Risk Factors for Death or Meningitis in Adults Hospitalized for Cutaneous Anthrax, 1950-2018: A Systematic Review.

BACKGROUND: Cutaneous anthrax accounts for approximately 95% of anthrax cases worldwide. About 24% of untreated patients die, and many cases are complicated by meningitis. Here, we explore clinical features of cutaneous disease associated with poor outcomes. METHODS: A systematic review identified 303 full-text articles published from 1950 through 2018 that met predefined inclusion criteria. Cases were abstracted, and descriptive analyses and univariate logistic regression were conducted to identify prognostic indicators for cutaneous anthrax. RESULTS: Of 182 included patients, 47 (25.8%) died. Previously reported independent predictors for death or meningitis that we confirmed included fever or chills; nausea or vomiting; headache; severe headache; nonheadache, nonmeningeal signs; leukocytosis; and bacteremia. Newly identified predictors included anxiety, abdominal pain, diastolic hypotension, skin trauma, thoracic edema, malignant pustule edema, lymphadenopathy, and evidence of coagulopathy (all with P < .05). CONCLUSIONS: We identified patient presentations not previously associated with poor outcomes.

Risk Factors for Severe Cutaneous Anthrax in a Retrospective Case Series and Use of a Clinical Algorithm to Identify Likely Meningitis and Evaluate Treatment Outcomes, Kyrgyz Republic, 2005-2012.

BACKGROUND: US Centers for Disease Control and Prevention guidelines currently recommend triple-therapy antimicrobial treatment for anthrax meningitis. In the Kyrgyz Republic, a country with endemic anthrax, cutaneous anthrax patients are routinely hospitalized and treated successfully with only monotherapy or dual therapy. Clinical algorithms have been developed to identify patients with likely anthrax meningitis based on signs and symptoms alone. We sought to retrospectively identify likely meningitis patients in the Kyrgyz Republic using a clinical algorithm and evaluate risk factors and their outcomes by type of treatment. METHODS: We conducted a retrospective chart review of cutaneous anthrax patients in the Kyrgyz Republic from 2005 through 2012. Using previous methods, we developed a highly specific algorithm to categorize patients by meningitis status. We then evaluated patient risk factors, treatments, and outcomes by disease severity and meningitis status. RESULTS: We categorized 37 of 230 cutaneous anthrax patients as likely having meningitis. All 37 likely meningitis patients survived, receiving only mono- or dual-therapy antimicrobials. We identified underlying medical conditions, such as obesity, hypertension, and chronic obstructive pulmonary disease, and tobacco and alcohol use, as potential risk factors for severe anthrax and anthrax meningitis. CONCLUSIONS: Based on our analyses, treatment of anthrax meningitis may not require 3 antimicrobials, which could impact future anthrax treatment recommendations. In addition, chronic comorbidities may increase risk for severe anthrax and anthrax meningitis. Future research should further investigate potential risk factors for severe anthrax and their impact on laboratory-confirmed meningitis and evaluate mono- and dual-therapy antimicrobial regimens for anthrax meningitis.

Welder's Anthrax: A Review of an Occupational Disease.

Since 1997, nine cases of severe pneumonia, caused by species within the B. cereus group and with a presentation similar to that of inhalation anthrax, were reported in seemingly immunocompetent metalworkers, with most being welders. In seven of the cases, isolates were found to harbor a plasmid similar to the B. anthracis pXO1 that encodes anthrax toxins. In this paper, we review the literature on the B. cereus group spp. pneumonia among welders and other metalworkers, which we term welder's anthrax. We describe the epidemiology, including more information on two cases of welder's anthrax in 2020. We also describe the health risks associated with welding, potential mechanisms of infection and pathological damage, prevention measures according to the hierarchy of controls, and clinical and public health considerations. Considering occupational risk factors and controlling exposure to welding fumes and gases among workers, according to the hierarchy of controls, should help prevent disease transmission in the workplace.

Analysis of Anthrax Immune Globulin Intravenous with Antimicrobial Treatment in Injection Drug Users, Scotland, 2009-2010.

We studied anthrax immune globulin intravenous (AIG-IV) use from a 2009-2010 outbreak of Bacillus anthracis soft tissue infection in injection drug users in Scotland, UK, and we compared findings from 15 AIG-IV recipients with findings from 28 nonrecipients. Death rates did not differ significantly between recipients and nonrecipients (33% vs. 21%). However, whereas only 8 (27%) of 30 patients at low risk for death (admission sequential organ failure assessment score of 0-5) received AIG-IV, 7 (54%) of the 13 patients at high risk for death (sequential organ failure assessment score of 6-11) received treatment. AIG-IV recipients had surgery more often and, among survivors, had longer hospital stays than did nonrecipients. AIG-IV recipients were sicker than nonrecipients. This difference and the small number of higher risk patients confound assessment of AIG-IV effectiveness in this outbreak.

Neural tube defects on the Texas-Mexico border: what we've learned in the 20 years since the Brownsville cluster.

We reviewed the published findings from the Texas Neural Tube Defect Project, a 6-year case-control study (1995-2000) of neural tube defects (NTDs) on the Texas-Mexico border. In this review, we highlight what was learned about environmental, genetic, and nutritional factors (i.e., those related to the folate and other metabolic pathways) and the novel putative risk factors that emerged from this study of Mexican American women living on the Texas-Mexico border. Our investigations of the micronutrients and metabolic pathways involved confirmed the findings of other researchers that increased folate intake has a protective effect and that low serum B(12) , high serum homocysteine levels, and obesity independently contribute to risk. Studies of this population also have implicated hyperinsulinemia and low ferritin, metabolic risk factors, which require additional study to elucidate their physiologic mechanism. Environmental contaminants such as heavy metals, pesticides, and polychlorinated biphenyls (PCBs), which were of community concern, did little to explain NTD risk. Studies in this folic acid deficit-population also revealed several novel risk factors, namely, diarrhea, stress, fumonisins, and the combination of nitrosatable drug exposure with high nitrate/nitrite intake. In conclusion, the 23 studies among the Mexican American women living along the Texas-Mexico border have demonstrated the multifactorial nature of NTDs and that a population deficient in folic acid will be vulnerable to a variety of insults whether brought on by individual behaviors (e.g., obesity) or through the surrounding environment (e.g., fumonisins). Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.

Can programmed cell death be induced in post-ejaculatory bull and stallion spermatozoa?

Apoptosis is common during spermatogenesis. Here, it was tested whether apoptosis could be induced in sperm after ejaculation. There were several lines of evidence to indicate that sperm are resistant to induction of apoptosis. First, incubation of bull sperm at temperatures characteristic of normothermia (38.5 degrees C) or heat shock (40 and 41 degrees C) for 4h did not increase the proportion of sperm positive for the TUNEL reaction. There was also no reduction in mitochondrial polarity caused by exposure to 40 or 41 degrees C. Incubation at 38.5 degrees C (least-squares mean+/-SEM=4.0+/-1.4%), 40 degrees C (6.2+/-1.4%), and 41 degrees C (7.0+/-1.4%) for 24h did increase the proportion of sperm that were TUNEL positive slightly as compared to non-incubated control sperm (1.0+/-1.4%). However, the increase in TUNEL labeling was not affected by incubation temperature and occurred even in the presence of the group II caspase inhibitor, z-DEVD-fmk. In addition, exposure of bull sperm to carbonyl cyanide 3-chlorophenylhydrazone (CCCP), which depolarizes mitochondrial membranes, did not increase TUNEL labeling. Stallion sperm were also resistant to increased TUNEL labeling in response to incubation at 41 degrees C for 4h or exposure to CCCP. Western blotting was performed to determine whether failure of induction of apoptosis was due to aberrant caspase activation. Procaspase-9 was detected in bull sperm, but cleavage to caspase-9 was not induced by short-term aging at 38.5, 40, or 41 degrees C, or exposure to CCCP. Procaspase-3 was not detected in bull spermatozoa. In conclusion, post-ejaculatory bull and stallion sperm were resistant to induction of apoptosis; this resistance, at least in bulls, was due to refractoriness of mitochondria to heat shock-induced depolarization, lack of activation of procaspase-9, and an absence of procaspase-3.

Exposure to fumonisins and the occurrence of neural tube defects along the Texas-Mexico border.

Along the Texas-Mexico border, the prevalence of neural tube defects (NTDs) among Mexican-American women doubled during 1990-1991. The human outbreak began during the same crop year as epizootics attributed to exposure to fumonisin, a mycotoxin that often contaminates corn. Because Mexican Americans in Texas consume large quantities of corn, primarily in the form of tortillas, they may be exposed to high levels of fumonisins. We examined whether or not maternal exposure to fumonisins increases the risk of NTDs in offspring using a population-based case-control study. We estimated fumonisin exposure from a postpartum sphinganine:sphingosine (sa:so) ratio, a biomarker for fumonisin exposure measured in maternal serum, and from maternal recall of periconceptional corn tortilla intake. After adjusting for confounders, moderate (301-400) compared with low (< or = 100) consumption of tortillas during the first trimester was associated with increased odds ratios (ORs) of having an NTD-affected pregnancy (OR = 2.4; 95% confidence interval, 1.1-5.3). No increased risks were observed at intakes higher than 400 tortillas (OR = 0.8 for 401-800, OR = 1.0 for > 800). Based on the postpartum sa:so ratio, increasing levels of fumonisin exposure were associated with increasing ORs for NTD occurrences, except for the highest exposure category (sa:so > 0.35). Our findings suggest that fumonisin exposure increases the risk of NTD, proportionate to dose, up to a threshold level, at which point fetal death may be more likely to occur. These results also call for population studies that can more directly measure individual fumonisin intakes and assess effects on the developing embryo.

Maternal exposure to arsenic, cadmium, lead, and mercury and neural tube defects in offspring.

Arsenic, cadmium, lead, and mercury are neurotoxins, and some studies suggest that these elements might also be teratogens. Using a case-control study design, we investigated the relation between exposure to these heavy metals and neural tube defects (NTDs) in offspring of Mexican-American women living in 1 of the 14 Texas counties bordering Mexico. A total of 184 case-women with NTD-affected pregnancies and 225 control-women with normal live births were interviewed about their environmental and occupational exposures during the periconceptional period. Biologic samples for blood lead and urinary arsenic, cadmium, and mercury were also obtained for a subset of these women. Overall, the median levels of these biomarkers for heavy metal exposure did not differ significantly (P > 0.05) between case- and control-women. However, among women in the highest income group, case-women were nine times more likely (95% confidence interval (CI) 1.4-57) than control-women to have a urinary mercury 5.62 microg/L. Case-women were 4.2 times more likely (95% CI 1.1-16) to report burning treated wood during the periconceptional period than control-women. Elevated odds ratios (ORs) were observed for maternal and paternal occupational exposures to arsenic and mercury, but the 95% CIs were consistent with unity. The 95% CIs of the ORs were also consistent with unity for higher levels of arsenic, cadmium, lead, and mercury in drinking water and among women who lived within 2 miles at the time of conception to industrial facilities with reported emissions of any of these heavy metals. Our findings suggest that maternal exposures to arsenic, cadmium, or lead are probably not significant risk factors for NTDs in offspring. However, the elevated urinary mercury levels found in this population and exposures to the combustion of treated wood may warrant further investigation.

Dietary nitrites and nitrates, nitrosatable drugs, and neural tube defects.

BACKGROUND: Amine-containing (nitrosatable) drugs can react with nitrite to form N-nitroso compounds, some of which are teratogenic. Data are lacking on whether dietary intake of nitrates and nitrites modifies the association between maternal nitrosatable drug exposure and neural tube defects (NTDs) in offspring. METHODS: We examined nitrosatable drug exposure and NTD-affected pregnancies in relation to dietary nitrite and total nitrite intake in a case-control study of Mexican American women. We interviewed 184 women with NTD-affected pregnancies and 225 women with normal live births, including questions on periconceptional drug exposures and dietary intake. For 110 study participants, nitrate was also measured in the usual source of drinking water. RESULTS: Women who reported taking drugs classified as nitrosatable were 2.7 times more likely to have an NTD-affected pregnancy than women without this exposure (95% confidence interval [CI] = 1.4-5.3). The effect of nitrosatable drugs was observed only in women with higher intakes of dietary nitrite and total nitrite (dietary nitrite + 5% dietary nitrate). Women within the highest tertile (greater than 10.5 mg/day) of total nitrite were 7.5 times more likely to have an NTD-affected pregnancy if they took nitrosatable drugs (95% CI = 1.8-45.4). The association between nitrosatable drug exposure and NTDs was also stronger in women whose water nitrate levels were higher. CONCLUSIONS: Findings suggest that effects of nitrosatable drug exposure on risk for neural tube defects in offspring could depend on the amounts of dietary nitrite and total nitrite intake.

Fumonisins disrupt sphingolipid metabolism, folate transport, and neural tube development in embryo culture and in vivo: a potential risk factor for human neural tube defects among populations consuming fumonisin-contaminated maize.

Fumonisins are a family of toxic and carcinogenic mycotoxins produced by Fusarium verticillioides (formerly Fusarium moniliforme), a common fungal contaminant of maize. Fumonisins inhibit ceramide synthase, causing accumulation of bioactive intermediates of sphingolipid metabolism (sphinganine and other sphingoid bases and derivatives) as well as depletion of complex sphingolipids, which interferes with the function of some membrane proteins, including the folate-binding protein (human folate receptor alpha). Fumonisin causes neural tube and craniofacial defects in mouse embryos in culture. Many of these effects are prevented by supplemental folic acid. Recent studies in LMBc mice found that fumonisin exposure in utero increases the frequency of developmental defects and administration of folate or a complex sphingolipid is preventive. High incidences of neural tube defects (NTD) occur in some regions of the world where substantial consumption of fumonisins has been documented or plausibly suggested (Guatemala, South Africa, and China); furthermore, a recent study of NTD in border counties of Texas found a significant association between NTD and consumption of tortillas during the first trimester. Hence, we propose that fumonisins are potential risk factors for NTD, craniofacial anomalies, and other birth defects arising from neural crest cells because of their apparent interference with folate utilization.

Parental occupation and neural tube defect-affected pregnancies among Mexican Americans.

In a case-control study, we examined whether parental occupational exposures were related to neural tube defect (NTD)-affected pregnancies among Mexican Americans living along the Texas-Mexico border. Case women were 184 Mexican-American women with NTD-affected pregnancies; control women were 225 study-area residents who delivered normal babies during the same period as the case women. The women were interviewed in person about maternal and paternal occupations and work exposures during the periconceptional period. Compared with control women, case women were more likely to have had occupational exposures to solvents (odds ratio [OR], infinity; 95% confidence interval [CI], 2.4-infinity) and also were more likely to have worked in cleaning (OR 9.5; 95% CI, 1.1 to 82.2) or health care occupations (OR 3.0; 95% CI, 1.0 to 9.0) than control women. No compelling associations were found between paternal work exposures or occupations and NTDs in offspring in this population.