Full-genome sequence analyses of hepatitis B virus (HBV) strains recovered from chimpanzees infected in the wild: implications for an origin of HBV.
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Hepatitis B virus (HBV) belongs to the genus Orthohepadnavirus of the family Hepadnaviridae. Having been found in various animals (duck, heron, woodchuck, ground squirrel, and primates), hepadnaviruses must have undergone a long history of evolution and may comprise more members than currently recognized. Chimpanzees may also have their own hepadnavirus, even if it might be very close to HBV. We analyzed HBV-like sequences from three chimpanzees (Pan troglodytes) that were most likely infected during their life in Africa in the wild. Two chimpanzees (Ch256 and Ch258) possessed a viral genome of 3182 nt in length with a 33-nt deletion in the preS1 region, which could not be classified into any of the six genotypes (A-F) of human HBV but was very homologous to a previously reported isolate from a London Zoo chimpanzee. Phylogenetically distinct from the HBV-like sequences from gibbons, orangutans, and a gorilla so far reported, the Ch256 and Ch258 isolates would represent an indigenous chimpanzee HBV (tentatively ChHBV). A third chimpanzee (Ch195) had a 3212-nt genome, classifiable into the genotype E of HBV. Because HBV-E has been found mostly in Africans, Ch195 may have been infected from a human source in Africa. However, an inverse scenario is also possible: a spread of HBV-E might have occurred from chimpanzees to humans a long time ago in Africa. Analysis of the arginine-rich C-terminal region of the core protein, which is well conserved among mammalian hepadnaviruses, indicated that HBV-E/F and nonhuman primate hepadnaviruses are much closer than HBV-A/B/C/D to the hepadnaviruses of woodchuck and ground squirrel. Our results support an "ex-nonhuman primate" hypothesis for the origin of HBV. (+info)
Prenatal or early postnatal events predict infectious deaths in young adulthood in rural Africa.
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BACKGROUND: Research over the past decade has suggested that prenatal and early postnatal nutrition influence the risk of developing chronic degenerative diseases up to 60 years later. We now present evidence that risk of death from infectious diseases in young adulthood is similarly programmed by early life events. METHODS: In three rural Gambian villages, affected by a marked annual seasonality in diet and disease, we have kept detailed demographic, anthropometric and health records since 1949. Fate was known with certainty for 3,162 individuals (2,059 alive/1,103 dead, most dying in childhood). For this case-control analysis of antecedent predictors of premature mortality, all adult deaths (n = 61) were paired with two randomly selected controls matched for sex and year of birth. RESULTS: Mean age at death was 25 (SD: 8) years. Adult death was associated with a profound bias in month of birth with 49 cases born in the nutritionally-debilitating hungry season (Jul-Dec) versus 12 in the harvest season (Jan-Jun). Relative to harvest season the hazard ratio for early death in hungry-season births rose from 3.7 (for deaths >14.5 years, P = 0.000013) to 10.3 (for deaths >25 years, P = 0.00002). Anthropometric and haematological status at 18 months of age was identical in cases and controls, indicating an earlier origin to the defect. Most deaths for which cause was known had a definite or possible infectious aetiology; none were from degenerative diseases of affluence. CONCLUSIONS: Early life exposures, correlated with season of birth, strongly influence susceptibility to fatal infections in young adulthood. The evidence suggests that nutritionally-mediated intrauterine growth retardation may permanently impair the development of immune function. (+info)
Broader vaccination of expatriates against HBV infection: do we reach those at highest risk?
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BACKGROUND: The effects of the implementation of a new Dutch hepatitis B virus (HBV) vaccination strategy (1991) for expatriates on HBV vaccination status and HBV infection prevalence were evaluated in a group of 864 expatriates returning from HBV-endemic areas. METHODS: During a routine medical examination at the participating medical centres Dutch expatriates were asked to complete a questionnaire and to donate a serum sample for HBV testing. Blood was tested for antibodies against the hepatitis B core (anti-HBc) and surface antigens (anti-HBs). The serological data were related to information gathered on aspects of residence, sexual risk behaviour and occupational risks. RESULTS: A significantly higher percentage of expatriates (37%) were vaccinated compared to a previous study in 1987-1989 (14%). However, the percentage of expatriates with HBV infection markers (5%) had not decreased significantly. Moreover, the risk for HBV infection, as determined with a questionnaire, was still affected by well-known risk factors such as homosexual contacts (odds ratio [OR] = 6.6, 95% CI: 1.7-26), more than five casual local partners (OR = 3.6, 95% CI: 1.2-11) and more than five occupational accidents in the last 3 years (OR = 20, 95% CI: 2-187). Detailed analysis of the vaccination status indicated that especially young female expatriates with low risk behaviour (65%) were protected, while older male expatriates with high risk behaviour were less protected (20%). CONCLUSION: We conclude that the new vaccination strategy has resulted in a higher percentage of expatriates protected. However, only a small proportion was reached of those at highest risk for HBV infection. (+info)
Modelling the incidence of congenital rubella syndrome in developing countries.
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BACKGROUND: As of 1997, less than one-third of developing countries included rubella vaccine in their national immunization programme. In countries that have achieved high coverage of measles vaccine, an ideal opportunity exists to include control of rubella and congenital rubella syndrome (CRS) in enhanced measles control activities. Data on the burden of congenital rubella syndrome are important to guide rubella vaccination policies. METHODS: We reviewed the literature to identify studies of rubella antibody prevalence in developing countries that were conducted on populations with no major selection bias, prior to wide-scale rubella vaccination in the country. We used a simple catalytic model to describe the age-specific prevalence of susceptibility to rubella virus infection in given populations. Estimates of the incidence of infection among pregnant women were calculated using expressions for the average prevalence of susceptibility to infection and the incidence of infection during gestation. To estimate the number of cases of CRS, we assumed an overall risk of 65% after infection in the first 16 weeks of pregnancy and zero risk thereafter. These estimates were derived for each country for which data were available, then for each World Health Organization region, excluding Europe. RESULTS: The estimated mean incidence of CRS per 100,000 live births was lowest in the Eastern Mediterranean region (77.4, range 0-212) and highest in the Americas (175, range 0-598). The mean of the estimates of the total number of cases of CRS in developing countries in 1996 was approximately 110,000. The range was, however, very wide, from as few as 14,000 to as many as 308,000 cases. CONCLUSIONS: Congenital rubella syndrome is an under-recognized public health problem in many developing countries. There is an urgent need for collection of appropriate data to estimate the cost-effectiveness of a potential global rubella control programme. (+info)
Human immunodeficiency virus (HIV) subtype surveillance of African-born persons at risk for group O and group N HIV infections in the United States.
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A population-based surveillance registry was used to identify human immunodeficiency virus (HIV)-infected persons in the United States at increased risk for group O and group N infections (those born in or near African countries where group O infection has been reported). Of 155 eligible subjects, 37 gave samples. By phylogenetic and serologic analysis, 32 were infected with group M (16 with subtype A, 5 with B, 7 with C, and 1 each with subtypes D, F2, G, and recombinant A/J) and 2 with group O but none with group N virus. For 3, samples could not be typed by serology or amplified by polymerase chain reaction using group M-, O-, or N-specific primers. In the United States, group O HIV infection is uncommon; no case of group N infection was found. African-born persons may have HIV strains typical of their birth country. Ongoing subtype surveillance may allow early identification of novel or emerging HIV strains. (+info)
From genotype to phenotype: genetics and medical practice in the new millennium.
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The completion of the human genome project will provide a vast amount of information about human genetic diversity. One of the major challenges for the medical sciences will be to relate genotype to phenotype. Over recent years considerable progress has been made in relating the molecular pathology of monogenic diseases to the associated clinical phenotypes. Studies of the inherited disorders of haemoglobin, notably the thalassaemias, have shown how even in these, the simplest of monogenic diseases, there is remarkable complexity with respect to their phenotypic expression. Although studies of other monogenic diseases are less far advanced, it is clear that the same level of complexity will exist. This information provides some indication of the difficulties that will be met when trying to define the genes that are involved in common multigenic disorders and, in particular, in trying to relate disease phenotypes to the complex interactions between many genes and multiple environmental factors. (+info)
Stable isotopes examined across a migratory divide in Scandinavian willow warblers (Phylloscopus trochilus trochilus and Phylloscopus trochilus acredula) reflect their African winter quarters.
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The C and N isotopes of feathers from two subspecies of willow warblers Phylloscopus trochilus trochilus and Phylloscopus trochilus acredula) are isotopically distinct. Our analysis of 138 adult males from 14 sites distributed across Sweden shows that the mean delta15N and delta13C values of subspecies acredula (from latitudes above 63 degrees N) were significantly higher than the mean delta15N and delta13C values of subspecies trochilus (from latitudes below 61 degrees N). The analysed willow warbler feathers had been moulted in the winter quarters and the observed isotopic signatures should thus reflect the isotopic pattern of food assimilated in Africa. The isotopic data observed in Sweden match the cline in morphology, both showing abrupt changes around 62 degrees N. This result agrees with data from ringing recoveries indicating that the two subspecies occupy geographically and isotopically distinct wintering grounds in Africa. Our isotopic data suggest that analysis of stable isotopes of C and N is a promising method to track wintering quarters of European birds that migrate to Africa. (+info)
Molecular epidemiology of Blastomyces dermatitidis.
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The inhalation of conidia of Blastomyces dermatitidis, a fungus found in soil, causes disease in humans and animals. We studied the genetic diversity of this pathogen by extracting DNA yeasts and analyzing them with a polymerase chain reaction (PCR)-based typing system we developed, which used restriction fragment analysis of amplicons from the regions between the rDNA repeats and allowed us to class isolates into 3 major groups. Strains were further differentiated by use of PCR fingerprinting with 3 different primers. Fifty-nine isolates collected over 35 years from 15 regions (United States, India, Africa, Canada) were analyzed. Genotypic groups A, B, and C contained 17, 23, and 19 isolates, which were divided into 5, 15, and 12 types, respectively. All 16 isolates from North America in group A were from the upper midwestern United States or Canada, whereas 0 of 20 isolates from the southeastern United States were in group A. Studies of the largest collection from 1 locale (Eagle River, WI), revealed that the soil isolates studied were not responsible for the majority of cases in this outbreak, as previously proposed, and that >1 strain was present in the environment and in patients. Overall, these results provide a tool for the epidemiological study of blastomycosis and illuminate the genetic and geographic diversity of this important pathogen. (+info)