MEDICC Review

Cytomegalovirus and Herpes Simplex Infections in Mothers and Newborns in a Havana Maternity Hospital
January 2015, Vol 17, No 1

INTRODUCTION Cytomegalovirus and herpes simplex virus are associated with congenital or perinatal infection, causing potential damage to the newborn.

OBJECTIVES Determine the prevalence of active or latent infection by cytomegalovirus and herpes simplex virus in a population of mothers, congenital infection by these agents in their infants, and association between prevalence of virus infection in mothers and in their newborns.

METHODS A cross-sectional study was conducted from June to September 2012 in a population of 95 pregnant women admitted to the Dr Ramón González Coro University Maternity Hospital during the third trimester of pregnancy, and their infants (98). Patients were tested for antibodies specific to these viruses; vaginal swabs and urine from the women and serum and urine from the newborns were tested for viral genome. The Fisher exact test with 95% confidence interval was used for comparisons.

RESULTS Of the women studied, 89.5% tested positive for cytomegalovirus and 83.2% for herpes simplex. Active infection from cytomegalovirus was detected in 16.7%, and from herpes simplex in 3.2%. Congenital cytomegalovirus infection was detected in 4.1% of newborns; no herpes simplex virus infection was found in this group. Two newborns of women with active cytomegalovirus infection were congenitally infected.

CONCLUSIONS Serology demonstrated that most of the women were immune to both viruses. Active cytomegalovirus infections are common in this population, and newborns of women with active cytomegalovirus infection during pregnancy are at increased risk of congenital infection.

KEYWORDS Congenital infection, perinatal infection, cytomegalovirus, herpes simplex virus, pregnant women, newborns, Cuba

INTRODUCTION Herpesvirus infections are prevalent worldwide, but most run their course asymptomatically. Clinical presentations in symptomatic cases vary widely and include febrile and mononucleosis-like syndromes. In immunocompromised patients, herpetic infection can be lethal and routine laboratory tests are of little use. Use of novel techniques may provide important improvements in diagnosis and treatment of these patients.

OBJECTIVE Investigate association between different herpesviruses and the etiology of mononucleosis and febrile syndromes in Cuban immunocompetent and immunocompromised patients.

METHODS The study used multiplex nested polymerase chain reaction, enabling simultaneous detection of six herpesviruses—cytomegalovirus, herpes simplex (1 and 2), Epstein–Barr, varicella–zoster and human herpesvirus 6—to study 1157 samples (770 urine and 387 serum samples) from 1140 patients with mononucleosis-like syndrome or febrile syndrome, classified according to history of immunosuppressive disease. Samples were analyzed at the Laboratory for Sexually Transmitted Diseases (Virology) of the Pedro Kourí Tropical Medicine Institute from January 2006 through December 2009. SPSS statistical package was used and incidence rates calculated.

RESULTS Of samples studied, 20.1% were positive for some herpesvirus. Higher risk of developing active herpesvirus infections was detected in samples from immunocompromised patients with febrile syndrome compared to those of immunocompetent ones (OR 2.02, CI 1.20–3.42, p=0.007). Cytomegalovirus was the most frequently found herpesvirus in both mononucleosis-like syndrome (60.4%) and febrile syndrome (63.6%) and in both children (69.2%) and adults (55.2%), followed by Epstein–Barr virus. Cytomegalovirus was detected in 68.9% of positive urine samples and in just 47.2% of serum samples.

CONCLUSIONS This is the first Cuban study demonstrating the pathogenic role of herpesviruses, particularly cytomegalovirus, in patients with febrile or mononucleosis-like syndrome, in both immunocompetent and immunocompromised patients. Results highlight the importance of including molecular diagnosis of the herpesvirus family in investigating mononucleosis and febrile syndromes of unknown etiology and demonstrate that etiologic diagnosis would not have been feasible in many cases without the use of this diagnostic tool.

KEYWORDS Herpesvirus, HHV-1, HHV-2, HHV-6, varicella zoster, CMV, EBV, PCR, mononucleosis, fever, immunosuppression, Cuba

INTRODUCTION The use of highly active antiretroviral therapy has reduced progression to AIDS and increased survival among seropositive persons; yet, appearance of resistant viruses may jeopardize these benefits. In Cuba, HIV mainly affects adults; at the end of 2009 of the 41 children infected, 25 were still alive; of these, 22 were under antiretroviral treatment. Until now, nothing was known about HIV-1 antiviral resistance and viral subtypes in the pediatric population in Cuba.

OBJECTIVE This study aims to identify presence of antiretroviral-resistant HIV-1 strains in Cuban children and their mothers, and to provide a phylogenetic characterization and comparison of pol gene sequences in the same.

METHODS Plasma samples were collected from 22 children and their mothers, all HIV-1–infected, from 2004 through 2009. Reverse transcription polymerase chain reaction was used to amplify the pol gene fragment coding for HIV protease and reverse transcriptase enzymes; this was then sequenced and subjected to phylogenetic analysis of HIV subtypes and recombinant forms to compare sequences between mothers and children. HIV mutations conferring antiretroviral resistance were determined.

RESULTS Viral amplification was achieved in samples from 11 children and 8 mothers. Subtypes detected were: CRF19_cpx in five children, subtype B in three, CRF18_cpx in two, and subtype C in one child. In all mother–child pairs, samples were grouped within the same viral subtype in the phylogenetic tree. One mother was under treatment and five children had been treated before the sample was collected. In viruses amplified from samples of children under treatment, resistance was most frequently found to lamivudine (3 cases) and nevirapine (4 cases). Two untreated children carried resistant viruses possibly acquired from their mothers.

CONCLUSIONS This is the first study to describe HIV-1 antiviral resistance in the pediatric population in Cuba; it also identified viral subtypes infecting the mother−child pairs studied. We recommend antiretroviral resistance assays before initiating treatment in pregnant seropositive women and their newborns.

KEYWORDS HIV, AIDS, antiretroviral therapy, antiviral drug resistance, phylogeny, infectious disease transmission, vertical, Cuba

The following errata have been corrected in all versions of this article

Page 24: Byline, ”Joan Alemán” should read “Yoan Alemán.”

Page 31, The Authors: ”Joan Alemán” should read “Yoan Alemán Campos.”