David Harley

Introduction This thesis concerns the mosquito-borne arbovirus Ross River (RR) virus. The main objectives were to determine the vector associations, the incidence, costs and natural history of disease, and behavioural and environmental risks for infection in tropical ...

To investigate the long term survival of MDR-TB patients compared to non-MDR-TB in Henan province in 2010. Participants were randomly selected in 2010 from a dataset generated by an anti-TB drug resistance surveillance survey conducted by the Tuberculosis Control Institute, Henan Centre for Disease Control and Prevention in 2001, supported by the World Health Organization. Information on patient's demographic profile and medical records was extracted by trained doctors and nurses at local anti-TB dispensaries. Interviews were carried out using questionnaires to collect information on the socioeconomic features and survival status. Bivariate and multivariate with logistic regression were performed for data analysis. The long term outcome of MDR-TB patients was much poorer when compared to non-MDR-TB patients. The case fatality was much higher among MDR-TB than non-MDR-TB patients (22.1% vs. 6.7%). The risk factors associated with the poorer outcome would include drug resistance status, disease relapse, hospitalization for treatment and long treatment period. Compared to non-MDR-TB, the survival time for MDR-TB was much shorter after having had the disease (6.7 years vs. 8.0 years). MDR-TB patients had poor long term outcomes. As most of the cured TB patients were under productive age in the society, the high case fatality rate of MDR-TB would impose big burden on the related family and communities. Findings from this study suggested that the TB control programs should involve more efforts be paid on MDR-TB control, in order to reduce the burden of the disease.

Tuberculosis (TB) poses a significant public health challenge in the 22 Pacific island countries and territories. Using TB surveillance data and World Health Organization (WHO) estimates from 2000 to 2013, we summarize the epidemiology of TB in the Pacific. This was a descriptive study of incident TB cases reported annually by Pacific island national TB programmes to WHO. We counted cases and calculated proportions and case notification rates per 100 000 population. We calculated the proportion of TB patients who completed TB treatment and summed estimates of national incidence, prevalence and mortality, provided by WHO, to produce regional incidence, prevalence and mortality rates per 100 000 population. Estimated TB incidence in the Pacific has remained high but stable from 2000 to 2013; estimated prevalence and mortality have fallen by 20% and 47%, respectively. The TB case notification rate increased by 58%, from 146 to 231 per 100 000 population in the same time period. In 2013, 24 145 TB cases were notified, most (94% or 22 657) were from Papua New Guinea. Kiribati had the highest TB case notification rate at 398 cases per 100 000 population. TB case notification rates were also high in Papua New Guinea, the Marshall Islands and Tuvalu (309, 283 and 182, respectively). TB in the Pacific is improving in some areas; however, high rates affect many countries and the estimated regional incidence rate is stable. To further reduce the burden of TB, a combination of dedicated public health and system-wide approaches are required along with poverty reduction and social protection initiatives.

Dengue occurred sporadically in Bangladesh from 1964 until a large epidemic in 2000 established the virus. We trace dengue from the time it was first identified in Bangladesh and identify factors favourable to future dengue haemorrhagic fever epidemics. The epidemic in 2000 was likely due to introduction of a dengue virus strain from a nearby endemic country, probably Thailand. Cessation of dichlorodiphenyltrichloroethane (DDT) spraying, climatic, socio-demographic, and lifestyle factors also contributed to epidemic transmission. The largest number of cases was notified in 2002 and since then reported outbreaks have generally declined, although with increased notifications in alternate years. The apparent decline might be partially due to public awareness with consequent reduction in mosquito breeding and increased prevalence of immunity. However, passive hospital-based surveillance has changed with mandatory serological confirmation now required for case reporting. Further, a large number of cases remain undetected because only patients with severe dengue require hospitalisation. Thus, the reduction in notification numbers may be an artefact of the surveillance system. Indeed, population-based serological survey indicates that dengue transmission continues to be common. In the future, the absence of active interventions, unplanned urbanisation, environmental deterioration, increasing population mobility, and economic factors will heighten dengue risk. Projected increases in temperature and rainfall may exacerbate this.

During 1996-1998 60,619 mosquitoes were collected around Cairns, Australia and processed for Alphavirus isolation. Thirty-three isolates of Ross River (RR) virus were made from 9 species, Aedes imprimens, Aedes kochi, Aedes notoscriptus, Aedes vigilax, Culex annulirostris, Culex gelidus, Mansonia septempunctata, Verrallina (formerly Aedes) carmenti, and Verrallina lineatus. Attempts to isolate RR virus from 121 Aedes aegypti were unsuccessful. Twenty-six (79%) of the isolates came from within 1 km of a colony of spectacled flying-foxes, Pteropus conspicillatus. The minimum infection rate for these mosquitoes was 1.0 compared with 0.2 per 1,000 for mosquitoes trapped at all other sites. Ross River virus has not previously been isolated from Ae. imprimens, Cx. gelidus, Ma. septempunctata, Ve. carmenti, or Ve. lineatus. This is also the first isolation of an arbovirus from Cx. gelidus in Australia. In conclusion, the vector status of Ve. carmenti, Ae. aegypti and Ma. septempunctata war...

A follow-up study of musculoskeletal symptoms after Pogosta virus infection. Twenty-six patients with earlier serologically confirmed Pogosta disease were examined. Ultrasonography of affected joints was performed in patients who had chronic musculoskeletal symptoms. Serum antibodies against Sindbis virus were determined. The patients were typed for HLA-DR and B27. Efforts were made using the polymerase chain reaction to demonstrate the virus. Only 50% of the patients were symptomless 2.5 yr after onset of Pogosta disease. Three patients had fibromyalgia, six had occasional arthralgia and two had chronic arthritis. The epidemiology of Pogosta disease is changing and practitioners should be better aware of it. Pogosta virus infection may lead to chronic musculoskeletal discomfort and arthritis.

Aggressive challenging behaviour is frequently reported in adults with intellectual disability and it is often treated with antipsychotic drugs. However, no adequate evidence base for this practice exists. We compared flexible doses of haloperidol (a typical, first-generation antipsychotic drug), risperidone (an atypical, second-generation antipsychotic), and placebo, in the treatment of this behaviour. 86 non-psychotic patients presenting with aggressive challenging behaviour from ten centres in England and Wales, and one in Queensland, Australia, were randomly assigned to haloperidol (n=28), risperidone (n=29), or placebo (n=29). Clinical assessments of aggression, aberrant behaviour, quality of life, adverse drug effects, and carer uplift (positive feelings about the care of the disabled person) and burden, together with total costs, were recorded at 4, 12, and 26 weeks. The primary outcome was change in aggression after 4 weeks' treatment, which was recorded with the modifie...

Climate change is predicted to increase the transmission of many vector-borne pathogens, representing an increasing threat to a safe blood supply. In early 2011, Australia experienced catastrophic rainfall and flooding, coupled with increased arbovirus transmission. We used Ross River (RRV) and Barmah Forest (BFV) viruses as test cases to investigate the potential risk posed to Australia's blood supply after this period of increased rainfall . We estimated the risk of collecting an infected donation as one in 2,500-58,000 for RRV and one in 2,000-28,000 for BFV. Climate change may incrementally increase the arbovirus threat to blood safety.

: Corticosteroid use during acute viral arthritis is considered to be contraindicated as a result of the risk of immunosuppression causing enhanced infection and disease exacerbation. : The objective of this study was to analyze the effect of oral corticosteroid therapy on symptoms of the viral arthritic disease, Ross River virus disease (RRVD). : Patients with RRVD were enrolled in 2 prospective longitudinal studies. Medications and comorbidities were recorded and the patients' health was assessed using 2 validated quality-of life-questionnaires, the Comparison of Clinical Health Assessment Questionnaire (CLINHAQ) and the Medical Outcomes Study Short Form (SF-36). : Six patients taking corticosteroids showed no exacerbation of RRVD compared with patients not taking steroids. The CLINHAQ Functional Disability Index also indicated that corticosteroid users recovered faster compared with patients using nonsteroidal antiinflammatory drugs. : Conventional concern that corticosteroid treatment will exacerbate disease appears unjustified for alphaviral arthritides once serodiagnosis has demonstrated antiviral immunity.

Climate change will have significant and diverse impacts on human health. These impacts will include changes in infectious disease incidence. In this article, the authors review the current situation and potential future climate change impacts for respiratory, diarrheal, and vector-borne diseases in Australia. Based on this review, the authors suggest adaptive strategies within the health sector and also recommend future research priorities.

Studies on socioeconomic and epidemiological effects of hearing impairment in middle-income countries of Southeast Asia are still quite scarce. This study examines the association between hearing impairment and health outcomes in Thailand. Data derived from a cohort of 87 134 Open University adults aged 15 to 87 years residing throughout Thailand. Approximately 8.5% of cohort members reported trouble hearing and 0.13% reported being deaf. After adjusting for age and gender, poor self-assessed health was strongly associated with some trouble hearing (odds ratio [OR] = 2.70, 95% confidence interval [CI] = 2.48-2.93) and deafness (OR = 3.08, 95% CI = 1.73-5.50). Population attributable fractions for hearing impairment were 12.9% for poor self-assessed health, 9.8% for poor psychological health, 3.3% for metabolic disorders, and 4.1% for cardiovascular conditions. More attention needs to be paid on hearing impairment with regular check-ups and early detections.

Background: This study was conducted in the Pacific island nation of Vanuatu. Our objective was to assess knowledge, attitudes and practice of traditional healers who treat lung diseases and tuberculosis (TB), including their willingness to collaborate with the national TB programme.

Background: Ross River virus (RRV) disease is the most widespread mosquito-borne disease in Australia. The disease is maintained in enzootic cycles between mosquitoes and reservoir hosts. During outbreaks and in endemic regions, RRV transmission can be sustained between vectors and reservoir hosts in zoonotic cycles with spillover to humans. Symptoms include arthritis, rash, fever and fatigue and can persist for several months. The prevalence and associated morbidity make this disease a medically and economically important mosquito-borne disease in Australia. Methods: Climate, environment, and RRV vector and reservoir host information were used to develop pre-dictive models in four regions in NSW over a 13-year period (1991–2004). Polynomial distributed lag (PDL) models were used to explore long-term influences of up to 2 years ago that could be related to RRV activity. Results: Each regional model consisted of a unique combination of predictors for RRV disease highlighting the differences in the disease ecology and epidemiology in New South Wales (NSW). Events up to 2 years before were found to influence RRV activity. The shorter-term associations may reflect conditions that promote virus amplification in RRV vectors whereas long-term associations may reflect RRV reservoir host breeding and herd immunity. The models indicate an association between host populations and RRV disease, lagged by 24 months, suggesting two or more generations of susceptible juveniles may be necessary for an outbreak. Model sensitivities ranged from 60.4% to 73.1%, and model specificities ranged from 57.9% to 90.7%. This was the first study to include reservoir host data into statistical RRV models; the inclusion of host parameters was found to improve model fit significantly. Conclusion: The research presents the novel use of a combination of climate, environment, and RRV vector and reservoir host information in statistical predictive models. The models have potential for public health decision-making.

SUMMARY We aimed to reparameterize and validate an existing dengue model, comprising an entomological component (CIMSiM) and a disease component (DENSiM) for application in Malaysia. With the model we aimed to measure the effect of importation rate on dengue incidence, and to determine the potential impact of moderate climate change (a 1 °C temperature increase) on dengue activity. Dengue models (comprising CIMSiM and DENSiM) were reparameterized for a simulated Malaysian village of 10 000 people, and validated against monthly dengue case data from the district of Petaling Jaya in the state of Selangor. Simulations were also performed for 2008-2012 for variable virus importation rates (ranging from 1 to 25 per week) and dengue incidence determined. Dengue incidence in the period 2010–2012 was modelled, twice, with observed daily weather and with a 1 °C increase, the latter to simulate moderate climate change. Strong concordance between simulated and observed monthly dengue cases was observed (up to r = 0·72). There was a linear relationship between importation and incidence. However, a doubling of dengue importation did not equate to a doubling of dengue activity. The largest individual dengue outbreak was observed with the lowest dengue importation rate. Moderate climate change resulted in an overall decrease in dengue activity over a 3-year period, linked to high human seroprevalence early on in the simulation. Our results suggest that moderate reductions in importation with control programmes may not reduce the frequency of large outbreaks. Moderate increases in temperature do not necessarily lead to greater dengue incidence.

Background: We conducted a cohort study to compare the characteristics of MDR-TB with non-MDR-TB patients and to measure long term (9-year) mortality rate and determine factors associated with death in China. Methods: We reviewed the medical records of 250 TB cases from a 2001 survey to compare 100 MDR-TB patients with 150 non-MDR-TB patients who were treated in 2001-2002. Baseline attributes extracted from the records were compared between the two cohorts and long-term mortality and risk factors were determined at nine-year follow-up in 2010.

This article reviews the theoretical basis and methods for disability measurement. Different methods arise from different theoretical perspectives. Recent efforts to develop a general international disability measure consistent with the social model of disability aim to produce an internationally comparable measure of disability with which to assess the equalisation of opportunities. Such a measure cannot consistently identify disabled people in need of health and social services. Correctly identifying those in need of these services particularly concerns developing countries where government revenues and disability services are severely limited. This review highlights the need for multiple disability measures to meet different purposes of measurement. The Washington Group general measure on disability and Katz's Activities of Daily Living Index are recommended as valid measures of varying functioning level consistent with the International Classification of Functioning, Disability and Health. The article draws the links between different models of disability and measurement methods. The social model of disability is important for defining general disability prevalence for the purpose of assessing equalisation of opportunities, but is unsuitable for identifying the proportion of the disabled population in need of health and social services. We advocate the use of multiple disability measures to meet different policy objectives: a general disability measure to monitor the level of functioning in a population and formulate disability-inclusive policies, and a measure of severe disability to identify persons with high service needs for the purpose of health and social policy design. Estimation of severe disability is pertinent in developing countries where disability services and public resources are severely limited.

Local weather influences the transmission of the dengue virus. Most studies analyzing the relationship between dengue and climate are based on relatively coarse aggregate measures such as mean temperature. Here, we include both mean temperature and daily fluctuations in temperature in modelling dengue transmission in Dhaka, the capital of Bangladesh. We used a negative binomial generalized linear model, adjusted for rainfall, anomalies in sea surface temperature (an index for El Niño-Southern Oscillation), population density, the number of dengue cases in the previous month, and the long term temporal trend in dengue incidence. In addition to the significant associations of mean temperature and temperature fluctuation with dengue incidence, we found interaction of mean and temperature fluctuation significantly influences disease transmission at a lag of one month. High mean temperature with low fluctuation increases dengue incidence one month later. Besides temperature, dengue incidence was also influenced by sea surface temperature anomalies in the current and previous month, presumably as a consequence of concomitant anomalies in the annual rainfall cycle. Population density exerted a significant positive influence on dengue incidence indicating increasing risk of dengue in over-populated Dhaka. Understanding these complex relationships between climate, population, and dengue incidence will help inform outbreak prediction and control. The sensitivity of mosquito vector and dengue virus biology to diurnal temperature variability has been established, but this study is the first analyzing these relations with dengue occurrence. We show that Dhaka's tropical hot monsoon climate and small variation in daily temperature enhance dengue transmission one month later. Large-scale climatic events like El Niño-Southern Oscillation and increasing population density of Dhaka also increase incidence. Our results therefore enable us to accurately estimate dengue transmission dynamics in densely populated areas that are also vulnerable to global warming by considering diurnal variability. Our approach reduces the chance of overestimating the PLOS Neglected Tropical Diseases |

Climatic and ecological change threaten human health globally. Manifestations include lost species, vanishing glaciers and more frequent heavy rain. In the second half of this century, accelerating sea level rise is likely to cause crop loss, and population dislocation. These problems may be magnified by dysfunctional human responses, including conflict. The population health consequences of these events can be classified as primary, secondary and tertiary. Primary signs include the acute and chronic stress of heat waves, and trauma from increased bush fires and flooding. Secondary signs are indirect, such as an altered distribution of arthropod vectors, intermediate hosts and pathogens that will produce changes in the epidemiology of many infectious diseases. More severe future health consequences of climate change are classified here as tertiary effects. If moderate or severe climate change scenarios prove accurate then these manifestations will occur over large areas, and could include famine, war and significant population displacement. Such effects would threaten governance and health. The health professions must respond to these challenges, especially the task of recognising and seeking to minimise tertiary health consequences. The gap between what we know and what we need to know concerning these issues can be narrowed by a new field of medical practice. The framework for this emerging discipline includes climate change, ecology and global health. Combined, these dimensions may be called ecomedicine. Actions to reduce individual emissions, to promote active transport (with its 'co-benefit' of preventing chronic disease), and involvement in group action to protect the environment and to prevent war, informed by understanding of the health of individual patients and populations, will be central to the practice of ecomedicine.