Outbreak of Foodborne Botulism in Alexandria, Egypt: Modulating Indications for Administration of Heptavalent Botulinum Antitoxin

Outbreak of Foodborne Botulism in Alexandria, Egypt: Modulating Indications for Administration of Heptavalent Botulinum Antitoxin | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Outbreak of Foodborne Botulism in Alexandria, Egypt: Modulating Indications for Administration of Heptavalent Botulinum Antitoxin Sara A Ghitani, Maha A Ghanem, Eman A Sultan, Maram Atef, Maii F Henaidy This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-267943/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Jan, 2022 Read the published version in Environmental Science and Pollution Research → Version 1 posted 6 You are reading this latest preprint version Abstract Background: In October 2019, 94 patients were admitted into Alexandria Poison Center (APC) with a history of ingestion of Feseekh (salted fish). As a trial to allocate the resources, not all patients were given Heptavalent botulinum antitoxin (HBAT) immediately. The current study aimed to portray the clinical characteristics of the cases, explore the possible relation between these characteristics and necessity of HBAT administration, explore the reliability of MLT, and to establish a clinical guide for management with preservation of resources. Subject and Method: the current prospective study included 94 patients who were admitted to Alexandria Poison Center (APC) in the period from 29 th September to 27 th October 2019. The patients' data was recorded using a checklist that includes: personal data, past medical history, clinical assessment, investigations, treatment and the outcome. The checklist was carried out to assess and follow up each patient. Hospitalized patients were categorized according to symptoms consistent with botulism. The equine HBAT, made by Emergent BioSolutions Canada Inc. (formerly Can gene Corporation) was used in the treatment. Results: HBAT was given to (36.2%) patients only out of the total admission. However, 87.2% of patients were completely cured, whereas 10.6% of patients were discharged with mild neurological sequelea and death occurred only in two cases (2.2%). Conclusion: 63.8% of cases with suspected foodborne botulism toxicity could be managed by supportive treatment only with no need for HBAT. Environmental Engineering Environmental Policy Alexandria Poison Center (APC) Heptavalent botulinum antitoxin (HBAT) mild neurological sequelea Introduction Botulism is considered one of the recurrent events that confront poison centers, in Egypt, each year due to a traditional salted fish meal which is consumed each spring (Weber et al.1993). In the spring of 2019, there were 58 cases of botulism admitted to APC and only 3 cases needed botulinum antitoxin . However, they suffered from side effects where 2 cases had severe epistaxis and one case arrested during anti-toxin administration. On 29 September, a child was transferred to APC for differential diagnosis of paralytic ileus as her family said she was given a piece of salted fish (feseekh) and she was considered the first case of the outbreak. Preliminary assessment of the situation was carried out and preparations were made to confront a large outbreak out of season. A collaborative team from APC doctors with Egyptian Ministry of Health (EMOH) was initiated to conduct interviews with the cases about the source, the time of the start of symptoms, other personnel of same family exposed to same meal…. etc. Blood specimens were collected from the cases. Identified factors common to all cases and formulated preliminary hypotheses were issued. The team delivered a daily report to the authorities, and all types of media were used to issue a warning until the outbreak was stopped on 27-10-2019. The Egyptian news declared previously the death of almost 100 tons of "mullet" fish and veterinarians warning of the mass death of fish in a small town called Rashid which was considered the source of that outbreak (Veterinarians warn of the mass death of fish in Lake Rashid.2019). Due to delay in results of mouse lethal test (MLT) and its positive and negative fallacies, the APC team treated the cases depending on the clinical picture (Lindstrom et al 2006, Chaudhry.2011, Wilder-Kofie et al. 2011, Wheeler et al.2009). We tried to decrease the exposure of the patients to the side effects of the antitoxin due to our unpleasant experience with Heptavalent botulinum antitoxin in spring of the same year. (Richardson et al 2020). The current study aimed to portray the clinical characteristics of the cases, to explore the possible relation between these characteristics and necessity of HBAT administration, to explore the reliability of MLT and to establish a clinical guide of management of the suspected cases of botulism with preservation of resources. Subjects And Methods I. Research strategy and design: The descriptive epidemiological approach is selected. II. Research setting: Target population and place: All patients admitted to APC - The Main University Hospital, with history of salted fish (Feseekh) ingestion during the outbreak (94 cases) Time: from 29 September to 27 October 2019 Ethical consideration: The approval of the Ethical Committee of the Faculty of Medicine for the present study was obtained. III. Research tools: A checklist and record review were carried out for collection of data to assess and follow up each patient. The equine Heptavalent Botulism Antitoxin (A, B, C, D, E, F, G), made by Emergent BioSolutions Canada Inc. (formerly Can gene Corporation) was used in treatment. (8) Mouse Bioassay for Clostridium botulinum toxin was performed following FDA's Bacteriological Analytical Manual. IV. Categorization of patients: Clinical assessment was completed to all cases and a checklist including different signs and symptoms of botulinum toxicity was fulfilled on admission. To properly manage the resources, the patients were classified into the groups according to their clinical assessment that was repeated everyone hour. If the signs and symptoms were improving, assessment follow up would be every 6 hours. The patients’ groups were as the following: Group A: included those with history of Feseekh ingestion and were completely normal on their first assessment and throughout their hospital stay (3 cases). Group B: included patients complained of typical gastroenteritis throughout their course i.e., nausea, vomiting, diarrhea, abdominal pain, and mild abdominal distention (38 cases). Group C: included all cases who developed neurological or autonomic dysfunction symptoms whether GIT symptoms were present or not. They were further subdivided into two groups: 1. Group C1: those at time of admission presented with evident serious neuromuscular dysfunction signs as ptosis, peripheral muscle weakness or hypoventilation (20 cases). 2. Group C2: those at time of admission presented with mild cranial nerve deficit manifestations as dilated fixed pupil &/or blurring of vision, dry mouth &/or mild dysphagia, mild dysphonia and patients complained of constipation &/or severe abdominal distention were further classified according to their disease course into: Patients with progressive course whose signs increased in severity or who developed evident neuromuscular dysfunction signs or any other cranial deficit within 24 hours of observation. (14 cases) Patients with stationary course who did not develop any additional neuromuscular paralysis signs during their period of observation. (19 cases) V. Method of statistical analysis: The data were collected and stored into a computer. Statistical analysis was done using Statistical Package for Social Sciences (SPSS/version 20) software. Data was presented as numbers and percentages for categorical variables and mean ± standard deviation (SD) for continuous variables. For testing associations between qualitative variables, the chi square test was used. Significance of the obtained results was judged at the 5% level. Results I. Demographic data: The highest percentage of the participated cases (42.6%) were in the age group 20 - < 40 years. This was followed in a descending manner by the age group <20 years (34%), then the age group of 40-<60 years (21.3%) and the age group ≥ 60 years (2.1%). More than two thirds (69.1%) were females while 30.9% were males. As regard residence, 36.2% of the cases were from Alexandria, 35.1% came from Kafr El-Sheikh, 27.6% were from Elbehira and only one case (1.1%) was living in Al-Ismailia. Past medical history: In the current study, medical history of previous diseases, injuries and operative procedures were taken from all participants. However, most of the studied patients (91.5%) had no history of chronic diseases. History of salted fish (Feseekh) ingestion: All the participated cases presented to the hospital from six hours to nine days after Feseekh ingestion with a mean value of 1.70 ± 1.49 days. Assessment of the cases: The most common findings observed in admitted patients were nausea and vomiting (76.6%), abdominal distension (41.5%) and dilated fixed pupil (29.8%). (Table 1) Administration of HBAT: All cases with serious evident neurological signs either at time of admission or during observation received HBAT immediately. They were Thirty-four patients (36.2%). The first dose of HBAT was given through 0.33 - 6 days from Feseekh intake. Among those who received the first dose of HBAT, more than half (55.9%) of the cases improved completely. On the other hand, six patients (17.7%) showed no improvement with persistent symptoms and 9 cases (26.4%) showed temporary improvement followed by relapse. Those fifteen patients were given the second vial of the HBAT. The time interval between the first and second vials was 1-4 days with a mean of 2.03± 0.93 days. Only one patient needed a third vial of the botulinum antitoxin. This was attributed to the persistence of hypoventilation one day after the second dose. The patients in group C2 were further categorized according to the number of mild cranial deficit complains and the need for HBAT administration and the results revealed that: All patients who admitted to hospital complaining of only one symptom of autonomic dysfunction did not need the antitoxin, while 100% of patients presented with four autonomic symptoms needed the antitoxin during their period of observation. On the other hand, 77.8% of those with three autonomic dysfunction symptoms needed the antitoxin. However, half of those with only two autonomic symptoms developed neurological signs later and needed the antitoxin. And this difference is statistically significant with p< 0.001. (Table 2) 6. Result of mouse bioassay test: A blood sample was withdrawn from patients on admission to the poison center even after days of ingestion time of the Feseekh and serum was prepared and transferred to the lab. Mouse bioassay test was carried out to 82 out of 94 cases and 87.8 % was negative. It means that 24 cases with negative mouse bioassay test developed neurological symptoms and needed HBAT. (Table 3) 7. Duration of hospitalization, ICU admission and need to mechanical ventilation support: The duration of hospital admission was 1-12 days with a mean of 3.71 ± 2.75 days. Moreover, 30 patients (31.9%) admitted to ICU for a period ranged from 1-8 days with a mean of 3.40 ± 1.81 days. Eight patients (26.7%) from group C1 needed mechanical ventilation for a period of 1-5 days with a mean of 2.50 ±1.60 days. 8. The outcome: Recovery was the major outcome (87.2%) whereas neurological sequalae were present in 10.6% of patients -in the form of persistent constipation, distention, dry mouth with a very mild dysphagia and death occurred only in two cases (2.2%). Discussion On spring, Egyptians’ celebration of eastern festival is accompanied with eating Feseekh (salted fish). However, unexpected outbreak occurred in Autumn and it was justified by contamination of marine mullet meat during that time, where some of those contaminated fish were taken by some individuals and salted in their homes. (Veterinarians warn of the mass death of fish in Lake Rashid 2019). The outbreak started with a 1.5-year-old child referred from Pediatric University Hospital to APC for differential diagnosis. She presented with paralytic ileus that raised the suspicion of intussusception and surgical abdomen. On examination the surgical emergency was eliminated. A similar scenario was mentioned by Spini et al (2015). Due to the unusual young age of the child with the absence of the common paralytic manifestations of botulism, pediatricians doubted botulism. Pisani et al (2009) had explained a similar situation as the initial symptoms of the disease are often like several diseases and therefore differential diagnosis is very difficult and rarely suspected by the pediatrician. Although the highest percentage of the patients were in the middle age group (20 - < 40 years), extremes of age were also involved, and females outnumbered males. This could be explained by the Egyptian culture where the ladies prepared the meals to the families as well as tasting it before meals. All family members gathered for celebration and ate the same food so different ages are usually affected. APC is serving Alexandria and all-around governorates (Elbehira, Kafr el-Sheikh, Marsa Matrouh, etc.). As the accident of contamination of the mullet fish meat occurred in Elbehira governorate so, all patients were directed to APC as in all other poisons. In the current work, 91.5% of the cases had no previous medical or surgical history. Past medical and surgical history was taken to exclude neurological diseases, previous stroke, and other gastrointestinal problems. All patient’s symptoms started to appear after eating the Feseekh meal. All the participated cases presented to the hospital from six hours up to nine days after Feseekh ingestion with a mean of 1.70 ± 1.49 days. In their systematic review, Fleck-Derderian et al (2017) reported a median duration between exposure and symptom onset as approximately one day. This difference is expected due to the long incubation period of foodborne botulism which would reach up to 16 days. The mouse lethal test (MLT) is the standard procedure for detection of botulism. Mouse bioassay test was carried out to 82 out of 94 cases. The results delivered several days after the clinical diagnosis revealed that 87.8% of cases were negative despite presence of clinical neurological manifestations. These negative results could be explained by the long period between the Feseekh ingestion and the withdrawal of serum sample as the samples were obtained from patients at the time of admission and many patients admitted to hospital few days after the appearance of symptoms. This result is in accordance with Temeri et al (2011) who stated that many clinical specimens have low levels of toxin which may not be evident within 4 days. Although the clinical syndrome of botulism is distinctive, it needs a high index of suspicion to be diagnosed. In the current study, patients were presented with mydriasis (29.8%), blurred vision (14.9%), ptosis (11.7%), dysphagia (24.5%) and muscle weakness in 21.3% of patients. This is in accordance with Gaware et al (2011) who reported these symptoms as the classic for botulism. On contrary to most of previous studies on Botulism that recommend early antitoxin administration to reduce mortality Gaware et al (2011), Kongsaengdao et al (2006) and Yu (2015). The current study aimed to manage the resources and to decrease the exposure of the patients to the side effects of the unnecessary administration of antitoxin. Thus, the patients in current study were classified at the time of admission into three groups. Only twenty patients - group C1- who presented with severe evident neurological symptoms; ptosis, muscle weakness or respiratory muscle affection with hypoventilation were given the BAT immediately. While the rest of patients didn’t receive the BAT immediately but they were put under close observation. Patients in group A who presented to hospital with just a history of Feseekh ingestion as members of their family ate the same meal and developed botulism manifestations and also patients in group B who presented with only gastroenteritis didn’t develop any additional symptoms during their period of hospitalization and did not need to receive the BAT. Moreover, patients in group C2 who presented with mild cranial deficit didn’t receive the BAT immediately as most of cranial deficits complain of patients in group C2 might be just a subjective feeling due to the fear or anxiety that result from the warnings spread at that time on the media or due to their affection by other patients in the outbreak. However, in order to identify patients likeliest to benefit from the antitoxin treatment, patients in group C2 were categorized according to the number of cranial deficit signs on initial assessment to anticipate the deterioration and to predict who would need the antitoxin administration which may be valuable for further development of guidelines. The initial assessment of cases with suspected food-born botulism is very important. In our opinion, this classification reduced the unnecessary administration of the HBAT to 60 patients who were managed by supportive treatment only. This protocol helped avoidance of many side effects of the antitoxin including the most severe ones as anaphylaxis and hypersensitivity reactions and other delayed allergic reactions as serum sickness. Schussler et al (2017) reported anaphylactic reactions in 1%-2% of botulinum antitoxin recipients that would be severe enough and necessitate intensive care. Also, this is very important for prioritizing antitoxin treatment when its availability is limited especially in outbreaks where the number of patients is large and unpredicted. This was contradictory to O'Horo et al (2017), in their systematic review, as they could not identify patients likeliest to benefit from the antitoxin treatment. But this was in agreement with Anderson et al (2019) and Barker et al (2019). In addition, after receiving the first dose of HBAT, (17.7%) of the cases showed no improvement and (26.4%) showed temporary improvement and relapsed later which necessitated the administration of further HBAT doses. These results may be explained by the mechanism of HBAT; it interacts only with unbound toxin, patients who admitted early were improved on one vial, while those arrived late needed second and third vials and 2 of them died in the hospital. (O'Horo et al 2017; Anderson et al 2019; Barker et al 2019). Those who suffered rebound after initial improvement were mentioned in a study of Fagan et al (2011). The only drawback of the current protocol is prolongation of hospitalization due to monitoring of the patients which reaches up to 12 days in some cases to avoid missing the unpredicted side effects of the antitoxin. Following the theory in current study, complete recovery occurred in (87.2%). Complications were present in 10.6% of patients while death occurred only in two cases (2.2%). All those 10.6% of patients who discharged with complications received the HBAT. They complained of persistent dry mouth with a very mild dysphagia not interfering with fluid, solid or semisolid food ingestion. Some complained of constipation which improved also with the usage of laxatives. This is like Gottlieb et al (2007) who concluded that previous symptoms of cholinergic autonomic blockade that are prominent during botulism as dry mouth would persist for a long-term later. Regarding the two cases who died, both were in group C1 with evident neurological paralysis, they received the antitoxin, and both were in need for mechanical ventilation in ICU. They arrested in the ICU; one after 2 days and the other after 4 days without receiving any further doses of HBAT. According to the critical care physicians the cause of death was a superadded chest infection. This point is very important as the appropriate supportive care is still the cornerstone in recovery and survival after botulism. As those cases suffered respiratory compromise so a high-quality intensive care is needed. This is in accordance with Sheth et al (2008). Conclusions Evidence based from that research that the course of cases with suspected botulism often has a stationary course and 63.8% of cases could be managed by supportive treatment with no need for HBAT, so we advise to keep the patient under close observation instead of rushing to give the anti-botulinum antitoxin, so we can protect him from the side effects of HBAT and manage resources at the same time especially in outbreaks. However, in evident neurological manifestations HBAT administration should be administered immediately. Declarations Author’s contribution: Sara A ghitani participated in the design of the study, drafted the manuscript, and participated in reviewing its final version, Maha A Ghanem participated in data collection and in drafting the manuscript and reviewing the final version, Eman A Sultan participated in the design of the study and performed the statistical analysis, Maram Atef participated in data collection and storage and reviewing the final version and Maii F Henaidy participated in writing the results section. Funding The authors received no financial support for this research, authorship, and/or publication of this article. Availability of data and materials The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials. Compliance with ethical standards Competing interests None of the authors have any competing interests in the manuscript. Ethics approval and consent to participate: Approval was obtained from the Research Ethics Committee of Faculty of Medicine, Alexandria University (IRB NO:00012098, FWA NO: 00018699, serial protocol NO:0304565). Adherence to national and international regulations The Ethics Committee is constituted and operates according to ICH GCP Guidelines and applicable local and institutional regulations and guidelines that govern ethics committees’ operation. Consent for publication : Not applicable as the research didn’t include any individual person’s data in any form. References Anderson DM, Kumar VR, Arper DL, Kruger E, Bilir SP, Richardson JS. Cost savings associated with timely treatment of botulism with botulism antitoxin heptavalent product. PloS One. 2019;14(11): e0224700. Barker D, Gillum KT, Niemuth NA, Kodihalli S. Therapeutic efficacy of equine botulism heptavalent antitoxin against all seven botulinum neurotoxins in symptomatic guinea pigs. PLoS One. 2019;14(9): e0222670. Chaudhry R. Botulism: A Diagnostic Challenge. Indian J Med Res. 2011;134(1):10-2. Fagan RP1, Neil KP, Sasich R, Luquez C, Asaad H, Maslanka S et al. Initial recovery and rebound of type f intestinal colonization botulism after administration of investigational heptavalent botulinum antitoxin. Clin Infect Dis. 2011 Nov;53(9): e125-8. Fleck-Derderian S, Shankar M, Rao AK, Chatham-Stephens K, Adjei S, Sobel J et al. The Epidemiology of Foodborne Botulism Outbreaks: A Systematic Review. Clin Infect Dis. 2017;66(suppl_1): S73-S81. DOI: 10.1093/cid/cix846. Gaware VM, Kotade KB, Dolas RT, Dhamak KB, Somawanshi SB, Nikam VK. Botulism Foodborne Disease: A Review. J Chem Pharm Res. 2011;3(1):84-92. Gottlieb SL, Kretsinger K, Tarkhashvili N, Chakvetadze N, Chokheli M, Chubinidze M et al. Long-term Outcomes of 217 Botulism Cases in the Republic of Georgia. Clin Infect Dis. 2007; 45 (2): 174-80. Kongsaengdao S, Samintarapanya K, Rusmeechan S, Wongsa A, Pothirat C, Permpikul C et al.; Thai Botulism Study Group. An outbreak of botulism in Thailand: clinical manifestations and management of severe respiratory failure. Clin Infect Dis. 2006; 43:1247–56. Lindstrom M, Korkeala H. Laboratory Diagnostics of Botulism. Clin Microbiol Rev. 2006;19(2):298-314. DOI: 10.1128/CMR.19.2.298-314.2006 O'Horo JC, Harper EP, El Rafei A, Ali R, DeSimone DC, Sakusic A et al. Efficacy of Antitoxin Therapy in Treating Patients with Foodborne Botulism: A Systematic Review and Meta-analysis of Cases, 1923-2016. Clin Infect Dis. 2017;66(suppl_1): S43-S56. Pisanti R, Vitiello R, Formicola S, Pisanti A. Infant Botulism Mimicking an Acute Abdomen. Infez Med. 2009;17 (4): 254-6. Richardson JS, Parrera GS, Astacio H, Sahota H, Anderson DM, Hall C, Babinchak T. Safety, and clinical outcomes of an equine-derived heptavalent botulinum antitoxin treatment for confirmed or suspected botulism in the United States. Clin Infect Dis. 2020;70(9):1950-1957. DOI: 10.1093/cid/ciz515. Schussler E, Sobel J, Hsu J, Yu P, Meaney-Delman M, Grammer LC et al. Workgroup Report by the Joint Task Force Involving American Academy of Allergy, Asthma & Immunology (AAAAI); Food Allergy, Anaphylaxis, Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and Latex Committee); And the Centers for Disease Control and Prevention Botulism Clinical Treatment Guidelines Workgroup-Allergic Reactions to Botulinum Antitoxin: A Systematic Review. Clin Infect Dis. 2017; 66 (suppl_1): S65-S72. Sheth AN, Wiersma P, Atrubin D, Dubey V, Zink D, Skinner G et al. International outbreak of severe botulism with prolonged toxemia caused by commercial carrot juice. Clin Infect Dis. 2008; 47:1245–51. Spini RG, Ferraris V, Glasman MP, Orofino G, Casanovas A, Debaisi G. Intussusception in infant with diagnostic botulism: A case report. Arch Argent Pediatr. 2015;113(5): e286-9. DOI: 10.5546/aap. 2015.e286. Veterinarians warn of the mass death of fish in Lake Rashid. Thursday 26/ September/2019-06:13PM https://translate.google.com/translate?hl=en&sl=ar&u=https://www.elbalad.news/3995937&prev=search Weber JT, Hibbs RG Jr, Darwish A, Mishu B, Corwin AL, Rakha M et al. A massive outbreak of type E botulism associated with traditional salted fish in Cairo. J Infect Dis. 1993;167(2):451-4. DOI: 10.1093/infdis/167.2.451. Wheeler C, Inami G, Mohle-Boetani J, Vugia D. Sensitivity of Mouse Bioassay in Clinical Wound Botulism. Clin Infect Dis. 2009;48(12):1669-73. DOI: 10.1086/599029. Wilder-Kofie TD, Lúquez C, Adler M, Dykes JK, Coleman JD et al. An Alternative in Vivo Method to Refine the Mouse Bioassay for Botulinum Toxin Detection. Comp Med. 2011;61(3):235-42. Yu P. Heptavalent botulinum antitoxin (BAT) use in patients treated under CDC’s expanded access IND, 2010–2013. Atlanta, GA: CDC, 2015. Tables Table (1): Distribution of studied patients' group according to clinical assessment on admission (n=94) Clinical assessment No. % Ocular Blurred vision 14 14.9 Ptosis 11 11.7 Mydriasis 28 29.8 Bucco-pharyngeal Dry mouth 14 14.9 Dysphagia 23 24.5 Dysphonia 3 3.2 Digestive Abdominal pain 7 7.4 Constipation 24 25.5 Distention 39 41.5 Diarrhea 13 13.8 Nausea & vomiting 72 76.6 Muscle weakness Grade: 20 21.3 II 2 2.1 III 1 1.1 IV 17 18.1 Respiratory Dyspnea 12 12.7 Gasping 1 1.1 Respiratory distress 1 1.1 Table (2): Relation between mild cranial deficit signs and administration of anti-toxin (n =33) Statistical significance Total Anti-toxin Number of mild cranial deficit signs No Yes P MC = < 0.001* 14 14 (100.0%) 0 (0.0%) 1 6 3 (50.0%) 3 (50.0%) 2 9 2 (22.2%) 7 (77.8%) 3 4 0 (0.0%) 4(100.0%) 4 33 19 (57.6%) 14 (42.4%) Total * Minor cranial deficit signs include: Dilated fixed pupil &/or blurred vision Mild dysphagia & / or dry mouth Mild dysphonia Constipation &/or abdominal distension Feeling of dyspnea without any signs of respiratory distress Table (3): Distribution of the studied cases according to mouse bioassay test (n=82) Mouse bioassay technique (n=82) No. % Negative 72 87.8 Positive 10 12.2 Cite Share Download PDF Status: Published Journal Publication published 27 Jan, 2022 Read the published version in Environmental Science and Pollution Research → Version 1 posted Editorial decision: Major Revision 14 Apr, 2021 Reviews received at journal 21 Mar, 2021 Reviewers invited by journal 16 Mar, 2021 Editor invited by journal 15 Mar, 2021 Editor assigned by journal 11 Mar, 2021 First submitted to journal 22 Feb, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-267943","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":17196574,"identity":"091ca692-b51d-449f-98ea-a0cc9b38876b","order_by":0,"name":"Sara A Ghitani","email":"","orcid":"","institution":"Faculty of Medicine of Alexandria University: Alexandria University Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sara","middleName":"A","lastName":"Ghitani","suffix":""},{"id":17196575,"identity":"4c7cf0db-8b0c-475f-90df-8aafd479fb96","order_by":1,"name":"Maha A Ghanem","email":"","orcid":"","institution":"Faculty of Medicine of Alexandria University: Alexandria University Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maha","middleName":"A","lastName":"Ghanem","suffix":""},{"id":17196576,"identity":"2bceaee3-32a0-47fa-aaae-d874459fca62","order_by":2,"name":"Eman A Sultan","email":"","orcid":"","institution":"Alexandria Medicine: Alexandria University Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Eman","middleName":"A","lastName":"Sultan","suffix":""},{"id":17196577,"identity":"ed008247-f493-42d9-8485-65c6d9fe0696","order_by":3,"name":"Maram Atef","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYDAD9vbmgw+ANA8fkRoMGHjOHEs2AGlhI17LjRwzCRCToBbd9rMPP92o+SPHI5FjVvk1x06GjYH54aMbeLSYnUk3ls45ZmDMw/Os7LbstmSgw9iMjXPwaTmQxiCdw2aQuJ89edttyW3MQC08bNJ4tZx/xvw7559BfQ9Dglmx5LZ6IrTcSGOTzm0zSODhSDFj/LjtMDFanrFZ5/YZG/bwHEuWZtx2nIeNmZBfzqcx3875JifPw9588OPPbdX2/OzNDx/j04ICmHnAJLHKQYDxBymqR8EoGAWjYMQAAG9URJRvxEiYAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-4646-1326","institution":"Alexandria University Faculty of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Maram","middleName":"","lastName":"Atef","suffix":""},{"id":17196578,"identity":"d888690f-1c52-43b8-a27e-41d47af2d444","order_by":4,"name":"Maii F Henaidy","email":"","orcid":"","institution":"Faculty of Medicine of Alexandria University: Alexandria University Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maii","middleName":"F","lastName":"Henaidy","suffix":""}],"badges":[],"createdAt":"2021-02-22 17:54:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-267943/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-267943/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11356-021-18031-y","type":"published","date":"2022-01-28T00:45:03+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":17719896,"identity":"eeda55aa-71ea-401b-84c2-3099aa76d328","added_by":"auto","created_at":"2022-01-28 00:45:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":507783,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-267943/v1/37df76a9-4ecc-4e98-bc69-4353ce774304.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eOutbreak of Foodborne Botulism in Alexandria, Egypt: Modulating Indications for Administration of Heptavalent Botulinum Antitoxin\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBotulism is considered one of the recurrent events that confront poison centers, in Egypt, each year due to a traditional salted fish meal which is consumed each spring (Weber et al.1993). \u0026nbsp;In the spring of 2019, there were 58 cases of botulism admitted to APC and only 3 cases needed \u003cstrong\u003ebotulinum antitoxin\u003c/strong\u003e. However, they suffered from side effects where 2 cases had severe epistaxis and one case arrested during anti-toxin administration. On 29 September, a child was transferred to APC for differential diagnosis of paralytic ileus as her family said she was given a piece of salted fish (feseekh) and she was considered the first case of the outbreak. Preliminary assessment of the situation was carried out and preparations were made to confront a large outbreak out of season.\u003c/p\u003e\n\u003cp\u003eA collaborative team from APC doctors with Egyptian Ministry of Health (EMOH) was initiated to conduct interviews with the cases about the source, the time of the start of symptoms, other personnel of same family exposed to same meal\u0026hellip;. etc. Blood specimens were collected from the cases. Identified factors common to all cases and formulated preliminary hypotheses were issued. The team delivered a daily report to the authorities, and all types of media were used to issue a warning until the outbreak was stopped on 27-10-2019. \u0026nbsp;The Egyptian news declared previously the death of almost 100 tons of \"mullet\" fish and veterinarians warning of the mass death of fish in a small town called Rashid which was considered the source of that outbreak (Veterinarians warn of the mass death of fish in Lake Rashid.2019).\u003c/p\u003e\n\u003cp\u003eDue to delay in results of mouse lethal test (MLT) and its positive and negative fallacies, the APC team treated the cases depending on the clinical picture (Lindstrom et al 2006, Chaudhry.2011, Wilder-Kofie et al. 2011, Wheeler et al.2009). We tried to decrease the exposure of the patients to the side effects of the antitoxin due to our unpleasant experience with Heptavalent botulinum antitoxin in spring of the same year. (Richardson et al 2020).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eThe current study aimed to\u003c/em\u003e\u003c/strong\u003e portray the clinical characteristics of the cases, to explore the possible relation between these characteristics and necessity of HBAT administration, to explore the reliability of MLT and to establish a clinical guide of management of the suspected cases of botulism with preservation of resources.\u003c/p\u003e"},{"header":"Subjects And Methods","content":"\u003cp\u003e\u003cstrong\u003eI. Research strategy and design:\u003c/strong\u003e The descriptive epidemiological approach is selected.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eII. Research setting:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTarget population and place: All patients admitted to APC - The Main University Hospital, with history of salted fish (Feseekh) ingestion during the outbreak (94 cases)\u003c/p\u003e\n\u003cp\u003eTime: from 29 September to 27 October 2019\u003c/p\u003e\n\u003cp\u003eEthical consideration: The approval of the Ethical Committee of the Faculty of Medicine for the present study was obtained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIII. Research tools: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;A checklist and record review were carried out for collection of data to assess and follow up each patient. The equine Heptavalent Botulism Antitoxin (A, B, C, D, E, F, G), made by Emergent BioSolutions Canada Inc. (formerly Can gene Corporation) was used in treatment. \u003csup\u003e(8) \u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eMouse Bioassay for\u0026nbsp;Clostridium botulinum\u0026nbsp;toxin was performed following \u003cstrong\u003eFDA's\u003c/strong\u003e\u0026nbsp;Bacteriological Analytical Manual.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIV. Categorization of patients:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical assessment was completed to all cases and a checklist including different signs and symptoms of botulinum toxicity was fulfilled on admission.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo properly manage the resources, the patients were classified into the groups according to their clinical assessment that was repeated everyone hour. If the signs and symptoms were improving, assessment follow up would be every 6 hours.\u003c/p\u003e\n\u003cp\u003eThe patients\u0026rsquo; groups were as the following:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eGroup A:\u003c/em\u003e\u003c/strong\u003e included those with history of Feseekh ingestion and were completely normal on their first assessment and throughout their hospital stay \u003cstrong\u003e(3 cases).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eGroup B:\u003c/em\u003e\u003c/strong\u003e included patients complained of typical gastroenteritis throughout their course i.e., nausea, vomiting, diarrhea, abdominal pain, and mild abdominal distention \u003cstrong\u003e(38 cases).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eGroup C:\u003c/em\u003e\u003c/strong\u003e included all cases who developed neurological or autonomic dysfunction symptoms whether GIT symptoms were present or not. They were further subdivided into two groups:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1. Group C1: \u003c/strong\u003ethose at time of admission presented with evident serious neuromuscular dysfunction signs as ptosis, peripheral muscle weakness or hypoventilation \u003cstrong\u003e(20 cases).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2. Group C2: \u003c/strong\u003ethose at time of admission presented with mild cranial nerve deficit manifestations as dilated fixed pupil \u0026amp;/or blurring of vision, dry mouth \u0026amp;/or mild dysphagia, mild dysphonia and patients complained of constipation \u0026amp;/or severe abdominal distention were further classified according to their disease course into:\u003c/p\u003e\n\u003cp\u003ePatients with progressive course whose signs increased in severity or who developed evident neuromuscular dysfunction signs or any other cranial deficit within 24 hours of observation. \u003cstrong\u003e(14 cases)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients with stationary course who did not develop any additional neuromuscular paralysis signs during their period of observation. \u003cstrong\u003e(19 cases)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eV. Method of statistical analysis: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data were collected and stored into a computer. Statistical analysis was done using Statistical Package for Social Sciences (SPSS/version 20) software. Data was presented as numbers and percentages for categorical variables and mean \u0026plusmn; standard deviation (SD) for continuous variables. For testing associations between qualitative variables, the chi square test was used. Significance of the obtained results was judged at the 5% level.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eI. Demographic data:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe highest percentage of the participated cases (42.6%) were in the age group 20 - \u0026lt; 40 years.\u0026nbsp; This was followed in a descending manner by the age group \u0026lt;20 years (34%), then the age group of 40-\u0026lt;60 years (21.3%) and the age group \u0026ge; 60 years (2.1%). More than two thirds (69.1%) were females while 30.9% were males.\u0026nbsp; As regard residence, 36.2% of the cases were from Alexandria, 35.1% came from Kafr El-Sheikh, 27.6% were from Elbehira and only one case (1.1%) was living in Al-Ismailia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePast medical history:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the current study, medical history of previous diseases, injuries and operative procedures were taken from all participants. However, most of the studied patients (91.5%) had no history of chronic diseases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHistory of salted fish (Feseekh) ingestion: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the participated cases presented to the hospital from six hours to nine days after Feseekh ingestion with a mean value of 1.70 \u0026plusmn; 1.49 days.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessment of the cases:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe most common findings observed in admitted patients were nausea and vomiting (76.6%), abdominal distension (41.5%) and dilated fixed pupil (29.8%). (Table 1)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdministration of HBAT:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll cases with serious evident neurological signs either at time of admission or during observation received HBAT immediately. They were Thirty-four patients (36.2%). The first dose of HBAT was given through 0.33 - 6 days from Feseekh intake. Among those who received the first dose of HBAT, more than half (55.9%) of the cases improved completely. On the other hand, six patients (17.7%) showed no improvement with persistent symptoms and 9 cases (26.4%) showed temporary improvement followed by relapse. Those fifteen patients were given the second vial of the HBAT. The time interval between the first and second vials was 1-4 days with a mean of 2.03\u0026plusmn; 0.93 days. Only one patient needed a third vial of the botulinum antitoxin. This was attributed to the persistence of hypoventilation one day after the second dose.\u003c/p\u003e\n\u003cp\u003eThe patients in group C2 were further categorized according to the number of mild cranial deficit complains and the need for HBAT administration and the results revealed that:\u003c/p\u003e\n\u003cp\u003eAll patients who admitted to hospital complaining of only one symptom of autonomic dysfunction did not need the antitoxin, while 100% of patients presented with four autonomic symptoms needed the antitoxin during their period of observation. On the other hand, 77.8% of those with three autonomic dysfunction symptoms needed the antitoxin. However, half of those with only two autonomic symptoms developed neurological signs later and needed the antitoxin. And this difference is statistically significant with p\u0026lt; 0.001. (Table 2)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e6. Result of mouse bioassay test:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA blood sample was withdrawn from patients on admission to the poison center even after days of ingestion time of the Feseekh and serum was prepared and transferred to the lab.\u0026nbsp; Mouse bioassay test was carried out to 82 out of 94 cases and 87.8 % was negative. It means that 24 cases with negative mouse bioassay test developed neurological symptoms and needed HBAT. \u003cstrong\u003e(Table 3)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7. Duration of hospitalization, ICU admission and need to mechanical ventilation support:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe duration of hospital admission was 1-12 days with a mean of 3.71 \u0026plusmn; 2.75 days. Moreover, 30 patients (31.9%) admitted to ICU for a period ranged from 1-8 days with a mean of 3.40 \u0026plusmn; 1.81 days.\u0026nbsp; Eight patients (26.7%) from group C1 needed mechanical ventilation for a period of 1-5 days with a mean of 2.50 \u0026plusmn;1.60 days.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e8. The outcome:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRecovery was the major outcome (87.2%) whereas neurological sequalae were present in 10.6% of patients -in the form of persistent constipation, distention, dry mouth with a very mild dysphagia and death occurred only in two cases (2.2%).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOn spring, Egyptians\u0026rsquo; celebration of eastern festival is accompanied with eating Feseekh (salted fish). However, unexpected outbreak occurred in Autumn and it was justified by contamination of marine mullet meat during that time, where some of those contaminated fish were taken by some individuals and salted in their homes. (Veterinarians warn of the mass death of fish in Lake Rashid 2019). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe outbreak started with a 1.5-year-old child referred from Pediatric University Hospital to APC for differential diagnosis. She presented with paralytic ileus that raised the suspicion of intussusception and surgical abdomen. On examination the surgical emergency was eliminated. A similar scenario was mentioned by Spini et al (2015).\u003c/p\u003e\n\u003cp\u003eDue to the unusual young age of the child with the absence of the common paralytic manifestations of botulism, pediatricians doubted botulism. Pisani et al (2009) had explained a similar situation as the initial symptoms of the disease are often like several diseases and therefore differential diagnosis is very difficult and rarely suspected by the pediatrician.\u003c/p\u003e\n\u003cp\u003eAlthough the highest percentage of the patients were in the middle age group (20 - \u0026lt; 40 years), extremes of age were also involved, and females outnumbered males.\u0026nbsp; This could be explained by the Egyptian culture where the ladies prepared the meals to the families as well as tasting it before meals. All family members gathered for celebration and ate the same food so different ages are usually affected.\u003c/p\u003e\n\u003cp\u003eAPC is serving Alexandria and all-around governorates (Elbehira, Kafr el-Sheikh, Marsa Matrouh, etc.). As the accident of contamination of the mullet fish meat occurred in Elbehira governorate so, all patients were directed to APC as in all other poisons.\u003c/p\u003e\n\u003cp\u003eIn the current work, 91.5% of the cases had no previous medical or surgical history. Past medical and surgical history was taken to exclude neurological diseases, previous stroke, and other gastrointestinal problems. All patient\u0026rsquo;s symptoms started to appear after eating the Feseekh meal. All the participated cases presented to the hospital from six hours up to nine days after Feseekh ingestion with a mean of 1.70 \u0026plusmn; 1.49 days. In their systematic review, Fleck-Derderian et al (2017) \u003csup\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/sup\u003ereported a median duration between exposure and symptom onset as approximately one day. This difference is expected due to the long incubation period of foodborne botulism which would reach up to 16 days.\u003c/p\u003e\n\u003cp\u003eThe mouse lethal test (MLT) is the standard procedure for detection of botulism. Mouse bioassay test was carried out to 82 out of 94 cases. The results delivered several days after the clinical diagnosis revealed that 87.8% of cases were negative despite presence of clinical neurological manifestations. These negative results could be explained by the long period between the Feseekh ingestion and the withdrawal of serum sample as the samples were obtained from patients at the time of admission and many patients admitted to hospital few days after the appearance of symptoms. This result is in accordance with Temeri et al (2011) who stated that many clinical specimens have low levels of toxin which may not be evident within 4 days.\u003c/p\u003e\n\u003cp\u003eAlthough the clinical syndrome of botulism is distinctive, it needs a high index of suspicion to be diagnosed. In the current study, patients were presented with mydriasis (29.8%), blurred vision (14.9%), ptosis (11.7%), dysphagia (24.5%) and muscle weakness in 21.3% of patients. This is in accordance with Gaware et al (2011) who reported these symptoms as the classic for botulism.\u003c/p\u003e\n\u003cp\u003eOn contrary to most of previous studies on Botulism that recommend early antitoxin administration to reduce mortality Gaware et al (2011), Kongsaengdao et al (2006) and Yu (2015). \u0026nbsp;\u0026nbsp;\u0026nbsp;The current study aimed to manage the resources and to decrease the exposure of the patients to the side effects of the unnecessary administration of antitoxin. Thus, the patients in current study were classified at the time of admission into three groups. Only twenty patients -\u003cstrong\u003egroup C1-\u003c/strong\u003e who presented with severe evident neurological symptoms; ptosis, muscle weakness or respiratory muscle affection with hypoventilation were given the BAT immediately. While the rest of patients didn\u0026rsquo;t receive the BAT immediately but they were put under close observation.\u003c/p\u003e\n\u003cp\u003ePatients in \u003cstrong\u003egroup A\u003c/strong\u003e who presented to hospital with just a history of Feseekh ingestion as members of their family ate the same meal and developed botulism manifestations and also patients in \u003cstrong\u003egroup B\u003c/strong\u003e who presented with only gastroenteritis didn\u0026rsquo;t develop any additional symptoms during their period of hospitalization and did not need to receive the BAT. Moreover, patients in \u003cstrong\u003egroup C2 \u003c/strong\u003ewho presented with mild cranial deficit didn\u0026rsquo;t receive the BAT immediately as most of cranial deficits complain of patients in group C2 might be just a subjective feeling due to the fear or anxiety that result from the warnings spread at that time on the media or due to their affection by other patients in the outbreak.\u003c/p\u003e\n\u003cp\u003eHowever, in order to identify patients likeliest to benefit from the antitoxin treatment, patients in group C2 were categorized according to the number of cranial deficit signs on initial assessment to anticipate the deterioration and to predict who would need the antitoxin administration which may be valuable for further development of guidelines. The initial assessment of cases with suspected food-born botulism is very important.\u003c/p\u003e\n\u003cp\u003eIn our opinion, this classification reduced the unnecessary administration of the HBAT to 60 patients who were managed by supportive treatment only. This protocol helped avoidance of many side effects of the antitoxin including the most severe ones as anaphylaxis and hypersensitivity reactions and other delayed allergic reactions as serum sickness. Schussler et al (2017) reported anaphylactic reactions in 1%-2% of botulinum antitoxin recipients that would be severe enough and necessitate intensive care.\u003c/p\u003e\n\u003cp\u003eAlso, this is very important for prioritizing antitoxin treatment when its availability is limited especially in outbreaks where the number of patients is large and unpredicted. This was contradictory to O'Horo et al (2017), in their systematic review, as they could not identify patients likeliest to benefit from the antitoxin treatment.\u0026nbsp; But this was in agreement with Anderson et al (2019) and Barker et al (2019).\u003c/p\u003e\n\u003cp\u003eIn addition, after receiving the first dose of HBAT, (17.7%) of the cases showed no improvement and (26.4%) showed temporary improvement and relapsed later which necessitated the administration of further HBAT doses.\u0026nbsp; These results may be explained by the mechanism of HBAT; it interacts only with unbound toxin, patients who admitted early were improved on one vial, while those arrived late needed second and third vials and 2 of them died in the hospital. (O'Horo et al 2017; Anderson et al 2019; Barker et al 2019). Those who suffered rebound after initial improvement were mentioned in a study of Fagan et al (2011).\u003c/p\u003e\n\u003cp\u003eThe only drawback of the current protocol is prolongation of hospitalization due to monitoring of the patients which reaches up to 12 days in some cases to avoid missing the unpredicted side effects of the antitoxin.\u003c/p\u003e\n\u003cp\u003eFollowing the theory in current study, complete recovery occurred in (87.2%). Complications were present in 10.6% of patients while death occurred only in two cases (2.2%). All those 10.6% of patients who discharged with complications received the HBAT. They complained of persistent dry mouth with a very mild dysphagia not interfering with fluid, solid or semisolid food ingestion. Some complained of constipation which improved also with the usage of laxatives. This is like Gottlieb et al (2007) who concluded that previous symptoms of cholinergic autonomic blockade that are prominent during botulism as dry mouth would persist for a long-term later.\u003c/p\u003e\n\u003cp\u003eRegarding the two cases who died, both were in group C1 with evident neurological paralysis, they received the antitoxin, and both were in need for mechanical ventilation in ICU. They arrested in the ICU; one after 2 days and the other after 4 days without receiving any further doses of HBAT. According to the critical care physicians the cause of death was a superadded chest infection. This point is very important as the appropriate supportive care is still the cornerstone in recovery and survival after botulism.\u0026nbsp; As those cases suffered respiratory compromise so a high-quality intensive care is needed.\u0026nbsp; This is in accordance with Sheth et al (2008).\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eEvidence based from that research that the course of cases with suspected botulism often has a stationary course and 63.8% of cases could be managed by supportive treatment with no need for HBAT, so we advise to keep the patient under close observation instead of rushing to give the anti-botulinum antitoxin, so we can protect him from the side effects of HBAT and manage resources at the same time especially in outbreaks. However, in evident neurological manifestations HBAT administration should be administered immediately.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthor\u0026rsquo;s contribution:\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSara A ghitani participated in the design of the study, drafted the manuscript, and participated in reviewing its final version, Maha A Ghanem participated in data collection and in drafting the manuscript and reviewing the final version, Eman A Sultan participated in the design of the study and performed the statistical analysis, Maram Atef participated in data collection and storage and reviewing the final version and Maii F Henaidy participated in writing the results section.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no financial support for this research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompliance with ethical standards\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests \u003c/strong\u003eNone of the authors have any competing interests in the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e Approval was obtained from the Research Ethics Committee of Faculty of Medicine, Alexandria University (IRB NO:00012098, FWA NO: 00018699, serial protocol NO:0304565).\u003c/p\u003e\n\u003cp\u003eAdherence to national and international regulations The Ethics Committee is constituted and operates according to ICH GCP Guidelines and applicable local and institutional regulations and guidelines that govern ethics committees\u0026rsquo; operation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable as the research didn\u0026rsquo;t include any individual person\u0026rsquo;s data in any form.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAnderson DM, Kumar VR, Arper DL, Kruger E, Bilir SP, Richardson JS. Cost savings associated with timely treatment of botulism with botulism antitoxin heptavalent product. PloS One. 2019;14(11): e0224700.\u003c/li\u003e\n\u003cli\u003eBarker D, Gillum KT, Niemuth NA, Kodihalli S.\u0026nbsp; Therapeutic efficacy of equine botulism heptavalent antitoxin against all seven botulinum neurotoxins in symptomatic guinea pigs. PLoS One. 2019;14(9): e0222670.\u0026nbsp;\u003c/li\u003e\n\u003cli\u003eChaudhry R. Botulism: A Diagnostic Challenge. Indian J Med Res. 2011;134(1):10-2.\u003c/li\u003e\n\u003cli\u003eFagan RP1, Neil KP, Sasich R, Luquez C, Asaad H, Maslanka S et al. Initial recovery and rebound of type f intestinal colonization botulism after administration of investigational heptavalent botulinum antitoxin. Clin Infect Dis. 2011 Nov;53(9): e125-8.\u003c/li\u003e\n\u003cli\u003eFleck-Derderian S, Shankar M, Rao AK, Chatham-Stephens K, Adjei S, Sobel J et al. The Epidemiology of Foodborne Botulism Outbreaks: A Systematic Review. Clin Infect Dis. 2017;66(suppl_1): S73-S81. DOI: 10.1093/cid/cix846.\u003c/li\u003e\n\u003cli\u003eGaware VM, Kotade KB, Dolas RT, Dhamak KB, Somawanshi SB, Nikam VK. Botulism Foodborne Disease: A Review. J Chem Pharm Res. 2011;3(1):84-92.\u003c/li\u003e\n\u003cli\u003eGottlieb SL, Kretsinger K, Tarkhashvili N, Chakvetadze N, Chokheli M, Chubinidze M et al. Long-term Outcomes of 217 Botulism Cases in the Republic of Georgia. Clin Infect Dis. 2007; 45 (2): 174-80.\u003c/li\u003e\n\u003cli\u003eKongsaengdao S, Samintarapanya K, Rusmeechan S, Wongsa A, Pothirat C, Permpikul C et al.; Thai Botulism Study Group. An outbreak of botulism in Thailand: clinical manifestations and management of severe respiratory failure. Clin Infect Dis. 2006; 43:1247\u0026ndash;56.\u003c/li\u003e\n\u003cli\u003e\u0026nbsp;Lindstrom M, Korkeala H. Laboratory Diagnostics of Botulism. Clin Microbiol Rev. 2006;19(2):298-314. DOI: 10.1128/CMR.19.2.298-314.2006\u003c/li\u003e\n\u003cli\u003eO'Horo JC, Harper EP, El Rafei A, Ali R, DeSimone DC, Sakusic A et al. Efficacy of Antitoxin Therapy in Treating Patients with Foodborne Botulism: A Systematic Review and Meta-analysis of Cases, 1923-2016. Clin Infect Dis. 2017;66(suppl_1): S43-S56.\u003c/li\u003e\n\u003cli\u003ePisanti R, Vitiello R, Formicola S, Pisanti A. Infant Botulism Mimicking an Acute Abdomen. Infez Med. 2009;17 (4): 254-6.\u003c/li\u003e\n\u003cli\u003eRichardson JS, Parrera GS, Astacio H, Sahota H, Anderson DM, Hall C, Babinchak T. Safety, and clinical outcomes of an equine-derived heptavalent botulinum antitoxin treatment for confirmed or suspected botulism in the United States. Clin Infect Dis. 2020;70(9):1950-1957. DOI: 10.1093/cid/ciz515.\u003c/li\u003e\n\u003cli\u003eSchussler E, Sobel J, Hsu J, Yu P, Meaney-Delman M, Grammer LC et al. Workgroup Report by the Joint Task Force Involving American Academy of Allergy, Asthma \u0026amp; Immunology (AAAAI); Food Allergy, Anaphylaxis, Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and Latex Committee); And the Centers for Disease Control and Prevention Botulism Clinical Treatment Guidelines Workgroup-Allergic Reactions to Botulinum Antitoxin: A Systematic Review.\u0026nbsp; Clin Infect Dis. 2017; 66 (suppl_1): S65-S72.\u003c/li\u003e\n\u003cli\u003eSheth AN, Wiersma P, Atrubin D, Dubey V, Zink D, Skinner G et al. International outbreak of severe botulism with prolonged toxemia caused by commercial carrot juice. Clin Infect Dis. 2008; 47:1245\u0026ndash;51.\u003c/li\u003e\n\u003cli\u003eSpini RG, Ferraris V, Glasman MP, Orofino G, Casanovas A, Debaisi G. Intussusception in infant with diagnostic botulism: A case report. Arch Argent Pediatr. 2015;113(5): e286-9. DOI: 10.5546/aap. 2015.e286.\u003c/li\u003e\n\u003cli\u003eVeterinarians warn of the mass death of fish in Lake Rashid. Thursday 26/ September/2019-06:13PM \u003ca href=\"https://translate.google.com/translate?hl=en\u0026amp;sl=ar\u0026amp;u=https://www.elbalad.news/3995937\u0026amp;prev=search\"\u003ehttps://translate.google.com/translate?hl=en\u0026amp;sl=ar\u0026amp;u=https://www.elbalad.news/3995937\u0026amp;prev=search\u003c/a\u003e\u003c/li\u003e\n\u003cli\u003eWeber JT, Hibbs RG Jr, Darwish A, Mishu B, Corwin AL, Rakha M et al. A massive outbreak of type E botulism associated with traditional salted fish in Cairo. J Infect Dis. 1993;167(2):451-4. DOI: 10.1093/infdis/167.2.451.\u003c/li\u003e\n\u003cli\u003eWheeler C, Inami G, Mohle-Boetani J, Vugia D. Sensitivity of Mouse Bioassay in Clinical Wound Botulism. Clin Infect Dis. 2009;48(12):1669-73. DOI: 10.1086/599029.\u003c/li\u003e\n\u003cli\u003eWilder-Kofie TD, L\u0026uacute;quez C, Adler M, Dykes JK, Coleman JD et al. An Alternative in Vivo Method to Refine the Mouse Bioassay for Botulinum Toxin Detection. Comp Med. 2011;61(3):235-42.\u003c/li\u003e\n\u003cli\u003eYu P. Heptavalent botulinum antitoxin (BAT) use in patients treated under CDC\u0026rsquo;s expanded \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;access IND, 2010\u0026ndash;2013. Atlanta, GA: CDC, 2015.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable (1): Distribution of studied patients' group according to clinical assessment on admission (n=94)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003e\u003cstrong\u003eClinical assessment\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003e\u003cstrong\u003eOcular\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Blurred vision\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u003cstrong\u003e14.9\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003ePtosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e11.7\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eMydriasis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u003cstrong\u003e29.8\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003e\u003cstrong\u003eBucco-pharyngeal\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eDry mouth\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e14.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eDysphagia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u003cstrong\u003e24.5\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eDysphonia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e3.2\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003e\u003cstrong\u003eDigestive\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eAbdominal pain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e7.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eConstipation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e25.5\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eDistention\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u003cstrong\u003e41.5\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eDiarrhea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e13.8\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eNausea \u0026amp; vomiting\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e72\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u003cstrong\u003e76.6\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003e\u003cstrong\u003eMuscle weakness\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGrade:\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u003cstrong\u003e20\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u003cstrong\u003e21.3\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eII\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e2.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eIII\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e1.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eIV\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e18.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003e\u003cstrong\u003eRespiratory \u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eDyspnea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u003cstrong\u003e12.7\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eGasping\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e1.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eRespiratory distress\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e1.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (2): Relation between mild cranial deficit signs and administration of anti-toxin (n =33)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"157\"\u003e\n\u003cp\u003eStatistical significance\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"114\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"227\"\u003e\n\u003cp\u003eAnti-toxin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"164\"\u003e\n\u003cp\u003eNumber of mild cranial deficit signs\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"5\" width=\"157\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eP \u003csup\u003eMC\u003c/sup\u003e = \u0026lt; 0.001*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e14 (100.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"164\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e3 (50.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e3 (50.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"164\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e2 (22.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e7 (77.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"164\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e4(100.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"164\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e19 (57.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e14 (42.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"164\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* Minor cranial deficit signs include:\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003eDilated fixed pupil \u0026amp;/or blurred vision\u003c/li\u003e\n\u003cli\u003eMild dysphagia \u0026amp; / or dry mouth\u003c/li\u003e\n\u003cli\u003eMild dysphonia\u003c/li\u003e\n\u003cli\u003eConstipation \u0026amp;/or abdominal distension\u003c/li\u003e\n\u003cli\u003eFeeling of dyspnea without any signs of respiratory distress\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (3):\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Distribution of the studied cases according to mouse bioassay test (n=82)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"271\"\u003e\n\u003cp\u003e\u003cstrong\u003eMouse bioassay technique (n=82)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"88\"\u003e\n\u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"88\"\u003e\n\u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"271\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"88\"\u003e\n\u003cp\u003e72\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"88\"\u003e\n\u003cp\u003e87.8\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"271\"\u003e\n\u003cp\u003e\u003cstrong\u003ePositive\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"88\"\u003e\n\u003cp\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"88\"\u003e\n\u003cp\u003e\u003cstrong\u003e12.2\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"environmental-science-and-pollution-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"espr","sideBox":"Learn more about [Environmental Science and Pollution Research](https://www.springer.com/journal/11356)","snPcode":"11356","submissionUrl":"https://submission.nature.com/new-submission/11356/3","title":"Environmental Science and Pollution Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Alexandria Poison Center (APC), Heptavalent botulinum antitoxin (HBAT), mild neurological sequelea","lastPublishedDoi":"10.21203/rs.3.rs-267943/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-267943/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u0026nbsp;\u003c/strong\u003eIn October 2019, 94 patients were admitted into Alexandria Poison Center (APC) with a history of ingestion of Feseekh (salted fish). As a trial to allocate the resources, not all patients were given Heptavalent botulinum antitoxin (HBAT) immediately.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eThe current study aimed to\u0026nbsp;\u003c/strong\u003eportray the clinical characteristics of the cases, explore the possible relation between these characteristics and necessity of HBAT administration, explore the reliability of MLT, and to establish a clinical guide for management with preservation of resources.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eSubject and Method:\u0026nbsp;\u003c/strong\u003ethe current prospective study included 94 patients who were admitted to Alexandria Poison Center (APC) in the period from 29\u0026nbsp;\u003csup\u003eth\u0026nbsp;\u003c/sup\u003eSeptember to 27\u0026nbsp;\u003csup\u003eth\u0026nbsp;\u003c/sup\u003eOctober 2019.\u0026nbsp;The patients' data was recorded using a checklist that includes: personal data, past medical history, clinical assessment, investigations, treatment and the outcome. The checklist was carried out to assess and follow up each patient. Hospitalized patients were categorized according to symptoms consistent with botulism. The equine HBAT, made by Emergent BioSolutions Canada Inc. (formerly Can gene Corporation) was used in the treatment.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u0026nbsp;\u003c/strong\u003eHBAT was given to (36.2%) patients only out of the total admission. However, 87.2% of patients were completely cured, whereas 10.6% of patients were discharged with mild neurological sequelea and death occurred only in two cases (2.2%).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u0026nbsp;\u003c/strong\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;63.8% of cases with suspected foodborne botulism toxicity could be managed by supportive treatment only with no need for HBAT.\u003c/p\u003e","manuscriptTitle":"Outbreak of Foodborne Botulism in Alexandria, Egypt: Modulating Indications for Administration of Heptavalent Botulinum Antitoxin","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-03-22 12:49:40","doi":"10.21203/rs.3.rs-267943/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revision","date":"2021-04-14T04:05:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-03-22T00:00:00+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-03-17T00:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Environmental Science and Pollution Research","date":"2021-03-16T00:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-03-12T00:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"Environmental Science and Pollution Research","date":"2021-02-22T12:53:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"environmental-science-and-pollution-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"espr","sideBox":"Learn more about [Environmental Science and Pollution Research](https://www.springer.com/journal/11356)","snPcode":"11356","submissionUrl":"https://submission.nature.com/new-submission/11356/3","title":"Environmental Science and Pollution Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a2df98a3-cfd7-4d01-b760-72d3026e8ff9","owner":[],"postedDate":"March 22nd, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":3113228,"name":"Environmental Engineering"},{"id":3113229,"name":"Environmental Policy"}],"tags":[],"updatedAt":"2022-01-28T00:45:03+00:00","versionOfRecord":{"articleIdentity":"rs-267943","link":"https://doi.org/10.1007/s11356-021-18031-y","journal":{"identity":"environmental-science-and-pollution-research","isVorOnly":false,"title":"Environmental Science and Pollution Research"},"publishedOn":"2022-01-28 00:45:03","publishedOnDateReadable":"January 28th, 2022"},"versionCreatedAt":"2021-03-22 12:49:40","video":"","vorDoi":"10.1007/s11356-021-18031-y","vorDoiUrl":"https://doi.org/10.1007/s11356-021-18031-y","workflowStages":[]},"version":"v1","identity":"rs-267943","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-267943","identity":"rs-267943","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}