[Typewritten copy] / 210 p. : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, 1923

Thesis (M.D.) -- University of Adelaide, 1923. / [Typewritten copy].

This dissertation contrasts Hong Kong’s and the International Settlement’s management of malaria and of leprosy from the 1880s through the 1940s. This dissertation has two main objectives. Firstly it examines the historical management of malaria and leprosy within specific geo-political contexts. By focusing on British possessions in coastal China, this project explores the production of colonial medical knowledge within a transnational context, presents new and original analyses of the local history of the disease, and bridges the historiography of the British Empire and that of modern China. Secondly this dissertation contrasts Hong Kong’s and the International Settlement’s management of each of these two diseases. By focusing specifically on these two British possessions in coastal China, this project provides insights into the Imperial conceptualisation and management of Chinese bodies and Chinese environments, sheds light on broader historiographical debates regarding the role of colonial medicine, and complicates modern debates about the nature of colonialism in China.

Investigation of the relationship between iron deficiency, iron supplementation and susceptibility to infection, was suggested by the author's initial observations of an association of anaemia with serious bacterial infections in infancy in Papua New Guinea. The bulk of previous longitudinal clinical intervention studies in infancy showed beneficial effects of iron supplementation. However, defects of control and design and recording in these studies and contradictory anecdotal reports left the question unresolved. A prospective, placebo-controlled, randomised, double-blind trial of iron prophylaxis (3ml intramuscular iron dextran = 150mg Fe) to two month old infants was carried out on the North Coast of Papua New Guinea where there is high transmission of malaria. A literature review, pilot studies, protocol, demography, geography and laboratory methods developed are described. Findings indicate that the placebo control group became relatively iron deficient over the first year of life and that the iron dextran group had adequate, although not excessive iron stores and a higher mean haemoglobin; however, the prevalence and effects of malaria recorded in the field were higher in the iron dextran group. Analysis of field and hospital infectious morbidity in the trial indicated a deleterious association with iron dextran for all causes including respiratory infections (the main single reason for admission). Total duration of hospitalisation was significantly increased in the iron dextran group. Analysis of other factors showed (1) a higher admission rate associated with low weight-for-height recorded at the start of the trial; (2) a significant positive correlation between birth haemoglobin and hospital morbidity rates; (3) increased malaria rates in primiparous mothers of the cohort infants who received iron infusion during pregnancy; (4) lower relative risk of malaria associated with iron prophylaxis in individuals with alpha thalassaemia, which was found to be highly prevalent in this region. In conclusion, it is suggested that policies of iron supplementation, total dose iron injection and routine presumptive iron therapy for anaemia which are widely in practice in malaria endemic areas should be closely reviewed.

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 Queensland. 1. Literature review On the basis of the literature review there is strong evidence that Aedes vigilax, Ae. camptorhynchus and Culex annulirostris are important vectors in Australia. Aedes camptorhychus does not occur in Queensland. There is evidence that two peri-domestic container-breeding mosquitoes, Ae. notoscriptus and Ae. aegypti, may be vectors of the virus. The virus has been isolated from many other species but the role of most of these is unclear. It is unclear which vertebrate species are the major reservoirs for human infection. Studies are inconsistent with regard to the prevalence, duration and severity of symptoms and debility during RR virus disease. Nearly all epidemiological studies of RR virus have been descriptive. Therefore one can only surmise what the risks for human infection might be. Epidemiological studies to determine the associations between exposures and risk for disease do not exist. 2. Virus isolation from mosquitoes During 1996-1998 61,619 mosquitoes were processed for virus isolation. Thirty-three isolates of RR virus were made. The largest number (14) were from Ae. carmenti. The minimum infection rate (MIR) per 1,000 was 2.4. Isolates were also made from Ae. imprimens (1 isolate, MIR 10.3), Ae. kochi (2, 0.2), Ae. lineatus (1, 0.2), Ae. notoscriptus (1, 1.6), Ae. vigilax (1, 0.3), Cx. annulirostris (9, 0.3), Cx. vicinus (1, 4.0) and Mansonia septempunctata (3, 5.8). Ross River virus has been isolated from Cx. annulirostris, Ae. vigilax, Ae. notoscriputus and Ae. kochi but not from the other species. Ross River virus was not isolated from Ae. aegypti. Twenty-six isolates came from in or near a colony of 15,000 spectacled flying-fox, Pteropus conspicillatus. The proportion of RR virus positive pools from within 1 km. of this colony was significantly greater than elsewhere for all species combined and for Cx. annulirostris but not for Ae. carmenti. 3. The incidence and costs of Ross River virus disease Unpublished data on National, State and Territory notifications was collected. Crude incidence rates using census figures for denominator data were calculated. The same was done for the areas in which the other studies described in the thesis were carried out. An estimate of the cost of Ross River virus disease in Australia was made. During the period 1991-1998 of the States and Territories the Northern Territory (NT) had the highest and the Australian Capital Territory (ACT) the lowest notification incidences. These were 62-281 and 0-3 per 100,000 per annum, respectively. During this period the notification incidence for Queensland ranged from 70 to 149 per 100,000 per annum. For the local government areas of Cairns and Mareeba, where the majority of cases of RR virus disease for the studies described in this thesis were recruited, the notification incidences were between 74 and 267, and 28 and 200, respectively. On the basis of an average of 4,800 cases per annum in Australia the cost of serological testing and medical consultations were estimated at $443,520 and $105,600. Lost earnings were estimated at $1,798,560. The total cost for medical consultations, serological testing and lost earnings will therefore be over $2 million in an average year. 4. The natural history of Ross River virus disease In 1998 incident cases of RR virus disease were ascertained. Fifty-seven eligible cases were recruited but only 47 could be reviewed on 3 occasions and data on these were analysed. Cases were followed for up to 197 days. Review included history, examination and the administration of the Clinical Health Assessment Questionnaire (CLINHAQ) and Short Form-36 (SF-36) . On initial review the 3 most common symptoms were arthralgia, joint stiffness and myalgia affecting 97.9, 89.4 and 59.6% of cases, respectively. The joint types most commonly affected by pain at the initial review were the ankles, wrists, interphalangeal joints of the fingers, knees and metacarpophalangeal joints. Objective signs of joint inflammation were rare. The prevalence of signs of inflammation decreased and the prevalence of normal joints on examination increased through the reviews. The prevalence of use of NSAIDs decreased through the reviews. On the basis of CLINHAQ items regarding work performance functioning at work improved through the course of the reviews. Linear regression with days since symptom onset as the independent variable was performed for some variables. The 8 dimensions of the SF-36 were standardized to the Queensland population and analyzed longitudinally . Analyses of the CLINHAQ functional disability index (FDI) and the visual analogue scales (VASs) for pain, global severity, fatigue, gastrointestinal complaints and sleep, and the depression and anxiety scales were also performed. The slopes of all fitted regressions except the SF-36 general health dimension were significantly different from zero. All measures of disease severity returned to normal by 8 months from onset, many in a shorter period. 5. Behavioural and environmental risks for infection Fifty-five incident cases of RR virus disease were recruited and formed the basis of a case-control study of behavioural and environmental risks. They were matched to 85 controls. In the year prior to symptom onset the only leisure exposure that significantly altered risk was camping [Odds ratio (OR) = 2.15; 95% confidence interval (CI) = 1.07-4.35]. No peri-domestic activities in the year prior to onset significantly altered disease risk. Leisure exposures were also assessed in a 3-week exposure period ending 4 days prior to symptom onset. None significantly altered risk. No peri-domestic activity in this period significantly altered risk and nor did exposure to vertebrates or mosquitoes. Containers and vegetation around the subject's dwelling did not significantly increase risk. The presence of ice cream containers and buckets was significantly protective when assessed by questionnaire, however this was also assessed by inspection and was found to increase risk though not significantly so. It was concluded that the former finding was due to differential misclassification of exposure status. The premise condition index (PCI) was measured. A low PCI for the subject's house was associated with a significantly increased risk (3-4 relative to 7-9 as reference category: OR = 3.15, 95% CI = 1.07-9.25). Window screening did not alter disease risk and air-conditioning in the house or the bedroom decreased risk but not significantly so. Use of protective measures, except bed nets, in the year prior to onset was found to decrease disease risk. Personal repellents, mosquito coils and citronella candles significantly decreased risk. A dose response was shown for the number of protective measures from personal repellents, aerosol and surface sprays, mosquito coils, citronella candles and mosquito "zappers" used in the year prior to symptom onset. Pet ownership and proximity of dwelling to horses did not significantly alter risk. A preference for light coloured clothing was significantly protective (0.37, 0.15-0.89). Stratification by gender, date of symptom onset and geographical area was performed. Stratification by geographical area included a coastal and tablelands stratum. There were differences between the stratum-specific odds ratios for camping in the year prior to symptom onset, the presence of bromeliads in the subject's garden and a preference for light coloured clothing. Multivariate analysis demonstrated confounding by use of personal repellents, mosquito coils and citronella candles. When modeled together these were found to cause confounding among themselves. They also caused significant confounding of camping, outdoor work and the presence of banana trees in the subject's yard. Multivariate analysis of the association between PCI and disease risk failed to demonstrate confounding by use of protective measures or time between symptom onset and review. 6. Synthesis and conclusions The three research Chapters form a coherent body of public health research on the epidemiology (Chapters 5 and 6) and ecology (Chapters 4 and 7) of RR virus, and the natural history of RR virus disease (Chapter 6) in tropical Queensland. Conclusions are drawn from the research in the thesis. A set of priorities for future public health research on RR virus is suggested, and a pilot control program for Ross River virus disease in tropical Queensland is recommended.