Strengthening capacity of health workers to diagnose birth defects in Ugandan hospitals from 2015 to 2021.

BACKGROUND: Limited diagnostic capabilities, resources and health worker skills have deterred the advancement of birth defects surveillance systems in most low- and middle-income countries (LMICs). Empowering health workers to identify and diagnose major external birth defects (BDs) is crucial to establishing effective hospital-based BD surveillance. Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration BD Surveillance System consists of three diagnostic levels: (1) surveillance midwives, (2) MU-JHU clinical team, and (3) U.S. Centers for Disease Control and Prevention (CDC) birth defects subject matter experts (SMEs) who provide confirmatory diagnosis. The diagnostic concordance of major external BDs by surveillance midwives or MU-JHU clinical team with CDC birth defects SMEs were estimated. METHODS: Study staff went through a series of trainings, including birth defects identification and confirmation, before surveillance activities were implemented. To assess the diagnostic concordance, we analyzed surveillance data from 2015 to 2021 for major external BDs: anencephaly, iniencephaly, encephalocele, spina bifida, craniorachischisis, microcephaly, anophthalmia/microphthalmia, anotia/microtia, cleft palate alone, cleft lip alone, cleft lip with cleft palate, imperforate anus, hypospadias, talipes equinovarus, limb reduction, gastroschisis, and omphalocele. Positive predictive value (PPV) as the proportion of BDs diagnosed by surveillance midwives or MU-JHU clinical team that were confirmed by CDC birth defects SMEs was computed. PPVs between 2015 and 2018 and 2019-2021 were compared to assess the accuracy of case diagnosis over time. RESULTS: Of the 204,332 infants examined during 2015-2021, 870 infants had a BD. Among the 1,245 BDs identified, 1,232 (99.0%) were confirmed by CDC birth defects SMEs. For surveillance midwives, PPV for 7 of 17 BDs was > 80%. For the MU-JHU clinical team, PPV for 13 of 17 BDs was > 80%. Among surveillance midwives, PPV improved significantly from 2015 to 2018 to 2019-2021, for microcephaly (+ 50.0%), cleft lip with cleft palate (+ 17.0%), imperforate anus (+ 30.0%), and talipes equinovarus (+ 10.8%). Improvements in PPV were also observed among MU-JHU clinical team; however, none were significant. CONCLUSION: The diagnostic accuracy of the midwives and clinical team increased, highlighting that BD surveillance, by front-line health care workers (midwives) in LMICs is possible when midwives receive comprehensive training, technical support, funding and continuous professional development.

Comparative analysis of perinatal outcomes and birth defects amongst adolescent and older Ugandan mothers: evidence from a hospital-based surveillance database.

BACKGROUND: Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12-19 years) and mothers (age 20-34 years) in four urban hospitals. METHODS: Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortions delivered from August 2015 to December 2018 were extracted from a hospital-based birth defects surveillance database. Differences in the distributions of maternal and infant characteristics by maternal age groups were tested with Pearson's chi-square. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated using logistic regression to compare the prevalence of adverse birth outcomes among adolescents to mothers 20-34 years. RESULTS: A total of 100,189 births were analyzed, with 11.1% among adolescent mothers and 89.0% among older mothers. Adolescent mothers had an increased risk of preterm delivery (aOR: 1.14; CI 1.06-1.23), low birth weight (aOR: 1.46; CI 1.34-1.59), and early neonatal deaths (aOR: 1.58; CI 1.23-2.02). Newborns of adolescent mothers had an increased risk of major external birth defects (aOR: 1.33; CI 1.02-1.76), specifically, gastroschisis (aOR: 3.20; CI 1.12-9.13) compared to mothers 20-34 years. The difference between the prevalence of gastroschisis among adolescent mothers (7.3 per 10,000 births; 95% CI 3.7-14.3) was statistically significant when compared to mothers 20-34 years (1.6 per 10,000 births; 95% CI 0.9-2.6). CONCLUSIONS: This study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20-34 years, similar to findings in the region and globally. Interventions are needed to improve birth outcomes in this vulnerable population.

Adolescent pregnancies are a global problem occurring in high-, middle-, and low-income countries with Uganda having one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes, including major external birth defects, between adolescents, (age 12­19 years) and mothers (age 20­34 years) in four urban hospitals.All informative births, including live births, stillbirths, and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2018 were examined. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes.Of the 100,189 births, 11.0% were among adolescent mothers and 89.0% among mothers (20­34 years). Adolescent mothers were more likely than mothers (20­34 years) to have an infant with preterm delivery, low birth weight, early neonatal death, and major external birth defects. Adolescent pregnancies were also associated with an increased risk of gastroschisis when compared to mothers (20­34 years).In conclusion, this study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20­34 years. Research on the potential underlying causes or mechanisms for these adverse outcomes among adolescent births is necessary to identify possible interventions.

A hospital-based birth defects surveillance system in Kampala, Uganda.

BACKGROUND: In 2010, the World Health Assembly passed a resolution calling upon countries to prevent birth defects where possible. Though birth defects surveillance programs are an important source of information to guide implementation and evaluation of preventive interventions, many countries that shoulder the largest burden of birth defects do not have surveillance programs. This paper shares the results of a hospital-based birth defects surveillance program in Uganda which, can be adopted by similar resource-limited countries. METHODS: All informative births, including live births, stillbirths and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2017 were examined for birth defects. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes and entered in an electronic data collection tool. Identified birth defects were confirmed through bedside examination by a physician and review of photographs and a narrative description by a birth defects expert. Informative births (live, still and spontaneous abortions) with a confirmed birth defect were included in the numerator, while the total informative births (live, still and spontaneous abortions) were included in the denominator to estimate the prevalence of birth defects per 10,000 births. RESULTS: The overall prevalence of birth defects was 66.2/10,000 births (95% CI 60.5-72.5). The most prevalent birth defects (per 10,000 births) were: Hypospadias, 23.4/10,000 (95% CI 18.9-28.9); Talipes equinovarus, 14.0/10,000 (95% CI 11.5-17.1) and Neural tube defects, 10.3/10,000 (95% CI 8.2-13.0). The least prevalent were: Microcephaly, 1.6/10,000 (95% CI 0.9-2.8); Microtia and Anotia, 1.6/10,000 (95% CI 0.9-2.8) and Imperforate anus, 2.0/10,000 (95% CI 1.2-3.4). CONCLUSION: A hospital-based surveillance project with active case ascertainment can generate reliable epidemiologic data about birth defects prevalence and can inform prevention policies and service provision needs in low and middle-income countries.

Are Birth Certificate and Hospital Discharge Linkages Performed in 52 Jurisdictions in the United States?

OBJECTIVES: The purpose of this study was to determine the number and characteristics of US State Registrars of Vital Statistics (Vital Registrars) and State Systems Development Initiative (SSDI) Coordinators that link birth certificate and hospital discharge data as well as using linkage processes. METHODS: Vital Registrars and SSDI Coordinators in all 52 vital records jurisdictions (50 states, District of Columbia, and New York City) were asked to complete a 41-question survey. We examined frequency distributions among completed surveys using SAS 9.3. RESULTS: The response rate was 100% (N = 52) for Vital Registrars and 96% (N = 50) for SSDI Coordinators. Nearly half of Vital Registrars (n = 22) and SSDI Coordinators (n = 23) reported that their jurisdiction linked birth certificate and hospital discharge records at least once in the last 4 years. Among those who link, the majority of Vital Registrars (77.3%) and SSDI Coordinators (82.6) link both maternal and infant hospital discharge records to the birth certificate. Of those who do not link, 43% of the Vital Registrars and 55% of SSDI Coordinators reported an interest in linking birth certificate and hospital discharge data. Reasons for not linking included lack of staff time, inability to access raw data, high cost, and unavailability of personal identifiers to link the two sources. CONCLUSIONS: Results of our analysis provide a national perspective on data linkage practices in the US. Our findings can be used to promote further data linkages, facilitate sharing of data and linkage methodologies, and identify uses of the resulting linked data.

More Frequent HIV Viral Load Testing With Point-Of-Care Tests Detects Elevated Viral Load Earlier in Postpartum HIV-Positive Women in a Randomized Controlled Trial in Two Clinics in Johannesburg, South Africa.

BACKGROUND: Elevated maternal HIV viral load (VL) increases vertical transmission risk for breastfeeding children. This randomized controlled trial in Johannesburg primarily evaluated whether 3-monthly point-of-care testing, with laboratory-based standard-of-care testing (arm 2), compared with 6-monthly laboratory-based VL testing (arm 1) in postpartum women living with HIV receiving first-line tenofovir-emtricitabine-efavirenz antiretroviral treatment improved VL suppression, factors associated with nonsuppression, and drug resistance in those with virologic failure. METHODS: Mother-child pairs were enrolled July 2018-April 2019 at the child's 6/10/14-week clinic visit. Women were randomized 1:1 to arm 1 or 2. Trained staff performed point-of-care VL testing using the Cepheid's Xpert HIV-1 VL assay. We fitted a generalized linear mixed model with VL suppression (<50 copies/mL (cps/mL) and <1000 cps/mL) at enrollment and 6, 12, and 18 months postpartum as the outcome and indicator variables for time, study site, study arm, and interaction variables. The final model tested for a difference by study arm, pooling across time points. RESULTS: Of 405 women enrolled (204 arm 1 and 201 arm 2), 249 (61%) remained in follow-up through 18 months. There was no difference in VL suppression between arms at 6, 12, or 18 months. VL suppression rate (<50 cps/mL) at 18 months was 64.8% in arm 1 and 63.0% in arm 2 (P = 0.27). On bivariate analysis, there was an association with late antenatal booking and being in arm 2 for nonsuppressed VL, but no significant association with breastfeeding. HIV drug resistance was found in 12 of 23 participants (52.2%). CONCLUSION: We found no significant difference in VL suppression with more frequent VL testing in postpartum women living with HIV receiving first-line efavirenz-based antiretroviral treatment.

A Model for Accelerating Access to Care and Treatment for Children and Adolescents Living with HIV in Nigeria, Tanzania, Uganda, and Zambia: The Faith-Based Action for Scaling-Up Testing and Treatment for the Epidemic Response (FASTER) Initiative.

The number of children newly infected with HIV dropped by 50%, from 320 000 in 2010 to 160 000 in 2021. Despite progress, ongoing gaps persist in diagnosis, continuity of care, and treatment optimization. In response, the United States President's Emergency Plan for AIDS Relief created the Faith-based Action for Scaling-Up Testing and Treatment for Epidemic Response (FASTER). Faith-based Action for Scaling-Up Testing and Treatment for Epidemic Response addressed gaps in countries with the highest unmet need by working with government to operationalize innovative interventions and ensure alignment with national priorities and with communities living with HIV to ensure the change was community-led. Between 2019 and 2021, FASTER's interventions were incorporated into national policies, absorbed by Ministries of Health, and taken up in subsequent awards and country operating plans. Continued effort is needed to sustain gains made during the FASTER initiative and to continue scaling evidence-based interventions to ensure that children and adolescents are not left behind in the global HIV response.

California Very Preterm Birth Study: design and characteristics of the population- and biospecimen bank-based nested case-control study.

Very preterm birth (VPTB) is a leading cause of infant mortality, morbidity and racial disparity in the US. The underlying causes of VPTB are multiple and poorly understood. The California Very Preterm Birth Study was conducted to discover maternal and infant genetic and environmental factors associated with VPTB. This paper describes the study design, population, data and specimen collection, laboratory methods and characteristics of the study population. Using a large, population-based cohort created through record linkage of livebirths delivered from 2000 to 2007 in five counties of southern California, and existing data and banked specimens from statewide prenatal and newborn screening, 1100 VPTB cases and 796 control mother-infant pairs were selected for study (385/200 White, 385/253 Hispanic and 330/343 Black cases/controls, respectively). Medical record abstraction of cases was conducted at over 50 hospitals to identify spontaneous VPTB, improve accuracy of gestational age, obtain relevant clinical data and exclude cases that did not meet eligibility criteria. VPTB was defined as birth at <32 weeks in Whites and Hispanics and <34 weeks in Blacks. Approximately 55% of all VPTBs were spontaneous and 45% had medical indications or other exclusions. Of the spontaneous VPTBs, approximately 41% were reported to have chorioamnionitis. While the current focus of the California Very Preterm Birth Study is to assess the role of candidate genetic markers on spontaneous VPTB, its design enables the pursuit of other research opportunities to identify social, clinical and biological determinants of different types of VPTB with the ultimate aim of reducing infant mortality, morbidity and racial disparities in these health outcomes in the US and elsewhere.

"Testing Can Be Done Anywhere": A Qualitative Assessment of Targeted Community-Based Point-of-Care Early Infant Diagnosis of HIV in Lusaka, Zambia.

INTRODUCTION: Delayed HIV diagnosis in HIV-exposed infants (HEIs) results in missed opportunities for early antiretroviral therapy (ART), causing significant morbidity and mortality. Early infant diagnosis (EID) depends on the availability of accessible and reliable testing services. We explored the acceptability, appropriateness, and feasibility of deploying a targeted community-based point-of-care (POC) EID testing model (i.e., "community POC model") to reach high-risk mother-infant pairs (MIPs) in Lusaka, Zambia. METHODS: We conducted in-depth interviews with a purposive sample of health care workers, study staff, and caregivers in high-risk MIPs at 6 health facilities included in a larger implementation research study evaluating the community POC model. We defined "high-risk MIPs" as mothers who did not receive antenatal testing or an attended delivery or infants who missed EID testing milestones. Interviews were audio-recorded, translated, and transcribed verbatim in English. Content and thematic analysis were done using NVivo 10 software. RESULTS: Health care workers (n=20) and study staff (n=12) who implemented the community POC model noted that the portability and on-screen prompts of the POC platform made it mobile and easy to use, but maintenance and supply chain management were key to field operations. Respondents also felt that the community POC model reached more infants who had never had EID testing, allowing them to find infants with HIV infection and immediately initiate them on ART. Caregivers (n=22) found the community POC model acceptable, provided that privacy could be ensured because the service was convenient and delivered close to home. CONCLUSION: We demonstrate the acceptability, appropriateness, and feasibility of implementing the community POC model in Zambia, while identifying potential challenges related to client privacy and platform field operations. The community POC model may represent a promising strategy to further facilitate active HIV case finding and linkage to ART for children with undiagnosed HIV infection in the community.

Mobile tablets for real-time data collection for hospital-based birth defects surveillance in Kampala, Uganda: Lessons learned.

Sustainable birth defects surveillance systems provide countries with estimates of the prevalence of birth defects to guide prevention, care activities, and evaluate interventions. We used free and open-source software (Open Data Kit) to implement an electronic system to collect data for a hospital-based birth defects surveillance system at four major hospitals in Kampala, Uganda. We describe the establishment, successes, challenges, and lessons learned from using mobile tablets to capture data and photographs. After intensive training, surveillance midwives collected data using Android tablets with inbuilt logic checks; another surveillance midwife checked the quality of the data in real-time before data were securely uploaded onto a local server. Paper forms were used when needed as a backup for the electronic system. We experienced several challenges implementing the surveillance system, including forgotten passwords, unstable network, reduced tablet speed and freezing, loss of touch-screen sensitivity, decreased battery strength, and repetitive extensive retraining. We addressed these challenges by backing up and removing all photos from the tablet, uninstalling irrelevant applications to the study to increase storage space and speed, and monitoring and updating the system based mainly on feedback from the midwives. From August 2015 to December 2018, surveillance midwives documented information on 110,752 births at the participating hospitals. Of these, 110,573 (99.8%) were directly entered into the electronic data system and 179 (0.2%) were captured on paper forms. The use of mobile tablets for real-time data collection was successful in a hospital-based birth defects surveillance system in a resource-limited setting. Extensive training and follow-up can overcome challenges and are key to preparing staff for a successful data collection system.

Prevalence of neural tube defects, maternal HIV status, and antiretroviral therapy from a hospital-based birth defect surveillance in Kampala, Uganda.

BACKGROUND: The estimated prevalence of neural tube defects (NTDs) in Africa is 11.7 per 10,000 live births; however, data on the impact of antiretroviral therapy (ART) during pregnancy and the risk for birth defects in Africa are limited. METHODS: Data from a hospital-based surveillance program at four hospitals in Kampala, Uganda were used to estimate the baseline prevalence of NTDs and assess potential associations with HIV status and ART use. All live births, stillbirths, and spontaneous abortions delivered at the participating hospitals affected with selected birth defects between August 2015 and December 2018 were included. Trained midwives collected data from hospital records, maternal interviews, photographs, and narrative descriptions of birth defects. We estimated NTD prevalence per 10,000 births (live, stillbirths, spontaneous abortions), prevalence ratios, and 95% confidence intervals (CIs). RESULTS: A total of 110,752 births from 107,133 women were included in the analysis; 9,394 (8.8%) women were HIV-infected and among those with HIV infection, 95.6% (n = 8,977) were on ART at delivery. Overall, 109 births were affected with NTDs, giving a prevalence of 9.8 (95% CI [8.2, 11.9]). Spina bifida (n = 63) was the most common type of NTD, with a prevalence of 5.7 (95% CI [4.4, 7.3]), followed by anencephaly (n = 31), with a prevalence of 2.8 (95% CI [2.0, 4.0]). CONCLUSION: The prevalence of NTDs among births in Kampala, Uganda is consistent with current estimates for Africa. With the continued introduction of new medications that may be taken during pregnancy, sustainable birth defect surveillance systems and pharmacovigilance are indicated.

The prevalence of multiple sclerosis in 3 US communities.

INTRODUCTION: We estimated the prevalence of multiple sclerosis (MS) in 3 large geographic areas in the southern, middle, and northern United States. METHODS: The primary data source was medical records from office visits to private neurologists' practices or to neurology departments in tertiary care facilities during a 3-year period. Additional data sources included patient advocacy groups, nursing homes, and general practitioners. RESULTS: Three-year US age-adjusted prevalence estimates for the study areas varied substantially. The prevalence was lowest (47.2 per 100,000 population) in the Texas study area (33 degrees 30' north latitude), intermediate (86.3 per 100,000 population) in the Missouri study area (39 degrees 07' north latitude), and highest (109.5 per 100,000 population) in the Ohio study area (41 degrees 24' north latitude). The geographic differences remained strong after age-adjustment to the world standard population. The inverse association between UV light exposure and MS prevalence estimates was consistent with this observed latitude gradient. In all 3 areas, MS prevalence was highest among women, people aged 40 to 59 years, and non-Hispanics. CONCLUSION: These results provide necessary prevalence estimates for community cluster investigations and establish baseline estimates for future studies to evaluate temporal trends in disease prevalence.

Multiple sclerosis prevalence and possible lead exposure.

This study was conducted to estimate the current prevalence of multiple sclerosis (MS) in Jefferson County, Missouri, USA, and to address community concerns about a perceived excess of MS around an active lead smelter. The study population consisted of the residents of Jefferson County, Missouri between 1998 and 2002. An aggressive MS case finding with capture-recapture analysis was used. The spatial clustering was examined using a spatial scan statistic. The capture-recapture analysis showed the case ascertainment to be 95%. The crude five-year period prevalence of MS in Jefferson County was 105 per 100,000 population (95% confidence interval [CI], 91-121), and 107 per 100,000 (95% CI, 95-119) when age-standardized to the 2000 U.S. population. No significant spatial clusters of MS cases were identified in the study area. The estimates of MS prevalence in Mid-western community of USA appeared to be comparable to estimates from other areas of similar latitude in the United States and Western Europe. The MS cases did not appear to cluster around the lead smelter.

An epidemiologic investigation of amyotrophic lateral sclerosis in Jefferson County, Missouri, 1998-2002.

Amyotrophic lateral sclerosis (ALS) cases diagnosed between 1998 and 2002 were identified to study ALS prevalence and spatial clustering in Jefferson County, Missouri, where an active lead smelter is located. The study used the El Escorial criteria for ALS diagnosis, the capture-recapture analysis for ALS case ascertainment, and the spatial scan statistic for cluster analysis. The estimated crude prevalence of ALS in Jefferson County was 3.9 per 100,000 population (95% CI, 1.7-7.7) at the time point on December 31, 2002. After age-adjustment to the 2002 U.S. population, the prevalence was 4.2 per 100,000 (95% CI, 1.9-6.6). This prevalence estimate was comparable to recent prevalence estimates from Western Europe. A small but significant cluster (p=0.04) was detected around the smelter area. An ALS registry utilizing outpatient, inpatient, and death certificate data is needed to provide comprehensive information for ALS case ascertainment. Etiologic studies are needed to assess whether living in proximity to a lead smelter is associated with the development of ALS.

Sickle cell disease: current activities, public health implications, and future directions.

Sickle cell disease (SCD) is a genetic blood disorder caused by abnormal hemoglobin that damages and deforms red blood cells (RBCs). The abnormal red cells break down, causing anemia, and obstruct blood vessels, leading to recurrent episodes of severe pain and multiorgan ischemic damage. SCD affects millions of people throughout the world and is particularly common among people whose ancestors come from sub-Saharan Africa. Sickle cell trait (SCT) is an inherited condition in which both normal hemoglobin and sickle hemoglobin are produced in the RBCs. SCT is not a type of sickle cell disease. People with SCT are generally healthy. In SCD, clinical severity varies, ranging from mild and sometimes asymptomatic states to severe symptoms requiring hospitalization. Symptomatic treatments exist, but there is no cure for SCD. Although there has been extensive clinical and basic science research in SCD, many public health issues, such as blood safety surveillance, compliance with immunizations, follow-up of newborns with positive screening tests, stroke prevention, pregnancy complications, pain prevention, quality of life, and thrombosis, in people with SCT remain unaddressed. Currently, efforts are under way to strengthen SCD-related activities within the Centers for Disease Control and Prevention (CDC). To date, several activities are being or have been conducted by centers within CDC, including quality assurance of newborn screening tests for SCD, morbidity and mortality studies, genetic studies, and studies focusing on the protective effects of SCT for malaria. This paper discusses the public health implications of SCD, summarizes SCD-related activities within CDC, and points to future directions that the agency can take to begin to address some of these issues.

Prevalence of multiple sclerosis in 19 Texas counties, 1998-2000.

The study reported here determined the prevalence of multiple sclerosis (MS) between January 1, 1998, and December 31, 2000, for a 19-county study area surrounding Lubbock, Texas. The primary data source for case ascertainment was medical records from the offices of neurologists practicing in the study area. The study found that the overall prevalence for the 19-county study area was 42.8 per 100,000 population (95 percent CI = 36.8-49.5). The prevalence estimate for females was 68.6 per 100,000 (95 percent CI = 58.0-80.6), and for males it was 16.6 per 100,000 (95 percent CI = 11.6-23.1). The prevalence estimate for non-Hispanic whites was 56.0 per 100,000 (95 percent CI = 47.1-66.1); the next highest prevalence was among non-Hispanic blacks at 22.1 per 100,000 (95 percent Cl = 8.1-48.1), and Hispanics at 11.2 per 100,000 (95 percent CI = 6.4-18.2). This project generated the first Texas-specific population-based MS prevalence estimates, including prevalence estimates specific to Hispanics and blacks in Texas. The results underscore the need for additional epidemiologic information on the distribution of MS in other areas of Texas and the United States, as well as information on the underlying etiology of the disease.

Investigation of a cluster of multiple sclerosis in two elementary school cohorts.

The authors investigated a cluster of multiple sclerosis (MS) among people who had attended two elementary schools in El Paso, Texas, from 1948 through 1970. The community was concerned about the possibility of childhood exposure to heavy metals from a large nearby smelter because historical environmental and biological sampling data demonstrated the potential for study cohort members to have been exposed to heavy metals during their pre-adolescent years. One cohort had no reported cases of MS. In the second cohort, 22 members self-reported a diagnosis of MS, and 16 of these cases were confirmed as MS by an independent board-certified neurologist. The crude MS prevalence estimate was 411 per 100,000 (95 percent confidence interval [CI] = 197-603), Prevalence estimates from four different populations were used for calculation of standardized morbidity ratios (SMRs). At the extremes, the study cohort represents a deficit of cases (SMR= 0.9; 95 percent CI = 0.51-1.44) or a four-fold excess (SMR = 4.0; 95 percent Cl = 2.29-6.5).

Evaluation of serum immunoglobulins among individuals living near six Superfund sites.

Residents living in communities near Superfund sites have expressed concern that releases from these facilities affect their health, including adverse effects on their immune systems. We used data from six cross-sectional studies to evaluate whether people who live near several Superfund sites are more likely to have individual immunoglobulin test results (IgA, IgG, and IgM) below or above the reference range than those who live in comparison areas with no Superfund site. Study participants consisted of target-area residents who lived close to a Superfund site and comparison-area residents who were not located near any Superfund or hazardous waste sites. A consistent modeling strategy was used across studies to assess the magnitude of the relationship between area of residence and immunoglobulin test results, adjusting for potential confounders and effect modifiers. In all study areas, the results suggest that people who live near a Superfund site may have been more likely to have IgA test results above the reference range than comparison areas residents regardless of modeling strategy employed. The effect measures were larger for residents who lived in communities near military bases with groundwater contamination. For all analyses the wide confidence intervals reflect uncertainty in the magnitude of these effects. To adequately address the question of whether the immune system is affected by low-level exposures to hazardous substances, we recommend that more functional immunotoxicity tests be conducted in human populations where individual exposure information is available or when it can be reasonably estimated from environmental exposure measurements.

Studies of multiple sclerosis in communities concerned about environmental exposures.

Multiple sclerosis (MS) is an autoimmune disease that differentially affects women, people 30-60 years old, and Caucasians. Evidence indicates that it is a complex disease determined by both environmental factors and genetic susceptibility. People across the United States have expressed concern about perceived clusters of MS in their communities and the role of environmental exposures in the development of the disease. The Agency for Toxic Substances and Disease Registry (ATSDR) has funded several studies to address this issue, including a cluster investigation, several prevalence studies, and a case-control study. The cluster investigation illustrated that there are few data regarding the number of individuals with MS in the United States. Prevalence studies were conducted in Ohio, Missouri, and Texas to address this deficiency. The results support a regional difference in MS prevalence, although the reason for this difference is unclear. The results also underscore the need for additional epidemiological information about the distribution of MS in other areas of the United States and information on the underlying etiology of the disease. A case-control study is currently being conducted to examine potential risk factors for MS, including the role of environmental exposures and genetic susceptibility. Future research on MS should focus on large-scale studies and include collaboration among researchers with varied fields of expertise, such as epidemiology, neurology, and genetics.

Heavy metals, organic solvents, and multiple sclerosis: An exploratory look at gene-environment interactions.

Exposure to heavy metals and organic solvents are potential etiologic factors for multiple sclerosis (MS), but their interaction with MS-associated genes is under-studied. The authors explored the relationship between environmental exposure to lead, mercury, and solvents and 58 single-nucleotide polymorphisms (SNPs) in MS-associated genes. Data from a population-based case-control study of 217 prevalent MS cases and 496 age-, race-, gender-, and geographically matched controls were used to fit conditional logistic regression models of the association between the chemical, gene, and MS, adjusting for education and ancestry. MS cases were more likely than controls to report lead (odds ratio [OR] = 2.03; 95% confidence interval [CI]: 1.07, 3.86) and mercury exposure (OR = 2.06; 95% CI: 1.08, 3.91). Findings of potential gene-environment interactions between SNPs in TNF-α, TNF-ß, TCA-ß, VDR, MBP, and APOE, and lead, mercury, or solvents should be considered cautiously due to limited sample size.