Microbiology
Pathogens
A 25 year old patient presents to ED complaining of painful ulcerations on her vulva. She has felt a little flu-like over the past few days and felt some tingling in the the same area before blisters erupted. On examination you see the rash below, and note tender inguinal lymphadenopathy. Which of the following pathogens is the most likely cause:
(Image by SOA-AIDS Amsterdam, via Wikimedia Commons)
Answer:
The patient most likely has genital herpes, most commonly caused by herpes simplex type 2 infection.Herpes Simplex
Microbiology / Pathogens / Herpes Viruses
Last Updated: 21st April 2019
Herpes simplex virus may be subtype 1 or type 2; HSV-1 is generally associated predominantly with the mouth, eye, and central nervous system and HSV-2 is found most often in the anogenital tract, although this is not mutually exclusive.
Pathogenesis
Herpes simplex is transmitted through direct contact. It invades skin locally producing skin vesicles by its cytolytic activity. Local multiplication is followed by viraemia and systemic infection (although this may go unnoticed) and subsequent lifelong latent infection.
The virus enters peripheral sensory nerves in primary infection and migrates along axons to sensory ganglia in the CNS where it remains latent. Reactivation may be triggered by physical factors e.g. injury, hormones, UV light, or psychological stress.
Cell-mediated immunity, especially the action of cytotoxic T-cells, is essential in the control of herpesvirus infections and patients with T-cell deficiency are at particular risk of reactivation and severe infection.
Clinical Disease
Clinical manifestations include:
- HSV-1
- acute febrile vesicular gingivostomatitis (more common in younger children)
- herpes labialis (cold sores)
- genital herpes (although usually HSV-2)
- HSV keratoconjunctivitis (corneal dendritic ulcers may lead to scarring and blindness)
- HSV-2
- genital herpes (painful shallow ulcers affecting the genitals, rectum, mouth and oropharynx associated with lymphadenopathy, dysuria, fever, myalgia and headache)
- herpes labialis (although usually HSV-1)
- neonatal herpes (vertical perinatal transmission leads to skin, eye and mucous membrane disease, disseminated disease or neonatal encephalitis)
- HSV-1 and HSV-2
- systemic infection (common among immunocompromised)
- herpetic whitlow (primary skin infection typically occurring on the hands and fingers following direct contact with the virus)
- eczema herpeticium (infection of eczema lesions)
- herpes simplex meningitis (uncommon, usually self-limiting)
- herpes simplex encephalitis (most frequent cause of infectious encephalitis, may be severe, predilection for temporal lobe, treated with intravenous aciclovir)
Diagnosis
Diagnosis of herpes simplex by nucleic acid amplification testing (NAAT) of vesicle fluid, genital or mouth swabs is the most sensitive and specific method of diagnosis, although the virus grows readily and can be visualised by electron microscopy (EM).
The ratio between serum and CSF antibody may indicate local production and can help in the diagnosis of HSV encephalitis. CT/MRI of the brain may detect temporal lobe lesions that are typical of herpes encephalitis.
Treatment
Treatment of herpes simplex infection should start as early as possible and usually within 5 days of the appearance of the infection.
In individuals with good immune function, mild infection of the eye (ocular herpes) and of the lips (herpes labialis or cold sores) is treated with a topical antiviral drug. Primary herpetic gingivostomatitis is managed by changes to diet and with analgesics. Severe infection, neonatal herpes infection or infection in immunocompromised individuals requires treatment with a systemic antiviral drug. Primary or recurrent genital herpes simplex infection is treated with an antiviral drug given by mouth. Persistence of a lesion or recurrence in an immunocompromised patient may signal the development of resistance.
Specialist advice should be sought for systemic treatment of herpes simplex infection in pregnancy.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
