Virology

Here are two useful resources:

1. http://www-micro.msb.le.ac.uk
2. http://www.virology.net/Video.html

AMH.

Maraviroc a new class of antiretroviral which targets chemokine receptor CCR5, a host protein, is claimed to be the 'promising new antiretroviral'.

The following are reasons to believe:

-Inhibits viral entry, the most vital mechanism of viral inhibition, unlike any of its predecessors

-It was found to have antiviral activity in vitro against various clades of different origins of HIV-1

The boosting of PIs is a therapeutic strategy wherein a small dose of ritonavir is given concurrently with another PI to pharmacologically enhance exposure to the latter PI through the inhibition of the enzyme cytochrome p450. For many of the PIs, ritonavir boosting results in improved drug levels that can increase efficacy, decrease pill burden, add flexibility to the dosing schedule, and remove fasting restrictions. However, with increased drug exposure, there is the potential for increased toxicity, which has manifested in greater gastrointestinal intolerance (lopinavir/ritonavir), nephrolithiasis (indinavir), hyperbilirubinemia (indinavir, atazanavir), and hyperlipidemia (many PIs). Boosting can also result in significant drug interactions with other compounds metabolized by the cytochrome p450 pathway. Whether boosting increases lipodystrophy remains unclear.

At this point in time, most PIs -- including lopinavir, saquinavir, indinavir, and amprenavir -- are given in the boosted form. Whether atazanavir should be administered without boosting to antiretroviral-naive patients remains an issue of debate, but it is generally boosted when prescribed for treatment-experienced patients and must be boosted when used in tandem with an NNRTI or tenofovir. Nelfinavir, which is naturally boosted by food, remains the only PI for which boosting with ritonavir is not recommended.

AMH.

Chronic Immune Active HBV (Precore and Core Promoter Mutants)

Some individuals with chronic hepatitis B are infected with a mutant HBV variant that results in HBeAg negative chronic hepatitis. In such patients, viral mutations in the precore or core promoter regions prevent HBeAg production in an otherwise normally replicating HBV. Thus, these patients typically have high serum HBV DNA levels, but negative HBeAg titers. The prevalence of precore or core promoter mutations is highest among persons from Southern Europe and Asia, with prevalence estimates of 60-70%. Chronic HBeAg-negative hepatitis B is diagnosed in a patient with the following laboratory profile:

• HBsAg positive longer than 6 months
• HBeAg negative, anti-HBe positive
• Serum HBV DNA greater than 10⁴ copies/ml
• Persistently elevated or intermittently normal hepatic aminotransferase levels

You might find this useful.

AMH

Bacterial vaccines

Human Immunoglobulin

Some things require further discussion:

1) Varicella Vaccine:

• This is licenced in the UK, and there are two preparations.
• 10% of the UK population are not immune and also 10% of HCWs.
• The vaccine is for HCWs in GP or hospital who are VZV IgG (-).
• Non-immune HCWs should receive two doses of live attenuated varicella vaccine 4-8 weeks apart. Routine post-vaccination serological testing is not advised.
• HCWs should be told at the time of vaccination that they may experience a local rash around the site of injection or a more generalised rash in the month after vaccination. In either case they should report to their occupational health department for assessment. If the rash is generalised and consistent with a vaccine-associated rash (papular or vesicular) the HCW should avoid patient contact until all the lesions have crusted. HCWs with localised vaccine rashes that can be covered with a bandage and/or clothing should be allowed to continue working unless in contact with high risk patients when an individual risk assessment should be made.
• The vaccine is contraindicated in pregnancy and this should be avoided for at three months after vaccination.

2) Rotavirus Vaccine:

There was a problem with intersucception not mentioned on this list. The withdrawl last year was felt to be premature, as there is a significant mortality.

AMH.

P.S. Which vaccines are live attenuated?

MMR is for Posh Randy Virgins! = Measles, Mumps, Rubella, Polio, Rotavirus & Varicella.

Mollaret’s Meningitis is a rare form of recurrent meningitis originally described by Mollaret in 1944. In 1962, Bryun proposed the clinical diagnostic criteria of:

• Recurrent episodes of severe headache, meningismus, and fever
• Cerebrospinal fluid (CSF) pleocytosis with large "endothelial" cells, neutrophils, and lymphocytes
• Attacks separated by symptom-free periods of weeks to months
• Spontaneous remission of symptoms and signs
• No causative etiologic agent detected.

In 1979, Goldi observed that Mollaret’s meningitis could occur without fever, have symptom-free periods from days to years, have increased CSF gamma globulin, and have transient neurologic signs and symptoms.

Clinical Presentation

Mollaret’s meningitis is characterized by repeated episodes of fever (up to 104oF), meningismus, and severe headache separated by symptom-free intervals. Individual attacks are sudden, with signs and symptoms reaching maximum intensity within a few hours. Headache, neck pain, generalized muscle aches, and neck stiffness usually persist from one to three days, but may be present for up to three weeks. Following a number of recurrences, which can span a period of years, the disease suddenly disappears. The long-term health of the patient seems not to be adversely affected. Transient neurologic abnormalities (seizures, diplopia, pathologic reflexes, cranial nerve paresis, hallucinations, and coma) occur in as many as 50% of cases. However, persistence of neurologic defects should call the diagnosis into question. CSF obtained early in the course of the illness usually demonstrates large, friable "endothelial" cells termed Mollaret’s cells. Mollaret’s cells can be demonstrated by the Papanicolaou stain, and are now considered to be large activated cells of monocyte/macrophage lineage. Mollaret’s cells are considered by many to be the hallmark of Mollaret’s meningitis, and early on may comprise 60% to 70% of the CSF cells. These cells are usually present for only the first 24 hours and can be missed easily. Furthermore, "Mollaret’s cells" are not pathognomonic for Mollaret’s meningitis. After the first 24 hours, the CSF shows a lymphocytic predominance with cell counts usually less than 3,000/mm3 [one case had 9,300 cells/mm3]. Hypoglycorrhachia, low CSF glucose concentration, is reported in one-third of patients. CSF protein, especially the gamma globulin fraction, is usually mildly elevated.

Etiology

Recent data suggest that Herpes simplex Type II and, less frequently, Herpes simplex Type I may be etiologic in some if not most cases of Mollaret’s meningitis. Picard et al. have reported three well documented patients with Mollaret’s meningitis, each of whom had Herpes simplex Type II DNA demonstrated in their CSF by the polymerase chain reaction (PCR)*. In a more recent study, Tedder et al. (Ann Int Med. 212:334-338, 1994) reported on thirteen patients with benign recurrent lymphocytic meningitis. Eleven of the thirteen patients had H. simplex Type II DNA demonstrated in their CSF by PCR. The remaining two patients had anti-H. simplex antibody demonstrated in their CSF. Although all thirteen of these patients fit most of the clinical diagnostic criteria for Mollaret’s meningitis, none had Mollaret’s cells demonstrated in their CSF. Furthermore, none of these thirteen patients showed the expected transition from a mainly neutrophilic pleocytosis early in the course to a mainly lymphocytic pleocytosis as the disease progressed. Thus, these patients may have presented with Mollaret’s meningitis without Mollaret’s cells being demonstrated, or they may represent a Mollaret’s-like syndrome caused by H. simplex Type II. Other etiologic agents that have been considered over the years include trauma and viral infections other than H. simplex. The differential diagnosis includes several diseases of unknown etiology (Behcet’s syndrome, sarcoidosis, and uveoencephalitis [Vogt-Koyanagi and Harada syndromes]) as well as neurenteric cyst of the foramen magnum and ruptured pineal cyst.

Therapy

Mollaret’s meningitis is a syndrome rather than a disease. As such, the syndrome of Mollaret’s meningitis appears to have multiple etiologies. Presently, H. simplex Type II, and to a lesser extent Type I, appear to be etiologic in most cases. Because of the rarity of this syndrome, there are no large clinical trials comparing one therapy against another. However, acyclovir (intravenous or oral) or valacyclovir (oral only) are worthy of consideration for both therapy and prophylaxis. Other therapies tried include steroids (no benefit) and colchicine 0.5 mg BID (apparent prophylactic benefit in some cases).

Points to Remember

Suggested Reading

*Picard FJ, Dekaban, GA, Silva J, and Rice GPA: Mollaret’s meningitis associated with Herpes Simplex type 2 Infection. Neurology 43:1722-1727. 1993.