Safety and Immunogenicity of Cuban Antipneumococcal Conjugate Vaccine PCV7-TT in Healthy Adults
October 2015, Vol 17, No 4

INTRODUCTION Pneumococcal infections are a major cause of mor­bidity and mortality and are associated with considerable economic burden on health systems. To prevent pneumococcal infections, 7-valent conjugate vaccines have been available for over a decade; more recently, 10- and 13-valent conjugate vaccines have been for­mulated, which are more immunogenic than vaccines with capsular polysaccharides only. In Cuba, a new vaccine candidate has been developed, PCV7-TT, a conjugate of tetanus toxoid with antigens of seven of the serotypes of Streptococcus pneumoniae with highest circu­lation in Cuba and in the world: 1, 5, 6B, 14, 18C, 19F and 23F.

OBJECTIVE Assess the safety of the vaccine candidate PCV7-TT in healthy adults and conduct a preliminary assessment of its immuno­genicity.

METHODS A phase I, double-blind clinical trial was performed at the National Toxicology Center in Havana, Cuba. Healthy male volunteers aged 18-35 years were randomly assigned to two groups: 20 received the vaccine candidate PCV7-TT and 20 the polyvalent antipneumo­coccal vaccine PNEUMO-23 used as control, each in a single intra­muscular dose. To assess safety, the occurrence of adverse events was monitored for 30 days following inoculation. To explore immuno­genicity, concentrations of serotype-specific antibodies was quantified before and 30 days after inoculation, as well titers of opsonophago­cytic antibodies. (National Clinical Trial Registry RPCEC00000133)

RESULTS Local adverse events were pain, redness, induration, increased sensitivity to touch, and warmth in the injection area. Pain was registered in 70% of individuals who received PCV7-TT and in 75% of those vaccinated with PNEUMO-23. Reported systemic adverse events were general malaise, headache and drowsiness. All adverse events appeared in the first 72 hours post inoculation and lasted no lon­ger than 3 days. One event was reported that was classified as severe in intensity and serious in consequences, but it was unrelated to vacci­nation appendicitis in one individual inoculated with the control vaccine. Before vaccination, all participants but one had antibody con­centrations ≥0.20 µg/ml against the vaccine strains; after vaccination 100% of individuals were positive and the concentrations of antibodies increased in previously positive volunteers. Some individuals had opso­nophagocytic antibodies against serotypes 1, 14, 19F and 23F before vaccination, with highest concentrations against serotypes 14 and 19F. After vaccination, the percent of individuals with opsonophagocytic titers ≥1:8 for all serotypes in the vaccine was >50% in both groups.

CONCLUSIONS A single dose of candidate vaccine PCV7-TT was safe when used in healthy adults. Preliminary results showed that it was able to activate an immune response against the serotypes of Streptococcus pneumoniae used.

KEYWORDS Invasive pneumococcal diseases, pneumococcal vac­cines, conjugate vaccines, immunization, randomized clinical trial, safety, Cuba

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Role of Herpesvirus as a Cause of Mononucleosis-Like and Febrile Syndromes in Cuba, 2006–2009
October 2011, Vol 13, No 4
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
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Occult Hepatitis B in Cuban HIV Patients
April 2011, Vol 13, No 2

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.”

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