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EPIDEMIOLOGY

The bacteria of modern life

The level of infestation by Escherichia coli is changing in Brazil and brings with it serious public health problems

Luiz Rachid Trabulsi, responsible for the Special Microbiology Laboratory of the Butantan Institute of São Paulo, is an implacable pursuer of the bacterium Escherichia coli, which causes diarrhea in children. With the authority of someone who for more than forty years has dedicated himself to the study of this microorganism, he is giving out an alert: new and dangerous forms have been showing themselves firstly in first world countries and their presence is being more and more detected here in Brazil.

They are types of the bacterium called emergents, associated with modern life style: they are normally present in industrialized foods and badly cooked meats. Trabulsi, who is continuing to study the question within a project financed through FAPESP, does not discard the hypothesis of epidemics caused by these bacteria in Brazil, and reveals that new strains could provoke deadly diseases if they are not adequately treated. “When some Escherichia become less frequent, others appear and occupy their space. This is precisely what the public health system is looking into with this new situation”, the researcher emphasizes.

One of the major difficulties in combating Escherichia coli is the fact that it is very diversified. Some types have already been studied in depth, while others – exactly those classed as “emergents” – have only begun to be understood. There are strains that live in symbiosis in the intestines of human beings, where there are also the synthesizers of vitamins K and B. Nonetheless, when they leave their natural habitats and reach other organs, they can cause serious damage, among them urinary infections, child meningitis and even a generalized infection (septicemia).

The pathogenics
Other strains do not live in the intestines, and, when they arrive there, bring on diarrhea and infections. Among these pathogenic strains there are three most common and important groups. The first is that of the enteropathogenics by the acronym EPEC and responsible for children’s diarrhea. In May, in a specialized publication on new infectious diseases – Emerging Infectious Diseases, of the Center for Disease Control in the United States -, Trabulsi published an article about the typical and untypical EPEC bacteria, highlighting the characteristics that distinguish them – such as the antigen, its genetic characteristics and the mechanisms related to virulence.

The Enterotoxigenics, of the ETEC group, are those that bring on the so-called travelers’ diarrhea, a result of the consumption of food that do not make up part of the day-to-day diet of the patient. The third group is the STEC (Shiga toxin producing Escherichia coli), made up by bacteria that form hemorrhaging colitis (diarrhea with blood), and in extreme situations, the hemolytic uremic syndrome. This syndrome, characterized by anemia, acute renal insufficiency and the lowering of the number of platelets, affects mainly children and the elderly and, if it is not well treated, can lead to death. In the STEC group is the sub-group EHEC, of the Enterohemorrhagic Escherichia coli, which acts in the same manner, but is in general associated with more serious situations.

First case
Trabulsi emphasized a key to understanding the question: in the typical case of EPEC – the first type to be identified, way back in the 40s -, the only possible reservoir was man himself. In all of the other strains cited, characterized more recently, both the human beings and the animals could serve as a reservoir. And it is exactly for this reason that they are associated to the habits of modern day life, among them that of fast foods. “The genetic make up of the bacteria is what determines, to a large part, the reservoirs that they could reach”, he explains.

The new scenario that involves the Echerichia coli has been known to the Europeans and the Americans since the 70s. The first epidemic brought on by the Ehec happened in 1982 in the city of Pittsburgh in the United States, caused by the consumption of contaminated hamburgers. Afterwards, other outbreaks occurred in Finland, Germany, England, Scotland, Canada and Japan. The coming forth of these new strains began to call the attention of the Brazilian researchers at the beginning of the 90s – and, since then, various studies have been published about the question.

The issue of the last month of Emerging Infectious Diseases also brought the description of the first registered case in Brazil of Escherichia coli a producer of the toxin Shiga, associated with the hemolytic uremic syndrome. The text is accredited to Beatriz Ernestina Cabilio Guth, of the Microbiology Department of the Federal University of São Paulo (Unifesp), which tells of the case of an eight-month year old baby that presented anemia, shortage of urination (diminution in the volume of urine) and a prior situation of diarrhea. It was dealt with in March of 2001 at the São Paulo Hospital of Unifesp, and the syndrome diagnosed – the laboratory examinations clearly pointed towards the presence of an E. coli that was producing the toxin Shiga. The baby was treated and recovered.

However, in the opinion of Beatriz, it is not easy to clear up these cases. Renal insufficiency, when it appears, is already a consequence of the action of the toxin Shiga, and, in the majority of cases, the Escherichia cannot be isolated to make the diagnosis. The use of antibiotics can also help to mask the situation. “The discovery of the syndrome in the baby is an important alert and reinforces the findings that these bacteria are around and can be associated to much more serious cases”, emphasizes the researcher.

Another article in the April issue of the same magazine – resulting from as study carried out in a partnership between the Unifesp group and a team from the Adolfo Lutz Institute – had already cited the identification, in the State of São Paulo, of three pioneering cases of diarrhea caused by an Ehec of the same type which in 1982 brought about the epidemic in Pittsburgh. The first three situations involving the diarrhea brought about by the Stec had been related at the beginning of the 90s by the Butantan group, in conjunction with the Unifesp team.

Typical and atypical
At the age of seventy four, and already twice retired – in 1988 from the São Paulo School of Medicine (today Unifesp) and in 1998 from the University of São Paulo (USP), in the position of an emeritus professor -, Trabulsi continues in activity, as the May article in Emerging proves, in which he characterizes the EPEC bacteria as typical and atypical.

The first major distinction that he makes is with respect to the reservoir that can house them: only in man in the case of the typical type and as well in animals for the atypical types. And the two types are formed by serotypes or different antigens. The typical types have plasmids (extra chromosome genetic material) which allow them to adhere in block to the wall of the intestine.The power of the virulence of these bacteria is associated with the plasmid. The atypical types, in which the plasmid does not show itself, attack the intestine in a diffuse manner and produces the toxins. Genetically, the atypical types are much closer to the EHEC and STEC groups than of the types of the group itself, the EPEC. In the end, it is known that the two lineages produce varied types of intimin protein- but the consequences of this still have to be studied. As well, it is not known for certain which of two strains can cause more damage to the health of humans.

In Brazil, the typical EPEC bacteria dominated the scene until the end of the 80s, when they accounted for close to 30% of the cases of child diarrhea registered in the country. Today, according to the researcher, this rate has fallen to between 1% and 2%. In compensation, the diarrhea in Brazilian children caused by atypical Epecs have reached 7% of the total. “There is a clear tendency of inversion in the behavior of the bacteria”, assures Trabulsi.

Ideal conditions
The researcher looked for the causes for the consolidation of this new scenario of infestation and concluded: in a large part, modern society has managed to overcome the problems of hygiene and of basic sanitation that favor the transmission of these well known EPEC bacteria. However, ideal conditions for that new strains were developed: the higher the consumption of industrialized food and badly cooked meat, the greater the possibility of us being surprised by an emergent Echerichia.

The large number of cattle herds and the importing of meats are other factors that favor the spreading of these bacteria in Brazil. It could well be that we have lived through an epidemic without even knowing it. “The problem is that our sanitary authorities don’t worry themselves about identifying the agents that cause diarrhea”, underlines Trabulsi, in whose homage, as a matter of fact, researchers at the American CDC gave the name of Trabulsiella guamensis to a bacterium that causes hospital infection.

For Trabulsi, combating the emergent bacteria should involve a more active attitude from the sanitary authorities and more responsible individual actions in relation to the origin, hygiene and cooking of food. As well there must be the creation of conditions for laboratories to analyze more rapidly patients’ feces samples. An alternative are the vaccines, some of them already in the test phase, that will permit the cutting off of the malady at the root.To speed up discoveries, the Butantan Institute keeps partnerships with institutions abroad such as the Pasteur Institute of Paris (France), Imperial College of Science in London and the Institute of Child Health of Birmingham (England), Institute for Vaccine Development of Baltimore (United States) and Robert Koch-Institute (Germany). In Brazil, the closest relations are with Unifesp and the Adolfo Lutz Institute, as well as the Institute of Microbiology of Rio de Janeiro.

Starting in September, Trabulsi intends to concentrate on an updating of his books Microbiology (3rd edition, 1996, Editor Ateneu, Rio de Janeiro) and Microbiology of Intestinal Infections (1982, Ateneu). “I would like to leave a contribution, revised and modern, about the E. coli”, he says. “Even after forty years of research, I don’t get tired of these small beings”.

THE PROJECT
Characterization of Virulence Factors and Mechanisms of Pathogenicity of Some Special Serotypes of EPEC and EAEC (nº 01/08570-3); Modality Regular line of research assistance; Coordinator Luiz Rachid Trabulsi – Butantan Institute; Investment R$ 144,200 and US$ 17,578

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