ICU Bed Utilization During the Coronavirus Disease 2019 Pandemic in a Multistate Analysis-March to June 2020.

OBJECTIVES: Given finite ICU bed capacity, knowledge of ICU bed utilization during the coronavirus disease 2019 pandemic is critical to ensure future strategies for resource allocation and utilization. We sought to examine ICU census trends in relation to ICU bed capacity during the rapid increase in severe coronavirus disease 2019 cases early during the pandemic. DESIGN: Observational cohort study. SETTING: Thirteen geographically dispersed academic medical centers in the United States. PATIENTS/SUBJECTS: We obtained daily ICU censuses from March 26 to June 30, 2020, as well as prepandemic ICU bed capacities. The primary outcome was daily census of ICU patients stratified by coronavirus disease 2019 and mechanical ventilation status in relation to ICU capacity. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Prepandemic overall ICU capacity ranged from 62 to 225 beds (median 109). During the study period, the median daily coronavirus disease 2019 ICU census per hospital ranged from 1 to 84 patients, and the daily ICU census exceeded overall ICU capacity for at least 1 day at five institutions. The number of critically ill patients exceeded ICU capacity for a median (interquartile range) of 17 (12-50) of 97 days at these five sites. All 13 institutions experienced decreases in their noncoronavirus disease ICU population, whereas local coronavirus disease 2019 cases increased. Coronavirus disease 2019 patients reached their greatest proportion of ICU capacity on April 12, 2020, when they accounted for 44% of ICU patients across all participating hospitals. Maximum ICU census ranged from 52% to 289% of overall ICU capacity, with three sites less than 80%, four sites 80-100%, five sites 100-128%, and one site 289%. CONCLUSIONS: From March to June 2020, the coronavirus disease 2019 pandemic led to ICU censuses greater than ICU bed capacity at fives of 13 institutions evaluated. These findings demonstrate the short-term adaptability of U.S. healthcare institutions in redirecting limited resources to accommodate a public health emergency.

Effect of Age at Vaccination on Rotavirus Vaccine Effectiveness in Bolivian Infants.

BACKGROUND: Rotavirus vaccines are less effective in developing countries versus developed countries. One hypothesis for this difference in performance is that higher levels of maternal antibodies in developing countries may interfere with vaccine response, suggesting that delayed dosing could be beneficial. The present analysis aims to assess whether rotavirus vaccine effectiveness (VE) varies by age at vaccination during routine use in Bolivia. METHODS: Data were merged from 2 postlicensure evaluations of monovalent rotavirus vaccine (RV1) in Bolivia, where 2 doses of RV1 are recommended at 2 and 4 months of age. For each dose, children were classified as receiving each dose "early," "on-time" or "late." Stratified unconditional logistic regression models were used to estimate VE, using unvaccinated children as the referent. VE was calculated as (1 - odds ratio) × 100%. Models were adjusted for hospital, age and time since RV1 introduction (via including terms for month and year of birth). RESULTS: VE for 2 doses of RV1 tended to be higher in infants receiving the first dose early (VE, 92%; 95% confidence interval: 70%-98%), when compared with infants receiving their first dose on-time [72% (62%-81%)] or late [68% (51%-79%)]. Estimates of VE were not substantially different when comparing children by age at second dose [early: VE, 76% (50%-89%); on-time: VE, 70% (50%-89%); late: VE, 75% (60%, 84%)], including all children. CONCLUSIONS: Our results indicate that early administration may improve VE and support the current World Health Organization recommendations for the RV1 schedule.

Breastfeeding linked to the reduction of both rotavirus shedding and IgA levels after Rotarix® immunization in Mexican infants.

We examined potential risk factors on vaccine virus shedding and antibody seroresponse to human rotavirus vaccine (Rotarix) in Mexican infants. Two doses of Rotarix were administered to infants during the first two visits for their routine childhood immunization (∼8 and 15weeks of age) in Mexico City. Infant's characteristics and socioeconomic indicators were obtained, including history of long-term feeding practices (exclusively/predominantly breastfed and exclusively/predominantly non-breastfed). Two serum specimens were collected, one during the second rotavirus vaccine visit and one 7weeks later. Stool specimens were collected between days 4-7 after each of the two rotavirus vaccine doses. Rotavirus IgA and IgG titers in serum were determined by enzyme immunoassays (EIA) and rotavirus shedding in stool was assessed by EIA and confirmed by RT-PCR. The overall rotavirus IgA geometric mean titers (GMT) increased significantly post dose 2 from post dose 1 [176 (95%CI: 113-273) to 335 (238-471); p=0.020). Infants who were exclusively/predominantly breastfed were less likely to shed vaccine virus in stool than those who were formula-fed (22% vs. 43%, p=0.016). Infants who were breastfed had lower rotavirus IgA titers than those who were formula-fed after dose 1 [GMT: 145 (84-250) vs. 267 (126-566) p=0.188] and dose 2 [236 (147-378) vs.578 (367-910), p=0.007]. Infants who shed vaccine virus post dose 1 had significantly higher serum IgA GMT than those who did not shed [425 (188-965) vs. 150 (84-266), p=0.038]. Breastfeeding was linked with the reduction of both stool vaccine shedding, and IgA seroresponse. The reduced rotavirus replication in the gut and shedding after dose 1 may explain in part the lower IgA response in serum.

Sustained Effectiveness of Rotavirus Vaccine Against Very Severe Rotavirus Disease Through the Second Year of Life, Bolivia 2013-2014.

BACKGROUND: In Bolivia, monovalent rotavirus vaccine was introduced in 2008 and a previous evaluation reported a vaccine effectiveness (VE) of 77% with 2 doses of vaccine in children aged <3 years. This evaluation sought to determine if rotavirus vaccine provided protection through the second year of life against circulating genotypes. METHODS: A case-control study was performed in 5 hospitals from April 2013 to March 2014. Among enrolled participants who met study criteria and had rotavirus stool testing performed and vaccine status confirmed, we calculated VE using a logistic regression model. Subgroup analyses were performed among children aged <1 year and those aged ≥1 year, among children with severe diarrhea (Vesikari score ≥11) and very severe diarrhea (Vesikari score ≥15), and among G and P strains with at least 40 specimens. RESULTS: A total of 776 children were enrolled. For children <1 year and ≥1 year of age with severe diarrhea, VE for 2 doses was 75% (95% confidence interval [CI], 46%-88%) and 53% (95% CI, 9%-76%), respectively. For children <1 year and ≥1 year of age with very severe diarrhea, VE for 2 doses was 80% (95% CI, 44%-93%) and 74% (95% CI, 35%-90%), respectively. Genotype-specific analysis demonstrated similar VE for the 4 most common G and P types (G3, G9, P[6] and P[8]). CONCLUSIONS: A monovalent rotavirus vaccine remains effective against a broad range of circulating strains as part of a routine immunization program >5 years after its introduction in Bolivia. Although VE appears to wane in children aged ≥1 year, it still provides significant protection, and does not wane against severe disease.

Effectiveness of Monovalent and Pentavalent Rotavirus Vaccines in Guatemala.

BACKGROUND: Concerns remain about lower effectiveness and waning immunity of rotavirus vaccines in resource-poor populations. We assessed vaccine effectiveness against rotavirus in Guatemala, where both the monovalent (RV1; 2-dose series) and pentavalent (RV5; 3-dose series) vaccines were introduced in 2010. METHODS: A case-control evaluation was conducted in 4 hospitals from January 2012 to August 2013. Vaccine status was compared between case patients (children with laboratory-confirmed rotavirus diarrhea) and 2 sets of controls: nondiarrhea "hospital" controls (matched by birth date and site) and nonrotavirus "test-negative" diarrhea controls (adjusted for age, birth month/year, and site). Vaccine effectiveness ([1 - odds ratio of vaccination] × 100%) was computed using logistic regression models. RESULTS: We evaluated 213 case patients, 657 hospital controls, and 334 test-negative controls. Effectiveness of 2-3 doses of a rotavirus vaccine against rotavirus requiring emergency department visit or hospitalization was 74% (95% confidence interval [CI], 58%-84%) with hospital controls, and 52% (95% CI, 26%-69%) with test-negative controls. Using hospital controls, no significant difference in effectiveness was observed between infants 6-11 months (74% [95% CI, 18%-92%]) and children ≥12 months of age (71% [95% CI, 44%-85%]) (P= .85), nor between complete courses of RV1 (63% [95% CI, 23%-82%]) and RV5 (69% [95% CI, 29%-87%]) (P= .96). An uncommon G12P[8] strain, partially heterotypic to strains in both vaccines, was identified in 89% of cases. CONCLUSIONS: RV1 and RV5 were similarly effective against severe rotavirus diarrhea caused by a heterotypic strain in Guatemala. This supports broader implementation of rotavirus vaccination in low-income countries where >90% global deaths from rotavirus occur.

Effectiveness of Pentavalent Rotavirus Vaccine Against a Diverse Range of Circulating Strains in Nicaragua.

BACKGROUND: Because >60 rotavirus strains have been reported worldwide, concerns exist about strain replacement after the introduction of rotavirus vaccines, particularly in developing countries with diverse strains and lower efficacy. METHODS: We used the case-control design in 4 hospitals in Nicaragua to assess strain-specific vaccine effectiveness (VE) of a pentavalent rotavirus vaccine (RotaTeq) against rotavirus diarrhea. Cases were identified through prospective strain surveillance with reverse transcription-polymerase chain reaction for 3 years among children hospitalized for diarrhea, and controls were children negative for rotavirus. RESULTS: We enrolled 1178 case-patients, 1082 (92%) with G and P typing, and 4927 controls. A different strain predominated each year with increasing age of the vaccine-eligible cohort during the study period: G2P[4] in 2008 (97%; mean age, 11.9 months), G1P[8] in 2009 (55%; mean age, 17.0 months), and G3P[8] in 2010 (78%; mean age, 17.3 months). Overall VE was 45% (95% confidence interval, 25%-59%). Regardless of the strain, VE estimates were 12%-79% lower among children aged ≥12 months relative to those 6-11 months of age. The lower VE for G3P[8] was related to the higher mean age of cases (17.3 months) compared with the G2P[4] strains (11.9 months), with a significant trend (R(2)= 0.819;P< .001) of declining effectiveness with increasing mean age of the cases. CONCLUSIONS: Introduction of RotaTeq did not result in sustained emergence of any particular strain in Nicaragua. Variation in strain-specific effectiveness was due to an age-related decline in effectiveness rather than differences in protection against the observed strains.

Hospital-based surveillance of intussusception among infants / Vigilância hospitalar de intussuscepção entre neonatos

Abstract Objective: Intussusception surveillance was initiated after the nationwide introduction of live attenuated monovalent rotavirus vaccine (RV1). The objective is to assess the epidemiology of intussusception and compare the number of cases before and after the introduction of rotavirus vaccine. Methods: Cases of intussusception occurring between March 2006 and January 2008 were identified through a prospective enhanced passive surveillance system established in sentinel state hospitals. Retrospective review of medical records was used to identify cases, which occurred in sentinel hospitals between January 2001 and February 2006. Results: From 2001 to 2008, 331 intussusception cases were identified, 59.5% were male, with peak incidence among those 18–24 weeks of age. Overall <10% of cases were among infants 6–14 weeks of age (when the first dose of RV1 is administered). The most frequently observed signs or symptoms of intussusception included vomiting (89.4%), bloody stool (75.5%), and abdominal distention (71.8%). A majority (92.1%) of the case-patients required surgery for treatment; 31.8% of those who underwent surgery required bowel resection, and 13 (3.9%) died. Among the 21 hospitals that reported cases throughout the entire surveillance period (2001–2008), the number of intussusception events during 2007 (n = 26) and 2008 (n = 19) was not greater than the average annual number (n = 31, range 24–42) during baseline years 2001–2005. Conclusions: Although this analysis did not identify an increase in intussusception cases during the two years after RV1 introduction, these results support the need for special epidemiologic methods to assess the potential link between rotavirus vaccine and this very rare adverse event.

Resumo Objetivo: A vigilância da intussuscepção foi iniciada após a introdução da vacina monovalente viva atenuada contra rotavírus (RV1) em todo o país. O objetivo é avaliar a epidemiologia da intussuscepção e comparar a quantidade de casos antes e depois da introdução da vacina contra rotavírus. Métodos: Os casos de intussuscepção entre março de 2006 e janeiro de 2008 foram identificados por meio de um sistema de vigilância passivo prospectivo aprimorado estabelecido em hospitais-sentinela estaduais. A análise retrospectiva de prontuários médicos foi usada para identificar os casos que ocorreram em hospitais-sentinela entre janeiro de 2001 e fevereiro de 2006. Resultados: De 2001-2008, identificamos 331 casos de intussuscepção, 59,5% dos quais ocorreram em pacientes do sexo masculino, com pico de incidência entre aqueles com 18-24 semanas de idade. Em geral, < 10% dos casos ocorreram entre neonatos com 6-14 semanas de idade (quando a 1a dose de RV1 é administrada). Os sinais ou sintomas de intussuscepção observados com mais frequência incluíam vômito (89,4%), fezes com sangue (75,5%) e distensão abdominal (71,8%). A maioria (92,1%) dos pacientes precisou de cirurgia para o tratamento; 31,8% dos que se submeteram à cirurgia precisaram de ressecção intestinal e 13 (3,9%) vieram a óbito. Entre os 21 hospitais que relataram casos durante todo o período de vigilância (2001-2008), a quantidade de casos de intussuscepção em 2007 (n = 26) e 2008 (n = 19) não foi maior do que a quantidade média anual (31, faixa de 24-42) durante os anos-base de 2001-2005. Conclusões: Embora esta análise não tenha identificado um aumento nos casos de intussuscepção nos dois anos após a introdução da RV1, esses resultados justificam a necessidade de métodos epidemiológicos especiais para avaliar a possível associação entre a vacina contra rotavírus e esse evento adverso muito raro.

Hospital-based surveillance of intussusception among infants.

OBJECTIVE: Intussusception surveillance was initiated after the nationwide introduction of live attenuated monovalent rotavirus vaccine (RV1). The objective is to assess the epidemiology of intussusception and compare the number of cases before and after the introduction of rotavirus vaccine. METHODS: Cases of intussusception occurring between March 2006 and January 2008 were identified through a prospective enhanced passive surveillance system established in sentinel state hospitals. Retrospective review of medical records was used to identify cases, which occurred in sentinel hospitals between January 2001 and February 2006. RESULTS: From 2001 to 2008, 331 intussusception cases were identified, 59.5% were male, with peak incidence among those 18-24 weeks of age. Overall <10% of cases were among infants 6-14 weeks of age (when the first dose of RV1 is administered). The most frequently observed signs or symptoms of intussusception included vomiting (89.4%), bloody stool (75.5%), and abdominal distention (71.8%). A majority (92.1%) of the case-patients required surgery for treatment; 31.8% of those who underwent surgery required bowel resection, and 13 (3.9%) died. Among the 21 hospitals that reported cases throughout the entire surveillance period (2001-2008), the number of intussusception events during 2007 (n=26) and 2008 (n=19) was not greater than the average annual number (n=31, range 24-42) during baseline years 2001-2005. CONCLUSIONS: Although this analysis did not identify an increase in intussusception cases during the two years after RV1 introduction, these results support the need for special epidemiologic methods to assess the potential link between rotavirus vaccine and this very rare adverse event.

Impact of rotavirus vaccination on diarrhea-related hospitalizations in São Paulo State, Brazil.

INTRODUCTION: Following introduction of routine infant rotavirus vaccination, severe diarrhea hospitalization rates declined among children aged <5 years throughout Brazil. Ensuring equity of rotavirus vaccine impact is important in countries that self-finance immunization programs. The objective of this study was to examine rotavirus vaccine impact on diarrhea admission rates among children aged <5 years in Brazil's public health system, according to area-based measures of human development in the state of São Paulo, Brazil. METHODS: Ecological analysis of public health system hospitalization rates for acute gastroenteritis among children aged <5 years in the state of São Paulo, Brazil, according to five categories of municipal development based on a modified Human Development Index for municipalities. Acute gastroenteritis hospitalization rates among children aged <5 years after national rotavirus vaccine introduction (2008-2011) were compared to rates in pre-vaccine years (2000-2005) to calculate percent decline in rates (1-rate ratio) and 95% confidence intervals (CI) for each municipal development category. Direct hospitalization costs during the two periods were compared. RESULTS: Annual rates declined by 40% (95% CI, 39-42%) from 631 diarrhea hospitalizations per 100,000 person years pre-rotavirus vaccination to 377 per 100,000 post-vaccination among children aged <5 years and 50% (95% CI, 48-52%) from 1009 to 505 per 100,000 among infants. Highest rates were observed in least developed municipalities. Significant declines of 26-52% among children <5 years and 41-63% among infants were observed in all categories of municipal development. Lower diarrhea hospitalization rates resulted in annual savings of approximately 2 million USD for the state of São Paulo. Savings in direct hospitalization costs benefitted municipalities in all five categories. CONCLUSION: The introduction of rotavirus vaccination was associated with substantial reductions of diarrhea-related admissions at all levels of municipal development in São Paulo State, Brazil.

Effectiveness of the monovalent rotavirus vaccine in Colombia: a case-control study.

OBJECTIVE: To assess the effectiveness of the monovalent rotavirus vaccine (RV1) to prevent rotavirus diarrhea admissions to emergency departments (ED) in Colombia. METHODS: A multicenter case-control study was carried out in six Colombian cities from 2011 to January, 2013. Cases were laboratory confirmed rotavirus diarrhea patients admitted to ED of selected health centers. Controls were patients with non-rotavirus diarrhea. Vaccination status was card-confirmed. Vaccine effectiveness and 95% confidence intervals (CI) were calculated from the conditional logistic regression models using the formula 1-adjusted odds ratio×100. RESULTS: 1051 fecal samples were collected from 193 cases and 858 controls. Vaccination history was confirmed on 173 cases (90%) and 801 controls (93%). Among the rotavirus-positive samples with vaccination history, 57% were G2P[4], 9.8% G9P[8], 6% G9P[6]. Median age of cases (17 months) was greater than controls (15 months) (P<0.001), and mothers of cases had lower level of education (P=0.025). The adjusted effectiveness was 79.19% (95% CI, 23.7 to 94.32) among children 6-11 months of age and -39.75% (95% CI, -270.67 to 47.24) among those >12 months of age. Against overnight rotavirus hospitalizations, RV1 provided protection of 84.42% (95% CI, 22.68 to 96.86) among children 6-11 months of age, and -79.49% (95% CI, -555.8 to 51.08) among those >12 months. CONCLUSIONS: RV1 provided significant protection against rotavirus hospitalization among children under 1 year of age in the Colombian setting. The observation of lower effectiveness in children >12 months requires further assessment.

Diarrhoea-related hospitalizations in children before and after implementation of monovalent rotavirus vaccination in Mexico.

OBJECTIVE: To assess, by socioeconomic setting, the effect of nationwide vaccination against species A rotavirus (RVA) on childhood diarrhoea-related hospitalizations in Mexico. METHODS: Data on children younger than 5 years who were hospitalized for diarrhoea in health ministry hospitals between 1 January 2003 and 31 December 2011 were collected from monthly discharge reports. Human development indexes were used to categorize the states where hospitals were located as having generally high, intermediate or low socioeconomic status. Annual rates of hospitalization for diarrhoea--per 10,000 hospitalizations for any cause--were calculated. Administrative data were used to estimate vaccine coverage. FINDINGS: In the states with high, intermediate and low socioeconomic status, coverage with a two-dose monovalent RVA vaccine--among children younger than 5 years--had reached 93%, 86% and 71%, respectively, by 2010. The corresponding median annual rates of hospitalization for diarrhoea--per 10,000 admissions--fell from 1001, 834 and 1033 in the "prevaccine" period of 2003-2006, to 597, 497 and 705 in the "postvaccine" period from 2008 to 2011, respectively. These decreases correspond to rate reductions of 40% (95% confidence interval, CI: 38-43), 41% (95% CI: 38-43) and 32% (95% CI: 29-34), respectively. Nationwide, RVA vaccination appeared to have averted approximately 16,500 hospitalizations for childhood diarrhoea in each year of the postvaccine period. CONCLUSION: Monovalent RVA vaccination has substantially reduced childhood diarrhoea-related hospitalizations for four continuous years in discretely different socioeconomic populations across Mexico.

Characterization of rotavirus genotypes before and after the introduction of a monovalent rotavirus vaccine in Colombia.

Strain monitoring for emergence of novel strains after the introduction of rotavirus vaccine is an integral component of routine rotavirus immunization programs. Using a laboratory based strain surveillance system between 2008 and 2012, a wide variation in strain pattern in Colombia was founded both before and after the introduction of a monovalent rotavirus vaccine in 2009. G2P[4], a strain fully heterotypic to the vaccine was predominant before vaccine introduction in 2008 (47%) and after vaccine introduction in 2010 (54%), 2011 (86%), and 2012 (32%). The presence of this strain before the introduction of vaccine and decreasing prevalence during the most recent surveillance year suggests secular variation rather than vaccine pressure as a cause for this fluctuation. While strain monitoring can be valuable after vaccine introduction, these surveillance data alone without information on disease incidence or strain specific vaccine effectiveness can be prone to misinterpretation with regard to the role of vaccine pressure on emergence of new or persistent strains.

Incidence and Epidemiology of Intussusception among Infants in Ho Chi Minh City, Vietnam.

OBJECTIVE: To evaluate rates of intussusception hospitalization among infants in Vietnam before the introduction of rotavirus vaccine. STUDY DESIGN: Between 2009 and 2011, we identified intussusception hospitalizations among infants using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Clinical Modification code K56.1 at 2 large pediatric hospitals in Ho Chi Minh City, Vietnam that treat most of the intussusception cases in the city. We reviewed all medical records to confirm a Brighton level 1 case definition for intussusception. RESULTS: We identified a total of 869 intussusception cases in Ho Chi Minh City during the 3-year study period, for an annual rate of 296 per 100,000 infants. The mean age of intussusception was ∼ 37 weeks (8.6 months), with <2% of the cases occurring before age 15 weeks. Cases of intussusception were observed year-round in these hospitals with no evident seasonal pattern. Ultrasonography was used to diagnose most cases (97%), and reduction was performed by air enema in >95% of the cases, with only 1% of cases at 1 hospital and 5% at the other hospital requiring surgical intervention. Ultrasound diagnosis was confirmed by an independent radiologist in 94% of a randomly selected group of intussusception cases at 1 of the 2 hospitals. No mortality was reported. CONCLUSION: Vietnam has a substantially higher rate of intussusception in children aged >15 weeks compared with most other regions of the world. Most of our cases were diagnosed by ultrasound, and only a small proportion required surgical intervention with no fatalities, suggesting that the higher rates may be related in part to better and earlier detection of intussusception.

Effectiveness of monovalent rotavirus vaccine in Bolivia: case-control study.

OBJECTIVE: To evaluate the effectiveness of two doses of a monovalent rotavirus vaccine (RV1) against hospital admission for rotavirus in Bolivia. DESIGN: Case-control study. SETTING: Six hospitals in Bolivia, between March 2010 and June 2011. PARTICIPANTS: 400 hospital admissions for rotavirus, 1200 non-diarrhea hospital controls, and 718 rotavirus negative hospital controls. MAIN OUTCOME MEASURES: Odds of antecedent vaccination between case patients and controls; effectiveness of vaccination ((1-adjusted odds ratio)×100), adjusted for age and other confounders; and stratified effectiveness by dose, disease severity, age group, and serotype. RESULTS: In comparison with non-diarrhea controls, case patients were more likely to be male and attend day care but less likely to have chronic underlying illness, higher level maternal education, and telephones and computers in their home. Rotavirus negative controls were somewhat more similar to case patients but also were more likely to be male and attend day care and less likely to have higher level maternal education and computers in their homes. The adjusted effectiveness of RV1 against hospital admission for rotavirus was 69% (95% confidence interval 54% to 79%) with rotavirus negative controls and 77% (65% to 84%) with non-diarrhea controls. The effectiveness of one dose of RV1 was 36% and 56%, respectively. With both control groups, protection was sustained through two years of life, with similar efficacy against hospital admission among children under 1 year (64% and 77%) and over 1 year of age (72% and 76%). RV1 provided significant protection against diverse serotypes, partially and fully heterotypic to the G1P[8] vaccine. Effectiveness using the two control groups was 80% and 85% against G9P[8], 74% and 93%% against G3P[8], 59% and 69% against G2P[4], and 80% and 87% against G9P[6] strains. CONCLUSION: The monovalent rotavirus vaccine conferred high protection against hospital admission for diarrhea due to rotavirus in Bolivian children. Protection was sustained through two years of life against diverse serotypes different from the vaccine strain.

Effect of rotavirus vaccine on diarrhea mortality in different socioeconomic regions of Mexico.

OBJECTIVE: In Mexico, declines in childhood diarrhea deaths have been documented during 2008-2010 after rotavirus vaccine introduction in 2007. Because of concerns about variation in rotavirus vaccine efficacy by socioeconomic status, we compared reductions in diarrhea mortality in the lesser developed southern region versus the more developed northern and central regions of Mexico. METHODS: We obtained data from national vital statistics on diarrhea deaths among children aged <5 years from 2002 through 2011. We compared region-specific diarrhea mortality before (2003-2006) and after (2009-2011) vaccine introduction. Regional vaccine coverage was estimated from administrative data, and socioeconomic status was assessed by using the Human Development Index. RESULTS: In northern, central, and southern Mexico, the 2007 Human Development Index was 0.84, 0.82, and 0.77, respectively, and by 2010 an estimated 99%, 84%, and 89% of children aged <12 months had completed rotavirus vaccination. Diarrhea mortality among children <5 years old declined from 8.3, 17.9, and 28.5 deaths per 100,000 children during 2003-2006 to 4.5, 8.1, and 16.2 in 2009-2011 in northern, central, and southern Mexico, respectively, corresponding to rate reductions of 45%, 55%, and 43%. No significant differences were observed in rate reductions between regions (P > .8). CONCLUSIONS: After introduction of rotavirus vaccination, marked and sustained declines in diarrhea deaths were seen among children in all regions of Mexico, including in the least developed southern region with the highest baseline diarrhea mortality. This finding indicates equitable vaccine delivery to children with varying risk of mortality and reaffirms the beneficial effects of rotavirus vaccination against fatal diarrheal disease.

Risk Factors Associated With Rotavirus Gastroenteritis During a Community Outbreak in Chiapas, Mexico During the Postvaccination Era.

BACKGROUND: In January 2010, surveillance detected a rotavirus gastroenteritis outbreak in Chiapas, Mexico. We aimed to identify risk and protective factors for developing rotavirus gastroenteritis of any severity among children in the epidemic setting. METHODS: A case-control study was conducted, comparing case patients (defined as children <36 months of age with acute gastroenteritis of any severity whose stool tested positive for rotavirus by enzyme immunoassay) with age- and municipality-matched controls. Information was obtained through face-to-face interviews on clinical outcome, demographics, breastfeeding history, rotavirus immunization status, and indicators of socioeconomic status. RESULTS: Eighty-five case patients and 170 controls were enrolled. Factors associated with lower risk of rotavirus gastroenteritis included current breastfeeding, owning a refrigerator, and being immunized with 1 or 2 doses of a live-attenuated monovalent rotavirus vaccine. History of previous diarrheal episodes and living with 7 or more people in the same household were associated with higher risk of developing rotavirus gastroenteritis. CONCLUSION: During this outbreak, dietary, socioeconomic, and environmental factors were independently associated with risk of developing rotavirus disease. Rotavirus vaccine also offered significant protection against rotavirus disease of any severity, emphasizing the value of vaccination as a simple and highly effective public health strategy for prevention of rotavirus illness.

The rotavirus experience in Mexico: discovery to control.

The recent introduction of a rotavirus vaccine program in Mexico to control rotavirus disease, a common killer of children worldwide, has dramatically reduced the number of Mexican children dying and being hospitalized because of diarrhea. The successful introduction of a rotavirus vaccine program was preceded by several decades of focused research efforts to document the burden of disease and to generate the knowledge base to develop and deploy a vaccine. The postlicensure experience from Mexico demonstrates that evaluating the impact and safety of the vaccination program is vitally necessary for sustaining it. All in all, the immensely successful Mexico experience with control of rotavirus disease, if copied, could yield tremendously favorable results for children and parents worldwide.

Understanding reduced rotavirus vaccine efficacy in low socio-economic settings.

INTRODUCTION: Rotavirus vaccine efficacy ranges from >90% in high socio-economic settings (SES) to 50% in low SES. With the imminent introduction of rotavirus vaccine in low SES countries, understanding reasons for reduced efficacy in these settings could identify strategies to improve vaccine performance. METHODS: We developed a mathematical model to predict rotavirus vaccine efficacy in high, middle and low SES based on data specific for each setting on incidence, protection conferred by natural infection and immune response to vaccination. We then examined factors affecting efficacy. RESULTS: Vaccination was predicted to prevent 93%, 86% and 51% of severe rotavirus gastroenteritis in high, middle and low SES, respectively. Also predicted was that vaccines are most effective against severe disease and efficacy declines with age in low but not high SES. Reduced immunogenicity of vaccination and reduced protection conferred by natural infection are the main factors that compromise efficacy in low SES. DISCUSSION: The continued risk of severe disease in non-primary natural infections in low SES is a key factor underpinning reduced efficacy of rotavirus vaccines. Predicted efficacy was remarkably consistent with observed clinical trial results from different SES, validating the model. The phenomenon of reduced vaccine efficacy can be predicted by intrinsic immunological and epidemiological factors of low SES populations. Modifying aspects of the vaccine (e.g. improving immunogenicity in low SES) and vaccination program (e.g. additional doses) may bring improvements.