A survey on Mycobacterium ulcerans in Mosquitoes and March flies captured from endemic areas of Northern Queensland, Australia.

Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU). This nontuberculous mycobacterial infection has been reported in 34 countries worldwide. In Australia, the majority of cases of BU have been recorded in coastal Victoria and the Mossman-Daintree areas of north Queensland. Mosquitoes have been postulated as a vector of M. ulcerans in Victoria, however the specific mode of transmission of this disease is still far from being well understood. In the current study, we trapped and analysed 16,900 (allocated to 845 pools) mosquitoes and 296 March flies from the endemic areas of north Queensland to examine for the presence of M. ulcerans DNA by polymerase chain reaction. Seven of 845 pools of mosquitoes were positive on screening using the IS2404 PCR target (maximum likelihood estimate 0.4/1,000). M. ulcerans DNA was detected from one pool of mosquitoes from which all three PCR targets: IS2404, IS2606 and the ketoreductase B domain of mycolactone polyketide synthase gene were detected. None of the March fly samples were positive for the presence of M. ulcerans DNA.

Potential Animal Reservoir of Mycobacterium ulcerans: A Systematic Review.

Mycobacterium ulcerans is the causative agent of Buruli ulcer, also known in Australia as Daintree ulcer or Bairnsdale ulcer. This destructive skin disease is characterized by extensive and painless necrosis of the skin and soft tissue with the formation of large ulcers, commonly on the leg or arm. To date, 33 countries with tropical, subtropical and temperate climates in Africa, the Americas, Asia and the Western Pacific have reported cases of Buruli ulcer. The disease is rarely fatal, although it may lead to permanent disability and/or disfigurement if not treated appropriately or in time. It is the third most common mycobacterial infection in the world after tuberculosis and leprosy. The precise mode of transmission of M. ulcerans is yet to be elucidated. Nevertheless, it is possible that the mode of transmission varies with different geographical areas and epidemiological settings. The knowledge about the possible routes of transmission and potential animal reservoirs of M. ulcerans is poorly understood and still remains patchy. Infectious diseases arise from the interaction of agent, host and environment. The majority of emerging or remerging infectious disease in human populations is spread by animals: either wildlife, livestock or pets. Animals may act as hosts or reservoirs and subsequently spread the organism to the environment or directly to the human population. The reservoirs may or may not be the direct source of infection for the hosts; however, they play a major role in maintenance of the organism in the environment, and in the mode of transmission. This remains valid for M. ulcerans. Possums have been suggested as one of the reservoir of M. ulcerans in south-eastern Australia, where possums ingest M. ulcerans from the environment, amplify them and shed the organism through their faeces. We conducted a systematic review with selected key words on PubMed and INFORMIT databases to aggregate available published data on animal reservoirs of M. ulcerans around the world. After certain inclusion and exclusion criteria were implemented, a total of 17 studies was included in the review. A variety of animals around the world e.g., rodents, shrews, possums (ringtail and brushtail), horses, dogs, alpacas, koalas and Indian flap-shelled turtles have been recorded as being infected with M. ulcerans. The majority of studies included in this review identified animal reservoirs as predisposing to the emergence and reemergence of M. ulcerans infection. Taken together, from the selected studies in this systematic review, it is clear that exotic wildlife and native mammals play a significant role as reservoirs for M. ulcerans.

Mycoplasma genitalium in the Far North Queensland backpacker population: An observational study of prevalence and azithromycin resistance.

BACKGROUND: Mycoplasma genitalium is a sexually transmitted infection (STI), and a common cause of non-gonococcal urethritis (NGU). There is concern regarding the rise in prevalence of M. genitalium and rates of resistance to macrolide antibiotics. International backpackers represent a unique population that may be at an increased risk of STIs. The purpose of this study was to determine the prevalence of M. genitalium and antibiotic resistance in international backpackers. METHODS: First void urine samples were obtained utilising opportunistic sampling from 294 non-treatment-seeking international backpackers at a variety of hostels in Cairns, Queensland Australia. Participants also answered a fixed-answer survey regarding sociodemographic characteristics and sexual risk behaviours. Samples were tested for M. genitalium, Chlamydia trachomatis and Neisseria gonorrhoeae using polymerase chain reaction (PCR). Samples positive for M. genitalium were investigated for macrolide resistance-associated mutations in the 23S rRNA genome at positions A2058G, A2058C, A2058T, A2059G and A2059C (Escherichia coli numbering). RESULTS: Of the 294 samples, 23 failed the internal control. The prevalence of M. genitalium was 1.8% (5/271, 95% confidence interval [CI] ± 1.58), C. trachomatis was 4.1% (11/271, 95% CI ± 2.36) and N. gonorrhoeae was not detected. Macrolide resistance-associated mutations were identified in 40% (2/5) of M. genitalium-positive samples. M. genitalium infection was associated with reporting symptoms (odds ratio [OR] 14.36, 95% CI 2.17-94.94, p < 0.05). CONCLUSIONS: M. genitalium and C. trachomatis are relatively common amongst non-treatment seeking international backpackers, but may not differ from Australian population prevalence. This article provides evidence to further support the increased utilisation of M. genitalium PCR in the diagnosis of NGU, and for macrolide resistance testing for all identified M. genitalium infections.

Re-establishing safer medical-circumcision-integrated initiation ceremonies for HIV prevention in a rural setting in Papua New Guinea. A multi-method acceptability study.

BACKGROUND: Efforts to stem the spread of Human Immunodeficiency Virus (HIV) in Papua New Guinea (PNG) are hampered by multiple interrelated factors including limited health services, extreme diversities in culture and language and highly prevalent gender inequity, domestic violence and poverty. In the rural district of Yangoru-Saussia, a revival of previously ceased male initiation ceremonies (MICs) is being considered for a comprehensive approach to HIV prevention. In this study, we explore the local acceptability of this undertaking including replacing traditional penile cutting practices with medical male circumcision (MMC). METHODS: A multi-method study comprising three phases. Phase one, focus group discussions with male elders to explore locally appropriate approaches to HIV prevention; Phase two, interviews and a cross-sectional survey with community men and women to assess views on MICs that include MMC for HIV prevention; Phase three, interviews with cultural leaders and a cross sectional survey to assess the acceptability of replacing traditional penile bleeding with MMC. RESULTS: Cultural leaders expressed that re-establishing MICs was locally appropriate for HIV prevention given the focus on character building and cultural preservation. Most surveyed participants (81.5%) supported re-establishing MICs and 92.2% supported adapting MICs with MMC. Changes to penile bleeding emerged as a contentious and contested issue given its cultural significance in symbolizing initiates' transition from childhood to adulthood. Participants were concerned about potential clash with modern education, introduced religious beliefs and limited government support in leadership and funding. CONCLUSIONS: Most people in this study in Yangoru-Saussia support re-establishing MICs and replacing traditional penile bleeding with MMC. This culturally-sensitive alignment of MMC (and HIV prevention) with revived MICs responds to a national health priority in PNG and acts as an example of providing culturally-sensitive male circumcision for HIV prevention recommended by WHO/UNAIDS. However, the implementation of this undertaking will require considerable effort, especially when modern pursuits in education and religion must be factored and when there is expectation for local authorities to lead and provide funding.

Synthetic B-Cell Epitopes Eliciting Cross-Neutralizing Antibodies: Strategies for Future Dengue Vaccine.

Dengue virus (DENV) is a major public health threat worldwide. A key element in protection from dengue fever is the neutralising antibody response. Anti-dengue IgG purified from DENV-2 infected human sera showed reactivity against several peptides when evaluated by ELISA and epitope extraction techniques. A multi-step computational approach predicted six antigenic regions within the E protein of DENV-2 that concur with the 6 epitopes identified by the combined ELISA and epitope extraction approach. The selected peptides representing B-cell epitopes were attached to a known dengue T-helper epitope and evaluated for their vaccine potency. Immunization of mice revealed two novel synthetic vaccine constructs that elicited good humoral immune responses and produced cross-reactive neutralising antibodies against DENV-1, 2 and 3. The findings indicate new directions for epitope mapping and contribute towards the future development of multi-epitope based synthetic peptide vaccine.

Chest pain risk assessment in Indigenous and non-Indigenous Australians using HEART Score.

OBJECTIVE: The objectives of this study were to investigate factors that correlate to cardiac events within 30 days in Indigenous and non-Indigenous Australians who present to ED with chest pain and to describe the predictive ability of the HEART Score in these groups. METHODS: Patients who presented with chest pain between 1 January 2013 and 16 May 2013 in a university hospital were retrospectively enrolled in the study. HEART Scores were retrospectively assigned to participants. The study's end-point was Major Adverse Cardiac Events (MACE) within 30 days. RESULTS: Participants (678) were enrolled in the study, of which 148 were Indigenous Australian. Twenty-eight percent of Indigenous Australian participants and 19% of non-Indigenous Australian participants were diagnosed with MACE within 30 days. Within the Indigenous Australian participant cohort, 1.6% of those with HEART Scores 0-3, 29% of those with HEART Scores 4-6 and 96% of those with HEART Scores 7-10 were diagnosed with MACE within 30 days. Within the non-Indigenous Australian participant cohort, 0.58% of those with HEART Scores 0-3, 17% of those with HEART Scores 4-6 and 79% of those with HEART Scores 7-10 were diagnosed with MACE within 30 days. The negative predictive value of HEART Scores 0-3 for ruling out MACE within 30 days was 98% for Indigenous participants and 99% for non-Indigenous participants. CONCLUSION: The HEART Score is a reliable predictor of patient outcome in both Indigenous and non-Indigenous Australians. Modification of the HEART Score may not be required for use in the Indigenous Australian population who present to the ED with chest pain.

Men in Papua New Guinea accurately report their circumcision status.

BACKGROUND: Male circumcision (MC) is a well-established component of HIV prevention in countries with high HIV prevalence and heterosexually driven epidemics. Delivery and monitoring of MC programs are reliant on good quality MC data. Such data are often generated through self-reported MC status surveys. This study examined self-reported MC status in comparison with genital photographs from men in Papua New Guinea (PNG). METHODS: This retrospective non-interventional study collated self-reported MC status data from the 'acceptability and feasibility of MC' study at 4 sites in PNG during 2010-2011. Participants reported their MC status based on an 8-category photographic classification covering the range of foreskin cutting practices in PNG. Genital photographs of 222 participants from this study were independently classified by 2 investigators. The 8-category photographic classification was simplified into a 3 category classification of 'no cut', 'straight cut' and 'round cut' before comparing for agreement between self-reporting and investigator assessment using Cohen's Kappa measure. RESULTS: Using the 3-category classification, there was 90.6% (201/222) agreement between self-assessment and investigator classification (κ value 0.805). Of the discordant 9.4% (21/222), 3.6% (8/222) self-classified as having a cut foreskin (5 straight cut; 3 round cut) while investigators classified as having no cut; 4.1% (9/222) self-classified as having no cut while investigators classified them as having had a cut (6 straight cut; 3 round cut) and 1.8% (4/222) self-classified as having a round cut while investigators classified as having a straight cut. Given the great variety of foreskin cutting practices and appearances, feasible explanations are suggested for two-thirds (13/21) of these discordant results. CONCLUSIONS: This study demonstrates a high level of agreement between self-reporting and investigator assessment of MC status in PNG and suggests self-reporting of MC status to be highly reliable among men in PNG.

Undiagnosed undifferentiated fever in Far North Queensland, Australia: a retrospective study.

OBJECTIVES: This study aimed to describe the causes of acute undifferentiated fever (AUF) and to develop a robust definition of undiagnosed undifferentiated fever (UUDF). METHODS: This was a retrospective study of AUF over 3 years (2008-2011) in an Australian tertiary hospital. Request for laboratory investigation of one or more infectious agents was used as the search tool. RESULTS: A total of 340 patients with AUF, aged 15-65 years, were identified over the study period. A final diagnosis was made in 147 (43.2%) patients, dengue fever being the most frequent. The aetiology of fever was not determined in 193 (56.8%) patients. Elevations of C-reactive protein (CRP) and hepatic aminotransferase levels were common in these patients; two patients died. The characteristics of UUDF were fever for ≤21 days and failure to reach a diagnosis after clinical evaluation and specific laboratory investigations. CONCLUSION: The high burden of UUDF argues for a better diagnostic approach to fever that is capable of identifying a broad range of infectious agents.

Researching male circumcision for HIV prevention in Papua New Guinea: a process that incorporates science, faith and culture.

BACKGROUND: Undertaking HIV research in the culturally diverse Pacific nation of Papua New Guinea (PNG) requires careful consideration of social, cultural and religious beliefs and practices. Here, we share a detailed description of culturally informed research processes and lessons learned from the first ever study undertaken on male circumcision for HIV prevention at a faith-based university in PNG. METHODS: Male and female staff and students at Pacific Adventist University were invited to complete an anonymous self-administered questionnaire, and/or participate in a semi-structured interview or focus group discussion. Male participants were invited for clinical examination. Results were collated and disseminated to the university community in gender segregated sessions. The study deliberately partnered with student leaders and centralised social, cultural, and religious paradigms. Student leaders were interviewed about their experience of partnering in sensitive health research. RESULTS: The student leaders reported that pre-existing relationships, cultural ties, gendered sensitivity and regular communication reinforced trust between researchers, student leaders and participants, and helped the success of the study. The amount of time, complex logistics and social and cultural relationships between single and married staff and students were highlighted as challenges. CONCLUSIONS: Partnering with regional student leaders to plan and implement the study gave a legitimate and immediate mechanism for involving PNG staff and students in this sensitive health research. Gendered research processes utilised established social and cultural structures and ensured the safety of participants; all of these factors contributed to the acceptability of the study. Capacity was strengthened in PNG and Australian researchers to undertake sensitive HIV research in PNG. The study demonstrated that it is possible to conduct sensitive sexual health research at a faith-based university in PNG.

Foreskin cutting beliefs and practices and the acceptability of male circumcision for HIV prevention in Papua New Guinea.

BACKGROUND: Male circumcision (MC) reduces HIV acquisition and is a key public health intervention in settings with high HIV prevalence, heterosexual transmission and low MC rates. In Papua New Guinea (PNG), where HIV prevalence is 0.8%, there is no medical MC program for HIV prevention. There are however many different foreskin cutting practices across the country's 800 language groups. The major form exposes the glans but does not remove the foreskin. This study aimed to describe and quantify foreskin cutting styles, practices and beliefs. It also aimed to assess the acceptability of MC for HIV prevention in PNG. METHODS: Cross-sectional multicentre study, at two university campuses (Madang Province and National Capital District) and at two 'rural development' sites (mining site Enga Province; palm-oil plantation in Oro Province). Structured questionnaires were completed by participants originating from all regions of PNG who were resident at each site for study or work. RESULTS: Questionnaires were completed by 861 men and 519 women. Of men, 47% reported a longitudinal foreskin cut (cut through the dorsal surface to expose the glans but foreskin not removed); 43% reported no foreskin cut; and 10% a circumferential foreskin cut (complete removal). Frequency and type of cut varied significantly by region of origin (p < .001). Most men (72-82%) were cut between the ages of 10-20 years. Longitudinal cuts were most often done in a village by a friend, with circumferential cuts most often done in a clinic by a health professional. Most uncut men (71%) and longitudinal cut men (84%) stated they would remove their foreskin if it reduced the risk of HIV infection. More than 95% of uncut men and 97% of longitudinal cut men would prefer the procedure in a clinic or hospital. Most men (90%) and women (74%) stated they would remove the foreskin of their son if it reduced the risk of HIV infection. CONCLUSION: Although 57% of men reported some form of foreskin cut only 10% reported the complete removal of the foreskin, the procedure on which international HIV prevention strategies are based. The acceptability of MC (complete foreskin removal) is high among men (for themselves and their sons) and women (for their sons). Potential MC services need to be responsive to the diversity of beliefs and practices and consider health system constraints. A concerted research effort to investigate the potential protective effects of longitudinal cuts for HIV acquisition is essential given the scale of longitudinal cuts in PNG.

Biogeography of Burkholderia pseudomallei in the Torres Strait Islands of Northern Australia.

It has been hypothesized that biogeographical boundaries are a feature of Burkholderia pseudomallei ecology, and they impact the epidemiology of melioidosis on a global scale. This study examined the relatedness of B. pseudomallei sourced from islands in the Torres Strait of Northern Australia to determine if the geography of isolated island communities is a determinant of the organisms' dispersal. Environmental sampling on Badu Island in the Near Western Island cluster recovered a single clone. An additional 32 clinical isolates from the region were sourced. Isolates were characterized using multilocus sequence typing and a multiplex PCR targeting the flagellum gene cluster. Gene cluster analysis determined that 69% of the isolates from the region encoded the ancestral Burkholderia thailandensis-like flagellum and chemotaxis gene cluster, a proportion significantly lower than that reported from mainland Australia and consistent with observations of isolates from southern Papua New Guinea. A goodness-of-fit test indicated that there was geographic localization of sequence types throughout the archipelago, with the exception of Thursday Island, the economic and cultural hub of the region. Sequence types common to mainland Australia and Papua New Guinea were identified. These findings demonstrate for the first time an environmental reservoir for B. pseudomallei in the Torres Strait, and multilocus sequence typing suggests that the organism is not randomly distributed throughout this region and that seawater may provide a barrier to dispersal of the organism. Moreover, these findings support an anthropogenic dispersal hypothesis for the spread of B. pseudomallei throughout this region.

Contribution of dengue fever to the burden of acute febrile illnesses in Papua New Guinea: an age-specific prospective study.

Malaria is a major contributor to the burden of febrile illnesses in Papua New Guinea (PNG). Dengue fever (DF) is likely to contribute; however, its epidemiology in PNG is poorly understood. We performed a prospective age-stratified study in outpatient clinics investigating the prevalence of DF; 578 patients were enrolled, and 317 patients with a negative rapid diagnostic test (RDT) for malaria were tested for dengue. Malaria was confirmed in 52% (301/578, 95% confidence interval [CI] = 48-56%), DF was diagnosed in 8% (46/578, 95% CI = 6-10%), and 40% (95% CI = 36-44%) had neither diagnosis. Among the 317 malaria RDT-negative patients, 14% (45/317, 95% CI = 10-18%) had DF. The seroprevalence of dengue immunoglobulin G (IgG) was 83% (204/247, 95% CI = 78-87%), and no dengue hemorrhagic fever was seen. This study provides good evidence for the first time that DF is common in PNG and is responsible for 8% of fever episodes. The common occurrence of DF in a population with presumed previous exposure to dengue is an important observation.

Human immunodeficiency virus and respiratory disorders: clinical and diagnostic considerations.

Respiratory infections are a major health burden for the people of Papua New Guinea (PNG) who are positive for human immunodeficiency virus (HIV). In the face of an ongoing HIV epidemic, little is known about the epidemiology and aetiology of respiratory infections in people living with HIV in PNG. In this article we provide an overview of the most important respiratory pathogens in HIV-positive people globally, focusing primarily on adults. Particular attention is given to respiratory viruses, bacterial pathogens such as Streptococcus pneumoniae and Mycobacterium tuberculosis, and Pneumocystis jiroveci. In doing so we highlight the need for a better understanding of the aetiology of respiratory infections in HIV-positive people in PNG. A study is underway that aims to determine the aetiology of common infectious illnesses in HIV-positive people in PNG, focusing on respiratory infections, diarrhoeal diseases and febrile illness. The results of this study should guide future prevention, diagnostic and treatment strategies.

Evaluation of dengue NS1 test kits for the diagnosis of dengue fever.

Detection of the dengue NS1 antigen during the symptomatic phase of illness represents an important advance in the diagnosis of dengue fever. The sensitivity of 2 commercial kits was evaluated in a panel of 91 serum samples collected at defined intervals after onset of symptomatic dengue fever. The sensitivity of the Bio-Rad Platelia (Bio-Rad Laboratories, Marnes-La-Coquette, France) dengue NS1 assay was 73.6% (95% confidence interval [CI], 63.7-81.6). The Panbio Early ELISA (Panbio Diagnostics, Brisbane, Australia) had a sensitivity of 63.7% (95% CI, 53.5-72.9). Four samples were equivocal in the Panbio assay. The sensitivity of both assays was highest on the 2nd to 4th day after illness onset and in primary dengue infections. Both assays will be useful for the detection of dengue viral infections early in the course of the infection, especially in nonendemic countries.

Infections in travellers arriving from Australia.

An unwell traveller whose itinerary has included Australia may be infected with agents that are uniquely found in that country or by more cosmopolitan agents that exist there. This brief review will discuss some of the more common or important infectious disease diagnoses and discuss some features that can be elicited on examination or from the history that would be useful in directing investigation and treatment. Diseases discussed include epidemic polyarthritis, dengue fever, Murray Valley encephalitis, melioidosis, leptospirosis, Buruli ulcer, scrub typhus and spotted fever.