A 35-year-old Canadian businessman developed watery diarrhea when he visited Mexico a week ago.
Assuming this was caused by the most common infectious agent of traveler’s diarrhea, which of the following statements about vaccination against this disease is correct?
Correct Answer B:
This patient presents with traveler’s diarrhea and the most common cause is Enterotoxigenic Escherichia coli (ETEC). ETEC infection is transmitted by ingestion of contaminated food or water. Disease results from adherence and colonization of the small intestine and the subsequent elaboration of two distinct enterotoxins: heat-labile toxin and heat-stable toxin. Heat-labile toxin leads to secretory diarrhea by activating cAMP while heat-stable toxin activates cGMP.
Although there is no effective ETEC vaccine available yet, there is strong evidence to support that such a vaccine may be developed. It has been observed that in regions of the world where ETEC is highly endemic there is a decline in ETEC diarrheal incidence with increasing age whereas no such age-related association is evident in short time visitors to endemic areas. However, the incidence of ETEC rapidly decreases also in persons from developed countries during prolonged stay in ETEC endemic areas. These observations strongly suggest that effective immunity may develop after repeated infections and, as a consequence protection by way of an effective ETEC vaccine is achievable.
Since the key pathogenic mechanisms that contribute to the pathogenesis of ETEC are the production of colonization factors (CFs) and a heat-labile enterotoxin and/or a heat-stable enterotoxin, an ideal vaccine with broad-spectrum protection should contain colonization factor antigens, coli surface (CS) antigens 1 through 6, which are associated with majority of E. coli-linked diarrhea, and the labile toxin (choice B).
→ ETEC vaccines should contain aroC, ompC, and ompF and delivered orally (choice A) is incorrect. AroC, ompC, and ompF are toxin genes and are generally deleted to attenuate potential vaccines.
→ ETEC vaccines should be live attenuated three-strain recombinant delivered by injection (choice C) is incorrect. While studies involving live attenuated three-strain recombinant bacterial vaccine are on-going and have shown promises, they can be taken orally and do not have to be injected. Potential vaccines given by sublingual routes have been shown to be very efficient in inducing intestinal immune responses.
→ ETEC vaccine should contain heat stable strains expressing CS 13 and CS 23 (choice D) is incorrect. The presence of CS13 is not frequent within ETEC strains causing diarrhea in humans. Moreover, studies have recently shown that CS 23 is similar to CS 13 in this regard. If widely distributed ETEC adhesins are to be considered in a strategy for vaccine development, CS 13 and CS 23 would most likely not be suitable candidates compared with others (such as CS6) that are more commonly identified in clinical isolates.
→ The oral cholera killed whole-cell vaccine is recommended for protection (choice E) is incorrect. The cholera vaccine, dukoral, has shown some minimal benefits in protecting people against Enterotoxigenic E. coli-associated diarrhea, but this is not recommended for vaccination against E. coli infection.
Key point:
A 69-year-old female presents with postmenopausal bleeding. You consider whether to begin your evaluation with vaginal probe ultrasonography to assess the thickness of her endometrium.
In evaluating the usefulness of this test to either support or exclude a diagnosis of endometrial cancer, which one of the following statistics is most useful?
Correct Answer A:
There has been a large increase in the number of diagnostic tests available over the past 20 years. Although tests may aid in supporting or excluding a diagnosis, they are associated with expense and the potential for harm. In addition, the characteristics of a particular test and how the results will affect management and outcomes must be considered. The statistics that are clinically useful for evaluating diagnostic tests include the positive predictive value, negative predictive value, and likelihood ratios.
Likelihood ratios indicate how a positive or negative test correlates with the likelihood of disease. Ratios greater than 5-10 greatly increase the likelihood of disease, and those less than 0.1-0.2 greatly decrease it. In the example given, if the patient’s endometrial stripe is > 25 mm, the likelihood ratio is 15.2 and her post-test probability of endometrial cancer is 63%. However, if it is 4mm, the likelihood ratio is 0.02 and her post-test probability of endometrial cancer is 0.2%.
→ The number needed to treat (choice B) is useful for evaluating data regarding treatments, not diagnosis.
→ Prevalence (choice C) is the existence of a disease in the current population, and incidence (choice D) describes the occurrence of new cases of disease in a population over a defined time period.
→ The relative risk (choice E) is the risk of an event in the experimental group versus the control group in a clinical trial.
A 5-year-old female is brought to the ED by ambulance with her mother. Both patients have been in a motor vehicle accident. The daughter is unresponsive. Upon arrival the mother is agitated and conscious, but is hypotensive. Upon attempting to obtain consent for a blood transfusion, the mother states that they are devout Jehovah's witnesses, and neither she, nor her daughter would want any blood products for any reason, and she understands the risks associated with not receiving a blood transfusion if needed. The father arrives shortly after, and confirms his desire that neither his wife nor daughter be treated with any blood products. Both patients clinically deteriorate, and it is decided that they require immediate blood transfusions.
Which of the following is the best decision with respect to a blood transfusion for these patients?
This situation is difficult, requiring the balance of beneficence, and patient autonomy, and is further complicated by applying those to a minor. However, there are two key principles here:
In this case, it is not only acceptable, but mandatory to withhold the blood transfusion from the mother, since she understands the risks of not receiving the transfusion, and has clearly stated her desire to abstain from it. Transfusing her against her will would be unacceptable.
However, you must transfuse the child. She is a minor in need of emergent lifesaving treatment, and her parents do not have the right to withhold that treatment, and that the obligation to protect the child supersedes religious freedom. As this is an emergency, and the child needs an immediate blood transfusion, obtaining a court order would take too long, and could fatally delay the administration of the transfusion.
→ Adhere to the mother and father's wishes and do not transfuse either patient (choice A) would be an inappropriate action in this case, because parents cannot refuse lifesaving treatment for their children.
→ Contacting child and family services (choice C) does not address the emergent nature of the situation, nor would it be the best way to make the child a ward of the state in order to administer necessary treatment.
→ Obtaining a court order (choice D) would be appropriate if the nature of the intervention was not so time sensitive (the transfusion is required immediately). In this case there is not time to get a court order.
→ Transfusing both the mother and the child (choice E) is incorrect. There is no indication that the mother is incompetent to make medical decisions. She understands the consequences of not receiving the transfusion and should be granted the autonomy to make such a decision. Transfusing the child is the correct option, since competent or not, parents cannot withhold lifesaving treatments from their children.
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