The Combination of Aroxybutynin and Atomoxetine in the Treatment of Obstructive Sleep Apnea (MARIPOSA): A Randomized Controlled Trial.

Rationale: Obstructive sleep apnea (OSA) is a common sleep disorder for which the principal treatment option, continuous positive airway pressure, is often poorly tolerated. There is currently no approved pharmacotherapy for OSA. However, recent studies have demonstrated improvement in OSA with combined antimuscarinic and noradrenergic drugs. Objectives: The aim of this study was to evaluate the efficacy and safety of AD109, a combination of the novel antimuscarinic agent aroxybutynin and the norepinephrine reuptake inhibitor atomoxetine, in the treatment of OSA. Methods: Phase II randomized, double-blind, placebo-controlled, parallel-group, 4-week trial comparing AD109 2.5/75 mg, AD109 5/75 mg, atomoxetine 75 mg alone, and placebo (www.clinicaltrials.gov identifier NCT05071612). Measurements and Main Results: Of 211 randomized patients, 181 were included in the prespecified efficacy analyses. Sleep was assessed by two baseline and two treatment polysomnograms. Apnea-hypopnea index with a 4% desaturation criterion (primary outcome) was reduced from a median (IQR) of 20.5 (12.3-27.2) to 10.8 (5.6-18.5) in the AD109 2.5/75 mg arm (-47.1%), from 19.4 (13.7-26.4) to 9.5 (6.1-19.3) in the AD109 5/75 mg arm (-42.9%; both P < 0.0001 vs. placebo), and from 19.0 (11.8-28.8) to 11.8 (5.5-21.5) with atomoxetine alone (-38.8%; P < 0.01 vs. placebo). Apnea-hypopnea index with a 4% desaturation criterion decreased from 20.1 (11.9-25.9) to 16.3 (11.1-28.9) in the placebo arm. Subjectively, there was improvement in fatigue with AD109 2.5/75 mg (P < 0.05 vs. placebo and atomoxetine). Atomoxetine taken alone decreased total sleep time (P < 0.05 vs. AD109 and placebo). The most common adverse events were dry mouth, insomnia, and urinary hesitancy. Conclusions: AD109 showed clinically meaningful improvement in OSA, suggesting that further development of the compound is warranted. Clinical trial registered with www.clinicaltrials.gov (NCT05071612).

Efficacy of atomoxetine plus oxybutynin in the treatment of obstructive sleep apnea with moderate pharyngeal collapsibility.

PURPOSE: Preliminary studies have shown a significant decrease in severity of obstructive sleep apnea (OSA) with the use of a combination of atomoxetine and oxybutynin, with patients having moderate pharyngeal collapsibility during sleep more likely to respond. This study evaluated the efficacy and safety of AD036 (atomoxetine 80 mg and oxybutynin 5 mg) in the treatment of OSA. METHODS: This trial was a phase 2, randomized, placebo-controlled crossover study comparing AD036, atomoxetine 80 mg alone, and placebo during three home sleep studies, each separated by about 1 week. The trial included patients with OSA and moderate pharyngeal collapsibility as defined by a higher proportion of hypopneas to apneas and mild oxygen desaturation. RESULTS: Of 62 patients who were randomized, 60 were included in efficacy analyses. The apnea-hypopnea index (AHI) from a median (interquartile range) of 14.2 (5.4 to 22.3) events/h on placebo to 6.2 (2.8 to 13.6) with AD036 and 4.8 (1.4 to 11.6) with atomoxetine alone (p < .0001). Both drugs also decreased the oxygen desaturation index (ODI) and the hypoxic burden (p < .0001). AD036, but not atomoxetine alone, reduced the respiratory arousal index and improved ventilation at the respiratory arousal threshold (greater Vactive). There was a trend for total sleep time to be decreased more with atomoxetine alone than with AD036. The most common adverse event was insomnia (12% with AD036, 18% with atomoxetine). CONCLUSION: AD036 significantly improved OSA severity in patients with moderate pharyngeal collapsibility. Atomoxetine may account for the majority of improvement in OSA severity, while the addition of oxybutynin may mitigate the disruptive effect of atomoxetine on sleep and further improve ventilation. TRIAL REGISTRATION: Clinical trial registered with www. CLINICALTRIALS: gov (NCT04445688).

Isometric-based test improves EMG-threshold determination in boys vs. men.

BACKGROUND: Children have been hypothesized to utilize higher-threshold (type-II) motor units (MUs) to a lesser extent than adults. Two recent studies, using a cycling-based EMG-threshold (EMGTh) protocol, supported the hypothesis, showing children's EMGTh intensities to be higher than adults'. Conclusions, however, were hampered by children's low EMGTh detection rates. Insufficiently high contractile forces at exhaustion were postulated as the reason for non-detection, predominantly in children. An intermittent isometric contraction test (IICT) protocol facilitates higher contractile forces prior to exhaustion and was shown effective in EMGTh testing of adults. PURPOSE: Determine whether an IICT protocol would enhance EMGTh detection in children, and consequently increase the magnitude of the previously observed child-adult EMGTh differences. METHODS: 18 boys and 21 men completed one-repetition-maximum (1RM) isometric knee-extension test. The IICT protocol followed, commencing at 25%1RM and comprising five isometric contractions per load, incremented by ~ 3%1RM to exhaustion. Vastus lateralis surface EMG was recorded and EMGTh, expressed as %1RM, was defined as the onset of the EMG-response's steeper segment. RESULTS: EMGTh was detected in 88.9% of boys and 95.2% of men, and occurred at higher relative intensities in boys (56.4 ± 9.2%1RM) than in men (46.0 ± 6.8%1RM). This 10.4% difference was 57% greater than the corresponding, previously reported cycling-based age-related difference. CONCLUSIONS: With the boys' detection rate nearly on par with the men's, the IICT protocol appears to overcome much of the intensity limitation of cycling-based protocols and provide a more sensitive EMGTh detection tool, thus extending the previously observed boys‒men difference. This difference adds supports to the notion of children's more limited type-II MU recruitment capacity.

Efavirenz modulation of sleep spindles and sleep spectral profile.

Non-nucleoside reverse transcriptase inhibitors are important antiretroviral agents for the treatment of human immunodeficiency virus. Some non-nucleoside reverse transcriptase inhibitors, in particular efavirenz, have prominent effects on sleep, cognition and psychiatric variables that limit their tolerability. To avoid confounds due to drug-drug and drug-disease interactions, we assessed the effects of efavirenz in healthy volunteers on sleep, cognition and psychological endpoints during the first week of treatment. Forty healthy male subjects were randomized to receive placebo or efavirenz 600 mg nightly for 7 days after completion of a 3-day placebo run-in period. Treatment with efavirenz was associated with reduced time to sleep onset in the Maintenance of Wakefulness Test, an increase in non-rapid eye movement sleep, a large exposure-related decrease in sigma band spectral density and sleep spindle density during non-rapid eye movement sleep, and reduced performance on an attention switching task. Because efavirenz has been shown to have serotonin 2A receptor partial-agonist properties, we reasoned that antagonism of serotonin 2A receptor signalling in the thalamic reticular nucleus, which generates sleep spindles and promotes attention, may be responsible. Consistent with predictions, treatment of healthy volunteers with a single dose of a serotonin 2A receptor antagonist was found to significantly suppress sigma band spectral density in an exposure-related manner and modulated the overall spectral profile in a manner highly similar to that observed with efavirenz, consistent with the notion that efavirenz exhibits serotonin 2A receptor partial-agonist pharmacology in humans.

Safety and pharmacodynamics of a single infusion of danavorexton in adults with obstructive sleep apnea experiencing excessive daytime sleepiness despite adequate use of CPAP.

BACKGROUND: Sleep disruptions experienced by patients with obstructive sleep apnea (OSA) can lead to excessive daytime sleepiness (EDS) and significantly impact patients' quality of life. EDS may persist despite use of continuous positive airway pressure (CPAP) therapy. Small molecules that target the orexin system, which has a known role in sleep-wake regulation, show therapeutic potential for the treatment of EDS in patients with hypersomnia. This randomized, placebo-controlled, phase 1b study aimed to investigate the safety of danavorexton, a small-molecule orexin-2 receptor agonist, and its effects on residual EDS in patients with OSA. METHODS: Adults with OSA aged 18-67 years with adequate CPAP use were randomized to one of six treatment sequences of single IV infusions of danavorexton 44 mg, danavorexton 112 mg, and placebo. Adverse events were monitored throughout the study. Pharmacodynamic assessments included maintenance of wakefulness test (MWT), Karolinska Sleepiness Scale (KSS), and the psychomotor vigilance test (PVT). RESULTS AND CONCLUSION: Among 25 randomized patients, 16 (64.0%) had treatment-emergent adverse events (TEAEs) and 12 (48.0%) had TEAEs considered related to treatment, all mild or moderate. Seven patients (28.0%) had urinary TEAEs: three, seven, and none while taking danavorexton 44 mg, danavorexton 112 mg, and placebo, respectively. There were no deaths or TEAEs leading to discontinuation. Improvements in mean MWT, KSS, and PVT scores were observed with danavorexton 44 mg and 112 mg vs placebo. These findings show that danavorexton can improve subjective and objective measures of EDS in patients with OSA and residual EDS despite adequate CPAP use.

Increase in Volitional Muscle Activation from Childhood to Adulthood: A Systematic Review and Meta-analysis.

INTRODUCTION: Children's maximal muscle strength is consistently lower than adults', even when normalized to body size. Lower volitional muscle activation (VA) in children is often considered one of the main reasons for age-related differences in muscular performance. However, some recent studies have reported similar VA in children and adults, bringing into question whether there is indeed an age-related increase in VA. The purpose of this review was to determine the effect of age on VA during maximal isometric contractions. METHODS: Literature examining VA differences, using twitch interpolation in children (7-14 yr) and adults (16-28 yr), was systematically reviewed. Of the 1915 studies initially identified, 19 data sets were eligible for inclusion in the qualitative analysis and 14 in the quantitative meta-analysis (comprising 207 children and 193 adults). RESULTS: Significantly lower VA in children was reported in 9/19 (47%) studies. A random-effects meta-analysis found a strong effect of age on VA, supporting lower VA in children compared with adults (Hedges' g = 1.55; confidence interval: 0.9-2.13). Moderator analysis included muscle group, sex, children's age, stimulation number (singlet, multiple), type (electric, magnetic), and location (muscle, nerve), of which only muscle group was significant (P < 0.001). A significant Egger's regression test and asymmetrical funnel plot suggest that publication bias may be present. CONCLUSIONS: Overall, these findings suggest that compared with adults, children activate their motor-unit pool less compared with adults. Moreover, that the degree of VA increase with age may be influenced by the muscle examined (upper vs lower extremity). However, more research is needed to elucidate the influence of this possible factor, as the current review contains limited data from upper body muscles. The developmental mechanism responsible for children's lower VA requires further research.

Effects of Solriamfetol on Quality-of-Life Measures from a 12-Week Phase 3 Randomized Controlled Trial.

Rationale: Excessive daytime sleepiness in patients with obstructive sleep apnea is associated with substantial burden of illness.Objectives: To assess treatment effects of solriamfetol, a dopamine/norepinephrine reuptake inhibitor, on daily functioning, health-related quality of life, and work productivity in participants with obstructive sleep apnea and excessive daytime sleepiness as additional outcomes in a 12-week phase 3 trial (www.clinicaltrials.gov identifier NCT02348606).Methods: Participants (N = 476) were randomized to solriamfetol 37.5, 75, 150, or 300 mg or to placebo. Outcome measures included the Functional Outcomes of Sleep Questionnaire short version, Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, and 36-item Short Form Health Survey version 2. A mixed-effects model with repeated measures was used for comparisons with placebo.Results: Demographics, baseline disease characteristics, daily functioning, health-related quality of life, and work productivity were similar across groups. At Week 12, increased functioning and decreased impairment were observed with solriamfetol 150 and 300 mg (mean difference from placebo [95% confidence interval]) on the basis of Functional Outcomes of Sleep Questionnaire total score (1.22 [0.57 to 1.88] and 1.47 [0.80 to 2.13], respectively), overall work impairment (-11.67 [-19.66 to -3.69] and -11.75 [-19.93 to -3.57], respectively), activity impairment (-10.42 [-16.37 to -4.47] and -10.51 [-16.59 to -4.43], respectively), physical component summary (2.07 [0.42 to 3.72] and 1.91 [0.22 to 3.59], respectively), and mental component summary (150 mg only, 2.05 [0.14 to 3.96]). Common adverse events were headache, nausea, decreased appetite, and anxiety.Conclusions: Solriamfetol improved measures of functioning, quality of life, and work productivity in participants with obstructive sleep apnea and excessive daytime sleepiness. Safety was consistent with previous studies.Clinical trial registered with www.clinicaltrials.gov (NCT02348606).

A Pivotal Study to Validate the Performance of a Novel Wearable Sensor and System for Biometric Monitoring in Clinical and Remote Environments.

BACKGROUND: Increasingly, drug and device clinical trials are tracking activity levels and other quality of life indices as endpoints for therapeutic efficacy. Trials have traditionally required intermittent subject visits to the clinic that are artificial, activity-intensive, and infrequent, making trend and event detection between visits difficult. Thus, there is an unmet need for wearable sensors that produce clinical quality and medical grade physiological data from subjects in the home. The current study was designed to validate the BioStamp nPoint® system (MC10 Inc., Lexington, MA, USA), a new technology designed to meet this need. OBJECTIVE: To evaluate the accuracy, performance, and ease of use of an end-to-end system called the BioStamp nPoint. The system consists of an investigator portal for design of trials and data review, conformal, low-profile, wearable biosensors that adhere to the skin, a companion technology for wireless data transfer to a proprietary cloud, and algorithms for analyzing physiological, biometric, and contextual data for clinical research. METHODS: A prospective, nonrandomized clinical trial was conducted on 30 healthy adult volunteers over the course of two continuous days and nights. Supervised and unsupervised study activities enabled performance validation in clinical and remote (simulated "at home") environments. System outputs for heart rate (HR), heart rate variability (HRV) (including root mean square of successive differences [RMSSD] and low frequency/high frequency ratio), activity classification during prescribed activities (lying, sitting, standing, walking, stationary biking, and sleep), step count during walking, posture characterization, and sleep metrics including onset/wake times, sleep duration, and respiration rate (RR) during sleep were evaluated. Outputs were compared to FDA-cleared comparator devices for HR, HRV, and RR and to ground truth investigator observations for activity and posture classifications, step count, and sleep events. RESULTS: Thirty participants (77% male, 23% female; mean age 35.9 ± 10.1 years; mean BMI 28.1 ± 3.6) were enrolled in the study. The BioStamp nPoint system accurately measured HR and HRV (correlations: HR = 0.957, HRV RMSSD = 0.965, HRV ratio = 0.861) when compared to ActiheartTM. The system accurately monitored RR (mean absolute error [MAE] = 1.3 breaths/min) during sleep when compared to a Capnostream35TM end-tidal CO2 monitor. When compared with investigator observations, the system correctly classified activities and posture (agreement = 98.7 and 92.9%, respectively), step count (MAE = 14.7, < 3% of actual steps during a 6-min walk), and sleep events (MAE: sleep onset = 6.8 min, wake = 11.5 min, sleep duration = 13.7 min) with high accuracy. Participants indicated "good" to "excellent" usability (average System Usability Scale score of 81.3) and preferred the BioStamp nPoint system over both the Actiheart (86%) and Capnostream (97%) devices. CONCLUSIONS: The present study validated the BioStamp nPoint system's performance and ease of use compared to FDA-cleared comparator devices in both the clinic and remote (home) environments.

Incidences of vaccine-preventable Haemophilus influenzae type b pneumonia and meningitis in Indonesian children: hamlet-randomised vaccine-probe trial.

BACKGROUND: Most studies of Haemophilus influenzae type b (Hib) disease in Asia have found low rates, and few Asian countries use Hib vaccine in routine immunisation programmes. Whether Hib disease truly is rare or whether many cases remain undetected is unclear. METHODS: To estimate incidences of vaccine-preventable Hib pneumonia and meningitis among children younger than 2 years in Lombok, Indonesia, during 1998-2002, we undertook a hamlet-randomised, controlled, double-blind vaccine-probe study (818 hamlets). Children were immunised (WHO schedule) with diphtheria, tetanus, pertussis (DTP) or DTP-PRP-T (Hib conjugate) vaccine. Vaccine-preventable disease incidences were calculated as the difference in rates of clinical outcomes between DTP and DTP-PRP-T groups. Analyses included all children who received at least one vaccine dose. FINDINGS: We enrolled 55073 children: 28147 were assigned DTP-PRP-T and 26926 DTP. The proportion of pneumonia outcomes prevented by vaccine ranged from less than 0 to 4.8%. Calculated incidences of vaccine-preventable Hib disease (per 10(5) child-years of observation) for outcome categories were: substantial alveolar consolidation or effusion, less than zero (-43 [95% CI -185 to 98]); all severe pneumonia, 264 (95% CI less than zero to 629); all clinical pneumonia, 1561 (270 to 2853); confirmed Hib meningitis, 16 (1.4 to 31); meningitis with cerebrospinal-fluid findings consistent with a bacterial aetiology, 67 (22 to 112); and admission for suspected meningitis or presenting to a clinic with convulsions, 158 (42 to 273). INTERPRETATION: Hib vaccine did not prevent the great majority of pneumonia cases, including those with alveolar consolidation. These results do not support a major role for Hib vaccine in overall pneumonia-prevention programmes. Nevertheless, the study identified high incidences of Hib meningitis and pneumonia; inclusion of Hib vaccine in routine infant immunisation programmes in Asia deserves consideration.

Immunogenicity of a locally produced hepatitis B vaccine with the birth dose stored outside the cold chain in rural Vietnam.

The heat stability of hepatitis B vaccine (HepB vaccine) should enable its storage outside the cold chain (OCC), increasing access to the birth dose in areas lacking refrigeration. We compared the immunogenicity of a locally produced vaccine among infants who received three doses stored within the cold chain (n = 358) or for whom the first dose was stored OCC for up to one month (n = 748). Serum was collected from these infants at age 9-18 months. The vaccine was protective in 80.3% of all infants. There were no differences in the prevalence of a protective level of antibody or antibody titer among groups of infants according to storage strategy. Differences in antibody titer between certain groups of infants could be explained by different vaccination schedules. Where birth dose coverage will be improved, HepB vaccine can be taken OCC for up to one month without affecting its immunogenicity.

Pharmacokinetics, pharmacodynamics and safety of CEP-26401, a high-affinity histamine-3 receptor antagonist, following single and multiple dosing in healthy subjects.

CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement. Two randomized, double-blind, placebo-controlled dose escalation studies with single (0.02 to 5 mg) or multiple administration (0.02 to 0.5 mg once daily) of CEP-26401 were conducted in healthy subjects. Plasma and urine samples were collected to investigate CEP-26401 pharmacokinetics. Pharmacodynamic endpoints included a subset of tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and nocturnal polysomnography. Population pharmacokinetic-pharmacodynamic modeling was conducted on one CANTAB and one polysomnography parameter of interest. CEP-26401 was slowly absorbed (median tmax range 3-6 hours) and the mean terminal elimination half-life ranged from 24-60 hours. Steady-state plasma concentrations were achieved within six days of dosing. CEP-26401 exhibits dose- and time-independent pharmacokinetics, and renal excretion is a major elimination pathway. CEP-26401 had a dose-dependent negative effect on sleep, with some positive effects on certain CANTAB cognitive parameters seen at lower concentrations. The derived three compartment population pharmacokinetic model, with first-order absorption and elimination, accurately described the available pharmacokinetic data. CEP-26401 was generally well tolerated up to 0.5 mg/day with most common treatment related adverse events being headache and insomnia. Further clinical studies are required to establish the potential of low-dose CEP-26401 in cognition enhancement.

Hepatitis B infection in rural Vietnam and the implications for a national program of infant immunization.

To ascertain hepatitis B virus (HBV) infection rates for Vietnam, we surveyed HBV markers in two districts of Thanh Hoa province. We randomly selected 536 infants (9- < or = 18 months old), 228 children (4 to < or = 6 years old), 219 adolescents (14 to < or = 16 years old), and 596 adults (25 to < or = 40 years old). On questioning, none of those surveyed had received vaccine against HBV. Hepatitis B virus surface antigen (HBsAg) and total HBV core antibody (anti-HBc) were measured in all specimens, and HBV e antigen (HBeAg) in those positive for HBsAg, and HBV surface antibody (anti-HBs) were measured in all others. Current infection (HBsAg+) rates were infants = 12.5%, children = 18.4%, adolescents = 20.5%, and adults = 18.8%. Current or previous infection (HBsAg+, anti-HBc+, or anti-HBs+) increased with age (infants = 19.6%, children = 36.4%, adolescents = 55.3%, adults = 79.2%). Rates of HBeAg among those HBsAg+ were infants = 85.1%, children = 88.1%, adolescents = 71.1%, and adults = 30.4%. The epidemiology of HBV in Vietnam resembles that of many southeast Asian nations before introduction of vaccine. Immunization of newborns will have enormous impact on HBV-related morbidity and mortality there.

Improving birth dose coverage of hepatitis B vaccine.

Administration of a birth dose of hepatitis B vaccine (HepB vaccine) to neonates is recommended to prevent mother-to-infant transmission and chronic infection with the hepatitis B virus (HBV). Although manufacturers recommend HepB vaccine distribution and storage at 2-8 degrees C, recognition of the heat stability of hepatitis B surface antigen stimulated research into its use after storage at, or exposure to, ambient or high temperatures. Storage of HepB vaccine at ambient temperatures would enable birth dosing for neonates delivered at home in remote areas or at health posts lacking refrigeration. This article reviews the current evidence on the thermostability of HepB vaccine when stored outside the cold chain (OCC). The reports reviewed show that the vaccines studied were safe and effective whether stored cold or OCC. Field and laboratory data also verifies the retained potency of the vaccine after exposure to heat. The attachment of a highly stable variety of a vaccine vial monitor (measuring cumulative exposure to heat) on many HepB vaccines strongly supports policies allowing their storage OCC, when this will benefit birth dose coverage. We recommend that this strategy be introduced to improve birth dose coverage, especially in rural and remote areas. Concurrent monitoring and evaluation should be undertaken to affirm the safe implementation of this strategy, and assess its cost, feasibility and effect on reducing HBV infection rates. Meanwhile, release of manufacturer data verifying the potency of currently available HepB vaccines after exposure to heat will increase confidence in the use of vaccine vial monitors as a managerial tool during storage of HepB vaccine OCC.

Comparative evaluation of a combined DTP-HB vaccine in the EPI in Chiangrai Province, Thailand.

Combined vaccines have been advocated as an efficient method of paediatric vaccine delivery. This study examined the performance and cost implications for the use of combined DTP-HB vaccine in the Thai immunisation program. Separate DTP and HB and then combined DTP-HB vaccines were used in the infant immunisation program in Chiangrai Province during a 4-year period. DTP vaccination coverage was maintained with the combined vaccine and HB coverage was improved (95.7% for DTP-HB1, 95.2% for DTP-HB2 and 93.8% for DTP-HB3). Seroconversion rates for anti-HBs rose from a baseline of 88.4 to 94.8% with use of the combined vaccine. Seroconversion rates for anti-D (97.5%) and anti-P (89.6%) were higher in the separate vaccine regimen. Although this study was not able to demonstrate that DTP-HB vaccine was more cost saving than the vaccines given separately as baseline vaccine coverage was already high, in settings where coverage rates are much lower the increased cost of combined vaccines may be more justifiable.

Prospective population-based incidence of Haemophilus influenzae type b meningitis in Thailand.

There are limited prospective data for Haemophilus influenzae type b (Hib) disease in Asia, where some countries are considering vaccine introduction. A prospective population-based study was conducted to measure the incidence of Hib meningitis in children in two northern provinces of Thailand. Children <5 years with symptoms consistent with bacterial meningitis were enrolled in the study if inclusion criteria were met. The study enrolled 598 children with clinical meningitis, 76% of whom received lumbar puncture. The rate of probable bacterial meningitis was 26.6/100,000 children <5 years per year. There were four cases of laboratory confirmed Hib meningitis (rate 3.8/100,000 children <5 years per year). These findings suggest a relatively low incidence of Hib meningitis. However, additional data from studies of pneumonia are needed to define the Hib disease burden in Thailand.

Características serológicas y epidemiológicas de la hepatitis vírica aguda en la cuenca Amazónica del Brasil / Serologic and epidemiologic characteristics of acute viral hepatitis in the Amazon Basin of Brazil

From June 1979 to December 1984 a study was made of the frequency and causes of acute hepatitis, including the fulminant form, in Boca do Acre municipality, in the extreme southwestern corner of the Amazon Basin of Brazil. Serologic studies were done by the radioimmunoassay and enzyme immunoassay techniques. Earlier studies of serologic prevalence had indicated that hepatitis Aand hepatitis B were highly endemic throughout the region and that most people were infected during the first ten years of life. Hepatitis A caused 37 per cent of reported cases; it was the predominant type among children over 5 years of age and produced an epidemic pattern. Hepatitis B accounted for 48 per cent of the cases and was a leading cause of disease in both children and adults. Non-A, non-B hepatitis was encountered chiefly in older adults. The incidence of acute and fulminant hepatitis was 3.33 and 0.365 cases per 1 000 persons/year, respectively. In more than 85 per cent of the cases of fulminant hepatitis there was an active hepatitis B virus infection (HBV) and patient sera tested positive for the hepatitis B surface antigen (HBsAg). The most frequent single cause of fulminant hepatitis was superinfection by delta virus of carriers of HBV. The rates of fulminant acute hepatitis found in Boca do Acre are considerably higher than those reported previously in other parts of Brazil or of the Americas

La hepatitis en las Américas : informe del grupo colaborador de la OPS / Hepatitis in the Americas: report of the PAHO collaborating group

Viral hepatitis is a major public health problem throughout the Americas. Each of the several types of hepatitis (A, B, delta, non-A non B) causes significant morbidity and mortality in the Region. Hepatitis B (HB) infection, now a vaccine-preventable disease, requires the most urgent attention at this time. HB infection endemicity in the Region varies from low (temperate North and South America) to moderate (Tropical Central and South America), but high HBV endemicity occurs throughout the Amazon Basin, in Hispaniola, and in certain population of several other tropical countries. Factors such as race, socioeconomic status, and urban-rural status as well as lifestyle (homosexuality, prostitution) and occupational (health care) factors increase HB prevalence in segments of populations, and it is likely that the number of persons at high risk of HB infection is currently underestimated. Chronic consequences of HB infection are likely proportional to disease endemicity and, in high endemicity areas, comparable to those in Africa and Southeast Asia. In addition, delta infection causes high mortality due to fulminant and chronic hepatitis throughout the high HBV endemicity areas in northern South America. Hepatitis A is a disease of childhood throughout the Region, and causes significant morbidity in older children

La hepatitis en las Americas: informe del grupo colaborador de la OPS / Hepatitis in the Americas: report of the PAHO collaborating group

La hepatitis vírica es uno de los principales problemas de salud pública en todas partes de las Américas. Todos los tipos de hepatitis (A, B, delta, no-A, no-B) son causas importantes de morbilidad y mortalidad en la Región. La infección por el virus de la hepatitis B (VHB), actualmente prevenible mediante vacunación, requiere atención inmediata. La endemicidad de esta infección varía de baja (en zonas templadas de América del Norte y América del Sur) a moderada (en zonas tropicales de América Central y América del Sur), pero es muy alta en toda la cuenca del Amazonas, en La Española y en ciertas poblaciones de otros países tropicales. La prevalencia de VHB en grupos de población aumenta conforme a ciertos factores como raza, condición socioeconómica, ambiente urbano o rural, estilo de vida (homosexualidad, prostitución) y factores ocupacionales (servicios de salud), y es posible que se haya subestimado el número de habitantes actualmente en alto riesgo de contraer la infección. Es probable que las consecuencias crónicas de la infección por VHB se relacionen proporcionalmente con la endemicidad y que las zonas más endémicas sean comparables a las de Africa y Asia Sudoriental. Además, la infección delta causa alta mortalidad por hepatitis fulminante y crónica en las zonas de alta endemicidad en el norte de América del Sur. La hepatitis A en la Región es una enfermedad de la niñez y produce altas tasas de morbilidad entre los niños mayores. En los adultos, otra causa importante de morbilidad es la hepatitis no-A, no-B; los tipos de esta hepatitis que se transmiten a través de la sangre existen en todas partes de la Región, pero será necesario realizar estudios adicionales para confirmar la presencia del tipo entérico o epidémico. El control de la infección por hepatitis merece alta prioridad en la Región. Deben dedicarse esfuerzos especiales a la producción de reactivos diagnósticos de bajo costo y al fortalecimiento de los programas de laboratorio...