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While actual, 'objective' experiences with crime in school are very important, so too are 'subjective' experiences with crime--including cognitive perceptions of the likelihood of experiencing school crime and the emotionally-based fear of school crime. Moreover, objective and subjective experiences with crime (and the differences among them) might be quite different depending upon the type of crime in question; patterns of objective versus subjective experiences may not be generalizable but instead might be crime-specific. The present study extends the literature by providing a descriptive comparison of objective versus subjective experiences with school-based crime. More specifically, we compare the prevalence of actual victimization experiences with subjective cognitive-based risk perceptions and emotionally-based, fears of crime for seven different specific offenses and then compare the relationships between these various school-crime experiences and sociodemographic covariates in order to see how objective and subjective experiences are affected similarly or differently by race, class, gender, and place of residence. Finally, we examine the inter-relationships among victimization, risk and [ABSTRACT FROM AUTHOR]

Ovulation is a spatiotemporally coordinated process that involves several tightly controlled events, including oocyte meiotic maturation, cumulus expansion, follicle wall rupture and repair, and ovarian stroma remodeling. To date, no studies have detailed the precise window of ovulation at single-cell resolution. Here, we performed parallel single-cell RNA-seq and spatial transcriptomics on paired mouse ovaries across an ovulation time course to map the spatiotemporal profile of ovarian cell types. We show that major ovarian cell types exhibit time-dependent transcriptional states enriched for distinct functions and have specific localization profiles within the ovary. We also identified gene markers for ovulation-dependent cell states and validated these using orthogonal methods. Finally, we performed cell-cell interaction analyses to identify ligand-receptor pairs that may drive ovulation, revealing previously unappreciated interactions. Taken together, our data provides a rich and comprehensive resource of murine ovulation that can be mined for discovery by the scientific community.

Motivation: Imaging Spatial Transcriptomics techniques characterize gene expression in cells in their native context by imaging barcoded probes for mRNA with single molecule resolution. However, the need to acquire many rounds of high-magnification imaging data limits the throughput and impact of existing methods., Results: We describe the Joint Sparse method for Imaging Transcriptomics, an algorithm for decoding lower magnification Imaging Spatial Transcriptomics data than that used in standard experimental workflows. Joint Sparse method for Imaging Transcriptomics incorporates codebook knowledge and sparsity assumptions into an optimization problem, which is less reliant on well separated optical signals than current pipelines. Using experimental data obtained by performing Multiplexed Error-Robust Fluorescence in situ Hybridization on tissue from mouse brain, we demonstrate that Joint Sparse method for Imaging Transcriptomics enables improved throughput and recovery performance over standard decoding methods., Availability and Implementation: Software implementation of JSIT, together with example files, is available at https://github.com/jpbryan13/JSIT., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: To describe the epidemiology of laboratory-confirmed Diarrhoeagenic Escherichia coli (DEC) cases from active facility-based surveillance in Guatemala., Methods: We collected clinical and risk factor data on enrolled patients (aged 0-52 years) with acute diarrhoea at government healthcare facilities (1 hospital and 6 clinics) in Santa Rosa, Guatemala, during 2008-2009 and 2014-2015. Stool samples were analysed, E. coli identified through culture and biochemical tests, PCR amplification of genes encoding pathotype-specific virulence factors identified specific DEC pathotypes. Healthcare-seeking adjusted incidence rates were calculated., Results: A total of 3041 diarrhoea cases were captured by surveillance (647 hospitalisations (H), 2394 clinic visits (CV)); general E. coli prevalence was 17.9%. DEC pathotypes were identified in 19% (n = 95/497) and 21% (n = 450/2113) in diarrhoea H and CV, respectively. Enteropathogenic E. coli (EPEC) was most frequently isolated (8.2% (n = 41) in diarrhoea H, 12.0% (n = 255) in diarrhoea CV), followed by ETEC (6.8% (n = 34) in H, 6% (n = 128) in CV) and STEC (0.6% (n = 3) in H, 0.6% (n = 13) in CV). We did not find evidence of a difference in severity between DEC and non-DEC diarrhoea. Incidence of DEC clinic visits and hospitalisations was 648.0 and 29.3, respectively, per 10,000 persons aged ≤5 years and 36.8 and 0.4, respectively, per 10,000 persons aged >5 years., Conclusions: DEC pathotypes, especially EPEC and ETEC, were detected frequently from patients presenting with diarrhoeal illness in Santa Rosa, Guatemala. Our findings suggest that preventive interventions should be prioritised for young children., (© 2022 John Wiley & Sons Ltd.)

Household air pollution (HAP) due to solid fuel use during pregnancy is associated with adverse birth outcomes. The real-life effectiveness of clean cooking interventions has been disappointing overall yet variable, but the sociodemographic determinants are not well described. We measured personal 24-h PM 2.5 (particulate matter <2.5 µm in aerodynamic diameter) thrice in pregnant women ( n = 218) gravimetrically with Teflon filter, impactor, and personal pump setups. To estimate the effectiveness of owning chimney and liquefied petroleum gas (LPG) stoves (i.e., proportion of PM 2.5 exposure that would be prevented) and to predict subject-specific typical exposures, we used linear mixed-effects models with log (PM 2.5 ) as dependent variable and random intercept for subject. Median (IQR) personal PM 2.5 in µg/m 3 was 148 (90-249) for open fire, 78 (51-125) for chimney stove, and 55 (34-79) for LPG stoves. Adjusted effectiveness of LPG stoves was greater in women with ≥6 years of education (49% (95% CI: 34, 60)) versus <6 years (26% (95% CI: 5, 42)). In contrast, chimney stove adjusted effectiveness was greater in women with <6 years of education (50% (95% CI: 38, 60)), rural residence (46% (95% CI: 34, 55)) and lowest SES (socio-economic status) quartile (59% (95% CI: 45, 70)) than ≥6 years education (16% (95% CI: 22, 43)), urban (23% (95% CI: -164, 42)) and highest SES quartile (-44% (95% CI: -183, 27)), respectively. A minority of LPG stove owners (12%) and no chimney owner had typical exposure below World Health Organization Air Quality guidelines (35 μg/m 3 ). Although having a cleaner stove alone typically does not lower exposure enough to protect health, understanding sociodemographic determinants of effectiveness may lead to better targeting, implementation, and adoption of interventions.

Background: Diarrhea is a major cause of morbidity and mortality, yet incidence and etiology data are limited. We conducted laboratory-based diarrhea surveillance in Guatemala., Methods: A diarrhea case was defined as ≥3 loose stools in a 24-h period in a person presenting to the surveillance facilities. Epidemiologic data and stool specimens were collected. Specimens were tested for bacterial, parasitic, and viral pathogens. Yearly incidence was adjusted for healthcare seeking behaviors determined from a household survey conducted in the surveillance catchment area., Results: From November 2008 to December 2012, the surveillance system captured 5331 diarrhea cases; among these 1381 (26%) had specimens tested for all enteric pathogens of interest. The adjusted incidence averaged 659 diarrhea cases per 10,000 persons per year, and was highest among children aged < 5 years, averaging 1584 cases per 10,000 children per year. Among 1381 (26%) specimens tested for all the pathogens of interest, 235 (17%) had a viral etiology, 275 (20%) had a bacterial, 50 (4%) had parasites, and 86 (6%) had co-infections. Among 827 (60%) specimens from children aged < 5 years, a virus was identified in 196 (23%) patients; 165 (20%) had norovirus and 99 (12%) rotavirus, including co-infections. Among 554 patients aged ≥5 years, 103 (19%) had a bacterial etiology, including diarrheagenic Escherichia coli in 94 (17%) cases, Shigella spp. in 31 (6%), Campylobacter spp. in 5 (1%), and Salmonella spp. in 4 (1%) cases. Detection of Giardia and Cryptosporidium was infrequent (73 cases; 5%)., Conclusions: There was a substantial burden of viral and bacterial diarrheal diseases in Guatemala, highlighting the importance of strengthening laboratory capacity for rapid detection and control and for evaluation of public health interventions.

The American Society for Tropical Medicine and Hygiene recently inaugurated an award for the best clinical research article published in the society's journal in the previous year. This article summarizes both the process of selecting the winner and several themes that stood out in those articles which rose to the top for consideration. Themes of note included the importance of doing clinical research outside of referral centers, the complexity that must be considered when implementing interventions, incorporation of both ends of the age spectrum into studies, and considering cost-effectiveness and opportunity cost of interventions.

Background: Influenza is a major cause of respiratory illness resulting in 3-5 million severe cases and 291,243-645,832 deaths annually. Substantial health and financial burden may be averted by annual influenza vaccine application, especially for high risk groups., Methods: We used an active facility-based surveillance platform for acute respiratory diseases in three hospitals in Guatemala, Central America, to estimate the incidence of laboratory-confirmed hospitalized influenza cases and identify risk factors associated with severe disease (defined as admission to the intensive care unit (ICU) or death). We enrolled patients presenting with signs and symptoms of acute respiratory infection (ARI) and obtained naso- and oropharyngeal samples for real-time reverse transcriptase polymerase chain reaction (RT-PCR). We used multivariable logistic regression to identify risk factors for ICU admission or death, adjusted for age and sex., Results: From May 2008 to July 2012, among 6326 hospitalized ARI cases, 446 (7%) were positive for influenza: of those, 362 (81%) had influenza A and 84 (18%) had influenza B. Fifty nine percent of patients were aged ≤ 5 years, and 10% were aged ≥ 65 years. The median length of hospitalization was 5 days (interquartile range: 5). Eighty of 446 (18%) were admitted to the ICU and 28 (6%) died. Among the 28 deaths, 7% were aged ≤ 6 months, 39% 7-60 months, 21% 5-50 years, and 32% ≥ 50 years. Children aged ≤ 6 months comprised 19% of cases and 22% of ICU admissions. Women of child-bearing age comprised 6% of cases (2 admitted to ICU; 1 death). In multivariable analyses, Santa Rosa site (adjusted odds ratio [aOR] = 10, 95% confidence interval [CI] = 2-50), indigenous ethnicity (aOR = 4, 95% CI = 2-13, and radiologically-confirmed pneumonia (aOR = 5, 95% CI = 3-11) were independently associated with severe disease. Adjusted for hospital utilization rate, annual incidence of hospitalized laboratory-confirmed influenza was 24/100,000 overall, 93/100,000 for children aged < 5 years and 50/100,000 for those ≥ 65 years., Conclusions: Influenza is a major contributor of hospitalization and death due to respiratory diseases in Guatemala. Further application of proven influenza prevention and treatment strategies is warranted.

Background: We describe the epidemiology and antimicrobial susceptibility patterns of culture-confirmed Shigella infections in facility-based surveillance sites in Guatemala. Current studies using quantitative molecular diagnostics suggest Shigella may contribute most to the global diarrheal disease burden. Since identification of Shigella requires culturing techniques using stool specimens and few laboratories in Guatemala routinely culture for this pathogen, little is known about the true burden of Shigella in Guatemala or, importantly, the antimicrobial resistance patterns., Methods: Clinical, epidemiological, and laboratory data were collected on 5399 patients with acute diarrhea (≥3 loose stools in 24 h) from June 2007-August 2012. Multidrug resistance (MDR) was defined as resistance to ampicillin and trimethoprim/sulfamethoxazole., Results: Five percent (261) of stool specimens yielded Shigella spp. The annual incidence of laboratory-confirmed infections ranged from 5.0 to 24.1 per 100,000 persons in Santa Rosa and 0.3 to 6.2 per 100,000 in Quetzaltenango; 58% of cases occurred in children < 5 years of age. Thirty patients were hospitalized; one patient died. Oral rehydration or intravenous solution was used to treat 72% of hospitalized and 15% of ambulatory cases. Fifty-nine percent of cases were S. flexneri and 51% of cases were MDR., Conclusions: Shigella is an important cause of bacterial diarrhea in children and prevalence of MDR highlights the importance of appropriate treatment regimens. This study demonstrates that strengthening laboratory capacity in Guatemala can help determine causes which can lead to prevention of diarrheal diseases, particularly in children. Such capacity building is also critical for rapid detection and control of public health threats at their source and therefore for global health security.

Background: Acute respiratory infection (ARI) is an important cause of mortality in children and adults. However, studies assessing risk factors for ARI-related deaths in low- and middle-income settings are limited. We describe ARI-related death and associated factors among children aged < 2 years and adults aged ≥18 years hospitalized with ARI in Guatemala., Methods: We used respiratory illness surveillance data in Guatemala from 2007 to 2013. ARI was defined as evidence of acute infection and ≥ 1 sign/symptom of respiratory disease in hospitalized patients. Clinical, sociodemographic, and follow-up data were gathered. Nasopharyngeal/oropharyngeal swabs were collected from patients with ARI and tested for 6 respiratory viruses; urine was collected only from adults with ARI and tested for pneumococcal antigen. Blood cultures and chest radiographs were performed at the physician's discretion. Radiographs were interpreted per World Health Organization guidelines to classify endpoint pneumonia (i.e. suggestive of bacterial pneumonia). Multivariable logistic regression was used to compare characteristics of patients with fatal cases, including those who died in-hospital or were discharged in a moribund state, with those of patients with non-fatal cases., Results: Among 4109 ARI cases identified in hospitalized children < 2 years old, 174 (4%) were fatal. Median age at admission was 4 and 6 months for children with fatal and non-fatal cases, respectively. Factors associated with fatality included low weight-for-age, low family income, heart disease, and endpoint pneumonia; breastfeeding and respiratory syncytial virus (RSV) detection were negatively associated with fatality. Among 1517 ARI cases identified in hospitalized adults ≥18 years, 181 (12%) episodes were fatal. Median age at admission was 57 years for adults with fatal and non-fatal cases. Low body mass index, male sex, kidney disease, and endpoint pneumonia were significantly more common among patients with fatal versus non-fatal cases., Conclusions: Our findings highlight some of the factors that must be addressed in order to reduce ARI-related mortality, including promotion of good nutrition, breastfeeding, management and prevention of chronic comorbidities, and poverty reduction. Although no specific pathogen increased risk for death, endpoint pneumonia was significantly associated with fatality, suggesting that the pneumococcal conjugate vaccine could contribute to future reductions in ARI-related mortality.

Background: Acute diarrhea is an important cause of morbidity and mortality in children and is associated with approximately 500,000 deaths/year globally. Rotavirus and norovirus are leading causes of acute diarrhea accounting for more than half of this burden., Objective/study Design: To determine the prevalence and genotype distribution of acute diarrhea caused by rotavirus, norovirus, sapovirus and astrovirus among children <5 years of age at two departments in Guatemala from January 2014 to December 2015, we tested 471 stool specimens (202 samples from hospitalized children and 269 samples from children in ambulatory clinics) by real-time reverse transcription-PCR and genotyped positive samples., Results: Rotavirus was detected in 20.4%, norovirus in 18.5%, sapovirus in 7% and astrovirus in 4.2% of the samples. Co-infection of rotavirus and norovirus was found in 2.6% of the samples. Most norovirus (87.4%) and rotavirus (81.3%) infections were detected in children in the 6-12 months age group. The proportion of patients with rotavirus (34%) and norovirus (23%) was higher in hospitalized patients compared to ambulatory patients, whereas the prevalence of sapovirus and astrovirus was similar in both settings. Of the 40 genotyped norovirus strains, 62.5% were GII.4 and 15% GII.3. Sapovirus genotypes included GI.1 (15.4%), GII.2 (15.4%), GII.5 (38.5%) and GIV.1 (30.8%)., Conclusions: Our data demonstrate that in 2014-2015, gastroenteritis viruses account for 50% of acute diarrhea in children younger than 5 years of age in Guatemala, highlighting the importance of continuous surveillance to guide impact of the current rotavirus vaccine and formulation of future norovirus vaccines., (Copyright © 2019. Published by Elsevier B.V.)

Background: Pertussis is an important cause of hospitalization and death in infants too young to be vaccinated (aged <2 months). Limited data on infant pertussis have been reported from Central America. The aim of this study was to characterize acute respiratory illnesses (ARIs) attributable to Bordetella pertussis among infants enrolled in an ongoing surveillance study in Guatemala., Methods: As part of a population-based surveillance study in Guatemala, infants aged <2 months who presented with ARI and required hospitalization were enrolled, and nasopharyngeal and oropharyngeal swab specimens were obtained. For this study, these specimens were tested for B pertussis using real-time polymerase chain reaction (PCR)., Results: Among 301 infants hospitalized with ARI, we found 11 with pertussis confirmed by PCR (pertussis-positive infants). Compared to pertussis-negative infants, pertussis-positive infants had a higher mean admission white blood cell count (20900 vs 12579 cells/μl, respectively; P = .024), absolute lymphocyte count (11517 vs 5591 cells/μl, respectively; P < .001), rate of admission to the intensive care unit (64% vs 35%, respectively; P = .054), and case fatality rate (18% vs 3%, respectively; P = .014). Ten of the 11 pertussis-positive infants had cough at presentation; the majority (80%) of them had a cough duration of <7 days, and only 1 had a cough duration of >14 days. Fever (temperature ≥ 38°C) was documented in nearly half (45%) of the pertussis-positive infants (range, 38.0-38.4°C)., Conclusions: In this study of infants <2 months of age hospitalized with ARI in Guatemala, pertussis-positive infants had a high rate of intensive care unit admission and a higher case fatality rate than pertussis-negative infants.

Introduction: Chagas disease, a neglected tropical disease that affects millions of Latin Americans, has been effectively controlled in Guatemala after multiple rounds of indoor residual insecticide spraying (IRS). However, a few foci remain with persistent Triatoma dimidiata infestation. One such area is the municipality of Comapa, Department of Jutiapa, in the southeastern region of Guatemala, where control interventions appear less effective. We carried out three cross sectional entomological and serological surveys in Comapa to evaluate a decade of vector control activities. Baseline serological (1999) and entomological (2001-2) surveys were followed by three rounds of insecticide applications (2003-2005) and intermittent focal spraying of infested houses, until approximately 2012. Household inspections to determine entomological indices and construction materials were conducted in 2001, 2007 and 2011. Seroprevalence surveys were conducted in school-age children in 1999, 2007 and 2015, and in women of child bearing age (15-44 years) only in 2015. After multiple rounds of indoor residual sprayings (IRS), the infestation index decreased significantly from 39% (2001-2) to 27% (2011). Household construction materials alone predicted <10% of infested houses. Chagas seroprevalence in Comapa declined in school-aged children by 10-fold, from 10% (1999) to 1% (2015). However, seroprevalence in women of child bearing age remains >10%., Conclusion: After a decade of vector control activities in Comapa, there is evidence of significantly reduced transmission. However, the continued risk for vector-borne and congenital transmission pose a threat to the 2022 Chagas disease elimination goal. Systematic integrated vector control and improved Chagas disease screening and treatment programs for congenital and vector-borne disease are needed to reach the elimination goal in regions with persistent vector infestation., Competing Interests: The authors have declared that no competing interests exist.

Background: Preterm birth is the leading cause of death among children <5 years of age. Accurate determination of prematurity is necessary to provide appropriate neonatal care and guide preventive measures. To estimate the most accurate method to identify infants at risk for adverse outcomes, we assessed the validity of two widely available methods-last menstrual period (LMP) and the New Ballard (NB) neonatal assessment-against ultrasound in determining gestational age and preterm birth in highland Guatemala., Methods: Pregnant women (n = 188) were recruited with a gestational age <20 weeks and followed until delivery. Ultrasound was performed by trained physicians and LMP was collected during recruitment. NB was performed on infants within 96 hours of birth by trained study nurses. LMP and NB accuracy at determining gestational age and identifying prematurity was assessed by comparing them to ultrasound., Results: By ultrasound, infant mean gestational age at birth was 38.3 weeks (SD = 1.6) with 16% born at less than 37 gestation. LMP was more accurate than NB (mean difference of +0.13 weeks for LMP and +0.61 weeks for NB). However, LMP and NB estimates had low agreement with ultrasound-determined gestational age (Lin's concordance<0.48 for both methods) and preterm birth (κ<0.29 for both methods). By LMP, 18% were judged premature compared with 6% by NB. LMP underestimated gestational age among women presenting later to prenatal care (0.18 weeks for each additional week). Gestational age for preterm infants was overestimated by nearly one week using LMP and nearly two weeks using NB. New Ballard neuromuscular measurements were more predictive of preterm birth than those measuring physical criteria., Conclusion: In an indigenous population in highland Guatemala, LMP overestimated prematurity by 2% and NB underestimated prematurity by 10% compared with ultrasound estimates. New, simple and accurate methods are needed to identify preterm birth in resource-limited settings worldwide.

Chagas disease is a neglected tropical disease that continues to affect populations living in extreme poverty in Latin America. After successful vector control programs, congenital transmission remains as a challenge to disease elimination. We used the PRECEDE-PROCEED planning model to develop strategies for neonatal screening of congenital Chagas disease in rural communities of Guatemala. These communities have persistent high triatomine infestations and low access to healthcare. We used mixed methods with multiple stakeholders to identify and address maternal-infant health behaviors through semi-structured interviews, participatory group meetings, archival reviews and a cross-sectional survey in high risk communities. From December 2015 to April 2016, we jointly developed a strategy to illustratively advertise newborn screening at the Health Center. The strategy included socioculturally appropriate promotional and educational material, in collaboration with midwives, nurses and nongovernmental organizations. By March 2016, eight of 228 (3.9%) pregnant women had been diagnosed with T. cruzi at the Health Center. Up to this date, no neonatal screening had been performed. By August 2016, seven of eight newborns born to Chagas seropositive women had been parasitologically screened at the Health Center, according to international standards. Thus, we implemented a successful community-based neonatal screening strategy to promote congenital Chagas disease healthcare in a rural setting. The success of the health promotion strategies developed will depend on local access to maternal-infant services, integration with detection of other congenital diseases and reliance on community participation in problem and solution definition.

AbstractThe Department of Santa Rosa, Guatemala, is targeted for malaria elimination. However, compared with 2011, a 13-fold increase in cases was reported in 2012. To describe the epidemiology of malaria in Santa Rosa in the setting of the apparent outbreak, demographic and microscopic data from 2008 to 2013 were analyzed. In April 2012, a new surveillance strategy, funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, was introduced involving more active case detection, centralized microscopy, increased community engagement, and expanded vector control. Interviews with vector control personnel and site visits were conducted in June 2013. From 2008 to 2013, 337 cases of malaria were reported. The increase in cases occurred largely after the new surveillance strategy was implemented. Most (137/165; 83%) 2012 cases came from one town near a lake. Plasmodium vivax was the malaria species detected in all cases. Cases were detected where malaria was not previously reported. Monthly rainfall or/and temperature did not correlate with cases. Interviews with public health personnel suggested that the new funding, staffing, and strategy were responsible for improved quality of malaria detection and control and thus the increase in reported cases. Improvements in surveillance, case detection, and funding appear responsible for the temporary increase in cases, which thus may paradoxically indicate progress toward elimination.

Poor sanitation could pose greater risk for enteric pathogen transmission at higher human population densities because of greater potential for pathogens to infect new hosts through environmentally mediated and person-to-person transmission. We hypothesized that incidence and prevalence of diarrhea, enteric protozoans, and soil-transmitted helminth infections would be higher in high-population-density areas compared with low-population-density areas, and that poor sanitation would pose greater risk for these enteric infections at high density compared with low density. We tested our hypotheses using 6 years of clinic-based diarrhea surveillance (2007-2013) including 4,360 geolocated diarrhea cases tested for 13 pathogens and a 2010 cross-sectional survey that measured environmental exposures from 204 households (920 people) and tested 701 stool specimens for enteric parasites. We found that population density was not a key determinant of enteric infection nor a strong effect modifier of risk posed by poor household sanitation in this setting., (© The American Society of Tropical Medicine and Hygiene.)

Background: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children globally, with the highest burden in low- and middle-income countries where the association between RSV activity and climate remains unclear., Methods: Monthly laboratory-confirmed RSV cases and associations with climate data were assessed for respiratory surveillance sites in tropical and subtropical areas (Bangladesh, China, Egypt, Guatemala, Kenya, South Africa, and Thailand) during 2004-2012. Average monthly minimum and maximum temperatures, relative humidity, and precipitation were calculated using daily local weather data from the US National Climatic Data Center., Results: RSV circulated with 1-2 epidemic periods each year in site areas. RSV seasonal timing and duration were generally consistent within country from year to year. Associations between RSV and weather varied across years and geographic locations. RSV usually peaked in climates with high annual precipitation (Bangladesh, Guatemala, and Thailand) during wet months, whereas RSV peaked during cooler months in moderately hot (China) and arid (Egypt) regions. In South Africa, RSV peaked in autumn, whereas no associations with seasonal weather trends were observed in Kenya., Conclusions: Further understanding of RSV seasonality in developing countries and various climate regions will be important to better understand the epidemiology of RSV and for timing the use of future RSV vaccines and immunoprophylaxis in low- and middle-income countries.

The epidemiology of malaria among U.S. government personnel attached to diplomatic posts has not been reported. We reviewed malaria surveillance reports on persons with onset of symptoms between January 1988 and December 2004. Among 684 slide-proven cases, the median age was 36 years. There were 565 (82.6%) cases of Plasmodium falciparum malaria and 56 (8.2%) of P. vivax malaria. A total of 89.9% were infected in Africa and 5.8% were infected in Asia; 95% of the P. falciparum cases originated in sub-Saharan Africa. One-fourth of all cases were reported in 1990-1991. The average annual incidence (per 1,000 personnel) of Plasmodium between 1995 and 1999 was highest in west Africa (8.96), followed by central Africa (8.08), and east Africa (4.27). No or irregular chemoprophylaxis was reported by 58.5%. Among those who indicated regular prophylaxis, 78% took regimens no longer considered adequate. In sub-Saharan Africa, cases were reported in every month. There were three deaths. Prevention of malaria among U.S. Government employees attached to diplomatic posts should particularly focus on those serving in sub-Saharan Africa and malarious areas of Asia.

The costs of mefloquine, chloroquine, doxycycline, primaquine, and atovaquone/proguanil are calculated for various durations of exposure to malaria. The cost is included for detecting glucose 6-phosphate dehydrogenase (G6PD) deficiency before administering primaquine for primary or terminal prophylaxis. For durations of exposure ranging from 3 to 730 days, if no terminal prophylaxis is given, doxycycline (generic) is the least expensive regimen. Compared with doxycycline hyclate, chloroquine costs three to four times more, and primaquine, after screening for G6PD, costs about eight times more. Atovaquone/proguanil is less expensive than mefloquine for a 3-day exposure, but more expensive for 7 or more days. When terminal chemoprophylaxis with primaquine for 14 days is used in addition to doxycycline, mefloquine, chloroquine, or atovaquone/proguanil, primaquine alone is the least expensive regimen for exposures of < 10 days. Thereafter, doxycycline plus 14 days of primaquine is most economical. For subsequent exposures when G6PD status is already known, primaquine alone is the least expensive regimen for up to 9 days of exposure, but doxycycline is less expensive thereafter. In general, generic doxycycline hyclate is the least expensive regimen. Primaquine alone is economically attractive. Mefloquine, doxycyline monohydrate, and atovaquone/proguanil, the most expensive regimens, are similar in cost for a 7-day exposure, but thereafter, atovaquone/proguanil is much more expensive.

The measurement of antibodies to hepatitis E virus (anti-HEV) has been essential for understanding the epidemiology of hepatitis E. Studies to determine the prevalence of HEV infections require a reliable serologic assay that is sensitive and specific. It is also important to distinguish the acute from the convalescent phase of an infection; this usually requires the detection of the immunoglobulin M (IgM) class of antibody. Few enzyme immunoassays (EIAs) that measure IgM anti-HEV have been described, and most have utilized the sandwich method. The present study describes an EIA that detects IgM anti-HEV by antibody class capture methodology. The assay was validated by using serum and/or plasma panels from experimentally infected nonhuman primates. It was used to demonstrate an anamnestic response and the reappearance of IgM anti-HEV in a chimpanzee experimentally challenged with HEV at two different times 45 months apart. The class capture method was more sensitive than the sandwich EIA when used to test clinical samples from two hepatitis E epidemics in Pakistan; it also had the advantage of distinguishing IgM anti-HEV in the presence of high titers of IgG anti-HEV.

An outbreak of hepatitis caused by hepatitis E virus (HEV) in Abbottabad, Pakistan was traced to fecal contamination of a water system. Of 109 men hospitalized with hepatitis, 104 (95%) had serologic evidence of acute hepatitis E (IgM antibody to HEV [anti-HEV]), three (3%) probably had acute hepatitis E (high titers of IgG anti-HEV without IgM), and two had acute hepatitis A. Among a subset of 44 men with acute hepatitis E from whom three serum specimens were obtained over a four-month period, the anti-HEV IgG geometric mean titers (GMTs) decreased from 1,519 during the outbreak to 657 at four months. The IgM anti-HEV was detected in 40 (91%) of 44 sera obtained at admission (GMT = 533 during acute disease), but in only six (14%) four months later. The prevalence of anti-HEV in this population before the outbreak was estimated to be 30%. The presence of IgG anti-HEV appeared to protect against clinical hepatitis or development of serologic evidence of new infection with HEV. This is the second major epidemic of hepatitis E in the Pakistani military confirmed by an anti-HEV enzyme-linked immunosorbent assay (ELISA). Evidence that pre-existing antibody as measured by this ELISA protects against disease is important for assessment of vaccine development.

Hepatitis is common in the Stann Creek District of southern Belize. To determine the etiologies, incidence, and potential risk factors for acute jaundice, we conducted active surveillance for cases. Cases of jaundice diagnosed by a physician within the previous 6 weeks were enrolled. Evaluation included a questionnaire and laboratory tests for hepatitis A, B, C, D, and E, a blood film for malaria, and a serologic test for syphilis. Etiologies of jaundice among 62 evaluable patients included acute hepatitis A, 6 (9.7%), acute hepatitis B, 49 (79.0%), hepatitis non-A-E, 2 (3.2%), and malaria, 5 (8.1%). There were no cases of acute hepatitis E. One patient each with antibody to hepatitis C and D were detected. The annualized incidence of hepatitis A was 0.26 per 1,000. All cases of hepatitis A were in children 4-16 years of age. The annualized incidence of hepatitis B, 2.17 per 1,000, was highest in adults aged 15-44 years (4.4 per 1,000) and was higher in men (36 cases; 3.09 per 1,000) than women (13 cases; 1.19 per 1,000). Four (31%) of the women with hepatitis B were pregnant. The annualized incidence was significantly higher in Mestizo (6.18 per 1000) and Maya (6.79 per 1,000) than Garifuna (0.38 per 1,000) or Creole (0.36 per 1,000). Persons with hepatitis B were significantly more likely to be born outside of Belize (82%), had been in Belize < 5 years (73%), and lived and worked in rural areas (96%) than was the general population. Of those > or = 14 years of age with hepatitis B, only 36% were married. Few persons admitted to transfusions, tattoos, IV drug use, multiple sexual partners, visiting prostitutes, or sexually transmitted diseases. Only 1 of 49 had a reactive test for syphilis. Six patients were hospitalized (including 3 with acute hepatitis B and one with hepatitis A), and none to our knowledge died. Acute hepatitis B is the most common cause of viral hepatitis in the Stann Creek District, but the modes of transmission remain obscure. Infants, women attending prenatal clinics, and new workers are potential targets for immunization with hepatitis B vaccine.

Hepatitis A and B viruses are threats to deployed military forces. The objective of this study was to determine the feasibility of concurrent vaccination against hepatitis A and B viruses. One hundred five healthy persons, 20 to 49 years of age and without serologic markers to hepatitis A or B viruses, were randomized to receive an inactivated hepatitis A vaccine (HEP A; 25 units in 0.5 mL), recombinant hepatitis B vaccine (HEP B; 10 micrograms in 1.0 mL), or both (HEP A & B) concurrently in separate arms. Vaccines were administered intramuscularly at 0, 1, and 6 months. Sera obtained at 1, 2, 6, 7, and 12 months after the first dose were tested for quantitative antibody to hepatitis A virus (anti-HAV) and antibody to hepatitis B surface antigen. Local reactions (e.g., pain) were reported by less than half of the volunteers and were similar at the site of HEP A, whether given alone or concurrently. However, more persons complained of pain (usually mild) at the HEP B site when HEP B was given concurrently with HEP A compared with HEP B alone (43% vs. 15%, 34% vs. 9%, and 42% vs. 15% for doses 1, 2, and 3, respectively; p < 0.05 for each dose). Among persons immunized with HEP A alone or HEP A & B, the proportion with > or = 10 mIU/mL anti-HAV was 83% in both groups 1 month after dose 1 and 100% at months 2, 7, and 12. The geometric mean concentrations of anti-HAV increased from 21 mIU/mL at month 1 to 2,649 and 2,312 mIU/mL in the HEP A and HEP A & B groups, respectively, at month 7. The response to HEP B was similar whether administered alone or concurrently. Antibody responses were similar in those receiving HEP A or HEP B concurrently or alone, but more subjects reported pain (usually mild) at the HEP B site after concurrent vaccination than after HEP B alone. Further work should be conducted to approve HEP A for patients younger than 2 years of age and to develop combined HEP A and HEP B vaccines in the United States.

The immunogenicity, tolerability and interchangeability of two hepatitis A vaccines, Vaqta (Merck and Co.) and Havrix (SmithKline) were studied in a randomized, crossover, controlled clinical trial. Vaccine was administered to 201 volunteers at 0 and 26 weeks in one of four vaccine regimens: Havrix-Havrix; Havrix-Vaqta; Vaqta-Havrix or Vaqta-Vaqta. Seroconversion rates (>/=10 mIU/ml) for those whose first dose was Vaqta or Havrix, respectively, were: 41/96 (43%) versus 30/95 (32%) (P=0.15) at 2 weeks and 91/98 (93%) versus 84/97 (87%) (P=0.43) at 4 weeks, and 100% at 26 weeks. Geometric mean concentrations (GMC) of total antibody to hepatitis A virus (anti-HAV) for Vaqta and Havrix were 189 and 114 mIU/ml (P=0.011) at 4 weeks and 234 and 136 mIU/ml (P<0.001) at 26 weeks. At 30 weeks, the GMC after two doses of Havrix was 2612 mIU/ml compared with 5497 after two doses of Vaqta (P<0.001). The GMC in the Havrix-Vaqta group was 5672 mIU/ml compared with 3077 mIU/ml in the Vaqta-Havrix group (P<0.001). Less than half of vaccine recipients reported tenderness or pain. In this study, seroconversion rates of the two vaccines were similar. Vaqta produces significantly higher anti-HAV antibody than Havrix. Crossover immunization is well tolerated and results in high antibody concentrations, especially when Vaqta is the booster dose. The significance of higher anti-HAV antibody concentrations in terms of long-term protection is unknown.

The dose response relationship of 25-, 50-, and 100-U doses of an inactivated hepatitis A vaccine was examined in 358-seronegative volunteers in a 2-dose schedule. The 50-U and 100-U groups had statistically significantly higher seroconversion rates than the 25-U group at weeks 2, 4, 8, and 24. Seroconversion was statistically significantly greater for the 100-U compared with the 25- and 50-U doses 2 weeks after the first injection but was not significantly different by 4 weeks after the first injection in the 50- and 100-U dose groups. After 2 injections, all subjects in all groups seroconverted. The vaccine was well tolerated at all dosage levels.

Cross-sectional studies were conducted to determine the prevalence of antibody to Trypanosoma cruzi, the agent of Chagas' disease among three populations in Belize. Specimens were tested using a second-generation enzyme-linked immunoassay (EIA). Confirmatory testing with three single-antigen EIAs and a radioimmunoprecipitation assay (RIPA) were performed. Five (0.5%) of 962 blood donors at the Belize City Hospital were reactive including four (6%) of 65 donors from countries known to be endemic for Chagas' disease and one (0.1%) of 861 from Belize (P < 0.001). Among 467 healthy members of the Belize Defense Force, none were reactive. The third group included workers and families primarily from other Central American countries living on a banana plantation in a rural area of the country. Twenty-seven (6.1%) of 442 sera were reactive. The prevalence was 5.3% of 75 < 15 years of age, 4.2% of 236 15-34 years of age, and 9.7% of 124 > or = 35 years of age (P = 0.11, by chi-square for trend). The prevalence was similar in males (6.7% of 280) and females (5.8% of 154). The prevalence of those born in Belize (4 of 56, 7.1%) was similar with that of those born in El Salvador (9 of 110, 8.2%), Guatemala (6 of 117, 5.1%), and Honduras (8 of 129, 6.2%). Of the four persons with reactive sera who were born in Belize, the immigrant mother of one was also reactive, suggesting possible congenital transmission. Among 31 sera repeatedly reactive by EIA to T. cruzi that were further studied, 22 (71%) were reactive by at least two of three single-antigen confirmatory EIAs and 29 (94%) by RIPA. Additional studies should focus on the epidemiology of T. cruzi and ways to reduce risk of transfusion-related infections in Belize.

Background: The timing and best regimen for a booster dose of hepatitis B vaccine have not been determined., Methods: Two studies were conducted to determine the response to a booster dose of 5 micrograms recombinant hepatitis B vaccine. In the first study, a 5 micrograms (0.5 ml) dose of Recombivax HB was administered intramuscularly 38 months after the initial dose to 71 volunteers. In a second study, we offered a 5 micrograms dose recombinant hepatitis B vaccine, either Recombivax HB (0.5 ml) or Engerix B (0.25 ml), to students who had previously been immunized with three doses of vaccine., Results: In the first study, among the 44 persons for whom postbooster sera were available, the geometric mean concentration of anti-hepatitis B surface antigens increased from 42 to 2090 mIU/ml after the 5 micrograms (0.5 ml) dose of Recombivax. In the second study, after a 5 micrograms (0.5 ml) dose of Recombivax, the geometric mean concentration increased from 43 to 990 mIU/ml (n = 48), and in the group that received a 5 micrograms (0.25 ml) dose of Engerix B, the concentration increased from 83 to 2337 mIU/ml (n = 45) (p = 0.18 for postdose concentrations)., Conclusion: A 5 micrograms dose of recombinant vaccine results in an excellent booster response at a cost one fourth to one half that of a full 1 ml dose of vaccine.

To determine the characteristics of clinical illness accompanying Plasmodium falciparum infection induced by controlled exposure to infected mosquitoes, records of 118 volunteers participating in studies conducted between 1985 and 1992 were reviewed. One hundred fourteen volunteers (97%) reported at least one symptom attributable to malaria, with fatigue, myalgias or arthralgias, headache, and chills most commonly reported. The median duration of symptoms was 3 days. Fever was recorded in 61% of volunteers; 4 volunteers had temperatures >40 degrees C. Neutropenia and thrombocytopenia were present in 9% and 12% of volunteers, respectively. Despite counts as low as 658/microL (neutrophils) or 73,000/microL (platelets), no secondary infectious or hemorrhagic complications occurred. In all cases, volunteers recovered completely and laboratory values returned to baseline after specific antimalarial therapy. Recrudescence did not occur in any volunteer. In this model, mosquito inoculation of P. falciparum is a reliable, safe, and well-tolerated method of experimental challenge.

Women and their infants may benefit from therapeutic interventions when hepatitis B, human immunodeficiency virus (HIV), or syphilis are detected during the prenatal period. We initiated hepatitis B and HIV screening of women attending prenatal clinics in Belize. Risk factor assessment information for hepatitis B infection and demographic data were determined by interview. Of 543 evaluable women, 81 (14.9%) were seropositive for hepatitis B core antibody (anti-HBc); one woman had asymptomatic hepatitis B surface antigenemia. Antibodies to HIV-1 were detected in one woman. Reactive syphilis serologies were detected in 15 (2.8%) women. Anti-HBc seroprevalence varied by district (range 3.1-43.5%) and by ethnicity (range 0.0-40.9%). Significant identified risks for anti-HBc seropositivity from univariate analyses included being of the Garifuna ethnic group, residence or birth in the Stann Creek or Toledo districts, a reactive syphilis serology, a household size of eight or greater, and five or more lifetime sexual partners. Multivariate analyses identified ethnicity and a reactive rapid plasma reagin as the best predictors of anti-HBc seropositivity. Highly variable differences in anti-HBc prevalence by district may permit the targeting of limited public health resources for education, screening, and prevention programs.

Medical preparation of travelers to overseas locations is an important part of military medical care. We reviewed pre-travel records of patients attending the travel clinic at the National Naval Medical Center (NNMC) and used a post-travel questionnaire to determine the most frequent medical problems associated with international travel. Among 1,416 individuals who received pre-travel care at NNMC, there were 760 (54%) males and 656 (46%) females, the median patient age was 48 years, the most common reason for travel was pleasure, and the median duration of travel was 21 days. The most common destinations were Asia (27%), Africa (15%), Europe (13%), Central America/Caribbean (12%), and South America (11%). The median number of immunizations prescribed was three. Malaria chemoprophylaxis was prescribed to 45%. The average cost of vaccines and medications to medically prepare a traveler was $67. Among 271 (82%) who returned the post-travel questionnaire, the most common illnesses reported were diarrhea (23%) and upper respiratory infections (19%); medical treatment was sought by 9%. Properly informed, military physicians can provide a valuable service at a reasonable cost to reduce the risk of travel-acquired medical problems and illnesses.

Adults in the Stann Creek District of Belize have a high prevalence of hepatitis B virus (HBV) infection, but the age of onset of these infections is unclear. We conducted a seroprevalence study of hepatitis B markers among Stann Creek school-age children to provide information for planning a hepatitis B vaccine program. The overall prevalence in 587 students was high for antibody to hepatitis B core antigen (anti-HBc) (43.3%) and hepatitis B surface antigen (HBsAg) (7.7%). There was marked variation of anti-HBc by school and by the predominant ethnic groups attending those schools. Maya had the highest prevalence (76%), followed by Mestizo (50%), Garifuna (37%), and Creole (25%). Children less than nine years of age attending the rural primary schools (mostly Mayan and Mestizo) had significantly higher prevalence of anti-HBc than did children attending the urban primary school (mostly Garifuna and Creole) (P < 0.05). Anti-HBc was found in 42% and 36% of students at the two high schools. Of the five schools tested, only at the urban primary school did anti-HBc positivity increase with age. Based on an analysis of the cost of serologic screening before immunization compared with mass vaccination, preimmunization serologic screening resulted in vaccine program cost savings in four of the five schools. Because most children in the rural areas contract hepatitis B before entering school, immunization against HBV should be integrated into the routine infant immunization program.

To determine the prevalence of antibodies to viral diseases known or suspected to be present in Pakistan, we studied 570 sera from three groups of adults; two of the groups were involved in outbreaks of hepatitis, and the third included men admitted to a hospital for evaluation of febrile illnesses. Immunoglobulin G antileptospiral antibody was found in 1 to 6% of the subjects, with the highest rate in enlisted military personnel hospitalized for febrile illness. One man in the group with febrile illness had significantly elevated immunoglobulin M antileptospiral antibody titers. However, in a group of recruits experiencing suspected non-A, non-B hepatitis, 19 (11%) of 173 had a 4-fold rise in immunoglobulin M antibody to leptospirosis. Antibody to sand fly fever viruses was found in 27 to 70%. Antibody to West Nile virus was present in 33 to 41% of subjects. Antibody reactive with Japanese encephalitis virus was present in 25%, but plaque reduction neutralization tests suggested this to be cross-reaction with West Nile virus. All 212 specimens tested for antibody to Crimean-Congo hemorrhagic fever and Hantaan viruses were negative. This study indicates that diseases known to be prevalent in other areas of southwest Asia and the Middle East are also prevalent in northern Pakistan and may impact on those traveling or working in this area.

A seroprevalence survey of hepatitis B virus (HBV) markers was conducted among health care workers in Belize to help determine the epidemiology of hepatitis B and to determine if screening before immunization might lower vaccine costs. Of the 330 workers tested, 94 (29%) were positive for antibody to HBV core antigen (anti-HBc) and three (1%) had HBV surface antigen. The presence of anti-HBc increased significantly with age from 12% in those 18-24 years old to 52% in those > or = 50 years old. The rate was 17% of 48 men compared with 30% of 282 women (P = 0.05). Rates increased with years of medical service and were higher among nurses (69 of 228; 30%) and nonprofessional staff (15 of 44; 34%) than among physicians (0 of 20). The presence of anti-HBc also differed significantly among ethnic groups: Mestizo, 4%; Creole, 33% and Garifuna, 57%. Rates differed by district ranging from 3% in a northern district (mostly Mestizo) to 67% in a southern district (mostly Garifuna). Parental exposure to hepatitis B through needle stick injuries and blood transfusions was not associated with anti-HBc. Multiple logistic regression analysis confirmed ethnicity, district of residence, and age as the best predictors of anti-HBc in health care workers. Cost analysis suggests that because of regional differences in exposure, testing of health care workers for anti-HBc in the Belize and Stann Creek districts in southern Belize before hepatitis B immunization would result in vaccine program cost savings.

Unlabelled: The high cost of hepatitis B vaccines remains an obstacle to their use. Since the recommended adult dose of Recombivax HB (MSD) is 10 micrograms and that of Engerix B (SKB) is 20 micrograms, we sought to determine if 10 microgram doses of each vaccine are equally immunogenic. Further, since 5 microgram doses of Recombivax are routinely used in those < or = 29 years of age in the US military, we sought to compare this dose with 5 microgram doses of Engerix B. Lower doses of Engerix would result in vaccine cost savings., Methods: members of the Belize Defence Force who were > or = 18 years of age (median 24) without detectable anti-HBc were randomly assigned to receive Recombivax, 5 or 10 micrograms, or ENgerix, 5 or 10 micrograms IM at 0, 1, and 6 months. Randomization was weighted toward Engerix., Results: after 3 doses, geometric mean concentrations (GMC) of anti-HBs were highest among those receiving Recombivax 10 micrograms (n=22) or 5 micrograms (n=46) with GMC anti-HBs of 744 and 570 mIU ml-1, respectively. Similar proportions in the two groups developed > or = 10 mIU m-1 anti-HBs (100 and 98%). Among the 91 people who received Engerix 10 micrograms, the GMC anti-HBs was 325 mIU ml-1 and 91% developed > or = 10 mIU ml-1. The 87 people who received Engerix 5 micrograms had the lowest GMC, 177 mIU ml-1 (p < 0.05 compared with either Recombivax group). Only 86% attained > or = 10 mIU ml-1 anti-HBs (p > 0.05 compared with other regimens). The proportion attaining > or = 100 mIU ml-1 was lower in the 5 microgram Engerix group (63%) compared with 80% in the 5 microgram or 95% in the 10 microgram Recombivax groups (p < 0.05)., Conclusions: Engerix administered in 5 microgram doses is less immunogenic than 5 or 10 microgram doses of Recombivax. In healthy populations < 30 years of age, regimens of half the recommended adult dose (5 micrograms of Recombivax or 10 micrograms of Engerix) are highly immunogenic and may result in significant vaccine cost savings.

A Plasmodium falciparum circumsporozoite protein (PfCSP) recombinant fusion protein, R32NS1(81), formulated with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane (Detox) was administered to 12 volunteers. One volunteer had malaise and self-limited painful induration at the injection site after the second dose and declined further immunization. The other 11 volunteers tolerated the three doses of 1,230 micrograms of vaccine, but most complained of sore arms; in five cases the pain or malaise was severe enough to interfere with work or sleep. Two weeks after the third dose of vaccine, four of the 11 immunized volunteers had > or = 14 micrograms/ml of antibodies to the repeat region of the PfCSP in their serum. Two of these four volunteers did not develop P. falciparum parasitemia when challenged by the bite of five mosquitoes carrying P. falciparum sporozoites. The seven volunteers with lower levels of antibodies and 11 of 11 controls developed parasitemia. These data are consistent with other studies, and indicate that vaccine-induced antibodies against the repeat region of PfCSP can prevent effective sporozoite infection of hepatocytes in humans. The challenge is to improve the immunogenicity of PfCSP-based vaccines, and to develop methods for including PfCSP peptides as components of multitarget malaria vaccines.

IgM and IgG anti-hepatitis E virus (HEV) patterns were determined in sera collected during a hepatitis outbreak in Pakistan. HEV infection was detected serologically in 122 patients. IgM anti-HEV was detected in specimens collected up to 2 weeks before and 5-7 weeks after hospitalization in 91% and 100%, respectively, of 122 HEV-infected patients. IgG followed a similar pattern. Peak antibody titers appeared 2-4 weeks after hospitalization. At 20 months after hospitalization, IgM anti-HEV was not detected in any of 33 patients; IgG was found in all. IgG anti-HEV appeared to be protective in contracts of patients. This study confirms HEV as the cause of the outbreak, quantifies IgM and IgG anti-HEV responses, provides evidence that IgG anti-HEV protects against hepatitis E, and demonstrates that IgG anti-HEV persists, but at diminished titer, after infection. Hepatitis E in young adults is the result of primary infection with HEV and, if reinfection occurs, it does not commonly cause serious illness.

Background: The introduction of new vaccines to prevent hepatitis A infection raises the question of the cost of these vaccines relative to immune globulin when short-term protection against hepatitis A is required. Since the prevalence of hepatitis A antibodies (anti-HAV) in the US population increases rapidly with age, testing for anti-HAV may decrease the cost of vaccination programs., Methods: A cost-analysis model was developed that incorporates the cost of immune globulin or hepatitis A vaccine, the number of doses of vaccine, the cost of testing for anti-HAV in either commercial or public-sector laboratories, and the prevalence of anti-HAV in the general population by age., Results: In comparison with hepatitis A vaccines, with expected costs between $10 and $25 per dose, use of immune globulin for postexposure prophylaxis or preexposure short-term (< or = 6 months) prophylaxis is much less expensive for all age groups. Testing for anti-HAV does not significantly diminish the cost of immune globulin regimens. In contrast, if anti-HAV testing is performed in a public-sector laboratory at $10 per test, and hepatitis A vaccine costs $10 per dose, testing reduces vaccination costs in those 40 years of age or older for a two-dose vaccine regimen and in those 30 years of age or older for a three-dose regimen. At the other end of the spectrum, if vaccine costs $35 per dose, commercial testing for anti-HAV at $25 per person reduces the costs in those 30 years of age or older if either a two- or three-dose regimen is elected. However, vaccine savings are realized in those 10 years and older if public-sector testing is performed and three doses of vaccine at $35 per dose are utilized. In an intermediate scenario of public-sector testing and vaccines costing $25 per dose, the cost would also be reduced in those 30 years old or older., Conclusions: Testing for anti-HAV in frequent travelers, international government, business, and volunteer workers, military personnel, etc, may be an effective means of decreasing costs of hepatitis A prevention.

Little is known about the prevalence of infection with hepatitis viruses in Belize, Central America. We conducted a serologic survey among members of the Belize Defence Force (BDF), which is composed of the five major ethnic groups in Belize, to estimate prevalence rates of hepatitis A, B, and C among military-aged men and women in Belize. Of approximately 600 men and women in the BDF, 492 (82%) completed a questionnaire and blood collection. Antibody to hepatitis A was found in 94%, with similar rates by age, sex, rank, and ethnicity. Antibody to hepatitis B core antigen (anti-HBc) was found in 31%. Rates of anti-HBc varied significantly among the ethnic groups with the lowest rates in Mestizo (5%) and Mayan Indians (9%), and significantly higher rates among Creoles (30%) and Garifuna (56%). Rates increased with increasing age from 28% in those 18-24 years old to 35% in those > or = 35 years old (P = 0.07, by chi-square test for trend). Hepatitis B surface antigen was found in 21 (4%) overall. Antibody to hepatitis C was found in two (0.4%). In this young healthy population, exposure to hepatitis A before the age of 18 is almost universal, while exposure to hepatitis B is related to age and ethnic origin.

The prevalence of hepatitis A, B, C, and D viruses was studied in 467 military personnel with human immunodeficiency virus type 1 (HIV-1) infection. Antibody to hepatitis C virus (anti-HCV) by first-generation ELISA was found in 136 (29%). Of sera repeatedly reactive for anti-HCV by first-generation ELISA, two-antigen recombinant immunoblot assay (RIBA) was positive in 41 (32%) and four-antigen RIBA was positive in 55 (41%). Four-antigen RIBA was positive in 33 (30%) of the 109 with an OD on ELISA of < or = 2.0 compared with 22 (81%) of the 27 with an OD > 2.0 (P < .001). Anti-HCV detected by four-antigen RIBA was associated with increasing age, black or Hispanic race, and antibody to hepatitis B core antigen. When patients with hepatitis B surface antigen were excluded, elevated alanine aminotransferase was found in 5 (8%) of 63 with a negative RIBA and 13 (28%) of 47 with a positive RIBA (P = .006). While RIBA was negative in more than half of those with anti-HCV by ELISA, 55 (12%) of these HIV-1 infected personnel had anti-HCV detected by RIBA, which was associated with a strong reaction by ELISA, elevated liver enzymes, coinfection with hepatitis B, minority race, and older age.

In many areas of the developing world, Salmonella spp. account for greater than 50% of the gram-negative enteric organisms isolated from cerebrospinal fluid (CSF). The response of Salmonella meningitis to conventional therapy (chloramphenicol and/or ampicillin) is slow, complications arise frequently, and mortality rates of 60 to 80% are common. Two newer agents, ceftriaxone and imipenem, were compared with ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (TMP-SMX) in the therapy of experimental Salmonella meningitis beginning 14 h after intracisternal inoculation and continued by constant intravenous infusion for 8 h. Drug concentrations in serum and CSF closely approximated those achieved in the sera and CSF of humans receiving standard parenteral regimens. Penetration into purulent CSF [(concentration of drug in CSF/concentration of drug in serum) x 100] ranged from 18 to 41%. The rate of bacterial killing in CSF was significantly (P less than 0.001) more rapid during therapy with ceftriaxone and imipenem than it was during therapy with chloramphenicol or TMP-SMX. Ceftriaxone and imipenem sterilized the CSF of six of seven animals at 8 h, whereas it sterilized the CSF of three of eight animals treated with ampicillin (P = 0.18), one of eight animals treated with chloramphenicol, and none of seven animals treated with TMP-SMX (P less than or equal to 0.01; ceftriaxone or imipenem versus chloramphenicol or TMP-SMX). New beta-lactams, including ceftriaxone and imipenem, appear to be effective therapy against Salmonella spp. in this animal model and deserve further evaluation in humans.

Hepatitis B and its sequelae are global problems preventable by immunization. Expense limits the use of hepatitis B vaccines, but low-dose intradermal immunization has been evaluated as a cost-saving strategy in numerous studies. With few exceptions, low-dose intradermal plasma-derived vaccines have elicited protective levels of antibody in 82%-100% of young healthy adults--a proportion similar to that noted with full-dose regimens; peak levels of antibody to hepatitis B surface antigen (HBsAg) are lower with reduced doses, however. Although children respond well to low-dose intradermal immunization, this procedure is technically difficult in neonates and should not be used for those born to HBsAg-positive mothers. For persons at high risk, antibody to HBsAg must be assessed after immunization to determine the need for a booster dose. A fourth dose 1-2 years after the initial series substantially increases antibody concentrations. In low intradermal doses, recombinant vaccine elicits lower rates of seroconversion than plasma-derived vaccine. However, low intramuscular doses of recombinant vaccine give favorable results. In short, low-dose intradermal or intramuscular immunization offers protection against hepatitis B at significant savings and may be useful for mass immunization of populations at high risk.

Hepatitis E virus (HEV), a positive-strand RNA agent, has been associated with enterically transmitted non-A, non-B hepatitis in Asia, Africa, and Mexico. To evaluate the role of HEV in an outbreak of hepatitis in Pakistan, we used immune electron microscopy to detect 1) antibody to HEV, for evidence of infection, and 2) virus, to determine the pattern of HEV excretion. Paired sera from 2 patients were assayed for antibody by using reference HEV: one seroconverted, an atypical finding for HEV infections; the other had high levels of anti-HEV in both sera. Virus particles with the size (29 x 31 nm) and morphology of HEV were detected in feces from 10 of 85 patients and serologically identified as HEV by using reference antibodies from an HEV-infected chimpanzee. One of these HEV-containing specimens was collected 9 days before the onset of jaundice; it was among feces from 38 outpatients with nonspecific symptoms and biochemical hepatitis, 12 of whom subsequently developed jaundice. The other 9 feces with HEV were among 36 collected within 7 days of the onset of acute icteric hepatitis; all 11 feces from days 8 to 15 were negative for HEV. Fecal concentrations of HEV appeared to be lower than those of many enteric viruses: only one specimen contained as many as 5 particles per EM grid square. It is concluded that HEV was etiologically associated with the epidemic and was predominantly excreted at very low levels during the first week of jaundice.

To determine the duration of antibody after low-dose, intradermal (i.d.), plasma-derived hepatitis B vaccination and the response to a booster dose, we studied two classes of medical students who were immunized with 2 micrograms doses i.d. In one class, 73/88 (85%) who had been immunized by skilled personnel at 0, 1 and 6 months, had protective concentrations (greater than or equal to 10 mIU ml-1) of anti-HBs at 20 months after the first dose. Twelve (92%) out of 13 students who received only two doses at 0 and 1 months also had protective concentrations at month 20. At month 27, 11/16 (69%) with antibody less than or equal to 10 mIU ml-1 responded to a fourth dose of 2 micrograms i.d. with protective concentrations of anti-HBs. In the second class, after three doses of vaccine at 0, 1, and 6 months, protective concentrations of anti-HBs were present in 90/93 (97%) at 14 months and in 71/80 (89%) at 25 months. In those who received only two doses, protective concentrations were found in 24/31 (74%) at 14 months and 9/16 (56%) at 25 months. After a booster dose of 2 micrograms i.d. at month 25, anti-HBs concentrations rose from a geometric mean of 78 to 1198 mIU ml-1 in 60 subjects previously immunized with three doses and from 18 to 1054 mIU ml-1 in 16 students previously immunized with only two doses. Overall, 73/76 (96%) of students in the second group had protective concentrations of antibody after the booster dose.(ABSTRACT TRUNCATED AT 250 WORDS)

The immunogenicity and reactogenicity of low-dose, recombinant DNA and plasma-derived hepatitis B vaccines were investigated in a prospective, double-blind, randomized, controlled trial. Volunteers (153) received either recombinant vaccine, 10 micrograms in 1 ml intramuscularly; plasma-derived vaccine, 2 micrograms in 0.1 ml intradermally or recombinant vaccine, 1 microgram in 0.1 ml intradermally at 0, 30, and 150 days. Peak geometric mean concentrations of antibody to hepatitis B surface antigen at day 200 were 1094, 387, and 43 mIU/ml, respectively. By day 360, these concentrations had fallen to 346, 124, and 19 mIU/ml, respectively (P less than .05 between groups both dates). Number of subjects with antibody greater than or equal to 10 mIU/ml at day 200 was similar between the 10-micrograms recombinant and 2-micrograms plasma-derived groups (94% vs. 90%), while only 78% of the 1-microgram recombinant group had protective concentrations of antibodies (P less than .05). Erythema and induration occurred in most subjects in both intradermal groups, while pain was prominent at the intramuscular site especially after the second dose. Thus, plasma-derived vaccine, 2 micrograms in 0.1 ml intradermally, appears to be an acceptable cost-saving method for hepatitis B immunization, while recombinant-derived vaccine, 1 microgram in 0.1 ml intradermally, produced less satisfactory results.

The prevalence of Chlamydia trachomatis infections among male patients with gonococcal urethritis in the sexually transmitted diseases (STDs) clinic at UTH, Lusaka, was determined by two methods to be around 4.7%. Methods used were specific for C. trachomatis (Syva Microtrak), and second isolation of C. trachomatis. The results indicate that with a prevalence rate of 4-7% for concurrent gonococcal and chlamydial infection, it is not financially or medically practical to treat all cases of gonorrhoea in Zambia for possible chlamydial infection, as is advocated in some countries. The findings further suggest that the commercially available Syva Microtrak test should probably be considered positive when one or two monoclonal-stained elementary bodies are seen, rather than ten, to avoid false-negative results.

Neisseria gonorrhoeae strains resistant to treatment with penicillin, tetracycline, and/or spectinomycin are increasing in prevalence in many parts of the world. In Zambia, 52% of N. gonorrhoeae isolates produced beta-lactamase in 1986. Few oral regimens have proven effective for treatment of resistant N. gonorrhoeae. We conducted a prospective, double-blind, randomized clinical trial of 250 mg of ciprofloxacin given orally versus 250 mg of ceftriaxone given intramuscularly for treatment of uncomplicated gonococcal urethritis in adult males. Two hundred men were enrolled and treated. The two groups were comparable in age (27.5 years), prevalence of latent syphilis (14 and 10%), and human immunodeficiency virus infection (32 and 38%). Of 165 patients with cultures positive for N. gonorrhoeae who returned for follow-up, ciprofloxacin cured 83 of 83 (100%), including 26 with penicillinase-producing N. gonorrhoeae (PPNG) and 21 with N. gonorrhoeae with chromosomally mediated resistance to multiple antibiotics (CMRNG), and ceftriaxone cured 81 of 82 (98.7%), including 30 with PPNG and 19 with CMRNG. Both treatment regimens were well tolerated. Chlamydia trachomatis in urethral exudate was found by direct fluorescent-antibody microscopic examination or by culture in 10 (5%) participants. All N. gonorrhoeae isolates were inhibited by ceftriaxone at 0.06 micrograms/ml, except one which was inhibited at 0.125 micrograms/ml, while ciprofloxacin inhibited all isolates at 0.03 micrograms/ml. Ciprofloxacin is a safe and effective therapy for uncomplicated gonococcal urethritis, including that caused by PPNG and CMRNG in human immunodeficiency virus-infected men.

The activity of tosufloxacin (A-60969), a new oral quinolone, and clarithromycin (A-56268, TE-031), a new oral macrolide, was compared in vitro to that of other oral quinolones and beta-lactam antimicrobial agents against clinical isolates of ampicillin and/or chloramphenicol resistant Haemophilus influenzae, penicillin resistant Streptococcus pneumoniae and beta-lactamase producing Branhamella catarrhalis. Results were compared to those for sensitive isolates. Tosufloxacin was the most active compound against Haemophilus influenzae and was more active than ciprofloxacin or ofloxacin against all strains of Streptococcus pneumoniae. Tosufloxacin was also more active than any of the beta-lactam drugs tested against penicillin resistant or relatively penicillin resistant isolates. Clarithromycin was the most active compound tested against both penicillin sensitive and penicillin resistant Streptococcus pneumoniae, and was as active as ciprofloxacin against Branhamella catarrhalis. In view of the favourable in vitro activity against common bacterial respiratory pathogens, tosufloxacin should be considered for clinical trials in adults with respiratory tract infections, while clarithromycin might be useful in treatment of infection with these organisms in all age groups.