The seasonality of infections in tropical Far North Queensland, Australia: A 21-year retrospective evaluation of the seasonal patterns of six endemic pathogens.

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 aureus infections 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.

Genetic Variation of G6PD and CYP2D6: Clinical Implications on the Use of Primaquine for Elimination of Plasmodium vivax.

Primaquine, an 8-aminoquinoline, is the only medication approved by the World Health Organization to treat the hypnozoite stage of Plasmodium vivax and P. ovale malaria. Relapse, triggered by activation of dormant hypnozoites in the liver, can occur weeks to years after primary infection, and provides the predominant source of transmission in endemic settings. Hence, primaquine is essential for individual treatment and P. vivax elimination efforts. However, primaquine use is limited by the risk of life-threatening acute hemolytic anemia in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. More recently, studies have demonstrated decreased efficacy of primaquine due to cytochrome P450 2D6 (CYP2D6) polymorphisms conferring an impaired metabolizer phenotype. Failure of standard primaquine therapy has occurred in individuals with decreased or absent CYP2D6 activity. Both G6PD and CYP2D6 are highly polymorphic genes, with considerable geographic and interethnic variability, adding complexity to primaquine use. Innovative strategies are required to overcome the dual challenge of G6PD deficiency and impaired primaquine metabolism. Further understanding of the pharmacogenetics of primaquine is key to utilizing its full potential. Accurate CYP2D6 genotype-phenotype translation may optimize primaquine dosing strategies for impaired metabolizers and expand its use in a safe, efficacious manner. At an individual level the current challenges with G6PD diagnostics and CYP2D6 testing limit clinical implementation of pharmacogenetics. However, further characterisation of the overlap and spectrum of G6PD and CYP2D6 activity may optimize primaquine use at a population level and facilitate region-specific dosing strategies for mass drug administration. This precision public health approach merits further investigation for P. vivax elimination.

An Update on the Laboratory Diagnosis of Rickettsia spp. Infection.

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.

Tuberculous bronchopleural fistula.

Tuberculous bronchopleural fistula is a rare complication of pulmonary tuberculosis with presentation ranging from patients who are asymptomatic with incidental findings on imaging to those who present with acute tension pneumothorax.

Prompt defervescence after initiation of treatment for rickettsial infections - time to dispense with the dogma?

INTRODUCTION: Clinicians are commonly taught that if patients with suspected rickettsial disease have continuing fever after 48 hours of anti-rickettsial therapy, an alternative diagnosis is likely. METHODS: This retrospective study of patients hospitalised with scrub typhus and Queensland tick typhus (QTT) in tropical Australia, examined the time to defervescence after initiation of the patients' anti-rickettsial therapy. It also identified factors associated with delayed defervescence (time to defervescence >48 hours after antibiotic commencement). RESULTS: Of the 58 patients, 32 (56%) had delayed defervescence. The median (interquartile range (IQR)) age of patients with delayed defervescence was 52 (37-62) versus 40 (28-53) years in those who defervesced within 48 hours (p = 0.05). Patients with delayed defervescence were more likely to require Intensive Care Unit (ICU) admission than those who defervesced within 48 hours (12/32 (38%) versus 3/26 (12%), p = 0.02). Even among patients not requiring ICU care, patients with delayed defervescence required a longer hospitalisation than that those who defervesced within 48 hours (median (IQR): 6 (3-8) versus 3 (2-5) days, p = 0.006). CONCLUSIONS: A significant proportion of patients with confirmed scrub typhus and QTT will remain febrile for >48 hours after appropriate anti-rickettsial therapy. Delayed defervescence is more common in patients with severe disease.

The Characteristics and Clinical Course of Patients with Scrub Typhus and Queensland Tick Typhus Infection Requiring Intensive Care Unit Admission: A 23-year Case Series from Queensland, Tropical Australia.

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 intensive care unit (ICU) of a tertiary referral hospital in tropical Australia between 1997 and 2019. Of the 22 patients, 13 had scrub typhus and nine had QTT. The patients' median (interquartile range [IQR]) age was 50 (38-67) years; 14/22 (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 (50%), 5/22 (22%) required only vasopressor support, 2/22 (9%) required only invasive ventilation, and 4/22 (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 (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.

Clinical Features of Rickettsial Infection in Children in Tropical Australia-A Report of 15 Cases.

Rickettsial infections are an under-recognized cause of acute, undifferentiated fever in the tropics. In Asia, intensive care unit (ICU) admission rates as high as 21% and case-fatality rates of up to 5% have been reported. This 20-year retrospective audit of children and adults with serologically confirmed scrub typhus or spotted fever group (SFG) infection was performed at a tertiary-referral hospital in tropical Australia. There were 15 paediatric cases during the study period (11 scrub typhus, 3 SFG and 1 undifferentiated). Hypotension [5/15 (33%)], tachycardia [6/15 (40%)] and tachypnoea [6/15 (40%)] were common at presentation. Children were more likely to be hypotensive at admission than adults [5/15 (33%) vs. 5/118 (4%), p = 0.002]. However, no child died or was admitted to ICU, compared with 18/120 (15%) adults who required ICU support during the study period, one of whom died. Paediatric rickettsial infections have a relatively benign clinical course in tropical Australia with serious complications appearing far less frequently than have been reported in the Asian literature.

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.