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ScienceWeek
MEDICAL BIOLOGY: ON SALMONELLA INFECTIONS
Notes by ScienceWeek:
The enterobacteria are a large heterogeneous group of gram-negative rods whose natural habitat is the intestinal tract of humans and animals. The family includes many genera, of which Salmonella is one. There are 1500 to 2000 types of salmonellae, with one type, S. typhi (typhoid fever), notorious, and another type, S. typhimurium, the most common enterocolitis (gastroenteritis) pathogen in the US.
The following points are made by D.M. Musher and B.L. Musher (New Engl. J. Med. 2004 351:2417):
1) Unlike agents that cause contagious respiratory infections,(1) which are largely or exclusively indigenous to humans, agents that cause acute gastrointestinal illness may spread from person to person or may be acquired from a common food or environmental source, often water; they may also result from exposure to animals. Food or water may serve as a primary source of contagion or may, in turn, have been contaminated by contact with an infected person or animal. Thus, the epidemiology of acute gastrointestinal illness is complex.(2,3)
2) A major cause of acute gastrointestinal illness is the pathogen Salmonella typhosa (S. enterica serotype typhi). Although physicians do not always associate this organism with a typical syndrome of acute gastrointestinal illness,(4) some studies suggest that diarrhea predominates in the majority of cases.(5) S. typhi is highly adapted to humans. Infection is virtually always acquired by transmission from one person to another; an inviolable rule of epidemiology is that the occurrence of a case of typhoid fever implies an epidemiologic link to another person who either is actively infected or is chronically carrying the organism and shedding it in feces. When cases result from food ingestion, individual food handlers, such as the infamous cook known as Typhoid Mary, are usually found to be responsible. An infection from drinking contaminated water can also usually be traced to one or more infected persons whose excreta have entered the water supply.
3) The current rarity of typhoid fever in the US reflects good hygiene, lack of crowding, and high public health standards for home and industrial sewage. During the late 1990s, a breakdown of the public health infrastructure in the former Soviet Union led to a cessation of chlorination, the pirating of water lines with the use of substandard pipe fittings, and the crossing of these fittings by sewage lines, which culminated in an outbreak of 10,000 cases of typhoid fever.
4) The likelihood of direct contagion depends on the number of organisms in feces or contaminated foods, their ability to survive, replicate, or both, and the infectivity of the species and the specific strain. Chronic carriers of S. typhi have 10^(6) to 10^(9) colony-forming units (CFU) per gram or more in their feces. In experimental studies, ingestion of 10^(3) CFU of the Quailes strain of S. typhi was not infectious in volunteers, whereas nearly 50 percent of volunteers were infected by ingesting 10^(5) or 10^(7) CFU, and 96 percent were infected by ingesting 10^(8) or more CFU. The results of these experimental studies indicate that a large inoculum is infective. However, infection in the real world will depend on the infectivity of the strain studied. In nature, such strains are almost certainly heterogeneous, as has been shown for other enteric and for respiratory pathogens(1). The early implications of the watchwords "fingers, food, and flies," and the frequent spread from patients to nurses and physicians in the era before antibiotics, are consistent, at least in some instances of natural infection, with low-inoculum contagion, under the assumption that large numbers of organisms would not be transmitted in these situations.
5) Infections with most other types of salmonella, except for S. paratyphi, derive from environmental sources, principally poultry and livestock. Despite the frequency with which these organisms cause acute gastrointestinal illness, there are remarkably few documented examples of person-to-person spread. An outbreak in a day-care facility was associated with an uncertain number of secondary cases, and long-term surveillance of 54 permanent carriers of nontyphoidal salmonella identified 10 instances of transmitted infection. On the basis of epidemiologic studies, the infective dose of nontyphoidal salmonella is thought to be small, not exceeding 100 CFU. The paucity of documented instances of contagion may reflect the difficulty of distinguishing person-to-person spread from that due to a common food source, rather than the true absence of human transmission.
References (abridged):
1. Musher DM. How contagious are common respiratory infections? N Engl J Med 2003;348:1256-1266
2. Mead PS, Slutsker L, Dietz V, et al. Food-related illness and death in the United States. Emerg Infect Dis 1999;5:607-625
3. Imhoff B, Morse D, Shiferaw B, et al. Burden of self-reported acute diarrheal illness in FoodNet surveillance areas, 1998-1999. Clin Infect Dis 2004;38:Suppl 3:S219-S226
4. Lesser CF, Miller SI. Salmonellosis. In: Braunweld E, Fauci AS, Kasper DL, Jameson JL, eds. Harrison's principles of internal medicine. 15th ed. New York: McGraw-Hill, 2001:970-5
5. Roy SK, Speelman P, Butler T, Nath S, Rahman H, Stoll BJ. Diarrhea associated with typhoid fever. J Infect Dis 1985;151:1138-1143
New Engl. J. Med. http://www.nejm.org
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Related Material:
ON THE MICROBIAL PATHOGEN SALMONELLA
Notes by ScienceWeek:
Salmonella (named after Daniel E. Salmon, pathologist [1850-1914]) is a genus of gram-negative rod-shaped bacteria various species of which cause food poisoning (salmonellosis), typhoid fever, paratyphoid fever, and some forms of gastroenteritis in humans.
In general, the term "serovar" (serotype) refers to a subdivision (strain) of a group or species or subspecies distinguishable from other strains in the group on the basis of immune responses of a host to the strain, i.e., on the basis of differences in strain antigens.
The following points are made by J.H. Brumell et al (Current Biology 2002 12:R15):
1) Many pathogenic microbes establish infection by colonizing and entering cells, and each invasive pathogen has a particular strategy for intracellular survival. For example, some pathogens escape the phagosome (intracellular digestive vacuole) and replicate in the nutrient-rich cytosol, while others alter the trafficking of their vacuolar niche to avoid antimicrobial agents elsewhere in the cell. Salmonella is a well-studied example of the latter strategy, altering endocytic trafficking of its vacuole in order to survive and replicate in host cells during disease.
2) The estimated 2200 different serovars of Salmonella can infect most animals, with the outcome of infection determined by the genetic complement and fitness of both the infecting Salmonella serovar and its host. Salmonella enterica serovar S. typhomurium is a leading cause of gastroenteritis (food poisoning) in humans, and causes a systemic disease resembling typhoid fever in genetically susceptible mice, making it a powerful model for the study of both diseases. Infections are initiated by the consumption of contaminated food or water, after which the bacteria breach the epithelial barrier of the small intestine and enter the bloodstream to colonize the liver, spleen, and other tissues. During this conquest of the host, S. typhimurium occupies an intracellular niche and is protected from cell-impermeant antibiotics. How this pathogen can perform such a feat during its interactions with many diverse cell types of the host is an important and hotly debated question. Recent studies have demonstrated that the fate of the intracellular vacuole containing the pathogen is different in various cell types.
Current Biology http://www.current-biology.com
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Related Material:
VIRULENCE OF ANTIBIOTIC RESISTANT SALMONELLA
The following points are made by Bjorkman et al (Proc. Nat. Acad. Sci. 1998 95:3949):
1) The authors report a study of the virulence of antibiotic resistant Salmonella typhimurium. During the last decade there has been an alarming increase in the appearance of antibiotic-resistant bacteria as a result of an increased use of antibiotics combined with the exceptional ability of bacteria to develop resistance.
2) One strategy to reverse this development is to decrease the use of antibiotics to promote the disappearance of the resistant bacteria present in human and environmental reservoirs. Implicit in this reasoning is that mutated resistant bacteria will be less viable in an antibiotic-free environment.
3) An associated question is whether resistant bacteria with reduced or no virulence might accumulate compensating mutations that restore fitness and virulence without loss of resistance.
4) In this study, the authors examined the fitness of S. typhimurium in mice, and their results indicate that most resistant mutants are less virulent than the wild type, but that the avirulent mutants rapidly accumulate various types of compensating mutations that restore virulence to wild-type levels without loss of high-level resistance.
5) The authors suggest that if their results are general and apply to other medically relevant pathogens, then the strategy of getting rid of antibiotic resistant bacteria by a decreased use of antibiotics may not be successful.
Proc. Nat. Acad. Sci. http://www.pnas.org
ScienceWeek http://scienceweek.com
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