Cytomegalovirus treatment options in immunocompromised patients.

Cytomegalovirus (CMV) infection was recognised in congenitally infected infants in the first half of the 20th century. Following the increased use of immunosuppressive regimens for bone marrow and solid organ transplantation, various manifestations of CMV disease were recognised. Milder symptoms included fever, anorexia and malaise but severe symptoms included pneumonitis, hepatitis, gastrointestinal ulceration, choreoretinitis and encephalopathy, all with a high morbidity or mortality. With the onset of the AIDS epidemic, manifestations of CMV became evident, predominantly retinitis. Ganciclovir used intravenously has been the principal anti-CMV agent investigated. However, ganciclovir has problems with suboptimal efficacy, toxicity, poor oral bioavailability and evolution of resistant strains. Additional studies have been performed on foscarnet and cidofovir, although the use of both have been limited by their nephrotoxicity. Combination therapy with ganciclovir and foscarnet for resistant strains has been used. There are promising newer drugs like the methylenecyclopropane nucleoside analogues and benzimidazole. The most novel compound is the antisense oligonucleotide fomivirsen that has been evaluated principally in CMV retinitis. The role of immunotherapy with either immunoglobulin prophylaxis or the novel adoptive immunotherapy needs further evaluation.

Human herpesvirus 6: its impact and influence on infectious diseases and their management.

Human herpesvirus (HHV)-6 was discovered 15 years ago and was then grouped as a member of the family human herpesviridae. Its first clinical manifestation was identified 2 years later as the agent responsible for exanthem subitum. With the advent of newer molecular techniques, its diagnosis is easier and prospective studies have shown that it is the most common pathogen responsible for febrile illness in infants. In some infants, it is associated with febrile convulsions. Two subtypes, A and B, have been identified, B subtype commonly being responsible for primary infection in infants. Primary infection in healthy adults is rare. Most of the clinical manifestations are mild, self-limiting and rarely fatal. Reactivation of HHV-6 is frequently found in bone marrow as well as solid organ transplant recipients. HHV-6 has been shown to be an independent risk factor responsible for recurrence of cytomegalovirus infection, especially in solid organ transplants. In bone marrow transplant recipients, HHV-6 has been associated with various manifestations like marrow suppression and graft versus host disease, although most infections present as usually mild febrile illness with or without rash. It has been reported to cause encephalitis in transplant recipients. Although HHV-6 has been shown to be responsible for upregulation of HIV in vitro studies, its exact role in AIDS is yet to be defined. In addition to its neurotropic manifestation of febrile convulsion in infancy, it has been found in plaques in the brain of multiple sclerosis and progressive multifocal leukoencephalopathy. Further studies are needed before its role in the pathogenesis of these neurological illnesses can be established. Its lymphotropic feature was responsible for its discovery and now it has only been detected in some lesions of primary ocular mucosa associated lymphoid tissue lymphoma. As HHV-6 is found to be responsible for more and more illnesses, especially causing serious illnesses in the immunocompromised, it is becoming necessary to find effective treatment. Some agents, like cidofovir and phosphonoformic acid, are effective in in vitro studies and some have shown effectiveness in a clinical setting. Further studies are needed to identify its role in the pathogenesis of various neurological and malignant lesions and AIDS. Various treatment regimens should be tested in clinical scenario and especially in immunocompromised transplant recipients.

Influenza.

The currently available antiviral drugs rimantadine and amantadine are effective only for influenza A viruses. Another class of influenza antiviral drugs is the neuraminidase inhibitors, which selectively inhibit both influenza A and B viruses. Recent studies have found the neuraminidase inhibitors zanamivir and oseltamivir to be 67-82% effective in preventing laboratory-confirmed infection when administered as prophylaxis during the influenza season. As treatment, they reduce the duration of illness by 1-1.5 days when started within 36-48 h of illness onset. The reported adverse effects of these drugs are minimal, and unlike amantadine and rimantadine, the drugs do not appear to affect the central nervous system. Poor oral bioavailability and rapid renal clearance limit the use of zanamivir to inhalation and concern has been raised about its use in asthmatics. The sialic acid analogue, GS4071, has been shown to be a potent inhibitor of neuraminidase activity and is shown to be effective in controlling influenza, and its prodrug form--GS4104 (oseltamivir) can be given orally. Direct comparison of zanamivir and oseltamivir, their use for prophylaxis and treatment in high-risk groups, and evaluation of their cost effectiveness are all required before they enter routine clinical practice.

Pulmonary manifestations of pediatric HIV infection.

Vertically acquired HIV infection is becoming increasingly common in India. The main clinical manifestations of HIV in childhood are growth failure, lymphadenopathy, chronic cough and fever, recurrent pulmonary infections, and persistent diarrhoea. Pulmonary disease is the major cause of morbidity and mortality in pediatric AIDS, manifesting itself in more than 80% of cases. The most common causes are Pneumocystis carinii pneumonia (PCP), lymphocytic interstitial pneumonitis (LIP), recurrent bacterial infections which include bacterial pneumonia and tuberculosis. The commonest AIDS diagnosis in infancy is PCP, presenting in infancy with tachypnea, hypoxia, and bilateral opacification on chest-X-ray (CXR). Treatment is with cotrimoxazole. LIP presents with bilateral reticulonodular shadows on CXR. It may be asymptomatic in the earlier stages, but children develop recurrent bacterial super infections, and can progress to bronchiectasis. LIP is a good prognostic sign in children with HIV infection in comparison to PCP. HIV should be considered in children with recurrent bacterial pneumonia, particularly with a prolonged or atypical course, or a recurrence after standard treatment. Pulmonary TB is common in children with HIV, but little data is available to guide treatment decisions. Much can be done to prevent PCP and bacterial infections with cotrimoxazole prophylaxis and appropriate immunisations, which may reduce hospital admissions and health care costs.

Diagnostic and prognostic value of CT brain scan in term neonates with moderate and severe birth asphyxia.

Twenty term neonates with moderate (stage II) and 5 with severe (stage III) hypoxic ischemic encephalopathy (HIE) were prospectively studied to determine diagnostic and prognostic value of CT brain scan. Three neonates expired, 4 were lost to follow up while 18 were followed up to 18 months of age. Cerebral hypodensities were noted in 20 and intracranial hemorrhage (ICH) in 8, of which 6 had both ICH and hypodensity. Twelve of 14 infants with hypodensities and 5 of 6 with ICH who were followed up were handicapped at 18 months. Thirteen of 18 babies followed up were subjected to repeat CT scans between 9 and 18 months of age for assessing extent and severity of brain damage. Major abnormality noted on repeat CT scans was cerebral atrophy. All 6 infants whose follow-up scans were abnormal had neurological sequelae, while of 7 infants who had normal repeat CT scans, 5 had neurological sequelae. We do not recommend repeat CT scans in patients with HIE as a parameter to predict neurologic outcome.