BIVARIATE BINOMIAL SPATIAL MODELLING LOA loa PREVALENCE IN TROPICAL AFRICA

We present a state-of-the-art application of smoothing for dependent bivariate binomial spatial data to Loa loa prevalence mapping in West Africa. This application is special because it starts with the non-spatial calibration of survey instruments, continues with the spatial model building and assessment and ends with robust, tested software that will be used by the field scientists of the World Health Organization for online prevalence map updating. From a statistical perspective several important methodological issues were addressed: (a) building spatial models that are complex enough to capture the structure of the data but remain computationally usable; (b)reducing the computational burden in the handling of very large covariate data sets; (c) devising methods for comparing spatial prediction methods for a given exceedance policy threshold.

Experimental infection of the pig with Mycobacterium ulcerans: a novel model for studying the pathogenesis of Buruli ulcer disease.

BACKGROUND Buruli ulcer (BU) is a slowly progressing, necrotising disease of the skin caused by infection with Mycobacterium ulcerans. Non-ulcerative manifestations are nodules, plaques and oedema, which may progress to ulceration of large parts of the skin. Histopathologically, BU is characterized by coagulative necrosis, fat cell ghosts, epidermal hyperplasia, clusters of extracellular acid fast bacilli (AFB) in the subcutaneous tissue and lack of major inflammatory infiltration. The mode of transmission of BU is not clear and there is only limited information on the early pathogenesis of the disease available. METHODOLOGY/PRINCIPAL FINDINGS For evaluating the potential of the pig as experimental infection model for BU, we infected pigs subcutaneously with different doses of M. ulcerans. The infected skin sites were excised 2.5 or 6.5 weeks after infection and processed for histopathological analysis. With doses of 2 × 10(7) and 2 × 10(6) colony forming units (CFU) we observed the development of nodular lesions that subsequently progressed to ulcerative or plaque-like lesions. At lower inoculation doses signs of infection found after 2.5 weeks had spontaneously resolved at 6.5 weeks. The observed macroscopic and histopathological changes closely resembled those found in M. ulcerans disease in humans. CONCLUSION/SIGNIFICANCE Our results demonstrate that the pig can be infected with M. ulcerans. Productive infection leads to the development of lesions that closely resemble human BU lesions. The pig infection model therefore has great potential for studying the early pathogenesis of BU and for the development of new therapeutic and prophylactic interventions.

Use of Recombinant Virus Replicon Particles for Vaccination against Mycobacterium ulcerans Disease.

Buruli ulcer, caused by infection with Mycobacterium ulcerans, is a necrotizing disease of the skin and subcutaneous tissue, which is most prevalent in rural regions of West African countries. The majority of clinical presentations seen in patients are ulcers on limbs that can be treated by eight weeks of antibiotic therapy. Nevertheless, scarring and permanent disabilities occur frequently and Buruli ulcer still causes high morbidity. A vaccine against the disease is so far not available but would be of great benefit if used for prophylaxis as well as therapy. In the present study, vesicular stomatitis virus-based RNA replicon particles encoding the M. ulcerans proteins MUL2232 and MUL3720 were generated and the expression of the recombinant antigens characterized in vitro. Immunisation of mice with the recombinant replicon particles elicited antibodies that reacted with the endogenous antigens of M. ulcerans cells. A prime-boost immunization regimen with MUL2232-recombinant replicon particles and recombinant MUL2232 protein induced a strong immune response but only slightly reduced bacterial multiplication in a mouse model of M. ulcerans infection. We conclude that a monovalent vaccine based on the MUL2232 antigen will probably not sufficiently control M. ulcerans infection in humans.

SOCIO-ENVIRONMENTAL FACTORS ASSOCIATED WITH THE DISTRIBUTION OF DRACUNCULUS MEDINENSIS (GUINEA WORM DISEASE) AND SUGGESTED METHODS FOR CONTROL, IBARAPA, NIGERIA, 1982 (AFRICA)

A population-based cross-sectional survey of socio-environmental factors associated with the prevalence of Dracunculus medinensis (guinea worm disease) was conducted in Idere, a rural agricultural community in Ibarapa, Oyo state, Nigeria, during 1982.^ The epidemiologic data were collected by household interview of all 501 households. The environmental data were collected by analysis of water samples collected from all domestic water sources and rainfall records.^ The specific objectives of this research were to: (a) Describe the prevalence of guinea worm disease in Idere during 1982 by age, sex, area of residence, drinking water source, religion and weekly amount of money spent by the household to collect potable drinking water. (b) Compare the characteristics of cases with non-cases of guinea worm in order to identify factors associated with high risk of infection. (c) Investigate domestic water sources for the distribution of Cyclops. (d) Determine the extent of potable water shortage with a view to identifying factors responsible for such shortage in the community. (e) Describe the effects of guinea worm on school attendance during 1980/1982 school years by class and location of school from piped water supply.^ The findings of this research indicate that during 1982, 31.8 percent of Idere's 6,527 residents experienced guinea worm infection, with higher prevalence of infection recorded in males in their most productive years and females in their teenage years. The role of sex and age to risk of higher infection rate was explained in the context of water related exposure and water intake due to dehydration from physical occupational actitives of subgroups.^ Potable water available to residents was considerably below the minimum recommended by WHO for tropical climates, with sixty-eight percent of water needs of the residents coming from unprotected surface water which harbour Cyclops, the obligatory intermediate host of Dracunculus medinensis. An association was found between periods of relative high density of Cyclops in domestic water and rainfall.^ Impact of guinea worm infection on educational activities was considerable and its implications were discussed, including the implications of the research findings in relation to control of guinea worm disease in Ibarapa. ^

Forchheimer's therapeusis of internal disease /

Vol. 5 edited by F. Billings and E.E. Irons.

Limitations to global disease control

In October 2000, Australia was declared poliomyelitis-free” by the World Health Organisation. This declaration followed some extensive six years of surveillance of all cases of acute flaccid paralysis, by the Poliomyelitis Expert Surveillance Committee (Centre for Disease Control, Commonwealth Department of Health and Aged Care, Canberra), chaired by the author. There have been seven attempts in the history of the world to eliminate a disease from the earth’s surface. The dramatic failure of five of these, the success of global smallpox eradication, and current successes and difficulties in the case of attempts to eliminate poliomyelitis worldwide, lead one to an analysis of the factors which led both to success and to failure. The global eradication of a specific disease is one of the most important endeavours which the international community can undertake. This audit reviews the details of such approaches; that such might be used as tools for the future.

Ross River virus disease in Australia, 1886-1998, with analysis of risk factors associated with outbreaks

Ross River virus (RE) is a mosquito-borne arbovirus responsible for outbreaks of polyarthritic disease throughout Australia. To better understand human and environmental factors driving such events, 57 historical reports oil RR Outbreaks between 1896 and 1998 were examined collectively. The magnitude, regularity, seasonality, and locality of outbreaks were found to be wide ranging; however, analysis of climatic and tidal data highlighted that environmental conditions let differently ill tropical, arid, and temperate regions. Overall, rainfall seems to be the single most important risk factor, with over 90% of major outbreak locations receiving higher than average rainfall in preceding mouths. Many temperatures were close to average, particularly in tropical populations; however, in arid regions, below average maximum temperatures predominated, and ill southeast temperate regions, above average minimum temperatures predominated. High spring tides preceded coastal Outbreaks, both in the presence and absence of rainfall, and the relationship between rainfall and the Southern Oscillation Index and Lit Nina episodes suggest they may be useful predictive tools, but only ill southeast temperate regions. Such heterogeneity predisposing outbreaks supports the notion that there are different RE epidemiologies throughout Australia but also Suggests that generic parameters for the prediction and control of outbreaks are of limited use at a local level.

Potential economic implications for regional tourism of a Foot and Mouth Disease outbreak in North Queensland

International and domestic tourism are sensitive to disastrous events which make areas inaccessible to visitors, less attractive or more dangerous. One form of tourism disaster is the outbreak of an exotic disease, of which Foot and Mouth Disease (FMD) is a prime case. It is now well documented that the 2001 FMD outbreak in the UK had a greater impact on tourism than on agriculture. It has been estimated than an FMD outbreak in Australia would impose a cost of about $13 million. The impact on tourism would be highly dependent on the extent and duration of an FMD outbreak, as well as on any management and containment restrictions imposed by the authorities in their attempt to control and eventually eradicate the disease. Public perception and thus the provision of accurate information and the way in which the media report disasters will also play an important role in determining the impact on the tourism industry. The economy of Tropical North Queensland relies heavily on international visitors, and an FMD outbreak in the region would impose a large cost to the regional economy, conservatively estimated here to be of the order of $200 million per year.

Identifying health centers in Honduras infested with Rhodnius prolixus using the seroprevalence of Chagas disease in children younger than 13 years

The objective of this study is to determine if a Chagas disease protocol starting with a serological survey is as reliable at identifying insect-infested areas as one using the gold standard entomological survey. The study found that health center areas infested with Rhodnius prolixus were identified using a threshold seroprevalence of 0.1%. The serological survey took half the time and was 30% less expensive than the entomological survey. Developing countries with limited resources may find this strategy useful in combating Chagas disease. This strategy also identifies seropositive children, which facilitates their treatment.

Measuring the global burden of disease and epidemiological transitions: 2002-2030

Any planning process for health development ought to be based on a thorough understanding of the health needs of the population. This should be sufficiently comprehensive to include the causes of premature death and of disability, as well as the major risk factors that underlie disease and injury. To be truly useful to inform health-policy debates, such an assessment is needed across a large number of diseases, injuries and risk factors, in order to guide prioritization. The results of the original Global Burden of Disease Study and, particularly, those of its 2000-2002 update provide a conceptual and methodological framework to quantify and compare the health of populations using a summary measure of both mortality and disability: the disability-adjusted life-year (DALY). Globally, it appears that about 5 6 million deaths occur each year, 10. 5 million (almost all in poor countries) in children. Of the child deaths, about one-fifth result from perinatal causes such as birth asphyxia and birth trauma, and only slightly less from lower respiratory infections. Annually, diarrhoeal diseases kill over 1.5 million children, and malaria, measles and HIV/AIDS each claim between 500,000 and 800,000 children. HIV/AIDS is the fourth leading cause of death world-wide (2.9 million deaths) and the leading cause in Africa. The top three causes of death globally are ischaemic heart disease (7.2 million deaths), stroke (5.5 million) and lower respiratory diseases (3.9 million). Chronic obstructive lung diseases (COPD) cause almost as many deaths as HIV/AIDS (2.7 million). The leading causes of DALY, on the other hand, include causes that are common at young ages [perinatal conditions (7. 1 % of global DALY), lower respiratory infections (6.7%), and diarrhoeal diseases (4.7%)] as well as depression (4.1%). Ischaemic heart disease and stroke rank sixth and seventh, retrospectively, as causes of global disease burden, followed by road traffic accidents, malaria and tuberculosis. Projections to 2030 indicate that, although these major vascular diseases will remain leading causes of global disease burden, with HIV/AIDS the leading cause, diarrhoeal diseases and lower respiratory infections will be outranked by COPD, in part reflecting the projected increases in death and disability from tobacco use.

Unplanned land clearing of Colombian rainforests: Spreading like disease?

Deforestation often occurs as temporal waves and in localized fronts termed 'deforestation hotspots' driven by economic pulses and population pressure. Of particular concern for conservation planning are 'biodiversity hotspots' where high concentrations of endemic species undergo rapid loss and fragmentation of habitat. We investigate the deforestation process in Caqueta, a biodiversity hotspot and major colonization front of the Colombian Amazon using multi-temporal satellite imagery of the periods 1989-1996-1999-2002. The probabilities of deforestation and regeneration were modeled against soil fertility, accessibility and neighborhood terms, using logistic regression analysis. Deforestation and regeneration patterns and rates were highly variable across the colonization front. The regional average annual deforestation rate was 2.6%, but varied locally between -1.8% (regeneration) and 5.3%, with maximum rates in landscapes with 40-60% forest cover and highest edge densities, showing an analogous pattern to the spread of disease. Soil fertility and forest and secondary vegetation neighbors showed positive and significant relationships with the probability of deforestation. For forest regeneration, soil fertility had a significant negative effect while the other parameters were marginally significant. The logistic regression models across all periods showed a high level of discrimination power for both deforestation and forest regeneration, with ROC values > 0.80. We document the effect of policies and institutional changes on the land clearing process, such as the failed peace process between government and guerillas in 1999-2002, which redirected the spread of deforestation and increased forest regeneration. The implications for conservation in biologically rich areas, such as Caqueta are discussed. (c) 2005 Elsevier B.V All rights reserved.

The isolation, characterization, and application of WRKY genes as useful molecular markers in tropical trees

The improvement of tropical tree crops using conventional breeding methods faces challenges due to the length of time involved. Thus, like most crops, there is an effort to utilize molecular genetic markers in breeding programs to select for desirable agronomic traits. Known as marker assisted breeding or marker assisted selection, genetic markers associated with a phenotype of interest are used to screen and select material reducing the time necessary to evaluate candidates. As the focus of this research was improving disease resistance in tropical trees, the usefulness of the WRKY gene superfamily was investigated as candidates for generating useful molecular genetic markers. WRKY genes encode plant-specific transcriptional factors associated with regulating plants' responses to both biotic and abiotic stress. ^ One pair of degenerate primers amplified 48 WRKY gene fragments from three taxonomically distinct, economically important, tropical tree crop species: 18 from Theobroma cacao L., 21 from Cocos nucifera L. and 9 from Persea americana Mill. Several loci from each species were polymorphic because of single nucleotide substitutions present within a putative non-coding region of the loci. Capillary array electrophoresis-single strand conformational polymorphism (CAE-SSCP) mapped four WRKY loci onto a genetic linkage map of a T. cacao F2 population segregating for resistance to witches' broom disease. Additionally, PCR primers specific for four T. cacao loci successfully amplified WRKY loci from 15 members of the Byttneriae tribe. A method was devised to allow the reliable discrimination of alleles by CAE-SSCP using only the mobility assigned to the sample peaks. Once this method was validated, the diversity of three WRKY loci was evaluated in a germplasm collection of T. cacao . One locus displayed high diversity in the collection, with at least 18 alleles detected from mobility differences of the product peaks. The number of WRKY loci available within the genome, ease of isolation by degenerate PCR, codominant segregation demonstrated in the F2 population, and usefulness for screening germplasm collections and closely related wild species demonstrates that the WRKY superfamily of genes are excellent candidates for developing a number of genetic molecular markers for breeding purposes in tropical trees. ^