Clinical Outcomes With Electronic Nudges to Increase Influenza Vaccination : A Prespecified Analysis of a Nationwide, Pragmatic, Registry-Based, Randomized Implementation Trial.

BACKGROUND: In the NUDGE-FLU (Nationwide Utilization of Danish Government Electronic letter system for increasing inFLUenza vaccine uptake) trial, electronic letters incorporating cardiovascular (CV) gain-framing and repeated messaging increased influenza vaccination by approximately 1 percentage point. OBJECTIVE: To evaluate the effects of the successful nudging interventions on downstream clinical outcomes. DESIGN: Prespecified exploratory analysis of a nationwide randomized implementation trial. (ClinicalTrials.gov: NCT05542004). SETTING: The 2022 to 2023 influenza season. PARTICIPANTS: 964 870 Danish citizens aged 65 years or older. INTERVENTION: Usual care or 9 different electronically delivered behavioral nudging letters. MEASUREMENTS: Cardiovascular, respiratory, and other clinical end points during follow-up from intervention delivery (16 September 2022) through 31 May 2023. RESULTS: The analysis set included 691 820 participants. Hospitalization for pneumonia or influenza occurred in 3354 of 346 327 (1.0%) participants in the usual care group, 396 of 38 586 (1.0%) in the CV gain-framing group (hazard ratio [HR], 1.06 [95% CI, 0.95 to 1.18]; versus usual care), and 403 of 38 231 (1.1%) in the repeated letter group (HR, 1.09 [CI, 0.98 to 1.21]; versus usual care). In the usual care group, 44 682 (12.9%) participants were hospitalized for any cause, compared with 5002 (13.0%) in the CV gain-framing group (HR, 1.00 [CI, 0.97 to 1.03]; versus usual care) and 4965 (13.0%) in the repeated letter group (HR, 1.01 [CI, 0.98 to 1.04]; versus usual care). A total of 6341 (1.8%) participants died in the usual care group, compared with 721 (1.9%) in the CV gain-framing group (HR, 1.02 [CI, 0.94 to 1.10]; versus usual care) and 646 (1.7%) in the repeated letter group (HR, 0.92 [CI, 0.85 to 1.00]; versus usual care). LIMITATION: Prespecified but exploratory analysis, potential misclassification of events in routinely collected registry data, and results may not be generalizable to other health systems or countries with other racial compositions and/or cultural or societal norms. CONCLUSION: In a prespecified exploratory analysis, modest increases in influenza vaccination rates seen with electronic nudges did not translate into observable improvements in clinical outcomes. Seasonal influenza vaccination should remain strongly recommended. PRIMARY FUNDING SOURCE: Sanofi.

Electronically Delivered Nudges to Increase Influenza Vaccination Uptake in Older Adults With Diabetes: A Secondary Analysis of the NUDGE-FLU Trial.

Importance: Influenza vaccination is associated with a reduced risk of mortality in patients with diabetes, but vaccination rates remain suboptimal. Objective: To assess the effect of electronic nudges on influenza vaccination uptake according to diabetes status. Design, Setting, and Participants: The NUDGE-FLU (Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake) trial was a nationwide clinical trial of Danish citizens 65 years or older that randomized participants at the household level to usual care or 9 different electronic nudge letters during the 2022 to 2023 influenza season. End of follow-up was January 1, 2023. This secondary analysis of the NUDGE-FLU trial was performed from May to July 2023. Intervention: Nine different electronic nudge letters designed to boost influenza vaccination were sent in September to October 2022. Effect modification by diabetes status was assessed in a pooled analysis of all intervention arms vs usual care and for individual letters. Main Outcomes and Measures: The primary end point was receipt of a seasonal influenza vaccine. Results: The trial included 964 870 participants (51.5% female; mean [SD] age, 73.8 [6.3] years); 123 974 had diabetes. During follow-up, 83.5% with diabetes vs 80.2% without diabetes received a vaccine (P < .001). In the pooled analysis, nudges improved vaccination uptake in participants without diabetes (80.4% vs 80.0%; difference, 0.37 percentage points; 99.55% CI, 0.08 to 0.66), whereas there was no evidence of effect in those with diabetes (83.4% vs 83.6%; difference, -0.19 percentage points; 99.55% CI, -0.89 to 0.51) (P = .02 for interaction). In the main results of NUDGE-FLU, 2 of the 9 behaviorally designed letters (cardiovascular benefits letter and a repeated letter) significantly increased uptake of influenza vaccination vs usual care; these benefits similarly appeared attenuated in participants with diabetes (cardiovascular gain letter: 83.7% vs 83.6%; difference, 0.04 percentage points; 99.55% CI, -1.52 to 1.60; repeated letter: 83.5% vs 83.6%; difference, -0.15 percentage points; 99.55% CI, -1.71 to 1.41) vs those without diabetes (cardiovascular gain letter: 81.1% vs 80.0%; difference, 1.06 percentage points; 99.55% CI, 0.42 to 1.70; repeated letter: 80.9% vs 80.0%; difference, 0.87 percentage points; 99.55% CI, 0.22 to 1.52) (P = .07 for interaction). Conclusions and Relevance: In this exploratory subgroup analysis, electronic nudges improved influenza vaccination uptake in persons without diabetes, whereas there was no evidence of an effect in persons with diabetes. Trials are needed to investigate the effect of digital nudges specifically tailored to individuals with diabetes. Trial Registration: ClinicalTrials.gov Identifier: NCT05542004.

Electronic nudges to increase influenza vaccination uptake among patients with heart failure: A pre-specified analysis of the NUDGE-FLU trial.

AIMS: Seasonal influenza vaccination is strongly recommended in patients with heart failure (HF). The NUDGE-FLU trial recently found two electronic behavioural nudging letter strategies - a letter highlighting potential cardiovascular benefits of vaccination and a repeated letter at day 14 -effective in increasing influenza vaccination in Denmark. The aims of this pre-specified analysis was to further examine vaccination patterns and effects of these behavioural nudges in patients with HF including potential off-target effects on guideline-directed medical therapy (GDMT) use. METHODS AND RESULTS: The nationwide NUDGE-FLU trial randomized 964 870 Danish citizens ≥65 years to usual care or nine different electronic nudging letter strategies. Letters were delivered through the official Danish electronic letter system. The primary endpoint was the receipt of an influenza vaccine; additional outcomes for this analysis included GDMT use. In this analysis, we also assessed influenza vaccination rates in the overall Danish HF population including those <65 years (n = 65 075). During the 2022-2023 season, influenza vaccination uptake was 71.6% in the overall Danish HF population but this varied considerably with only 44.6% uptake in those <65 years. A total of 33 109 NUDGE-FLU participants had HF at baseline. Vaccination uptake was higher among those on higher levels of baseline GDMT (≥3 classes: 85.3% vs. ≤2 classes: 81.9%; p < 0.001). HF status did not modify the effects of the two overall successful nudging strategies on influenza vaccination uptake (cardiovascular gain-framed letter: pinteraction = 0.37; repeated letter: pinteraction = 0.55). No effect modification was observed across GDMT use levels for the repeated letter (pinteraction = 0.88), whereas a trend towards attenuated effect among those on low levels of GDMT was observed for the cardiovascular gain-framed letter (pinteraction = 0.07). The letters had no impact on longitudinal GDMT use. CONCLUSIONS: Approximately one in four patients with HF did not receive influenza vaccination with a pronounced implementation gap in those <65 years where less than half were vaccinated. HF status did not modify the effectiveness of cardiovascular gain-framed and repeated electronic nudging letters in increasing influenza vaccination rates. No unintended negative effects on longitudinal GDMT use were observed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT05542004.

Effect of Electronic Nudges on Influenza Vaccination Rate in Older Adults With Cardiovascular Disease: Prespecified Analysis of the NUDGE-FLU Trial.

BACKGROUND: Influenza vaccines have been demonstrated to effectively reduce the incidence of influenza infection and potentially associated risks of cardiovascular events in patients with cardiovascular disease (CVD). Despite strong guideline and public health endorsements, global influenza vaccination rates in patients with CVD are highly variable. This prespecified analysis of NUDGE-FLU (Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake) examined the effect of digital behavioral nudges on influenza vaccine uptake based on the presence of CVD. METHODS: NUDGE-FLU was a randomized, pragmatic, nationwide, register-based trial that included Danish citizens 65 years of age or older during the 2022 to 2023 influenza season. Households were randomized in a 9:1:1:1:1:1:1:1:1:1 ratio to usual care or 9 electronic letters with designs based on behavioral concepts. Danish nationwide registers were used to collect baseline and outcome data. The primary end point was receipt of an influenza vaccine on or before January 1, 2023. The effects of the intervention letters were examined according to the presence of CVD and across cardiovascular subgroups that included heart failure, ischemic heart disease, and atrial fibrillation. RESULTS: Of 964 870 NUDGE-FLU participants from 691 820 households, 264 392 (27.4%) had CVD. During follow-up, 83.1% of participants with CVD versus 79.2% of participants without CVD received an influenza vaccination (P<0.001). Compared with usual care, a letter emphasizing the potential cardiovascular benefits of influenza vaccination increased vaccination rates; this effect was consistent in participants with CVD (absolute difference, +0.60 percentage points [99.55% CI, -0.48 to 1.68]) and without CVD (+0.98 percentage points [99.55% CI, 0.27-1.70; P for interaction=0.41). A repeated letter strategy with a reminder follow-up letter 14 days later was also effective in increasing influenza vaccination, irrespective of CVD (CVD: absolute difference, +0.80 percentage points [99.55% CI, -0.27 to 1.86]; no CVD: +0.67 percentage points [99.55% CI, -0.06 to 1.40]; P for interaction=0.77). Effectiveness of both nudging strategies was consistent across all major CVD subgroups. None of the other 7 nudging strategies were effective, regardless of CVD status. CONCLUSIONS: Electronic letter interventions emphasizing the potential cardiovascular benefits of influenza vaccination and using a reminder letter strategy were similarly beneficial in increasing influenza vaccination rates among older adults with and without CVD and across cardiovascular subgroups. Electronic nudges may improve influenza vaccine uptake in individuals with CVD. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05542004.

Electronic nudges to increase influenza vaccination uptake in Denmark: a nationwide, pragmatic, registry-based, randomised implementation trial.

BACKGROUND: Influenza vaccination rates remain suboptimal despite effectiveness in preventing influenza infection and related complications. We investigated whether behavioural nudges, delivered via a governmental electronic letter system, would increase influenza vaccination uptake among older adults in Denmark. METHODS: We did a nationwide, pragmatic, registry-based, cluster-randomised implementation trial during the 2022-23 influenza season in Denmark. All Danish citizens aged 65 years or older or turning 65 years by Jan 15, 2023 were included. We excluded individuals living in nursing homes and individuals who had an exemption from the Danish mandatory governmental electronic letter system. Households were randomly assigned (9:1:1:1:1:1:1:1:1:1) to usual care or nine different electronic letters designed on the basis of different behavioural nudging concepts. Data were sourced from nationwide Danish administrative health registries. The primary endpoint was receipt of influenza vaccination on or before Jan 1, 2023. The primary analysis assessed an analytical set of one randomly selected individual per household, and a sensitivity analysis included all randomly assigned individuals and accounted for within-household correlation. The trial is registered with ClinicalTrials.gov, NCT05542004. FINDINGS: We identified 1 232 938 individuals aged 65 years or older in Denmark and excluded 56 436 (4·6%) individuals living in nursing homes and 211 632 (17·2%) with an exemption from the electronic letter system. We randomly assigned 964 870 (78·3%) participants across 691 820 households. Compared with usual care, influenza vaccination rates were higher in the group receiving an electronic letter highlighting potential cardiovascular benefits of vaccination (81·00% vs 80·12%; difference 0·89 percentage points [99·55% CI 0·29-1·48]; p<0·0001) and the group receiving repeated letters at randomisation and at day 14 (80·85% vs 80·12%; difference 0·73 percentage points [0·13-1·34]; p=0·0006). These strategies improved vaccination rates across major subgroups including those with and without established cardiovascular disease. The cardiovascular gain-framed letter was particularly effective among participants who had not been vaccinated for influenza in the previous season (pinteraction=0·0002). A sensitivity analysis of all randomly assigned individuals accounting for within-household clustering yielded similar findings. INTERPRETATION: Electronically delivered letters highlighting potential cardiovascular benefits of influenza vaccination or sent again as a reminder significantly increased vaccination uptake across Denmark. Although the magnitude of effectiveness was modest, the low-touch, inexpensive, and highly scalable nature of these electronic letters might be informative for future public health campaigns. FUNDING: Sanofi.

Nationwide Utilization of Danish Government Electronic letter system for increasing inFLUenza vaccine uptake (NUDGE-FLU): Study protocol for a nationwide randomized implementation trial.

BACKGROUND: Annual influenza vaccination is widely recommended in older adults and other high-risk groups including patients with cardiovascular disease. The real-world effectiveness of influenza vaccination is limited by suboptimal uptake and effective strategies for increasing vaccination rates are therefore needed. The purpose of this trial is to investigate whether behavioral nudges digitally delivered via the Danish nationwide mandatory governmental electronic letter system can increase influenza vaccination uptake among older adults. METHODS: The NUDGE-FLU trial is a randomized implementation trial randomizing all Danish citizens aged 65 years and above without an exemption from the Danish mandatory governmental electronic letter system to receive no digitally delivered behavioral nudge (usual care arm) or to receive one of 9 electronic letters (intervention arms) each leveraging different behavioral science strategies. The trial has randomized 964,870 participants with randomization clustered at the household level (n = 691,820 households). Intervention letters were delivered on September 16, 2022, and follow-up is currently ongoing. All trial data are captured using the nationwide Danish administrative health registries. The primary end point is the receipt of an influenza vaccine on or before January 1, 2023. The secondary end point is time to vaccination. Exploratory end points include clinical events such as hospitalization for influenza or pneumonia, cardiovascular events, all-cause hospitalization, and all-cause mortality. DISCUSSION: The nationwide randomized NUDGE-FLU trial is one of the largest implementation trials ever conducted and will provide important insights into effective communication strategies to maximize vaccination uptake among high-risk groups. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05542004, registered September 15, 2022, https://clinicaltrials.gov/ct2/show/NCT05542004.

National burden of influenza-associated hospitalizations in Cambodia, 2015 and 2016.

INTRODUCTION: The burden of influenza in Cambodia is not well known, but it would be useful for understanding the impact of seasonal epidemics and pandemics and to design appropriate policies for influenza prevention and control. The severe acute respiratory infection (SARI) surveillance system in Cambodia was used to estimate the national burden of SARI hospitalizations in Cambodia. METHODS: We estimated age-specific influenza-associated SARI hospitalization rates in three sentinel sites in Svay Rieng, Siem Reap and Kampong Cham provinces. We used influenza-associated SARI surveillance data for one year to estimate the numerator and hospital admission surveys to estimate the population denominator for each site. A national influenza-associated SARI hospitalization rate was calculated using the pooled influenza-associated SARI hospitalizations for all sites as a numerator and the pooled catchment population of all sites as denominator. National influenza-associated SARI case counts were estimated by applying hospitalization rates to the national population. RESULTS: The national annual rates of influenza-associated hospitalizations per 100 000 population was highest for the two youngest age groups at 323 for < 1 year and 196 for 1-4 years. We estimated 7547 influenza-associated hospitalizations for Cambodia with almost half of these represented by children younger than 5 years. DISCUSSION: We present national estimates of influenza-associated SARI hospitalization rates for Cambodia based on sentinel surveillance data from three sites. The results of this study indicate that the highest burden of severe influenza infection is borne by the younger age groups. These findings can be used to guide future strategies to reduce influenza morbidity.

Viral etiology, seasonality and severity of hospitalized patients with severe acute respiratory infections in the Eastern Mediterranean Region, 2007-2014.

INTRODUCTION: Little is known about the role of viral respiratory pathogens in the etiology, seasonality or severity of severe acute respiratory infections (SARI) in the Eastern Mediterranean Region. METHODS: Sentinel surveillance for SARI was conducted from December 2007 through February 2014 at 20 hospitals in Egypt, Jordan, Oman, Qatar and Yemen. Nasopharyngeal and oropharyngeal swabs were collected from hospitalized patients meeting SARI case definitions and were analyzed for infection with influenza, respiratory syncytial virus (RSV), adenovirus (AdV), human metapneumovirus (hMPV) and human parainfluenza virus types 1-3 (hPIV1-3). We analyzed surveillance data to calculate positivity rates for viral respiratory pathogens, describe the seasonality of those pathogens and determine which pathogens were responsible for more severe outcomes requiring ventilation and/or intensive care and/or resulting in death. RESULTS: At least one viral respiratory pathogen was detected in 8,753/28,508 (30.7%) samples tested for at least one pathogen and 3,497/9,315 (37.5%) of samples tested for all pathogens-influenza in 3,345/28,438 (11.8%), RSV in 3,942/24,503 (16.1%), AdV in 923/9,402 (9.8%), hMPV in 617/9,384 (6.6%), hPIV1 in 159/9,402 (1.7%), hPIV2 in 85/9,402 (0.9%) and hPIV3 in 365/9,402 (3.9%). Multiple pathogens were identified in 501/9,316 (5.4%) participants tested for all pathogens. Monthly variation, indicating seasonal differences in levels of infection, was observed for all pathogens. Participants with hMPV infections and participants less than five years of age were significantly less likely than participants not infected with hMPV and those older than five years of age, respectively, to experience a severe outcome, while participants with a pre-existing chronic disease were at increased risk of a severe outcome, compared to those with no reported pre-existing chronic disease. CONCLUSIONS: Viral respiratory pathogens are common among SARI patients in the Eastern Mediterranean Region. Ongoing surveillance is important to monitor changes in the etiology, seasonality and severity of pathogens of interest.

Crimean Congo Hemorrhagic Fever Virus and Alkhurma (Alkhumra) Virus in Ticks in Djibouti.

Crimean Congo hemorrhagic fever virus and Alkhumra virus, not previously reported in Djibouti, were detected among 141 (infection rate = 15.7 per 100, 95% CI: 13.4-18.1) tick pools from 81 (37%) cattle and 2 (infection rate = 0.2 per 100, 95% CI: 0.0-0.7) tick pools from 2 (1%) cattle, respectively, collected at an abattoir in 2010 and 2011.

Sentinel surveillance for influenza among severe acute respiratory infection and acute febrile illness inpatients at three hospitals in Ghana.

BACKGROUND: Influenza epidemiology in Africa is generally not well understood. Using syndrome definitions to screen patients for laboratory confirmation of infection is an established means to effectively conduct influenza surveillance. METHODS: To compare influenza-related epidemiologic data, from October 2010 through March 2013, we enrolled hospitalized severe acute respiratory infection (SARI; fever with respiratory symptoms) and acute febrile illness (AFI; fever without respiratory or other localizing symptoms) patients from three referral hospitals in Ghana. Demographic and epidemiologic data were obtained from enrolled patients after which nasopharyngeal and oropharyngeal swabs were collected, and processed by molecular methods for the presence of influenza viruses. RESULTS: Of 730 SARI patients, 59 (8%) were influenza positive; of 543 AFI patients, 34 (6%) were positive for influenza. Both SARI and AFI surveillance yielded influenza A(H3N2) (3% versus 1%), A(H1N1)pdm09 (2% versus 1%), and influenza B (3% versus 4%) in similar proportions. Data from both syndromes show year-round influenza transmission but with increased caseloads associated with the rainy seasons. CONCLUSIONS: As an appreciable percentage of influenza cases (37%) presented without defined respiratory symptoms, and thus met the AFI but not the SARI definition, it is important to consider broader screening criteria (i.e., AFI) to identify all laboratory-confirmed influenza. The identified influenza transmission seasonality has important implications for the timing of related public health interventions.

The Burden of Influenza-Associated Hospitalizations in Oman, January 2008-June 2013.

INTRODUCTION: Acute respiratory infections (ARI), including influenza, comprise a leading cause of morbidity and mortality worldwide. Influenza surveillance provides important information to inform policy on influenza control and vaccination. While the epidemiology of influenza has been well characterized in western countries, few data exist on influenza epidemiology in the Eastern Mediterranean Region. We describe the epidemiology of influenza virus in Oman. METHODS: Using syndromic case definitions and protocols, patients from four regional hospitals in Oman were enrolled in a descriptive prospective study to characterize the burden of severe acute respiratory infections (SARI) and influenza. Eligible patients provided demographic information as well as oropharyngeal (OP) and nasopharyngeal (NP) swabs. Specimens were tested for influenza A and influenza B; influenza A viruses were subtyped using RT-PCR. RESULTS: From January 2008 through June 2013, a total of 5,147 cases were enrolled and tested for influenza. Influenza strains were detected in 8% of cases for whom samples were available. Annual incidence rates ranged from 0.5 to 15.4 cases of influenza-associated SARI per 100,000 population. The median age of influenza patients was 6 years with children 0-2 years accounting for 34% of all influenza-associated hospitalizations. By contrast, the median age of non-influenza SARI cases was 1 year with children 0-2 years comprising 59% of SARI. Compared to non-influenza SARI cases, a greater proportion of influenza cases had pre-existing chronic conditions and underwent ventilation during hospitalization. CONCLUSIONS: Influenza virus is associated with a substantial proportion of SARI in Oman. Influenza in Oman approximately follows northern hemisphere seasonality, with major peaks in October to December and a lesser peak around April. The burden of influenza was greatest in children and the elderly. Future efforts should examine the burden of influenza in other potential risk groups such as pregnant women to inform interventions including targeted vaccination.

Culture- and antigen-negative meningitis in Guatemalan children / Meningitis negativa a pruebas antigénicas y de cultivo en niños guatemaltecos

OBJECTIVE: To compare children with confirmed bacterial meningitis (CBM) and those with culture- and latex-negative meningitis (CLN). METHODS: Children 1 to 59 months of age admitted to three major referral hospitals in Guatemala City with clinical signs compatible with bacterial infections were evaluated prospectively between 1 October 1996 and 31 December 2005. Bacterial cultures and latex agglutination antigen testing were performed on samples of cerebrospinal fluid (CSF). RESULTS: The case-fatality rate was significantly higher in the 493 children with CBM than in the 528 children with CLN (27.6 percent and 14.9 percent, respectively; P < 0.001). Children with CBM were less likely to have received antibiotics and more likely to have seizures, shock, or coma on admission than children with CLN. Among the 182 CBM survivors and 205 CLN survivors studied between October 2000 and December 2005, clinically observed sequelae were present at discharge in a higher percentage of the CBM than of the CLN group (78.6 percent and 46.8 percent, respectively; P < 0.0001). CSF glucose < 10 mg/dL, peripheral neutrophils < 2 000 cells/mm³, coma or shock at admission, and concurrent sepsis or pneumonia were risk factors for mortality in children with CBM; only coma or shock at admission predicted mortality in children with CLN. CONCLUSIONS: The high case-fatality and sequelae rates suggest that many children with CLN may have had bacterial meningitis. Estimates based on confirmed meningitis alone underestimate the true vaccine-preventable disease burden. Additional studies to determine etiologies of CLN in this population are indicated.

OBJETIVO: Comparar los casos infantiles de meningitis bacteriana confirmada (MBC) y meningitis negativa a pruebas de látex y de cultivo (MNLC). MÉTODOS: Se evaluaron los niños de 1 a 59 meses de edad ingresados en tres grandes hospitales de referencia de la Ciudad de Guatemala entre el 1 de octubre de 1996 y el 31 de diciembre de 2005 con signos clínicos de infección bacteriana. Se realizaron cultivos bacterianos y pruebas de aglutinación antigénica con látex en muestras de líquido cefalorraquídeo (LCR). RESULTADOS: La tasa de letalidad fue significativamente mayor en los 493 niños con MBC que en los 528 niños con MNLC (27,6 por ciento y 14,9 por ciento, respectivamente; P < 0,001). Los niños con MBC tuvieron menor probabilidad de recibir antibióticos y mayor de sufrir convulsiones, choques o entrar en coma al ser ingresados que los niños con MNLC. Se observó un mayor porcentaje de manifestaciones clínicas de secuelas al alta hospitalaria en los 182 niños sobrevivientes con MBC que en los 205 sobrevivientes con MNLC estudiados entre octubre de 2000 y diciembre de 2005 (78,6 por ciento y 46,8 por ciento, respectivamente; P < 0,0001). Los factores de riesgo de muerte en los niños con MBC fueron: glucosa en LCR < 10 mg/dL, neutrófilos periféricos < 2 000 células/mm³, coma o choque al ingreso, y sepsis o neumonía concurrentes; solo el coma y el choque al ingreso predijeron la muerte en niños con MNLC. CONCLUSIONES: Las altas tasas de letalidad y de secuelas indican que muchos niños con MNLC pueden haber tenido meningitis bacteriana. Las estadísticas basadas solamente en los casos confirmados de meningitis subestiman la verdadera carga de enfermedad prevenible mediante vacuna. Se deben emprender estudios adicionales para determinar las etiologías de la MNLC en esta población.

Increasing penicillin and trimethoprim-sulfamethoxazole resistance in nasopharyngeal Streptococcus pneumoniae isolates from Guatemalan children, 2001--2006.

OBJECTIVES: We aimed to determine nasopharyngeal colonization rates and antibiotic resistance patterns of Streptococcus pneumoniae isolated from Guatemalan children, and to determine risk factors for colonization and antibiotic nonsusceptibility. METHODS: Isolates were obtained from children aged 5 to 60 months attending public and private outpatient clinics and daycare centers during August 2001--June 2002 and outpatient clinics during November 2005--February 2006 in Guatemala City. Minimal inhibitory concentrations of penicillin, trimethoprim-sulfamethoxazole (TMS), cefotaxime, and erythromycin were determined using the E-test. RESULTS: The overall nasopharyngeal colonization rate for S. pneumoniae was 59.1%. From 2001/2 to 2005/6 TMS nonsusceptibility increased from 42.4% to 60.8% (p<0.05) in public clinics and from 51.4% to 84.0% (p=0.009) in private clinics, and penicillin nonsusceptibility increased from 1.5% to 33.3% in public clinics (p<0.001). Reported antibiotic use was not strictly associated with nonsusceptibility to that same antibiotic. Resistance to three or four antibiotics increased in public clinics from 2001/2 (0%) to 2005/6 (10.7%; p<0.001). Risk factors for nasopharyngeal colonization with penicillin- or TMS-nonsusceptible S. pneumoniae were low family income, daycare center attendance, and recent penicillin use. CONCLUSIONS: Increasing antibiotic nonsusceptibility rates in nasopharyngeal S. pneumoniae isolates from Guatemalan children reflect worldwide trends. Policies encouraging more judicious use of TMS should be considered.

Culture- and antigen-negative meningitis in Guatemalan children.

OBJECTIVE: To compare children with confirmed bacterial meningitis (CBM) and those with culture- and latex-negative meningitis (CLN). METHODS: Children 1 to 59 months of age admitted to three major referral hospitals in Guatemala City with clinical signs compatible with bacterial infections were evaluated prospectively between 1 October 1996 and 31 December 2005. Bacterial cultures and latex agglutination antigen testing were performed on samples of cerebrospinal fluid (CSF). RESULTS: The case-fatality rate was significantly higher in the 493 children with CBM than in the 528 children with CLN (27.6% and 14.9%, respectively; P < 0.001). Children with CBM were less likely to have received antibiotics and more likely to have seizures, shock, or coma on admission than children with CLN. Among the 182 CBM survivors and 205 CLN survivors studied between October 2000 and December 2005, clinically observed sequelae were present at discharge in a higher percentage of the CBM than of the CLN group (78.6% and 46.8%, respectively; P < 0.0001). CSF glucose < 10 mg/dL, peripheral neutrophils < 2 000 cells/mm(3), coma or shock at admission, and concurrent sepsis or pneumonia were risk factors for mortality in children with CBM; only coma or shock at admission predicted mortality in children with CLN. CONCLUSIONS: The high case-fatality and sequelae rates suggest that many children with CLN may have had bacterial meningitis. Estimates based on confirmed meningitis alone underestimate the true vaccine-preventable disease burden. Additional studies to determine etiologies of CLN in this population are indicated.

Randomized trial of inactivated and live polio vaccine schedules in Guatemalan infants.

BACKGROUND: The immunogenicity of inactivated poliovirus vaccine (IPV) in developing countries is not well documented. This study compared the immune response to IPV with that to oral poliovirus vaccine (OPV) in Guatemalan infants. METHODS: This was an open-label, randomized comparison of IPV only, OPV only, or IPV followed by OPV in Guatemalan public health clinics. Serum samples were tested for neutralizing antibodies, and stool samples were tested for Sabin strain polioviruses. RESULTS: Seropositivity rates 2 months after 2 doses of IPV were 98%-100% for polio types 1, 2, and 3 and were 97.1%, 99.3%, and 92.1% for OPV-only recipients (P<.001 for the response to type 3). One month after the third dose, 100% of IPV-only recipients had protective antibodies against all 3 types, compared with 99%, 100%, and 97% against polio types 1, 2, and 3 respectively, among recipients of OPV only. Infants who received IPV only had higher geometric mean titers than infants who received OPV only. Maternal antibodies lowered the final antibody responses to IPV but did not prevent the development of protective levels of antibody. Of 191 stool samples from infants who received IPV only, 5 (2.6%) were positive for poliovirus vaccine strains. CONCLUSIONS: IPV alone and IPV followed by OPV are safe and effective for Guatemalan infants.

Efficacy of a long-acting formulation of ceftiofur crystalline-free acid for the treatment of naturally occurring infectious bovine keratoconjunctivitis.

OBJECTIVE: To evaluate the efficacy of ceftiofur crystalline-free acid (CCFA) administered into the posterior aspect of an ear for treatment of corneal ulceration associated with naturally occurring infectious bovine keratoconjunctivitis (IBK). ANIMALS: 78 beef calves located at Sierra Foothills Field Station (SFS) and 52 calves located at a commercial dairy (CD). All calves were from 3 to 9 months old. PROCEDURE: At each site, calves were randomly allocated to 1 of 2 treatment groups by use of a block design determined by corneal ulcer size. A single dose of CCFA (6.6 mg of ceftiofur equivalents/kg, s.c.) was administered into the posterior aspect of a pinna. A second group of calves received a single dose of vehicle (0.03 mL/kg, s.c.; controls). Corneal ulcers were photographed, and clinical signs were assessed in calves every 3 to 4 days for 21 days. RESULTS: A positive treatment effect was detected at SFS. Results at the CD were inconclusive because ulcer healing occurred rapidly in control and CCFA-treated calves. At SFS, treatment with CCFA resulted in shorter mean healing times, smaller corneal ulcer surface area measurements, amelioration of ocular discharge and photophobia, and a 50% increase in the percentage of calves healed by day 14. After adjustment for initial corneal ulcer size, treatment with CCFA resulted in a 4-fold increase in the odds of corneal ulcer healing by day 14, compared with controls. CONCLUSIONS AND CLINICAL RELEVANCE: A single dose of CCFA administered into the posterior aspect of a pinna had a positive treatment effect against naturally occurring IBK in calves with corneal ulcerations.

Evaluation of the enzyme-linked immunoelectrotransfer blot (EITB) for ovine hydatidosis relative to age and cyst characteristics in naturally infected sheep.

An enzyme-linked immunoelectrotransfer blot (EITB) for ovine echinococcosis was evaluated in an endemic area of the Peruvian central sierra. An overall test sensitivity of 91.4% was determined for 199 sheep. EITB sensitivity reached a plateau of nearly 100% at 3 years of age, while the prevalence of cystic disease peaked at 95% in sheep >/=6 years of age. In this highly endemic area, 61.7% of sheep without detectable cystic disease at necropsy (n=47) had positive EITB results. Relationships between EITB sensitivity, age, and cyst location, size, number, type, fertility, and viability were evaluated with logistic regression models. EITB sensitivity increased 14-fold in sheep with calcified cysts and 4-fold for each 1cm increase in pulmonary cyst size.