Arias and Murray discuss the factors that may have contributed to the rise of enterococci as nosocomial pathogens, with an emphasis on the epidemiology and pathogenesis of these species and their mechanisms of resistance to the most relevant anti-enterococcal agents used in clinical practice.

The rise of the Enterococcus : beyond vancomycin resistance

Naturally acquired immunity to falciparum malaria protects millions of people routinely exposed to Plasmodium falciparum infection from severe disease and death. There is no clear concept about how this protection works. There is no general agreement about the rate of onset of acquired immunity or what constitutes the key determinants of protection; much less is there a consensus regarding the mechanism(s) of protection. This review summarizes what is understood about naturally acquired and experimentally induced immunity against malaria with the help of evolving insights provided by biotechnology and places these insights in the context of historical, clinical, and epidemiological observations. We advocate that naturally acquired immunity should be appreciated as being virtually 100% effective against severe disease and death among heavily exposed adults. Even the immunity that occurs in exposed infants may exceed 90% effectiveness. The induction of an adult-like immune status among high-risk infants in sub-Saharan Africa would greatly diminish disease and death caused by P. falciparum. The mechanism of naturally acquired immunity that occurs among adults living in areas of hyper- to holoendemicity should be understood with a view toward duplicating such protection in infants and young children in areas of endemicity.

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Acquired immunity to malaria.

The microorganisms that inhabit the human gastrointestinal tract comprise a complex ecosystem with functions that significantly contribute to our systemic metabolism and have an impact on health and disease. In line with its importance, the human gastrointestinal microbiota has been extensively studied. Despite the fact that a significant part of the intestinal microorganisms has not yet been cultured, presently over 1000 different microbial species that can reside in the human gastrointestinal tract have been identified. This review provides a systematic overview and detailed references of the total of 1057 intestinal species of Eukarya (92), Archaea (8) and Bacteria (957), based on the phylogenetic framework of their small subunit ribosomal RNA gene sequences. Moreover, it unifies knowledge about the prevalence, abundance, stability, physiology, genetics and the association with human health of these gastrointestinal microorganisms, which is currently scattered over a vast amount of literature published in the last 150 years. This detailed physiological and genetic information is expected to be instrumental in advancing our knowledge of the gastrointestinal microbiota. Moreover, it opens avenues for future comparative and functional metagenomic and other high-throughput approaches that need a systematic and physiological basis to have an impact.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/1574-6976.12075

The first 1000 cultured species of the human gastrointestinal microbiota

Enterococci are commensal organisms well suited to survival in intestinal and vaginal tracts and the oral cavity. However, as for most bacteria described as causing human disease, enterococci also possess properties that can be ascribed roles in pathogenesis. The natural ability of enterococci to readily acquire, accumulate, and share extrachromosomal elements encoding virulence traits or antibiotic resistance genes lends advantages to their survival under unusual environmental stresses and in part explains their increasing importance as nosocomial pathogens. This review discusses the current understanding of enterococcal virulence relating to (i) adherence to host tissues, (ii) invasion and abscess formation, (iii) factors potentially relevant to modulation of host inflammatory responses, and (iv) potentially toxic secreted products. Aggregation substance, surface carbohydrates, or fibronectin-binding moieties may facilitate adherence to host tissues. Enterococcus faecalis appears to have the capacity to translocate across intact intestinal mucosa in models of antibiotic-induced superinfection. Extracellular toxins such as cytolysin can induce tissue damage as shown in an endophthalmitis model, increase mortality in combination with aggregation substance in an endocarditis model, and cause systemic toxicity in a murine peritonitis model. Finally, lipoteichoic acid, superoxide production, or pheromones and corresponding peptide inhibitors each may modulate local inflammatory reactions. Images

Virulence of enterococci.

The 1918-1919 H1N1 influenza pandemic was among the most deadly events in recorded human history, killing an estimated 50-100 million persons. Because recent H5N1 avian epizootics have been associated with sporadic human fatalities, concern has been raised that a new pandemic, as fatal as the pandemic of 1918, or more so, could be developing. Understanding the events and experiences of 1918 is thus of great importance. However, despite the genetic sequencing of the entire genome of the 1918 virus, many questions about the 1918 pandemic remain. In this review we address several of these questions, concerning pandemic-virus origin, unusual epidemiologic features, and the causes and demographic patterns of fatality. That none of these questions can yet be fully answered points to the need for continued pandemic vigilance, basic and applied research, and pandemic preparedness planning that emphasizes prevention, containment, and treatment with antiviral medications and hospital-based intensive care.

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The 1918 Influenza Pandemic: Insights for the 21st Century

1. Tetany occurs spontaneously in many forms and may also be produced by the destruction of the parathyroid glands. Recent researches tend to demonstrate an intimate relation between the various forms of tetany and relative or absolute insufficiency of the parathyroid gland. 2. The parathyroid glands are independent organs with definite specific function. Whether or not this function is intimately related to that of other organs of internal secretion is not as yet proven. 3. The number and distribution of the parathyroid glands varies. Failure to produce tetany experimentally is probably due to the fact that some parathyroid tissue remains after an apparently complete extirpation. When extirpation is complete tetany appears, even in herbivora. Only a very small amount of parathyroid tissue is required to prevent this. 4. The effect of the extirpation of the parathyroid glands may be annulled by the reintroduction of an extract of these glands even from an animal of widely different character. The active principle is associated with a nucleo-proteid in the extract and may be separated with this nucleo-proteid from the remaining inert albuminous substances. Its effect in counteracting tetany appears some hours after injection and lasts several days. 5. The parathyroid glands contain no considerable amount of iodine. The parathyroid extract is not an iodine containing compound. 6. In tetany there is apparently some disturbance of the composition of the circulating fluids ordinarily prevented by the secretion of the parathyroid, which disarranges the balance of the mineral constituents of the tissues. Possibly this consists in the appearance of an injurious substance of an acid nature for such tetany may he relieved by extensive bleeding with replacement of the blood by salt solution. No actual poisonous material has, however, been demonstrated by the transference of the blood of a tetanic animal to the veins of a normal one. 7. Numerous researches have shown the important relation of the calcium salts to the excitability of the central nervous system. Their withdrawal leaves the nerve cells in a state of hyperexcitability which can be made to disappear by supplying them with a solution of a calcium salt. 8. Tetany may be regarded as an expression of hyperexcitability of the nerve cells from some such cause. 9. The injection of a solution of a salt of calcium into the circulation of an animal in tetany promptly checks all the symptoms and restores the animal to an apparently normal condition. 10. Injections of magnesium salts probably have a similar effect but these effects are masked by the toxic action of the salt. 11. The injection of sodium or potassium salts has no such beneficial effect but rather tends to intensify the symptoms. This is true also of the alkaline salts of sodium which were studied especially in respect to their basic properties. 12. The effect of calcium is of value in human therapeutics in combating the symptoms of spontaneous forms of tetany and in relieving the symptoms in cases of operative tetany and thus tiding over the period of acute parathyroid insufficiency until remnants of parathyroid tissue can recover their function or new parathyroid tissue can be transplanted. It is in this way an important and convenient ally of the method of injecting parathyroid extract. 13. Studies of the metabolism in parathyroidectomized animals show: 1. A marked reduction in the calcium content of the tissues especially of the blood and brain, during tetany. 2. An increased output of calcium in the urine and faeces on the development of tetany. 3. An increased output of nitrogen in the urine. 4. An increased output of ammonia in the urine with 4a. an increased ammonia ratio in the urine. 5. An increased amount of ammonia in the blood. Much of this affords evidence of the existence of some type of acid intoxication. Its effects are, however, not neutralized by the introduction of alkaline sodium salts and may perhaps be regarded as especially important in producing a drainage of calcium salts from the tissues which can be remedied by the reintroduction of calcium salts. 14. Emphasis must be laid upon the remarkable difference which exists between the alterations inmetabolism following thyroidectomy and those following parathyroidectomy. In myxoedema there is lowered metabolism, decreased respiratory changes and lowered nitrogen output with depression of body temperature. In tetany there is increased metabolism, probably increased respiratory changes, certainly increase in nitrogen output and elevation of the temperature. 15. It is important, therefore, that in any experiments upon metabolism in relation to the thyroid and parathyroid gland, these glands should be clearly distinguished as structures exercising very different and in large part contrary effects upon metabolism. 16. In general the role of the calcium salts in connection with tetany may be conceived of as follows: These salts have a moderating influence upon the nerve cells. The parathyroid secretion in some way controls the calcium exchange in the body. It may possibly be that in the absence of the parathyroid secretion, substances arise which can combine with calcium, abstract it from the tissues and cause its excretion and that the parathyroid secretion prevents the appearance of such bodies. The mechanism of the parathyroid action is not determined, but the result, the impoverishment of the tissues with respect to calcium and the consequent development of hyperexcitability of the nerve cells, and tetany is proven. Only the restoration of calcium to the tissues can prevent this. 17. This explanation is readily applicable to spontaneous forms of tetany in which there is a drain of calcium for physiological purposes, or in which some other condition causes a drain of calcium. In such cases the parathyroid glands may be relatively insufficient.

https://rupress.org/jem/article-pdf/11/1/118/1081552/118.pdf

On the relation of tetany to the parathyroid glands and to calcium metabolism

From a case of acute endocarditis of the aortic and mitral valves with infarctions m the spleen and kidneys a micrococcus was twice isolated in pure culture from the blood during life and was demonstrated after death both microscopically and in pure culture in large numbers in the valvular vegetations, the infarctions and other parts. No other species of microorganism was found. This micrococcus is very small, occurs mainly in pairs, sometimes in short chains, stains by Gram's method, grows in small, pale, grayish-white colonies on gelatine and agar, at first clouds bouillon, which then becomes clear with a whitish sediment, does not produce gas in glucose media, liquefies gelatine slowly and to some extent also blood serum, and is especially characterized by its behavior in milk, which it acidifies, coagulates and subsequently liquefies. It produces a milk-curdling ferment and also a proteolytic ferment, each of which is separable from the bacterial cells. It remains viable for months in old cultures and is tolerably resistant to the action of heat and antiseptics. The micrococcus is pathogenic for mice and rabbits, causing either abscesses or general infections. Typical acute vegetative endocarditis was experimentally produced by intravenous inoculation of the organism in a rabbit and a dog, and the cocci were demonstrated in pure culture in the vegetations and other parts of these animals after death. Although the micrococcus here described has some points of resemblance to the pneumococcus and Streptococcus pyogenes on the one hand and to the pyogenic staphylococci on the other, it is readily distinguished from each of these species by cultural features which have been described and which are so obvious that the differentiation of these species from our micrococcus need not be discussed in detail. We have searched through the records concerning microorganisms described in association with endocarditis and other diseases, as well as those isolated from water, soil and other sources, and have been unable to find a description of a micrococcus identical in all particulars with that here described. Such points as staining by Gram, liquefaction of gelatine, coagulation and peptonization of milk, served singly or in combination to distinguish our micrococcus from other forms which in some respects might resemble it. We feel justified, therefore, in recognizing this organism as a new species and from its fermentative properties propose for it the name "Micrococcus zymogenes." Micrococcus zymogenes must be added to the already considerable list of bacteria which have been found as the specific infective agents in endocarditis. That it was the cause of this affection in our case was conclusively demonstrated by its repeated isolation in pure culture from the blood during life, by its presence in pure culture and large numbers after death in the cardiac vegetations, the infarctions, and other parts of the body, and by the experimental proof of its pathogenic properties, and notably its capacity to produce vegetative endocarditis by intravenous inoculation in animals.

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A case of acute endocarditis caused by micrococcus zymogenes (nov. spec.), with a description of the microorganism

On the flagellated form of the malarial parasite.

Early in February, a commission was sent by Surgeon-General Gorgas to Texas to study the pneumonia existing there. This commission was composed of Rufus Cole, W. G. MacCallum and Oswald T. Avery, Contract Surgeons, U. S. Army, Captains A. R. Dochez and R. A. Kinsella, and Lieutenants F. G. Blake, T. M. Rivers, H. John, F. A. Stevens and Wm. C. Von Glahn, Medical Reserve Corps. This special study was undertaken at the base hospital, Fort Sam Houston, San Antonio, Texas. This hospital was chosen for this work merely because pneumonia was prevailing there to a large extent at the time, and also because of its proximity to the laboratory of the Southern Department, where facilities were available for carrying out the bacteriologic and pathologic examinations. It was thought that any facts disclosed by the study there might be applicable to other camps and base hospitals. Any general application of

Pneumonia at a base hospital

https://rupress.org/jem/article-pdf/3/1/117/1176865/117.pdf

W. G. MacCallum

Papers

On the relation of tetany to the parathyroid glands and to calcium metabolism

A case of acute endocarditis caused by micrococcus zymogenes (nov. spec.), with a description of the microorganism

On the flagellated form of the malarial parasite.

Pneumonia at a base hospital

On the Haematozoan Infections of Birds