Neglected tropical diseases in Australia: a narrative review.

•Neglected tropical diseases (NTDs) represent a threat to the health, wellbeing and economic prosperity of billions of people worldwide, often causing serious disease or death. •Commonly considered diseases of low and middle-income nations, the presence of NTDs in high income countries such as Australia is often overlooked. •Seven of the 20 recognised NTDs are endemic in Australia: scabies, soil-transmitted helminths and strongyloidiasis, echinococcosis, Buruli ulcer, leprosy, trachoma, and snakebite envenoming. •Dengue, while not currently endemic, poses a risk of establishment in Australia. There are occasional outbreaks of dengue fever, with local transmission, due to introductions in travellers from endemic regions. •Similarly, the risk of introduction of other NTDs from neighbouring countries is a concern. Many NTDs are only seen in Australia in individuals travelling from endemic areas, but they need to be recognised in health settings as the potential consequences of infection can be severe. •In this review, we consider the status of NTDs in Australia, explore the risk of introducing and contracting these infections, and emphasise the negative impact they have on the health of Australians, especially Aboriginal and Torres Strait Islander peoples.

Enteric pathogen infection and consequences for child growth in young Aboriginal Australian children: a cross-sectional study.

BACKGROUND: To determine the prevalence of enteric infections in Aboriginal children aged 0-2 years using conventional and molecular diagnostic techniques and to explore associations between the presence of pathogens and child growth. METHODS: Cross-sectional analysis of Aboriginal children (n = 62) residing in a remote community in Northern Australia, conducted from July 24th - October 30th 2017. Stool samples were analysed for organisms by microscopy (directly in the field and following fixation and storage in sodium-acetate formalin), and by qualitative PCR for viruses, bacteria and parasites and serology for Strongyloides-specific IgG. Child growth (height and weight) was measured and z scores calculated according to WHO growth standards. RESULTS: Nearly 60% of children had evidence for at least one enteric pathogen in their stool (37/62). The highest burden of infection was with adenovirus/sapovirus (22.9%), followed by astrovirus (9.8%) and Cryptosporidium hominis/parvum (8.2%). Non-pathogenic organisms were detected in 22.5% of children. Ten percent of children had diarrhea at the time of stool collection. Infection with two or more pathogens was negatively associated with height for age z scores (- 1.34, 95% CI - 2.61 to - 0.07), as was carriage of the non-pathogen Blastocystis hominis (- 2.05, 95% CI - 3.55 to - 0.54). CONCLUSIONS: Infants and toddlers living in this remote Northern Australian Aboriginal community had a high burden of enteric pathogens and non-pathogens. The association between carriage of pathogens/non-pathogens with impaired child growth in the critical first 1000 days of life has implications for healthy child growth and development and warrants further investigation. These findings have relevance for many other First Nations Communities that face many of the same challenges with regard to poverty, infections, and malnutrition.

Chronic strongyloidiasis - Don't look and you won't find.

BACKGROUND: Strongyloidiasis is one of the most neglected tropical diseases and it exists in Australia. Patients may have acquired their initial infection while in an endemic area. Because of the autoinfective cycle of Strongyloides stercoralis, the causative agent, these patients may remain infected for life unless effectively treated. Corticosteroids have precipitated death in more than 60% of disseminated strongyloidiasis cases. OBJECTIVE: The aim of this article is to raise awareness of the unique features of S. stercoralis and outline the important role that general practitioners (GPs) have in diagnosing and treating chronic strongyloidiasis, as well as in preventing cases of fatal hyperinfection. DISCUSSION: Chronic strongyloidiasis is not an overt disease - if you don't look for it, you won't find it. In particular, patients who have lived in an endemic area or have unexplained eosinophilia must be checked for the presence of the parasite before initiation of steroid or immunosuppressive therapy. These patients, if infected, may develop hyperinfective syndrome, which has a high fatality rate.

Current pharmacotherapeutic strategies for Strongyloidiasis and the complications in its treatment.

INTRODUCTION: Strongyloidiasis, an infection caused by the soil-transmitted helminth Strongyloides stercoralis, can lead immunocompromised people to a life-threatening syndrome. We highlight here current and emerging pharmacotherapeutic strategies for strongyloidiasis and discuss treatment protocols according to patient cohort. We searched PubMed and Embase for papers published on this topic between 1990 and May 2022. AREAS COVERED: Ivermectin is the first-line drug, with an estimated efficacy of about 86% and excellent tolerability. Albendazole has a lower efficacy, with usage advised when ivermectin is not available or not recommended. Moxidectin might be a valid alternative to ivermectin, with the advantage of being a dose-independent formulation. EXPERT OPINION: The standard dose of ivermectin is 200 µg/kg single dose orally, but multiple doses might be needed in immunosuppressed patients. In the case of hyperinfection, repeated doses are recommended up to 2 weeks after clearance of larvae from biological fluids, with close monitoring and further dosing based on review. Subcutaneous ivermectin is used where there is impaired intestinal absorption/paralytic ileus. In pregnant or lactating women, studies have not identified increased risk with ivermectin use. However, with limited available data, a risk-benefit assessment should be considered for each case.

HTLV-I and Strongyloides in Australia: The worm lurking beneath.

Strongyloidiasis and HTLV-I (human T-lymphotropic virus-1) are important infections that are endemic in many countries around the world with an estimated 370 million infected with Strongyloides stercoralis alone, and 5-10 million with HTVL-I. Co-infections with these pathogens are associated with significant morbidity and can be fatal. HTLV-I infects T-cells thus causing dysregulation of the immune system which has been linked to dissemination and hyperinfection of S. stercoralis leading to bacterial sepsis which can result in death. Both of these pathogens are endemic in Australia primarily in remote communities in Queensland, the Northern Territory, and Western Australia. Other cases in Australia have occurred in immigrants and refugees, returned travellers, and Australian Defence Force personnel. HTLV-I infection is lifelong with no known cure. Strongyloidiasis is a long-term chronic disease that can remain latent for decades, as shown by infections diagnosed in prisoners of war from World War II and the Vietnam War testing positive decades after they returned from these conflicts. This review aims to shed light on concomitant infections of HTLV-I with S. stercoralis primarily in Australia but in the global context as well.

Patient narratives of illnesses requiring abdominal surgery in Cambodia: Heroic/stoic, and dealing with 'the ball of meat'.

This study describes the illness narratives that inform treatment-seeking behaviours for acute abdominal conditions in Cambodia, and thereby explores factors impeding the timely delivery of surgical intervention. Semi-structured qualitative interviews were undertaken with patients who had undergone abdominal surgery at Siem Reap Provincial Hospital between 2011 and 2014. Interviews collected basic demographic information and also patient narratives based on Groleau's McGill Illness Narrative Interview (MINI). Interviews were contemporaneously translated from Khmer to English and recorded for transcription. A content analysis of interview transcripts based on narrative enquiry was undertaken. Ninety-seven patients participated in the study and five themes emerged from the data. These were: Explanatory models about the causes of abdominal pain and effects of surgery; Pre-surgery stoicism and illness management; Fear of poor outcomes and death; Burden of treatment costs and anticipated recovery time; and, Enhancing community trust in surgery. Our findings add the patient voice to the limited evidence about access to surgery, and socio-cultural and financial barriers affecting treatment-seeking behaviours in Cambodia. By understanding the collective narratives surrounding experiences of abdominal surgery, efforts to improve surgical services in Cambodia may be better informed of the reasons patients delay treatment.

Integrating testing for chronic strongyloidiasis within the Indigenous adult preventive health assessment system in endemic communities in the Northern Territory, Australia: An intervention study.

BACKGROUND: The life-threatening clinical manifestations of strongyloidiasis are preventable with early detection and effective treatment. The aim of this study was to assess if there was an increase to the number and proportion of persons tested for chronic strongyloidiasis, as a result of integrating Strongyloides stercoralis serology into the existing preventive health assessment system in four Aboriginal health services in endemic communities. METHODOLOGY: A prospective, longitudinal, before-and-after intervention study was conducted in four Aboriginal health services in remote endemically infected communities in the Northern Territory, Australia, from July 2012 to December 2016. The electronic patient information and recall systems enabled the integration of Strongyloides stercoralis serology into the adult preventive health assessment. Strongyloides reports for each health service were extracted half-yearly to examine the number and proportion of persons tested for chronic strongyloidiasis during the study and to measure the effect of the intervention. PRINCIPAL FINDINGS: The number and proportion of persons tested increased significantly during the study. From a total resident population of 3650 Indigenous adults over 15 years of age, 1686 persons (47.4%) were tested. The percentage of adults who had at least one serology test increased in all four health services to between 41% (446/1086) and 81.9% (172/210). Of the 1686 persons tested, 680 positive cases of chronic strongyloidiasis (40.3%) were identified. CONCLUSIONS/SIGNIFICANCE: This population health systems intervention increased the number and proportion of persons tested for chronic strongyloidiasis in four health services in endemically infected communities. This intervention is relevant to other health services with high-risk populations.

Effective diagnostic tests and anthelmintic treatment for Strongyloides stercoralis make community control feasible.

Strongyloides stercoralis is endemic in tropical and subtropical countries, and is prevalent particularly in economically impoverished people. Although an estimated 30 to 100 million people world-wide suffer from S. stercoralis infection and it is a life-long disease, it remains a neglected tropical disease. Faecal testing for S. stercoralis is very insensitive. The prevalence of S. stercoralis in Indigenous Australians (up to 60%) is much higher than previously thought, and its prevalence in Papua New Guinea is likely to be much higher than currently believed. When S. stercoralis and the HTLV-1 virus coexist in the one person, both diseases progress more quickly than when either infection is on its own. When people become infected with S. stercoralis, they develop acute strongyloidiasis which may be life threatening. At any time during the course of the disease, if the immune system is suppressed, most often by corticosteroid drugs, infected people may develop hyperinfective strongyloidiasis and they will die unless the underlying S. stercoralis infection is effectively treated. The use of serology for diagnosis, together with ivermectin treatment, has revealed that it is possible to eradicate S. stercoralis from the patient, and serology can also define the effectiveness of treatment. The reservoir of infection is humans; the free-living stages are short-lived. Mass treatment may be effective at eliminating S. stercoralis from a community. Safe water and effective sanitation alone do not lead to elimination of S. stercoralis. Up-to-date knowledge of S. stercoralis has been revealed through the workshops of the National Strongyloides Working Group in Australia and is summarized here. Much of this information is now available on the world wide web, and the addresses of relevant web sites are given.

The Unique Life Cycle of Strongyloides stercoralis and Implications for Public Health Action.

Strongyloides stercoralis has one of the most complex life cycles of the human-infecting nematodes. A common misconception in medical and public health professions is that S. stercoralis in its biology is akin to other intestinal nematodes, such as the hookworms. Despite original evidence provided by medical and veterinary research about this unique helminth, many assumptions have entered the scientific literature. This helminth is set apart from others that commonly affect humans by (a) the internal autoinfective cycle with autoinfective larvae randomly migrating through tissue, parthenogenesis, and the potential for lifelong infection in the host, the profound pathology occurring in hyperinfection and systemic manifestations of strongyloidiasis, and (b) a limited external cycle with a single generation of free-living adults. This paper aims to review and discuss original research on the unique life cycle of S. stercoralis that distinguishes it from other helminths and highlight areas where increased understanding of the parasite's biology might lead to improved public health prevention and control strategies.

Argument for Inclusion of Strongyloidiasis in the Australian National Notifiable Disease List.

Strongyloidiasis is an infection caused by the helminth, Strongyloides stercoralis. Up to 370 million people are infected with the parasite globally, and it has remained endemic in the Indigenous Australian population for many decades. Strongyloidiasis has been also reported in other Australian populations. Ignorance of this disease has caused unnecessary costs to the government health system, and been detrimental to the Australian people's health. This manuscript addresses the 12 criteria required for a disease to be included in the Australian National Notifiable Disease List (NNDL) under the National Health Security Act 2007 (Commonwealth). There are six main arguments that provide compelling justification for strongyloidiasis to be made nationally notifiable and added to the Australian NNDL. These are: The disease is important to Indigenous health, and closing the health inequity gap between Indigenous and non-Indigenous Australians is a priority; a public health response is required to detect cases of strongyloidiasis and to establish the true incidence and prevalence of the disease; there is no alternative national surveillance system to gather data on the disease; there are preventive measures with high efficacy and low side effects; data collection is feasible as cases are definable by microscopy, PCR, or serological diagnostics; and achievement of the Sustainable Development Goal (SDG) # 6 on clean water and sanitation.

Strongyloides seroprevalence before and after an ivermectin mass drug administration in a remote Australian Aboriginal community.

BACKGROUND: Strongyloides seroprevalence is hyper-endemic in many Australian Aboriginal and Torres Strait Islander communities, ranging from 35-60%. We report the impact on Strongyloides seroprevalence after two oral ivermectin mass drug administrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community. METHODS: Utilizing a before and after study design, we measured Strongyloides seroprevalence through population census with sequential MDAs at baseline and month 12. Surveys at months 6 and 18 determined changes in serostatus. Serodiagnosis was undertaken by ELISA that used sonicated Strongyloides ratti antigen to detect anti-Strongyloides IgG. Non-pregnant participants weighing ≥15 kg were administered a single 200 µg/kg ivermectin dose, repeated after 10-42 days if Strongyloides and/or scabies was diagnosed; others followed a standard alternative algorithm. A questionnaire on clinical symptoms was administered to identify adverse events from treatment and self-reported symptoms associated with serostatus. FINDINGS: We surveyed 1013 participants at the baseline population census and 1060 (n = 700 from baseline cohort and 360 new entrants) at month 12. Strongyloides seroprevalence fell from 21% (175/818) at baseline to 5% at month 6. For participants from the baseline cohort this reduction was sustained at month 12 (34/618, 6%), falling to 2% at month 18 after the second MDA. For new entrants to the cohort at month 12, seroprevalence reduced from 25% (75/297) to 7% at month 18. Strongyloides positive seroconversions for the baseline cohort six months after each MDA were 2.5% (4/157) at month 6 and 1% at month 18, whilst failure to serorevert remained unchanged at 18%. At 12 months, eosinophilia was identified in 59% of baseline seropositive participants and 89% of seropositive new entrants, compared with 47%baseline seronegative participants and 51% seronegative new entrants. Seropositivity was not correlated with haemoglobin or any self-reported clinical symptoms. Clinical symptoms ascertained on the day of treatment and 24-72 hrs after, did not identify any adverse events. SIGNIFICANCE: Two community ivermectin MDAs delivered 12 months apart by trained Aboriginal researchers in collaboration with non-Indigenous researchers resulted in a sustained and significant reduction in Strongyloides seroprevalence over 18 months. Similar reductions were seen in the baseline cohort and new entrants.

Utility of serological follow-up of chronic strongyloidiasis after anthelminthic chemotherapy.

The difficulty of establishing a diagnosis and confirming cure of strongyloidiasis is widely appreciated. As parasitological diagnosis is often unsatisfactory, serodiagnosis is frequently relied upon. The aim of this study was to investigate changes in Strongyloides-specific antibody levels among a group of 79 seropositive Indigenous Australians living in a Strongyloides-endemic region. Testing before and after treatment revealed that seroreversion occurred most commonly after multiple courses of ivermectin therapy, with antibody titres of 35/42 (83%) subjects becoming negative. Seroreversion was also common following a single course of ivermectin or multiple courses of a 3-day regimen of albendazole, with seroreversion occurring in 13/19 (68%) and 7/10 (70%) subjects respectively. One 3-day course of albendazole was less effective with 4/10 (40%) subjects seroreverting, whereas none of the five subjects receiving a single dose of albendazole and 1/10 (10%) of subjects receiving no therapy seroreverted. These results support the use of serological follow-up for strongyloidiasis, and indicate that reversion to negative serostatus after ivermectin therapy is frequent.

Interns' Day in Surgery: improving intern performance through a simulation-based course for final year medical students.

BACKGROUND: The transition from final year medical student into the first year of clinical practice is known to be associated with anxiety and stress that ultimately affects job performance. Studies have shown that much of this stress and anxiety results from a junior doctor's lack of confidence in performing a number of basic tasks. We investigated if implementation of a half-day simulation-based course in the final year medical students results in increased confidence in performing these tasks. METHODS: Final year medical students of the University of Tasmania's School of Medicine posted at the Royal Hobart Hospital participated in a half-day simulation course, comprised of multiple simulation stations, which required students to perform the basic tasks a competent surgical intern would be expected to complete. Students completed a survey which investigated their confidence with each task before and after the course. RESULTS: Overall, the majority of students thought that the Interns' Day in Surgery course was useful. The most significant improvements perceived were in case presentation (57.5% to 94.6%; P = 0.02) and communication with patients and other professional colleagues (55.5% to 75.5%; P = 0.01). A follow-up survey of doctors who attended this course reinforced its benefits. CONCLUSION: Simulation-based courses in clinical practice provide good learning opportunities for final year medical students within the curriculum. This study confirms significant gains in all skills categories practised during the course with perceived benefits subsequently identified by interns. This should lead to a less stressful and more successful transition from student to doctor and ultimately, better patient care.

Impact of an Ivermectin Mass Drug Administration on Scabies Prevalence in a Remote Australian Aboriginal Community.

BACKGROUND: Scabies is endemic in many Aboriginal and Torres Strait Islander communities, with 69% of infants infected in the first year of life. We report the outcomes against scabies of two oral ivermectin mass drug administrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community. METHODS: Utilizing a before and after study design, we measured scabies prevalence through population census with sequential MDAs at baseline and month 12. Surveys at months 6 and 18 determined disease acquisition and treatment failures. Scabies infestations were diagnosed clinically with additional laboratory investigations for crusted scabies. Non-pregnant participants weighing ≥15 kg were administered a single 200 µg/kg ivermectin dose, repeated after 2-3 weeks if scabies was diagnosed, others followed a standard alternative algorithm. PRINCIPAL FINDINGS: We saw >1000 participants at each population census. Scabies prevalence fell from 4% at baseline to 1% at month 6. Prevalence rose to 9% at month 12 amongst the baseline cohort in association with an identified exposure to a presumptive crusted scabies case with a higher prevalence of 14% amongst new entries to the cohort. At month 18, scabies prevalence fell to 2%. Scabies acquisitions six months after each MDA were 1% and 2% whilst treatment failures were 6% and 5% respectively. CONCLUSION: Scabies prevalence reduced in the six months after each MDA with a low risk of acquisition (1-2%). However, in a setting where living conditions are conducive to high scabies transmissibility, exposure to presumptive crusted scabies and population mobility, a sustained reduction in prevalence was not achieved. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trial Register (ACTRN-12609000654257).

Strongyloidiasis: a review of the evidence for Australian practitioners.

OBJECTIVE: To summarise the available evidence concerning the prevalence, clinical manifestations, diagnosis and management of strongyloidiasis in Northern Australia. METHODS: We searched Medline, Clinical Evidence and the Cochrane Library using MeSH terms and text words 'strongyloides OR strongyloidiasis'. For Australian studies we included text words '(parasite* OR parasitic OR helminth*) AND Australia*'. We examined references contained in retrieved studies or identified from direct contact with researchers. Studies consistent with our objective that described their methods were eligible for inclusion. RESULTS: The prevalence in some tropical Aboriginal communities is high. Infection can be asymptomatic, cause a range of clinical syndromes or death. It may become chronic. Infected patients are at risk of developing severe disseminated disease particularly with immune compromise. There is little information about the relative frequency of different clinical outcomes. Available diagnostic tools are imperfect. Stool examination has a low sensitivity. Serology may have a low specificity in high prevalence populations and has not been evaluated in Aboriginal populations. Antihelmintic drugs are relatively safe and effective. Community programs based on treatment of stool-positive cases have been associated with a reduced prevalence of strongyloidiasis. We found no studies examining alternative public health interventions. CONCLUSION: There is a high prevalence in many Aboriginal communities. Strongyloides infection should be excluded prior to commencing immunosuppressive therapies in patients from endemic areas. Further studies examining the public health impact of strongyloidiasis, the role of the enzyme-linked immuno-sorbent assay serological test and population-based approaches to management of the disease in endemically infected Australian populations are needed.