Understanding the evolution and spread of chikungunya virus in the Americas using complete genome sequences.

Local transmission of chikungunya virus (CHIKV) was first detected in the Americas in December 2013, after which it spread rapidly throughout the Caribbean islands and American mainland, causing a major chikungunya fever epidemic. Previous phylogenetic analysis of CHIKV from a limited number of countries in the Americas suggests that an Asian genotype strain was responsible, except in Brazil where both Asian and East/Central/South African (ECSA) lineage strains were detected. In this study, we sequenced thirty-three complete CHIKV genomes from viruses isolated in 2014 from fourteen Caribbean islands, the Bahamas and two mainland countries in the Americas. Phylogenetic analyses confirmed that they all belonged to the Asian genotype and clustered together with other Caribbean and mainland sequences isolated during the American outbreak, forming an 'Asian/American' lineage defined by two amino acid substitutions, E2 V368A and 6K L20M, and divided into two well-supported clades. This lineage is estimated to be evolving at a mean rate of 5 × 10-4 substitutions per site per year (95% higher probability density, 2.9-7.9 × 10-4) and to have arisen from an ancestor introduced to the Caribbean (most likely from Oceania) in about March 2013, 9 months prior to the first report of CHIKV in the Americas. Estimation of evolutionary rates for individual gene regions and selection analyses indicate that (in contrast to the Indian Ocean Lineage that emerged from the ECSA genotype followed by adaptive evolution and with a significantly higher substitution rate) the evolutionary dynamics of the Asian/American lineage are very similar to the rest of the Asian genotype and natural selection does not appear to have played a major role in its emergence. However, several codon sites with evidence of positive selection were identified within the non-structural regions of Asian genotype sequences outside of the Asian/American lineage.

Dispersal and population structure of a New World predator, the army ant Eciton burchellii.

The army ant Eciton burchellii is probably the most important arthropod predator in the Neotropics, and many animal species depend upon it. Sex-biased dispersal with winged males and permanently wingless queens may render this species especially sensitive to habitat fragmentation and natural barriers, which might have severe impacts on population structure and lead to population decline. Using nuclear microsatellite markers and mitochondrial sequences, we investigated genetic differentiation in a fragmented population in the Panama Canal area. While nuclear markers showed little differentiation between subpopulations (F(ST) = 0.017), mitochondrial differentiation was maximal in some cases (Phi(ST) = 1). This suggests that, while females are not capable of crossing barriers such as large rivers, flying males are able to promote nuclear gene flow between the studied forest patches. Consistent with this interpretation, we did not find any evidence for inbreeding or genetic deterioration on Barro Colorado Island over the last 90 years since its formation.

How well does fetal ultrasound predict the date of birth in Antigua and Barbuda?

This study was done to determine the accuracy of fetal ultrasound (U.S.) predicting the estimated date of delivery (EDD) in a primarily Afro-Caribbean population in Antigua and Barbuda. A total of 206 women had retrospective review offetal ultrasound tests done between July 1994 and January 1996. The EDD based on last menstrual period (LMP) was calculated for 104 women with dates and compared with EDD calculated from ultrasound test. These were then compared with actual date of birth from maternity records. For women with unreliable menstrual data (102 women), ultrasound EDD was compared with actual date of birth. Ultrasound EDD demonstrated a trend toward being more accurate than menstrual history EDD, being 10.0 +/- 9.4 (mean +/- standard deviation) days off versus 13.3 +/- 15 days, p = 0.057, (n=104), CI: -0.1, 6.73 days. Ultrasound EDD was within ten days of delivery 60% of the time versus 57% for menstrual history EDD. The average error in estimating EDD was + 1.7 days for ultrasound and + 3.7 days for menstrual history. In women without menstrual history data (n=102), the ultrasound EDD was just as accurate in both the second trimester, 11.8 +/- 9.5 versus 11.4 +/- 10.7 days off (not statistically significant) and the third trimester, 10.0 +/- 8.0 versus 8.1 +/- 7.0 days off (not statistically significant). Fetal ultrasound is marginally better at predicting the date of birth compared with menstrual history but the difference does notjustify routine use for that purpose. When menstrual history is unknown, ultrasound EDD is just as accurate as when menstrual history is known, making it a very useful test.

How well does fetal ultrasound predict the date of birth in Antigua and Barbuda / Precisión del Ultrasonido Fetal en la Predicción de la fecha de Nacimiento en Antigua y Barbuda?

This study was done to determine the accuracy of fetal ultrasound (U.S.) predicting the estimated date of delivery (EDD) in a primarily Afro-Caribbean population in Antigua and Barbuda. A total of 206 women had retrospective review offetal ultrasound tests done between July 1994 and January 1996. The EDD based on last menstrual period (LMP) was calculated for 104 women with dates and compared with EDD calculated from ultrasound test. These were then compared with actual date of birth from maternity records. For women with unreliable menstrual data (102 women), ultrasound EDD was compared with actual date of birth. Ultrasound EDD demonstrated a trend toward being more accurate than menstrual history EDD, being 10.0 +/- 9.4 (mean +/- standard deviation) days off versus 13.3 +/- 15 days, p = 0.057, (n=104), CI: -0.1, 6.73 days. Ultrasound EDD was within ten days of delivery 60 of the time versus 57 for menstrual history EDD. The average error in estimating EDD was + 1.7 days for ultrasound and + 3.7 days for menstrual history. In women without menstrual history data (n=102), the ultrasound EDD was just as accurate in both the second trimester, 11.8 +/- 9.5 versus 11.4 +/- 10.7 days off (not statistically significant) and the third trimester, 10.0 +/- 8.0 versus 8.1 +/- 7.0 days off (not statistically significant). Fetal ultrasound is marginally better at predicting the date of birth compared with menstrual history but the difference does notjustify routine use for that purpose. When menstrual history is unknown, ultrasound EDD is just as accurate as when menstrual history is known, making it a very useful test

Este estudio fue hecho para determinar la exactitud del ultrasonido fetal (EEUU) en la predicción de la fecha estimada de parto (FEP) en una población principalmente afro-caribeña en Antigua y Barbuda. A un total de 206 mujeres, se les hizo una revisión retrospectiva de las pruebas de ultrasonido fetal, entre julio del 1994 y enero de 1996. La FEP basada en la historia menstrual (UPM) se le calculó a 104 mujeres con fechas, comparándosele luego con la FEP calculada mediante la prueba de ultrasonido. Estas fueron entonces comparadas con la fecha real de nacimiento tomada de los archivos de maternidad. Para las mujeres con datos menstruales inestables (102 mujeres), la FEP basada en ultrasonido fue comparada con la fecha real de nacimiento. La FEP basada en el ultrasonido, mostró una tendencia a ser más exacta que la FEP basada en la historia menstrual, con 10.0 + 9.4 (media + desviación estándar) días de diferencia, frente a 13.3 + 15 días, p = 0.057, (n = 104), CI: -0.1, 6.73 días. La FEP mediante ultrasonido estuvo dentro de los 10 días de parto 60% del tiempo frente al 57% en el caso de la FEP basada en historia menstrual. El error medio de estimación de la FEP fue de + 1.7 días para el ultrasonido y + 3.7 días para la historia menstrual. En mujeres sin datos de historia menstrual (n = 102), la FEP mediante ultrasonido fue igualmente exacta tanto en el segundo trimestre, 11.8 + 9.5 frente a 11.4 + 10.7 días de diferencia, (no significativo estadísticamente) y el tercer trimestre, 10.0 + 8.0 frente a 8.1 + 7.0 días de diferencia, (no significativo estadísticamente). El ultrasonido fetal es marginalmente mejor en predecir la fecha de nacimiento en comparación con el procedimiento basado en la historia mensual, pero la diferencia no justifica el uso rutinario para ese propósito. Cuando se desconoce la historia menstrual, la FEP mediante ultrasonido es tan exacta como cuando se sabe la historia mensual, lo cual la hace una prueba muy útil.

Heavy metal contamination of water, soil and produce within riverine communities of the Río Pilcomayo basin, Bolivia.

The Río Pilcomayo heads on the Cerro Rico de Potosí precious metal-polymetallic tin deposits of Southern Bolivia. Mining of the Potosí deposits began in 1545 and has led to the severe contamination of the Pilcomayo's water and sediments for at least 200 km downstream of the mines. This investigation addresses the potential human health affects of metal and As contamination on four communities located along the upper Río Pilcomayo by examining the potential significance of human exposure pathways associated with soils, crops and water (including river, irrigation and drinking water supplies). The most significantly contaminated agricultural soils occur upstream at Mondragón where Cd, Pb and Zn concentrations exceed recommended guideline values for agricultural use. Further downstream the degree of contamination decreases, and metal concentrations are below Dutch, German and Canadian guideline values. Metal and As concentrations in agricultural products from the four communities were generally below existing guidelines for heavy metal content in commercially-sold vegetables. Thus, the consumption of contaminated produce does not appear to represent a significant exposure pathway. A possible exception is Pb in carrots, lettuce and beetroots from Sotomayor and Tuero Chico; 37% and 55% of the samples, respectively, exceeded recommended guidelines. Most communities obtain drinking water from sources other than the Río Pilcomayo. In general, dissolved concentrations of metals and As in drinking water from the four studied communities are below the WHO guideline values with the exception of Sb, which was high at Tasapampa. The inadvertent ingestion of contaminated water from irrigation canals and the Río Pilcomayo represents a potential exposure pathway, but its significance is thought to be minimal. Given the degree of soil contamination in the area, perhaps the most significant exposure pathway is the ingestion of contaminated soil particles, particularly particles attached to, and consumed with vegetables. The risks associated with this pathway can be reduced by thoroughly washing or peeling the vegetables prior to consumption. Other exposure pathways that are currently under investigation include the consumption of contaminated meat from livestock and poultry, which drink polluted waters and the ingestion of contaminated wind-blown dust.

How well does foetal ultrasound predict date of birth in Antigua and Barbuda? - Poster abstract

OBJECTIVE: To determine the accuracy of foetal ultrasound (US) in predicting the estimated date of confinement (EDC) in a primarily Afro-Caribbean population in Antigua. DESIGN AND METHODS: A retrospective review of foetal ultrasound test done between July 1994 to January 1996 was performed. The EDC base on menstrual history (LMP) was calculated and compared with EDC calculated from ultrasound test. These were then compared with actual date of birth from Maternity records. For women with unreliable menstrual data, ultrasound EDC was compared with actual date of birth. Stillborn and premature or small for date pregnancies (birthweight < 2.5 kg) were excluded. CONCLUSIONS: Foetal ultrasound is significantly better at predicting data of birth than LMP, but the difference does not justify routine use for that purpose.(AU)

Effect of vitamin A therapy on serologic responses and viral load changes after influenza vaccination in children infected with the human immunodeficiency virus.

Vitamin A administered to children infected with the human immunodeficiency virus before influenza vaccination in a double-blind randomized study did not enhance vaccine serologic responses but did dampen the increase in the human immunodeficiency virus viral load 14 days after immunization (vitamin A, decrease of 0.13 +/- 0.09 log(10) copies/mL; placebo, increase of 0.14 +/- 0.08, P =.02).

Periodic fever syndrome in children.

OBJECTIVES: To describe the presentation, clinical course, therapeutic response, and long-term follow-up of patients with a syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA). STUDY DESIGN: Patients with PFAPA (n = 94) referred over a 10-year period completed a registry form and provided medical records. Follow-up telephone calls were made in late 1997 to determine the persistence of episodes and sequelae. RESULTS: PFAPA episodes lasted 4.8 days (95% confidence interval 4.5 to 5.1) and recurred every 28 days (confidence interval 26 to 30), with a maximal temperature of 40.5 degrees C (confidence interval 40. 4 degrees to 40.6 degrees ). Of the 83 children available for follow-up, 34 no longer had episodes. In the remainder the episodes did not differ in character but recurred less frequently over time. The affected children had no long-term sequelae. Glucocorticoids were highly effective in controlling symptoms. Tonsillectomy and cimetidine treatment were associated with remission in a small number of patients. CONCLUSIONS: PFAPA is a not uncommon cause of periodic fever in children. In some children the syndrome resolves, whereas symptoms in others persist. Long-term sequelae do not develop. The syndrome is easily diagnosed when regularly recurring episodes of fever are associated with aphthous stomatitis, pharyngitis, or cervical adenitis.

Streptococcus pneumoniae colonization in the young child: association with otitis media and resistance to penicillin.

OBJECTIVE: To determine the nasopharyngeal colonization rate of penicillin-susceptible and penicillin-resistant strains of Streptococcus pneumoniae in young children, and to assess its relationship with the incidence of otitis media. DESIGN: Observational study in 215 children younger than 6 years of age who received care in the Vanderbilt Vaccine Clinic from September 1, 1992, to August 31, 1993. RESULTS: Of 842 nasopharyngeal cultures obtained, results for 44% of the cultures were positive for S. pneumoniae; 73% of the isolates were serotypes 6, 14, 19, or 23. Younger children had significantly higher rates of pneumococcal colonization than older children, with a peak at 1 year of age. By microdilution susceptibility testing, 37% of the cultures with positive results were intermediately or highly resistant to penicillin. Significantly more serotype 19 and 23 isolates were penicillin resistant than organisms of other serotypes. Children younger than 2 years of age had a twofold higher percentage of resistant isolates than those older than 2 years of age. A significant association was noted between nasopharyngeal carriage of S. pneumoniae and acute otitis media (p = 0.0002); however, the incidence of acute otitis media did not differ significantly between children colonized with penicillin-susceptible or penicillin-resistant strains. Unresolved otitis media was diagnosed more often in children who were colonized with resistant organisms than in children colonized with susceptible strains (p = 0.04). CONCLUSIONS: There was a high rate of nasopharyngeal carriage of penicillin-resistant S. pneumoniae in this population of young children. Nasopharyngeal colonization was associated with an increased incidence of acute otitis media, and penicillin resistance was associated with an increased incidence of unresolved otitis media.

Double-blind, randomized trial of one versus three prophylactic doses of synthetic surfactant in 826 neonates weighing 700 to 1100 grams: effects on mortality rate. American Exosurf Neonatal Study Groups I and IIa.

At 33 hospitals in the United States, a double-blind, randomized clinical trial was performed to compare one versus three prophylactic doses of synthetic surfactant in 700 to 1100 gm inborn infants. All 826 infants received an initial prophylactic dose of surfactant within 30 minutes of birth. Subsequently 410 infants received two doses of placebo (air) 12 and 24 hours later, and 416 infants received two additional doses of surfactant. By the age of 28 days, 70 infants who received one dose of surfactant and 40 infants who received three doses were dead, a 43% relative reduction in the mortality rate (30 fewer deaths; p = 0.002). By the age of 1 year after term, 87 infants who received one dose and 62 infants who received three doses were dead: a 29% relative reduction in the mortality rate (25 fewer deaths; p = 0.027). Infants who received three doses of surfactant required significantly less oxygen and less mean airway pressure for the first week of life. Necrotizing enterocolitis (9 vs 25 infants; p = 0.005), and use of high-frequency ventilation (13 vs 26 infants; p = 0.037); pancuronium (43 vs 62 infants; p = 0.045); and leukocyte transfusions (0 vs 4 infants; p = 0.042) were less frequent in the three-dose group, but air leak, bronchopulmonary dysplasia, intraventricular hemorrhage, patent ductus arteriosus, pulmonary hemorrhage, and infections were not different. These results indicate that physiologic findings, mortality rates, and probably morbidity rates are improved by two additional prophylactic doses of synthetic surfactant.

Double-blind evaluation of developmental and health status to age 2 years of infants weighing 700 to 1350 grams treated prophylactically at birth with a single dose of synthetic surfactant or air placebo.

In a previously published article, we reported results of a two-center study of outcome to 28 days of 385 infants with birth weights from 700 to 1350 gm who were assigned randomly to receive a single 5 ml/kg intratracheal dose of either synthetic surfactant or air placebo. Infants treated with surfactant had a higher rate of survival to 28 days without bronchopulmonary dysplasia than did control subjects given an air placebo. The present study assessed survivors in early childhood to determine neurodevelopmental outcome and late morbidity. Two hundred fifty-eight surviving infants from both centers were evaluated at 1-year adjusted age; medical histories were obtained, standard physical and neurologic examinations were performed, and Bayley Scales of Infant Development were administered. Ophthalmologic examinations were performed at various times between 28 days and 1-year adjusted age. At 2-years adjusted age, 118 infants from one center were reevaluated with the same procedures and also had hearing and speech evaluations. Neither the 1-year assessment of the entire population nor the 2-year assessment of the one center's cohort revealed physical or neurodevelopmental differences between treatment groups. We conclude that administration of a single prophylactic dose of synthetic surfactant to premature infants with birth weights from 700 to 1350 grams results in improved survival rates to 28 days without bronchopulmonary dysplasia and is not associated with adverse health or neurodevelopmental effects at 1-year or 2-years adjusted age.

Enhanced antibody response in Venezuelan infants immunized with Haemophilus influenzae type b-tetanus toxoid conjugate vaccine.

The safety and immunogenicity of primary immunization at 2, 4 and 6 months of age with Haemophilus influenzae type b capsular polysaccharide conjugated to tetanus toxoid (PRP-T; Act-HIB) were evaluated in infants in Valencia, Venezuela. In order better to assess reactions to PRP-T, subjects received their initial PRP-T vaccine a mean of 6.5 days after their initial diphtheria-tetanus-pertussis (DTP) vaccine. The PRP-T vaccine was well tolerated. Serum was obtained at ages 2 and 7 months (before the first and 1 month after the third PRP-T dose). Antibody responses were compared with those from Nashville infants who had received PRP-T and DTP simultaneously in a previous trial. The preimmunization titers in the Venezuelan and Nashville infants did not differ. The geometric mean postimmunization titer in the Venezuelan infants was 37.9 micrograms/ml, as compared with 3.63 micrograms/ml in the Nashville infants (P < 0.00001). Possible explanations for the exceptional antibody response of these Venezuelan infants to PRP-T include carrier priming caused by prior DTP immunization, synergy associated with the specific DTP vaccine used, preimmunization immunologic experience that differed from their United States counterparts and genetic differences that altered response to the vaccines. Further studies are proposed to evaluate these possibilities.

Comparison of the effect of three doses of a synthetic surfactant on the alveolar-arterial oxygen gradient in infants weighing > or = 1250 grams with respiratory distress syndrome. American Exosurf Neonatal Study Group II.

The effect of a 50% increment or decrement in the recommended 5 ml/kg dose of a commercially available surfactant (Exosurf Neonatal) on the alveolar-arterial oxygen gradient was investigated in a multicenter, double-blind, placebo-controlled rescue trial conducted at 15 hospitals in the United States. Two doses of three different volumes (2.5, 5.0, and 7.5 ml/kg) were compared with two 5.0 ml/kg doses of air in 281 infants weighing > or = 1250 gm who had respiratory distress syndrome requiring mechanical ventilation and an arterial/alveolar oxygen ratio < 0.22. The first dose was given between 2 and 24 hours of age, and the second dose was given 12 hours later to all infants who still required mechanical ventilation. Infants were stratified at entry by gender and the magnitude of the arterial/alveolar oxygen ratio. The air placebo arm of the study was terminated early when reductions in mortality rates were proved in another rescue trial of this surfactant in infants with the same birth weights. For the first 48 hours, administration of a 2.5 ml/kg dose of surfactant provided less improvement in the alveolar-arterial oxygen gradient than doses of 5.0 and 7.5 ml/kg, which were equivalent. Similar results were observed in mean airway pressure (p < 0.05). There were no significant differences among the three dosage groups in mortality rate, air leak, bronchopulmonary dysplasia, and other complications of prematurity. There were no pulmonary hemorrhages in any group. Reflux of surfactant occurred more frequently in the 5.0 and 7.5 ml/kg groups. These results indicate that more sustained improvements in oxygenation are provided, with equal safety, by the standard two 5.0 ml/kg rescue doses of this surfactant than by the 2.5 ml/kg dose. No further benefit is gained from two larger doses given 12 hours apart.

Responses of children to booster immunization with their primary conjugate Haemophilus influenzae type B vaccine or with polyribosylribitol phosphate conjugated with diphtheria toxoid.

Children primed with one of four conjugate Haemophilus influenzae type b vaccines received booster immunization with their primary vaccine or with polyribosylribitol phosphate conjugated with diphtheria toxoid. The latter vaccine produced postbooster antibody levels that equaled or exceeded those produced by boosting with the original vaccine, and thus may be used as a booster irrespective of the original vaccine.

Antibody response to Bordetella pertussis antigens after immunization with American and Canadian whole-cell vaccines.

Because of apparent differences in the incidence and epidemiology of pertussis in the United States and Canada, we measured the antibody response to four Bordetella pertussis antigens and to a whole-bacteria preparation in children immunized with American and Canadian whole-cell pertussis vaccines. All infants received combined pertussis, tetanus, and diphtheria vaccines from one of two American manufacturers or a single Canadian manufacturer. The Canadian children received either oral poliomyelitis vaccine, inactivated poliomyelitis vaccine as a separate injection, or a product that combined inactivated poliomyelitis vaccine with diphtheria, tetanus, and pertussis components. The Canadian trivalent diphtheria, tetanus, and pertussis vaccine given with oral poliovirus vaccine induced lower anti-pertussis toxin antibody titers than did the American vaccines (p < or = to 0.05) but higher antifimbriae and anti-69-kilodalton outer-membrane protein (pertactin) antibody titers (p < or = to 0.02). Canadian children immunized with inactivated poliomyelitis vaccine either as a separate injection or as a combined diphtheria, tetanus, and pertussis vaccine had consistently lower pertussis antibody titers than did those who received oral poliomyelitis vaccine (p < or = 0.001). We conclude that there is a wide range of antibody responses to B. pertussis antigens after immunization with various whole-cell pertussis vaccines, and that these responses may be influenced by concurrent administration of other vaccines.

Comparative trial in infants of four conjugate Haemophilus influenzae type b vaccines.

We performed a double-blind, randomized trial to compare the immunogenicity and reactogenicity of four conjugate Haemophilus influenzae type b vaccines given to infants 2, 4, and 6 months of age. Adverse reactions attributable to the vaccines were few and minor. The rates of systemic reactions did not differ among the various vaccines and were similar to those seen among children receiving conventional diphtheria-tetanus-pertussis vaccine. However, the four conjugate H. influenzae type b vaccines differed markedly in ability to stimulate antibody production. Mean antibody levels after three injections of polyribosylribitol phosphate conjugated with mutant diphtheria protein (PRP-CRM) or polyribosylribitol phosphate conjugated with tetanus toxoid (PRP-T) were 3.08 micrograms/ml and 3.64 micrograms/ml, respectively, significantly higher than those after the use of polyribosylribitol phosphate conjugated with outer-membrane protein of Neisseria meningitidis (PRP-OMP) (1.14 micrograms/ml) or polyribosylribitol phosphate conjugated with diphtheria toxoid (PRP-D) (0.28 microgram/ml). Only PRP-OMP produced a clinically pertinent elevation in antibody level after two injections (0.84 microgram/ml); the third injection of PRP-OMP produced a modest but statistically significant further elevation in mean antibody level (1.14 micrograms/ml). Only 29% of infants receiving PRP-D had antibody levels of 1 micrograms/ml, compared with 55%, 75%, and 83% of those receiving PRP-OMP, PRP-CRM, and PRP-T, respectively. We conclude that all four vaccines are safe and that all but PRP-D appear appropriate for use in a primary immunization series during infancy. The unique serologic response to PRP-OMP offers both advantages and disadvantages in comparison with PRP-CRM and PRP-T.

Results of laboratory surveillance of very low birth weight infants treated with a synthetic surfactant.

During two randomized, controlled trials comparing single prophylactic doses of air placebo and a synthetic surfactant, Exosurf Neonatal, many routine laboratory measurements were made in small premature infants during the first week of life. Values for serum electrolytes, urea, creatinine, phospholipid, cholesterol, glucose, calcium, bilirubin, and liver enzymes, as well as for hemoglobin, leukocyte and platelet counts, and urinalysis, did not differ between the placebo- and surfactant-treated infants. There was no evidence that prophylactic administration of this synthetic surfactant causes alterations in standard laboratory tests in small premature infants.