria did not also have a dengue test, despite being indicated in 54% of this group. People tested for malaria usually lived in a residential house or unit (69.7%). Only 9% were staying in hotels and hostels. Oceania was the most commonly visited region in the two weeks prior to presentation. Malaria was diagnosed in 17.3% and dengue fever in 12% of patients tested. Patients with dengue fever were more likely than patients with malaria to self-refer to hospital, be staying in commercial accommodation and to have recently travelled to Southeast Asia. CONCLUSION: Both dengue fever and malaria occur predominantly in residents who reside in non-commercial accommodation. Efforts to identify imported dengue fever cases should focus on both tourists and local residents returning from overseas countries.

General practitioners' patterns of treatment of febrile travellers in north Queensland: an exploratory study.

In north Queensland, recurring epidemics of dengue fever are a public health concern. Each epidemic is initiated by an index case: an infected person arriving from an endemic country or region with dengue activity who then transmits the disease to local mosquitoes. A timely diagnosis of dengue in an index case and notification to public health services is essential to prevent epidemics. This qualitative study explores north Queensland general practitioners' experiences and patterns of treatment of febrile travellers. Individual, semi-structured interviews with 50 general practitioners working in north Queensland were conducted. Analysis of the data resulted in four themes for discussion: characteristics of febrile travellers presenting to local general practitioners, the cost of pathology tests as a barrier to diagnosis, appropriate pathology testing, and notifying tropical public health services. Recommendations from this study point to a need for ongoing education and training for general practitioners in best practice with regards pathology testing for suspected dengue fever cases. As well, there is a need to provide clearer guidelines to general practitioners on when to notify tropical public health services of suspicious diagnoses of dengue.

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.

Seroprevalence of herpes simplex virus type 1 and type 2 among the Indigenous population of Cape York, Far North Queensland, Australia.

BACKGROUND: The objective of this study was to obtain representative seroprevalence data for the Indigenous population of Far North Queensland by measuring the age- and sex-specific seroprevalence of the herpes simplex viruses (HSV-1 and HSV-2) in Cape York. METHODS: A cross-sectional seroprevalence study was conducted using de-identified serum samples collected from Indigenous patients living in Cape York, aged 16 years or older, who sought medical care between August 2007 and May 2008. An age- and sex-stratified random sample of 270 sera was tested for the presence of antibodies to HSV-1 and HSV-2 using commercially available enzyme-linked immunosorbent assays. Indeterminate results were resolved with western blot. RESULTS: The overall seroprevalence for the Indigenous population of Cape York was 97.8% for HSV-1 and 58.5% for HSV-2. There was a statistically significant difference in HSV-2 seroprevalence according to sex (P < 0.001). Females were more likely to be HSV-2 seropositive compared with males (72.1% and 43.8%, respectively). CONCLUSIONS: This is the first study to report on the seroprevalence of HSV-1 and HSV-2 among the Indigenous population of Cape York. This study has identified a population with an extremely high prevalence of HSV-1 and HSV-2 infection. The seroprevalence of HSV-2 in this population was found to be five times higher than that reported for the general adult Australian population. These results will be invaluable to the implementation of appropriate prevention and control strategies against HSV infection and are especially important considering the strong association between HSV-2 and the acquisition and transmission of HIV.