Pooling of six respiratory samples for the detection of SARS-CoV-2: A validation and cost study in a cohort in Lima, Peru.

Background: The continuous evolution of the SARS-CoV-2 pandemic has led to a high demand for diagnostic testing and major shortages in testing materials, especially in low- and middle-income countries. As an alternative to testing individual samples, pooling of respiratory samples has been suggested. Previous studies have assessed performance of pooling, mainly using nasopharyngeal samples for the detection of SARS-CoV-2, but few studies have examined the performance of pooling the more practical nasal swabs or saliva samples. Objective: To evaluate the sensitivity, specificity, and potential cost reduction of pooling of nasal swab (NS) and saliva (SL) samples for detection of SARS-CoV-2 in a community-based cohort study in Lima, Peru. Study design: A prospective cohort study was conducted in a community setting in San Juan de Lurigancho, Lima-Peru. NS and SL samples were collected from 132 participants twice-a-week for a 2-month period. Pools of 2 to 12 samples of the same type, from participants of the same household, were tested by RT-PCR. After pooled testing, all individual samples from positive pools and all individual samples from randomly chosen negative pools were evaluated. For assessment of diagnostic performance, pool testing results were compared with results from individual testing, which served as reference, and concordance in pooled and individual test detections was evaluated. Laboratory costs for both types of samples and testing were compared. Results: A total of 2008 NS and 2002 SL samples were collected from 132 study participants. We tested 329 NS and 333 SL pools. The mean pool size for NS and SL pools was 6.22 (SD = 0.92) and 6.39 (SD = 1.71), respectively. Using individual testing as reference, NS pooling of 6 had a sensitivity and specificity of 94% and 100%, respectively, with kappa of 0.97 (CI 95%: 0.93-1.00). The corresponding values for SL pooling of 6 were 83%, 100%, and 0.90 (CI 95%: 0.83-0.97). Compared with individual testing, pooling resulted in a cost reduction of 74.8% for NS and 72.4% for SL samples. Conclusions: Pooling easy-to-collect respiratory samples, especially NS, demonstrated very high diagnostic performance for detection of SARS-CoV-2 with substantial cost savings. This approach could be considered in large population screening programs, especially in LMIC.

Short-, mid-, and long-term complications after multisystem inflammatory syndrome in children over a 24-month follow-up period in a hospital in Lima-Peru, 2020-2022.

Objective: To determine the short-, mid-, and long-term complications after multisystem inflammatory syndrome in children (MIS-C) over a 24-month follow-up period in a hospital in Lima, Peru, 2020-2022, and to explore differences according to the immunomodulatory treatment received and type of SARS-CoV-2 virus circulating. Methods: Ambispective 24-month follow-up study in children <14 years of age diagnosed with MIS-C at the Hospital Nacional Edgardo Rebagliati Martins (HNERM). Results: A total of 62 children were admitted with MIS-C. The most common short-term complications and serious events were intensive care unit (ICU) admission, invasive mechanical ventilation (IMV) due to respiratory failure, and shock; predominantly during the second pandemic wave (lambda predominance) and in children that received intravenous immunoglobulin (IVIG) plus a corticosteroid. Two patients died during the first wave due to MIS-C. During prospective follow-up (median of 24 months; IQR: 16.7-24), only 46.7% of patients were followed for >18-24 months. Of the total, seven (11.3%) patients were identified with some sequelae on discharge. Among the 43 remaining children, sequelae persisted in five (11.6%) cases (neurological, hematological, and skin problems). Six patients (13.9%) presented with new onset disease (hematologic, respiratory, neurological, and psychiatric disorders). One patient died due to acute leukemia during the follow-up period. None of them were admitted to the ICU or presented with MIS-C reactivation. Two patients presented persistence of coronary aneurysm until 8- and 24-month post-discharge. Conclusion: In our hospital, children with MIS-C frequently developed short-term complications and serious events during the acute phase, with less frequent complications in the mid- and long-term. More studies are required to confirm these findings.

Corrigendum to "Safety and immunogenicity of mRNA-LNP COVID-19 vaccine CVnCoV in Latin American adults: A phase 2 randomized study" [Vaccine: X 11 (2022) 100189].

[This corrects the article DOI: 10.1016/j.jvacx.2022.100189.].

Concordance in RT-PCR detection of SARS-CoV-2 between samples preserved in viral and bacterial transport medium.

BACKGROUND: While the detection of SARS-CoV-2 in samples preserved in viral transport medium (VTM) by RT-PCR is a standard diagnostic method, this may preclude the study of bacterial respiratory pathogens from the same specimen. It is unclear if the use of skim milk, tryptone, glucose, and glycerin (STGG) transport media, used for study of respiratory bacteria, allows an efficient and concurrent study of SARS-CoV-2 infections. OBJECTIVES: To determine the concordance in SARS-CoV-2 detection by real time RT-PCR between paired nasopharyngeal (NP) swabs preserved in STGG and nasal (NS) swabs preserved in VTM. STUDY DESIGN: Paired samples of NP and NS swabs were collected between December 2020 and March 2021 from a prospective longitudinal cohort study of 44 households and 132 participants from a peri-urban community (Lima, Peru). NP and NS swabs were taken from all participants once and twice per week, respectively, independent of respiratory symptoms. STGG medium was used for NP samples and VTM for NS samples. Samples were analyzed for SARS-CoV-2 by RT-PCR for N, S and ORF1ab targets. We calculated the concordance in detections between sample types and compared the RT-PCR cycle thresholds (Ct). RESULTS: Among the 148 paired samples, we observed a high concordance in detections between NP and NS samples (agreement = 94.59%; Kappa = 0.79). Median Ct values were statistically similar between sample types for each RT-PCR target: N, S and ORF1ab (p = 0.11, p = 0.71 and p = 0.11, respectively). CONCLUSIONS: NP swabs collected in STGG medium are reliable alternatives to nasal swabs collected in VTM for the study of SARS-CoV-2.

SARS-CoV-2 infections in households in a peri-urban community of Lima, Peru: A prospective cohort study.

BACKGROUND: We assessed the prevalence and incidence of SARS-CoV-2 infections in a prospective study of households in Lima, Peru. METHODS: Households with a child, a young adult 18-50 years, and an adult age >50 years in peri-urban Lima were followed with twice-a-week household visits during a 2-month period. Nasal swabs and saliva specimens were collected twice weekly, and nasopharyngeal swabs were collected weekly from each participant, regardless of symptoms. Laboratory-confirmed SARS-CoV-2 infection was defined by two RT-PCR tests from any of the collected specimens within a week. Blood samples collected at enrollment and end of follow-up were tested with rapid serological tests. We calculated the prevalence and incidence of laboratory-confirmed SARS-CoV-2 infections. RESULTS: We enrolled 132 participants from 44 households: 44 children, 44 young adults, and 44 older adults. A total of 13 SARS-CoV-2 infections were detected in eight households, for an overall period prevalence of 9.85% (95% confidence interval [CI]: 5.35-16.25). Most (61.54%) infections were symptomatic. Eight of 11 (72.73%) SARS-CoV-2 detections corresponded to the Lambda variant. During 218.79 person-months at risk of follow-up, there were six new SARS-CoV-2 infections detected (2.74 per 100 person-month, 95% CI: 1.25-6.04). At enrollment, 59 of 128 participants tested had positive SARS-CoV-2 IgG serology (46.09%, 95% CI: 37.25-55.12). Five of six new infections occurred among participants with negative baseline serology. CONCLUSIONS: We demonstrated high incidence of SARS-CoV-2 infections in households, especially among subjects without evidence of prior infection, most of them not detected by the Ministry of Health system.

Safety and immunogenicity of mRNA-LNP COVID-19 vaccine CVnCoV in Latin American adults: A phase 2 randomized study.

Background: The COVID-19 vaccine candidate CVnCoV comprises sequence-optimized mRNA encoding SARS-CoV-2 S-protein encapsulated in lipid nanoparticles. In this phase 2a study, we assessed reactogenicity and immunogenicity of two or three doses in younger and older adults. Methods: Younger (18-60 years) and older (>60 years) adults were enrolled in two sites in Panama and Peru to receive either 6 or 12 µg doses of CVnCoV or licensed control vaccines 28 days apart; subsets received a 12 µg booster dose on Day 57 or Day 180. Solicited adverse events (AE) were reported for 7 days and unsolicited AEs for 4 weeks after each vaccination, and serious AEs (SAE) throughout the study. Humoral immunogenicity was measured as neutralizing and receptor binding domain (RBD) IgG antibodies and cellular immunogenicity was assessed as CD4+/CD8 + T cell responses. Results: A total of 668 participants were vaccinated (332 aged 18-60 years and 336 aged > 60 years) including 75 who received homologous booster doses. Vaccination was well tolerated with no vaccine-related SAEs. Solicited and unsolicited AEs were mainly mild to moderate and resolved spontaneously. Both age groups demonstrated robust immune responses as neutralizing antibodies or RBD-binding IgG, after two doses, with lower titers in the older age group than the younger adults. Neither group achieved levels observed in human convalescent sera (HCS), but did equal or surpass HCS levels following homologous booster doses. Following CVnCoV vaccination, robust SARS-CoV-2 S-protein-specific CD4 + T-cell responses were observed in both age groups with CD8 + T-cell responses in some individuals, consistent with observations in convalescing COVID-19 patients after natural infection. Conclusions: We confirmed that two 12 µg doses of CVnCoV had an acceptable safety profile, and induced robust immune responses. Marked humoral immune responses to homologous boosters suggest two doses had induced immune memory.

Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial.

BACKGROUND: Additional safe and efficacious vaccines are needed to control the COVID-19 pandemic. We aimed to analyse the efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate. METHODS: HERALD is a randomised, observer-blinded, placebo-controlled, phase 2b/3 clinical trial conducted in 47 centres in ten countries in Europe and Latin America. By use of an interactive web response system and stratification by country and age group (18-60 years and ≥61 years), adults with no history of virologically confirmed COVID-19 were randomly assigned (1:1) to receive intramuscularly either two 0·6 mL doses of CVnCoV containing 12 µg of mRNA or two 0·6 mL doses of 0·9% NaCl (placebo) on days 1 and 29. The primary efficacy endpoint was the occurrence of a first episode of virologically confirmed symptomatic COVID-19 of any severity and caused by any strain from 15 days after the second dose. For the primary endpoint, the trial was considered successful if the lower limit of the CI was greater than 30%. Key secondary endpoints were the occurrence of a first episode of virologically confirmed moderate-to-severe COVID-19, severe COVID-19, and COVID-19 of any severity by age group. Primary safety outcomes were solicited local and systemic adverse events within 7 days after each dose and unsolicited adverse events within 28 days after each dose in phase 2b participants, and serious adverse events and adverse events of special interest up to 1 year after the second dose in phase 2b and phase 3 participants. Here, we report data up to June 18, 2021. The study is registered at ClinicalTrials.gov, NCT04652102, and EudraCT, 2020-003998-22, and is ongoing. FINDINGS: Between Dec 11, 2020, and April 12, 2021, 39 680 participants were enrolled and randomly assigned to receive either CVnCoV (n=19 846) or placebo (n=19 834), of whom 19 783 received at least one dose of CVnCoV and 19 746 received at least one dose of placebo. After a mean observation period of 48·2 days (SE 0·2), 83 cases of COVID-19 occurred in the CVnCoV group (n=12 851) in 1735·29 person-years and 145 cases occurred in the placebo group (n=12 211) in 1569·87 person-years, resulting in an overall vaccine efficacy against symptomatic COVID-19 of 48·2% (95·826% CI 31·0-61·4; p=0·016). Vaccine efficacy against moderate-to-severe COVID-19 was 70·7% (95% CI 42·5-86·1; CVnCoV 12 cases in 1735·29 person-years, placebo 37 cases in 1569·87 person-years). In participants aged 18-60 years, vaccine efficacy against symptomatic disease was 52·5% (95% CI 36·2-64·8; CVnCoV 71 cases in 1591·47 person-years, placebo, 136 cases in 1449·23 person-years). Too few cases occurred in participants aged 61 years or older (CVnCoV 12, placebo nine) to allow meaningful assessment of vaccine efficacy. Solicited adverse events, which were mostly systemic, were more common in CVnCoV recipients (1933 [96·5%] of 2003) than in placebo recipients (1344 [67·9%] of 1978), with 542 (27·1%) CVnCoV recipients and 61 (3·1%) placebo recipients reporting grade 3 solicited adverse events. The most frequently reported local reaction after any dose in the CVnCoV group was injection-site pain (1678 [83·6%] of 2007), with 22 grade 3 reactions, and the most frequently reported systematic reactions were fatigue (1603 [80·0%] of 2003) and headache (1541 [76·9%] of 2003). 82 (0·4%) of 19 783 CVnCoV recipients reported 100 serious adverse events and 66 (0·3%) of 19 746 placebo recipients reported 76 serious adverse events. Eight serious adverse events in five CVnCoV recipients and two serious adverse events in two placebo recipients were considered vaccination-related. None of the fatal serious adverse events reported (eight in the CVnCoV group and six in the placebo group) were considered to be related to study vaccination. Adverse events of special interest were reported for 38 (0·2%) participants in the CVnCoV group and 31 (0·2%) participants in the placebo group. These events were considered to be related to the trial vaccine for 14 (<0·1%) participants in the CVnCoV group and for five (<0·1%) participants in the placebo group. INTERPRETATION: CVnCoV was efficacious in the prevention of COVID-19 of any severity and had an acceptable safety profile. Taking into account the changing environment, including the emergence of SARS-CoV-2 variants, and timelines for further development, the decision has been made to cease activities on the CVnCoV candidate and to focus efforts on the development of next-generation vaccine candidates. FUNDING: German Federal Ministry of Education and Research and CureVac.

Quantitative real-time polymerase chain reaction for enteropathogenic Escherichia coli: a tool for investigation of asymptomatic versus symptomatic infections.

BACKGROUND: Enteropathogenic Escherichia coli (EPEC) strains are pediatric pathogens commonly isolated from both healthy and sick children with diarrhea in areas of endemicity. The aim of this study was to compare the bacterial load of EPEC isolated from stool samples from children with and without diarrhea to determine whether bacterial load might be a useful tool for further study of this phenomenon. METHODS: EPEC was detected by polymerase chain reaction (PCR) of colonies isolated on MacConkey plates from 53 diarrheal and 90 healthy children aged <2 years. DNA was isolated from stool samples by cetyltrimethylammonium bromide extraction. To standardize quantification by quantitative real-time PCR (qRT-PCR), the correlation between fluorescence threshold cycle and copy number of the intimin gene of EPEC E2348/69 was determined. RESULTS: The detection limit of qRT-PCR was 5 bacteria/mg stool. The geometric mean load in diarrhea was 299 bacteria/mg (95% confidence interval [CI], 77-1164 bacteria/mg), compared with 29 bacteria/mg (95% CI, 10-87 bacteria/mg) in control subjects (P = .016). Bacterial load was significantly higher in children with diarrhea than in control subjects among children <12 months of age (178 vs 5 bacteria/mg; P = .006) and among children with EPEC as the sole pathogen (463 vs 24 bacteria/mg; P = .006). CONCLUSIONS: EPEC load measured by qRT-PCR is higher in diarrheal than in healthy children. qRT-PCR may be useful to study the relationship between disease and colonization in settings of endemicity.

Fecal leukocytes in children infected with diarrheagenic Escherichia coli.

The purpose of this study was to determine the presence and quantity of fecal leukocytes in children infected with diarrheagenic Escherichia coli and to compare these levels between diarrhea and control cases. We analyzed 1,474 stool samples from 935 diarrhea episodes and 539 from healthy controls of a cohort study of children younger than 2 years of age in Lima, Peru. Stools were analyzed for common enteric pathogens, and diarrheagenic E. coli isolates were studied by a multiplex real-time PCR. Stool smears were stained with methylene blue and read by a blinded observer to determine the number of polymorphonuclear leukocytes per high-power field (L/hpf). Fecal leukocytes at >10 L/hpf were present in 11.8% (110/935) of all diarrheal episodes versus 1.1% (6/539) in controls (P < 0.001). Among stool samples with diarrheagenic E. coli as the only pathogen isolated (excluding coinfection), fecal leukocytes at >10 L/hpf were present in 8.5% (18/212) of diarrhea versus 1.3% (2/157) of control samples (P < 0.01). Ninety-five percent of 99 diarrheagenic E. coli diarrhea samples were positive for fecal lactoferrin. Adjusting for the presence of blood in stools, age, sex, undernutrition, and breastfeeding, enterotoxigenic E. coli (ETEC) isolation as a single pathogen, excluding coinfections, was highly associated with the presence of fecal leukocytes (>10 L/hpf) with an odds ratio (OR) of 4.1 (95% confidence interval [CI], 1.08 to 15.51; P < 0.05). Although diarrheagenic E. coli was isolated with similar frequencies in diarrhea and control samples, clearly it was associated with a more inflammatory response during symptomatic infection; however, in general, these pathogens elicited a mild inflammatory response.

Physicians' responsibility for antibiotic use in infants from periurban Lima, Peru.

OBJECTIVE: To describe the use of antibiotics in Peruvian children under 1 year in a setting where they are available without a prescription. METHODS: Data were analyzed from a cohort study between September 2006 and December 2007 of 1 023 children < 2 months old in periurban Lima, Peru, followed until they were 1 year old. RESULTS: Seven hundred seventy of 1 023 (75.3%) children took 2 085 courses of antibiotics. There were two courses per child per year (range 0-12). Higher rates of antibiotic use were found in children 3-6 months old (37.2%). Antibiotics were given to children for 8.2% of common colds, 58.6% of all pharyngitis, 66.0% of bronchitis, 40.7% of diarrheas, 22.8% of dermatitis, and 12.0% of bronchial obstructions. A physician's prescription was the most common reason for antibiotic use (90.8%). Medication use without a prescription was found in 6.9% of children, and in 63.9% of them it was preceded by a physician's prescription. CONCLUSIONS: Infants are often exposed to antibiotics in this setting. Overuse of antibiotics is common for diagnoses such as pharyngitis, bronchitis, bronchial obstruction, and diarrhea but is typically inappropriate (83.1% of courses) based on the most common etiologies for this age group. Interventions to improve the use of antibiotics should focus on physicians, since a physician's prescription was the most common reason for antibiotic use.

Age-related susceptibility to infection with diarrheagenic Escherichia coli among infants from Periurban areas in Lima, Peru.

BACKGROUND: Diarrheagenic Escherichia coli strains are being recognized as important pediatric enteropathogens worldwide. However, it is unclear whether there are differences in age-related susceptibility to specific strains, especially among infants. METHODS: We conducted a passive surveillance cohort study of diarrhea that involved 1034 children aged 2-12 months in Lima, Peru. Control stool samples were collected from randomly selected children without diarrhea. All samples were analyzed for common enteric pathogens and for diarrheagenic E. coli with use of multiplex real-time polymerase chain reaction. RESULTS: The most frequently isolated pathogens in 1065 diarrheal episodes were diarrheagenic E. coli strains (31%), including enteroaggregative (15.1%) and enteropathogenic E. coli (7.6%). Diarrheagenic E. coli, Campylobacter species, and rotavirus were more frequently isolated from infants aged >or=6 months. Among older infants, diffusely adherent E. coli and enterotoxigenic E. coli were more frequently isolated from diarrheal samples than from control samples (P <.05). Children aged >or=6 months who were infected with enterotoxigenic E. coli had a 4.56-fold increased risk of diarrhea (95% confidence interval, 1.20-17.28), compared with younger children. Persistent diarrhea was more common in infants aged <6 months (13.5% vs 3.6%; P <.001). Among children with diarrheagenic E. coli-positive samples, coinfections with other pathogens were more common in children with diarrhea than in control children (40.1% vs 15.6%; P <.001). CONCLUSIONS: Diarrheagenic E. coli strains were more frequently isolated in samples from older infants. In this setting with high frequency of pathogen exposure and high frequency of breastfeeding, we hypothesize that the major age-related differences result from decreased exposure to milk-related protective factors and from increased exposure to contaminated food and water.

[Prevalence of purchase of antibiotics without prescription and antibiotic recommendation practices for children under five years of age in private pharmacies in peri-urban areas of Lima, Peru]. / Prevalencia de compra sin receta y recomendación de antibióticos para niños menores de 5 años en farmacias privadas de zonas periurbanas en Lima, Perú.

OBJECTIVES: To determine the prevalence of purchase of antibiotics without prescription and antibiotic recommendation for its use in children <5 years of age in private pharmacies in peri-urban areas of Lima. MATERIALS AND METHODS: An anonymous population survey was conducted among adults who bought an antibiotic for a child <5 years of age from a private pharmacy. Fictitious cases were applied in a subgroup of pharmacies to evaluate antibiotic recommendation practices. RESULTS: The prevalence of purchase of antibiotics without a prescription was 13%, including 1.7% that were chosen by consumers and 11.3% that were recommended by pharmacists. A total of 66.7% of the medications purchased to treat colds were antibiotics, 56.9% of which were prescribed. 64.4% of medications purchased to treat bronchospasm, 96.4% of the medications to treat watery diarrhea and 90.9% of the medications to treat pharyngitis were antibiotics. Amoxicillin (51.5%) and trimethoprim-sulfamethoxazole (20.6%) were the most commonly purchased antibiotics. A pharmacist suggested an antibiotic in 60% of the fictitious common cold cases, 76% of the bronchospasm cases, 44% of the watery diarrhea cases, and 76% of the dysentery cases. CONCLUSIONS: The purchase of antibiotics for children <5 years of age in private pharmacies primarily occurs with a medical prescription. The pharmacist commonly recommended an antibiotic in cases lacking a prescription. Measures are needed to reduce the inappropriate use of antibiotics at medical facilities and in pharmacies.

Vaccine schedule compliance among very low birth weight infants in Lima, Peru.

OBJECTIVE: There is little information about vaccine schedule compliance in very-low-birth-weight infants in developing countries. The aim of the study was to describe the compliance with the vaccine schedule among this population in Lima, Peru. PATIENTS AND METHODS: We conducted a prospective cohort study in four hospitals in Lima in infants with a birth-weight of less than 1500 g, followed from birth up to 12 months of age every 2 weeks. The date and age at administration of each vaccine was recorded RESULTS: 222 infants were enrolled. The median birth-weight was 1250 g (range 550-1499 g) and the median gestational age was 30.0 weeks (range 23-37 weeks). The mean age for the first pentavalent (DPT, Hib, HepB) and oral polio vaccine administration was 4.3 ± 1.4 months in infants with a birth-weight of < 1000 g vs. 3.1 ± 1.0 in infants with a birth-weight 1000-1500 g (p < 0.001); 4.1 ± 0.9 vs. 3.3 ± 1.1 for rotavirus (p < 0.05); and 5.1 ± 2.1 vs. 4.3 ± 1.8 for the 7-valent pneumococcal conjugated vaccine. Only 35% had received the three doses of oral polio and pentavalent vaccine by seven months, although by nine months 81% had received these vaccines. CONCLUSIONS: Vaccination of very-low-birth-weight infants in Peru is significantly delayed, especially in infants with a birth-weight of < 1000 g and lower gestational age. Urgent educational interventions targeting physicians and nurses should be implemented in order to improve vaccination rates and timing in these high risk populations.

Feeding of young children during diarrhea: caregivers' intended practices and perceptions.

Childhood diarrhea is an important cause of malnutrition, which can be worsened when caretakers limit nutritional support. We queried 390 caregivers and their children in a peri-urban community in Lima, Peru regarding general perceptions of feeding and feeding practices during diarrhea. Overall, 22.1% of caregivers perceived feeding during diarrhea to be harmful. At baseline, 71.9% of caregivers would discontinue normal feeding or give less food. Most would withhold milk, eggs, and meats. Approximately 40% of caregivers would withhold vegetables and fruits. A pilot educational intervention was performed to improve feeding during diarrhea. At follow-up survey 3 months later, none of the caregivers would recommend withholding food. Only 23.2% would recommend discontinuing normal feeding and 1.8% perceived food to be damaging. Misperceptions of the role of feeding during diarrhea pose a significant health risk for children, but a simple educational intervention might have a major impact on these perceptions and practices.

Respiratory syncytial virus-associated hospitalizations in pre-mature infants in Lima, Peru.

We conducted a prospective cohort study in four hospitals in Lima, Peru in infants with a birth weight ≤ 1,500 g followed from birth hospital discharge up to 1 year of age to determine the incidence of respiratory syncytial virus (RSV) hospitalizations. We enrolled 222 infants from March of 2009 to March of 2010: 48 infants with a birth weight < 1,000 g and 174 infants with a birth weight of 1,000-1,500 g (birth weight = 1,197 ± 224 g; gestational age = 30.1 ± 2.6 weeks). There were 936 episodes of respiratory infections; the incidence of respiratory infections during the first 1 year of life was 5.7 episodes/child-years. The incidence of RSV respiratory infections that required emergency room management was 103.9 per 1,000 child-years, and the incidence of RSV hospitalizations was 116.2 per 1,000 child-years (244.9 in infants with a birth weight < 1,000 g and 88.9 in infants 1,000-1,500 g; P < 0.05). The incidence of RSV respiratory infections that required emergency management or hospitalization is high among pre-mature infants in Lima.

Factors affecting caregivers' use of antibiotics available without a prescription in Peru.

OBJECTIVE: To determine factors that affect caregivers' decisions about antibiotic use in children in settings where antibiotics are available without prescription. METHODS: In a house-to-house survey, 1200 caregivers in 3 periurban districts of Lima, Peru, were asked about antibiotic use in young children. RESULTS: In this sample, 87.2% of children aged <5 years had received an antibiotic drug in their lives; 70.3% had received antibiotics before 1 year of age, and 98.8% of those had been prescribed by a physician. Given hypothetical cases of common cold and nondysenteric diarrhea, caregivers would seek medical advice in 76.4% and 87.1%, respectively, and 84.6% of caregivers said they respected medical decisions even if an antibiotic was not prescribed. Caregivers with high school-level education accepted 80% more medical decisions of not using an antibiotic and used fewer pharmacist-recommended antibiotics. For each additional year of life, the risk of self-medicated antibiotic use and the use of pharmacist-recommended antibiotics increased in 30%. (OR: 1.3, 95% CI: 1.1-1.4, P = .001 and OR: 1.3, 95% CI: 1.2-1.5, P < .001, respectively). Caregivers respected a medical decision of not prescribing an antibiotic 5 times more when physicians had explained the reason for their advice (OR: 5.0, 95% CI: 3.2-7.8, P < .001). CONCLUSIONS: Prescribed antibiotic use in these young children is common. Even if they are available without prescription, caregivers usually comply with medical advice and follow physicians' recommendations when antibiotics are not prescribed. Improving physician prescribing habits could reduce irrational antibiotic use, decreasing future caregiver-driven misuse.

[Preferences of antibiotic use in children less than five in physicians working health centers of primary level in peri-urban areas of Lima, Peru]. / Preferencias de uso de antibióticos en niños menores de cinco años por médicos de centros de salud de primer nivel en zonas periurbanas de Lima, Perú

OBJECTIVES: To describe physicians' preferences of antibiotic use in children less than 5 years in health centers of primary level in three periurban districts in Lima, Perú. MATERIAL AND METHODS: A structured survey was applied to 218 general practitioners from three health networks of Lima. The survey included six typical clinical cases in children under 5 years with questions about antibiotic use: the cases were common cold, pharyngitis, pneumonia, bronchial obstructive syndrome, watery diarrhea and dysentery. RESULTS: 81.6% of the physicians responded that more than a quarter of the patients they attended were children under five years. 15.6% of the general physicians would use an antibiotic for common cold treatment. For dysentery treatment 90.4% would use antibiotics, the frequently used were Trimethoprim-Sulfamethoxazole (TMP-SMX) and Furazolidone. 86.2% of physicians would recommend an antibiotic for pharyngitis. In a watery diarrhea case 32.7% of the doctors would use. In the case of bronchospasm, 73% of the doctors would recommend an antibiotic. 96.3% would recommend antibiotics for pneumonia. The perception of the degree of mother's satisfaction increased the risk of inappropriate prescription of antibiotics OR: 1.6, p=0.031, 95% CI: 1.1-2.6). CONCLUSIONS: There is tendency to overuse antibiotics for diagnoses such as pharyngitis and bronchospasm, as well as in cases of watery diarrhea and common cold, the reason could be that a large number of children under five years are treated by general practitioners without training in pediatric care.

Use of commercially available oral rehydration solutions in Lima, Peru.

Caregivers' practices concerning oral rehydration of young children during diarrheal illness were investigated in a periurban community of low socioeconomic level in Lima, Peru. Data of 330 caregivers of children aged 6-36 months were analyzed; 72.7% of all caregivers would give commercially available oral rehydration solutions (ORSs). However, only 58.6% of those caregivers with children that had experienced diarrhea during the previous week stated that they had used commercially available ORSs, a significantly lower percentage. The main reason for not using commercially available ORSs was that caregivers did not know about them. Of all recipes caregivers provided for homemade ORS, none contained the recommended concentrations of sugar and salt. Educating caregivers about availability, benefits, and use of commercially available ORSs as well as correct preparation of homemade ORS is urgently needed.

Safety and immunogenicity of an investigational fully liquid hexavalent DTaP-IPV-Hep B-PRP-T vaccine at two, four and six months of age compared with licensed vaccines in Latin America.

OBJECTIVE: This trial assessed the safety of a fully liquid investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine containing 10 µg Hansenula polymorpha-derived recombinant hepatitis B (hep B) antigen for primary vaccination of infants at 2, 4 and 6 months of age compared with licensed comparators. METHODS: Participants received the DTaP-IPV-Hep B-PRP-T vaccine (group 1, N = 1422) or licensed DTwP-Hep B//Hib (Tritanrix-Hep B/Hib) and oral poliovirus vaccines (group 2, N = 711). The incidence of severe fever (≥ 39.6°C rectal equivalent) in the 2 groups was compared statistically; reactogenicity was evaluated from parental reports. Anti-Hep B antibody titers were measured in a subset of participants (no hepatitis B vaccination at birth) 1 month after dose 3. RESULTS: The investigational vaccine was well tolerated. After any dose, fever (rectal equivalent temperature ≥ 38°C) was observed in 74.8% and 92.7% of participants in groups 1 and 2; severe fever was observed in 4.0% and 5.5% of participants. Solicited injection site and systemic reactions were numerically less frequent in group 1 than group 2, although this difference was not assessed statistically. In both groups, all participants included in the immunogenicity analysis achieved anti-Hep B ≥ 10 mIU/mL and ≥ 96.2% of participants achieved anti-Hep B ≥ 100 mIU/mL, although geometric mean titer was approximately 3-fold lower for the investigational vaccine. CONCLUSION: This new, fully liquid acellular pertussis hexavalent vaccine demonstrated less reactogenicity than the licensed comparator whole cell pertussis vaccine and was highly immunogenic for the new Hep B valence.

[Levels of quinolones resistance and other antimicrobial in non-pathogenic Escherichia coli strains in children from the periurban area of Lima, Peru]. / Niveles de resistencia a quinolonas y otros antimicrobianos en cepas de Escherichia coli comensales en niños de la zona periurbana de Lima, Perú.

The main aim of this study was to establish the resistance levels to antimicrobial agents, in 222 non-pathogenic E. coli strains of fecal origin in Peru. The proportion of resistance found to the evaluated antimicrobials was ampicillin (62.6%), cotrimoxazole (48,6%), tetracycline (43,0%) and chloramphenicol (15,8%). We emphasize the high resistance levels found for quinolones: 32% for nalidixic acid (NAL) and 12% for ciprofloxacin (CIP). These high levels of quinoloneresistance in non-pathogenic strains isolated from children in this age group highlight the extensive use and the impact of the intake of this kind of antimicrobials in the community, showing the potential risk of the loss of their utility in the area.