STUDIES ON TYPHUS FEVER : VII. ACTIVE IMMUNIZATION AGAINST MEXICAN TYPHUS FEVER WITH DEAD VIRUS

Guinea pigs can be immunized against Mexican typhus virus by peritoneal injections of formalinized Rickettsia material, provided sufficient amounts of the organisms are used. Our results in this respect are analogous to those of Spencer and Parker with carbolized virus of Rocky Mountain spotted fever. The Rickettsia suspensions appear to possess considerable toxicity. We do not wish to be misunderstood as implying that the results in guinea pigs offer anything more than a demonstration of the principle of active immunization with killed Rickettsiae. Application to man will have to be worked out, and preliminary to this, we are now attempting to apply the methods to a limited number of monkeys.     

STUDIES ON TYPHUS FEVER : III. STUDIES OF LICE AND BEDBUGS (CIMEX LECTULARIUS) WITH MEXICAN TYPHUS FEVER VIRUS

Our experiments have shown that the Mooser bodies or Rickettsiae derived from guinea pigs with Mexican typhus fever can survive in bedbugs after intra-coelomic injection for 10 days, remaining capable of infection. We have also succeeded in similarly infecting bedbugs by allowing them to feed on benzolized rats in whose blood Rickettsiae had been shown to be present. Injection of the organs of such bedbugs 5 days after the last, 9 days after the first infectious feeding into guinea pigs produced typical Mexican typhus fever. Some of the guinea pigs infected with such bedbug organs and passing through a typical typhus proved to be immune to subsequent inoculation with the European disease. Attempts to infect normal guinea pigs by allowing infected bedbugs to feed on them or by rubbing the feces into the uninjured skin have, so far, been unsuccessful. We have not, therefore, completed the cycle proving that bedbugs can transmit the disease, but we have shown that this is a possibility when dealing with man, obviously more susceptible to the disease than any of our experimental animals. The ease with which the Rickettsiae seem to survive in the bedbugs suggests the desirability of investigating other common insects for a similar capacity of harboring the typhus Rickettsiae-experiments which we have not yet had the time to carry out.     

THE ANTIGENIC RELATIONSHIP BETWEEN PROTEUS X-19 AND TYPHUS RICKETTSIAE : A STUDY OF THE WEIL-FELIX REACTION

1. The absorption of typhus sera (human or antityphus horse serum) with Proteus X-19 removes only the Proteus agglutinins, leaving the Rickettsia agglutinins intact. 2. The absorption of typhus sera with Mexican Rickettsiae removes the agglutinins for both the Rickettsia and Proteus X-19. 3. While normal or formalinized Rickettsiae are not agglutinated by anti-Proteus serum, these organisms—when formalinized and heated at 75°C.—become agglutinable by such serum. 4. The absorption of anti-Proteus serum with Mexican Rickettsiae removes agglutinins for formalinized and heated Rickettsiae but does not affect those for Proteus X-19.     

THE MULTIPLICATION OF THE VIRUS OF MEXICAN TYPHUS FEVER IN FLEAS

The virus of Mexican typhus has been shown to multiply abundantly in the following species of fleas: Xenopsylla cheopis, Ceratophyllus fasciatus, Leptopsylla musculi, Ctenocephalus canis, Ctenocephalus felis. In all fleas, Rickettsia prowazeki was demonstrated within the epithelial cells of the stomach and within the cells of the Malpighian tubules. Whereas in infected lice enormous numbers of these organisms are discharged from the disintegrating cells into the intestinal content, only few Rickettsiae are found in the lumen of the fleas'' intestines. They are held back by the peritrophic membrane, which covers the mucosa of the entire stomach. Rickettsiae seem to enter the lumen of the gut almost exclusively by the route of the Malpighian tubules. Observations were made which seem to indicate that the fleas recover from the infection and that they are able to regenerate the partly destroyed intestinal mucosa. An explanation is given for the relative harmlessness of fleas as vectors of typhus.     

Evaluation of the multimorbidity network and its relationship with clinical phenotypes in chronic obstructive pulmonary disease: The GALAXIA study

BackgroundChronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition, in which taking into consideration clinical phenotypes and multimorbidity is relevant to disease management. Network analysis, a procedure designed to study complex systems, allows to represent connections between the distinct features found in COPD.MethodsNetwork analysis was applied to a cohort of patients with COPD in order to explore the degree of connectivity between different diseases, taking into account the presence of two phenotypic traits commonly used to categorize patients in clinical practice: chronic bronchitis (CB⁺/CB⁻) and the history of previous severe exacerbations (Ex⁺/Ex⁻). The strength of association between diseases was quantified using the correlation coefficient Phi (ɸ).ResultsA total of 1726 patients were included, and 91 possible links between 14 diseases were established. Although the four phenotypically defined groups presented a similar underlying comorbidity pattern, with special relevance for cardiovascular diseases and/or risk factors, classifying patients according to the presence or absence of CB implied differences between groups in network density (mean ɸ: 0.098 in the CB⁻ group and 0.050 in the CB⁺ group). In contrast, between‐group differences in network density were small and of questionable significance when classifying patients according to prior exacerbation history (mean ɸ: 0.082 among Ex⁻ subjects and 0.072 in the Ex⁺ group). The degree of connectivity of any given disease with the rest of the network also varied depending on the selected phenotypic trait. The classification of patients according to the CB⁻/CB⁺ groups revealed significant differences between groups in the degree of conectivity between comorbidities. On the other side, grouping the patients according to the Ex⁻/Ex⁺ trait did not disclose differences in connectivity between network nodes (diseases).ConclusionsThe multimorbidity network of a patient with COPD differs according to the underlying clinical characteristics, suggesting that the connections linking comorbidities between them vary for different phenotypes and that the clinical heterogeneity of COPD could influence the expression of latent multimorbidity. Network analysis has the potential to delve into the interactions between COPD clinical traits and comorbidities and is a promising tool to investigate possible specific biological pathways that modulate multimorbidity patterns.     

Actualización en fascitis necrotizante

Necrotizing fasciitis is defined as a rapidly progressive infection of the skin and soft tissue that usually involves severe systemic toxicity. The incidence of this infection has increased in the last few decades and is estimated to affect one out of every 100,000 inhabitants in western European countries. This disease is the most serious form of skin and soft tissue infection, due to rapid destruction and necrosis of the fascia and subcutaneous fat, and the development of shock and multiorgan failure in about one third of patients.Although there are several predisposing factors for the development of the disease, especially for type I, or polymicrobial, necrotizing fasciitis, many patients are young and have no underlying chronic diseases, as is the case for type II, or streptococcal, necrotizing fasciitis. The diagnosis is mainly clinical, and urgent surgical consultation is required as soon as possible once suspicion is high, as the main determinant of mortality is the delay in surgical treatment. Overall mortality remains high, affecting more than 25% of patients. Surgical debridement is the mainstay of treatment, along with hemodynamic support and broad-spectrum antibiotics.