RÉSUMÉ
As individuals age, they become increasingly prone to infectious diseases, many of which are vaccine-preventable diseases (VPDs). Adult immunization has become a public health priority in the modern era, yet VPDs vaccination rates for adults are low worldwide. In Central America and Caribbean, national recommendations and vaccination practices in adults differ across countries, and adult vaccination coverage data are limited. An advisory board comprised infectious disease experts, pulmonologists, geriatricians, occupational health, and public health professionals for Central America and Dominican Republic was convened to: a) describe adult immunization practices in these countries; b) discuss challenges and barriers to adult vaccination; and c) find strategies to increase awareness about VPDs. The advisory board discussions reflect that national immunization guidelines typically do not include routine vaccine recommendations for all adults, but rather focus on those with risk factors. This is the case for influenza, pneumococcal, and hepatitis B immunizations. Overall, knowledge lacks about the VPD burden among health-care professionals and the general public. Even more, there is insufficient information on vaccinology for students in medical schools. Actions from the responsible authorities - medical schools and scientific societies which can advocate for vaccination and a better knowledge in vaccinology - can help address these issues. A preventive medicine culture in the workplace may contribute to the advancement of public opinion on vaccination. Promoting vaccine education and research could be facilitated via working groups formed by disease experts, public and private sectors, and supranational authorities, in an ethical and transparent manner.
Sujet(s)
Vaccins antigrippaux , Maladies évitables par la vaccination , Adulte , Humains , Antillais , Vaccination , Vaccins antipneumococciques , Amérique centrale , ImmunisationRÉSUMÉ
We previously reported 10-valent pneumococcal non-typeable Haemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) efficacy in a double-blind randomized trial (ClinicalTrials.gov: NCT00466947) against various diseases, including acute otitis media (AOM). Here, we provide further analyses. In the Panamanian subset, 7,359 children were randomized (1:1) to receive PHiD-CV or control vaccine at age 2/4/6 and 15-18 months. Of these, 2,000 had nasopharyngeal swabs collected. AOM cases were captured when parents sought medical attention for children with AOM symptoms; surveillance was enhanced approximately 2 y into the study through regular telephone calls or home visits by study personnel, who advised parents to visit the clinic if their child had AOM symptoms. Mean follow-up was 31.4 months. Clinical AOM (C-AOM) cases were assessed by physicians and confirmed by otorhinolaryngologists. Middle ear fluid samples, taken from children with C-AOM after specific informed consent, and nasopharyngeal samples were cultured for pathogen identification. For 7,359 children, 2,574 suspected AOM cases were assessed by a primary healthcare physician; 649 cases were C-AOM cases as per protocol definition. From the 503 MEF samples collected, 158 resulted in a positive culture. In the intent-to-treat cohort (7,214 children), PHiD-CV showed VE against first C-AOM (24.0% [95% CI: 8.7, 36.7]) and bacterial (B-AOM) episodes (48.0% [20.3, 66.1]) in children <24 months, which declined thereafter with age. Pre-booster VE against C-AOM was 30.7% [12.9, 44.9]; post-booster, -6.7% [-36.4, 16.6]. PHiD-CV VE was 17.7% [-6.1, 36.2] against moderate and 32.7% [-20.5, 62.4] against severe C-AOM. VE against vaccine-serotype pneumococcal NPC was 31.2% [5.3, 50.3] 3 months post-booster, and 25.6% [12.7, 36.7] across all visits. NTHi colonization rates were low and no significant reduction was observed. PHiD-CV showed efficacy against C-AOM and B-AOM in children younger than 24 months, and reduced vaccine-serotype NPC.
Sujet(s)
Protéines bactériennes/immunologie , Protéines de transport/immunologie , État de porteur sain/prévention et contrôle , Infections à Haemophilus/prévention et contrôle , Vaccins anti-Haemophilus/immunologie , Immunoglobuline D/immunologie , Lipoprotéines/immunologie , Otite moyenne/prévention et contrôle , Infections à pneumocoques/prévention et contrôle , Vaccins antipneumococciques/immunologie , Méthode en double aveugle , Oreille moyenne/microbiologie , Exsudats et transsudats/microbiologie , Femelle , Études de suivi , Vaccins anti-Haemophilus/administration et posologie , Humains , Nourrisson , Mâle , Partie nasale du pharynx/microbiologie , Panama , Vaccins antipneumococciques/administration et posologie , Résultat thérapeutiqueRÉSUMÉ
PURPOSE: In April 2007, Panama introduced Hepatitis A universal vaccination using a two-dose schedule (Havrix(®)junior; GSK Vaccines, Belgium). We assessed the impact of this hepatitis A vaccine three years after it was recommended for universal mass vaccination in Panama. MATERIALS AND METHODS: Hepatitis A vaccination impact was assessed using two different approaches. The first approach used retrospective data (incidence and number of cases for all age groups), collected from the passive surveillance of the Epidemiologic Surveillance System of the Ministry of Health of hepatitis A and unspecified hepatitis before (2000-2006) and after (2008-2010) introduction of hepatitis A vaccine. The second approach was a prospective hospital-based active surveillance for hepatitis cases conducted in subjects (0-14 years) during 2009-2011 at three sentinel hospitals in Panama. RESULTS: Overall, the annual incidence of hepatitis A and unspecified hepatitis in 2008, 2009 and 2010 were 13.1, 7.9 and 3.7 per 100,000 subjects, lower than the baseline incidence of 51.1 per 100,000 subjects. In comparison to the mean baseline period (2000-2006), there was an 82% mean reduction in the overall hepatitis-related outcomes (hepatitis A and unspecified hepatitis) after vaccine introduction (2008-2010) in all age groups. In the hospital-based surveillance (2009-2011), of the 42 probable viral hepatitis A cases, nine cases were confirmed as acute hepatitis A (8 in 2009, 1 in 2010). Of these confirmed cases, two belonged to the targeted vaccine group (1-4 years) but were not vaccinated. CONCLUSIONS: Our study suggests that the introduction of two-dose hepatitis A vaccines in Panama has contributed to the reduction in the incidence of overall hepatitis-related outcomes for all age groups, suggesting herd protection. Additional monitoring is required to document a sustained long-term effect.
Sujet(s)
Surveillance épidémiologique , Vaccins anti-hépatite A/administration et posologie , Hépatite A/prévention et contrôle , Calendrier vaccinal , Vaccination/statistiques et données numériques , Adolescent , Enfant , Enfant d'âge préscolaire , Femelle , Hépatite A/épidémiologie , Vaccins anti-hépatite A/immunologie , Humains , Immunité de groupe , Incidence , Nourrisson , Nouveau-né , Mâle , Panama/épidémiologie , Études prospectives , Études rétrospectives , Facteurs temps , Transaminases/sang , Vaccination/tendancesRÉSUMÉ
BACKGROUND: The relationship between pneumococcal conjugate vaccine-induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed. METHODS AND FINDINGS: This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15-18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization-defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28-30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n = 10,211; control, n = 10,140) and AOM (n = 3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: -1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9%) against vaccine serotype clinically confirmed AOM, 100% (95% CI: 74.3%, 100%) against vaccine serotype IPD, and 65.0% (95% CI: 11.1%, 86.2%) against any IPD. Results were consistent between intent-to-treat and per-protocol analyses. Serious adverse events were reported for 21.5% (95% CI: 20.7%, 22.2%) and 22.6% (95% CI: 21.9%, 23.4%) of PHiD-CV and control recipients, respectively. There were 19 deaths (n = 11,798; 0.16%) in the PHiD-CV group and 26 deaths (n = 11,799; 0.22%) in the control group. A significant study limitation was the lower than expected number of captured AOM cases. CONCLUSIONS: Efficacy was demonstrated against a broad range of pneumococcal diseases commonly encountered in young children in clinical practice. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00466947.
Sujet(s)
Protéines bactériennes/immunologie , Protéines de transport/immunologie , Haemophilus influenzae/immunologie , Immunoglobuline D/immunologie , Lipoprotéines/immunologie , Infections à pneumocoques/prévention et contrôle , Vaccins antipneumococciques/immunologie , Streptococcus pneumoniae/immunologie , Vaccination , Vaccins conjugués/immunologie , Anticorps antibactériens/sang , Enfant d'âge préscolaire , Méthode en double aveugle , Infections à Haemophilus/microbiologie , Humains , Rappel de vaccin , Nourrisson , Analyse en intention de traitement , Amérique latine , Otite moyenne/immunologie , Otite moyenne/microbiologie , Otite moyenne/prévention et contrôle , Infections à pneumocoques/immunologie , Infections à pneumocoques/microbiologie , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: Non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae are major causes of bacterial acute otitis media (AOM). Data regarding AOM are limited in Latin America. This is the first active surveillance in a private setting in Venezuela to characterize the bacterial etiology of AOM in children < 5 years of age. METHODS: Between December 2008 and December 2009, 91 AOM episodes (including sporadic, recurrent and treatment failures) were studied in 87 children enrolled into a medical center in Caracas, Venezuela. Middle ear fluid samples were collected either by tympanocentesis or spontaneous otorrhea swab sampling method. Standard laboratory and microbiological techniques were used to identify bacteria and test for antimicrobial resistance. The results were interpreted according to Clinical Laboratory Standards Institute (CLSI) 2009 for non-meningitis isolates. All statistical analyses were performed using SAS 9.1 and Microsoft Excel (for graphical purposes). RESULTS: Overall, bacteria were cultured from 69.2% (63 of the 91 episodes); at least one pathogen (S. pneumoniae, H. influenzae, S. pyogenes or M. catarrhalis) was cultured from 65.9% (60/91) of episodes. H. influenzae (55.5%; 35/63 episodes) and S. pneumoniae (34.9%; 22/63 episodes) were the most frequently reported bacteria. Among H. influenzae isolates, 62.9% (22/35 episodes) were non-capsulated (NTHi) and 31.4% (11/35 episodes) were capsulated including types d, a, c and f, across all age groups. Low antibiotic resistance for H. influenzae was observed to amoxicillin/ampicillin (5.7%; 2/35 samples). NTHi was isolated in four of the six H. influenzae positive samples (66.7%) from recurrent episodes. CONCLUSIONS: We found H. influenzae and S. pneumoniae to be the main pathogens causing AOM in Venezuela. Pneumococcal conjugate vaccines with efficacy against these bacterial pathogens may have the potential to maximize protection against AOM.
Sujet(s)
Capsules bactériennes/analyse , Infections à Haemophilus/épidémiologie , Infections à Haemophilus/microbiologie , Haemophilus influenzae/classification , Haemophilus influenzae/pathogénicité , Otite moyenne/épidémiologie , Otite moyenne/microbiologie , Enfant d'âge préscolaire , Exsudats et transsudats/microbiologie , Femelle , Haemophilus influenzae/isolement et purification , Humains , Nourrisson , Mâle , Tests de sensibilité microbienne , Moraxella catarrhalis/isolement et purification , Infections à Moraxellaceae/épidémiologie , Infections à Moraxellaceae/microbiologie , Infections à pneumocoques/épidémiologie , Infections à pneumocoques/microbiologie , Études prospectives , Streptococcus pneumoniae/isolement et purification , Venezuela/épidémiologieRÉSUMÉ
BACKGROUND: Rotavirus vaccination was introduced in Panama in March 2006. This study was carried out in order to describe the trends in gastroenteritis-related (GER) hospitalizations and mortality in children <5 years of age during the pre- and post-vaccination periods. METHODS: Data from the Expanded Program on Immunization (Ministry of Health) were used to calculate vaccine coverage. GER mortality and hospitalizations were obtained through database review of the Contraloría General de la República and hospital discharge databases of five sentinel hospitals, for the period 2000-2008. Mean rates of GER mortality and mean numbers of hospitalizations during the baseline pre-vaccination period (2000-2005) were compared to those of 2007 and 2008. RESULTS: National coverage for the second rotavirus vaccine dose increased from 30% in 2006 to 62% in 2007 and 71% in 2008, varying from 62% in the West region to 77% in the Panama region. Overall, at 2-years post-vaccine introduction, the GER mortality rate in Panama had decreased by 50% (95% confidence interval (CI) 46-54). During 2000-2005, the GER mortality rate in children (<1 year) was 73/100 000, decreasing by 45% (95% CI 40-51) in 2008. In children aged 1-4 years, the GER mortality rate was 20.3/100 000 (2000-2005), decreasing by 54% (95% CI 48-60) in 2008. The Panama region registered the highest mortality rate reduction (69%; 95% CI 58-81) for 2008. During 2008, GER hospitalizations among children <5 years of age decreased by 30% (95% CI 21-37) from the mean number of hospitalizations during 2000-2005. CONCLUSIONS: A substantial reduction in GER mortality and hospitalizations was observed following the introduction of rotavirus vaccine in Panama.
Sujet(s)
Gastroentérite/mortalité , Gastroentérite/prévention et contrôle , Infections à rotavirus/mortalité , Infections à rotavirus/prévention et contrôle , Vaccins anti-rotavirus/administration et posologie , Rotavirus/immunologie , Enfant d'âge préscolaire , Gastroentérite/immunologie , Gastroentérite/virologie , Hospitalisation , Humains , Immunisation/méthodes , Nourrisson , Nouveau-né , Panama/épidémiologie , Infections à rotavirus/immunologie , Infections à rotavirus/virologie , Vaccins anti-rotavirus/immunologieRÉSUMÉ
BACKGROUND: The pathogenesis of HIV encephalopathy is poorly understood especially in children. Studies suggest that HIV replication and the release of proinflammatory mediators in the central nervous system contribute to the pathogenesis of HIV dementia in adults. METHODS: Cerebrospinal fluid (CSF) and plasma samples from 23 HIV-infected children were longitudinally analyzed at Weeks 0, 8, 16 and 48 for HIV RNA and concentrations of the following proinflammatory mediators: monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha, regulated upon activation, normal T cell expressed and secreted (RANTES), macrophage-inflammatory protein (MIP)-1-alpha, MIP-1-beta and matrix metalloproteinase-9 (MMP-9). RESULTS: All 23 children had detectable concentrations of MCP-1 in the CSF at all time points evaluated. However, of the remaining of proinflammatory mediators measured in CSF at baseline, only a few children had detectable concentrations: tumor necrosis factor-alpha, n = 1; RANTES, n = 5; MMP-9, n = 9; MIP-1-alpha and MIP-1-beta, n = 0. A reduction from baseline to Week 48 was observed in CSF concentrations of MCP-1 and, among children with detectable values, MMP-9, which paralleled declines in CSF HIV RNA. CONCLUSION: These results suggest that MCP-1 and MMP-9 may be involved in the pathogenesis of central nervous system disease in HIV-infected children.
Sujet(s)
Démence associée au SIDA/diagnostic , Agents antiVIH/administration et posologie , Médiateurs de l'inflammation/sang , Médiateurs de l'inflammation/liquide cérébrospinal , Charge virale , Démence associée au SIDA/sang , Démence associée au SIDA/liquide cérébrospinal , Démence associée au SIDA/traitement médicamenteux , Chimiokine CCL2/sang , Chimiokine CCL2/liquide cérébrospinal , Chimiokine CCL5/liquide cérébrospinal , Enfant , Enfant d'âge préscolaire , Méthode en double aveugle , Femelle , Humains , Nourrisson , Mâle , Matrix metalloproteinase 9/analyse , Matrix metalloproteinase 9/sang , Matrix metalloproteinase 9/liquide cérébrospinal , Probabilité , Pronostic , ARN viral/analyse , Valeurs de référence , Sensibilité et spécificité , Statistique non paramétrique , Facteur de nécrose tumorale alpha/analyse , Réplication virale/effets des médicaments et des substances chimiquesRÉSUMÉ
BACKGROUND: Lopinavir/ritonavir has demonstrated antiviral activity in the HIV-infected adult. SUBJECTS: The objective of this study was to investigate a liquid coformulation of lopinavir/ritonavir, in combination with reverse transcriptase inhibitors, in HIV-infected children. METHODS: One hundred antiretroviral (ARV)-naive and ARV-experienced, nonnucleoside reverse transcriptase inhibitor-naive children between 6 months and 12 years of age participated in this Phase I/II, open label, multicenter trial. Subjects initially received either 230/57.5 mg/m(2) or 300/75 mg/m(2) lopinavir/ritonavir twice daily; ARV-naive subjects also received stavudine and lamivudine, whereas ARV-experienced subjects also received nevirapine and one or two nucleoside reverse transcriptase inhibitors. Lopinavir/ritonavir pharmacokinetics, safety and efficacy were evaluated. RESULTS: All subjects were escalated to the 300/75 mg/m(2) twice daily dose based on results from an interim pharmacokinetic and safety evaluation. The pharmacokinetics of lopinavir did not appear to be dependent on age when dosing was based on body surface area but were decreased on coadministration with nevirapine. Overall 79% of subjects had HIV RNA levels <400 copies/ml at Week 48 (intent-to-treat: missing = failure). Mean increases in absolute and relative (percent) CD4 counts from baseline to Week 48 were observed in both ARV-naive subjects (404 cells/mm(3); 10.3%) and ARV-experienced subjects (284 cells/mm(3); 5.9%). Only one subject prematurely discontinued the study because of a study drug-related adverse event. CONCLUSIONS: The liquid coformulation of lopinavir/ritonavir demonstrated durable antiviral activity and was safe and well-tolerated after 48 weeks of treatment in HIV-infected children.
Sujet(s)
Infections à VIH/traitement médicamenteux , Dose maximale tolérée , Pyrimidinones/administration et posologie , Inhibiteurs de la transcriptase inverse/administration et posologie , Ritonavir/administration et posologie , Administration par voie orale , Biodisponibilité , Chimie pharmaceutique , Enfant , Enfant d'âge préscolaire , Intervalles de confiance , Relation dose-effet des médicaments , Calendrier d'administration des médicaments , Association de médicaments , Femelle , Études de suivi , Infections à VIH/diagnostic , Humains , Nourrisson , Lopinavir , Mâle , Analyse multifactorielle , Pyrimidinones/pharmacocinétique , ARN viral/effets des médicaments et des substances chimiques , Inhibiteurs de la transcriptase inverse/pharmacocinétique , Ritonavir/pharmacocinétique , Indice de gravité de la maladie , Facteurs temps , Résultat thérapeutique , Charge viraleRÉSUMÉ
OBJECTIVES: This study evaluated the effect of treatment with abacavir/lamivudine/zidovudine versus lamivudine/zidovudine on cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) RNA and clinical manifestations of HIV encephalopathy in children. STUDY DESIGN: HIV-infected children 7 months to 10 years of age (n = 23) were studied. CSF and plasma were obtained at baseline and weeks 8, 16, and 48. Genotype analysis of HIV was attempted at baseline and week 48. Neurologic evaluations were performed at baseline and weeks 16, 32, and 48. RESULTS: At baseline, 83% of children had >2.00 log(10) copies/mL HIV RNA in CSF, but only 10% had HIV RNA measurable at week 48. Among children in whom paired genotyping of HIV was possible, 8 of 11 had identical patterns in both CSF and plasma at baseline, whereas at week 48, only 1 of 9 children had similar patterns. Neurologic abnormalities were observed in 83% of children at baseline but only 35% of children at week 48 (P =.004), suggesting a benefit of treatment. CONCLUSIONS: Antiretroviral therapy was associated with a decline in CSF HIV RNA and an improvement in neurologic status. The development of genotypic mutations was different in CSF and plasma, suggesting discordant viral evolution. These results suggest that antiretroviral treatment in children should include agents with activity in the CNS.