Mathematical modelling of schistosomiasis japonica: comparison of control strategies in the People's Republic of China

We present the first mathematical model on the transmission dynamics of Schistosoma japonicum. The work extends Barbour's classic model of schistosome transmission. It allows for the mammalian host heterogeneity characteristic of the S. japonicum life cycle, and solves the problem of under-specification of Barbour's model by the use of Chinese data we are collecting on human-bovine transmission in the Poyang Lake area of Jiangxi Province in China. The model predicts that in the lake/marshland areas of the Yangtze River basin: (1) once-early mass chemotherapy of humans is little better than twice-yearly mass chemotherapy in reducing human prevalence. Depending on the heterogeneity of prevalence within the population, targeted treatment of high prevalence groups, with lower overall coverage, can be more effective than mass treatment with higher overall coverage. Treatment confers a short term benefit only, with prevalence rising to endemic levels once chemotherapy programs are stopped (2) depending on the relative contributions of bovines and humans, bovine treatment can benefit humans almost as much as human treatment. Like human treatment, bovine treatment confers a short-term benefit. A combination of human and bovine treatment will dramatically reduce human prevalence and maintains the reduction for a longer period of time than treatment of a single host, although human prevalence rises once treatment ceases; (3) assuming 75% coverage of bovines, a bovine vaccine which acts on worm fecundity must have about 75% efficacy to reduce the reproduction rate below one and ensure mid-term reduction and long-term elimination of the parasite. Such a vaccination program should be accompanied by an initial period of human treatment to instigate a short-term reduction in prevalence, following which the reduction is enhanced by vaccine effects; (4) if the bovine vaccine is only 45% efficacious (the level of current prototype vaccines) it will lower the endemic prevalence, but will not result in elimination. If it is accompanied by an initial period of human treatment and by a 45% improvement in human sanitation or a 30% reduction in contaminated water contact by humans, elimination is then possible. (C) 2002 Elsevier Science B.V. All rights reserved.

Chloroquine or sulfadoxine-pyrimethamine for the treatment of uncomplicated, Plasmodium falciparum malaria during an epidemic in Central Java, Indonesia

A recent malaria epidemic in the Menoreh Hills of Central Java has increased concern about the re-emergence of endemic malaria on Java, which threatens the island's 120 million residents. A 28-day, in-vivo test of the efficacy of treatment of malaria with antimalarial drugs was conducted among 16 7 villagers in the Menoreh Hills. The treatments investigated, chloroquine (CQ) and sulfadoxine pyrimethamine (SP), constitute, respectively, the first- and second-line treatments for uncomplicated malaria in Indonesia. The prevalence of malaria among 1389 residents screened prior to enrollment was 33%. Treatment outcomes were assessed by microscopical diagnoses, PCR-based confirmation of the diagnoses, measurement of the whole-blood concentrations of CQ and desethylchloroquine (DCQ), and identification of the Plasmodium falciparum genotypes. The 28-day cumulative incidences of therapeutic failure for CQ and SP were, respectively, 47% (N = 36) and 22% (N = 50) in the treatment of P. falciparum, and 18% (N = 77) and 67% (N = 6) in the treatment of P. vivax. Chloroquine was thus an ineffective therapy for P. falciparum malaria, and the presence of CQ-resistant P. vivax and SP-resistant P. falciparum will further compromise efforts to control resurgent malaria on Java.

Enhancing the immunogenicity and modulating the fine epitope recognition of antisera to a helical group A streptococcal peptide vaccine candidate from the M protein using lipid-core peptide technology

A conserved helical peptide vaccine candidate from the M protein of group A streptococci, p145, has been described. Minimal epitopes within p145 have been defined and an epitope recognized by protective antibodies, but not by autoreactive T cells, has been identified. When administered to mice, p145 has low immunogenicity. Many boosts of peptide are required to achieve a high antibody titre (> 12 800). To attempt to overcome this low immunogenicity, lipid-core peptide technology was employed. Lipid-core peptides (LCP) consist of an oligomeric polylysine core, with multiple copies of the peptide of choice, conjugated to a series of lipoamino acids, which acts as an anchor for the antigen. Seven different LCP constructs based on the p145 peptide sequence were synthesized (LCP1-->LCP7) and the immunogenicity of the compounds examined. The most immunogenic constructs contained the longest alkyl side-chains. The number of lipoamino acids in the constructs affected the immunogenicity and spacing between the alkyl side-chains increased immunogenicity. An increase in immunogenicity (enzyme-linked immunosorbent assay (ELISA) titres) of up to 100-fold was demonstrated using this technology and some constructs without adjuvant were more immunogenic than p145 administered with complete Freund's adjuvant (CFA). The fine specificity of the induced antibody response differed for the different constructs but one construct, LCP4, induced antibodies of identical fine specificity to those found in endemic human serum. Opsonic activity of LCP4 antisera was more than double that of p145 antisera. These data show the potential for LCP technology to both enhance immunogenicity of complex peptides and to focus the immune response towards or away from critical epitopes.

Immunity to asexual blood stage malaria and vaccine approaches

The development of a malaria vaccine seems to be a definite possibility despite the fact that even individuals with a life time of endemic exposure do not develop sterile immunity. An effective malaria vaccine would be invaluable in preventing malaria-associated deaths in endemic areas, especially amongst children less than 5 years of age and pregnant women. This review discusses our current understanding of immunity against the asexual blood stage of malaria - the stage that is responsible for the symptoms of the disease - and approaches to the design of an asexual blood stage vaccine.

Immune correlate study on human Schistosoma japonicum in a well-defined population in Leyte, Philippines: I. Assessment of 'resistance' versus 'susceptibility' to S-japonicum infection

This study describes the categorical classification of 155 individuals living in an endemic village in Macanip, Leyte, Philippines as 'resistant' or 'susceptible' to Schistosoma japonicum infection using available exposure, infection and reinfection data collected from a 3-year water contact (WC) study. Epidemiological parameters including age, sex, and infection intensities in relation to observed reinfection patterns are also described. This classification was used in subsequent immunological studies described in two accompanying papers to identify protective immune mechanisms among resistant individuals induced by defined candidate vaccine molecules for S. japonicum. The study suggests that individuals who were most vulnerable to rapid reinfection were children belonging to the 5-14 age group. A drop in incidence at age group 15-19 and decreased intensity of infection starting at this age group and older (15+) suggests development of immunity. Controlling for the effect of the other variables, a multivariate analysis showed significant association for sex, in that females were more likely to be resistant. This implies that other than acquired immunity to infection, some age-dependent host factors may also play an important role in the overall changes of reinfection patterns seen in schistosomiasis japonica in this population. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved.

Isolation and characterization of nine microsatellite loci from the Hawaiian grouper Epinephelus quernus (Serranidae) for population genetic analyses

The availability of variable genetic markers for groupers (Serranidae) has generally been limited to mitochondrial DNA. For studies of population genetic structure, more loci are usually required; particularly useful are those that are nuclear in origin such as microsatellites. Here, we isolated and characterized 9 microsatellite loci from the endemic Hawaiian grouper Epinephelus quernus using a biotin-labeled oligonucleotide-streptavidin-coated magnetic bead approach. Of the 20 repeat-containing fragments isolated, 15 had sufficient flanking region in which to design primers. Among these, 9 produced consistent polymerase chain reaction product, and 6 were highly variable. These 6 loci were all composed of dinucleotide repeats, with the number of alleles ranging from 6 to 18, and heterozygosities from 33.3% to 91.7%. The high levels of variability observed should make these markers useful for population genetic studies of E. quernus, and potentially other epinephelines.

Western Images of Islam, 1700-1900

This paper traces fluctuating attitudes to Islam and its Prophet, particularly in the eighteenth and nineteenth. Western perceptions, as revealed by writers of the period, encyclopaedias, biographies and commentaries, were sometimes sympathetic, sometimes dismissive; sometimes celebrating Islam's piousness; sometimes accusing it of fraud. Sometimes Islam is seen as benign; sometimes its violence is seen as endemic. Often the cultural biases of western observers are obvious: the west is progressive and historically dominant, the east (and its cultural accoutrements) is degenerate and over-zealous. But we ought not judge religions or cultures by their worst manifestations alone. Oriental societies were never just Islamic or traditional. They comprise not only those who perpetuate oppressive practices towards women but also modernizers who seek change.

Cross-protective and Infection-Enhancing Immunity in Mice Vaccinated Against Flaviviruses Belonging to the Japanese Encephalitis Virus Serocomplex

The Japanese encephalitis virus serocomplex is a group of mosquito-borne flaviviruses that cause severe encephalitic disease in humans. The recent emergence of several members of this serocomplex in geographic regions where other closely related flaviviruses are endemic has raised urgent human health issues. Thus, the impact of vaccination against one of these neurotropic virus on the outcome of infection with a second, serologically related virus is unknown. We show here that immunity against Murray Valley encephalitis virus in vaccinated mice can cross-protect but also augment disease severity following challenge with Japanese encephalitis virus. Immunepotentiation of heterologous flavivirus disease was apparent in animals immunized with a 'killed' virus preparation when humoral antiviral immunty of low magnitude was elicited. (C) 2002 Elsevier Science Ltd. All rights reserved.

A molecular phylogeny of the Australian skink genera Eulamprus, Gnypetoscincus and Nangura

Skinks from the genera Eulamprus, Gnypetoscincus and Nangura are a prominent component of the reptile fauna of the mesic forests of the east coast of Australia and have been the subject of numerous ecological studies. Highly conserved morphology and the retention of ancestral traits have limited our understanding of the relationships within and among these genera beyond an initial identification of species groups within Eulamprus. To address this deficit and to explore the relationships between Eulamprus and the monotypic genera Nangura and Gnypetoscincus, sections of two mitochondrial genes (ND4 and 16S rRNA) were sequenced and subjected to Bayesian phylogenetic analysis. This phylogenetic analysis supports recognition of the three species groups proposed for Eulamprus (murrayi, quoyii and tenuis) and indicates that this genus is paraphyletic, with Gnypetoscincus and Nangura being proximal to basal lineages of the tenuis group. To resolve these and broader problems of paraphyly, we suggest that each of the species groups from 'Eulamprus' should be recognised as a distinct genus. The phylogenetically and ecologically distinct water skinks of the quoyii group would be retained within Eulamprus and the diverse species of the tenuis group allocated to Concinnia. We suggest placing the monophyletic murrayi group, endemic to the rainforests of central eastern Australia, in a new genus ( yet to be formally described). The sequencing data also revealed the existence of a genetically divergent but morphologically cryptic lineage within E. murrayi and substantial diversity within E. quoyii. There is evidence for two major habitat shifts from rainforest towards drier habitats, one leading to the quoyii group and the second defining a clade of three species within the tenuis complex. These ecological transitions may represent adaptations to general drying across eastern Australia during the late Miocene - Pliocene. Each of the major areas of east coast tropical or subtropical rainforest contains multiple phylogenetically diverse endemic species, reflecting the long-term persistence and high conservation value of wet forest habitats in each area.

A global health problem caused by arsenic from natural sources

Arsenic is a carcinogen to both humans and animals. Arsenicals have been associated with cancers of the skin, lung, and bladder. Clinical manifestations of chronic arsenic poisoning include non-cancer end point of hyper- and hypo-pigmentation, keratosis, hypertension, cardiovascular diseases and diabetes. Epidemiological evidence indicates that arsenic concentration exceeding 50 mug l(-1) in the drinking water is not public health protective. The current WHO recommended guideline value for arsenic in drinking water is 10 mug l(-1), whereas many developing countries are still having a value of 50 mug 1(-1). It has been estimated that tens of millions of people are. at risk exposing to excessive levels of arsenic from both contaminated water and arsenic-bearing coal from natural sources. The global health implication and possible intervention strategies were also discussed in this review article. (C) 2003 Elsevier Ltd. All rights reserved.