Potential health and economic impacts of dexamethasone treatment for patients with COVID-19.

Dexamethasone can reduce mortality in hospitalised COVID-19 patients needing oxygen and ventilation by 18% and 36%, respectively. Here, we estimate the potential number of lives saved and life years gained if this treatment were to be rolled out in the UK and globally, as well as the cost-effectiveness of implementing this intervention. Assuming SARS-CoV-2 exposure levels of 5% to 15%, we estimate that, for the UK, approximately 12,000 (4,250 - 27,000) lives could be saved between July and December 2020. Assuming that dexamethasone has a similar effect size in settings where access to oxygen therapies is limited, this would translate into approximately 650,000 (240,000 - 1,400,000) lives saved globally over the same time period. If dexamethasone acts differently in these settings, the impact could be less than half of this value. To estimate the full potential of dexamethasone in the global fight against COVID-19, it is essential to perform clinical research in settings with limited access to oxygen and/or ventilators, for example in low- and middle-income countries.

Compassionate drug (mis)use during pandemics: lessons for COVID-19 from 2009.

BACKGROUND: New emerging infections have no known treatment. Assessing potential drugs for safety and efficacy enables clinicians to make evidence-based treatment decisions and contributes to overall outbreak control. However, it is difficult to launch clinical trials in the unpredictable environment of an outbreak. We conducted a bibliometric systematic review for the 2009 influenza pandemic to determine the speed and quality of evidence generation for treatments. This informs approaches to high-quality evidence generation in this and future pandemics. METHODS: We searched PubMed for all clinical data (including clinical trial, observational and case series) describing treatment for patients with influenza A(H1N1)pdm09 and ClinicalTrials.gov for research that aimed to enrol patients with the disease. RESULTS: Thirty-three thousand eight hundred sixty-nine treatment courses for patients hospitalised with A(H1N1)pdm09 were detailed in 160 publications. Most were retrospective observational studies or case series. Five hundred ninety-two patients received treatment (or placebo) as participants in a registered interventional clinical trial with results publicly available. None of these registered trial results was available during the timeframe of the pandemic, and the median date of publication was 213 days after the Public Health Emergency of International Concern ended. CONCLUSION: Patients were frequently treated for pandemic influenza with drugs not registered for this indication, but rarely under circumstances of high-quality data capture. The result was a reliance on use under compassionate circumstances, resulting in continued uncertainty regarding the potential benefits and harms of anti-viral treatment. Rapid scaling of clinical trials is critical for generating a quality evidence base during pandemics.

Addressing challenges for clinical research responses to emerging epidemics and pandemics: a scoping review.

BACKGROUND: Major infectious disease outbreaks are a constant threat to human health. Clinical research responses to outbreaks generate evidence to improve outcomes and outbreak control. Experiences from previous epidemics have identified multiple challenges to undertaking timely clinical research responses. This scoping review is a systematic appraisal of political, economic, administrative, regulatory, logistical, ethical and social (PEARLES) challenges to clinical research responses to emergency epidemics and solutions identified to address these. METHODS: A scoping review. We searched six databases (MEDLINE, Embase, Global Health, PsycINFO, Scopus and Epistemonikos) for articles published from 2008 to July 2018. We included publications reporting PEARLES challenges to clinical research responses to emerging epidemics and pandemics and solutions identified to address these. Two reviewers screened articles for inclusion, extracted and analysed the data. RESULTS: Of 2678 articles screened, 76 were included. Most presented data relating to the 2014-2016 Ebola virus outbreak or the H1N1 outbreak in 2009. The articles related to clinical research responses in Africa (n = 37), Europe (n = 8), North America (n = 5), Latin America and the Caribbean (n = 3) and Asia (n = 1) and/or globally (n = 22). A wide range of solutions to PEARLES challenges was presented, including a need to strengthen global collaborations and coordination at all levels and develop pre-approved protocols and equitable frameworks, protocols and standards for emergencies. Clinical trial networks and expedited funding and approvals were some solutions implemented. National ownership and community engagement from the outset were a key enabler for delivery. Despite the wide range of recommended solutions, none had been formally evaluated. CONCLUSIONS: To strengthen global preparedness and response to the COVID-19 pandemic and future epidemics, identified solutions for rapid clinical research deployment, delivery, and dissemination must be implemented. Improvements are urgently needed to strengthen collaborations, funding mechanisms, global and national research capacity and capability, targeting regions vulnerable to epidemics and pandemics. Solutions need to be flexible to allow timely adaptations to context, and research led by governments of affected regions. Research communities globally need to evaluate their activities and incorporate lessons learnt to refine and rehearse collaborative outbreak response plans in between epidemics.

A rapid research needs appraisal methodology to identify evidence gaps to inform clinical research priorities in response to outbreaks-results from the Lassa fever pilot.

BACKGROUND: Infectious disease epidemics are a constant threat, and while we can strengthen preparedness in advance, inevitably, we will sometimes be caught unaware by novel outbreaks. To address the challenge of rapidly identifying clinical research priorities in those circumstances, we developed and piloted a protocol for carrying out a systematic, rapid research needs appraisal (RRNA) of existing evidence within 5 days in response to outbreaks globally, with the aim to inform clinical research prioritization. METHODS: The protocol was derived from rapid review methodologies and optimized through effective use of pre-defined templates and global time zones. It was piloted using a Lassa fever (LF) outbreak scenario. Databases were searched from 1969 to July 2017. Systematic reviewers based in Canada, the UK, and the Philippines screened and extracted data using a systematic review software. The pilot was evaluated through internal analysis and by comparing the research priorities identified from the data, with those identified by an external LF expert panel. RESULTS: The RRNA pilot was completed within 5 days. To accommodate the high number of articles identified, data extraction was prioritized by study design and year, and the clinical research prioritization done post-day 5. Of 118 potentially eligible articles, 52 met the data extraction criteria, of which 46 were extracted within the 5-day time frame. The RRNA team identified 19 clinical research priorities; the expert panel independently identified 21, of which 11 priorities overlapped. Each method identified a unique set of priorities, showing that combining both methods for clinical research prioritization is more robust than using either method alone. CONCLUSIONS: This pilot study shows that it is feasible to carry out a systematic RRNA within 5 days in response to a (re-) emerging outbreak to identify gaps in existing evidence, as long as sufficient resources are identified, and reviewers are experienced and trained in advance. Use of an online systematic review software and global time zones effectively optimized resources. Another 3 to 5 days are recommended for review of the extracted data and to formulate clinical research priorities. The RRNA can be used for a "Disease X" scenario and should optimally be combined with an expert panel to ensure breadth and depth of coverage of clinical research priorities.

Burden of disease and economic impact of human Streptococcus suis infection in Viet Nam.

BACKGROUND: Streptococcus suis is a zoonotic disease mainly affecting men of working age and can result in death or long-term sequelae, including severe hearing loss and vestibular dysfunction. We aimed to quantify the burden of disease and economic impact of this infection in Viet Nam. METHODS: The annual disease incidence for the period 2011-2014 was estimated based on surveillance data using a multiple imputation approach. We calculated disease burden in disability-adjusted life years (DALYs) and economic costs using an incidence-based approach from a patient's perspective and including direct and indirect impacts of S. suis infection and its long-term sequelae. RESULTS: The estimated annual incidence rate was 0.318, 0.324, 0.255 and 0.249 cases per 100 000 population in 2011, 2012, 2013 and 2014, respectively. The corresponding DALYs lost were 1832, 1866, 1467 and 1437. The mean direct cost per episode was US$1635 (95% confidence interval 1352-1923). The annual direct cost was US$370 000-500 000 and the indirect cost was US$2.27-2.88 million in this time period. CONCLUSIONS: This study showed a large disease burden and high economic impact of S. suis infection and provides important data for disease monitoring and control.

Assessment of Human-to-Human Transmissibility of Avian Influenza A(H7N9) Virus Across 5 Waves by Analyzing Clusters of Case Patients in Mainland China, 2013-2017.

Background: The 2016-17 epidemic of human infections with avian influenza A(H7N9) virus was alarming, due to the surge in reported cases across a wide geographic area and the emergence of highly-pathogenic A(H7N9) viruses. Our study aimed to assess whether the human-to-human transmission risk of A(H7N9) virus has changed across the 5 waves since 2013. Methods: Data on human cases and clusters of A(H7N9) virus infection were collected from the World Health Organization, open access national and provincial reports, informal online sources, and published literature. We compared the epidemiological characteristics of sporadic and cluster cases, estimated the relative risk (RR) of infection in blood relatives and non-blood relatives, and estimated the bounds on the effective reproductive number (Re) across waves from 2013 through September 2017. Results: We identified 40 human clusters of A(H7N9) virus infection, with a median cluster size of 2 (range 2-3). The overall RR of infection in blood relatives versus non-blood relatives was 1.65 (95% confidence interval [CI]: 0.88, 3.09), and was not significantly different across waves (χ2 = 2.66, P = .617). The upper limit of Re for A(H7N9) virus was 0.12 (95% CI: 0.10, 0.14) and was not significantly different across waves (χ2 = 1.52, P = .822). Conclusions: The small cluster size and low Re suggest that human-to-human transmissibility of A(H7N9) virus has not changed over time and remains limited to date. Continuous assessment of A(H7N9) virus infections and human case clusters is of crucial importance for public health.

Clinical assessment is a neglected component of outbreak preparedness: evidence from refugee camps in Greece.

BACKGROUND: Refugees may have an increased vulnerability to infectious diseases, and the consequences of an outbreak are more severe in a refugee camp. When an outbreak is suspected, access to clinical information is critical for investigators to verify that an outbreak is occurring, to determine the cause and to select interventions to control it. Experience from previous outbreaks suggests that the accuracy and completeness of this information is poor. This study is the first to assess the adequacy of clinical characterisation of acute medical illnesses in refugee camps. The objective is to direct improvements in outbreak identification and management in this vulnerable setting. METHODS: We collected prospective data in 13 refugee camps in Greece. We passively observed consultations where patients presented with syndromes that might warrant inclusion into an existing syndromic surveillance system and then undertook a structured assessment of routine clinical data collection to examine the extent to which key clinical parameters required for an outbreak response were ascertained and then documented. RESULTS: A total of 528 patient consultations were included. The most common presenting condition was an acute respiratory illness. Clinicians often made a comprehensive clinical assessment, especially for common syndromes of respiratory and gastrointestinal conditions, but documented their findings less frequently. For fewer than 5% of patients were a full set of vital signs ascertained and so the severity of patient illnesses was largely unknown. In only 11% of consultations was it verified that a patient who met the case criteria for syndromic surveillance reporting based on an independent assessment was reported into the system. DISCUSSION: Opportunities exist to strengthen clinical data capture and recording in refugee camps, which will produce a better calibrated and directed public health response. CONCLUSION: Information of significant utility for outbreak response is collected at the clinical interface and we recommend improving how this information is recorded and linked into surveillance systems.

Global health security: the wider lessons from the west African Ebola virus disease epidemic.

The Ebola virus disease outbreak in West Africa was unprecedented in both its scale and impact. Out of this human calamity has come renewed attention to global health security--its definition, meaning, and the practical implications for programmes and policy. For example, how does a government begin to strengthen its core public health capacities, as demanded by the International Health Regulations? What counts as a global health security concern? In the context of the governance of global health, including WHO reform, it will be important to distil lessons learned from the Ebola outbreak. The Lancet invited a group of respected global health practitioners to reflect on these lessons, to explore the idea of global health security, and to offer suggestions for next steps. Their contributions describe some of the major threats to individual and collective human health, as well as the values and recommendations that should be considered to counteract such threats in the future. Many different perspectives are proposed. Their common goal is a more sustainable and resilient society for human health and wellbeing.

The potential for a controlled human infection platform in Singapore.

For over 100 years, controlled human infection (CHI) studies have been performed to advance the understanding of the pathogenesis, treatment and prevention of infectious diseases. This methodology has seen a resurgence, as it offers an efficient model for selecting the most promising agents for further development from available candidates. CHI studies are utilised to bridge safety and immunogenicity testing and phase II/III efficacy studies. However, as this platform is not currently utilised in Asia, opportunities to study therapeutics and vaccines for infections that are important in Asia are missed. This review examines the regulatory differences for CHI studies between countries and summarises other regulatory differences in clinical trials as a whole. We found that the regulations that would apply to CHI studies in Singapore closely mirror those in the United Kingdom, and conclude that the regulatory and ethical guidelines in Singapore are compatible with the conduct of CHI studies.

Antibiotic use and resistance in emerging economies: a situation analysis for Viet Nam.

BACKGROUND: Antimicrobial resistance is a major contemporary public health threat. Strategies to contain antimicrobial resistance have been comprehensively set forth, however in developing countries where the need for effective antimicrobials is greatest implementation has proved problematic. A better understanding of patterns and determinants of antibiotic use and resistance in emerging economies may permit more appropriately targeted interventions.Viet Nam, with a large population, high burden of infectious disease and relatively unrestricted access to medication, is an excellent case study of the difficulties faced by emerging economies in controlling antimicrobial resistance. METHODS: Our working group conducted a situation analysis of the current patterns and determinants of antibiotic use and resistance in Viet Nam. International publications and local reports published between 1-1-1990 and 31-8-2012 were reviewed. All stakeholders analyzed the findings at a policy workshop and feasible recommendations were suggested to improve antibiotic use in Viet Nam.Here we report the results of our situation analysis focusing on: the healthcare system, drug regulation and supply; antibiotic resistance and infection control; and agricultural antibiotic use. RESULTS: Market reforms have improved healthcare access in Viet Nam and contributed to better health outcomes. However, increased accessibility has been accompanied by injudicious antibiotic use in hospitals and the community, with predictable escalation in bacterial resistance. Prescribing practices are poor and self-medication is common - often being the most affordable way to access healthcare. Many policies exist to regulate antibiotic use but enforcement is insufficient or lacking.Pneumococcal penicillin-resistance rates are the highest in Asia and carbapenem-resistant bacteria (notably NDM-1) have recently emerged. Hospital acquired infections, predominantly with multi-drug resistant Gram-negative organisms, place additional strain on limited resources. Widespread agricultural antibiotic use further propagates antimicrobial resistance. CONCLUSIONS: Future legislation regarding antibiotic access must alter incentives for purchasers and providers and ensure effective enforcement. The Ministry of Health recently initiated a national action plan and approved a multicenter health improvement project to strengthen national capacity for antimicrobial stewardship in Viet Nam. This analysis provided important input to these initiatives. Our methodologies and findings may be of use to others across the world tackling the growing threat of antibiotic resistance.

Diagnostic accuracy of microscopic Observation Drug Susceptibility (MODS) assay for pediatric tuberculosis in Hanoi, Vietnam.

INTRODUCTION: Microscopic [corrected] Observation Drug Susceptibility (MODS) has been shown to be an effective and rapid technique for early diagnosis of tuberculosis (TB). Thus far only a limited number of studies evaluating MODS have been performed in children and in extra-pulmonary tuberculosis. This study aims to assess relative accuracy and time to positive culture of MODS for TB diagnosis in children admitted to a general pediatric hospital in Vietnam. METHODS/PRINCIPAL FINDINGS: Specimens from children with suspected TB were tested by smear, MODS and Lowenstein-Jensen agar (LJ). 1129 samples from 705 children were analyzed, including sputum (n=59), gastric aspirate (n=775), CSF (n=148), pleural fluid (n=33), BAL (n=41), tracheal fluid (n=45), other (n=28). 113 TB cases were defined based on the "clinical diagnosis" (confirmed and probable groups) as the reference standard, in which 26% (n=30) were diagnosed as extra-pulmonary TB. Analysis by patient shows that the overall sensitivity and specificity of smear, LJ and MODS against "clinical diagnosis" was 8.8% and 100%, 38.9% and 100%, 46% and 99.5% respectively with MODS significantly more sensitive than LJ culture (P=0.02). When analyzed by sample type, the sensitivity of MODS was significantly higher than LJ for gastric aspirates (P=0.004). The time to detection was also significantly shorter for MODS than LJ (7 days versus 32 days, P<0.001). CONCLUSION: MODS [corrected] is a sensitive and rapid culture technique for detecting TB in children. As MODS culture can be performed at a BSL2 facility and is inexpensive, it can therefore be recommended as a routine test for children with symptoms suggestive of TB in resource-limited settings.

Understanding and managing zoonotic risk in the new livestock industries.

BACKGROUND: In many parts of the world, livestock production is undergoing a process of rapid intensification. The health implications of this development are uncertain. Intensification creates cheaper products, allowing more people to access animal-based foods. However, some practices associated with intensification may contribute to zoonotic disease emergence and spread: for example, the sustained use of antibiotics, concentration of animals in confined units, and long distances and frequent movement of livestock. OBJECTIVES: Here we present the diverse range of ecological, biological, and socioeconomic factors likely to enhance or reduce zoonotic risk, and identify ways in which a comprehensive risk analysis may be conducted by using an interdisciplinary approach. We also offer a conceptual framework to guide systematic research on this problem. DISCUSSION: We recommend that interdisciplinary work on zoonotic risk should take into account the complexity of risk environments, rather than limiting studies to simple linear causal relations between risk drivers and disease emergence and/or spread. In addition, interdisciplinary integration is needed at different levels of analysis, from the study of risk environments to the identification of policy options for risk management. CONCLUSION: Given rapid changes in livestock production systems and their potential health implications at the local and global level, the problem we analyze here is of great importance for environmental health and development. Although we offer a systematic interdisciplinary approach to understand and address these implications, we recognize that further research is needed to clarify methodological and practical questions arising from the integration of the natural and social sciences.

DodaLab: an urban health and demographic surveillance site, the first three years in Hanoi, Vietnam.

RATIONALE: Health and demographic surveillance sites (HDSSs) are important sources for health planning and policy in many low and middle income countries. Almost all HDSSs are in rural settings. The article aims to present the experiences and some concrete results for the first three years of operation of an urban HDSS in Hanoi, Vietnam, and discuss advantages and disadvantages of conducting health studies in HDSSs. DESIGN, POPULATION AND SAMPLE SIZE: The DodaLab urban HDSS was established in 2007 in three communes at different economic levels in Dong Da district, Hanoi, Vietnam. Demographic, social and economic information about 10,000 households and their 37,000 persons was obtained through household interviews. Quarterly follow-up was initiated to provide information about vital events, birth, death and migration. A new household survey was undertaken in 2009. The existing rural HDSS FilaBavi, started in 1999, with 12,000 households and 52,000 persons, was used as the blueprint. CONCLUSIONS: It was possible to establish and run an urban HDSS with experiences from the rural site. The urban and rural contexts are different and demographically, economically and socially complex, but the use of HDSSs can facilitate research beyond very simplified models for comparisons. General statements about external validity of results from the HDSS cannot be made. This issue has to be considered specifically in every situation as an integral part of the research so that the results can be made useful outside the researched HDSS and in performing relevant comparisons.

Studying the effectiveness of activated carbon R95 respirators in reducing the inhalation of combustion by-products in Hanoi, Vietnam: a demonstration study.

BACKGROUND: Urban air pollution is an increasing health problem, particularly in Asia, where the combustion of fossil fuels has increased rapidly as a result of industrialization and socio-economic development. The adverse health impacts of urban air pollution are well established, but less is known about effective intervention strategies. In this demonstration study we set out to establish methods to assess whether wearing an R95 activated carbon respirator could reduce intake of polycyclic aromatic hydrocarbons (PAH) in street workers in Hanoi, Vietnam. METHODS: In this demonstration study we performed a cross-over study in which non-smoking participants that worked at least 4 hours per day on the street in Hanoi were randomly allocated to specific respirator wearing sequences for a duration of 2 weeks. Urines were collected after each period, i.e., twice per week, at the end of the working day to measure hydroxy PAHs (OH-PAH) using gas chromatography/high resolution mass spectrometry. The primary endpoint was the urinary concentration of 1-hydroxypyrene (1-OHP). RESULTS: Forty-four participants (54.5% male, median age 40 years) were enrolled with the majority being motorbike taxi drivers (38.6%) or street vendors (34.1%). The baseline creatinine corrected urinary level for 1-OHP was much higher than other international comparisons: 1020 ng/g creatinine (IQR: 604-1551). Wearing a R95 mask had no significant effect on 1-OHP levels: estimated multiplicative effect 1.0 (95% CI: 0.92-1.09) or other OH-PAHs, except 1-hydroxynaphthalene (1-OHN): 0.86 (95% CI: 0.11-0.96). CONCLUSIONS: High levels of urine OH-PAHs were found in Hanoi street workers. No effect was seen on urine OH-PAH levels by wearing R95 particulate respirators in an area of high urban air pollution, except for 1-OHN. A lack of effect may be de to gaseous phase PAHs that were not filtered efficiently by the respirator. The high levels of urinary OH-PAHs found, urges for effective interventions. TRIAL REGISTRATION: ISRCTN74390617 (date of assignation: 04/08/2009).

Prevalence and determinants of influenza vaccination in Australians aged 40 years and over--a national survey.

OBJECTIVES: To determine influenza vaccination coverage in 2001 in Australian adults aged > or = 40 years, assess awareness of and attitudes to influenza vaccine, factors associated with vaccination, and estimate uptake of free vaccine provided to those aged > or = 65 years. METHODS: National computer-assisted telephone interview (CATI) survey in October/November 2001. RESULTS: Interviews were completed with 5,266 people aged > or = 65 and 2,415 aged 40-64 years. Thirty per cent of selected households participated. Overall, 67% of respondents believed that the vaccine was somewhat to very effective in preventing influenza. Seventy-eight per cent of those aged > or = 65 years reported influenza vaccination; 89% had received it free. Independent predictors of vaccination were: belief that influenza vaccine is effective in preventing influenza (OR=13.5, 95% CI 10.6-17.2); and the presence of chronic disease (OR=1.6, 95% CI 1.3-2.0). Overall, 24% of those aged 40-64 years were vaccinated; only 34% of those who met any of the criteria for vaccination (medical risk factor, at-risk occupation, or being Aboriginal or Torres Strait Islander) reported vaccination. CONCLUSIONS: Influenza vaccine coverage was high in those aged > or = 65 years, but coverage of those at-risk aged 40-64 years remained suboptimal. Immunisation against influenza was influenced more by beliefs about the vaccine's effectiveness and existing medical risk factors, rather than socio-demographic factors such as gender and income.

Using computer simulations to compare pertussis vaccination strategies in Australia.

High levels of notified pertussis in adolescents and adults, persisting severe disease (hospitalization and deaths) in infants despite high childhood immunization coverage, together with the availability of adult-formulated pertussis vaccines, have made alternate strategies for vaccine control of pertussis an important issue in Australia. An age-structured computer simulation model was used to compare the likely effects of adopting different vaccination strategies in Australia on pertussis transmission by age group over a 50 year time period. Epidemiological parameters and vaccination coverage in Australia were estimated from previous pertussis modeling studies and existing data. In the simulations, replacing the pertussis booster at 18 months with a booster dose for adolescents at an age between 12 and 17 years, assuming 80% coverage, led to decreases in pertussis cases of 30% in children of ages 0-23 months (who have the highest complication rates) and of 25% in adolescents, but an increase of 15% in cases in 2-4-year-old children. The simulations did not suggest any shift of pertussis cases into the adult child-bearing years. Varying parameter values in the simulations in a series of sensitivity analyses showed the model predictions to be robust over a plausible range. The results of these simulations suggest that the recent change in the Australian pertussis vaccination schedule, replacing the 18 month dose with a pertussis booster in 15-17-year-old adolescents, is very likely to reduce overall pertussis incidence in Australia without increasing the cost of the current vaccine program.

Progress towards eliminating Hib in Australia: an evaluation of Haemophilus influenzae type b prevention in Australia, 1 July 1993 to 30 June 2000.

The status of Haemophilus influenzae (Hib) disease and its prevention by vaccination was reviewed for the period 1997 to 2000. This forms the background to a change in national vaccine policy, from the use of two Hib vaccines to the use of PRP-OMP only throughout Australia from May 2000. Notifications of Hib in the 7-year period between 1993 and 2000 declined by 87 per cent among children 0-4 years of age; adjustment for likely under-reporting increase this to a 95 per cent reduction. Among age groups not included in the immunisation program, there was also a substantial decline in notified cases. Overall, a minimum 430 cases and 13 deaths were prevented by Hib immunisation annually in Australia. Enhanced Hib surveillance recorded 532 cases over seven years, with 353 in unvaccinated persons, 74 fulfilling criteria for true vaccine failure and 75 partially immunised. Of unvaccinated cases, 60 and 182 were eligible for routine and catch-up immunisation respectively. Although the overall incidence for 0-4 years of age declined from 15 to 1.2 cases per 100,000 population, the proportion of cases under six months of age increased from 11 per cent to 23 per cent. Overall vaccine effectiveness, estimated using data from the last five years of the program, was 83 per cent (95% CI 71-91%), increasing to 90 per cent (95% CI 83-94%) when adjusted for under-reporting to the Australian Childhood Immunisation Register. Among Aboriginal and Torres Strait Islander people, the incidence of invasive Hib disease fell from 4.6 cases per 100,000 population to 0.7 cases per 100,000 population but the proportion of cases now occurring among Aboriginal or Torres Strait Islander people increased significantly, from 7 to 15 per cent. The Hib immunisation program in Australia has been highly successful. Nevertheless, experience in Australia and elsewhere indicates that continued careful monitoring of Hib disease, with high quality laboratory surveillance, remains important.