Lead and δ-Aminolevulinic Acid Dehydratase Polymorphism: Where Does It Lead? A Meta-Analysis

BACKGROUND: Lead poisoning affects many organs in the body. Lead inhibits δ-aminolevulinic acid dehydratase (ALAD), an enzyme with two co-dominantly expressed alleles, ALAD1 and ALAD2. OBJECTIVE: Our meta-analysis studied the effects of the ALAD polymorphism on a) blood and bone lead levels and b) indicators of target organ toxicity. DATA SOURCE: We included studies reporting one or more of the following by individuals with genotypes ALAD1-1 and ALAD1-2/2-2: blood lead level (BLL), tibia or trabecular lead level, zinc protoporphyrin (ZPP), hemoglobin, serum creatinine, blood urea nitrogen (BUN), dimercaptosuccinic acid–chelatable lead, or blood pressure. DATA EXTRACTION: Sample sizes, means, and standard deviations were extracted for the genotype groups. DATA SYNTHESIS: There was a statistically significant association between ALAD2 carriers and higher BLL in lead-exposed workers (weighted mean differences of 1.93 μg/dL). There was no association with ALAD carrier status among environmentally exposed adults with BLLs < 10 μg/dL. ALAD2 carriers were potentially protected against adverse hemapoietic effects (ZPP and hemoglobin levels), perhaps because of decreased lead bioavailability to heme pathway enzymes. CONCLUSION: Carriers of the ALAD2 allele had higher BLLs than those who were ALAD1 homozygous and higher hemoglobin and lower ZPP, and the latter seems to be inversely related to BLL. Effects on other organs were not well delineated, partly because of the small number of subjects studied and potential modifications caused by other proteins in target tissues or by other polymorphic genes

Prevalence of CCHF Virus in Ticks and People and Public Awareness in Zhambyl Region, Kazakhstan

ObjectiveAs part of CDC’s Global Disease Detection work, in conjunction with Zhambyl Region Department of Health, we conducted a tick survey and human seroprevalence Knowledge, Attitudes, and Practices (KAP) survey of livestock-owning households in Zhambyl to assess CCHF seroprevalence and risk factors.IntroductionCrimean Congo Hemorrhagic Fever (CCHF) virus is a tick-borne pathogen that causes severe disease in people, with a distribution that extends from central Asia to southern Africa. In addition to tick bites, contact with bodily fluids from viremic livestock or from symptomatic humans are risk factors for infection. From 2000 to 2013, 73 cases of CCHF were reported in Zhambyl Region, Kazakhstan. CCHF virus is categorized as an “especially dangerous pathogen” in Kazakhstan and CCHF is prioritized for surveillance and treatment. Little is known about the seroprevalence of infection by CCHF virus in Zhambyl in ticks or people, and knowledge of risk factors for transmission of CCHF virus among at-risk populations is believed to be low.MethodsRural villages were classified as “endemic” or “non-endemic”, where endemic areas reported ≥1 CCHF case or a CCHF virus-positive tick in the past 5 years. In each group, 15 villages were chosen by population proportional to livestock population size. Livestock-owning households (n=969) were selected randomly from veterinary registries. One adult was randomly selected per house and ticks were collected from one randomly selected sheep or cow over 1 year of age per house. Data were weighted accounting for design and analyzed in R.ResultsKAP surveys were completed for 950 people (98%); of those, 923 (97%) submitted blood for ELISA testing using Vector-Best Kits. Median age of human respondents was 46 years (range: 19 – 90); 54% were male. Three individuals were anti-CCHF IgM positive, 12 anti-CCHF IgG positive and two positive for both. Weighted seroprevalence of CCHF in Zhambyl was 1.6% (95% CI: 0.9, 3.0). In endemic villages, seroprevalence was 1.8% (95% CI: 1.0, 3.0), compared to 1.2% (95% CI: 0.4, 4.0) in non-endemic villages. Of the 17 seropositive for CCHF, median age was 54 years; 58% were male. None reported previous CCHF diagnosis or illness with fever and hemorrhaging in the past five years. None reported high-risk tick exposure in the past four months. Controlling for age and sex, milking animals, an activity in which 40.3% of the population had engaged, was associated with infection in Poisson regression (OR: 2.53, 95% CI: 1.27, 4.81). Of respondents who had heard of CCHF (n=791), 99.8% knew transmission was caused by a tick bite; few identified contact with animal blood (8.2%) or tick crushing (20.8%) as potential causes. Of the five seropositive by IgM, four participated in at least one of the following activities in the last four months: milking (n=3), birthing (n=2), shearing and slaughtering (n=1). One reported experiencing an illness with joint pain within the past four months. Three were from non-endemic villages.Entomologists inspected 465 cows and 528 sheep for ticks. Ticks were found on 61.5% (95% CI: 48.1, 73.2) of cows (n=254) and 46.3% (95% CI: 24.3, 69.8) of sheep (n=264). Ticks were grouped into pools by animal source and species. Over ninety-seven percent of the tick pools were from the family Ixoidadae, with the remaining from family Argasidae. The genus Hyalomma accounted for 65.8% of tick pools, Rhipicephalus for 31.8%, Ornithodoros for 2.4%, and Argas for 0.5%. Pools contained an average of 4.5 ticks (range: 1 – 26). Ticks were stored live at 4°C for up to 24 hours before being crushed and extracts tested for CCHF virus by PCR and Antigen testing. Of the 155 pools tested, seven (2.4%, 95% CI: 1.1, 5.0) were positive for CCHF virus by either PCR (n=5) and/or antigen testing (n=4). A CCHF virus-positive tick was found on 1.4% (95% CI: 0.4, 4.8) of all sheep and 4.8% (95% CI: 2.3, 10.0) of all cows. All CCHF virus-positive ticks were hard ticks of family Ixodidae, belonging to either genus Hyalomma (n=5) or Rhipicephalus (n=2). Two pools were from non-endemic villages.ConclusionsPresence of CCHF virus-positive ticks and CCHF-seropositive humans in non-endemic areas may suggest a wider range of virus circulation. These findings will be used to inform and target public health messaging

Epidemic Cholera in a Crowded Urban Environment, Port-au-Prince, Haiti

We conducted a case–control study to investigate factors associated with epidemic cholera. Water treatment and handwashing may have been protective, highlighting the need for personal hygiene for cholera prevention in contaminated urban environments. We also found a diverse diet, a possible proxy for improved nutrition, was protective against cholera

Dengue Virus Infections among Haitian and Expatriate Non-governmental Organization Workers — Léogane and Port-au-Prince, Haiti, 2012

<div><p>In October 2012, the Haitian Ministry of Health and the US CDC were notified of 25 recent dengue cases, confirmed by rapid diagnostic tests (RDTs), among non-governmental organization (NGO) workers. We conducted a serosurvey among NGO workers in Léogane and Port-au-Prince to determine the extent of and risk factors for dengue virus infection. Of the total 776 staff from targeted NGOs in Léogane and Port-au-Prince, 173 (22%; 52 expatriates and 121 Haitians) participated. Anti-dengue virus (DENV) IgM antibody was detected in 8 (15%) expatriates and 9 (7%) Haitians, and DENV non-structural protein 1 in one expatriate. Anti-DENV IgG antibody was detected in 162 (94%) participants (79% of expatriates; 100% of Haitians), and confirmed by microneutralization testing as DENV-specific in 17/34 (50%) expatriates and 42/42 (100%) Haitians. Of 254 pupae collected from 68 containers, 65% were <i>Aedes aegypti</i>; 27% were <i>Ae. albopictus</i>. Few NGO workers reported undertaking mosquito-avoidance action. Our findings underscore the risk of dengue in expatriate workers in Haiti and Haitians themselves.</p></div