Clinical Manifestations and Genomic Evaluation of Melioidosis Outbreak among Children after Sporting Event, Australia.

Melioidosis, caused by the environmental gram-negative bacterium Burkholderia pseudomallei, usually develops in adults with predisposing conditions and in Australia more commonly occurs during the monsoonal wet season. We report an outbreak of 7 cases of melioidosis in immunocompetent children in Australia. All the children had participated in a single-day sporting event during the dry season in a tropical region of Australia, and all had limited cutaneous disease. All case-patients had an adverse reaction to oral trimethoprim/sulfamethoxazole treatment, necessitating its discontinuation. We describe the clinical features, environmental sampling, genomic epidemiologic investigation, and public health response to the outbreak. Management of this outbreak shows the potential benefits of making melioidosis a notifiable disease. The approach used could also be used as a framework for similar outbreaks in the future.

Public health response to an outbreak of meningococcal B disease in a secondary school in Far North Queensland.

This article describes the public health response to an outbreak of meningococcal B disease, linked to a secondary school in Far North Queensland. Tropical Public Health Services in Cairns were notified of three cases of meningococcal disease in the same week in May 2022. The cases occurred in individuals who all attended, or worked in, the same secondary school. All cases were serogroup B and shared the same molecular genotype. The public health response included prompt provision of information, distribution of clearance antibiotics and two doses of MenB-4C vaccine to the entire staff and student population. Antibiotic coverage and vaccination coverage were achieved in 99% and 85% of the student population respectively. Following the intervention, no further cases were detected in the region during the subsequent nine months.

Genomic analysis of an outbreak of toxin gene bearing Corynebacterium diphtheriae in Northern Queensland, Australia reveals high level of genetic similarity.

Toxigenic diphtheria is rare in Australia with generally fewer than 10 cases reported annually; however, since 2020, there has been an increase in toxin gene-bearing isolates of Corynebacterium diphtheriae cases in North Queensland, with an approximately 300% escalation in cases in 2022. Genomic analysis on both toxin gene-bearing and non-toxin gene-bearing C. diphtheriae isolated from this region between 2017 and 2022 demonstrated that the surge in cases was largely due to one sequence type (ST), ST381, all of which carried the toxin gene. ST381 isolates collected between 2020 and 2022 were highly genetically related to each other, and less closely related to ST381 isolates collected prior to 2020. The most common ST in non-toxin gene-bearing isolates from North Queensland was ST39, an ST that has also been increasing in numbers since 2018. Phylogenetic analysis demonstrated that ST381 isolates were not closely related to any of the non-toxin gene-bearing isolates collected from this region, suggesting that the increase in toxigenic C. diphtheriae is likely due to the expansion of a toxin gene-bearing clone that has moved into the region rather than an already endemic non-toxigenic strain acquiring the toxin gene.

Nurse-led initiation of hepatitis C care in rural Cambodia.

Objective: To determine whether a nurse-led model of care for patients with hepatitis C virus (HCV) infections can provide safe and effective diagnosis and treatment in a resource-poor setting in rural Cambodia. Methods: The nurse-led initiation pilot project was implemented by Médecins Sans Frontières in collaboration with the Cambodian health ministry in two operational districts in Battambang Province between 1 June and 30 September 2020. Nursing staff at 27 rural health centres were trained to identify signs of decompensated liver cirrhosis and to provide HCV treatment. Patients without decompensated cirrhosis or another comorbidity were initiated at health centres onto combined treatment with sofosbuvir, 400 mg/day, and daclatasvir, 60 mg/day, orally for 12 weeks. Treatment adherence and effectiveness were assessed during follow-up. Findings: Of 10 960 individuals screened, 547 had HCV viraemia (i.e. viral load ≥ 1000 IU/mL). Of the 547, 329 were eligible for treatment initiation at health centres through the pilot project. All 329 (100%) completed treatment and 310 (94%; 95% confidence interval: 91-96) achieved a sustained virological response 12 weeks post-treatment. Depending on patient subgroups, this response varied from 89% to 100%. Only two adverse events were recorded; both were determined as unrelated to treatment. Conclusion: The safety and effectiveness of direct-acting antiviral medication has previously been demonstrated. Models of HCV care now need to enable greater access for patients. The nurse-led initiation pilot project provides a model for use in other resource-poor settings to scale up national programmes.

Decentralised hepatitis C testing and treatment in rural Cambodia: evaluation of a simplified service model integrated in an existing public health system.

BACKGROUND: Direct-acting antiviral treatment for hepatitis C virus (HCV) has provided the opportunity for simplified models of care delivered in decentralised settings by non-specialist clinical personnel. However, in low-income and middle-income countries, increasing overall access to HCV care remains an ongoing issue, particularly for populations outside of urban centres. We therefore aimed to implement a simplified model of HCV care via decentralised health services within a rural health operational district in Battambang province, Cambodia. METHODS: The study cohort included adult residents (≥18 years) of the health operational district of Moung Russei who were voluntarily screened at 13 local health centres. Serology testing was done by a rapid diagnostic test using SD Bioline HCV (SD Bioline HCV, Standard Diagnostics, South Korea) with capillary blood. HCV viral load testing was done by GeneXpert (Cepheid, Sunnyvale, CA, USA). Viraemic patients (HCV viral load ≥10 IU/mL) received pretreatment assessment by a general physician and minimal treatment evaluation tests at the health operational district referral hospital. Viraemic patients who did not have additional complications received all HCV care follow-up at the local health centres, provided by nursing staff, and patients who had decompensated cirrhosis, previously treated with a direct-acting antiviral, HBV co-infection, or other comorbidities requiring observation continued receiving care at the referral hospital with a general physician. Patients deemed eligible for treatment were prescribed oral sofosbuvir (400 mg) and daclatasvir (60 mg) once a day for 12 weeks, or 24 weeks for patients with decompensated cirrhosis or those previously treated with a direct-acting antiviral. HCV cure was defined as sustained virological response at 12 weeks after treatment (HCV viral load <10 IU/mL). Patients were assessed for serious and non-serious adverse events at any time between treatment initiation and 12 weeks post-treatment testing. FINDINGS: Between March 12, 2018, and Jan 18, 2019, 10 425 residents (ie, 7·6% of the estimated 136 571 adults in the health operational district of Moung Russei) were screened. Of those patients screened, the median age was 44 years (IQR 31-55) and 778 (7·5%) were HCV-antibody positive. 761 (97·8%) of 778 antibody-positive patients received HCV viral load testing, and 540 (71·0%) of those tested were HCV viraemic. Among these 540 patients, linkage to treatment and follow-up care was high, with 533 (98·7%) attending a baseline consultation at the HCV clinic, of whom 530 (99·4%) initiated treatment. 485 (91·5%) of 530 patients who initiated treatment received follow-up at a health centre and 45 (8·5%) were followed up at the referral hospital. Of the 530 patients who initiated direct-acting antiviral therapy, 515 (97·2%) completed treatment. Subsequently, 466 (90·5%) of 515 patients completed follow-up, and 459 (98·5%) of 466 achieved a sustained virological response at 12 weeks after treatment. Two (0·4%) adverse events (fatigue [n=1] and stomach upset [n=1]) and five (0·9%) serious adverse events (infection [n=2], cardiovascular disease [n=1], and panic attack [n=1], with data missing for one of the causes of serious adverse events) were reported among patients who initiated treatment. All serious adverse events were deemed to be unrelated to therapy. INTERPRETATION: This pilot project showed that a highly simplified, decentralised model of HCV care can be integrated within a rural public health system in a low-income or middle-income country, while maintaining high patient retention, treatment efficacy, and safety. The project delivered care via accessible, decentralised primary health centres, using non-specialist clinical staff, thereby enhancing the efficient use of limited resources and maximising the potential to test and treat individuals living with HCV infection. FUNDING: Médecins Sans Frontières.

Hepatitis C viraemic and seroprevalence and risk factors for positivity in Northwest Cambodia: a household cross-sectional serosurvey.

BACKGROUND: Despite a dramatic reduction in HCV drug costs and simplified models of care, many countries lack important information on prevalence and risk factors to structure effective HCV services. METHODS: A cross-sectional, multi-stage cluster survey of HCV seroprevalence in adults 18 years and above was conducted, with an oversampling of those 45 years and above. One hundred forty-seven clusters of 25 households were randomly selected in two sets (set 1=24 clusters ≥18; set 2=123 clusters, ≥45). A multi-variable analysis assessed risk factors for sero-positivity among participants ≥45. The study occurred in rural Moung Ruessei Health Operational District, Battambang Province, Western Cambodia. RESULTS: A total of 5098 individuals and 3616 households participated in the survey. The overall seroprevalence was 2.6% (CI95% 2.3-3.0) for those ≥18 years, 5.1% (CI95% 4.6-5.7) for adults ≥ 45 years, and 0.6% (CI95% 0.3-0.9) for adults 18-44. Viraemic prevalence was 1.9% (CI95% 1.6-2.1), 3.6% (CI95% 3.2-4.0), and 0.5% (CI95% 0.2-0.8), respectively. Men had higher prevalence than women: ≥18 years male seroprevalence was 3.0 (CI95% 2.5-3.5) versus 2.3 (CI95% 1.9-2.7) for women. Knowledge of HCV was poor: 64.7% of all respondents and 57.0% of seropositive participants reported never having heard of HCV. Risk factor characteristics for the population ≥45 years included: advancing age (p< 0.001), low education (higher than secondary school OR 0.7 [95% CI 0.6-0.8]), any dental or gum treatment (OR 1.6 [95% CI 1.3-1.8]), historical routine medical care (medical injection after 1990 OR 0.7 [95% CI 0.6-0.9]; surgery after 1990 OR 0.7 [95% CI0.5-0.9]), and historical blood donation or transfusion (blood donation after 1980 OR 0.4 [95% CI 0.2-0.8]); blood transfusion after 1990 OR 0.7 [95% CI 0.4-1.1]). CONCLUSIONS: This study provides the first large-scale general adult population prevalence data on HCV infection in Cambodia. The results confirm the link between high prevalence and age ≥45 years, lower socio-economic status and past routine medical interventions (particularly those received before 1990 and 1980). This survey suggests high HCV prevalence in certain populations in Cambodia and can be used to guide national and local HCV policy discussion.

Cost and cost-effectiveness of a simplified treatment model with direct-acting antivirals for chronic hepatitis C in Cambodia.

BACKGROUND & AIMS: In 2016, Médecins Sans Frontières established the first general population Hepatitis C virus (HCV) screening and treatment site in Cambodia, offering free direct-acting antiviral (DAA) treatment. This study analysed the cost-effectiveness of this intervention. METHODS: Costs, quality adjusted life years (QALYs) and cost-effectiveness of the intervention were projected with a Markov model over a lifetime horizon, discounted at 3%/year. Patient-level resource-use and outcome data, treatment costs, costs of HCV-related healthcare and EQ-5D-5L health states were collected from an observational cohort study evaluating the effectiveness of DAA treatment under full and simplified models of care compared to no treatment; other model parameters were derived from literature. Incremental cost-effectiveness ratios (cost/QALY gained) were compared to an opportunity cost-based willingness-to-pay threshold for Cambodia ($248/QALY). RESULTS: The total cost of testing and treatment per patient for the full model of care was $925(IQR $668-1631), reducing to $376(IQR $344-422) for the simplified model of care. EQ-5D-5L values varied by fibrosis stage: decompensated cirrhosis had the lowest value, values increased during and following treatment. The simplified model of care was cost saving compared to no treatment, while the full model of care, although cost-effective compared to no treatment ($187/QALY), cost an additional $14 485/QALY compared to the simplified model, above the willingness-to-pay threshold for Cambodia. This result is robust to variation in parameters. CONCLUSIONS: The simplified model of care was cost saving compared to no treatment, emphasizing the importance of simplifying pathways of care for improving access to HCV treatment in low-resource settings.

High sustained viral response rate in patients with hepatitis C using generic sofosbuvir and daclatasvir in Phnom Penh, Cambodia.

Safe and efficacious pan-genotypic direct-acting antiviral (DAA) regimens, such as sofosbuvir and daclatasvir (SOF + DCV), facilitate simplified models of care for hepatitis C virus (HCV). However, in Cambodia access to HCV testing and treatment has typically been low. In response, Médecins Sans Frontières (MSF) implemented a HCV testing and treatment pilot project in Phnom Penh, Cambodia in 2016. This project provides the first real-world evidence of SOF + DCV effectiveness across a large patient cohort using a simplified care model in Cambodia. Patients treated with SOF + DCV from September 2016 to June 2019 were included in the analysis. Medical standard operational procedures (SOPs) were simplified significantly across the study period. Treatment effectiveness was assessed by sustained viral response at 12 weeks post-treatment (SVR12) according to a modified intention-to-treat methodology. Treatment safety was assessed by clinical outcome and occurrence of serious and nonserious adverse events (S/AE). Of 9158 patients, median age was 57 years and 39.6% were male. At baseline assessment, 27.2% of patients had compensated cirrhosis and 2.9% had decompensated cirrhosis. Genotype 6 was predominant (53.0%). Among patients analysed according to modified intention to treat (n = 8525), treatment effectiveness was high, with 97.2% of patients achieving SVR12. Occurrence of SAE was low (0.7%). Treatment effectiveness and safety was not affected by the iterative simplification to treatment modality. In conclusion, in this large treatment cohort in Phnom Penh, Cambodia, the SOF + DCV regimen showed high rates of treatment effectiveness and safety across patient sub-groups and during progressive simplification.

Demonstration of the diagnostic agreement of capillary and venous blood samples, using hepatitis-C virus SD Bioline© rapid test: A clinic-based study.

BACKGROUND: Simplifying hepatitis C virus (HCV) screening is a key step in achieving the elimination of HCV as a global public health threat by 2030. OBJECTIVES: The objective of this study was to demonstrate the agreement of capillary blood and venipuncture specimens when using SD Bioline© HCV, a low-cost rapid diagnostic test (RDT), prequalified by WHO in 2016 on venous blood samples. STUDY DESIGN: Recruitment was conducted prospectively among adult patients presenting for HCV testing at the Médecins Sans Frontières (MSF) clinic of Preah Kossamak Hospital (Phnom Penh, Cambodia) between October and November 2017. Capillary and venous blood samples were collected from consenting patients and tested with SD Bioline© HCV. Two independent, blinded readers, and in the case of disagreement, a third reader, interpreted the results of each blood sample. Concordance between results was compared using Cohen's Kappa interrater reliability statistic. Discrepant sample pairs were tested with an enzyme immunoassay, the reference standard, at the Institute Pasteur of Cambodia. RESULTS: Among 421 pairs of samples collected, reader disagreement occurred for 0.7% (n = 3) of the participants. Sixty-four percent of capillary and venous blood sample pairs tested positive for HCV, with a Kappa statistic of 0.985 between the two methods. Three participants with discrepant sample pair results tested positive with EIA. CONCLUSIONS: Capillary and venous blood samples were concordant when tested with HCV SD Bioline© in a clinical context. This simplified testing approach is essential to the scale-up of HCV screening and useful in resource-limited settings or among populations for whom venipuncture is problematic.

Use of fetal fibronectin testing in women transferred for threatened preterm labour in remote far north Queensland.

BACKGROUND: Threatened preterm labour is a common reason for medical transfer from remote communities; however, many transferred women do not deliver preterm. A tool for prediction of preterm birth such as fetal fibronectin may reduce transfers and related social and economic costs. AIM: To review the use of fetal fibronectin testing in women transferred for threatened preterm labour from Cape York to Cairns Hospital between 2011 and 2015 and determine the role testing could play in reducing transfers and associated costs. MATERIALS/METHODS: Records from the Royal Flying Doctor Service and Cairns Hospital were accessed. Women transferred solely for threatened preterm labour were included in the study. Fetal fibronectin testing, hospital admission, outpatient stays and birth outcome data were collated and analysed. Costs were assigned using the National Hospital Cost Data Collection, round 19. RESULTS: Forty-seven women were included in the study; however, only 20 underwent fetal fibronectin testing. Transfer of 30 women who had either a negative test or were not tested but delivered at term resulted in 41 inpatient nights and 443 excess outpatient nights, costing an estimated AU$57 408. Aeromedical transfers were estimated to cost a further $151 500. CONCLUSION: Adherence to clinical guidelines and greater availability and use of fetal fibronectin testing in Cape York have the potential to reduce aeromedical transfers for threatened preterm labour. Substantial inpatient and excess outpatient stays could be avoided with associated reduction in health system and social costs. Strategies to improve adherence to guidelines and increase access to testing are required.

Managing skin infections in Aboriginal and Torres Strait Islander children.

BACKGROUND: Skin infections are a cause of significant morbidity in Aboriginal and Torres Strait Islander populations. OBJECTIVE: This article gives an overview of some of the issues to consider when managing a patient with a skin infection. These issues may impact on completion of treatment and development of complications in the long term. DISCUSSION: Management should consist of treatment of the patient through medication and also general measures for the patient, their family and the community as a whole. There are significant health and socioeconomic burdens placed on communities as a result of the high rate of skin disease in some settings.