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Concept: Botulism

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Background The last case of infection with wild-type poliovirus indigenous to China was reported in 1994, and China was certified as a poliomyelitis-free region in 2000. In 2011, an outbreak of infection with imported wild-type poliovirus occurred in the province of Xinjiang. Methods We conducted an investigation to guide the response to the outbreak, performed sequence analysis of the poliovirus type 1 capsid protein VP1 to determine the source, and carried out serologic and coverage surveys to assess the risk of viral propagation. Surveillance for acute flaccid paralysis was intensified to enhance case ascertainment. Results Between July 3 and October 9, 2011, investigators identified 21 cases of infection with wild-type poliovirus and 23 clinically compatible cases in southern Xinjiang. Wild-type poliovirus type 1 was isolated from 14 of 673 contacts of patients with acute flaccid paralysis (2.1%) and from 13 of 491 healthy persons who were not in contact with affected persons (2.6%). Sequence analysis implicated an imported wild-type poliovirus that originated in Pakistan as the cause of the outbreak. A public health emergency was declared in Xinjiang after the outbreak was confirmed. Surveillance for acute flaccid paralysis was enhanced, with daily reporting from all public and private hospitals. Five rounds of vaccination with live, attenuated oral poliovirus vaccine (OPV) were conducted among children and adults, and 43 million doses of OPV were administered. Trivalent OPV was used in three rounds, and monovalent OPV type 1 was used in two rounds. The outbreak was stopped 1.5 months after laboratory confirmation of the index case. Conclusions The 2011 outbreak in China showed that poliomyelitis-free countries remain at risk for outbreaks while the poliovirus circulates anywhere in the world. Global eradication of poliomyelitis will benefit all countries, even those that are currently free of poliomyelitis.

Concepts: Flaccid paralysis, Symptoms, Vaccine, Epidemiology, Botulism, Polio vaccine, Enterovirus

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Foodborne and intestinal botulism are the most common forms of human botulism; both result from the absorption of botulinum neurotoxin (BoNT) from the digestive tract into the circulation. BoNT is a large protein toxin (approximately 150 kDa), but it is able to pass through the epithelial barrier in the digestive tract. Recent cellular and molecular biology studies have begun to unravel the mechanisms by which this large protein toxin crosses the intestinal epithelial barrier. This review provides an overview of current knowledge relating to the absorption of botulinum toxins (BoNT and BoNT complex) from the gastrointestinal tract, with particular emphasis on the interaction of these toxins with the intestinal epithelial barrier.

Concepts: Small intestine, Clostridium botulinum, Bacteria, Botulism, Digestive system, Microbial toxins, Digestion, Protein

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Human enteroviruses (HEVs) are endemic worldwide and among the most common viruses infecting humans. Nevertheless, there is very limited data on the circulation and genetic diversity of HEVs in developing countries, and sub-Saharan Africa in particular.We investigated the circulation and genetic diversity of HEVs among 436 healthy children in a limited area of the far North region of Cameroon in 2008 and 2009. We also characterized the genetic biodiversity of 146 non-polio enterovirus (NPEV) isolates obtained throughout the year 2008 from the stool specimens of patients with acute flaccid paralysis (AFP) in Cameroon, Chad and Gabon.We found a high rate of NPEV infections (36.9%) among healthy children in the far North region of Cameroon. Overall 45 different HEV types were found among healthy children and AFP patients. Interestingly, this study uncovered a high rate of HEVs of species C (HEV-C) among all typed NPEVs: 63.1% (94/149) and 39.5% (49/124) in healthy children and AFP cases, respectively. Besides extensive circulation, the most prevalent HEV-C type, coxsackievirus A-13, featured a tremendous intratypic diversity. African specific HEV lineages were discovered, including HEV-C lineages and the recently reported EV-A71 “genogroup E”.Virtually all pathogenic circulating vaccine-derived polioviruses (cVDPVs) that have been fully characterized were recombinants between oral poliovaccine (OPV) strains and co-circulating HEV-C. The extensive circulation of diverse HEV-C types and lineages in countries where OPV is massively used constitutes a major viral factor that could promote the emergence of recombinant cVDPVs in the Central African sub-region.

Concepts: Botulism, Central African Republic, Biodiversity, Africa, Far North Region, Flaccid paralysis, Cameroon, Enterovirus

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Background. On July 7 and 11, 2007, respectively, health officials in Texas and Indiana reported 4 possible cases of type A foodborne botulism to the US Centers for Disease Control and Prevention. Foodborne botulism is a rare and sometimes fatal illness caused by consuming foods containing botulinum neurotoxin.Methods. Investigators reviewed patients' medical charts and food histories. Clinical specimens and food samples were tested for botulinum toxin and neurotoxin-producing Clostridium spp. Investigators conducted inspections of the cannery that produced the implicated product.Results. Eight confirmed outbreak associated cases were identified from Indiana (2), Texas (3), and Ohio (3). Botulinum toxin type A was identified in leftover chili sauce consumed by the Indiana patients and one of the Ohio patients. Cannery inspectors found violations of federal canned-food regulations that could have led to survival of C. botulinum spores during sterilization. The company recalled 39 million cans of chili. Following the outbreak, the US Food and Drug Administration inspected other canneries with similar canning systems and issued warnings to the industry about the danger of C. botulinum and the importance of compliance with canned food manufacturing regulations.Conclusion. Commercially produced hot dog chili sauce caused these cases of type A botulism. This is the first US foodborne botulism outbreak involving a commercial cannery in more than 30 years. Sharing of epidemiologic and laboratory findings allowed for the rapid identification of implicated food items and swift removal of potentially deadly products from the market by US food regulatory authorities.

Concepts: Epidemiology, Microbial toxins, Food, Castleberry's Food Company, Canning, Clostridium botulinum, Botulism, Botulinum toxin

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SUMMARY Since 2004, efforts to improve poliovirus detection have significantly increased the volume of specimen testing from acute flaccid paralysis (AFP) patients in India. One option to decrease collection and testing burden would be collecting only a single stool specimen instead of two. We investigated stool specimen sensitivity for poliovirus detection in India to estimate the contribution of the second specimen. We reviewed poliovirus isolation data for 303984 children aged <15 years with AFP during 2000-2010. Using maximum-likelihood estimation, we determined specimen sensitivity of each stool specimen, combined sensitivity of both specimens, and sensitivity added by the second specimen. Of 5184 AFP patients with poliovirus isolates, 382 (7·4%) were identified only by the second specimen. Sensitivity was 91·4% for the first specimen and 84·5% for the second specimen; the second specimen added 7·3% sensitivity, giving a combined sensitivity of 98·7%. Combined sensitivity declined, and added sensitivity increased, as the time from paralysis onset to stool collection increased (P = 0·032). The sensitivity added by the second specimen is important to detect the last chains of poliovirus transmission and to achieve certification of polio eradication. For sensitive surveillance, two stool specimens should continue to be collected from each AFP patient in India.

Concepts: Polio vaccine, Poliomyelitis, Maximum likelihood, Symptoms, Flaccid paralysis, Estimation theory, Botulism, Enterovirus

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BACKGROUND: Use of Botulinum toxin type A (BTX-A) for facial wrinkles is well-documented, but current methods of subjective evaluation by clinicians and patients fail to objectively quantify the magnitude and duration of facial muscle paralysis. OBJECTIVE: (a) Determine the locus of facial muscular tension; (b) Quantify and monitor muscular paralysis and subsequent return; © Continuously correlate the appearance of wrinkles and muscular tension using non-invasive digital image speckle correlation (DISC) to measure treatment efficacy; (d) Corroborate objective data with existing rating scales (subject global assessment and facial lines outcome-11). METHODS: Two sequential images of slight facial motion (frowning, raising eyebrows) are taken with a camera for n = 6 patients pre- and post-treatment at different time points up to 24 weeks. DISC processes the images to produce a vector map of muscular displacement to obtain spatially resolved information regarding facial tension. RESULTS: We observed maximum paralysis (≥70%) at 2 weeks, and the rate of recovery varied widely ranging from 2 to 5 months, with two patients continuing to exhibit reduced contraction at 24 weeks. Vector analysis of pre-treatment contraction correctly predicted injection site and illustrated lines of maximum tension. CONCLUSIONS: Digital image speckle correlation can precisely track the degree of contraction of different muscle groups following BTX-A injection. It can help predict injection site, quantify muscle paralysis, and monitor the recovery following BTX-A injection. Results were found to be reproducible across six patients.

Concepts: Efficacy, Microbial toxins, Computer graphics, Botulism, Scientific method, Botulinum toxin, Muscle, Paralysis

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Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and cause the fatal disease botulism, a flaccid paralysis of the muscle. BoNTs are released together with several auxiliary proteins as progenitor toxin complexes (PTCs) to become highly potent oral poisons. Here, we report the structure of a ∼760 kDa 14-subunit large PTC of serotype A (L-PTC/A) and reveal insight into its absorption mechanism. Using a combination of X-ray crystallography, electron microscopy, and functional studies, we found that L-PTC/A consists of two structurally and functionally independent sub-complexes. A hetero-dimeric 290 kDa complex protects BoNT, while a hetero-dodecameric 470 kDa complex facilitates its absorption in the harsh environment of the gastrointestinal tract. BoNT absorption is mediated by nine glycan-binding sites on the dodecameric sub-complex that forms multivalent interactions with carbohydrate receptors on intestinal epithelial cells. We identified monosaccharides that blocked oral BoNT intoxication in mice, which suggests a new strategy for the development of preventive countermeasures for BoNTs based on carbohydrate receptor mimicry.

Concepts: Ion channel, X-ray crystallography, Toxin, Botulinum toxin, Microbial toxins, Protein, Clostridium botulinum, Botulism

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Background. Clostridium botulinum strain IBCA10-7060, isolated from a patient with infant botulism, produced botulinum neurotoxin type B (BoNT/B) and another BoNT that, by use of the standard mouse bioassay, could not be neutralized by any of the Centers for Disease Control and Prevention-provided monovalent polyclonal botulinum antitoxins raised against BoNT types A-G.Methods and Results. The combining of antitoxins to neutralize the toxicity of known bivalent C. botulinum strains Ab, Ba, Af, and Bf also failed to neutralize the second BoNT. Analysis of culture filtrate by double immunodiffusion yielded a single line of immunoprecipitate with anti-A, anti-B, and anti-F botulinum antitoxins but not with anti-E antitoxin. A heptavalent F(ab')2 botulinum antitoxin A-G obtained from the US Army also did not neutralize the second BoNT. An antitoxin raised against IBCA10-7060 toxoid protected mice against BoNT/B (Okra) and against the second BoNT but did not protect mice against BoNT/A (Hall) or BoNT/F (Langeland).Conclusions. The second BoNT thus fulfilled classic criteria for being designated BoNT/H. IBCA10-7060 is the first C. botulinum type Bh strain to be identified. BoNT/H is the first new botulinum toxin type to be recognized in >40 years, and its recognition could not have been accomplished without the availability of the mouse bioassay.

Concepts: Neurotoxin, Passive immunity, Honey, Microbial toxins, Castleberry's Food Company, Botulism, Botulinum toxin, Clostridium botulinum

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An outbreak of acute flaccid paralysis among children in the United States during summer 2014 was tentatively associated with enterovirus D68 infection. This syndrome in a child in fall 2014 was associated with enterovirus C105 infection. The presence of this virus strain in North America may pose a diagnostic challenge.

Concepts: Latin America, Americas, Virus, Flaccid paralysis, Botulism, Enterovirus, North America, United States

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Clostridium botulinum neurotoxin (BoNT) is released as a progenitor complex, in association with a non-toxic-non-hemagglutinin protein (NTNH) and other associated proteins. We have determined the crystal structure of M type Progenitor complex of botulinum neurotoxin E [PTC-E(M)], a heterodimer of BoNT and NTNH. The crystal structure reveals that the complex exists as a tight, interlocked heterodimer of BoNT and NTNH. The crystal structure explains the mechanism of molecular assembly of the complex and reveals several acidic clusters at the interface responsible for association at low acidic pH and disassociation at basic/neutral pH. The similarity of the general architecture between the PTC-E(M) and the previously determined PTC-A(M) strongly suggests that the progenitor M complexes of all botulinum serotypes may have similar molecular arrangement, although the neurotoxins apparently can take very different conformation when they are released from the M complex.

Concepts: Botulism, Toxin, Neurotoxin, Acid, Neurotoxins, Microbial toxins, Botulinum toxin, Clostridium botulinum