Prevalence and phylogenetic traits of nitrite-producing bacteria in raw ingredients and processed baby foods: Potential sources of foodborne infant methemoglobinemia.

Nitrite, which has been mainly regarded as a chemical hazard, can induce infant methemoglobinemia. As for nitrite as a product of microbial metabolism, the contribution of the oral or gut microbiome has mostly received attention, whereas the role of nitrite-producing bacteria (NPBs) in food has been less elucidated. In this study, mesophilic NPBs were isolated from food samples (n = 320) composed of raw ingredients for weaning foods (n = 160; beetroot, broccoli, carrot, lettuce, rice powder, spinach, sweet potato, and honey) and processed baby foods (n = 160; cereal snack, cheese, yogurt, powdered infant formula, sorghum syrup, vegetable fruit juice, and weaning food). The phylogenetic diversity of the NPB strains was analyzed via 16S rRNA sequencing. All 15 food items harbored NPBs, with a prevalence of 71.9 % and 34.4 % for the raw ingredients and processed foods, respectively. The NPBs isolated from the foods were identified as Actinomycetota (Actinomycetes), Bacteroidota (Flavobacteriia, Sphingobacteriia), Bacillota (Bacilli), or Pseudomonadota (Alpha-, Beta-, and Gammaproteobacteria). Among the raw and processed foods, beetroot (85.0 %) and powdered infant formula (70.0 %) showed had the highest NPB prevalence (P > 0.05). Bacillota predominated in both types of food. The contamination source of Pseudomonadota, which was another major phylum present in the raw ingredients, was presumed to be the soil and endophytes in the seeds, whereas that of Bacillota was the manufacturing equipment used with the raw ingredients. Common species for probiotics, such as Lacticaseibacillus, Leuconostoc, Enterococcus, and Bacillus, were isolated and identified as NPBs. To our knowledge, this is the first study to reveal the taxonomical diversity and omnipresence of NPBs in food for babies. The results of this study highlight the importance of food-mediated microbiological risks of infant methemoglobinemia which are yet underrecognized.

Impact of land use/land cover changes on water quality and human health in district Peshawar Pakistan.

The quality and quantity of groundwater resources are affected by landuse/landcover (LULC) dynamics, particularly the increasing urbanization coupled with high household wastewater discharge and decreasing open lands. This study evaluates temporal changes of groundwater quality for 2012 and 2019, its relation to Landuse/landcover, and its impact on Peshawar's residents (study area), Pakistan. A total of 105 and 112 groundwater samples were collected from tube wells in 2012 and 2019. Samples were then analyzed for seven standard water quality parameters (i.e., pH, electric conductivity (EC), turbidity, chloride, calcium, magnesium, and nitrate). Patient data for waterborne diseases were also collected for the years 2012 and 2019 to relate the impact of groundwater quality on human health. Landsat satellite images were classified for the years 2012 and 2019 to observe landuse/landcover dynamics concerning groundwater quality. Results manifested a decrease in groundwater quality for the year 2019 compared to 2012 and were more highlighted in highly populated areas. The nitrate concentration level was found high in the vicinity of agricultural areas due to the excessive use of nitrogenous fertilizers and pesticides, and thus the methemoglobinemia patients ratio increased by 14% (48-62% for the year 2012 and 2019, respectively). Besides, Urinary Tract Infections, Peptic Ulcer, and Dental Caries diseases increased due to the high calcium and magnesium concentration. The overall results indicate that anthropogenic activities were the main driver of Spatio-temporal variability in groundwater quality of the study area. The study could help district health administration understand groundwater quality trends, make appropriate site-specific policies, and formulate future health regulations.

Causative Agents in Clinically Significant Methemoglobinemia: A National Poison Data System Study.

BACKGROUND: Recognition of the agents most commonly implicated in causing methemoglobinemia can provide context for making therapeutic decisions and inform the diagnostic process. We evaluated the etiologic agents most commonly implicated in clinically significant methemoglobinemia using data from the National Poison Data System (NPDS). STUDY QUESTION: What are the most frequent etiologic agents associated with clinically significant methemoglobinemia. STUDY DESIGN: This was a retrospective cross-sectional chart review using electronic data from the NPDS. The NPDS database was queried to identify cases from July 1, 2007, to June 30, 2017, that were coded as methylene blue treatment recommended and/or performed. Cases were excluded if the substance(s) have never been known to cause methemoglobin or the substances suggested methylene blue was used adjunctively for refractory shock (eg, calcium channel or beta blocker). Multiple substance exposures were reviewed and substances not known to cause methemoglobinemia were excluded. MEASURES AND OUTCOMES: The primary end point was to summarize the most frequent etiologic agents associated with the administration of methylene blue for clinically significant methemoglobinemia. RESULTS: There were 2563 substances reported in 1209 cases. After excluding coingestants and cases not associated with methemoglobinemia, there were 1236 substances. The top 4 substance categories were benzocaine, phenazopyridine, dapsone, and nitrates/nitrites. CONCLUSIONS: This study reveals the relative contribution of various drugs and chemicals associated with methylene blue administration. Over two-thirds of all cases were associated with benzocaine, phenazopyridine, dapsone, and nitrates/nitrites.

Methemoglobinemia: Infants at risk.

Methemoglobin is formed when the iron center in hemoglobin is oxidized from ferrous iron to ferric iron. The functional consequence of this change is that hemoglobin is transformed to methemoglobin and cannot oxygenate tissues adequately, causing hypoxia and cyanosis. Infants have unique physiology that increases their risk of developing methemoglobinemia. Infants drink more water per body weight compared to children and adults, have lower NADH cyb5r reductase activity that converts methemoglobin to hemoglobin, and have a higher percentage of fetal hemoglobin, which is easier to convert to methemoglobin. A well-studied exposure to a chemical that can cause methemoglobinemia in infants is nitrate in well water. For the first part specifically about methemoglobin in infants, articles that were recent (2015-now) were given preference over articles that were older. Search terms included: methemoglobin, methemoglobinemia, infant, acquired, congenital, and methylene blue. For the latter half of the paper on nitrate and methemoglobinemia, preference was given to articles that described regionally important cases. In addition, search terms were: Minnesota, methemoglobinemia, nitrate, well water, drinking water, and infant. Acquired methemoglobinemia is rare, yet can still be seen in medical settings, and when an infant is exposed to nitrate in well water above 10 mg/L. To prevent exposure, parents should have their water tested for nitrate before the baby comes home. Physicians should make it practice to ask what the source of drinking water is for newly pregnant women and urge them to test for nitrate and bacteria if using a well. Using bottled water to make formula is also an option, but the best option is still breastfeeding.

Methemoglobinemia Associated with Late-Onset Neonatal Sepsis: A Single-Center Experience.

OBJECTIVE: Methemoglobinemia (MetHb) is a rare congenital or acquired cause of infantile cyanosis. We examined the role of MetHb in a neonatal intensive care unit (NICU). STUDY DESIGN: A retrospective observational study was conducted reviewing blood gas analyses of hospitalized newborns over a 2-year period. MetHb-positive patients (MetHb >1.8%) were matched with a control group for gestational age, weight, disease, and illness severity at admission. Maternal, neonatal, clinical, and laboratory parameters were collected and analyzed in both groups. RESULTS: MetHb incidence was 6%. The mean MetHb in the case group was 7.2%, and the first positive samples were observed at a mean of 22 days of life, 6 days prior to clinical or culture-proven sepsis. We identified low maternal age (31 vs. 34 years; p = 0.038), sepsis (90 vs. 45%; p = 0.022), and protracted parenteral nutrition (46 vs. 23 days; p = 0.013) as risk factors for MetHb, and early minimal enteral feeding as protective factor (12th vs. 9th day; p = 0.038). CONCLUSION: MetHb has a high occurrence in NICU and can be a helpful prognostic indicator of an infectious process. Understanding and prompt identification of MetHb can allow pediatricians to implement a life-saving therapy.

Does nitrite and nitrate levels in drinking water impact the health of people in Dakahlia governorate, Egypt?

A total of 1291 drinking water samples were examined for nitrite and nitrate during 6 months from December, 2015 to May, 2016 at 17 cities of Dakahlia governorate (Nile Delta, north of Egypt), and the results were utilized for assessment of health risk of the exposure from drinking water by calculating average daily intake (ADI), hazard quotient (HQ), and the hazard index (HI). The nitrite and nitrate in drinking water had a concentration range of 0.030-0.113 and 2.41-8.70 mg L-1, with mean values of 0.059 ± 0.014 and 5.25 ± 1.61 mg L-1, respectively. Nitrite and nitrate levels in rural areas and ground water samples were significantly higher than that in the urban ones. None of the analyzed samples exceeded WHO guideline values that set out to prevent methemoglobinemia. The values of HQ and HI for all age groups do not exceed unity indicating a low risk of methaemoglobinaemia for the population in this area. Results of the present study indicate that there is no health risk of residents from nitrite and nitrate through drinking water in the studied area. However, the other sources of exposure to nitrite and nitrate should be investigated in further studies.

Poppers regulation for public sale: No measure in France yet.

AIM: Poppers have become legal in France since June 2013. Is their liberalisation associated with an increase of severe side effects observed? METHODS: To identify elevated methaemoglobinaemia related to poppers abuse, we reviewed all methaemoglobin concentrations measured in Nantes university hospital, during 12 months. RESULTS: Methaemoglobin concentrations were superior to 25% in three cases of poppers consumption that occurred after the legalisation. CONCLUSION: Evaluating the prevalence of elevated methaemoglobinaemia could help to monitor severe complications of poppers use in France.

Methemoglobinemia incidence after the application of lidocaine for small surgical procedures.

OBJECTIVES: Methemoglobinemia (MetHb) is a rare condition that may have mortal consequences. Literature shows cases of methemoglobinemia due to the use of lidocaine and other local anesthetics. This is a cross-sectional study to determine the incidence of methemoglobinemia after the application of lidocaine. METHODS: In this study, 88 patients admitted to the emergency department of a university hospital between May 2014 and May 2015 and needed lidocaine application for small surgical procedures were included. When compared before and after the administration of lidocaine <2 mg/kg and >2 mg/kg, there was not a significant difference in the level of methemoglobin, hemoglobin, or in the hematocrit (p=0.604, p=0.502, and p=0.367, respectively). RESULTS: Mean age of the patients was 33.85 (±17.58) years, and 83% of the patients were male. Methemoglobin levels were not significantly different before and after the procedures (p>0.05). CONCLUSION: The results of our study were consistent with the literature; lidocaine associated methemoglobinemia is a rare complication.

The Experience of a District General Hospital with a Large Outdoor Music Festival in England.

OBJECTIVES: To assess the impact of the Parklife annual music festival on the local hospital, North Manchester General. METHODS: Data was obtained retrospectively by analysis of emergency department records during the weekend of Parklife 2015. RESULTS: 32 patients were identified, 56% reported taking drugs. 34% were admitted for overnight observation. 4 patients presented with methaemoglobinaemia following oral ingestion of amyl nitrate. One patient had a methaemoglobin fraction of 90.6%, which is amongst the most extreme recorded in literature. CONCLUSION: Music festivals can impose a burden on local health services. Organisers should operate an efficient surveillance system in order to prevent the sale and use of recreational drugs, providing adequate on-site health services and working in collaboration with local emergency services.

Enzymopenic Congenital Methemoglobinemia in Children of the Republic of Sakha (Yakutia).

Type I congenital methemoglobinemia is an autosomal recessive disorder. A high frequency of congenital methemoglobinemia has been reported among Native Americans inhabiting the Yukon-Kuskokwim Delta. Other rare cases of congenital methemoglobinemia of types I and II have been reported in Japan and other countries. In Russia-namely, in Yakutia-a high frequency of type I congenital methemoglobinemia has been reported. In 2009, the Consultation Polyclinic of the Pediatric Center in Yakutsk city established a registry of children with congenital methemoglobinemia. In total, 43 patients were registered between 2005 and 2009. The median methemoglobin level was 13.5% (ranging between 4.2% and 33.9%) and physical examination revealed cyanosis of the skin and mucus membranes. There were significant positive relationships between percentage of methemoglobin and erythrocyte count, hemoglobin concentration, and hematocrit among male patients, consistent with an upregulation of the hypoxic response. The prevalence per 100,000 children ranged from 12.7 to 47.0 in 3 geographic regions of Yakutia. Further research is needed to clarify the clinical consequences of congenital methemoglobinemia in the children of Yakutia and the reasons for the high variability in the prevalence of the condition.

Clinical spectrum and molecular basis of recessive congenital methemoglobinemia in India.

We report the clinical features and molecular characterization of 23 patients with cyanosis due to NADH-cytochrome b5 reductase (NADH-CYB5R) deficiency from India. The patients with type I recessive congenital methemoglobinemia (RCM) presented with mild to severe cyanosis only whereas patients with type II RCM had cyanosis associated with severe neurological impairment. Thirteen mutations were identified which included 11 missense mutations causing single amino acid changes (p.Arg49Trp, p.Arg58Gln, p.Pro145Ser, p.Gly155Glu, p.Arg160Pro, p.Met177Ile, p.Met177Val, p.Ile178Thr, p.Ala179Thr, p.Thr238Met, and p.Val253Met), one stop codon mutation (p.Trp236X) and one splice-site mutation (p.Gly76Ser). Seven of these mutations (p.Arg50Trp, p.Gly155Glu, p.Arg160Pro, p.Met177Ile, p.Met177Val, p.Ile178Thr, and p.Thr238Met) were novel. Two mutations (p.Gly76Ser and p.Trp236X) were identified for the first time in the homozygous state globally causing type II RCM. We used the three-dimensional (3D) structure of human erythrocyte NADH-CYB5R to evaluate the protein structural context of the affected residues. Our data provides a rationale for the observed enzyme deficiency and contributes to a better understanding of the genotype-phenotype correlation in NADH-CYB5R deficiency.

Ingesta dietética de nitratos en bebés y niños españoles y riesgo de metahemoglobinemia / Dietary intake of nitrate in Spanish infants and children and risk of methemoglobinemia

Pese a que el consumo de verduras y hortalizas es recomendable tanto en adultos como en bebés y niños pequeños, existe el riesgo de que estos últimos ingieran a través de dichos alimentos cantidades elevadas de nitratos que incrementen el riesgo de padecer metahemoglobinemia. Aunque la ingesta media de nitratos en la población infantil europea no supera los márgenes de seguridad, un análisis llevado a cabo por la Autoridad Europea de Seguridad Alimentaria (EFSA) en 2010 reveló que el consumo de espinacas puede estar implicado en ciertos casos de metahemoglobinemia infantil. La Agencia Española de Seguridad Alimentaria y Nutrición (AESAN) consideró en 2011 que las acelgas, debido a su notable consumo en España, también pueden suponer un riesgo para la población infantil si su ingesta es elevada. A las recomendaciones de la AESAN, que es conveniente que conozca cualquier profesional sanitario del ámbito de la nutrición infantil, resulta prudente añadir que un elevado consumo de borraja (Borago officinalis, una hortaliza muy consumida en Navarra, La Rioja y Aragón en la elaboración de purés hechos en casa) también puede estar implicado en la metahemoglobinemia infantil. En cualquier caso, tal y como señalan tanto la EFSA como la AESAN, cuando se comparan los riesgos/beneficios de la exposición de nitratos por el consumo de verduras y hortalizas, prevalecen los efectos beneficiosos de su consumo (AU)

Although the consumption of vegetables is recommended for adults, infants and young children, there is a risk that their consumption results in a high intake of nitrates that increases the risk of methemoglobinemia. Even though the average nitrate intake in children does not exceed the European safety threshold, an analysis conducted by the European Food Safety Authority (EFSA) in 2010 revealed that the consumption of spinach may be involved in certain cases of infant methemoglobinemia. The Spanish Agency for Food Safety and Nutrition (AESAN) found in 2011 that chards, because of its remarkable consumption in Spain, may also pose a risk for children. In addition to the AESAN recommendations, that any health care professional in the field of infant nutrition should know, it is prudent to add that a high consumption of borage (Borago officinalis, a vegetable widely consumed in Navarra, La Rioja and Aragón in homemade purees) may also be involved in infant methemoglobinemia. In any case, and as EFSA and AESAN point out, the benefits of eating vegetables prevail over the risks of the exposure to nitrates linked to their consumption (AU)

Dapsone-induced methemoglobinemia in renal transplant recipients: more prevalent than previously thought.

BACKGROUND: After an outbreak of Pneumocystis pneumonia (PCP) in our nephrology unit, dapsone was used as the second-line chemoprophylactic agent. Dapsone is the most common cause of drug-induced methemoglobinemia (MHb). Its prevalence is poorly described in the renal transplant population. Because dapsone is excreted by the kidneys, we hypothesized that the rate of MHb in these patients would be higher than previously reported. We aimed to describe the demographics, risk factors, and presenting features of MHb in these renal transplant patients. METHODS: Twenty-six transplant recipients commenced on dapsone for chemoprophylaxis against PCP from February to September 2011. All patients had normal glucose-6-phosphate dehydrogenase levels before treatment. Characteristics of patients with MHb were compared with those of the rest of the cohort to determine potential risk factors. RESULTS: Twelve (46%) patients developed MHb (levels 6.4 ± 4.1%). Six (50%) of the patients with MHb were asymptomatic on presentation. Cases had a mean drop in hemoglobin of 19 ± 7%. MHb led to five admissions (median length of stay 5 days, range 1-10 days). MHb level showed a strong correlation with the length of stay (correlation coefficient 0.762, P = 0.002). CONCLUSION: This is the highest reported prevalence of MHb, to our knowledge, in patients receiving dapsone, and its use led to significant hospitalization in this population. This study raises concerns about the use of dapsone as chemoprophylaxis in renal transplant recipients.

Risk of topical anesthetic-induced methemoglobinemia: a 10-year retrospective case-control study.

IMPORTANCE: Methemoglobinemia is a rare but serious disorder, defined as an increase in oxidized hemoglobin resulting in a reduction of oxygen-carrying capacity. Although methemoglobinemia is a known complication of topical anesthetic use, few data exist on the incidence of and risk factors for this potentially life-threatening disorder. OBJECTIVE: To examine the incidence of and risk factors for procedure-related methemoglobinemia to identify patient populations at high risk for this complication. DESIGN AND SETTING: Retrospective study in an academic research setting. PARTICIPANTS: Medical records for all patients diagnosed as having methemoglobinemia during a 10-year period were reviewed. EXPOSURES: All cases of methemoglobinemia that occurred after the following procedures were included in the analysis: bronchoscopy, nasogastric tube placement, esophagogastroduodenoscopy, transesophageal echocardiography, and endoscopic retrograde cholangiopancreatography. MAIN OUTCOMES AND MEASURES: Comorbidities, demographics, concurrent laboratory values, and specific topical anesthetic used were recorded for all cases. Each case was compared with matched inpatient and outpatient cases. RESULTS: In total, 33 cases of methemoglobinemia were identified during the 10-year period among 94,694 total procedures. The mean (SD) methemoglobin concentration was 32.0% (12.4%). The methemoglobinemia prevalence rates were 0.160% for bronchoscopy, 0.005% for esophagogastroduodenoscopy, 0.250% for transesophageal echocardiogram, and 0.030% for endoscopic retrograde cholangiopancreatography. Hospitalization at the time of the procedure was a major risk factor for the development of methemoglobinemia (0.14 cases per 10,000 outpatient procedures vs 13.7 cases per 10,000 inpatient procedures, P < .001). CONCLUSIONS AND RELEVANCE: The overall prevalence of methemoglobinemia is low at 0.035%; however, an increased risk was seen in hospitalized patients and with benzocaine-based anesthetics. Given the potential severity of methemoglobinemia, the risks and benefits of the use of topical anesthetics should be carefully considered in inpatient populations.

Sudden onset methaemoglobinaemia in a previously well Ugandan child: a case report and literature review.

Methaemoglobinaemia is a rare condition of unknown prevalence. Diagnostic tests in resource limited settings are very rare but clinical signs can be a good guide. We set out to describe a case of Methaemoglobinaemia, raise awareness among practitioners in resource limited settings and to share experiences in its diagnosis and management. A previously well three and a half year old girl was admitted with central cyanosis of sudden onset. She underwent clinical, laboratory and radiological evaluation. Having been in a resource limited setting, the process of making a diagnosis was slow and difficult. After the diagnosis, the treatment was not available in the country but we managed to get it all the way from Nairobi, Kenya. A diagnosis of Methaemoglobinaemia was made using Spectrophotometry and she was successfully treated using 2 doses of intravenous Methylene blue. The cause of Methaemoglobinaemia was established to have been nitrites from food preservatives.