Human strongyloidiasis: complexities and pathways forward.

Strongyloidiasis is a World Health Organization neglected tropical disease usually caused by Strongyloides stercoralis, a parasitic worm with a complex life cycle. Globally, 300-600 million people are infected through contact with fecally contaminated soil. An autoinfective component of the life cycle can lead to chronic infection that may be asymptomatic or cause long-term symptoms, including malnourishment in children. Low larval output can limit the sensitivity of detection in stool, with serology being effective but less sensitive in immunocompromise. Host immunosuppression can trigger catastrophic, fatal hyperinfection/dissemination, where large numbers of larvae pierce the bowel wall and disseminate throughout the organs. Stable disease is effectively treated by single-dose ivermectin, with disease in immunocompromised patients treated with multiple doses. Strategies for management include raising awareness, clarifying zoonotic potential, the development and use of effective diagnostic tests for epidemiological studies and individual diagnosis, and the implementation of treatment programs with research into therapeutic alternatives and medication safety.

Comparison of Loop-Mediated Isothermal Amplification and Real-Time PCR Assays for Detection of Strongyloides Larvae in Different Specimen Matrices.

Strongyloides stercoralis can cause disease that ranges from asymptomatic chronic infection to fatal hyperinfection. Diagnosis from stool can be challenging because the most sensitive conventional tests require live larvae to be effective and there can be low larval output in chronic infection. Nucleic acid amplification tests (NAAT) have been developed to complement existing diagnostic methods. We compared a recently developed loop-mediated isothermal amplification (LAMP) assay with a real-time PCR that has previously been validated with larval microscopy. The limits of detection-quantified using serial dilutions of DNA extracts from single Strongyloides ratti third-stage (L3) larvae spiked into approximately 250 µl of 5 different S. stercoralis-negative stool specimens-were 10-3 (1/5 replicates) and 10-2 (1/5 replicates) dilutions for PCR and LAMP, respectively. PCR was positive for 4/5 replicates at 10-2 LAMP was compared to PCR using extracts from 396 stool specimens collected in Bangladesh and Australia, of which 53 were positive and 343 were negative by PCR. The positive percentage agreement of LAMP was 77.3% (95% score confidence interval [CI], 64.5 to 86.6). The negative percentage agreement was 100% (95% CI, 98.9 to 100). In a preliminary investigation, PCR and LAMP assays were positive using DNA extracted from serum (PCR, 3/16 extracts; LAMP, 2/16 extracts) and bronchoalveolar lavage fluid (PCR and LAMP, 2/2 extracts), demonstrating proof of concept. Compared to PCR, the lower number of positive results using the LAMP assay may have been due to reaction inhibitors and DNA degradation, and strategies to improve the LAMP assay are discussed.

Anncaliia algerae Microsporidial Myositis, New South Wales, Australia.

We describe the successful management of Anncaliia algerae microsporidial myositis in a man with graft versus host disease after hemopoietic stem cell transplantation. We also summarize clinical presentation and management approaches and discuss the importance of research into the acquisition of this infection and strategies for prevention.

Development of fluconazole resistance in a series of Candida parapsilosis isolates from a persistent candidemia patient with prolonged antifungal therapy.

BACKGROUND: Candida parapsilosis was the most common species causing candidemia in the 2010 China Hospital Invasive Fungal Surveillance Net (CHIF-NET) database. Compared to Candida albicans, the description of azole resistance and mechanisms in C. parapsilosis is very limited. We report a patient with C. parapsilosis candidemia over several months, due to a probable intravascular source, who developed fluconazole resistance after prolonged treatment. CASE PRESENTATION: An 82 year-old male had a hospital admission of approximately 1.5 years duration. He was initially admitted with acute pancreatitis. Prior to succumbing to the illness, he developed candidemia and treated with three antifungal drugs for nearly 5 months, at suboptimal doses and without source control. Following treatment, 6 blood cultures were still positive for C. parapsilosis. The last 2 strains were resistant to fluconazole (MICs 32 µg/mL) and intermediate to voriconazole (MICs 0.5 µg/mL). Microsatellite multilocus analysis indicated that the 6 isolates from the patient belonged to a single genotype. The first 4 isolates were susceptible to fluconazole (MICs 2 µg/mL) and voriconazole (MICs 0.015-0.03 µg/mL), which were slightly higher than susceptible control strains from other patients. Overexpression of MDR1 genes were detected in the two resistant isolates, and this was associated with a homozygous mutation in MRR1 genes (T2957C /T2957C), with the amino acid exchange L986P. CONCLUSIONS: This case corroborates that the resistant C. parapsilosis isolates can emerge in the setting of complicated infections and the extensive use of antifungal agents, emphasizing the need for standardizing and improving the antifungal treatment as well as source control in the treatment of infection diseases.

Anncaliia algerae microsporidial myositis.

The insect microsporidian Anncaliia algerae was first described in 2004 as a cause of fatal myositis in an immunosuppressed person from Pennsylvania, USA. Two cases were subsequently reported, and we detail 2 additional cases, including the only nonfatal case. We reviewed all 5 case histories with respect to clinical characteristics, diagnosis, and management and summarized organism life cycle and epidemiology. Before infection, all case-patients were using immunosuppressive medications for rheumatoid arthritis or solid-organ transplantation. Four of the 5 case-patients were from Australia. All diagnoses were confirmed by skeletal muscle biopsy; however, peripheral nerves and other tissues may be infected. The surviving patient received albendazole and had a reduction of immunosuppressive medications and measures to prevent complications. Although insects are the natural hosts for A. algerae, human contact with water contaminated by spores may be a mode of transmission. A. algerae has emerged as a cause of myositis, particularly in coastal Australia.

Case Report: The Use of In Vivo Confocal Microscopy for Diagnosis and Monitoring in a Rare Case of Ancaliia algerae Microsporidial Keratitis in New South Wales, Australia.

We describe the successful management of Ancaliia Algerae microsporidial keratitis in an immunosuppressed 54-year-old woman with refractory linear IgA disease. The case highlights the challenges in diagnosis and management of this infection in immunocompromised individuals and emphasizes the usefulness of in vivo confocal microscopy as a novel, noninvasive tool to aid in the diagnosis and monitoring of microsporidial keratitis. We also discuss the possible mode of acquisition of this rare infection.

An Unusual Case of Lethal Strongyloides stercoralis-Associated Chronic Fulminant Colitis in an Immunocompetent Patient.

A 70-year-old immunocompetent Lebanese male presented with 3-month history of watery diarrhoea and abdominal pain after recently arriving to Australia from Lebanon. He had a colectomy for an iatrogenic bowel perforation associated with a colonoscopy in Lebanon several months prior. His computed tomography (CT) scan demonstrated pancolitis. Stool culture and polymerase chain reaction (PCR) were positive for Strongyloides stercoralis. Despite Strongyloides treatment and total parenteral nutrition, his pancolitis unexpectedly persisted despite negative stool cultures, and the patient failed to progress over several weeks with worsening abdominal pain. A colectomy was considered. However, due to his recent myocardial infarct requiring cardiac stenting, his anticoagulant and antiplatelets could not be ceased for at least 3 months without significant cardiac risk. After hospitalisation for several weeks in Australia, he was discharged against medical advice and flew back to Lebanon, where he presented with worsening pain and underwent a subtotal colectomy. Unfortunately, he developed multiorgan failure and died 3 weeks following his colectomy. Strongyloides-related pancolitis is a rare condition in immunocompetent adults that has the potential to persist and be lethal, despite microbiological antiparasitic eradication.

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.

The diagnosis of human and companion animal Strongyloides stercoralis infection: Challenges and solutions. A scoping review.

Strongyloidiasis is the infection caused by soil-transmitted nematodes of Strongyloides species, infecting humans and some animals. Strongyloides stercoralis is the species with most clinical and epidemiological relevance in humans and dogs, due to its high prevalence and its capacity of inducing a life-threatening hyperinfection. Diagnosis of strongyloidiasis is challenging, due to the absence of a single reference standard test with high sensitivity and specificity, which also hampers the estimation of the accuracy of other diagnostic tests. In this chapter, we review the deployment and performance of the parasitological, immunological, molecular tests for the diagnosis of strongyloidiasis in humans and in dogs. Further, we comment the available evidence from genotyping studies that have addressed the zoonotic potential of S. stercoralis. Finally, we discuss the use of different diagnostic methods in relation to the purpose (i.e., screening, individual diagnosis, inclusion in a clinical trial) and the setting (endemic/non-endemic areas) and report the accuracy figures reported by systematic reviews on either parasitological, serological or molecular techniques published in literature.

Editor's choice: Implications of isoniazid resistance in Mycobacterium bovis Bacillus Calmette-Guérin used for immunotherapy in bladder cancer.

We report a case of sepsis from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) with low-level isoniazid resistance following intravesical treatment for bladder cancer. Isoniazid resistance in BCG has therapeutic implications when it causes infections after intravesical instillation. For these circumstances, we propose some modifications to existing treatment guidelines for BCG infection.

Nocardia infections of the face and neck.

Involvement of the soft tissues of the face and neck by Nocardia spp. is uncommon. We review the epidemiology, clinical features, diagnosis, and management of such infections in the setting of primary cutaneous nocardiosis and disseminated disease. Although immune compromise is an important risk factor for these infections, they also occur in healthy individuals. Infection may arise through direct inoculation following injury or by hematogenous spread from a primary site, usually the lung. The rare variant of lymphocutaneous disease-cervicofacial nocardiosis-typically affects children, but can occur in adults. The diagnosis is made by conventional microscopy and culture, but radiological imaging is useful to delineate disease extent, and molecular methods are increasingly assisting the diagnosis by providing rapid detection and identification of the pathogen. Sulfonamides remain the preferred treatment for many cases and are an important component of the therapeutic armamentarium. Other therapeutic options include minocycline, the carbapenems, and linezolid.

Fatal disseminated Anncaliia algerae myositis mimicking polymyositis in an immunocompromised patient.

We report the first New Zealand case of Anncaliia algerae myositis in a 55-year-old man with a history of psoriatic arthritis, treated with long-term immunosuppressive therapy. He resided in the city of Rotorua, which is famous for geothermal hot springs. A vastus lateralis muscle biopsy was performed to investigate the cause of an unexplained myositis. Light microscopy demonstrated a necrotizing myositis with scattered clusters of ovoid spores within the myocyte cytoplasm resembling microsporidia. DNA analysis by PCR and electron microscopy confirmed microsporidial myositis with features characteristic of A. algerae. Immunosuppressive drugs were stopped and the patient was treated with cholestyramine wash and albendazole. The patient deteriorated with involvement of bulbar and respiratory muscles requiring intensive care and ventilation. He died 3 weeks after diagnosis. Post-mortem examination of skeletal muscle from tongue and intercostal muscles also revealed numerous organisms confirming disseminated disease.

Infection control professionals' and infectious diseases physicians' knowledge, preparedness, and experiences of managing COVID-19 in Australian healthcare settings.

BACKGROUND: COVID-19 has placed unprecedented demands on infection control professionals (ICPs) and infectious disease (ID) physicians. This study examined their knowledge, preparedness, and experiences managing COVID-19 in the Australian healthcare settings. METHODS: A cross-sectional study of ICPs and ID physician members of the Australasian College for Infection Prevention and Control (ACIPC) and the Australasian Society for Infectious Diseases (ASID) was conducted using an online survey. Descriptive statistics were used to summarise and report data. RESULTS: A total of 103 survey responses were included in the analysis for ICPs and 45 for ID physicians. A majority of ICPs (78.7%) and ID physicians (77.8%) indicated having 'very good' or 'good' level of knowledge of COVID-19. Almost all ICPs (94.2%) relied on state or territory's department of health websites to source up-to-date information While most ID physicians (84.4%) used scientific literature and journals. A majority of ICPs (96%) and ID physicians (73.3%) reported feeling 'moderately prepared' or 'extremely prepared' for managing COVID-19. Most respondents had received specific training about COVID-19 within their workplace (ICPs: 75%; ID physicians: 66.7%), particularly training/certification in PPE use, which made them feel 'mostly or entirely confident' in using it. Most ICPs (84.5%) and ID physicians (76.2%) reported having 'considerably' or 'moderately more' work added to their daily duties. Their biggest concerns included the uncertainties under a rapidly changing landscape, PPE availability, and the community's compliance. CONCLUSION: Harmonised information, specific COVID-19 training and education, and adequate support for front-line workers are key to successfully managing COVID-19 and other future outbreaks.

Use of Infliximab to Treat Paradoxical Tuberculous Meningitis Reactions.

We documented dramatic responses to infliximab in 4 tuberculous meningitis cases with severe paradoxical reactions after effective antibacterial treatment, despite high-dose steroids. In every instance, infliximab was used as a last resort after all other options were exhausted, resulting in delayed initiation that may have adversely affected patient outcomes.

Diagnosis of Queensland tick typhus and African tick bite fever by PCR of lesion swabs.

We report 3 cases of Queensland tick typhus (QTT) and 1 case of African tick bite fever in which the causative rickettsiae were detected by PCR of eschar and skin lesions in all cases. An oral mucosal lesion in 1 QTT case was also positive.