A multi-country study of intussusception in children under 2 years of age in Latin America: analysis of prospective surveillance data.

BACKGROUND: Intussusception (IS) is a form of acute intestinal obstruction that occurs mainly in infants and is usually of unknown cause. An association between IS and the first licensed rotavirus vaccine, a reassortant-tetravalent, rhesus-based rotavirus vaccine (RRV-TV), led to the withdrawal of the vaccine. New rotavirus vaccines have now been developed and extensively studied for their potential association with IS. This study aimed to describe the epidemiology and to estimate the incidence of IS in Latin American infants prior to new vaccine introduction. METHODS: Children under 2 years of age representing potential IS cases were enrolled in 16 centers in 11 Latin American countries from January 2003 to May 2005. IS cases were classified as definite, probable, possible or suspected as stated on the Brighton Collaboration Working Group guidelines. RESULTS: From 517 potential cases identified, 476 (92%) cases were classified as definite, 21 probable, 10 possible and 10 suspected for intussusception. Among the 476 definite IS cases, the median age at presentation was 6.4 months with 89% of cases aged <1 year. The male to female ratio was 1.5:1. The incidence of definite IS per 100,000 subject-years ranged from 1.9 in Brazil to 62.4 in Argentina for children <2 years of age, and from 3.8 in Brazil to 105.3 in Argentina for children aged <1 year. Median hospital stay was 4 days with a high prevalence of surgery as the primary treatment (65%). Most cases (88%) made a complete recovery, but 13 (3%) died. No clear seasonal pattern of IS cases emerged. CONCLUSIONS: This study describes the epidemiology and estimates the incidence of IS in Latin American infants prior to the introduction of new rotavirus vaccines. The incidence of IS was found to vary between different countries, as observed in previous studies. TRIAL REGISTRATION: Clinical study identifier 999910/204 (SERO-EPI-IS-204).

[Impact of a centralised hospital admission system on the efficacy and efficiency of a geriatric functional recovery unit]. / Repercusión de un sistema centralizado de ingresos sobre la eficacia y eficiencia de una unidad geriátrica de recuperación funcional.

OBJECTIVE: To evaluate the influence of a change in the management of admissions on the activity and care outcomes of a Geriatric Functional Recovery Unit (GFRU). MATERIAL AND METHODS: A retrospective observational study was conducted. Since 2000, the Hospital Central Cruz Roja GFRU has been collecting data grouped into periods of 4 years, except for the centralised admissions (September 2016-December 2018). The data collected on admission included the Red Cross Functional and Mental scales, the Barthel index, the main diagnosis of the functional decline (grouped into stroke, orthopaedic problem, and multifactorial immobility episodes), and comorbidity evaluated by the Charlson index. The following outcome variables were analysed: the overall and relative functional gain at discharge; length of hospital stay; the functional efficiency, discharges to nursing homes, and transfers to acute care units. An analysis was made of the relationship between the admissions from the centralised unit and the previous period (directly admission managed by GFRU), using multivariate analysis (linear regression for continuous outcome variables and logistic regression for the dichotomous ones), adjusted for admission variables. RESULTS: Patients admitted from the centralised unit showed a greater overall and relative functional gain (difference between both means: 3.49 points, 95% CI; 1.65-5.33, and 12.41%, 95% CI; 0.74-24.08, respectively), longer stay (12.92 days, 95% CI; 11.54-14.30) and lower efficiency (-0.36, 95% CI; -0.16 to -0.57), higher risk of institutionalisation (OR 1.61, 95% CI; 1.19-2.16), and transfers to acute care units (OR 3.16, 95% CI; 2.24-4.47). CONCLUSIONS: A centralised admissions system had an influence on the improvement of functional parameters in the patients, but with a longer length of hospital stay, and lower efficiency. Increases in institutionalisation at discharge and transfers to acute care units were also observed.

Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis.

BACKGROUND: The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial. METHODS: We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients). RESULTS: The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78). CONCLUSIONS: Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)

Hepatitis A as an etiologic agent of acute liver failure in Latin America.

BACKGROUND: This prospective, multicenter study examined the importance of hepatitis viruses as etiological agents of acute liver failure (ALF) and the outcome of ALF cases in Latin American children and adolescents. METHODS: The study was conducted for minimum 12 months in 9 centers in Argentina, Brazil, Chile, Colombia, Costa Rica, and Mexico during 2001-2002. Hospitalized patients aged 1-20 years with a suspected diagnosis of ALF were included in the study and tested for serologic markers for hepatitis A, B, and C viruses. RESULTS: Of the 106 patients enrolled, 88 were included in the analysis. Median age was 5 years, and 55% with ALF were aged 1-5 years. A total of 37 individuals (43%) tested positive for anti-hepatitis A virus (HAV) immunoglobulin M (IgM) as marker of acute HAV infection; one was positive for anti-hepatitis B core antigen IgM and negative for hepatitis B surface antigen. None had markers of hepatitis C virus infection. Mortality rates in the overall study cohort (45%) and for those who tested anti-HAV IgM positive (41%) were similar. Forty-one percent of all patients and 46% of those positive for anti-HAV IgM underwent transplantation. The mortality rate in those with liver transplantation was half of that in patients who were not transplanted (28% versus 57%). CONCLUSIONS: HAV was the main etiologic agent of ALF in the population studied.

Evaluation of safety, immunogenicity and efficacy of an attenuated rotavirus vaccine, RIX4414: A randomized, placebo-controlled trial in Latin American infants.

BACKGROUND: A live attenuated monovalent rotavirus vaccine RIX4414 was developed with a human strain of G1P1A P[8] specificity to reduce the rotavirus burden in children. METHODS: A double blind, randomized, placebo-controlled study evaluated the efficacy, immunogenicity, safety and reactogenicity of 2 oral doses of RIX4414 (10(4.7), 10(5.2) or 10(5.8) focus-forming units) at 2 and 4 months coadministered with routine vaccinations and oral poliovirus vaccine given for study purposes at least 14 days apart. The 2155 infants (1618 vaccine/537 placebo) enrolled in Brazil, Mexico and Venezuela were followed until 1 year of age. RESULTS: Antirotavirus IgA seroconversion rates 2 months after dose 2 ranged between 61% (10(4.7) ffu group) and 65% (10(5.8) ffu group), and most of the infants had seroprotective levels of antibodies to coadministered routine vaccinations. The reactogenicity profile of RIX4414 was similar to that of the placebo, and no vaccination-related serious adverse events were reported. Protective efficacy against severe and any rotavirus gastroenteritis from 15 days post-dose 2 was highest in the 10(5.8) ffu group [86%; 95% confidence interval (95% CI), 63-96% and 70% (95% CI 46-84%), P < 0.001, 2-sided Fisher's exact test]. The efficacy against hospitalization was 79% (95% CI 48-92%) for pooled vaccine groups. Multiple rotavirus serotypes [G1 (50%), G9 (40%), G2, G3 and G4] were identified from gastroenteritis stools (enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction) during the study period. For severe gastroenteritis caused by G9 serotypes, the protection reached 77% (95% CI 18-96%) in the 10(5.8) ffu group, providing proof of concept that the monovalent G1P1A P[8] human rotavirus vaccine elicits cross-protection against the G9 strain. A reduction in any and severe rotavirus gastroenteritis was already observed at post-dose 1 (period: day of dose 1 to 14 days post-dose 2) in vaccinees compared with placebo recipients. CONCLUSIONS: Two doses of RIX4414 are highly efficacious, providing cross-protection (G1 and G9 strains, prevalent during this study) and early protection against any and severe rotavirus gastroenteritis and hospitalization to infants in Latin America.

Diarrhea morbidity and mortality in Mexican children: impact of rotavirus disease.

AIM: To analyze changes in prevalence and seasonality of diarrhea morbidity and mortality and to evaluate the impact of rotavirus disease among Mexican children younger than 5 years old. METHODS: Diarrhea surveillance was performed from 1990 to 2002. Rotavirus testing was performed on stool specimens from 1996 to 2002. Data were obtained from different surveillance systems considering a nationwide representation in Mexico. Diarrhea morbidity and mortality rates were analyzed against time to determine trends or seasonal patterns. RESULTS: Improvement of surveillance for all diarrhea episodes denoted an initial morbidity increase from 1995 to 1999, followed by a decrease by 2002, without any seasonal pattern. However, from 1990 to 1995, morbidity for severe diarrhea decreased 63%. From 1996 to 2002, 62-68% of severe diarrhea episodes occurring during the fall-winter season (FWS) were rotavirus-positive compared with 6-12% in the spring-summer season (SSS). From 1990 to 2002, diarrhea mortality decreased 84%. Higher mortality rates for children younger than 1 year old coincided precisely during the FWS, annually. Both severe diarrhea episodes and diarrhea deaths denoted a changing seasonal pattern. In 1990-1991, 2 waves of increased diarrhea activity occurred. The increase in SSS was much more pronounced than that in FWS. From 1992 to 1995 for severe diarrhea and from 1993 to 2002 for diarrhea deaths, the SSS frequencies subsequently reduced, whereas the FWS peaks remained annually. CONCLUSIONS: A significant reduction in morbidity and mortality of severe diarrhea has occurred from 1990 and 2002 in Mexican children younger than 5 years old. This is a consequence of preventive programs initiated for cholera control since 1991, which had greater impact on SSS diarrhea and limited response for FWS diarrhea, when rotavirus is mainly present. Currently rotavirus diarrhea requires new prevention strategies and specific control measures, such as a specific national vaccine program.

A two-dose combined vaccine against hepatitis A and hepatitis B in healthy children and adolescents compared to the corresponding monovalent vaccines.

BACKGROUND: Immunization against hepatitis A and B has been available for some time, protecting against both infections. With a view to achieving further reduction in the number of interventions and increasing convenience of the vaccinee, we investigated the reactogenicity and immunogenicity of a combined hepatitis A and B vaccine in healthy 4- to 20-year-old subjects at a 0, 6-month schedule. METHODS: Two hundred forty-eight study subjects were allocated to two study groups and received either two doses of the combined hepatitis A and B vaccine (68% of subjects) or the corresponding monovalent hepatitis A and hepatitis B vaccines (32% of subjects) concomitantly in opposite arms. Reactogenicity was assessed via diary cards after each vaccination. Serum samples were analyzed at months 1, 2, 6, and 7. RESULTS: All vaccines were well tolerated and very few symptoms were scored as severe. All but one subject seroconverted for anti-hepatitis A virus (anti-HAV) antibodies (98.6%) and 100% of subjects seroconverted for anti-hepatitis B (HBs) antibodies, with respective seroprotection rates of 98.7% for the combined vaccine group and 95.9% for the concomitant vaccine group (p >0.05), respectively. Geometric mean titers were higher in the group receiving the combined vaccine: 6,635 mIU/mL vs. 2,728 mIU/mL (p = 0.0001) for anti-HAV and 3,362 mIU/mL vs. 1,724 mIU/mL (p = 0.0205) for anti-HBs, respectively. Younger subjects had a stronger immune response compared to older subjects. CONCLUSIONS: The combined hepatitis A and B vaccine was well tolerated at this two-dose schedule. The combined vaccine had higher immunogenicity, probably explained by a adjuvant effect of the antigens. Vaccination programs requiring fewer injections will most likely have a positive impact on compliance rate and comfort of the vaccinee.

Seroprevalence of hepatitis A virus in a cross-sectional study in Mexico: Implications for hepatitis A vaccination.

Hepatitis A virus (HAV) remains a public health concern worldwide contributing to significant morbidity in developed and developing countries. This cross-sectional database study estimated the overall HAV seroprevalence and the seroprevalence by gender, age, region and socioeconomic status in Mexico. Between January and October 2010, serum samples collected during the National Health and Nutrition survey (ENSANUT 2006) were obtained from subjects aged 1-95 y. Subjects' gender, age, geographical region and socioeconomic status were extracted from the survey and compiled into a subset database by the Mexican National Institute of Public Health. Anti-HAV antibodies were measured using a chemiluminescent immunoassay. A total of 3658 subjects were included in the according-to-protocol cohort. Overall, the HAV seroprevalence was 84.2%. The HAV seroprevalence rates were similar between females (86.1%) and males (82.2%). The percentage of subjects seropositive for anti-HAV antibodies was highest in adults aged ≥ 20 y (96.9%), followed by adolescents aged 10-19 y (80.1%) and lowest in children aged 1-9 y (45.0%) (p < 0.0001). Regionally, the highest HAV seroprevalence rate was observed in the South (88.8%) followed by Central and Northern Mexico and Mexico City (p = 0.02). The HAV seroprevalence was similar between subjects of high socioeconomic (90.1%) status and of low socioeconomic status (86.6%). This study confirms the intermediate HAV endemicity in Mexico. Cost-effectiveness studies are necessary to evaluate the inclusion of an effective hepatitis A vaccine from a population-based perspective in addition to continuous efforts to improve hygiene and sanitation that have a substantial impact on the disease burden.

Seroprevalences of varicella-zoster virus, herpes simplex virus and cytomegalovirus in a cross-sectional study in Mexico.

We estimated the seroprevalences of varicella-zoster virus (VZV), herpes simplex virus (HSV) and cytomegalovirus (CMV) in this cross-sectional database study. Serum samples collected during the National Health and Nutrition survey (ENSANUT 2006) were obtained from subjects aged 1-70 years between January and October 2010. Serological assays for the determination of antibodies against VZV, HSV and CMV were performed. The overall seroprevalences of VZV, HSV-1, HSV-2 and CMV were 85.8%, 80.9%, 9.9% and 89.2%, respectively. Seroprevalences of VZV, HSV-1 and CMV were comparable between males and females. For HSV-2, although the seroprevalence rate was higher in females when compared to males, this difference in seroprevalence was not statistically significant. Seroprevalence rates for VZV, HSV-1, HSV-2 and CMV increased with age (p-value<.0001). Differences in seroprevalence rate for VZV by socioeconomic status (SES) were significant (p-value<0001). Results of the serological analyses reported high VZV seroprevalence, indicating high transmission in the Mexican population with children and adolescents at risk of acquiring VZV. Global HSV-1 seroprevalence was high, especially in adults. HSV-1 and HSV-2 seroprevalences were consistently higher in women than men, particularly for HSV-2. CMV seroprevalence was higher in Mexico when compared to developed countries. Seroepidemiological data on VZV supports the fact that varicella vaccination may serve as an alternative effective solution to reduce transmission in the Mexican population. For CMV and HSV, since no vaccines are available, activities to reduce transmission are important to reduce the risk of complications and therefore need to be considered.

Bacterial etiology and serotypes of acute otitis media in Mexican children.

Streptococcus pneumoniae and Haemophilus influenzae have been consistently reported to be the two major bacterial pathogens responsible for acute otitis media (AOM), mainly from studies in the US and Europe. However, data on bacterial pathogens causing AOM in Latin America are limited. Understanding the relative importance of these pathogens in a specific setting, the serotype distribution, and their antibiotic susceptibility levels is important to provide local vaccine and treatment recommendations. We therefore conducted a prospective, multi-center, tympanocentesis-based epidemiological study of Mexican children three months to less than five years of age. Fifty percent of episodes were in children who had received at least one dose of PCV7. Overall, 64% of samples were culture positive for bacterial pathogens. H. influenzae and S. pneumoniae were the leading causes of bacterial AOM, detected in 34% and 29% of AOM episodes, respectively. The most commonly isolated S. pneumoniae serotypes were 19A, 19F and 23F. All H. influenzae isolates were identified as non-typeable. Seventy-four percent of S. pneumoniae were susceptible to penicillin, while 97% were susceptible to amoxicillin/clavulanate. All H. influenzae samples were susceptible to amoxicillin/clavulanate and cefotaxime, 95% to cefuroxime and 75% to ampicillin. Both S. pneumoniae and non-typable H. influenzae represent important targets for vaccination strategies to reduce AOM in Mexican children.

Repercusión de un sistema centralizado de ingresos sobre la eficacia y eficiencia de una unidad geriátrica de recuperación funcional / Impact of a centralised hospital admission system on the efficacy and efficiency of a geriatric functional recovery unit

OBJETIVO: Evaluar la influencia del cambio en la gestión de ingresos en una unidad geriátrica de recuperación funcional (UGRF) sobre su actividad y resultados asistenciales. MATERIAL Y MÉTODOS: Estudio observacional retrospectivo. Se recogieron datos registrados desde el año 2000 de la UGRF del Hospital Central Cruz Roja, agrupados en periodos de 4 años, salvo los ingresos centralizados (septiembre de 2016-diciembre de 2018). Los datos recogidos al ingreso fueron Escala Funcional y Mental de Cruz Roja, índice de Barthel, diagnóstico principal motivo del deterioro funcional (que se agrupó en ictus, patología ortopédica y cuadros de inmovilidad multifactorial) y comorbilidad evaluada por el índice de Charlson. Como variables de resultado se estudiaron la ganancia funcional al alta, tanto global como relativa, la estancia hospitalaria, la eficiencia funcional, las altas a residencia y los retraslados a unidad de agudos. Analizamos la relación entre los ingresos realizados de manera centralizada desde una unidad externa y el periodo previo (ingresos gestionados directamente desde la UGRF) en las variables resultados utilizando un análisis multivariante (regresión lineal para variables resultado continuas y regresión logística para las dicotómicas) ajustado por variables al ingreso. RESULTADOS: En el análisis multivariante los pacientes ingresados desde la unidad central presentaron una mayor ganancia funcional global y relativa (diferencia de medias de 3,49 puntos con IC 95%=1,65-5,33 y 12,41% con IC 95%=0,74-24,08, respectivamente), mayor estancia (12,92 días; IC 95%=11,54-14,30) y menor eficiencia (−0,36; IC 95%=−0,16 a −0,57), mayor riesgo de institucionalización (OR 1,61; IC 95%=1,19-2,16) y riesgo de retraslado a unidad de agudos (OR 3,16; IC 95%=2,24-4,47). CONCLUSIONES: El sistema centralizado de ingreso influyó en la mejora de parámetros funcionales, pero a costa de una mayor estancia y una menor eficiencia asistencial, objetivándose un incremento de la institucionalización al alta y de los retraslados a unidades de agudos

OBJECTIVE: To evaluate the influence of a change in the management of admissions on the activity and care outcomes of a Geriatric Functional Recovery Unit (GFRU). MATERIAL AND METHODS: A retrospective observational study was conducted. Since 2000, the Hospital Central Cruz Roja GFRU has been collecting data grouped into periods of 4 years, except for the centralised admissions (September 2016-December 2018). The data collected on admission included the Red Cross Functional and Mental scales, the Barthel index, the main diagnosis of the functional decline (grouped into stroke, orthopaedic problem, and multifactorial immobility episodes), and comorbidity evaluated by the Charlson index. The following outcome variables were analysed: the overall and relative functional gain at discharge; length of hospital stay; the functional efficiency, discharges to nursing homes, and transfers to acute care units. An analysis was made of the relationship between the admissions from the centralised unit and the previous period (directly admission managed by GFRU), using multivariate analysis (linear regression for continuous outcome variables and logistic regression for the dichotomous ones), adjusted for admission variables. RESULTS: Patients admitted from the centralised unit showed a greater overall and relative functional gain (difference between both means: 3.49 points, 95% CI; 1.65-5.33, and 12.41%, 95% CI; 0.74-24.08, respectively), longer stay (12.92 days, 95% CI; 11.54-14.30) and lower efficiency (−0.36, 95% CI; −0.16 to −0.57), higher risk of institutionalisation (OR 1.61, 95% CI; 1.19-2.16), and transfers to acute care units (OR 3.16, 95% CI; 2.24-4.47). CONCLUSIONS: A centralised admissions system had an influence on the improvement of functional parameters in the patients, but with a longer length of hospital stay, and lower efficiency. Increases in institutionalisation at discharge and transfers to acute care units were also observed

Economic impact of a rotavirus vaccination program in Mexico.

OBJECTIVES: To evaluate the cost and benefits of a national rotavirus childhood vaccination program in Mexico. METHODS: A decision-analysis model was designed to take the Mexican health care system's perspective on a comparison of two alternatives: to vaccinate against rotavirus or not. Using published, national data, estimations were calculated for the rotavirus illnesses, deaths, and disability-adjusted life years (DALYs) that would be averted and the incremental cost-effectiveness ratios (US$/DALY) of a hypothetical annual birth cohort of 2 285 000 children, with certain assumptions made for cost, coverage, and efficacy rates. RESULTS: With 93% coverage and a vaccine price of US$ 16 per course (2 doses), a rotavirus vaccination program in Mexico would prevent an estimated 651 deaths (or 0.28 deaths per 1 000 children); 13 833 hospitalizations (6.05 hospitalizations per 1 000 children); and 414 927 outpatient visits (182 outpatient visits per 1 000 children) for rotavirus-related acute gastroenteritis (AGE). Vaccination is likely to reduce the economic burden of rotavirus AGE in Mexico by averting US$ 14 million (71% of the overall health care burden). At a vaccine price of US$ 16 per course, the cost-effectiveness ratio would be US$ 1 139 per DALY averted. A reduction in the price of the rotavirus vaccination program (US$ 8 per course) would yield a lower incremental cost-effectiveness ratio of US$ 303 per DALY averted. CONCLUSIONS: A national rotavirus vaccination program in Mexico is projected to reduce childhood incidence and mortality and to be highly cost-effective based on the World Health Organization's thresholds for cost-effective interventions.

Dose response and efficacy of a live, attenuated human rotavirus vaccine in Mexican infants.

OBJECTIVE: Immunization against rotavirus has been proposed as the most cost-effective intervention to reduce the disease burden associated with this infection worldwide. The objective of this study was to determine the dose response, immunogenicity, and efficacy of 2 doses of an oral, attenuated monovalent G1[P8] human rotavirus vaccine in children from the same setting in Mexico, where the natural protection against rotavirus infection was studied. METHODS: From June 2001 through May 2003, 405 healthy infants were randomly assigned to 1 of 3 vaccine groups (virus concentrations 10(4.7), 10(5.2), and 10(5.8) infectious units) and to a placebo group and were monitored to the age of 2 years. The vaccine/placebo was administered concurrently with diphtheria-tetanus toxoid-pertussis/hepatitis B/Haemophilus influenzae type b vaccine at 2 and 4 months of age. After the administration of the first vaccine/placebo dose, weekly home visits to collect information regarding infant health were conducted. Stool samples were collected during each gastroenteritis episode and tested for rotavirus antigen and serotype. RESULTS: The vaccine was well tolerated and induced a greater rate of seroconversion than observed in infants who received placebo. For the pooled vaccine groups, efficacy after 2 oral doses was 80% and 95% against any and severe rotavirus gastroenteritis, respectively. Efficacy was 100% against severe rotavirus gastroenteritis and 70% against severe gastroenteritis of any cause with the vaccine at the highest virus concentration (10(5.8) infectious units). The predominant infecting rotavirus serotype in this cohort was wild-type G1 (85%). Adverse events, including fever, irritability, loss of appetite, cough, diarrhea, and vomiting, were similar among vaccinees and placebo recipients. CONCLUSION: This new oral, live, attenuated human rotavirus vaccine was safe, immunogenic, and highly efficacious in preventing any and, more importantly, severe rotavirus gastroenteritis in healthy infants. This vaccine produced comparable protection to natural infection.

Influenza vaccination in patients with breast cancer: a case-series analysis.

BACKGROUND: Our aim was to evaluate the serological response and safety of influenza vaccine in patients with breast cancer in Mexico. MATERIAL/METHODS: Between October and December 2001, patients with breast cancer were vaccinated with a split virus vaccine. Hemagglutination inhibition assay titers were measured before vaccination and 4-6 weeks later. Titer ratios were used as the primary measure of response. When comparing rate of response according to treatment, stage, or other patient-related variables, individuals with post vaccination titers >/=1:40 for all 3 antigen strains were called respondents. RESULTS: We analyzed 146 patients who were vaccinated and had influenza antibodies measured before and after vaccination. Seventy-two (49.3%) had locally advanced breast cancer, 117 (80.1%) were receiving cancer treatment, 91 (62.3%) were on chemotherapy. Response to vaccine was 47.2%; we found an additional 25.3% of patients who responded to two of the serotypes. In patients receiving chemotherapy the response rate was lower (p=NS). CONCLUSIONS: The results of the present study show that influenza vaccine is safe and well tolerated in patients with breast cancer, but we observed a lessening of the immune response among patients receiving chemotherapy. Influenza vaccination should be recommended in all patients with breast cancer, regardless of the anti-neoplastic treatment.

Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine.

OBJECTIVE: The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B (HB) and Haemophilus influenzae type b (Hib) vaccines into routine childhood vaccination programs. The objectives of this study were to: 1) analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2) in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster. METHODS: In the first part of the study (primary-vaccination stage), conducted in 1998-1999, we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2, 4, and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth. Later, in the booster-vaccination stage of the study, in 1999-2000, in a subset of the children (69 toddlers, now 15-18 months old), antibody persistence was measured, and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed. RESULTS: In both primary-vaccination groups, at least 97.5% of the infants reached protective levels of antibodies (seropositivity) against the antigens employed in the vaccines. The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone, and, in terms of general reactions, there was no clinically significant difference between the combination or separate injections, and with the pentavalent vaccine having the benefit of needing one less injection. Nine months after the third dose of the primary-vaccination course, antibody persistence was similar in both groups, with over 93% of children still having protective/seropositive titers for Hib, HB, and tetanus and about 50% for diphtheria and Bordetella pertussis. At 15 months of age, virtually all the toddlers responded with a strong boost response to all the vaccine antigens, whether they received the DTPw-HB/Hib pentavalent vaccine or the DTPw/Hib vaccine as a booster. Both booster regimens were equally well tolerated, indicating that up to five doses of the HB vaccine can be given without impact on safety. CONCLUSIONS: Our study confirms that the DTPw-HB/Hib pentavalent vaccine is highly immunogenic as a primary vaccination in children who received an HB vaccine at birth, with the pentavalent combination inducing both persisting immunity and boostable memory. The pentavalent vaccine was safe both for primary and booster vaccinations. Thus, this study in Costa Rican infants supports the routine use of the pentavalent DTPw-HB/Hib vaccine as part of childhood vaccination programs in Latin America and the Caribbean.

Economic impact of a rotavirus vaccination program in Mexico / Impacto económico de un programa de vacunación contra rotavirus en México

OBJECTIVES: To evaluate the cost and benefits of a national rotavirus childhood vaccination program in Mexico. METHODS: A decision-analysis model was designed to take the Mexican health care system's perspective on a comparison of two alternatives: to vaccinate against rotavirus or not. Using published, national data, estimations were calculated for the rotavirus illnesses, deaths, and disability-adjusted life years (DALYs) that would be averted and the incremental costeffectiveness ratios (US$/DALY) of a hypothetical annual birth cohort of 2 285 000 children, with certain assumptions made for cost, coverage, and efficacy rates. RESULTS: With 93 percent coverage and a vaccine price of US$ 16 per course (2 doses), a rotavirus vaccination program in Mexico would prevent an estimated 651 deaths (or 0.28 deaths per 1 000 children); 13 833 hospitalizations (6.05 hospitalizations per 1 000 children); and 414 927 outpatient visits (182 outpatient visits per 1 000 children) for rotavirus-related acute gastroenteritis (AGE). Vaccination is likely to reduce the economic burden of rotavirus AGE in Mexico by averting US$ 14 million (71 percent of the overall health care burden). At a vaccine price of US$ 16 per course, the cost-effectiveness ratio would be US$ 1 139 per DALY averted. A reduction in the price of the rotavirus vaccination program (US$ 8 per course) would yield a lower incremental cost-effectiveness ratio of US$ 303 per DALY averted. CONCLUSIONS: A national rotavirus vaccination program in Mexico is projected to reduce childhood incidence and mortality and to be highly cost-effective based on the World Health Organization's thresholds for cost-effective interventions.

OBJETIVOS: Evaluar el costo y los beneficios de un programa nacional de vacunación infantil contra el rotavirus en México. MÉTODOS: Se diseñó un modelo de análisis de decisión, desde la perspectiva del sistema de salud mexicano, para comparar dos alternativas: vacunar contra el rotavirus o no vacunar. A partir de datos nacionales publicados se estimó el número de casos y muertes por rotavirus, los años de vida ajustados por la discapacidad (AVAD) que se evitarían y la relación costo-efectividad incremental (US$/AVAD) de una cohorte anual hipotética de 2 285 000 niños; se partió de algunos supuestos sobre el costo, la cobertura y las tasas de eficacia. RESULTADOS: Con una cobertura de 93 por ciento y un precio de la vacuna de US$ 16,00 por esquema (dos dosis), se estima que un programa de vacunación contra rotavirus en México evitaría 651 muertes (0,28 muertes por 1 000 niños), 13 833 hospitalizaciones (6,05 hospitalizaciones por 1 000 niños) y 414 927 visitas de consulta externa (182 consultas por 1 000 niños) por gastroenteritis aguda asociada a rotavirus (GAR). La vacunación podría reducir la carga económica por GAR en México al evitar gastos por US$ 14 millones (71 por ciento de la carga total por atención sanitaria). A un precio de US$ 16,00 por esquema, la relación costo-efectividad sería de US$ 1 139,00 por AVAD evitado. Una reducción en el precio del programa de vacunación contra rotavirus (US $8,00 por esquema) generaría una menor relación costo-efectividad incremental de US$ 303,00 por AVAD evitado. CONCLUSIONES: Un programa nacional de vacunación contra rotavirus en México reduciría la incidencia y la mortalidad infantiles y sería altamente efectivo en función del costo, según los umbrales de las intervenciones de costo-efectividad de la Organización Mundial de la Salud.

DTPw-HB and Hib primary and booster vaccination: combined versus separate administration to Latin American children.

This multicentre study was designed to establish the reactogenicity and immunogenicity profiles of primary and booster vaccination with diphtheria, tetanus, and pertussis whole-cell-hepatitis B/Haemophilus influenzae type-b (DTPw-HB/Hib) administered as either a syringe mix or as separate injections in 400 Latin American children. Both vaccine regimens were equally well tolerated and elicited post-primary excellent seropositivity rates at or close to 100% for all five component antigens. With regard to HB, 100% of subjects in the combined vaccination group, and 98.8% subjects in the separate injection vaccination group reached seroprotective antibody concentrations (>or=10 mIU/ml) 1 month after the primary vaccination course. Equally high anti-PRP antibody concentrations were reached 1 month after vaccination, with 100% of seroprotected subjects in the combined vaccination group (antibody concentrations >or=0.15 microg/ml), against 99.4% in the separate injection vaccination group. Seroprotective anti-HBs and anti-PRP antibody concentration levels persisted approximately 1 year after the primary vaccination course, just prior to booster vaccination. Finally, a significant increase of all antibody concentrations could be observed after the booster vaccination, since all but one subject in the separate injection vaccination group had protective levels of anti-HBs and anti-PRP antibodies 1 month after the booster dose. These results suggest that the combination of DTPw-HB and Hib vaccines provides an effective means for increasing vaccine coverage in childhood vaccination programmes.

Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine

Objective. The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B (HB) and Haemophilus influenzae type b (Hib) vaccines into routine childhood vaccination programs. The objectives of this study were to: 1) analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2) in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster. Methods. In the first part of the study (primary-vaccination stage), conducted in 1998-1999, we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2, 4, and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth. Later, in the booster-vaccination stage of the study, in 1999-2000, in a subset of the children (69 toddlers, now 15-18 months old), antibody persistence was measured, and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed. Results. In both primary-vaccination groups, at least 97.5 percent of the infants reached protective levels of antibodies (seropositivity) against the antigens employed in the vaccines. The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone, and, in terms of general reactions, there was no clinically significant difference between the combination or separate injections, and with the pentavalent vaccine having the benefit of needing one less injection. Nine months after the third dose of the primary-vaccination course, antibody persistence was similar in both groups, with over 93 percent of children still having protective/seropositive titers for Hib, HB, and tetanus and about 50 percent for diphtheria and Bordetella pertussis. At 15 months of age, virtually all the toddlers responded with a strong boost response to all the vaccine antigens, whether they received the DTPw-HB/Hib pentavalent vaccine or the DTPw/Hib vaccine as a booster. Both booster regimens were equally well tolerated, indicating that up to five...