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CHAPTER 160: Food and Waterborne Illnesses 1063  PREVENTION Both the Centers for Disease Control and Prevention and World Health Organization publish information regarding prevention of malaria for residents of endemic areas and for travelers who are considering visiting those countries. These recommendations are updated at regular intervals. REFERENCES The complete reference list is available online at www.TintinalliEM.com. TABLE 159-4 Adverse Effects, Precautions, and Contraindications of Antimalarial Drugs Drug Minor Toxicity Major Toxicity Precautions/Contraindications Chloroquine Nausea/vomiting, diarrhea, pruritus, postural hypotension, rash, fever, headache, dizziness Rare; hypotension and shock after parenteral therapy Retinopathy after prolonged use Avoid in patients with severe psoriasis and some types of porphyria. Caution with decreased liver function. Quinine or quinidine Cinchonism (nausea and vomiting, headache, tinnitus, dizziness, visual disturbance) Hypotension, cardiac dysrhythmias, hypoglycemia, Coombs-positive hemolysis, abortions, neuromuscular paralysis (myasthenia) Contraindicated in cardiac disease. Caution in pregnancy, myasthenia gravis. Mefloquine Nausea/vomiting, cramps, diarrhea, anorexia, dizziness, headaches, nightmares, and bradycardia Rare unless underlying heart disease with bradycardia or the patient is on selected cardiotoxic medications (dysrhythmias, arrest); acute toxic confusional states may occur, as can seizures Precaution during pregnancy and in children weighing <10 kg. Avoid if the patient is receiving quinidine. Avoid if the patient has heart conduction disturbance or if underlying seizure or major neuropsychiatric disorders. Doxycycline GI disturbances, phototoxicity, vaginal candidiasis Rare; esophageal ulcerations if not taken with fluids Avoid during pregnancy and in children <8 y of age unless alternatives not available. May depress prothrombin time in patients receiving anticoagulants. Artemether-lumefantrine (Coartem ® ) Headache, dizziness, anorexia, and asthenia Rare; severe skin rash, QT prolongation Avoid use with other drugs that may prolong QT interval. Drug interactions with cytochrome P450 3A4 and cytochrome P450 2D6. Atovaquone-proguanil (Malarone ® ) Nausea, vomiting, cramps, oral ulcers, headaches, dizziness Rare serious allergic reactions and alopecia reported Contraindicated in pregnancy and in children <5 kg (no safety data) and in patients with creatinine clearance <30. Primaquine* Nausea, vomiting, diarrhea, cramps, methemoglobinemia Massive hemolysis in patients with G6PD deficiency Exacerbation of systemic lupus erythematosus or rheumatoid arthritis Contraindicated in G6PD deficiency, pregnancy. Abbreviation: G6PD = glucose-6-phosphate dehydrogenase. *Terminal treatment for Plasmodium vivax and Plasmodium ovale infections only. The Centers for Disease Control and Prevention estimates that food borne diseases affect 9 million Americans each year, leading to 128,000 hospitalizations and 3000 deaths.2,3 Children have the highest frequency of foodborne illness. Viruses are the most common cause of foodborne disease, with the norovirus causing more than half all cases and 26% of all admissions. 2 Other viral sources of infection include rotavirus, astrovirus, and enteric adenovirus. Although less frequent, bacterial causes tend to be more severe, with nontyphoidal Salmonella and Listeria most often resulting in fatality.

e disease, with the norovirus causing more than half all cases and 26% of all admissions. 2 Other viral sources of infection include rotavirus, astrovirus, and enteric adenovirus. Although less frequent, bacterial causes tend to be more severe, with nontyphoidal Salmonella and Listeria most often resulting in fatality. 2,3 Other common bacterial causes of foodborne illness include Clostridium perfringens, Campylobacter spp., Toxoplasma gondii, Shigella, Staphylococcus aureus, and Shiga toxin–producing Escherichia coli (STEC). The most common foods associated with foodborne illness outbreaks from any pathogen reported in the United States are poultry, leafy vegetables, and fruits/nuts. 2,3 For further discussion, see Chapter 73, “Disorders Presenting Primarily With Diarrhea. ” PATHOPHYSIOLOGY There are three basic mechanisms by which microbes cause illness. First, some pathogens such as S. aureus, Bacillus cereus, and Clostridium botulinum (botulism) produce toxins causing illness. These toxins are present in the food before ingestion and result in the rapid onset (1 to 6 hours) of symptoms. Preformed toxins such as staphylococcal enterotoxin stimulate the host immune system to release inflammatory cyto kines within the intestine. 4 These cytokines trigger the accompanying nausea and vomiting. The second method involves toxin production after ingestion, which interacts with intestinal epithelium; this occurs with Vibrio, Shigella, and STEC. These cause diarrhea (sometimes bloody) and lower abdominal cramping, with onset at approximately 24 hours after exposure. Some toxins produced by Vibrio and enterotoxigenic E. coli alter chloride and sodium transport across intestinal mucosal surfaces without destroying CHAPTER Food and Waterborne Illnesses Lane M. Smith Simon A. Mahler  FOODBORNE ILLNESSES INTRODUCTION AND EPIDEMIOLOGY Foodborne illness occurs after consumption of a food contaminated with bacteria, viruses, or protozoans. Outbreaks from contaminated food are often widespread due to advances in modern food logistics. International travel contributes to foodborne illnesses as travelers are exposed to new pathogens and migrants may introduce diseases, making foodborne disease a global public health concern. Tintinalli_Sec13_p0997-1100.indd 1063 8/2/19 8:12 PM

minated food are often widespread due to advances in modern food logistics. International travel contributes to foodborne illnesses as travelers are exposed to new pathogens and migrants may introduce diseases, making foodborne disease a global public health concern. Tintinalli_Sec13_p0997-1100.indd 1063 8/2/19 8:12 PM 1064 SECTION 13: Infectious Diseases cells.5 The resulting osmotic gradient produces a large fluid shift into the intestinal lumen, which overwhelms the absorptive capacity of the colon causing watery diarrhea. Other toxins produced disrupt host cell protein production, which causes death of the intestinal epithelium, resulting in bloody diarrhea and extraintestinal symptoms. Finally, direct invasion of the intestinal epithelium is a mechanism for the enteric viruses, notably Salmonella, enteroinvasive E. coli, and Campylobacter. These pathogens enter host cells and destroy intestinal epithelium.7 This causes diarrhea due to transient malabsorption that is frequently bloody and accompanied by fever. Illness requires ingestion of just a few pathogens to cause disease. The upper and lower GI symptoms from invasive organisms last from 24 hours to weeks (Table 160-1). The normal human digestive system defends against illness in many ways. The low gastric pH of 1 to 3 kills many ingested pathogens, whereas the intestinal flora competitively inhibits pathogens and secretes bactericidal fatty acids and other chemicals. 8,9 Intestinal motility prevents pathogens from having prolonged contact with mucosal surfaces and mixes organisms with mucus-containing protective glyco proteins. Immunologic cells also directly attack pathogens attempting transmural migration. Alteration of these protective mechanisms can increase susceptibility to foodborne disease. For example, proton pump inhibitors, histamine-2 blockers, and antacids reduce gastric acid production and increase susceptibility in foodborne illnesses. 8,9 Recent antibiotic use, chemo therapy or radiation therapy, and recent surgery alter the intestinal flora. Decreased intestinal motility from opioids, antiperistaltic drugs, or surgery encourages pathogen growth and migration. CLINICAL FEATURES Suspect a foodborne disease when two or more people in a household or close association (e.g., the same workplace or communal eating arrangement) develop GI symptoms at or near same onset time. The most common symptoms are nausea, vomiting, diarrhea, and abdomi nal cramping. Systemic symptoms of fever, dehydration, and malaise also occur. Neurologic symptoms of seizures and altered mental status are seen in approximately 10% of pediatric patients with Shigella and are associated with worse outcomes. Question patients about the types of food they have recently ingested, frequency of restaurant meals, consumption of public-vended or streetvended foods, ingestion of seafood, and consumption of raw foods. Ask about recent travel or camping, contact with food handlers, and diaper changing. Children who attend day care centers and residents of long-term care facilities are at increased risk for foodborne diseases. Individuals working in the food industry are other frequent victims or sources; ask them about their personal hygiene and food-handling practices. Finally, seek a history of comorbid conditions or influencing therapies, including human immunodeficiency virus (HIV) infection or immunosuppressive drug use. On exam, look for dehydration and systemic findings. Carefully look for blood in the stool and for alternative causes of symptoms such as appendicitis. The clinical features of specific foodborne infections are listed in Table 160-2.

including human immunodeficiency virus (HIV) infection or immunosuppressive drug use. On exam, look for dehydration and systemic findings. Carefully look for blood in the stool and for alternative causes of symptoms such as appendicitis. The clinical features of specific foodborne infections are listed in Table 160-2. TABLE 160-1 Etiologic Agents for Foodborne Diseases and Usual Incubation Periods 1–6 Hours 6–24 Hours 24–48 Hours 2–6 Days 1–2+ Weeks Astrovirus Bacillus cereus diarrhea toxin Clostridium botulinum Campylobacter Brucella B. cereus preformed toxin C. perfringens Enterotoxigenic Escherichia coli Shigella Cryptosporidium Ciguatoxin Vibrio parahaemolyticus Salmonella Enterohemorrhagic E. coli Entamoeba Heavy metals   Trichinella Vibrio cholerae Giardia Monosodium glutamate     Yersinia Hepatitis A Norovirus       Listeria Scombroid toxin       Salmonella typhi S. aureus toxin Tetrodotoxin TABLE 160-2 Clinical Features of Foodborne Infections Clinical Presentation Foodborne Pathogens Gastroenteritis with vomiting as the primary symptom Viral pathogens: norovirus, rotavirus, and astrovirus; preformed toxins: Staphylococcus aureus and Bacillus cereus Noninflammatory diarrhea (watery nonbloody) Can be any enteric pathogen, but classically: ETEC Giardia Vibrio cholerae Enteric viruses Cryptosporidium Cyclospora Inflammatory diarrhea (grossly bloody, fever) Shigella Campylobacter Salmonella EIEC Shiga toxin–producing Escherichia coli O157:H7 and non-O157:H7 Vibrio parahaemolyticus Yersinia Entamoeba Persistent diarrhea (>14 d) Parasites: Giardia Cyclospora Entamoeba Cryptosporidium Neurologic manifestations Botulism (Clostridium botulinum toxin) Scombroid fish poisoning Ciguatera fish poisoning Tetrodotoxin Toxic mushroom ingestion Paralytic shellfish poisoning Guillain-Barré syndrome Shigella (pediatric seizures, encephalopathy, and rarely coma) Systemic illness Listeria monocytogenes Brucella Salmonella typhi Salmonella paratyphi Vibrio vulnificus Hepatitis A, E Abbreviations: ETEC = enterotoxigenic E. coli; EIEC = enteroinvasive E. coli. Tintinalli_Sec13_p0997-1100.indd 1064 8/2/19 8:12 PM

ndrome Shigella (pediatric seizures, encephalopathy, and rarely coma) Systemic illness Listeria monocytogenes Brucella Salmonella typhi Salmonella paratyphi Vibrio vulnificus Hepatitis A, E Abbreviations: ETEC = enterotoxigenic E. coli; EIEC = enteroinvasive E. coli. Tintinalli_Sec13_p0997-1100.indd 1064 8/2/19 8:12 PM CHAPTER 160: Food and Waterborne Illnesses 1065 DIAGNOSIS Most patients with foodborne diseases do not require diagnostic testing; illnesses are usually self-limited. Routine stool testing is not indicated for uncomplicated, watery diarrhea. 11 However, electrolytes and a CBC aid in patients with systemic illness findings, serious comorbid conditions, or those with prolonged symptoms. Obtain a stool test in those with: • Watery diarrhea with signs of hypovolemia • Bloody diarrhea • Fever ≥38.5°C (101.3°F) • Duration of illness >1 week • Severe abdominal pain or tenderness • Hospitalized patients or recent antibiotic use • Elderly (≥70 years of age) or the immunocompromised • Pregnant women or those with comorbid conditions such as inflam matory bowel disease Diagnostic testing for a specific pathogen uses either stool staining/ culture or multipathogen molecular panel. Routine stool cultures will identify Salmonella, Campylobacter, and Shigella but may not detect enterotoxigenic E. coli, vibrios, fungi, and viruses. Newer molecular panels using polymerase chain reaction are sensitive and less dependent on sample quality than routine stool cultures and help identify a wide array of pathogens. 12 These assays have become the test of choice at most institutions since they can detect bacterial, viral, and parasitic infections in a single stool sample. Indirect tests for bacterial causes of diarrhea such as fecal leukocytes or lactoferrin are not recommended. Add testing for ova and parasites selectively (e.g., in the immunocompromised, travelers, patients with symptoms lasting longer than 2 weeks, community waterborne outbreaks, or men who have sex with men). The newer multipathogen molecular panels are sensitive and specific for these parasites. Elderly patients, young children, and the immunocompromised are more likely to have severe illness, atypical presentations, and longterm sequelae. Patients with acquired immunodeficiency syndrome or other immunocompromised states can rapidly develop life-threatening symptoms and should undergo additional testing for Cryptosporidium, Cyclospora, Microsporidia, Mycobacterium avium complex, and Cytomegalovirus. TREATMENT Most episodes of acute gastroenteritis require adequate hydration and supportive care. The World Health Organization recommends ini tial oral hydration with a glucose-containing fluid (i.e., Pedialyte ® or equivalent).13 Reserve parenteral rehydration for patients with severe dehydration or with continued vomiting and inability to tolerate oral fluids. Antiemetics may reduce vomiting, ED length of stay, and need for admission. 14,15 Antimotility medications, such as loperamide, may decrease illness duration for mild to moderate nonbloody diarrhea in adults without fever; avoid these in children and patients with dysentery (fever and bloody diarrhea) due to concerns of prolonging the illness. Empiric antibiotics do not dramatically alter the course of illness since most cases are viral or self-limited bacterial in origin.

for mild to moderate nonbloody diarrhea in adults without fever; avoid these in children and patients with dysentery (fever and bloody diarrhea) due to concerns of prolonging the illness. Empiric antibiotics do not dramatically alter the course of illness since most cases are viral or self-limited bacterial in origin. The 2017 Infectious Diseases Society of America guidelines recommend empiric treatment for patients with bloody diarrhea under the following circumstances 11: • Infants less than 3 months of age • Immunocompromised patients with severe illness • Ill immunocompetent people with documented fever, abdominal pain, bloody diarrhea, and bacillary dysentery presumptively due to Shigella • Recent international travelers with fever ≥38.5°C or signs of sepsis Avoid empiric antibiotics if you believe illness is from STEC O157 and other STEC that produce Shiga toxin due to increased risk of hemolytic-uremic syndrome (HUS). Empiric antibiotics are an option for well-appearing patients with watery diarrhea and a history of inter national travel, but these are not needed for most with other diarrheal illnesses, even when prolonged more than 14 days. A common bacterial enteritis regimen is oral ciprofloxacin, 500 milligrams twice daily, or levofloxacin, 500 milligrams once a day, each for 3 to 5 days. Azithromycin, 500 milligrams once daily for 3 days, is an alternative. 11 See Tables 160-3, 160-4, 160-5, and 160-6 for detailed treatment recommendations. DISPOSITION AND FOLLOW-UP Admit or observe for prolonged intervals those who have systemic symptoms, comorbid conditions, or severe dehydration with inability to tolerate oral fluids. Have a low threshold for admitting immunocompromised patients. Pregnant patients have increased risk of complications, especially with Listeria infection, and may require further monitoring. Discharged patients should receive instructions on proper hygiene, notably frequent hand washing to protect non-ill family members and contacts. Patients discharged with pending stool culture or other studies should have a clear plan for follow-up. SPECIAL CONSIDERATIONS  ENTEROHEMORRHAGIC E. COLI AND HEMOLYTIC-UREMIC SYNDROME Enterohemorrhagic E. coli that produces Shiga toxin is the most com mon cause of HUS in children. 17 The STEC strain O157:H7 is most commonly associated with pediatric HUS, but other organisms such as O104:H4, O111, and Shigella are also associated with adult HUS-like illnesses. 10 The Shiga toxin produced by these organisms halts protein synthesis in renal glomerular cells as the precipitating event in HUS. Toxin binding to the glomerular endothelium produces a thrombogenic environment, leading to microangiopathic hemolysis through multiple cellular mechanisms. 18 Antibiotics may promote Shiga toxin release, which increases the incidence of HUS; for this reason, avoid antibiotics when suspecting this pathogen. In addition, avoid antimotility agents. Treatment of HUS is supportive, although eculizumab, a monoclonal antibody to complement factor C5 that blocks complement activa tion, shows promise in severe cases. 19 Approximately 50% of pediatric patients with HUS require dialysis, and dehydration at the time of admission increases the frequency and duration of renal support.  SCOMBROID AND CIGUATERA POISONING Scombroid fish poisoning occurs after ingestion of fish of the family Scombridae (tuna, mackerel, and bonito). Other non-Scombridae fish such as mahi-mahi, bluefish, herring, and sardines are triggers. The disease occurs when histidine is metabolized by bacteria into histamine and other bioactive amines. 21 Improper temperature control allows high concentrations of these substances to accumulate in the fish.

kerel, and bonito). Other non-Scombridae fish such as mahi-mahi, bluefish, herring, and sardines are triggers. The disease occurs when histidine is metabolized by bacteria into histamine and other bioactive amines. 21 Improper temperature control allows high concentrations of these substances to accumulate in the fish. Symptoms usually begin 30 minutes to 24 hours after ingestion and include flush ing, headache, abdominal cramping, vomiting, and diarrhea. Symptoms are usually self-limited for 12 to 48 hours. However, severe cardiac and respiratory symptoms may occur in the elderly or patients with comor bid conditions. Treatment is with antihistamines (H 1 and H 2 blockers) such as diphenhydramine and cimetidine. Laboratory testing is not indicated in most cases. Ciguatera poisoning is caused by eating reef fish contaminated with the dinoflagellate Gambierdiscus toxicus, which produces ciguatoxin. The toxin is heat resistant and accumulates in large predatory fish such as grouper, snapper, amberjack, and barracuda. Ciguatoxin acts on sodium channels, resulting in membrane depolarization. Nausea, vomiting, and diarrhea occur 1 to 24 hours after ingestion, followed by hyp esthesias, paresthesias, numbness, malaise, generalized weakness, and sensitivity to temperature extremes. Bradycardia and hypotension are possible. 22 The GI symptoms typically resolve over a few days, whereas the neurologic symptoms may persist in a waxing and waning pattern Tintinalli_Sec13_p0997-1100.indd 1065 8/2/19 8:12 PM

paresthesias, numbness, malaise, generalized weakness, and sensitivity to temperature extremes. Bradycardia and hypotension are possible. 22 The GI symptoms typically resolve over a few days, whereas the neurologic symptoms may persist in a waxing and waning pattern Tintinalli_Sec13_p0997-1100.indd 1065 8/2/19 8:12 PM 1066 SECTION 13: Infectious Diseases TABLE 160-3 Clinical Features, Diagnosis, and Management of Bacterial Foodborne Illness Etiology Signs and Symptoms Duration of Illness Associated Foods Laboratory Testing Treatment Bacillus anthracis Nausea, vomiting, bloody diarrhea, abdominal pain, malaise Weeks Poorly cooked meat Blood Ciprofloxacin or doxycycline IV + PCN, vancomycin, rifampin, or clindamycin Bacillus cereus (preformed toxin) Sudden onset of nausea, vomiting; can have diarrhea 24 h — Clinical diagnosis; assay must be ordered specifically Supportive care B. cereus (diarrheal toxin) Watery diarrhea, cramping, nausea 1–2 d Meats, gravies, stew, vanilla sauces Not necessary Supportive care Brucella Fever, chills, myalgias, arthralgias, weakness, bloody diarrhea Weeks Raw milk, unpasteurized goat’s milk or cheese, contaminated meat Serology, blood culture Doxycycline 100 milligrams PO twice daily + streptomycin 1 gram IM for 14–21 d Campylobacter Diarrhea, cramping, nausea, vomiting, fever, often bloody diarrhea 2–10 d Contact with raw poultry, undercooked poultry, unpasteurized milk, contaminated water Routine stool culture on special media and temperature; MMP Ciprofloxacin 750 milligrams PO twice daily or levofloxacin 500 milligrams PO daily or azithromycin 500 milligrams daily for 3–5 d Clostridium botulinum (preformed toxin) Vomiting, diarrhea, blurred vision, diplopia, dysphagia, descending muscle weakness, paralysis Days to months Canned foods, canned fish, foods kept warm in dishes, herbed oils, cheese sauce Stool, serum, or food assay for toxin; stool culture Supportive care (may require intubation), botulism antitoxin C. botulinum—infants Infants <12 mo, lethargy, weakness, poor feeding, head control, and suck Variable Honey, home canned vegetables, corn syrup Stool, serum, or food for toxin; stool culture Botulism immunoglobulin; antitoxin not recommended in infants Clostridium perfringens Watery diarrhea, nausea, cramping 1–2 d Meat, poultry, dried or precooked foods, poor temperature control Stools for enterotoxin, stool culture Supportive care Enterohemorrhagic Escherichia coli and Shiga toxin–producing E. coli, O157:H7 Severe, often bloody diarrhea; abdominal pain; vomiting; little or no fever 5–10 d Undercooked beef (hamburger), unpasteurized milk, juices, raw fruits and vegetables Stool culture; may require special media; toxin assay; MMP Supportive; avoid antibiotics due to risk of hemolytic-uremic syndrome Enterotoxigenic E.

7:H7 Severe, often bloody diarrhea; abdominal pain; vomiting; little or no fever 5–10 d Undercooked beef (hamburger), unpasteurized milk, juices, raw fruits and vegetables Stool culture; may require special media; toxin assay; MMP Supportive; avoid antibiotics due to risk of hemolytic-uremic syndrome Enterotoxigenic E. coli Watery diarrhea, cramping, vomiting 3–7 d Water or food contaminated with human feces Stool culture; MMP Supportive; ciprofloxacin 500 milligrams PO twice per day or levofloxacin 500 milligrams PO once daily for 3 d Listeria monocytogenes Fever, myalgias, nausea, diarrhea; premature delivery if pregnant; meningitis Variable Fresh soft cheeses, poorly pasteurized dairy products, deli meats, hot dogs Blood or cerebrospinal fluid culture; listeriolysin O antibody assay Supportive care; ampicillin or penicillin G; TMP-SMX for PCN allergic Salmonella Diarrhea, vomiting, abdominal pain, fever, myalgia 4–7 d Eggs, poultry, unpasteurized dairy products, raw fruits and vegetables, street-vended food Routine stool culture; MMP Supportive care; ciprofloxacin 500 milligrams PO twice daily or levofloxacin 500 milligrams once daily for 3–5 d; ceftriaxone IV for severe disease or immunocompromised; vaccine for Salmonella typhi Shigella Abdominal cramping, fever, diarrhea with blood and mucus 4–7 d Fecal contamination of any food or water, person to person, prepared food Routine culture; MMP Supportive care; ciprofloxacin 500 milligrams PO twice per day or levofloxacin 500 milligrams once per day for 3–5 d or azithromycin 500 milligrams PO daily for 3 d Staphylococcus aureus (preformed toxin) Sudden-onset severe nausea, vomiting, diarrhea, fever 1–2 days Improperly refrigerated meats, potato or egg salad; left out pastries Clinical diagnosis; assay for toxin; culture if indicated Supportive care only Vibrio cholerae Profuse watery diarrhea and vomiting; life-threatening dehydration 3–7 d Contaminated water, fish, shellfish, street-vended foods Specifically ordered stool culture; MMP Aggressive PO or IV fluid replacement, azithromycin 1 gram PO once or doxycycline 300 milligrams once or ciprofloxacin 1 gram PO once Vibrio parahaemolyticus Watery diarrhea, cramping, vomiting 2–5 d Undercooked or raw fish or shellfish Stool culture (special media required); MMP Supportive care; antibiotics in severe illness: ciprofloxacin 500 milligrams PO twice daily or TMP-SMX double strength PO twice daily or doxycycline 100 milligrams PO twice daily for 3 d Vibrio vulnificus Vomiting, abdominal pain, diarrhea, skin infections; can be fatal in liver disease or immunocompromised patients 2–8 d Undercooked or raw fish or shellfish Specifically ordered stool, blood, or wound cultures; MMP See Table 160-8 Yersinia Pseudoappendicitis, fever, abdominal pain, vomiting, diarrhea, rash 1–3 wk Undercooked pork products, tofu, contaminated water Stool, blood, or vomitus cultures (special media); MMP Supportive care; antibiotics usually not required; if septic: gentamicin, 5 milligrams/ kg IV daily + ceftriaxone 2 grams IV daily Abbreviations: MMP = multipathogen molecular panel; PCN = penicillin; TMP-SMX = trimethoprim-sulfamethoxazole. Tintinalli_Sec13_p0997-1100.indd 1066 8/2/19 8:12 PM

ures (special media); MMP Supportive care; antibiotics usually not required; if septic: gentamicin, 5 milligrams/ kg IV daily + ceftriaxone 2 grams IV daily Abbreviations: MMP = multipathogen molecular panel; PCN = penicillin; TMP-SMX = trimethoprim-sulfamethoxazole. Tintinalli_Sec13_p0997-1100.indd 1066 8/2/19 8:12 PM CHAPTER 160: Food and Waterborne Illnesses 1067 for 3 months to years. 23 Acute treatment is supportive. A consensus review of nine articles reported that IV mannitol may aid severe acute cases, but the evidence is conflicting and mannitol doses were not well described.  CHRONIC SEQUELAE OF FOODBORNE ILLNESS Approximately 2% to 3% of patients with foodborne diseases have longer sequelae thought to be related to autoimmunity. 25,26 Protein virulence factors (superantigens) can initiate extreme immune responses. Salmonella, Shigella, and Campylobacter result in a seronegative reac tive arthritis in approximately 2% of those infected. 27 Campylobacter infection is associated with Guillain-Barré syndrome, with a reported rate as high as 30.4 per 100,000 cases. 26 Symptoms of Guillain-Barré syndrome typically occur 7 to 21 days after the GI symptoms resolve.25,26 Other autoimmune disorders potentially related to superantigens from foodborne pathogens include multiple sclerosis, rheumatoid arthritis, psoriasis, and Graves’ disease. 25,27 Infections with Salmonella, Yersinia, and Campylobacter may increase short- and long-term risk of death, even after accounting for comorbid diseases.28  WATERBORNE ILLNESSES INTRODUCTION AND EPIDEMIOLOGY Waterborne illnesses occur from ingestion or contact with contaminated water found in swimming pools, hot tubs, spas, and naturally occurring freshwater and saltwater during recreational use. 29 Numerous bacteria, viruses, and protozoans arrive in the water by fecal contamination and cause infections. However, some species of bacteria are indigenous aquatic organisms such as Pseudomonas aeruginosa, Vibrio, Aeromonas, nontuberculous Mycobacterium, and Legionella. Physiologic mechanisms intended to prevent infection from water borne pathogens are the same as those discussed earlier for foodborne diseases in the pathophysiology section. There were 493 recreational waterborne disease outbreaks in the United States reported to the Centers for Disease Control and Pre vention in 2000 to 2014, which resulted in at least 27,219 cases of disease and eight deaths. 29 The majority of these outbreaks started in treated water sources (such as swimming pools) or from chlorinetolerant organisms such as Cryptosporidium (which accounted for more than half of all cases). Legionella caused 16% of illnesses and 75% of deaths. BACTERIA AND WATERBORNE ILLNESS Implementation of water disinfection and filtration treatments reduced waterborne outbreaks from enteric bacteria. infections from V . cholerae and S. typhi are now extremely rare in the developed world, but both remain a major cause of illness in develop ing nations. 31 Several enteric bacteria are commonly implicated in waterborne dis ease outbreaks in the United States. Campylobacter is found in virtually all surface waters due to contamination from wild bird feces and is the most common bacteria associated with recreational waterborne disease outbreaks. 29 Several outbreaks of human campylobacteriosis came from contaminated drinking water. 32 STEC can also be transmitted from ingestion or contact with water contaminated by farm animal feces. 33 Shigella species, Salmonella species, and Yersinia enterocolitica are other enteric bacteria that can cause waterborne outbreaks. 30 Most enteric bacteria, including E. coli O157:H7 and Campylobacter , are susceptible to chlorination. Although V .

om ingestion or contact with water contaminated by farm animal feces. 33 Shigella species, Salmonella species, and Yersinia enterocolitica are other enteric bacteria that can cause waterborne outbreaks. 30 Most enteric bacteria, including E. coli O157:H7 and Campylobacter , are susceptible to chlorination. Although V . cholerae is an enteric organism acquired from water with fecal contamination, many other Vibrio species are endemic in marine and estuarine waters. Vibrio species can cause diarrheal illnesses or skin TABLE 160-4 Clinical Features, Diagnosis, and Management of Viral Foodborne Illness Etiology Signs and Symptoms Duration of Illness Associated Foods Laboratory Testing Treatment Hepatitis A Diarrhea, jaundice, dark urine, flulike illness, abdominal pain 2 wk to 3 mo Shellfish, raw produce, contaminated water, infected contacts Liver profile, bilirubin, positive immunoglobulin, and antihepatitis A antibodies Supportive care; prevention with immunization Norovirus, rotavirus, and other enterovirus Nausea, vomiting, abdominal cramping, diarrhea; sometimes fever, malaise, headache 12 h to 9 d Fecal contaminated foods; foods touched by infected workers (salads, sandwiches, produce); shellfish Clinical diagnosis; multipathogen molecular panel Supportive care, good hygiene, adequate fluid replacement TABLE 160-5 Clinical Features, Diagnosis, and Management of Parasitic Foodborne Illness Etiology Signs and Symptoms Duration of Illness Associated Foods Lab Testing Treatment Cryptosporidium Watery diarrhea, cramping, fever Weeks to months— may be relapsing Any contaminated uncooked food, water Specific stool examination; MMP Supportive care and HAART in HIV infected; nitazoxanide 500 milligrams PO twice daily for 3 d + azithromycin in patient with HIV and severe symptoms Cyclospora Watery diarrhea, weight loss, cramping, vomiting, fatigue Weeks to months, relapsing Various types of fresh produce Specific stool examination; MMP

cholerae is an enteric organism acquired from water with fecal contamination, many other Vibrio species are endemic in marine and estuarine waters. Vibrio species can cause diarrheal illnesses or skin TABLE 160-4 Clinical Features, Diagnosis, and Management of Viral Foodborne Illness Etiology Signs and Symptoms Duration of Illness Associated Foods Laboratory Testing Treatment Hepatitis A Diarrhea, jaundice, dark urine, flulike illness, abdominal pain 2 wk to 3 mo Shellfish, raw produce, contaminated water, infected contacts Liver profile, bilirubin, positive immunoglobulin, and antihepatitis A antibodies Supportive care; prevention with immunization Norovirus, rotavirus, and other enterovirus Nausea, vomiting, abdominal cramping, diarrhea; sometimes fever, malaise, headache 12 h to 9 d Fecal contaminated foods; foods touched by infected workers (salads, sandwiches, produce); shellfish Clinical diagnosis; multipathogen molecular panel Supportive care, good hygiene, adequate fluid replacement TABLE 160-5 Clinical Features, Diagnosis, and Management of Parasitic Foodborne Illness Etiology Signs and Symptoms Duration of Illness Associated Foods Lab Testing Treatment Cryptosporidium Watery diarrhea, cramping, fever Weeks to months— may be relapsing Any contaminated uncooked food, water Specific stool examination; MMP Supportive care and HAART in HIV infected; nitazoxanide 500 milligrams PO twice daily for 3 d + azithromycin in patient with HIV and severe symptoms Cyclospora Watery diarrhea, weight loss, cramping, vomiting, fatigue Weeks to months, relapsing Various types of fresh produce Specific stool examination; MMP TMP-SMX-DS PO twice per day or ciprofloxacin 500 milligrams twice daily for 7–10 d; nitazoxanide 500 milligrams PO twice daily for 7 d In HIV patients: TMP-SMX-DS PO 4 times a day for 21 d Entamoeba histolytica Bloody diarrhea, frequent stools, lower abdominal pain Weeks to months Any contaminated uncooked food, water Examination of stool for cysts and parasites; serology; MMP Metronidazole 750 milligrams PO 3 times daily for 5–10 d or paromomycin 500 milligrams PO 3 times daily for 7 d or tinidazole 2 grams PO for 3 d or nitazoxanide 500 milligrams PO twice daily for 3 d Giardia Diarrhea, cramping, copious flatus Months Any contaminated uncooked food Examination of stool for ova and parasites; MMP Metronidazole 250 milligrams PO 3 times daily for 7–10 d or tinidazole 2 grams PO once or nitazoxanide 500 milligrams PO twice daily for 3 d or paromomycin 500 milligrams PO 3 times daily for 7 d or albendazole 400 milligrams PO once daily for 5 d Abbreviations: HAART = highly active antiretroviral therapy; HIV = human immunodeficiency virus; MMP = multipathogen molecular panel; TMP-SMX-DS = trimethoprim-sulfamethoxazole double strength. Tintinalli_Sec13_p0997-1100.indd 1067 8/2/19 8:12 PM

3 times daily for 7 d or albendazole 400 milligrams PO once daily for 5 d Abbreviations: HAART = highly active antiretroviral therapy; HIV = human immunodeficiency virus; MMP = multipathogen molecular panel; TMP-SMX-DS = trimethoprim-sulfamethoxazole double strength. Tintinalli_Sec13_p0997-1100.indd 1067 8/2/19 8:12 PM 1068 SECTION 13: Infectious Diseases TABLE 160-6 Clinical Features, Diagnosis, and Management of Toxinogenic Foodborne Illness Etiology Signs and Symptoms Duration Foods Lab Tests Treatment Ciguatera toxin Abdominal pain, vomiting, diarrhea, paresthesias, reversal of hot and cold sensation, weakness, hypotension, bradycardia Days to months Large reef fish (barracuda most common) Clinical diagnosis Supportive care; high-dose atropine for bradycardia; IV mannitol for severe neurologic symptoms Tetrodotoxin (puffer fish) Paresthesias, headache, vomiting, diarrhea, abdominal pain, ascending paralysis, respiratory failure, death Death in 4–6 h Puffer fish Detection of tetrodotoxin in fish Emergent supportive care; anticholinesterases such as neostigmine and edrophonium Scombroid (histamine) Flushing, rash, burning sensation, dizziness, paresthesias 3–6 h Pelagic fish—tuna, mackerel, swordfish, mahi-mahi Clinical diagnosis, can assay for histamine in fish Antihistamines, supportive care Shellfish toxins Diarrhea, vomiting, abdominal pain, fever, numbness, dizziness, myalgias, confusion, memory loss, coma 2 h to 3 d Shellfish, mussels, clams Detection of toxin in shellfish Supportive care, self-limited infections. 34 Vibrio vulnificus is associated with life- and limb-threat ening necrotic wound infections. The organism is found predominantly along the Gulf Coast and is acquired by patients with open wounds that are exposed to seawater. The wound infections are associated with a high rate of sepsis and amputation. Cirrhosis and high iron levels are associated with worse outcome. Found in fresh and marine waters, Aeromonas species can cause gastroenteritis and wound infections. 35 The majority of wound infec tions are simple cellulitis, but necrotizing infections and septic arthritis occur. 36,37 In addition, immunocompromised patients may progress to develop peritonitis, cholangitis, and meningitis.35 P . aeruginosa is an opportunistic pathogen found in freshwater, with immunocompromised patients at particular risk. In normal hosts, Pseudomonas can cause otitis externa, keratitis in contact lens wearers, and folliculitis.38 Although Pseudomonas can contaminate drinking water, it does not cause a diarrheal illness in normal hosts. Nontuberculous Mycobacterium exists in saltwater and freshwater and can cause illness. 39 Mycobacterium marinum is associated with granu lomatous skin infections, also called fish tank or aquarium granuloma (Figure 160-1).40 Mycobacterium avium complex is associated with GI, pulmonary, or disseminated disease in immunocompromised patients, particularly patients with HIV . Legionella is a common inhabitant of freshwater, including water that meets the standards for drinking. 29 Infection occurs from inhalation of contaminated aerosols, resulting in one of two syndromes: Legionnaires disease and Pontiac fever . Pontiac fever is a flulike illness contracted by breathing mist that comes from a water source (e.g., air condition ing cooling towers, whirlpool spas, and showers) contaminated with the bacteria. Further discussion of Legionnaires disease is available in Chapter 65, “Community-Acquired Pneumonia, Aspiration Pneumonia, and Noninfectious Pulmonary Infiltrates. ” PROTOZOA AND WATERBORNE ILLNESS Giardia lamblia is a common protozoal cause of waterborne dis ease in the United States and accounts for 16,000 cases of diarrheal disease annually.

nnaires disease is available in Chapter 65, “Community-Acquired Pneumonia, Aspiration Pneumonia, and Noninfectious Pulmonary Infiltrates. ” PROTOZOA AND WATERBORNE ILLNESS Giardia lamblia is a common protozoal cause of waterborne dis ease in the United States and accounts for 16,000 cases of diarrheal disease annually. 41 It is frequently found in surface waters from mountain streams to municipal reservoirs and is resistant to common chlorination. A form of giardiasis, often called “ beaver fever, ” can result from contamination of natural waters by animals such as beavers. Backpack ers, campers, and travelers to disease-endemic areas are at high risk for waterborne giardiasis, as are children under 5 years of age. 41 Community outbreaks often start out as a waterborne disease, but subsequent transmission commonly occurs from person to person. Giardia is associated with acute and chronic forms of gastroenteritis, although many patients infected with Giardia remain asymptomatic. Cryptosporidium is an intracellular protozoan parasite and the most common cause of recreational waterborne GI illness in the United States. 29 The Centers for Disease Control and Prevention estimates 748,000 cases of cryptosporidiosis occur each year and result in hospital admissions costing $45.8 million. 42 The inoculum required to cause infection is low, and large numbers of oocysts are excreted in the feces of infected hosts. 43 Standard doses of chlorine and zonation used in water treatment are not effective against Cryptosporidium, which explains its association with recreational water sources. 42 Water filtration reduces the number of oocysts, but occasionally enough remain to be infective. Infection with Cryptosporidium in a normal host results in a self-limited diarrheal illness, and many exposures are asymptomatic. Immunocom promised patients may experience chronic diarrhea or life-threatening complications. 43 Cyclospora, Isospora, and Microspora are other proto zoan parasites that can cause severe disease in immunocompromised patients. Entamoeba histolytica is a protozoan that causes intestinal amebia sis. It is a significant waterborne pathogen in developing countries, but in the United States, it is most commonly seen in migrants, travelers to endemic areas, men who have sex with men, and institutionalized patients. 45,46 Symptoms range from asymptomatic infection to severe dysentery.45 Fulminant colitis with bowel necrosis and perforation occurs in <1% of cases but has a mortality rate >40%. 47 Seeding of the liver or brain can occur, particularly in men with underlying liver disease, resulting in the formation of amoebic hepatic abscesses. Naegleria fowleri is a thermophilic organism found in warm and hot freshwater ponds that is responsible for rare but often fatal primary amoebic meningoencephalitis. 48 Human disease occurs after inhalation of the trophozoites that invade the nasal cribriform plate, later digesting neurons. Symptoms begin after a 1- to 7-day incubation and include FIGURE 160-1. Skin infection from Mycobacterium marinum (fish tank or aquarium granuloma). A painful indurated plaque is noted on the dorsal surface of the proximal thumb. (Reproduced with permission from Wolff K, Johnson RA: Color Atlas and Synopsis of Clinical Dermatology, 5th ed, © 2005, McGraw-Hill, Inc., New York.) Tintinalli_Sec13_p0997-1100.indd 1068 8/2/19 8:12 PM

m (fish tank or aquarium granuloma). A painful indurated plaque is noted on the dorsal surface of the proximal thumb. (Reproduced with permission from Wolff K, Johnson RA: Color Atlas and Synopsis of Clinical Dermatology, 5th ed, © 2005, McGraw-Hill, Inc., New York.) Tintinalli_Sec13_p0997-1100.indd 1068 8/2/19 8:12 PM CHAPTER 160: Food and Waterborne Illnesses 1069 fever, headache, and altered mental status. Mortality rates approach 95% even with treatment.49 ENTERIC VIRUSES AND WATERBORNE INFECTION More than 100 enteric viruses are pathogenic in humans, many of which can be transmitted by drinking water and recreational water. 50 Several enteric viruses, including the Norwalk virus and rotaviruses, are chlo rine resistant. 29 Outbreaks can happen with contamination of private wells and community water systems.50 Hepatitis A and E trigger epidemic and sporadic infections from contaminated water. Infection from the hepatitis A virus typically results in an acute self-limited hepatitis, rarely leading to fulminant hepatic failure. Several outbreaks attributed to contaminated food led to an increased incidence of hepatitis A after a period of decline. 51 Once considered a disease confined to tropical regions, the incidence of hepatitis E in developed countries is rising. 52 In endemic and underdeveloped countries, morbidity and mortality from hepatitis E associated with pregnancy or preexisting liver disease are high due to hepatic failure. Noroviruses, including the Norwalk virus, are the leading cause of acute gastroenteritis across all age groups. 53 Outbreaks are often linked to contaminated drinking and recreational water, including on cruise ships. 54 Rotavirus and enteric adenoviruses are other important water borne enteric viruses. Noroviruses, rotaviruses, and enteric adenovi ruses typically cause a self-limited gastroenteritis, although dehydration from these infections can be severe in children. CLINICAL FEATURES OF WATERBORNE INFECTIONS The majority of patients with waterborne disease present with nausea, vomiting, and diarrhea. Think of this cause in symptomatic patients with recent travel, outdoor activities such as camping or backpacking, recent recreational water use, or those using a private drinking water supply rather than municipal drinking water or bottled water. Patients with severe or chronic gastroenteritis symptoms may have immune deficiency caused by HIV or immunosuppressive drugs. In patients with bloody diarrhea, suspect invasive enteric organisms. 11 Suspect Giardia and other protozoan parasites in patients with diarrhea lasting 2 or more weeks. 11 Consider invasive amoebic organisms in patients presenting with altered mental status, meningeal signs, or peritonitis after recreational water exposure. Physical examination seeks to identify signs of dehydration and any open skin wounds acquired in fresh or marine waters. The waterborne skin infections range in severity from simple cellulitis to necrotizing fasciitis. Patients with V . vulnificus present after recent exposure to saltwater with hemorrhagic bullae or signs of necrotizing infection (Figure 160-2). 33 Clinical features of waterborne pathogens are summarized in Table 160-7. DIAGNOSIS Criteria for testing are the same as noted in foodborne illness and usually not needed. Viral antigen tests for rotavirus may be helpful in children with severe or persistent symptoms to distinguish viral from bacterial pathogens. Testing with a multipathogen molecular panel is indicated in patients with recent travel to endemic countries, immunocompromised status, or diarrheal illness of 2 or more weeks; during community-wide waterborne outbreaks; or in men who have sex with men.

ersistent symptoms to distinguish viral from bacterial pathogens. Testing with a multipathogen molecular panel is indicated in patients with recent travel to endemic countries, immunocompromised status, or diarrheal illness of 2 or more weeks; during community-wide waterborne outbreaks; or in men who have sex with men. 11,30 Because parasite excretion may not be continuous, three specimens separated by at least 24 hours may be needed to identify the causative pathogen when performing stool microscopic inspection. The diagnosis of waterborne skin infections is based primarily on the patient’s physical examination findings and history of water exposure. Identification of the causative agent can be attempted by Gram stain and wound culture (acid-fast staining if M. marinum is suspected). Reserve blood cultures for systemically ill patients and children less than 3 months of age. TREATMENT In most cases of acute gastroenteritis from waterborne pathogens, treatment is rehydration. Use empiric antibiotic therapy for patients with moderate to severe disease, recent travel history, or symptoms lasting more than 1 week; those needing hospitalization; and immunocompromised hosts. 11 Avoid antibiotics in cases of suspected E. coli O157:H7 due to an increased risk of development of HUS. Appropriate anti biotic regimens are 3 to 5 days of oral ciprofloxacin 500 milligrams twice daily, levofloxacin 500 milligrams once daily, or double-strength trimethoprim-sulfamethoxazole twice daily. 11Azithromycin 500 mil ligrams orally once daily for 3 to 5 days is used in pregnant women, FIGURE 160-2. Skin infection from Vibrio vulnificus. V. vulnificus was cultured from the bulla aspirates from this patient with hemorrhagic and bullous skin lesions of the lower legs. (Reproduced with permission from Wolff K, Johnson R: Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology, 6th ed, © 2009 McGraw-Hill, Inc., New York.) TABLE 160-7 Type of Transmission and Clinical Features Associated With Waterborne Pathogens Pathogen Drinking Water Recreational Water Clinical Features Campylobacter + + Gastroenteritis; can be associated with Guillain-Barré syndrome Escherichia coli O157H7 + + Gastroenteritis; can be associated with hemolytic-uremic syndrome Salmonella species + + Gastroenteritis, typhoid fever Shigella species + + Gastroenteritis Yersinia species + + Gastroenteritis Vibrio species + + Gastroenteritis; skin infections Aeromonas species + + Gastroenteritis; skin infections Pseudomonas _ + Skin infections; nosocomial infections Nontuberculous Mycobacterium +/– + Skin infections; disseminated disease in immunocompromised Giardia + + Acute and chronic gastroenteritis; asymptomatic carriage Cryptosporidium + + Acute and chronic gastroenteritis, severe among immunocompromised Entamoeba + + Acute and chronic gastroenteritis; rare fulminant colitis; liver or rare brain abscess Naegleria fowleri +/– + Acute meningoencephalitis Hepatitis A + + Acute hepatitis; rare liver failure Hepatitis E + + Acute hepatitis; fulminant and severe in pregnancy Enteric viruses + + Gastroenteri Tintinalli_Sec13_p0997-1100.indd 1069 8/2/19 8:12 PM