Host genetics and population structure effects on parasitic disease

Host genetic factors exert significant influences on differential susceptibility to many infectious diseases. In addition, population structure of both host and parasite may influence disease distribution patterns. In this study, we assess the effects of population structure on infectious disease in two populations in which host genetic factors influencing susceptibility to parasitic disease have been extensively studied. The first population is the Jirel population of eastern Nepal that has been the subject of research on the determinants of differential susceptibility to soil-transmitted helminth infections. The second group is a Brazilian population residing in an area endemic for Trypanosoma cruzi infection that has been assessed for genetic influences on differential disease progression in Chagas disease. For measures of Ascaris worm burden, within-population host genetic effects are generally more important than host population structure factors in determining patterns of infectious disease. No significant influences of population structure on measures associated with progression of cardiac disease in individuals who were seropositive for T. cruzi infection were found.     

Cellular mechanisms of microbial proteins contributing to invasion of the blood-brain barrier

One of the least understood issues in the pathogenesis and pathophysiology of microbial infection of the central nervous system (CNS) is how microorganisms cross the blood–brain barrier (BBB), which separates brain interstitial space from blood and is formed by the tight junctions of brain microvascular endothelial cells (BMEC). BMEC monolayer and bilayer culture systems have been developed as in vitro models to dissect the mechanisms of adhesion and invasion involved in pathogenesis of CNS infection caused by microbes. Viral, bacterial, fungal and parasitic pathogens may breach the BBB and enter the CNS through paracellular, transcellular and/or Trojan horse mechanisms. Conceivable evidence suggests that microbial proteins are the major genetic determinants mediating penetration across the BBB. Several bacterial proteins including IbeA, IbeB, AslA,YijP, OmpA, PilC and InlB contribute to transcellular invasion of BMEC. Viral proteins such as gp120 of HIV have been shown to play a role in penetration of the BBB. Fungal and parasitic pathothogens may follow similar mechanisms. SAG1 of Toxoplasma gondii has been suggested as a ligand to mediate host-cell invasion. Understanding the fundamental mechanisms of microbial penetration of the BBB may help develop novel approaches to prevent the mortality and morbidity associated with central nervous system (CNS) infectious diseases.     

New approaches in vaccine development for parasitic infections

Vaccines have had a tremendous impact on the control of infectious diseases. Not only are vaccines potentially the least expensive mechanism to combat infectious diseases, under optimal conditions, widespread vaccination can result in disease eradication - as in the case of smallpox. Despite this great potential, vaccines have had little impact on human parasitic infections. The reasons for this are many - these eukaryotic pathogens are genetically and biologically complex organisms, some with elaborate life cycles and well-honed immune evasion mechanisms. Additionally, our understanding of the mechanisms of immune control of many parasitic infections -- of what constitutes an effective immune response and of how to induce high-quality immunological memory -- is not fully developed. This review attempts to highlight recent advances that could impact vaccine discovery and development in parasitic infections and proposes areas where future studies may lead to breakthroughs in vaccines for the agents of parasitic diseases. There are several other recent reviews highlighting the results of vaccine trials, specifically in the malaria field.     

The Okinawa Infectious Diseases Initiative

At the Kyushu-Okinawa Group of Eight summit in 2000, Japan announced the Okinawa Infectious Diseases Initiative (IDI) and pledged to spend US$3 billion over a five year period to combat infectious and parasitic diseases in developing countries. The IDI has exceeded expectations, spending more than US$4 billion over four years. The IDI is a unique initiative with its own philosophical basis and specifically tailored interventions and measures that helped to initiate worldwide political and financial commitments in the fight against infectious diseases. Notably, it promoted partnerships among stakeholders and emphasized comprehensive and inter-sectoral approaches (i.e. coordination and collaboration between health and other sectors). It helped to create a new vision of what is possible in the global effort against communicable diseases and has been instrumental in shaping the changing environments of development assistance, poverty reduction and other trends to reduce the impact of infectious and parasitic diseases.     

Is the siesta an adaptation to disease?

Why does the practice of the siesta vary across human cultures? One explanation is that it is a form of energy conservation in environments with high temperatures and/or agricultural labor. Disease palliation and prevention represents another area where the siesta might be beneficial. A preliminary study used the Human Relations Area Files (HRAF) to examine the characteristics associated with siesta occurrence. Siestas were not statistically associated with high temperatures or agricultural labor (p>.05). They were, however, statistically associated with the occurrence of malaria (p<.05) and marginally associated with parasitic and chronic infectious disease. Preliminary results suggest that siestas could be adaptive in environments with chronic infectious disease.     

Influence of livestock,habitat type,and density of roe deer (<Emphasis Type="Italic">Capreolus capreolus</Emphasis>) on parasitic larvae abundance and infection seroprevalence in wild populations of roe deer from central Iberian Peninsula

Livestock farming is a common human activity that not only modifies natural habitat but also may lead to interactions with other wild animal species. We studied whether health status of roe deer (Capreolus capreolus) is influenced by density, livestock, and type of habitat. We analyzed 208 samples (120 fecal and 88 sera) from roe deer populations of central Iberian Peninsula to evaluate both presence and abundance of parasitic oocysts, eggs, and/or larvae, especially of gastrointestinal and bronchopulmonary parasites, as well as the prevalence of five infectious diseases (infectious bovine rhinotracheitis (IBR), pestivirosis (BVD/BD), paratuberculosis (PTB), bluetongue (BT), and brucellosis). Fecal samples were collected in transects in pine and oak forests and endoparasites were detected by means of coprological techniques. Serum samples were obtained from hunted individuals and the serological testing for the infectious pathogens was performed by ELISA and Rose Bengal tests. Livestock and habitat type were associated both with the presence and the number of bronchopulmonary nematode L1-larvae per gram of feces (lpg), which was higher in areas with livestock and in pine forests. However, roe deer density neither influenced parasite presence nor lpg values. Regarding infectious pathogens, only seropositive samples for PTB and pestivirus were obtained indicating a possible transmission between domestic and wild ungulates in the study area. The low prevalence found is consistent with other studies in the Iberian Peninsula suggesting that roe deer have little contact with the infectious agents studied. Our results highlight that both habitat type and livestock significantly mediate abundance of parasitic larvae in roe deer, being higher under competition scenarios and in habitats of lower quality, a valuable aspect to be considered in future management and conservation strategies.     

Sea lice as a density-dependent constraint to salmonid farming

Fisheries catches worldwide have shown no increase over the last two decades, while aquaculture has been booming. To cover the demand for fish in the growing human population, continued high growth rates in aquaculture are needed. A potential constraint to such growth is infectious diseases, as disease transmission rates are expected to increase with increasing densities of farmed fish. Using an extensive dataset from all farms growing salmonids along the Norwegian coast, we document that densities of farmed salmonids surrounding individual farms have a strong effect on farm levels of parasitic sea lice and efforts to control sea lice infections. Furthermore, increased intervention efforts have been unsuccessful in controlling elevated infection levels in high salmonid density areas in 2009-2010. Our results emphasize host density effects of farmed salmonids on the population dynamics of sea lice and suggest that parasitic sea lice represent a potent negative feedback mechanism that may limit sustainable spatial densities of farmed salmonids.     

Assessing the contribution of age-sex differentials in causes of death due to infectious and parasitic diseases to the trends in age-sex differentials in life expectancy in Mauritius

This study applies two methodologies to Mauritian life tables and cause-of-death data: (1) the decomposition of sex differentials in life expectancy using Arriaga's approach and (2) the estimation of the effect of marginal reduction in deaths from infectious and parasitic diseases on life expectancy using Keyfitz's methodology on cause-specific entropy and that of Nanjo. The findings in this paper support earlier findings about the importance of the period 1969-1976 in the mortality transition in Mauritius, a period in which sex differentials in life expectancies reached a peak level. The results suggest that the driving force behind those sex differentials in life expectancy was the sex differential in mortality in infectious and parasitic diseases, first among the young (ages below 10 years) and second among the older population (ages above 50 years). If the decline in mortality due to infectious and parasitic diseases was differentially greater in the older ages compared to the younger ages, that difference would have gone a long way toward reducing the magnitude of the historic peak sex differential in life expectancy achieved in 1976.     

The future impact of societal and cultural factors on parasitic disease -- some emerging issues

A variety of societal and cultural factors will increase host exposure or susceptibility to infectious agents, particularly parasites. Such factors have already had a major impact on the emergence of infectious diseases and the situation is likely to worsen further as we enter the new millennium. The changes that are enhancing the spread and transmission of parasitic diseases, as well as those which are adversely affecting host responsiveness, are examined with reference to specific parasites.     

Brazilian flora extracts as source of novel antileishmanial and antifungal compounds

Natural products have long been providing important drug leads for infectious diseases. Leishmaniasis is a protozoan parasitic disease found mainly in developing countries, and it has toxic therapies with few alternatives. Fungal infections have been the main cause of death in immunocompromised patients and new drugs are urgently needed. In this work, a total of 16 plant species belonging to 11 families, selected on an ethnopharmacological basis, were analyzed in vitro against Leishmania (L.) chagasi, Leishmania (L.) amazonensis, Candida krusei, and C. parapsilosis. Of these plant species, seven showed antifungal activity against C. krusei, five showed antileishmanial activity against L. chagasi and four against L. amazonensis, among them species of genus Plectranthus. Our findings confirm the traditional therapeutic use of these plants in the treatment of infectious and inflammatory disorders and also offer insights into the isolation of active and novel drug prototypes, especially those used against neglected diseases as Leishmaniasis.     

Polyamine transport in parasites: a potential target for new antiparasitic drug development

The metabolism of the naturally occurring polyamines-putrescine, spermidine and spermine-is a highly integrated system involving biosynthesis, uptake, degradation and interconversion. Metabolic differences in polyamine metabolism have long been considered to be a potential target to arrest proliferative processes ranging from cancer to microbial and parasitic diseases. Despite the early success of polyamine inhibitors such as alpha-difluoromethylornithine (DFMO) in treating the latter stages of African sleeping sickness, in which the central nervous system is affected, they proved to be ineffective in checking other major diseases caused by parasitic protozoa, such as Chagas' disease, leishmaniasis or malaria. In the use and design of new polyamine-based inhibitors, account must be taken of the presence of up-regulated polyamine transporters in the plasma membrane of the infectious agent that are able to circumvent the effect of the drug by providing the parasite with polyamines from the host. This review contains information on the polyamine requirements and molecular, biochemical and genetic characterization of different transport mechanisms in the parasitic agents responsible for a number of the deadly diseases that afflict underdeveloped and developing countries.     

Does coevolution promote species richness in parasitic cuckoos?

Why some lineages have diversified into larger numbers of species than others is a fundamental but still relatively poorly understood aspect of the evolutionary process. Coevolution has been recognized as a potentially important engine of speciation, but has rarely been tested in a comparative framework. We use a comparative approach based on a complete phylogeny of all living cuckoos to test whether parasite–host coevolution is associated with patterns of cuckoo species richness. There are no clear differences between parental and parasitic cuckoos in the number of species per genus. However, a cladogenesis test shows that brood parasitism is associated with both significantly higher speciation and extinction rates. Furthermore, subspecies diversification rate estimates were over twice as high in parasitic cuckoos as in parental cuckoos. Among parasitic cuckoos, there is marked variation in the severity of the detrimental effects on host fitness; chicks of some cuckoo species are raised alongside the young of the host and others are more virulent, with the cuckoo chick ejecting or killing the eggs/young of the host. We show that cuckoos with a more virulent parasitic strategy have more recognized subspecies. In addition, cuckoo species with more recognized subspecies have more hosts. These results hold after controlling for confounding geographical effects such as range size and isolation in archipelagos. Although the power of our analyses is limited by the fact that brood parasitism evolved independently only three times in cuckoos, our results suggest that coevolutionary arms races with hosts have contributed to higher speciation and extinction rates in parasitic cuckoos.     

First indication of gas embolism in a harbour porpoise (Phocoena phocoena) from German waters

In the last decade, a number of cetacean strandings have gas embolic pathology analogous to decompression sickness in man and experimental animals. Acute gas and fat embolic lesions have also been found in mass-stranded beaked whales causally linked to high-intensity anthropogenic mid-frequency sonar activities. Sporadic chronic gas embolic lesions have also been described. This communication describes a first case of numerous gas-filled fibrous cavities in the markedly enlarged liver of a dead adult male harbour porpoise stranded at the North Sea coast of Schleswig-Holstein, Germany. Additional pathological findings consisted of chronic parasitic granulomatous cholangiohepatitis, hepatic vein thrombosis, parasitic infestations of the bronchial tree and pulmonary blood vessels associated with bronchopneumonia and severe parasitic burden in both ear sinuses. The hepatic cavernous lesions are similar to those described in chronic gas bubble disease in other cetaceans, most likely resulting from decompression-related tissue supersaturation with nitrogen.     

Parasitic nematodes, proteinases and transgenic plants.

Parasite proteinases have important functions in host-parasite interactions. Consequently, they have been investigated as targets for the control of both plant and animal parasites. Plant parasitic nematodes cause estimated annual losses to world agriculture of US$100 billion and, currently, their control often relies on highly toxic nematicides, with associated environmental risks. The potential of disrupting digestive proteinases for plant parasitic nematode control, via expression of proteinase inhibitors in transgenic plants, is summarized here by Catherine Lilley, Pauline Devlin, Peter Urwin and Howard Atkinson. They then consider whether the approach of expressing antinematode proteins in plants can be adapted for control of certain animal parasitic nematodes.     

Beyond strain typing and molecular epidemiology: integrated genetic epidemiology of infectious diseases

In the past 20 years, genetic and molecular methods for characterizing pathogen strains have taken a major place in modern approaches to epidemiology of parasitic and other infectious diseases. Here, Michel Tibayrenc explains the main concepts used in this field of research, with special emphasis on the approaches developed in his team, and suggests future avenues to explore.     

Anatomical relations among endophytic holoparasitic angiosperms, autotrophic host plants and mycorrhizal fungi: A novel tripartite interaction

Mycorrhizae are widespread mutualistic symbioses crucial for the functioning of terrestrial ecosystems. Not all plants associate with mycorrhizae; most parasitic plants have been suggested to be nonmycorrhizal because they have developed alternative strategies to obtain nutrients. In endophytic parasitic plants, whose vegetative bodies grow completely inside their mycorrhizal host roots, the opportunity for establishing a tripartite association seems evident, but information on these systems is lacking. In studying natural associations among the endophytic holoparasite Cytinus hypocistis, their Cistaceae host species, and associated mycorrhizal fungi, we found that mycorrhizae were associated with the hosts and the parasites, reaching high frequencies of colonization. In parasitic and host root tissues, mycorrhizal fungi spread in the parenchymatic cells by intracellular growth and formed hyphal coils and vesicles, while the cambium and the vascular tissues were never colonized. This report is the first on a tripartite association of an endophytic parasitic plant, its host, and mycorrhizae in natural conditions, representing a novel trophic interaction not previously reported within the angiosperms. Additional studies on the interactions occurring among these three players are needed because they may be crucial to our understanding of how this mutualistic-antagonistic system is functioning and evolving.     

环介导等温基因扩增技术及其在病毒检测中的应用

环介导等温扩增是一门新兴的分子生物学检测技术,因其具有特异性高、敏感性高、简单、快捷及不需要昂贵的仪器设备等特点,受到了生物医学研究者的高度关注。目前,该方法已经被广泛应用于各种病原微生物检测。简要综述了环介导等温扩增技术的原理、特点,及其在病毒检测中的应用。     

Leptin,a tool of parasites?

One common physiological phenomenon that is involved both in infectious and in malignant processes is the reduction in appetite: disease anorexia. An increase in plasma levels of leptin with inflammation is thought to be involved in this process. However, from an evolutionary perspective, in certain cases, it would be more adaptive for an internal parasite to stimulate the appetite of the host instead of causing its suppression. We tested whether a parasitic infection with the larvae of the helminth parasite Taenia taeniaformis affects the levels of appetite-regulating proteins, such as leptin, ghrelin and neuropeptide-Y (NPY) in wild yellow-necked mouse (Apodemus flavicollis). We found that infected mice had lower plasma levels of leptin and increased levels of NPY than the uninfected subjects. Ghrelin levels were not associated with the occurrence of the parasites; however, these levels strongly correlated with the levels of NPY. This study suggests a possible manipulation by parasitic larvae of appetite regulation in infected subjects.     

Nucleic acid techniques and the detection of parasitic diseases

The detection of infectious disease-causing organisms is important for the initiation of effective treatment, in monitoring response to therapy and in epidemiological studies of disease of human or animal hosts. In this article Stuart Wilson primarily considers parasitic diseases, but much can be applied to infectious diseases in general.     

Symbiosis is a biological basis of infection

Symbiosis has been considered as a biological basis of the infectious process. Attention has been paid to the change of paradigm in symbiology and to the appearance of a new term: associative symbiosis. The main structural-functional elements of associative symbiosis have been assessed, and three vectors of the infectious process have been detected: (1) host-normoflora, (2) host-associants, and (3) associants-indigenous microflora (microsymbiocenosis). Functions of microsymbionts determining host colonization resistance and development of disbioses and pathobiocenoses have been considered. Resistance of organism biotopes to microbes is associated with substrates which are overcome by associants with persistent potential. Antagonism and change of persistent potential in both the infectious agent itself and commensal microorganisms are the basis of symbiont interactions. The given material describes the role of intercellular interactions of symbionts at the level of proprokaryotes, proeukaryotes during the infectious pathology.