Estudio descriptivo de los casos de malaria en la población pediátrica en un hospital de referencia de Valencia, España, entre 1993 y 2015 / Descriptive study of malaria cases in the paediatric population in a reference hospital in Valencia, Spain, between 1993 and 2015

Introducción: La malaria es considerada la cuarta causa de mortalidad infantil después de la neumonía, las complicaciones por parto prematuro y la asfixia perinatal. Material y métodos: Estudio retrospectivo y descriptivo de los casos de paludismo confirmados y tratados en la Unidad de Enfermedades Infecciosas Pediátricas (edad inferior a 15 años) del Hospital La Fe (Valencia) en el período comprendido entre 1993 y 2015. Resultados: Durante el período 1993-2015 se diagnosticaron 54 casos de malaria infantil, el 51,8% en varones. El 46,2% eran menores de 5 años. La mayoría de los niños procedían de Guinea Ecuatorial (68,5%). Solo en el 5,6% de los pacientes se pudo constatar que recibieran profilaxis antimalárica. Se evidenció que Plasmodium falciparum fue la especie causal del 81,4% de los episodios. Siete casos (13%) presentaron malaria complicada. El tratamiento más empleado fue la quinina, sola o en combinación con otros fármacos: atovacuona-proguanil fue empleada a partir del año 2010 y estuvo indicada en el 20,3% de los pacientes. A partir del año 2013 se inició la utilización de: artesunato, piperaquina y dihidroartemisina. No hubo mortalidad ni efectos adversos relevantes, siendo la respuesta clínica favorable en el 100% de los niños. Conclusiones: La malaria sigue siendo una enfermedad vigente en nuestra población, consecuencia de la inmigración y del turismo a países endémicos. Debe ser considerada como diagnóstico probable ante un niño febril que procede o ha viajado a un área endémica en el último año

Introduction: Malaria is considered to be the fourth leading cause of infant mortality after pneumonia, complications related to premature birth, and perinatal asphyxia. Material and methods: A retrospective and descriptive study of cases of malaria confirmed and treated by the Paediatric Infectious Diseases Unit (age lower than 15 years) at the La Fe Hospital, Valencia, over the period 1993 to 2015. Results: A total of 54 cases of paediatric malaria were diagnosed in the period 1993-2015, with 51.8% of these occurring in males, and 46.2% of patients were aged below 5 years. The majority of children came from Equatorial Guinea (68.5%). Only 5.6% had received antimalarial prophylaxis. Plasmodium falciparum was found to be the causal species in 81.4% of cases. Seven patients (13%) presented with complicated malaria. The most widely used treatment was quinine, either alone or in combination with other drugs. Atovaquone/proguanil was used from 2010 onwards and was indicated in 20.3% of the patients. The combination of artesunate/piperaquine/dihydroartemisinin began to be used in 2013. No deaths or relevant side effects were reported, and the clinical response was favourable in all children (100%). Conclusions: Malaria is still a prevalent disease in this population, a consequence of immigration, and tourism to endemic countries. Malaria should be considered as a likely diagnosis in a febrile child who comes from, or has travelled to, an endemic region in the past year

[Descriptive study of malaria cases in the paediatric population in a reference hospital in Valencia, Spain, between 1993 and 2015]. / Estudio descriptivo de los casos de malaria en la población pediátrica en un hospital de referencia de Valencia, España, entre 1993 y 2015.

INTRODUCTION: Malaria is considered to be the fourth leading cause of infant mortality after pneumonia, complications related to premature birth, and perinatal asphyxia. MATERIAL AND METHODS: A retrospective and descriptive study of cases of malaria confirmed and treated by the Paediatric Infectious Diseases Unit (age lower than 15 years) at the La Fe Hospital, Valencia, over the period 1993 to 2015. RESULTS: A total of 54 cases of paediatric malaria were diagnosed in the period 1993-2015, with 51.8% of these occurring in males, and 46.2% of patients were aged below 5 years. The majority of children came from Equatorial Guinea (68.5%). Only 5.6% had received antimalarial prophylaxis. Plasmodium falciparum was found to be the causal species in 81.4% of cases. Seven patients (13%) presented with complicated malaria. The most widely used treatment was quinine, either alone or in combination with other drugs. Atovaquone/proguanil was used from 2010 onwards and was indicated in 20.3% of the patients. The combination of artesunate/piperaquine/dihydroartemisinin began to be used in 2013. No deaths or relevant side effects were reported, and the clinical response was favourable in all children (100%). CONCLUSIONS: Malaria is still a prevalent disease in this population, a consequence of immigration, and tourism to endemic countries. Malaria should be considered as a likely diagnosis in a febrile child who comes from, or has travelled to, an endemic region in the past year.

Immunogenicity and safety of 11- and 12-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccines (11vPHiD-CV, 12vPHiD-CV) in infants: Results from a phase II, randomised, multicentre study.

BACKGROUND: We assessed 2 investigational 11- and 12-valent vaccines, containing capsular polysaccharides of 10 serotypes as in the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and CRM197-conjugated capsular polysaccharides of serotypes 19A (11-valent) or 19A and 6A (12-valent). METHODS: In this phase II, partially-blind, multicentre study (NCT01204658), healthy infants were randomised (1:1:1:1) to receive 11vPHiD-CV, 12vPHiD-CV, PHiD-CV, or 13-valent CRM197-conjugate pneumococcal vaccine (PCV13), at 2, 3, and 4 (primary series), and 12-15 months of age (booster dose), co-administered with DTPa-HBV-IPV/Hib. Confirmatory objectives assessed non-inferiority of investigational vaccines to comparators (PHiD-CV for common serotypes; PCV13 for 19A and 6A), in terms of percentage of infants with pneumococcal antibody concentrations ≥0.2 µg/mL and antibody geometric mean concentrations, post-primary vaccination. Reactogenicity and safety were assessed. RESULTS: 951 children received ≥1 primary dose, 919 a booster dose. Pre-defined immunological non-inferiority criteria were met simultaneously for 9/11 11vPHiD-CV serotypes (all except 23F and 19A) and 10/12 12vPHiD-CV serotypes (all except 19A and 6A); thus, non-inferiority objectives were reached. For each PHiD-CV serotype, percentages of children with antibody concentrations ≥0.2 µg/mL were ≥96.7% post-primary (except 6B [≥75.2%] and 23F [≥81.1%]), and ≥98.1% post-booster vaccination. For each PHiD-CV serotype except serotype 1, ≥81.0% and ≥93.9% of children had opsonophagocytic activity titres ≥8, post-primary and booster vaccination. AEs incidence was similar across all groups. SAEs were reported for 117 children (29 in the 11vPHiD-CV group, 26 in the 12vPHiD-CV group, 38 in the PHiD-CV group and 24 in the PCV13 group); 4 SAEs were considered vaccination-related. No fatal events were recorded. CONCLUSION: Addition of 19A and 6A CRM197-conjugates did not alter immunogenicity of the PHiD-CV conjugates; for both investigational vaccines post-booster immune responses to 10 common serotypes appeared similar to those elicited by PHiD-CV. Safety and reactogenicity profiles of the investigational vaccines were comparable to PHiD-CV. Clinical trial registry: NCT01204658.

Immunogenicity and Reactogenicity of DTPa-HBV-IPV/Hib and PHiD-CV When Coadministered With MenACWY-TT in Infants: Results of an Open, Randomized Trial.

BACKGROUND: This study evaluated the immunogenicity and reactogenicity of a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus virus-Haemophilus influenzae type b vaccine (DTPa-HBV-IPV/Hib) and a 10-valent pneumococcal conjugate vaccine (PHiD-CV) coadministered with a quadrivalent meningococcal conjugate vaccine (MenACWY-TT) in infants/toddlers. METHODS: In this open, controlled, phase III study (NCT01144663), 2095 healthy infants were randomized (1:1:1:1) into 4 groups to receive MenACWY-TT at 2, 3, 4 and 12 months of age or MenACWY-TT, MenC-CRM197, or MenC-TT at 2, 4 and 12 months of age. All participants received PHiD-CV and DTPa-HBV-IPV/Hib at 2, 3, 4 and 12 months of age. Immunogenicity of DTPa-HBV-IPV/Hib was evaluated in exclusive randomized subsets of 25% of participants from each group postprimary, prebooster and postbooster vaccination, whereas immunogenicity of PHiD-CV was evaluated at all time points. Reactogenicity was evaluated on the total vaccinated cohorts during 8 days after each vaccination. RESULTS: For each DTPa-HBV-IPV/Hib antigen, ≥97.2%, ≥76.5% and ≥97.9% of participants had seropositive/seroprotective levels 1 month postprimary vaccination, before the booster dose and 1 month postbooster, respectively. For each vaccine pneumococcal serotype, ≥74.0% of infants had antibody concentrations ≥0.35 µg/mL at 1 month postprimary vaccination, and robust increases in antibody geometric mean concentrations were observed from prebooster to postbooster. Redness was the most frequent solicited local symptom at the DTPa-HBV-IPV/Hib and PHiD-CV injection sites, reported after up to 47.7% and 57.0% of doses postprimary and postbooster vaccination, respectively. CONCLUSIONS: Primary and booster vaccinations of infants/toddlers with DTPa-HBV-IPV/Hib and PHiD-CV coadministered with MenACWY-TT were immunogenic with clinically acceptable reactogenicity profiles. These results support the coadministration of MenACWY-TT with routine childhood vaccines.

Safety and Immunogenicity of the Quadrivalent Meningococcal Serogroups A, C, W and Y Tetanus Toxoid Conjugate Vaccine Coadministered With Routine Childhood Vaccines in European Infants: An Open, Randomized Trial.

BACKGROUND: This was the first study evaluating the immunogenicity and safety of the quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACWY-TT) coadministered with routine childhood vaccines in young infants. METHODS: In this open, randomized, controlled, phase III study (NCT01144663), 2095 infants (ages 6-12 weeks) were randomized (1:1:1:1) into 4 groups to receive MenACWY-TT at 2, 3, 4 and 12 months of age, or MenACWY-TT, MenC-cross-reactive material (CRM197) or MenC-TT at 2, 4 and 12 months of age. All participants received PHiD-CV and DTPa-HBV-IPV/Hib at 2, 3, 4 and 12 months of age. Immune responses were measured by serum bactericidal activity assays using rabbit (rSBA) and human (hSBA) complement. Solicited and unsolicited symptoms were recorded during 8 and 31 days post-vaccination, respectively, and serious adverse events throughout the study. RESULTS: Noninferiority of immune responses to MenC induced by 2 or 3 doses of MenACWY-TT versus 2 doses of MenC-TT or MenC-CRM197 was demonstrated. Predefined criteria for the immunogenicity of MenACWY-TT to MenA, MenW and MenY were met. One month after 2 or 3 primary MenACWY-TT doses, ≥93.1% and ≥88.5% of infants had rSBA and hSBA titers ≥1:8 for all serogroups. The robust increases in rSBA and hSBA titers observed for all vaccine serogroups postbooster vaccination suggested that MenACWY-TT induced immune memory. MenACWY-TT coadministered with childhood vaccines had a clinically acceptable safety profile. CONCLUSIONS: This study supports the coadministration of MenACWY-TT with routine childhood vaccines as 2 or 3 primary doses during infancy followed by a booster dose in the second year of life.

Influenza vaccine effectiveness in preventing influenza A(H3N2)-related hospitalizations in adults targeted for vaccination by type of vaccine: a hospital-based test-negative study, 2011-2012 A(H3N2) predominant influenza season, Valencia, Spain.

BACKGROUND: Most evidence of the effectiveness of influenza vaccines comes from studies conducted in primary care, but less is known about their effectiveness in preventing serious complications. Here, we examined the influenza vaccine effectiveness (IVE) against hospitalization with PCR-confirmed influenza in the predominant A(H3N2) 2011-2012 influenza season. METHODS: A hospital-based, test-negative study was conducted in nine hospitals in Valencia, Spain. All emergency admissions with a predefined subset of symptoms were eligible. We enrolled consenting adults age 18 and over, targeted for influenza vaccination because of comorbidity, with symptoms of influenza-like-illness within seven days of admission. We estimated IVE as (1-adjusted vaccination odds ratio)*100 after accounting for major confounders, calendar time and recruitment hospital. RESULTS: The subjects included 544 positive for influenza A(H3N2) and 1,370 negative for influenza admissions. Age was an IVE modifying factor. Regardless of vaccine administration, IVE was 72% (38 to 88%) in subjects aged under 65 and 21% (-5% to 40%) in subjects aged 65 and over. By type of vaccine, the IVE of classical intramuscular split-influenza vaccine, used in subjects 18 to 64, was 68% (12% to 88%). The IVE for intradermal and virosomal influenza vaccines, used in subjects aged 65 and over, was 39% (11% to 58%) and 16% (-39% to 49%), respectively. CONCLUSIONS: The split-influenza vaccine was effective in preventing influenza-associated hospitalizations in adults aged under 65. The intradermal vaccine was moderately effective in those aged 65 and over.