Joseph Kado

Pacific Rheumatic Heart Disease (RHD) Program

The goal of the program is to establish the foundations of an effective, sustainable and equitable response to RHD in the Pacific.

Pharmacokinetics of intramuscular versus subcutaneous administration of Benzathine Penicillin G

Benzathine penicillin G (BPG) has been in use since the 1950s for treatment of skin infections, bacterial pharyngitis, syphilis and prevention of recurrent episodes of acute rheumatic fever (ARF)

Improving Wellbeing for Young People Living with Rheumatic Heart Disease: A peer support program through Danila Dilba Health Service

This project seeks to conduct a focus group for young people (aged 11-14) and their parents/family members through the Danila Dilba Health Service (DDHS) in Darwin with the aim of identifying consumer needs and perspectives on next steps and priorities for peer support in RHD.

Improving delivery of secondary prophylaxis for rheumatic heart disease

Continued progress in controlling RHD requires an understanding of how to improve delivery of regular injections of penicillin - secondary prophylaxis (SP).

Head-to-head Pharmacokinetic Comparison of Bicillin ® L-A versus Lyophilised (Powdered) Benzathine Penicillin G administered by the Intramuscular and Subcutaneous Routes

Fiji has one of the highest burdens of RHD is in the world and RHD is the second most common cause of death in young people in Fiji.

Development of a longer acting formulation of Penicillin G for the treatment and prevention of acute rheumatic fever and rheumatic heart disease

This project aims to develop a longer acting formulation of penicillin, such that frequency of the injection can be increased up to 3-6 months.

Defining target penicillin concentrations for subsequent studies of a reformulated long-acting benzathine penicillin prototype

Aims: To determine the minimum inhibitory concentrations of penicillin G against a representative collection of Strep A strains; and to evaluate the impact of penicillin G concentration and size of bacterial inoculum on the prophylactic effect for Strep A strains

BPG Formulation Preferences Study: Exploring patient, family and clinician reformulations preferences for BPG

The key objective of this study is to collect data about patient and clinician preferences about reformulations.

Acceptability of sonicated versus unsonicated reconstituted (powdered) benzathine penicillin G for rheumatic fever prophylaxis

Powdered benzathine penicillin G (BPG) crystals vary widely in size and shape and are larger and less uniform than crystals found in pre-mixed suspensions of BPG like Bicillin ® L-A.

Acute rheumatic fever

Acute rheumatic fever is an autoimmune disorder resulting from Group A Streptococcus pharyngitis or impetigo in children and adolescents, which may evolve to rheumatic heart disease (RHD) with persistent cardiac valve damage. RHD causes substantial mortality and morbidity globally, predominantly among socioeconomically disadvantaged populations, with an interplay of social determinants of health and genetic factors determining overall risk.

High dose, subcutaneous injections of benzathine penicillin G (SCIP) to prevent rheumatic fever: A single arm, phase IIa trial of safety and pharmacokinetics

This Phase-IIa trial evaluates the safety and pharmacokinetics of high-dose, 10 weekly subcutaneous injections of penicillin (SCIP) in young people with a history of acute rheumatic fever (ARF).

Establishing the lowest penicillin concentration to prevent pharyngitis due to Streptococcus pyogenes using a human challenge model (CHIPS)

The in-vivo plasma concentration of penicillin needed to prevent Streptococcus pyogenes pharyngitis, recurrent acute rheumatic fever, and progressive rheumatic heart disease is not known. We used a human challenge model to assess the minimum penicillin concentration required to prevent streptococcal pharyngitis.

Costs of primary healthcare presentations and hospital admissions for scabies and related skin infections in Fiji, 2018–2019

Scabies and related bacterial skin and soft tissue infections are highly prevalent in many tropical, low- and middle-income settings. These skin conditions contribute to higher healthcare costs and burdens on healthcare systems. 

"Hurts less, lasts longer"; a qualitative study on experiences of young people receiving high-dose subcutaneous injections of benzathine penicillin G to prevent rheumatic heart disease in New Zealand

Four-weekly intramuscular benzathine penicillin G injections to prevent acute rheumatic fever progression have remained unchanged since 1955. A Phase-I trial in healthy volunteers demonstrated the safety and tolerability of high-dose subcutaneous infusions of BPG which resulted in a much longer effective penicillin exposure, and fewer injections. Here we describe the experiences of young people living with ARF participating in a Phase-II trial of SubCutaneous Injections of BPG.

Could late-latent syphilis be treated with a single subcutaneous infusion of long-acting penicillin?

Syphilis is an important global health threat and little has changed in its treatment since the mid-20th century. For late-latent or syphilis infection of unknown duration, the standard treatment of multiple intramuscular injections of benzathine penicillin G (BPG) are associated with significant pain and distress to clients and caregivers, negatively impacting on treatment completion.

Clinical practice guidelines: Their utility, dissemination and monitoring at Colonial War Memorial Hospital: A mixed methods study from Fiji

Clinical practice guidelines (CPGs) improve patient care by standardising medical practice. However, little is known about their applicability in low-resource settings. Since 2010, Fiji has introduced guidelines to increase the application of evidence-based practice.

Subcutaneous infusion of high-dose benzathine penicillin G is safe, tolerable, and suitable for less-frequent dosing for rheumatic heart disease secondary prophylaxis: a phase 1 open-label population pharmacokinetic study

Since 1955, the recommended strategy for rheumatic heart disease secondary prophylaxis has been benzathine penicillin G injections administered intramuscularly every 4 weeks. Due to dosing frequency, pain, and programmatic challenges, adherence is suboptimal. It has previously been demonstrated that BPG delivered subcutaneously at a standard dose is safe and tolerable and has favorable pharmacokinetics, setting the scene for improved regimens with less frequent administration.

2023 World Heart Federation guidelines for the echocardiographic diagnosis of rheumatic heart disease

Rheumatic heart disease (RHD) is an important and preventable cause of morbidity and mortality among children and young adults in low-income and middle-income countries, as well as among certain at-risk populations living in high-income countries. The 2012 World Heart Federation echocardiographic criteria provided a standardized approach for the identification of RHD and facilitated an improvement in early case detection.

Development of a sustained release implant of benzathine penicillin G for secondary prophylaxis of rheumatic heart disease

Regular intramuscular (i.m.) benzathine penicillin G (BPG) injections have been the cornerstone of rheumatic heart disease (RHD) secondary prophylaxis since the 1950s. Patient adherence to IM BPG is poor, largely due to pain, the need for regular injections every 3-4 weeks and health sector delivery challenges in resource-limited settings. There is an urgent need for new approaches for secondary prophylaxis, such as an implant which could provide sustained penicillin concentrations for more than 6 months.

Population-based assessment of cardiovascular complications of rheumatic heart disease in Fiji: a record-linkage analysis

To determine population-based rates of non-fatal complications of rheumatic heart disease (RHD).

Qualitative assessment of healthy volunteer experience receiving subcutaneous infusions of high-dose benzathine penicillin G (SCIP) provides insights into design of late phase clinical studies

Secondary prophylaxis to prevent rheumatic heart disease (RHD) progression, in the form of four-weekly intramuscular benzathine benzylpenicillin G (BPG) injections, has remained unchanged since 1955. Qualitative investigations into patient preference have highlighted the need for long-acting penicillins to be delivered less frequently, ideally with reduced pain.

Study protocol for controlled human infection for penicillin G against Streptococcus pyogenes: a double-blinded, placebo-controlled, randomised trial to determine the minimum concentration required to prevent experimental pharyngitis (the CHIPS trial)

Regular intramuscular benzathine penicillin G injections have been the cornerstone of rheumatic heart disease (RHD) secondary prophylaxis since the 1950s. As the pharmacological correlate of protection remains unknown, it is difficult to recommend changes to this established regimen. Determining the minimum effective penicillin exposure required to prevent Streptococcus pyogenes infection will accelerate development of new long-acting penicillins for RHD prevention as well as inform opportunities to improve existing regimens. The CHIPS trial will address this knowledge gap by directly testing protection afforded by different steady state plasma concentrations of penicillin in an established model of experimental human S. pyogenes pharyngitis.

Population pharmacokinetic study of benzathine penicillin G administration in Indigenous children and young adults with rheumatic heart disease in the Northern Territory, Australia

Benzathine penicillin G is the cornerstone of secondary prophylaxis to prevent Streptococcus pyogenes infections, which precede acute rheumatic fever.

Prevention of bacterial complications of scabies using mass drug administration: A population-based, before-after trial in Fiji, 2018–2020

Scabies is an important predisposing factor of impetigo which can lead to serious bacterial complications. Ivermectin-based mass drug administration can substantially reduce scabies and impetigo prevalence in endemic settings, but the impact on serious bacterial complications is not known.

Costs of mass drug administration for scabies in Fiji

In 2019, the Murdoch Children's Research Institute in partnership with the Fiji Ministry of Health and Medical Services carried out an integrated mass drug administration (MDA) for the treatment of scabies and lymphatic filariasis in the Northern Division of Fiji. We conducted a retrospective micro-costing exercise focused on the cost of scabies control in order to inform budgeting and policy decision making in an endemic setting.