Infectious Diseases

Question 1

How do vaccines work?

Answer 1

Induction of antibodies - Neutralizing capacity - Promoting opsonophagocytosis - Clearance of extracellular pathogens Induction of T cells - Support antibody induction - Produce cytokine / cytolytic activities - Clearance of intracellular pathogens

Question 2

Location of antigen migration in non live vs live vaccines

Answer 2

Non live vaccines - Ag uptake + transport by APC and/ or free fluid diffusion of soluble Ag - Deltoid –> axillary lymph node - Thigh –> inguinal lymph node *Mostly LOCAL + UNILATERAL lymph node activation* Live vaccines - Minimal local retention / reaction - Replication - dissemination - pathogen specific pattern *MULTIFOCAL lymph node activation - stronger responses*

Question 3

What are the different types of vaccines?

Answer 3

Live attenuated Inactivated - Polysaccaride - Protein - Conjugate - Toxoid

Question 4

Live vaccines

Answer 4

BCG Oral poliovirus MMR Varicella Oral typhoid Rotavirus Smallpox Yellow fever Zoster Japanese encephalitis

Question 5

Advantages + disadvantages of LIVE vaccines

Answer 5

Advantages - Organism multiplies (amplification) - Mimics natural infection - Generally induced T + B lymphocyte response - Provides long-lasting protection Disadvantages - Required a good cold chain - May retain some pathogenicity - May not be safe enough to vaccinate immunocompromised

Question 6

Trajectory + type of Ig transport maternal - fetal unit

Answer 6

Placental transfer is highly selective for monomeric IgG + occurs by receptor mediated active transport NO transfer of IgM, IgA or IgE IgG transfer begins at 17 weeks By 33 weeks maternal = fetal IgG levels 40 weeks fetal > maternal IgG levels

Question 7

What vaccines are contraindicated for a child with an egg allergy?

Answer 7

Yellow fever Rabies Q fever *MMR cultured on chicken cells but contains no egg allergen therefore safe to give*

Question 8

Common adverse effects with vaccination: - MMR - HPV - VZV - Rotavirus - DTPa

Answer 8

MMR: high fever + rash for 5-12 days post vaccination HPV: headache, nausea VZV: maculopapular or papulovesicular rash Rotavirus: diarrhoea DTPa: extensive limb swelling reaction (not a contraindication for further)

Question 9

Vaccine classification

Answer 9

Question 10

What is the MOST important factor for beta lactam effect?

Question 11

What antibiotic has concentration dependent killing

Answer 11

Aminoglycosides - also has signigicant post antibiotic effect

Question 12

What antibiotic do you use for the treatment of Stenotrophomonas maltophilia?

Answer 12

Co-trimoxazole (trimethoprim + sulfamethoxazole)

Question 13

What chemotherapy agent is associated with strep mitis?

Question 14

What CT signs are associated with fungal infections?

Question 15

What is the most appropriate 1st treatment for aspergillus?

Answer 15

Voriconazole

Question 16

What antifungal agent do you avoid when using vincristine?

Answer 16

• Voriconazole due to hepatic toxicity

Question 17

Which of the following is NOT an effect of CMV infection in a stem cell transplant recipient?

Question 18

How do you treat PTLD?

Answer 18

• Monoclonal antibodies
  
  • Rituximab
• Low dose chemotherapy

Question 19

What is the varicella post exposure prophylaxis recommendations?

• Immune compromised
• Immune competent

Answer 19

Question 20

What is the mechanism of action of eculizumab + what is an important consideration if you need to start it immediately?

Answer 20

• Mechanism of action: terminal complement inhibitor. Binds to complement protein C5
• Reduces complement activity
• Increases susceptibility to meningococcal infections therefore should be given a meningococcal vaccine before starting treatment
  
  • Takes 2 weeks for the vaccine to amount a suitable response therefore if therapy can’t be delayed until then need to vaccinate + cover with amoxicillin OR ciprofloxacin

Question 21

• What is the clinical diagnosis?
• What is the treatment?
• You are the registrar who has been looking after this baby for the last 4 days prior to the diagnosis is there anything you need to do?

Answer 21

Congenital syphillis

• Syphilis is caused by the bacterial spirochete Treponema pallidum
• During pregnancy there is a high risk of vertical transmission in early syphilis (~50% of infants are infected) and a lower risk in late syphilis (~40% in early latency and 10% in late latency)

Management of infants with congenital syphilis

• Infants should be treated with Intravenous benzyl penicillin 50mg/kg bd for 10 days.
• Follow up at 1,2,4, 6,12 months and until RPR negative.
• Infants with evidence of neurosyphilis should have repeat CSF at 6-monthly intervals to ensure changes have resolved.
• Infants with persistently reactive RPR should be re-evaluated (including CSF) and treated for 10 days with IV benzyl penicillin

Post exposure prophylaxis

• Asymptomatic persons exposed or possibly exposed should have Benzathine penicillin G x 1 IM dose of doxycycline BD for 2 weeks

Question 22

What are diagnostic modalities for syphilis?

Answer 22

Non-treponemal tests are serological tests that detect lipoidal substances released from cells during syphilis infection.

• Tests include the RPR (Rapid Plasma Reagin) and VDRL (Venereal Diseases Research Laboratory).
• These tests are more sensitive but less specific than treponemal tests.
• False positives are common (EBV,hepatitis, varicella, measles, lymphoma, TB, malaria, pregnancy, cord blood).
• These tests usually correlate with disease activity and become negative after adequate treatment. Successful therapy is generally regarded as a 4-fold fall in RPR titre (e.g. from 1:32 to 1:8).

Treponemal tests are serological tests that detect syphilis antigens.

• These assays include TPPA (Treponema Pallidum Particle Agglutination), TPHA (Treponema Pallidum Haemagglutination), FTA (Fluorescent Treponemal Antibody absorption) and syphilis EIA (enzyme immunoassay).
• These tests are generally more specific and less sensitive than non-treponemal tests.
• These tests do not correlate with disease activity and usually remain positive for life.

Darkfield microscopy can be used to visualise treponemes from a primary chancre or nasal secretions. Failure to identify treponemes does not exclude a syphilis diagnosis. Note – it is not possible to culture T Pallidum using standard media

Syphilis PCR can be performed on swabs from a primary chancre, nasal secretions or CSF. It is not adequately sensitive for screening (e.g. on blood).

CSF should be collected for VDRL, FTA-Abs or PCR testing where neurosyphilis is suspected.

In Australia, pregnant women are screened for syphilis (preferably in the first trimester) using a treponemal test. Women will then be offered treatment with penicillin (usually benzathine penicillin, according to the Australian Therapeutic Guidelines[9]) and their RPR titre will be monitored to ensure that is has fallen 4-fold prior to delivery.

Question 23

A 3 yr old girl has fever. Urine is collected by catheterization for culture. What is the minimum concentration of bacterial growth in the culture that would generally be considered diagnostic of a urinary tract infection in this young girl?

1 bacterium/mL

10 bacteria/mL

10³ bacteria/mL

10⁵ bacteria/mL

Answer 23

10³ bacteria/mL

Urine obtained by suprapubic puncture is normally sterile. Urine collected by catheterization is likely to reflect infection if there are ≥ 10³ organisms/mL. Clean-voided urine is considered abnormal if ≥ 10⁵ organisms/mL are present and possibly abnormal if 10⁴-10⁵ organisms/mL are present.

Question 24

What is MAB used to prevent severe RSV?

Answer 24

Palivizumab – humanized monoclonal antibody (IgG) directed against an epitope in the A antigenic site of the F protein of RSV. It is used in the prevention of Respiratory syncytial virus

Palivizumab Adverse reactions:

Common (>1%)
Fever, rash, rhinitis, wheeze, cough, diarrhoea, injection site reaction

Infrequent (.01-1%)
Anaemia, elevated liver enzymes

Rare (<0.1%)
Hypersensitivity (including anaphylaxis)

Question 25

What is the meaning of antibiotic susceptibility: * Sensitive * Intermediate * Resistant

Answer 25

* **Sensitive (S):** organism is inhibited by the serum concentration of the drug that is achieved using the usual dosage * MIC \< 2 mcg/mL * **Intermediate (I):** organisms are inhibited only by the maximum recommended dosage * MIC 4-8 mcg/mL * **Resistant (R):** organisms are resistant to the usually achievable serum drug levels. * MIC \>8 mcg/mL (\>4 for amoxicillin) \*\*However in serious conditions e.g. meningitis have a WAY lower MIC\*

Question 26

Why is salmonella rarely associated with outbreaks of diarrhoea in child care setting?

Answer 26

Person to person spread with salmonella is uncommon

Question 27

What diseases are causes by; - Night biting mosquitos - Day biting mosquitos

Answer 27

* Night biting mosquitos * Malaria * Yellow fever * Japanese encephalitis * Filariasis * Day biting mosquitos * Dengue

Question 28

Where is body temperature regulated?

Answer 28

Thermosensitive neurons located in the preoptic or anterior hypothalamus

Question 29

What 3 mechanisms can produce fever?

Answer 29

**Endogenous pyrogens** * IL1 + IL6 * TNF * INF beta + gamma * Prostagalndin E **Exogenous pyrogens** * Microbes, toxins etc which stimulate macrophages to produce endogenous pyrogens **Endotoxins** * Drugs: vancomycin, amphotericin B, allopurinol

Question 30

What causes a tertian fever?

Answer 30

Fever on 1st and 3rd days Malaria caused by *Plasmodium vivax*

Question 31

What causes a quartan fever?

Answer 31

Fever on 1st + 4th day Malaria caused by *Plasmodium malariae*

Question 32

What are the periodic fever syndromes?

Answer 32

Familial Mediterranean fever Cyclic neutropenia Periodic fever, aphthous stomatitis, pharyngitis, and adenopathy (PFAPA) Hyper–immunoglobulin D syndrome Hibernian fever (tumor necrosis factor superfamily immunoglobulin A–associated syndrome [TRAPS]) Muckle-Wells syndrome

Question 33

A 4 yr old girl has a temperature of 41.8°C. Which of the following is the most likely cause? Cerebellar disorders Hypothalamic disorders Excessive sweating Ventricular shunt malfunction Most bacterial infections

Answer 33

**Hypothalamic disorders** Similarly, temperatures in excess of 41°C are most often associated with a noninfectious cause. Causes for very high temperatures (\>41°C) include central fever (resulting from central nervous system (CNS) dysfunction involving the hypothalamus), malignant hyperthermia, malignant neuroleptic syndrome, drug fever, or heatstroke.

Question 34

All of the following organisms are recognized as an important cause of occult bacteremia of infants and children EXCEPT: Haemophilus influenzae type b (Hib) Moraxella catarrhalis Neisseria meningitidis Salmonella Streptococcus pneumoniae

Answer 34

**Moraxella catarrhalis** Approximately 30% of febrile children in the 3-36 mo age group have no localizing signs of infection. Viral infections are the cause of the vast majority of fevers in this population, but serious bacterial infections do occur and are caused by the same pathogens listed for patients 1-3 mo of age, except for the perinatally acquired infections. S. pneumoniae, N. meningitidis, and Salmonella account for most cases of occult bacteremia. Hib was an important cause of occult bacteremia in young children before universal immunization with conjugate Hib vaccines and remains common in underdeveloped countries that have not implemented these vaccines.

Question 35

What are the mechanisms of resistance to beta-lactam antibiotics?

Answer 35

* ALTER the target site (PBP) * Destroy the beta-lactam antibiotic * Decrease the concentration of beta-lactam antibiotics inse the cell

Question 36

What are poor prognostic factors for meningococcal disease?

Answer 36

Poor prognostic factors on presentation include * hypothermia or extreme hyperpyrexia * hypotension or shock * purpura fulminans * seizures * leukopenia * thrombocytopenia (including DIC) * acidosis * high circulating levels of endotoxin and TNF-α. The presence of petechiae for \< 12 hr before admission absence of meningitis, low or normal ESR indicate rapid, fulminant progression and poorer prognosis.

Question 37

Which of the following is associated with a poorer prognosis for persons presenting with meningococcal disease? Presence of petechiae for \< 12 hr Meningitis Thrombocytosis Leukocytosis High ESR

Answer 37

**Presence of petechiae for \< 12 hr**

Question 38

Which of the following contacts should receive rifampin chemoprophylaxis after diagnosis of invasive Neisseria meningitidis in a child? All children and adults in the same household if there is an unimmunized or partially immunized child younger than 48 mo All children and adults in the same household or daycare facility regardless of immunization history All healthcare workers involved in care of the child, as well as household and daycare contacts Unimmunized or partially immunized children in the same household and in the same daycare facility All unimmunized or partially immunized healthcare workers involved in care of the child, as well as unimmunized or partially immunized household contacts

Answer 38

**All children and adults in the same household or daycare facility regardless of immunization history** Close contacts of patients with meningococcal disease are at increased risk for infection. Antibiotic prophylaxis is indicated for household, daycare, and nursery school contacts and for anyone who has had contact with the patient’s oral secretions during the 7 days before onset of illness. Prophylaxis of contacts should be offered as soon as possible, ideally within 24 hr of diagnosis of the patient. Because prophylaxis is not 100% effective, close contacts should be carefully monitored and brought to medical attention if they experience fever. Prophylaxis is not routinely recommended for medical personnel except those with intimate exposure, such as through mouth-to-mouth resuscitation, intubation, or suctioning before antibiotic therapy was begun.

Question 39

A 13 yr old boy develops fever with petechiae and a few purpura. Mild hypotension responds to intravenous fluids without the need for pressor support. A blood culture yields Neisseria meningitidis. The patient improves greatly after 7 days of antibiotic therapy and is ready for discharge. Which of the following is most likely to reveal an abnormality that may have predisposed him to develop meningococcal disease? * Quantitative immunoglobulins (IgM, IgG, and IgA) * Serial complete blood counts to assess for cyclic neutropenia * Genotype analysis of the TNF-α promoter region * Screening assay for deficiencies of complement factors (CH50) * Total lymphocyte subsets (B cells, CD4+ T cells, CD8+ T cells)

Answer 39

**Screening assay for deficiencies of complement factors (CH50)** Persons with inherited deficiencies of properdin, factor D, or terminal complement components have up to a 1000-fold higher risk for development of meningococcal disease than complement-sufficient persons. Among persons with complement deficiencies, meningococcal disease is more prevalent during late childhood and adolescence, when carriage rates are higher than in children \< 10 yr; meningococcal infections may be recurrent. Although meningococcal disease can occasionally be overwhelming in patients with late complement component deficiency, cases are more typically described as being less severe than in complement-sufficient persons, perhaps reflecting the fact that these cases are often caused by unusual capsular groups such as W-135 and X. Although protective against early infection, extensive complement activation and bacteriolysis may contribute to the pathogenesis of severe disease once bacterial invasion has occurred.

Question 40

What is the treatment for pertussis?

Answer 40

* Neonate: azithromycin for 5 days * Children: azithromycin or clarithromycin for 5 days * IF macrolide contraindicated: bactrim for 7 days