Infectious diseases exert a constant evolutionary pressure on the genetic makeup of our innate immune system. Polymorphisms in Toll-like receptor 4 (TLR4) have been related to susceptibility to Gram-negative infections and septic shock. Here we show that two polymorphisms of TLR4, Asp299Gly and Thr399Ile, have unique distributions in populations from Africa, Asia, and Europe. Genetic and functional studies are compatible with a model in which the nonsynonymous polymorphism Asp299Gly has evolved as a protective allele against malaria, explaining its high prevalence in subSaharan Africa. However, the same allele could have been disadvantageous after migration of modern humans into Eurasia, putatively because of increased susceptibility to severe bacterial infections. In contrast, the Asp299Gly allele, when present in cosegregation with Thr399Ile to form the Asp299Gly/Thr399Ile haplotype, shows selective neutrality. Polymorphisms in TLR4 exemplify how the interaction between our innate immune system and the infectious pressures in particular environments may have shaped the genetic variations and function of our immune system during the out-of-Africa migration of modern humans.cytokines ͉ human migration ͉ innate immunity ͉ Toll-like receptor 4 ͉ sepsis

Acute gastroenteritis is a major source of morbidity and mortality among young children in developed and developing countries. Enteropathogenic viruses are regarded as particularly relevant causative agents. Between February 2001 and January 2002, fecal specimens were obtained from German children admitted to hospital with acute gastroenteritis and examined for rotaviruses, Noroviruses, enteric adenoviruses, and astroviruses using (RT-)PCR methods. Of the 59% (129/217) samples positive for > or =1 viral agent, 79% (102/129) carried rotavirus, whereas Norovirus was detected in 35% (45/129), enteric adenovirus in 14% (18/129), and astrovirus in 4% (5/129). Thirty-eight specimens contained at least two enteropathogenic viruses, with the majority of coinfections attributable to rotavirus/Norovirus dual infections. Sequence analysis revealed a cocirculation of G1, G3, G4, and G9 type rotavirus with G1 being the most common and G9 the second most common rotavirus G-type. Emergence of G9 rotaviruses in Germany may have implications for future vaccine development. A variety of Norovirus genotypes, most belonging to GGII, were found. Apart from subgenus F, adenovirus related genetically to subgenera A-C were detected. All astroviruses belonged to genotype 1. This is the first study concerning German children admitted to hospital that assesses the relative importance of these viruses by nested (RT-) PCR methods.

A German mining lake and the supplying surface waters, which are located downstream of a sewage plant, were examined regarding their microbiological and virological quality. Between October 2002 and September 2003, specific PCR methods were used to determine the occurrence of enteric viruses in 123 water specimens drawn at different sites downstream of the waste water treatment plant and in 9 samples from the sewage plant influent. Detection rates in sewage plant effluents and surface water samples depended on sampling sites and were: 29-76% for enterovirus (EntV), 24-42% (astrovirus, AstV), 15-53% (norovirus, NV), 3-24% (rotavirus, RoV), 5-20% (hepatitis A virus, HAV) and 20% (adenovirus, AdV). AstV genome load of selected samples was between 3.7 x 10(3) to 1.2 x 10(8) genome equivalents per liter (gen.equ./l), depending on sampling location; NV average genome load ranged from 1.8 x 10(4) to 9.7 x 10(5) gen.equ./l. Cell culture methods showed that three out of 18 PCR positive samples contained infectious EntV. Even though microbiological parameters such as Escherichia coli, enterococci and coliphages indicated acceptable microbiological water quality, the virological data of this study suggest the possibility that surface waters may be a source for enteric viral infections.

The occurrence of Aichi virus, a picornavirus associated with acute gastroenteritis, has so far only been described in Asian countries. This study reports the first finding of Aichi virus in clinical specimens from Germany and Brazil. The nucleotide sequences of both a German and a Brazilian isolate were determined, analyzed, and compared to known Aichi sequences. The German strain turned out to be a member of genogroup A, while the Brazilian belonged to genogroup B. For a primary assessment of the epidemiological importance of Aichi virus in Germany, a panel of 485 German serum samples was screened for antibody to Aichi virus, and a seroprevalence of 76% was found.