15-year experience with rotavirus vaccination in Mexico: a systematic literature review.

A systematic review was conducted in Mexico to consolidate and evaluate evidence after 15 years of rotavirus vaccination, according to the National Immunization Program. Five databases were screened to identify published articles (January 2000-February 2020) with evidence on all clinical and epidemiological endpoints (e.g. immunogenicity, safety, efficacy, impact/effectiveness) of rotavirus vaccination in Mexico. Twenty-two articles were identified (observational studies including health-economic models: 17; randomized controlled trials: 5). Fourteen studies evaluated a human attenuated vaccine (HRV), four studies evaluated both vaccines, and only two evaluated a bovine-human reassortant vaccine, with local efficacy data only for HRV. Local evidence shows vaccines are safe, immunogenic, efficacious, and provide an acceptable risk-benefit profile. The benefits of both vaccines in alleviating the burden of all-cause diarrhea mortality and morbidity are documented in several local post-licensure studies. Findings signify overall benefits of rotavirus vaccination and support the continued use of rotavirus vaccine in Mexico.

Can two different pneumococcal conjugate vaccines be used to complete the infant vaccination series? A randomized trial exploring interchangeability of the 13-valent pneumococcal conjugate vaccine and the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine.

Background: We assessed the safety and immunogenicity of 2 + 1 infant regimens initiated with the 13-valent pneumococcal conjugate vaccine (PCV13) and completed with the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV). Methods: This partially blinded study randomized 6-12-week-old infants to receive two-dose priming and a booster (at ages 2, 4, 12-15 months) with: PCV13 at priming and PHiD-CV at boosting (PPS); PCV13 then PHiD-CV at priming and PHiD-CV at boosting (PSS); or PHiD-CV at priming and boosting (SSS control). All analyses were descriptive, i.e., no statistical significance tests were done. Results: The total vaccinated cohort at priming comprised 294 infants. Grade 3 adverse events were reported after 8.7% (PPS), 11.4% (PSS), and 16.9% (SSS) of primary doses (primary objective). No serious adverse events were considered vaccination-related. For most PHiD-CV serotypes, observed percentages of children reaching antibody concentrations ≥0.2 µg/mL and opsonophagocytic activity (OPA) titers above cutoffs were similar across groups 1 month post-priming and post-booster. Observed geometric mean antibody concentrations and OPA titers were lower for some PHiD-CV serotypes with the mixed regimens than with PHiD-CV only, especially for PSS. However, no tests of statistical significance were performed. Conclusions: Immunogenicity of the two mixed PCV13/PHiD-CV regimens seemed mostly similar to that of a PHiD-CV-only series, although observed antibody GMCs and OPA GMTs for some PHiD-CV serotypes were lower. No safety concerns were raised. The clinical relevance of the observed differences is unknown. Clinical trial registration: ClinicalTrials.gov: NCT01641133.

Focus on the patientWhat is the context? Infant immunization programs worldwide include the pneumococcal conjugate vaccines Synflorix and Prevnar 13 to help combat pneumococcal diseases. Countries or regions choose whether to use Synflorix or Prevnar 13 and may decide to switch from one vaccine to the other. This can result in infants receiving a mixed vaccination regimen. Limited information is available about such mixed regimens. What is new? We assessed the immunogenicity of three infant vaccination regimens: 1) priming with two doses of Prevnar 13 and boosting with Synflorix; 2) priming with one dose of Prevnar 13 followed by one dose of Synflorix and boosting with Synflorix; 3) priming and boosting with Synflorix. The study showed that: Switching from Prevnar 13 to Synflorix at any time during the vaccination regimen did not seem to affect safety. When switching from Prevnar 13 to Synflorix at the time of boosting, immunogenicity was mostly similar to that of the Synflorix- only regimen. Switching vaccines during priming resulted in a trend toward lower immune responses for some vaccine components. What is the impact? This piece of evidence can be considered by doctors and health authorities when evaluating the possibility of switching pneumococcal vaccines in an immunization program or individual immunization regimen. Further effectiveness studies from countries or regions switching from Prevnar 13 to Synflorix (or vice versa) may shed more light on the feasibility of switching between these vaccines.

Vaccine coverage and compliance in Mexico with the two-dose and three-dose rotavirus vaccines.

Worldwide, rotavirus infection has been a leading cause of severe diarrhea morbidity and mortality. Two rotavirus vaccines have been used in the National Immunization Program (NIP) in Mexico; two-dose Rotarix from 2006 to 2011 and three-dose RotaTeq since 2011. This study assessed coverage (receiving at least one dose or full dose series) in eligible infants, compliance (% completing dose series and % completing series on schedule) in eligible infants vaccinated with Rotarix (2010) versus RotaTeq (2012), using Mexican Social Security Institute data nationwide and by regions. In 2010, 80.7% received at least one dose of Rotarix, 75.6% received both doses and 57.0% received both doses on schedule. In 2012, 85.7% received at least one dose of RotaTeq, 61.0% received all three doses and 43.2% received all three doses on schedule. More eligible infants received all doses with Rotarix versus RotaTeq (p < 0.001). Among infants vaccinated with Rotarix versus RotaTeq, 93.7% versus 71.1% completed full series (p < 0.001), and 75.5% versus 70.9% completed full series on schedule (p = 0.105), respectively. The full series coverage and compliance decreased in all regions with RotaTeq compared with Rotarix. In conclusion, rotavirus vaccination has successfully reduced morbidity and mortality in children under 5 years in Mexico. This study found significant differences in full series coverage and compliance among infants and a higher proportion of completed scheduled at an earlier age in Mexico when comparing a two-dose vaccine in 2010 with a three-dose vaccine in 2012. Such differences might need to be taken into consideration to maximize NIP benefits, including early protection of the rotavirus vaccination program.

Economic burden of varicella complications in two referral centers in Mexico.

Varicella-zoster virus causes varicella (chicken-pox), mainly in young children. Most cases are mild but serious complications can occur, resulting in significant morbidity and mortality. The objective of this study was to estimate the cost burden of varicella hospitalizations in two pediatric reference hospitals in Mexico. This retrospective observational study collected data on patients aged <18 years admitted to two third-level referral hospitals in Mexico. Cases were identified from hospital records using International Classification of Diseases Ninth Revision (ICD-9) codes 052 Chickenpox, or Tenth Revision (ICD-10) codes B01 Varicella (chickenpox). Data on demographic and clinical characteristics and resource use were collected from hospital records. Costs for hospital stay and interventions were obtained from the Mexican Institute for Social Security for 2015 and updated to 2017 costs. A total of 172 hospitalized varicella clinically-confirmed cases and 121 varicella- contacts (with epidemiological linkage to a clinically-confirmed case) were included. Thirty eight of the 172 cases (22.0%) experienced complications. There were no deaths. The median duration of hospitalization was 12 days for cases and 23 days for contacts. The median hospitalization cost was MXN 82,572 (USD 4,434) per case, and MXN 89,453 (USD 4,804) per contact. Although considered a mild disease, varicella was associated with a substantial cost burden in two Mexican third-level referral hospitals.

Association of PDCD1 polymorphisms with childhood-onset systemic lupus erythematosus.

A regulatory single nucleotide polymorphism (SNP) PD1.3G/A located on programmed cell death 1 (PDCD1) gene, was shown to be involved in susceptibility to systemic lupus erythematosus (SLE) in Swedish, European American, and Mexican cases. However, association to childhood-onset SLE has not been analyzed. The aim of this study was to investigate the association of PDCD1 polymorphisms and haplotypes with susceptibility to childhood-onset SLE in Mexican population. Three PDCD1 SNPs, PD1.3G/A, PD1.5C/T, PD1.6G/A, were analyzed in 250 childhood-onset SLE Mexican patients and 355 healthy controls in a case-control association study. Polymorphisms were genotyped by TaqMan technology. Stratification analysis was performed on the SLE cohort to investigate the SNP association with renal disorder. In addition, haplotypes were constructed with these three SNPs. The PD1.3A allele was significantly associated to childhood-onset SLE (P=0.0019, odds ratio (OR) 2.73, 95% confidence interval (95% CI) 1.35-5.56). The other PDCD1 SNPs did not show association. A total of 155 patients (62%) had nephritis, and no association was observed with PDCD1 SNPs. The ACG haplotype (PD1.3A, PD1.5C, PD1.6G) included almost all PD1.3A alleles, and it was more frequent in SLE patients (5.5%) than in controls (2.1%) (P=0.003; OR 2.73, 95% CI 1.37-5.46). The haplotype structure in Mexican controls was significantly different from those reported in Spanish and Swedish. Our results support association of the PD1.3A SNP to susceptibility of childhood-onset SLE in Mexican population and does not show association to lupus nephritis in this age group.

Púrpura de Henoch-Schönlein: Reporte de 105 pacientes pediátricos / Henoch-Schönlein purpura in children: Report of 105 patients

Introducción. La púrpura de Henoch-Schönlein (PHS) es la vasculitis más frecuente en niños. Objetivo: conocer la presentación clínica y evolución de los pacientes con PHS que se han tratado en el hospital en los últimos 5 años. Material y métodos. Estudio retrospectivo en pacientes que acudieron al Hospital Infantil de México Federico Gómez, del 1 de enero de 2000 al 31 de diciembre de 2005, con diagnóstico de PHS. Resultados. Se encontraron 105 pacientes con una mediana de edad de 6 años. El tiempo promedio de seguimiento fue de 15 meses. Todos presentaron lesiones dérmicas, 49.5% dolor abdominal y 41% artritis; 45 (42.9%) pacientes manifestaron nefropatía, con un promedio de aparición de 4.5 meses después de las lesiones dérmicas. Sólo en 37.7% de los casos con nefropatía desaparecieron las alteraciones urinarias. Se realizó biopsia renal en 14 pacientes. La lesión histopatológica más frecuente fue el grado IIIA. La edad de presentación tuvo relación estadísticamente significativa con la presencia de nefritis, los mayores de 10 años tuvieron mayor incidencia de nefritis y los menores de 5 años menor incidencia (Chi cuadrada, P < 0.05). La incidencia global de insuficiencia renal crónica fue de 0.95%. Conclusión. La edad de presentación es un factor pronóstico para la evolución de la enfermedad. Si bien la púrpura es una vasculitis, la principal complicación a largo plazo es renal, por lo que el seguimiento de los pacientes debe ser supervisado por un nefrólogo pediatra.

Introduction. Henoch-Schönlein purpura (HSP) is the most frequent vasculitis in children. Objective: To describe the clinical presentation and clinical outcome in children with HSP treated in our hospital in the last 5 years. Material and methods. A retrospective study was performed in HSP patients diagnosed between January 1st 2001 and December 31st 2005. Results. HSP was diagnosed in 105 patients, median age 6 years old. All had the skin manifestations, 49.5% abdominal pain and 41% arthritis; 45 patients developed HSP nephritis (42.9%), mean presentation time was 4.5 months after HSP diagnosis. Renal biopsy was performed in 14 patients, and the most common histopathological finding was HSP nephritis grade III A. Age of onset older than 10 years was statistically significant for nephritis development (Chi Square < 0.05). Chronic renal insufficiency incidence was 0.95%. Conclusions. The main complication of HSP is nephritis. Follow-up should include evaluation by a pediatric nephrologist. Age of onset older than 10 years is an important risk factor for HSP nephritis.

Miositis osificante progresiva con buena respuesta a tratamiento con esteroide intravenoso / Progressive myositis ossificans with good response to intravenous steroid treatment

Introducción. La miositis osificante progresiva es una causa rara de miositis en la infancia, se trata de una alteración que se hereda de forma autosómica dominante, caracterizada por inflamación muscular seguida de fibrosis y calcificación. Material y métodos. Dos pacientes con diagnóstico de miositis osificante cuyas manifestaciones fueron: acortamiento de pulgares y primeros ortejos, así como endurecimiento de tejidos blandos y calcificaciones en cuello y tórax. Recibieron tratamiento convencional con difosfonatos e isotretinoína, con pobre respuesta. Se decidió el empleo de metilprednisolona, se aplicaron tres dosis iniciales a 30 mg por kg de peso por dosis por vía intravenosa, y posteriormente cada mes. Resultados. Los pacientes presentaron mejoría clínica tanto en la clase funcional como en la sintomatología, la cual se ha mantenido a largo plazo. Conclusión. Se propone como alternativa de tratamiento la utilización de metilprednisolona por sus efectos inmunosupresores y antiinflamatorios, sobre todo en aquellos pacientes que no han tenido respuesta al manejo farmacológico convencional.

Introduction. Progressive myositis ossificans is a rare cause of myositis in childhood, is an autosomal dominant inflammatory disorder that results in swelling of muscle followed by fibrosis and calcification. Material and methods. We present 2 cases in which, the main clinical manifestations were congenitally short great toes and thumbs; and hardening of the soft tissues; in both cases calcifications of the neck and the thorax were demonstrated by roentgenograms. The 2 patients received conventional management with diphosphonates and isotretinoine, with poor response to these therapies; because of this we decided to use 3 initial doses of intravenous methylprednisolone (30 mg/kg/doses), and after that, we continued the treatment with monthly applications of methylprednisolone. Results. With this therapy our patients improved; and this was evidenciated by diminishing of calcifications and by improvement in their functional status. Conclusion. In this paper we propose an alternative pharmacological therapy with intravenous methylprednisolone, looking for its antiinflammatory and immunosuppressive effects of steroids; mainly in patients with poor response to conventional treatments.