Cases in Medical Microbiology and Infectious Diseases. Melissa B. Miller
It is hoped that these new vaccination strategies will break the chain of transmission of a pathogen that only infects humans.
6. Hospitalized patients with pertussis should be on droplet precautions as pertussis is transmitted by large respiratory droplets produced when coughing, sneezing, or talking. Pertussis is highly communicable, with household attack rates of 80 to 100%. Droplet precautions should be maintained until the patient has received 5 days of appropriate antimicrobial therapy. There is no evidence of fomite transmission, which would require contact precautions as well. Close contacts of a person diagnosed with pertussis should be assessed for the infectiousness of the patient (e.g., which stage of disease), the intensity of the exposure, and the risks to the contact of getting pertussis or transmitting it to vulnerable populations (e.g., infants, pregnant women, and health care personnel). If warranted, postexposure prophylaxis with a macrolide should be administered to contacts within 21 days of onset of cough in the index patient. Alternatively, low-risk contacts can be monitored for pertussis symptoms for 21 days.
REFERENCES
1. Guiso N. 2009. Bordetella pertussis and pertussis vaccines. Clin Infect Dis 49:1565–1569.
2. Klein NP, Bartlett J, Rowhani-Rahbar A, Fireman B, Baxter R. 2012. Waning protection after fifth dose of acellular pertussis vaccine in children. N Engl J Med 367:1012–1019.
3. Loeffelholz M. 2012. Towards improved accuracy of Bordetella pertussis nucleic acid amplification tests. J Clin Microbiol 50:2186–2190.
4. Mandal S, Tatti KM, Woods-Stout D, Cassiday PK, Faulkner AE, Griffith MM, Jackson ML, Pawloski LC, Wagner B, Barnes M, Cohn AC, Gershman KA, Messonnier NE, Clark TA, Tondella ML, Martin SW. 2012. Pertussis pseudo-outbreak linked to specimens contaminated by Bordetella pertussis DNA from clinic surfaces. Pediatrics 129:e424–e430.
5. Murphy TV, Slade BA, Broder KR, Kretsinger K, Tiwari T, Joyce PM, Iskander JK, Brown K, Moran JS; Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). 2008. Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants; recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 57:1–51.
6. Wood N, McIntyre P. 2008. Pertussis: review of epidemiology, diagnosis, management and prevention. Paediatr Respir Rev 9:201–212.
CASE 10
In December 2009, a 45-year-old female presented to the emergency department (ED) 2 days following abrupt onset of sore throat, nonproductive cough, chills, and mild fever. A chest radiograph was performed, which was normal. She was diagnosed with bronchitis and asked to follow up with her primary care physician, who subsequently started her on levofloxacin and albuterol. Four days later she presented again to the ED with worsening cough, dyspnea, fever (38.3°C; 101°F), and generalized lethargy. Additionally, she reported new symptoms including a global headache, dizziness, myalgias, and arthralgias. She had no abdominal pain, but reported nausea and anorexia. Her chest radiograph showed diffuse reticulonodular opacities throughout the left lung, which were not present on her visit 4 days previously. The patient was admitted for further evaluation. Questioning revealed the following: she had a history of diabetes and hypertension, she smoked an average of a pack of cigarettes daily, and she had received the seasonal influenza vaccine. Her husband was recently ill with cough, but no other symptoms.
On day 2 of hospitalization the patient’s respiratory rate increased from 22 to 46 and her oxygen saturation dropped while on oxygen administered by nasal cannula. She was transferred to an intensive care unit, where her respiratory status quickly deteriorated, necessitating emergency intubation. A new chest radiograph showed bilateral involvement, and she was begun on vancomycin, aztreonam, and azithromycin. Blood cultures drawn on her admission were negative, and an expectorated sputum sample taken at the same time was not processed due to poor specimen quality. A PCR test performed on a nasopharyngeal swab was positive for a viral agent, revealing the etiology of her infection (Fig. 10.1).
1 1. What is the agent causing her infection? What are the key virulence factors of this agent?
2 2. How does this virus change over time? What made this virus unique in 2009?
3 3. Why was PCR used to diagnose this infection? What do the curves in Fig. 10.1 represent?
4 4. What is the usual outcome of this infection in this patient population? What groups of people are at greater risk of a poor outcome when they are infected with this virus? How did these groups differ in 2009?
5 5. What are the common complications associated with this infection that lead to increased morbidity and mortality? How are these complications diagnosed?
6 6. What antiviral drugs are available to treat this infection, and how do they work? Is there any concern for antiviral resistance?
7 7. Two types of licensed vaccines are available that can prevent this disease. Describe the nature of both of these vaccines and how they are used.
Figure 10.1 Amplification curves of a real-time PCR test.
CASE 10 CASE DISCUSSION
1. Although a number of respiratory viruses could explain this patient’s symptoms, influenza is the most common febrile respiratory illness in adults, particularly during the winter months, when influenza activity normally peaks. In pediatric patients (particularly <1 year old), respiratory syncytial virus should also be considered. The clinical clues of her influenza infection are the abrupt onset of fever and sore throat with nonproductive cough seen at her initial presentation to the ED. Clinically it is difficult to distinguish infections due to influenza A and influenza B, though influenza A tends to be associated with more severe disease, is generally the cause of annual epidemics, and has been responsible for all described pandemics.
Influenza virus has two major envelope proteins that contribute to its pathogenesis: neuraminidase and hemagglutinin. Neuraminidase likely has at least two functions. Its major function seems to be the cleavage of sialic acid from the cell surface and progeny virions, which facilitates the spread of new virions from infected respiratory cells. There is also evidence supporting the role of neuraminidase in viral entry to the cell. One mechanism that has been proposed is that neuraminidase cleaves decoy receptors on mucins, cilia, and cellular glycocalix so that the virus can have greater access to the functional receptors on the cell membrane. Once the virus penetrates to the cell surface, binding to specific sialic acid-rich receptors is mediated by hemagglutinin. Proteolytic cleavage of hemagglutinin by lung serine proteases is required for hemagglutinin activity. After the virus is endocytosed into the cell, hemagglutinin plays a role in the formation of channels through which viral RNA can enter the cytoplasm and initiate the viral replicative cycle.
2. In recent years only two hemagglutinin types (H1 and H3) and two neuraminidase types (N1 and N2) of influenza A virus have been circulating in humans (H1N1 and H3N2). However, due to antigenic variation, there are annual influenza epidemics and, in 2009, a pandemic. Why does this happen? There are two major evolutionary concepts related to influenza virus—antigenic drift and antigenic shift.
A unique property of influenza viruses is that they have single-stranded RNA genomes made of eight segments. Each influenza gene is found on a separate viral RNA segment. Since the mutation