Severe illness associated with reported use of synthetic cannabinoids: a public health investigation (Mississippi, 2015).

STUDY OBJECTIVES: In April 2015, a multistate outbreak of illness linked to synthetic cannabinoid (SC) use was unprecedented in magnitude and severity. We identified Mississippi cases in near-real time, collected information on cases to characterize the outbreak, and identified the causative SC. METHODS: A case was defined as any patient of a Mississippi healthcare facility who was suspected of SC use and presenting with ≥2 of the following symptoms: sweating, severe agitation, or psychosis during April 2-May 3, 2015. Clinicians reported cases to the Mississippi Poison Control Center (MPCC). We used MPCC data to identify cases at the University of Mississippi Medical Center (UMMC) to characterize in further detail, including demographics and clinical findings. Biologic samples were tested for known and unknown SCs by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). RESULTS: Clinicians reported 721 cases (11 deaths) statewide; 119 (17%) were UMMC patients with detailed data for further analysis. Twelve (10%) were admitted to an intensive care unit and 2 (2%) died. Aggression (32%), hypertension (33%), and tachycardia (42%) were common. SCs were identified in serum from 39/56 patients (70%); 33/39 patients (85%) tested positive for MAB-CHMINACA (N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide) or its metabolites. Compared to all patients tested for SCs, those positive for MAB-CHMINACA were more likely to have altered mental status on examination (OR = 3.3, p = .05). CONCLUSION: SC use can cause severe health effects. MAB-CHMINACA was the most commonly detected SC in this outbreak. As new SCs are created, new strategies to optimize surveillance and patient care are needed to address this evolving public health threat.

Description of a Mass Poisoning in a Rural District in Mozambique: The First Documented Bongkrekic Acid Poisoning in Africa.

Background: On 9 January 2015, in a rural town in Mozambique, >230 persons became sick and 75 died of an illness linked to drinking pombe, a traditional alcoholic beverage. Methods: An investigation was conducted to identify case patients and determine the cause of the outbreak. A case patient was defined as any resident of Chitima who developed any new or unexplained neurologic, gastrointestinal, or cardiovascular symptom from 9 January at 6:00 am through 12 January at 11:59 pm. We conducted medical record reviews, healthcare worker and community surveys, anthropologic and toxicologic investigations of local medicinal plants and commercial pesticides, and laboratory testing of the suspect and control pombe. Results: We identified 234 case patients; 75 (32%) died and 159 recovered. Overall, 61% of case patients were female (n = 142), and ages ranged from 1 to 87 years (median, 30 years). Signs and symptoms included abdominal pain, diarrhea, vomiting, and generalized malaise. Death was preceded by psychomotor agitation and abnormal posturing. The median interval from pombe consumption to symptom onset was 16 hours. Toxic levels of bongkrekic acid (BA) were detected in the suspect pombe but not the control pombe. Burkholderia gladioli pathovar cocovenenans, the bacteria that produces BA, was detected in the flour used to make the pombe. Conclusions: We report for the first time an outbreak of a highly lethal illness linked to BA, a deadly food-borne toxin in Africa. Given that no previous outbreaks have been recognized outside Asia, our investigation suggests that BA might be an unrecognized cause of toxic outbreaks globally.

Bongkrekic Acid-a Review of a Lesser-Known Mitochondrial Toxin.

INTRODUCTION: Bongkrekic acid (BA) has a unique mechanism of toxicity among the mitochondrial toxins: it inhibits adenine nucleotide translocase (ANT) rather than the electron transport chain. Bongkrekic acid is produced by the bacterium Burkholderia gladioli pathovar cocovenenans (B. cocovenenans) which has been implicated in outbreaks of food-borne illness involving coconut- and corn-based products in Indonesia and China. Our objective was to summarize what is known about the epidemiology, exposure sources, toxicokinetics, pathophysiology, clinical presentation, and diagnosis and treatment of human BA poisoning. METHODS: We searched MEDLINE (1946 to present), EMBASE (1947 to present), SCOPUS, The Indonesia Publication Index ( http://id.portalgaruda.org/ ), ToxNet, book chapters, Google searches, Pro-MED alerts, and references from previously published journal articles. We identified a total of 109 references which were reviewed. Of those, 29 (26 %) had relevant information and were included. Bongkrekic acid is a heat-stable, highly unsaturated tricarboxylic fatty acid with a molecular weight of 486 kDa. Outbreaks have been reported from Indonesia, China, and more recently in Mozambique. Very little is known about the toxicokinetics of BA. Bongkrekic acid produces its toxic effects by inhibiting mitochondrial (ANT). ANT can also alter cellular apoptosis. Signs and symptoms in humans are similar to the clinical findings from other mitochondrial poisons, but they vary in severity and time course. Management of patients is symptomatic and supportive. CONCLUSIONS: Bongkrekic acid is a mitochondrial ANT toxin and is reported primarily in outbreaks of food-borne poisoning involving coconut and corn. It should be considered in outbreaks of food-borne illness when signs and symptoms manifest involving the liver, brain, and kidneys and when coconut- or corn-based foods are implicated.

Influenza-like illness in an urban community of Salvador, Brazil: incidence, seasonality and risk factors.

BACKGROUND: Our understanding of the epidemiology of influenza is limited in tropical regions, which in turn has hampered identifying optimal region-specific policy to diminish disease burden. Influenza-like illness (ILI) is a clinical diagnosis that can be used as a surrogate for influenza. This study aimed to define the incidence and seasonality of ILI and to assess its association with climatic variables and school calendar in an urban community in the tropical region of Salvador, Brazil. METHODS: Between 2009 and 2013, we conducted enhanced community-based surveillance for acute febrile illnesses (AFI) among patients ≥ 5 years of age in a slum community emergency unit in Salvador, Brazil. ILI was defined as a measured temperature of ≥ 37.8 °C or reported fever in a patient with cough or sore throat for ≤ 7 days, and negative test results for dengue and leptospirosis. Seasonality was analyzed with a harmonic regression model. Negative binomial regression models were used to correlate ILI incidence with rainfall, temperature, relative humidity and the number of days per month that schools were in session while controlling for seasonality. RESULTS: There were 2,651 (45.6% of 5,817 AFI patients) ILI cases with a mean annual incidence of 60 cases/1,000 population (95% CI 58-62). Risk of ILI was highest among 5-9 year olds with an annual incidence of 105 cases/1,000 population in 2009. ILI had a clear seasonal pattern with peaks between the 35-40th week of the year. ILI peaks were higher and earlier in 5-9 year olds compared with > 19 year olds. No association was seen between ILI and precipitation, relative humidity or temperature. There was a significant association between the incidence of ILI in children 5-9 years of age and number of scheduled school days per month. CONCLUSIONS: We identified a significant burden of ILI with distinct seasonality in the Brazilian tropics and highest rates among young school-age children. Seasonal peaks of ILI in children 5-9 years of age were positively associated with the number of school days, indicating that children may play a role in the timing of seasonal influenza transmission.

Severe Illness Associated with Reported Use of Synthetic Cannabinoids - Mississippi, April 2015.

On April 2, 2015, four patients were evaluated at the University of Mississippi Medical Center (UMMC) in Jackson, Mississippi, for agitated delirium after using synthetic cannabinoids. Over the next 3 days, 24 additional persons went to UMMC with illnesses suspected to be related to synthetic cannabinoid use; one patient died. UMMC notified the Mississippi State Department of Health, which issued a statewide alert via the Health Alert Network on April 5, requesting that health care providers report suspected cases of synthetic cannabinoid intoxication to the Mississippi Poison Control Center (MPCC). A suspected case was defined as the occurrence of at least two of the following symptoms: sweating, severe agitation, or psychosis in a person with known or suspected synthetic cannabinoid use. A second statewide alert was issued on April 13, instructing all Mississippi emergency departments to submit line lists of suspected patients to MPCC each day. By April 21, 16 days after the first alert was issued, MPCC had received reports of approximately 400 cases, including eight deaths possibly linked to synthetic cannabinoid use; in contrast, during April 2012­March 2015, the median number of telephone calls to MPCC regarding synthetic cannabinoid use was one per month (range = 0­11). The Mississippi State Department of Health, with the assistance of CDC, initiated an investigation to better characterize the outbreak, identify risk factors associated with severe illness, and prevent additional illnesses and deaths.

Spatial Distribution of Dengue in a Brazilian Urban Slum Setting: Role of Socioeconomic Gradient in Disease Risk.

BACKGROUND: Few studies of dengue have shown group-level associations between demographic, socioeconomic, or geographic characteristics and the spatial distribution of dengue within small urban areas. This study aimed to examine whether specific characteristics of an urban slum community were associated with the risk of dengue disease. METHODOLOGY/PRINCIPAL FINDINGS: From 01/2009 to 12/2010, we conducted enhanced, community-based surveillance in the only public emergency unit in a slum in Salvador, Brazil to identify acute febrile illness (AFI) patients with laboratory evidence of dengue infection. Patient households were geocoded within census tracts (CTs). Demographic, socioeconomic, and geographical data were obtained from the 2010 national census. Associations between CTs characteristics and the spatial risk of both dengue and non-dengue AFI were assessed by Poisson log-normal and conditional auto-regressive models (CAR). We identified 651 (22.0%) dengue cases among 2,962 AFI patients. Estimated risk of symptomatic dengue was 21.3 and 70.2 cases per 10,000 inhabitants in 2009 and 2010, respectively. All the four dengue serotypes were identified, but DENV2 predominated (DENV1: 8.1%; DENV2: 90.7%; DENV3: 0.4%; DENV4: 0.8%). Multivariable CAR regression analysis showed increased dengue risk in CTs with poorer inhabitants (RR: 1.02 for each percent increase in the frequency of families earning ≤1 times the minimum wage; 95% CI: 1.01-1.04), and decreased risk in CTs located farther from the health unit (RR: 0.87 for each 100 meter increase; 95% CI: 0.80-0.94). The same CTs characteristics were also associated with non-dengue AFI risk. CONCLUSIONS/SIGNIFICANCE: This study highlights the large burden of symptomatic dengue on individuals living in urban slums in Brazil. Lower neighborhood socioeconomic status was independently associated with increased risk of dengue, indicating that within slum communities with high levels of absolute poverty, factors associated with the social gradient influence dengue transmission. In addition, poor geographic access to health services may be a barrier to identifying both dengue and non-dengue AFI cases. Therefore, further spatial studies should account for this potential source of bias.

A multicenter study of Clostridium difficile infection-related colectomy, 2000-2006.

OBJECTIVE: To assess Clostridium difficile infection (CDI)-related colectomy rates by CDI surveillance definitions and over time at multiple healthcare facilities. SETTING: Five university-affiliated acute care hospitals in the United States. DESIGN AND METHODS: Cases of CDI and patients who underwent colectomy from July 2000 through June 2006 were identified from 5 US tertiary care centers. Monthly CDI-related colectomy rates were calculated as the number of CDI-related colectomies per 1,000 CDI cases, and cases were categorized according to recommended surveillance definitions. Logistic regression was performed to evaluate risk factors for CDI-related colectomy. RESULTS: In total, 8,569 cases of CDI were identified, and 75 patients underwent CDI-related colectomy. The overall colectomy rate was 8.7 per 1,000 CDI cases. The CDI-related colectomy rate ranged from 0 to 23 per 1,000 CDI episodes across hospitals. The colectomy rate for healthcare-facility-onset CDI was 4.3 per 1,000 CDI cases, and that for community-onset CDI was 16.5 per 1,000 CDI cases (P < .05). There were significantly more CDI-related colectomies at hospitals B and C (P < .05). CONCLUSIONS: The overall CDI-related colectomy rate was low, and there was no significant change in the CDI-related colectomy rate over time. Onset of disease outside the study hospital was an independent risk factor for colectomy.