Rickettsia species causing human illness are present globally and can cause significant disease. Diagnosis and identification of this intracellular bacteria are challenging with many available diagnostic modalities suffering from several shortcomings. Detection of antibodies directed against Rickettsia spp. via serological methods remains widely used with a broad range of sensitivity and specificity values reported depending on the assay. Molecular methods, including polymerase chain reaction (PCR) testing, enables species-specific identification with a fast turnaround time; however, due to resource requirements, use in some endemic settings is limited. Reports on the use of next-generation sequencing (NGS) and metagenomics to diagnose Rickettsia spp. infection have been increasing. Despite offering several potential advantages in the diagnosis and surveillance of disease, genomic approaches are currently only limited to reference and research laboratories. Continued development of Rickettsia spp. diagnostics is required to improve disease detection and epidemiological surveillance, and to better understand transmission dynamics.

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. 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. 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). 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.

An understanding of the seasonality of infections informs public health strategies and assists clinicians in their management of patients with undifferentiated illness. The seasonality of infections is driven by a variety of environmental and human factors; however, the role of individual climatic factors has garnered much attention. This study utilises Poisson regression models to assess the seasonality of six important infections in tropical Australia and their association with climatic factors and severe weather events over a 21-year period. Melioidosis and leptospirosis showed marked wet season predominance, while more cases of rickettsial disease and cryptococcosis were seen in cooler, drier months.Staphylococcus aureusinfections were not seasonal, while influenza demonstrated inter-seasonality. The climate did not significantly change during the 21 years of the study period, but the incidence of melioidosis and rickettsial disease increased considerably, highlighting the primacy of other factors—including societal inequality, and the impact of urban expansion—in the incidence of these infections. While anthropogenic climate change poses a threat to the region—and may influence the burden of these infections in the future—this study highlights the fact that, even for seasonal diseases, other factors presently have a greater effect on disease incidence. Public health strategies must also target these broader drivers of infection if they are to be effective.

Rapid diagnosis and appropriate treatment is imperative in bacterial sepsis due increasing risk of mortality with every hour without appropriate antibiotic therapy. Atypical infections with fastidious organisms may take more than 4 days to diagnose leading to calls for improved methods for rapidly diagnosing sepsis. Capnocytophaga canimorsus is a slow-growing, fastidious gram-negative bacillus which is a common commensal within the mouths of dogs, but rarely cause infections in humans. C. canimorsus sepsis risk factors include immunosuppression, alcoholism and elderly age. Here we report on the application of emerging nanopore sequencing methods to rapidly diagnose an atypical case of C. canimorsus septic shock. A 62 year-old female patient was admitted to an intensive care unit with septic shock and multi-organ failure six days after a reported dog bite. Blood cultures were unable to detect a pathogen after 3 days despite observed intracellular bacilli on blood smears. Real-time nanopore sequencing was subsequently employed on whole blood to detect Capnocytophaga canimorsus in 19 h. The patient was not immunocompromised and did not have any other known risk factors. Whole-genome sequencing of clinical sample and of the offending dog’s oral swabs showed near-identical C. canimorsus genomes. The patient responded to antibiotic treatment and was discharged from hospital 31 days after admission. Use of real-time nanopore sequencing reduced the time-to-diagnosis of Capnocytophaga canimorsus in this case from 6.25 days to 19 h. Capnocytophaga canimorsus should be considered in cases of suspected sepsis involving cat or dog contact, irrespective of the patient’s known risk factors.

: Many patients with leptospirosis, melioidosis, and rickettsial infection require intensive care unit (ICU) admission in tropical Australia every year. The multi-organ dysfunction associated with these infections results in significantly elevated severity of illness (SOI) scores. However, the accuracy of these SOI scores in predicting death from these tropical infections is incompletely defined. This retrospective study was performed at Cairns Hospital, a tertiary-referral hospital in tropical Australia. All patients admitted to ICU with laboratory-confirmed leptospirosis, melioidosis, and rickettsial disease between January 1, 1999 and June 30, 2020, were eligible for the study. The ability of Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, Simplified Acute Physiology Scores (SAPS) II, and Sequential Organ Failure Assessment (SOFA) scores to predict death before ICU discharge was evaluated. Overall, 18 (12.1%) of the 149 included patients died: 15/74 (20.3%) with melioidosis, 2/54 (3.7%) with leptospirosis and 1/21 (4.8%) with rickettsial disease. However, the APACHE II, APACHE III, SAPS II, and SOFA scores significantly overestimated the case-fatality rate of all the infections; the disparity between the predicted and observed mortality was most marked in the cases of leptospirosis and rickettsial disease. Commonly used SOI scores significantly overestimate the case-fatality rate of melioidosis, leptospirosis, and rickettsial infections in Australian ICU patients. This may be at least partly explained by the unique pathophysiology of these infections, particularly leptospirosis and rickettsial disease. However, SOI scores may still be useful in facilitating the comparison of disease severity in clinical trials that examine patients with these pathogens.

Scrub typhus and Queensland tick typhus (QTT)—rickettsial infections endemic to tropical Australia—can cause life-threatening disease. This retrospective study examined the clinical course of all patients with laboratory-confirmed scrub typhus or QTT admitted to the ICU of a tertiary referral hospital in tropical Australia between 1997 and 2019. Among 22 patients, 13 had scrub typhus and nine had QTT. The patients’ median (interquartile range [IQR]) age was 50 (38–67) years; 14/22 patients (64%) had no comorbidity. Patients presented a median (IQR) of seven (5–10) days after symptom onset. Median (IQR) Acute Physiology and Chronic Health Evaluation II scores were 13 (9–17) for scrub typhus and 13 (10–15) for QTT cases (P = 0.61). Following hospital admission, the median (IQR) time to ICU admission was five (2–19) hours. The median (IQR, range) length of ICU stay was 4.4 (2.9–15.9, 0.8–33.8) days. Multi-organ support was required in 11/22 patients (50%), 5/22 patients (22%) required only vasopressor support, 2/22 patients (9%) required only invasive ventilation, and 4/22 patients (18%) were admitted for monitoring. Patients were ventilated using protective lung strategies, and fluid management was conservative. Standard vasopressors were used, indications for renal replacement therapy were conventional, and blood product usage was restrictive; 9/22 patients (41%) received corticosteroids. One patient with QTT died, and two (8%) additional patients with QTT developed purpura fulminans requiring digital amputation. Death or permanent disability occurred in 3/9 (33%) QTT and 0/13 scrub typhus cases (P = 0.055). Queensland tick typhus and scrub typhus can cause multi-organ failure requiring ICU care in otherwise well individuals. Queensland tick typhus appears to have a more severe clinical phenotype than previously believed.