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Biomedical subjects

A J McMichael

Publications and source records attributed to A J McMichael.

At least 19 recordsLinked to original sources
PubMed2005

Climatic, high tide and vector variables and the transmission of Ross River virus.

This report assesses the impact of the variability in environmental and vector factors on the transmission of Ross River virus (RRV) in Brisbane, Australia. Poisson time series regression analyses were conducted using monthly data on the counts of RRV cases, climate variables (Southern Oscillation Index and rainfall), high tides and mosquito density for the period of 1998-2001. The results indicate that increases in the high tide (relative risk (RR): 1.65; 95% confidence interval (CI): 1.20-2.26), rainfall (RR: 1.45; 95% CI: 1.21-1.73), mosquito density (RR: 1.17; 95% CI: 1.09-1.27), the density of Culex annulirostris (RR: 1.25; 95% CI: 1.13-1.37) and the density of Ochlerotatus vigilax (RR: 2.39; 95% CI: 2.30-2.48), each at a lag of 1 month, were statistically significantly associated with the rise of monthly RRV incidence. The results of the present study might facilitate the development of early warning systems for reducing the incidence of this wide-spread disease in Australia and other Pacific island nations.

Alphavirus Infections↗
PubMed2004

Environmental and social influences on emerging infectious diseases: past, present and future.

During the processes of human population dispersal around the world over the past 50 000-100 000 years, along with associated cultural evolution and inter-population contact and conflict, there have been several major transitions in the relationships of Homo sapiens with the natural world, animate and inanimate. Each of these transitions has resulted in the emergence of new or unfamiliar infectious diseases. The three great historical transitions since the initial advent of agriculture and livestock herding, from ca. 10 000 years ago, occurred when: (i) early agrarian-based settlements enabled sylvatic enzootic microbes to make contact with Homo sapiens; (ii) early Eurasian civilizations (such as the Greek and Roman empires, China and south Asia) came into military and commercial contact, ca. 3000-2000 years ago, swapping their dominant infections; and (iii) European expansionism, over the past five centuries, caused the transoceanic spread of often lethal infectious diseases. This latter transition is best known in relation to the conquest of the Americas by Spanish conquistadores, when the inadvertent spread of measles, smallpox and influenza devastated the Amerindian populations.Today, we are living through the fourth of these great transitional periods. The contemporary spread and increased lability of various infectious diseases, new and old, reflect the combined and increasingly widespread impacts of demographic, environmental, behavioural, technological and other rapid changes in human ecology. Modern clinical medicine has, via blood transfusion, organ transplantation, and the use of hypodermic syringes, created new opportunities for microbes. These have contributed to the rising iatrogenic problems of hepatitis C, HIV/AIDS and several other viral infections. Meanwhile, the injudicious use of antibiotics has been a rare instance of human action actually increasing 'biodiversity'. Another aspect of this fourth transition is that modern hyper-hygienic living restricts microbial exposure in early life. This, in the 1950s, may have contributed to an epidemic of more serious, disabling, poliomyelitis, affecting older children than those affected in earlier, more endemic decades. As with previous human-microbe transitions, a new equilibrial state may lie ahead. However, it certainly will not entail a world free of infectious diseases. Any mature, sustainable, human ecology must come to terms with both the need for, and the needs of, the microbial species that help to make up the interdependent system of life on Earth. Humans and microbes are not "at war"; rather, both parties are engaged in amoral, self-interested, coevolutionary struggle. We need to understand better, and therefore anticipate, the dynamics of that process.

Agriculture↗
PubMed2004

Heterogeneity of breast cancer risk within the South Asian female population in England: a population-based case-control study of first-generation migrants.

South Asian women in England have a lower breast cancer risk than their English-native counterparts, but less is known about variations in risk between distinct South Asian ethnic subgroups. We used the data from a population-based case-control study of first-generation South Asian migrants to assess risks by ethnic subgroup. In all, 240 breast cancer cases, identified through cancer registries, were individually matched on age and general practitioner to two controls. Information on the region of origin, religious and linguistic background, and on breast cancer risk factors was obtained from participants. Breast cancer odds varied significantly between the ethnic subgroups (P=0.008), with risk increasing in the following order: Bangladeshi Muslims (odds ratio (OR) 0.33, 95% confidence interval (CI): 0.10, 1.06), Punjabi Hindu (OR 0.59, 95% CI: 0.33, 1.27), Gujarati Hindu (1=reference group), Punjabi Sikh (OR 1.23, 95% CI: 0.72, 2.11) and Pakistani/Indian Muslims (OR 1.76, 95% CI: 1.10, 2.81). The statistically significant raised risk in Pakistani/Indian Muslims increased with adjustment for socioeconomic and reproductive risk factors (OR 2.12, 95% CI: 1.25, 3.58), but was attenuated, and no longer significant, with further adjustment for waist circumference and intake of nonstarch polysaccharides and fat (OR 1.49, 95% CI: 0.85, 2.63). These findings reveal differences in breast cancer risk between South Asian ethnic subgroups, which were not fully explained by reproductive differences, but were partly accounted for by diet and body size.

Asia, Southeastern↗
PubMed2004

Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa.

For the development of human immunodeficiency virus type 1 (HIV-1) vaccines, traditional approaches inducing virus-neutralizing antibodies have so far failed. Thus the effort is now focused on elicitation of cellular immunity. We are currently testing in clinical trials in the United Kingdom and East Africa a T-cell vaccine consisting of HIV-1 clade A Gag-derived immunogen HIVA delivered in a prime-boost regimen by a DNA plasmid and modified vaccinia virus Ankara (MVA). Here, we describe engineering and preclinical development of a second immunogen RENTA, which will be used in combination with the present vaccine in a four-component DNA/HIVA-RENTA prime-MVA/HIVA-RENTA boost formulation. RENTA is a fusion protein derived from consensus HIV clade A sequences of Tat, reverse transcriptase, Nef and gp41. We inactivated the natural biological activities of the HIV components and confirmed immunogenicities of the pTHr.RENTA and MVA.RENTA vaccines in mice. Furthermore, we demonstrated in mice and rhesus monkeys broadening of HIVA-elicited T-cell responses by a parallel induction of HIVA- and RENTA-specific responses recognizing multiple HIV epitopes.

AIDS Vaccines↗
PubMed2004

Climate variability and Ross River virus transmission in Townsville Region, Australia, 1985-1996.

BACKGROUND: How climate variability affects the transmission of infectious diseases at a regional level remains unclear. We assess the impact of climate variation on the Ross River virus (RRv) transmission in the Townsville region, Queensland, north-east Australia. METHODS: We obtained population-based information on monthly variations in RRv cases, climatic factors, sea level, and population growth between 1985 and 1996. Cross-correlations were computed for a series of associations between climate variables (rainfall, maximum temperature, minimum temperature, relative humidity and high tide) and the monthly incidence of RRv disease over a range of time lags. We assessed the impact of climate variability on RRv transmission using the seasonal auto-regressive integrated moving average (SARIMA) model. RESULTS: There were significant correlations of the monthly incidence of RRv to rainfall, maximum temperature, minimum temperature and relative humidity, all at a lag of 2 months, and high tide in the current month. The results of SARIMA models show that monthly average rainfall (beta = 0.0007, P = 0.01) and high tide (beta = 0.0089, P = 0.04) were significantly associated with RRv transmission and maximum temperature was also marginally significantly associated with monthly incidence of RRv (beta = 0.0412, P = 0.07), although relative humidity did not seem to have played an important role in the Townsville region. CONCLUSIONS: Rainfall, high tide and maximum temperature were likely to be key determinants of RRv transmission in the Townsville region.

Alphavirus Infections↗
PubMed2004

Racial differences in the treatment of pigmentation disorders in outpatient settings: analysis of US national practice data.

OBJECTIVE: Pigmentary disorders tend to disproportionately affect individuals with darker skin pigmentation. An understanding of why certain patients or races present more frequently to physicians would help guide attempts for early interventions and education for these patients. METHODS: Data from the National Ambulatory Medical Care Survey (1996-2000) were used to examine associations between the race/ethnicity of the patient and the type of skin-related visit. We examined the impact of non-white (and separately, black) individuals and Hispanic ethnicity on the probability of a pigmentary disorder or non-pigmentary disorder-related outpatient physician visit in weighted multivariate logistic regression models. RESULTS: Non-white patients have a higher probability of a pigmentary disorder-related skin condition visit than white patients (RR: 1.30; 95% CI: 1.29, 1.31). Black patients are more likely than non-black patients to be seen for a pigmentary disorder (RR: 1.04; 95% CI: 1.03, 1.04). Hispanic patients are less likely to be seen for a pigmentary disorder (RR: 0.90; 95% CI: 0.90, 0.91). This is in contrast to non-pigmentary skin disorder-related visits, where non-white, black, as well as Hispanic patients have a lower probability of visits than white individuals. CONCLUSIONS: There is a race-related differential in the treatment of pigmentary skin disorders, with non-white patients having a probability of receiving more care for these conditions in US outpatient settings. This lends support to our hypothesis that darker pigmentation in non-white populations is the driver of a differential in the utilization of pigmentation-related skin visits.

Ambulatory Care↗
PubMed2003

New visions for addressing sustainability.

Attaining sustainability will require concerted interactive efforts among disciplines, many of which have not yet recognized, and internalized, the relevance of environmental issues to their main intellectual discourse. The inability of key scientific disciplines to engage interactively is an obstacle to the actual attainment of sustainability. For example, in the list of Millennium Development Goals from the United Nations World Summit on Sustainable Development, Johannesburg, 2002, the seventh of the eight goals, to "ensure environmental sustainability," is presented separately from the parallel goals of reducing fertility and poverty, improving gains in equity, improving material conditions, and enhancing population health. A more integrated and consilient approach to sustainability is urgently needed.

Conservation of Natural Resources↗
PubMed2003

Development and validation of a health-related quality of life instrument for women with melasma.

BACKGROUND: Melasma can have significant emotional and psychological effects on those affected with the condition. In the past, the impact of melasma on health-related quality of life (HRQoL) has been assessed using general measures of skin disease that equally weigh both the physical and psychosocial distress arising from the presence of a dermatological condition. OBJECTIVES: Our purpose was to develop and validate a disease-specific HRQoL instrument to identify the areas of the patient's life most impaired by melasma as well as the effects of the condition on their level of functioning in correlation with disease severity: the Melasma Quality of Life scale (MELASQOL). PATIENTS AND METHODS: A random sample of 102 women identified by an investigator as having melasma were evaluated by the investigator using the Melasma Area and Severity Index (MASI). The patients were then anonymously surveyed with the SKINDEX-16, the Fear of Negative Evaluation scale, the Dermatology Life Quality Index (DLQI), a skin discoloration evaluation questionnaire, and a measure of perceived life quality difference without melasma. The 10-item MELASQOL scale was devised from the comprehensive HRQoL assessment battery. RESULTS: The psychometric properties of the MELASQOL were comparable with the properties of the DLQI and the SKINDEX-16. The MELASQOL scores were highly correlated with the other HRQoL measures. The discriminatory ability of the MELASQOL is superior to the SKINDEX-16 and the DLQI for melasma. The three life domains most adversely affected by melasma (social life, recreation/leisure and emotional well-being) were highlighted by this instrument. These were the same three areas of life that patients believed would improve the most if they no longer were affected by the disease. CONCLUSIONS: The MELASQOL can be used to evaluate objectively the effect of melasma on a patient's HRQoL. The high correlation with the DLQI, the SKINDEX-16 and the skin discoloration questionnaire suggests that the new scale is a valid instrument, which can be used to monitor the level of impairment individuals suffer due to their melasma. The MELASQOL scores can help guide treatment methods as well as track the improvement of patients' HRQoL.

Adult↗
PubMed2002

Lack of toxicity and persistence in the mouse associated with administration of candidate DNA- and modified vaccinia virus Ankara (MVA)-based HIV vaccines for Kenya.

Toxicity, biodistribution and persistence of candidate HIV vaccines pTHr.HIVA, a recombinant DNA, and MVA.HIVA, a recombinant modified vaccinia virus Ankara, were determined in the Balb/c mouse. The mice were injected with either two doses of intramuscular pTHr.HIVA DNA (50 microg each, separated by an interval of 14 days), two doses of intradermal MVA.HIVA (10(6) plaque-forming units each, separated by an interval of 14 days), or a combination of the two vaccines, each given in two doses, in a prime-boost regimen. The study showed no significant toxic effects, either local or systemic, under any of these employed dosing regimens. With the exception of the sites of delivery, the vaccine-derived HIVA DNA sequences were undetectable 5 weeks after the last dosing. Thus, both the vaccines alone and in a combination were considered safe and suitable for the use in phase I trials in humans.

AIDS Vaccines↗
PubMed2002

Climate variability and Ross River virus transmission.

OBJECTIVES: (1) To examine the feasibility to link climate data with monthly incidence of Ross River virus (RRv). (2) To assess the impact of climate variability on the RRv transmission. DESIGN: An ecological time series analysis was performed on the data collected between 1985 to 1996 in Queensland, Australia. METHODS: Information on the notified RRv cases was obtained from the Queensland Department of Health. Climate and population data were supplied by the Australian Bureau of Meteorology and the Australian Bureau of Statistics, respectively. Spearman's rank correlation analyses were performed to examine the relation between climate variability and the monthly incidence of notified RRv infections. The autoregressive integrated moving average (ARIMA) model was used to perform a time series analysis. As maximum and minimum temperatures were highly correlated with each other (r(s)=0.75), two separate models were developed. RESULTS: For the eight major cities in Queensland, the climate-RRv correlation coefficients were in the range of 0.12 to 0.52 for maximum and minimum temperatures, -0.10 to 0.46 for rainfall, and 0.11 to 0.52 for relative humidity and high tide. For the whole State, rainfall (partial regression coefficient: 0.017 (95% confidence intervals 0.009 to 0.025) in Model I and 0.018 (0.010 to 0.026) in Model II), and high tidal level (0.030 (0.006 to 0.054) in Model I and 0.029 (0.005 to 0.053) in Model II) seemed to have played significant parts in the transmission of RRv in Queensland. Maximum temperature was also marginally significantly associated with the incidence of RRv infection. CONCLUSION: Rainfall, temperature, and tidal levels may be important environmental determinants in the transmission cycles of RRv disease.

Alphavirus Infections↗
PubMed2001

Early effects of climate change: do they include changes in vector-borne disease?

The world's climate appears now to be changing at an unprecedented rate. Shifts in the distribution and behaviour of insect and bird species indicate that biological systems are already responding to this change. It is well established that climate is an important determinant of the spatial and temporal distribution of vectors and pathogens. In theory, a change in climate would be expected to cause changes in the geographical range, seasonality (intra-annual variability), and in the incidence rate (with or without changes in geographical or seasonal patterns). The detection and then attribution of such changes to climate change is an emerging task for scientists. We discuss the evidence required to attribute changes in disease and vectors to the early effects of anthropogenic climate change. The literature to date indicates that there is a lack of strong evidence of the impact of climate change on vector-borne diseases (i.e. malaria, dengue, leishmaniasis, tick-borne diseases). New approaches to monitoring, such as frequent and long-term sampling along transects to monitor the full latitudinal and altitudinal range of specific vector species, are necessary in order to provide convincing direct evidence of climate change effects. There is a need to reassess the appropriate levels of evidence, including dealing with the uncertainties attached to detecting the health impacts of global change.

Animals↗
PubMed2001

Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma.

Acquired immunodeficiency syndrome-related non-Hodgkin lymphomas (AIDS-NHL) are thought to arise because of loss of Epstein-Barr Virus (EBV)-specific cellular immunity. Here, an investigation was done to determine whether cellular immunity to EBV is lost because of physical loss or dysfunction of EBV-specific cytotoxic T cells. Data on EBV-specific cellular immunity were correlated with EBV load. For comparison, individuals who progressed to AIDS with opportunistic infections (AIDS-OI) and long-term asymptomatics (LTAs) were studied. The number of virus-specific T cells was detected using tetrameric HLA-EBV-peptide complexes; function of these EBV-specific T cells was determined using the interferon-gamma (IFN-gamma) Elispot assay. It was observed that EBV-specific CD8(+) T cells were present in normal numbers in human immunodeficiency virus (HIV)-infected individuals. However, their functional capacity was decreased compared with HIV(-) individuals. In AIDS-NHL patients, EBV-specific T cells were not physically lost in the course of HIV-1 infection but showed progressive loss of their capability to produce IFN-gamma in response to EBV peptides. This loss of function correlated with lower CD4(+) T-cell numbers and was accompanied by increasing EBV load. In HIV-1-infected LTA individuals, in whom CD4(+) T-cell numbers were maintained, and progressors to AIDS-OI, IFN-gamma-producing EBV-specific T cells were stable and EBV load remained stable or decreased in the course of HIV infection, suggestive of immune control. Our data indicate that functional loss of EBV-specific CD8(+) T cells with a concomitant increase in EBV load may play a role in the pathogenesis of AIDS-NHL.

AIDS-Related Opportunistic Infections↗
PubMed2001

Cytotoxic T-cell abundance and virus load in human immunodeficiency virus type 1 and human T-cell leukaemia virus type 1.

The correlation between virus load and specific cytotoxic T-lymphocyte (CTL) frequency during the chronic phase in human immunodeficiency virus type 1 (HIV-1) infection has been found to be negative in cross-sectional studies. We report here that, in infection with the related retrovirus human T-cell leukaemia virus type 1 (HTLV-1), the correlation is positive in asymptomatic carriers and zero in patients with the associated inflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We demonstrate that the direction of the correlation may depend on the efficacy of the CTL response using mathematical models. We conclude that the CTL response is effective in asymptomatic carriers of HTLV-1, but ineffective in patients with HAM/TSP. Virus-mediated impairment of specific CTL production in HIV-1 infection can account for the negative correlation observed.

Carrier State↗