Nontyphoidal salmonella infection: causes, symptoms, diagnosis, treatment, prognosis, and prevention

Nontyphoidal salmonella infection, also known as nontyphoidal salmonellosis, is an acute infectious disease caused by various serovars of salmonella. The main mode of transmission is ingestion of meat, poultry, egg products, and dairy products contaminated with salmonella. Due to the difference in pathogenic bacteria and body reaction, nontyphoidal salmonellosis can be manifested by gastroenteritis, enteric fever, bacteremia, and focal salmonella infection, as well as urinary tract infections and asymptomatic infections.


Causes

Salmonella is a rod-shaped, 0.6 - 1.5μm x 2.0 - 5.0μm, unencapsulated, non-spore-forming, Gram-negative bacillus, with many flagella. Most salmonella can move and are quite active.

More than 2,000 serovars of salmonella have been discovered to date. According to its biochemical characteristics, it can be divided into six subgenus of 1, 2, 3a, 3b, 4, and 5. Each subgenus is divided into various serotypes according to the structural characteristics of somatic antigen (O) and flagellar antigen (H). Most pathogenic salmonella serovars, such as salmonella typhi, salmonella paratyphi, salmonella enterica, salmonella typhimurium, salmonella enteritidis, salmonella bovismorbificans, and salmonella anatis, are members of subgenus 1.

Most salmonella can grow in common media and develop well. After 18 - 24 hours of culture, the bacterial colony is round, smooth, translucent, moist, and with a diameter up to 2 - 3mm. The bacterial colony isolated from sewage or foods may be rough, dry, and dull. A small number of salmonella, such as salmonella enterica, salmonella pullorum, and salmonella aborigis, grow poorly in common culture media.

The optimal growth temperature is 37 °C, and the optimal pH is 6.8 - 7.8. Salmonella is more resistant to the environment and can survive for months in water, milk, and meat. At 22 - 30 °C, the bacteria can rapidly reproduce in foods in 2 - 4 hours, and can also survive in frozen soil in winters. The bacteria are not strongly resistant to heat, and can be disinfected at 55 °C for 1 hour or 60 °C for 15 - 30 minutes. The bacteria can be disinfected in 5% phenol solution or 0.2% mercury chloride solution for 15 minutes.

Source of infection

The main source of infection is infected poultry, livestock such as chickens, turkeys, ducks, pigs, cattle, goats, and sheep, followed by infected rodents and other wild animals. The infection rate is 1% - 40% or more. Human carriers can also be sources of infection. Most of these carriers are with asymptomatic infections or mild symptoms, and the bacteria can be shedding in the stools. Temporary asymptomatic infections are more common in persons in occupational contact with salmonella, such as butchers or food processors. Asymptomatic salmonella carriers can sometimes shed a large amount of bacteria, and if their occupation is meat and other foods processor, they can be an important source of infection.

Mode of transmission

Contaminated meat, eggs, egg products, undercooked meat, milk, fishes, and shellfishes are the main route of human salmonella transmission.

Various animal derived drugs, such as bile salts, gelatin, pepsin, and trypsin, may cause the transmission of salmonella.

Infection can occur when drinking water contaminated with salmonella in animal and human feces. The water supply system contaminated by salmonella can cause epidemic.

Salmonella can be transmitted by direct contact with the patient or the contaminated utensils. This type of transmission can be seen in hospitals, and is more common in nursery rooms and pediatric wards.

Flies and cockroaches can be the mechanical carriers of salmonella. It has been reported that individuals with immune dysfunction can be infected through airborne transmission.

Pathogenesis

Salmonella enters the human body through mouth, and its reproduction can cause mucosal inflammation in the intestinal tract. The clinical manifestation is gastrointestinal inflammation. Studies in some experimental animal models have shown that salmonella does not produce enterotoxin. Ingestion of a large number of dead bacteria does not cause disease, suggesting that salmonella infection is caused by live bacteria. The pathogens propagate in the intestines, causing focal inflammation, resulting in congestion, edema, and exudation of the colonic mucosa, as well as hemorrhage, erosion, and ulceration in severe cases. When salmonella reaches the submucosal lamina propria, if the defense functions are relatively inadequate, salmonella can enter the blood circulation, leading to bacteremia and focal infection.

The consequences of salmonella entering the human body depend on the serovars and count of the bacteria, virulence, and immune status of the host. Various salmonella can cause different clinical manifestations such as asymptomatic infection, acute gastroenteritis, bacteremia or sepsis, focal suppurative infection, and conditions resembling typhoid fever. However, some salmonella have a tendency to cause a certain clinical manifestation. For example, salmonella anatis often causes asymptomatic infection or gastroenteritis, but rarely invade the blood circulation, whereas salmonella enterica occasionally causes gastroenteritis or asymptomatic infection, but often cause bacteremia or focal purulent infection. Different serovars, even different strains, may have differences in pathogenicity. Studies in human volunteers have shown that a large amount of salmonella is required to cause gastroenteritis in healthy adults, and few bacteria can only make persons to be temporary bacterial carriers. There are also large differences in the amount of bacteria that can cause infection in different serotypes. Different from normal adults, infants, old adults, and individuals with reduced immune function may develop the disease with a small amount of salmonella. Health status plays an important role in whether or not the disease occurs. Some patients with chronic diseases have increased risks of severe salmonellosis. Patients with cirrhosis are also more susceptible to salmonella infection as the gastrointestinal tract circulation disorder or dysfunction caused by cirrhosis results in decreased systemic resistance. In addition, the liver can filter bacteria in the blood in the portal vein from the intestines, and liver dysfunction can cause bacteremia. Communicating branches in the portal vein and hepatic vein can cause the portal vein blood from the intestinal tract directly entering the systemic circulation without filtering through the liver. Moreover, due to portal hypertension during cirrhosis, blood from the intestines can bypass the liver and enter the systemic circulation through the collateral circulation. Therefore, a large number of patients with cirrhosis can develop bacteremia. In various diseases, such as malignant histiocytosis, lymphoma, dermatomyositis, and systemic lupus erythematosus, treatment with adrenocortical hormone can reduce the resistance to various infections, and these patients are susceptible to salmonella infection. Patient with gastric surgery, such as subtotal gastrectomy and gastrointestinal anastomosis, is susceptible to gastroenteritis caused by salmonella, which may be associated with the decrease of gastric acid secretion after surgery, the rapid entry of food into the small intestine and colon, the changes of normal intestinal microflora, the changes of intestinal hydrogen-ion concentration, and the decrease of nutrient absorption after gastrointestinal anastomosis.


Signs and Symptoms

The duration of the incubation period is related to the count of salmonella, pathogenicity, and serovars. After ingestion of food contaminated with salmonella, gastrointestinal symptoms often occur in 8 - 48 hours, and may occur within 12 hours if infected by a large number of bacteria. The incubation period can be up to about 48 hours if infected by few bacteria. The incubation period of enteric fever and bacteremia is up to about 1 to 2 weeks.

Nontyphoidal salmonellosis can be mostly manifested by gastroenteritis, enteric fever, bacteremia, and focal salmonella infection.

Gastroenteritis

Gastroenteritis, also known as salmonella food poisoning, is the most common clinical manifestation, accounting for 70% of nontyphoidal salmonella infection. The incubation period is 6 - 48 hours, minimally 2 hours, maximally up to 3 days. Rapid onset is present, and initial nausea and vomiting are followed rapidly by abdominal cramps and diarrhea. Initial loose stools are followed by a large amount of yellow watery stools, with little or no fecal matter, or occasionally mucoid, bloody, and purulent stools. Bowel movements vary from several times to dozens of times a day. Patients often have fever, and body temperature can reach 38 - 40 °C, probably with chills or shaking chills. The severity of gastroenteritis varies greatly. A small number of patients can have no fever, only with loose stools, whereas in fulminant cases, patients may develop rapidly dehydration, causing shock, kidney failure, and even death due to severe dehydration. This condition is more likely to occur in premature and malnourished infants. Symptoms of gastroenteritis can subside 2 - 3 days after treatment, and occasionally the disease can persist for 2 weeks. The mortality can exceed 1%, and almost all dead patients are infants, old adults, and debilitated patients.

The count of white blood cells in patients is mostly in the normal range, but neutrophil left shift is present. Blood cultures are almost negative in all patients. Pathogens can be isolated and cultured with stools in almost all patients in the acute phase. Pathogen growth in stool culture in about 50% of patients is still visible 2 weeks after gastroenteritis. The common pathogen is salmonella typhimurium. In recent years, the number of reported cases of salmonella typhimurium infection has increased, which has been the main pathogen causing acute food poisoning. In the reported salmonella food poisoning, the most common bacterium is salmonella typhimurium, followed by salmonella enterica.

The incubation period of salmonella typhimurium food poisoning is short, mostly 2 - 24 hours. Clinical manifestations include rapid onset, chills, fever, body temperature generally up to 38 - 39 °C, headache, anorexia, nausea, vomiting, abdominal pain, diarrhea, several to dozens of daily bowel movements, initial loose stools followed by yellow watery stools, mucoid stools, bloody and purulent stools in few patients, and putrid odors. Children patients can have high fever, convulsions, coma, dehydration, circulatory failure, and oliguria or anuria.

Enteric fever

The clinical symptoms are similar to those of mild typhoid fever, but the incubation period is shorter, averagely 3 - 10 days. The duration of the disease is also short, usually 1 - 2 weeks, and the condition is generally mild. Patients present with remittent fever or continuous fever, apathy, relative bradycardia, and occasionally roseola. Diarrhea is more common, but enterorrhagia and enterobrosis rarely occur. Occasionally gastroenteritis can be the premonitory symptoms, and enteric fever is preceded by typical gastroenteritis. The count of white blood cells in the blood is reduced, and pathogen growth can be seen in the blood and stool culture. Enteric fever is usually caused by salmonella enterica.

Bacteremia

Bacteremia is mostly sporadic and is common in children and patients with chronic diseases. Rapid or slow onset is present. Patients present with fever, chills, sweating, and gastrointestinal symptoms. Fever is irregular, remittent, or intermittent, and high fever can last for 1 - 3 weeks. If with complications, such as purulent lesions, fever can persist for a long time, up to several months, or repeatedly recurrent fever can be present. Liver and spleen are often swollen, and occasionally jaundice, deliration, and meningeal irritation can be seen. In most patients, the count of white blood cells is in the normal range. Pathogens grow in blood culture, but stool culture is often negative. Different from persistent bacteremia in typhoid fever, the pathogens intermittently enter the blood circulation. The most common pathogen is salmonella enterica.

Focal salmonella infection

Patients have bacteremia in the past or during hospital admission. During or after fever, one or multiple focal suppurative lesions occur. Mild symptoms or complete absence of symptoms can be present before onset. Suppurative lesions can occur in any part of the body and are the major clinical manifestation. Bronchopneumonia, pulmonary abscess, pleurisy, empyema, endocarditis, pericarditis, pyelonephritis, arthritis, costal cartilage abscess, rib osteomyelitis, and meningitis are more common. In addition, mumps, orchitis, spleen abscess, intraperitoneal abscess, mammary abscess, and subcutaneous abscess have also been reported. The clinical manifestations of patients vary widely, but most patients have a transient increase in body temperature and an increase in the count of peripheral white blood cells. Patients with diseases such as sickle cell anemia are susceptible to focal purulent lesions. Suppurative lesions are more likely to occur in preexisting lesions, such as hematoma, infarction, cysts, neoplasms, and aneurysms. Meningitis caused by salmonella is more common in infants, especially neonates. The clinical manifestations are similar to those of other bacterial meningitis, but the duration of the disease is longer and it is easier to relapse. The mortality rate can reach 40% - 60%. Pneumonia caused by salmonella is more common in older patients, especially those with underlying diabetes, cancer, cardiovascular disease, and chronic lung disease. Pulmonary abscesses may occur, with a high mortality rate of up to 50%.

The four clinical manifestations of salmonella infection are often difficult to distinguish clearly, and they are often accompanied by each other. For instance, gastroenteritis may be accompanied by or followed by bacteremia, and bacteremia is often accompanied by focal suppurative lesions. In addition, salmonella infection can also be manifested by acute genitourinary tract infections. Poultry, livestock, or wild animals can be infected by various salmonella simultaneously, and meat can be contaminated during processing, storage, transportation, and sale, so humans can also be infected by two or more salmonella.


Diagnosis

If patients have a history of ingestion of undercooked meat, eggs, egg products, milk, or milk products, and have clinical manifestations such as gastroenteritis, diarrhea, high fever, and chills, the disease should be suspected.

Bacterial culture can help to diagnose. In recent years, lytic phage test, DNA hybridization, and polymerase chain reaction (PCR) have been introduced in the clinical practices.

Differential diagnosis

Staphylococcus aureus food poisoning

Staphylococcus aureus can produce exotoxins when growing, which can cause food poisoning. The incubation period is short. 1 - 5 hours after ingestion, patients develop nausea and headache, followed by severe abdominal pain and vomiting. The body temperature is mostly normal or only low fever is present. Many bowel movements daily are present, and the stools are yellow watery and usually odorous. Each bowel movement is with a small amount of feces, and rectal tenesmus may be present. Severe patients can be dehydrated due to frequently repeated diarrhea. Staphylococcus aureus can be cultured with the leftover foods and stools.

Vibrio parahaemolyticus food poisoning

Vibrio parahaemolyticus is also known as halophile. The incubation period is 6 - 12 hours. Initial abdominal pain, chills, and fever are followed by severe diarrhea and vomiting. The stools are yellow watery or bloody and may be with some mucus, pus, and blood, with strong odor. Patients have some repeated defecation daily, and each defecation is with a large amount of feces, so patients are susceptible to dehydration. Rectal tenesmus may be present. Vibrio parahaemolyticus growth can be seen in the bacterial culture with stools and leftover foods. The disease is more common in residents or tourists in the coastal areas.

Escherichia coli food poisoning

The pathogen is enterotoxigenic or invasive Escherichia coli, commonly known as Escherichia coli. The incubation period is 2 - 20 hours, usually 4 - 6 hours. Initial anorexia, abdominal pain, and nausea are followed by diarrhea, but vomiting is less common. The stools are mostly yellow watery, with mucus, pus, and blood, with malodor. Patients have many repeated defecations daily, with a large amount of feces. Rectal tenesmus is usually absent. Severe patients can develop dehydration. Enterotoxigenic or invasive Escherichia coli growth can be seen in the bacterial culture with stools and leftover foods.

Clostridium botulinum food poisoning

Clostridium botulinum food poisoning is caused by ingestion of meat contaminated by clostridium botulinum. The incubation period is 2 - 72 hours, mostly 12 - 36 hours. Sudden onset is often present. Initial general malaise, weakness, headache, and dizziness are followed by blurred vision, diplopia, and ophthalmoplegia. Severe patients develop dysphonia, dysphagia, and dyspnea. The body temperature is normal or only low fever is present, and patients are always conscious. Patients can have mild gastrointestinal symptoms, such as nausea, constipation, and abdominal distension, but diarrhea is less common. Clostridium botulinum can be found in the bacterial culture with the leftover foods.

Proteus mirabilis food poisoning

The incubation period is generally 4 - 12 hours. Initial abdominal pain, nausea, and fever are followed by vomiting and diarrhea. The stools are yellow watery. Patients have many bowel movements daily, with a large amount of feces, which can cause dehydration. Rectal tenesmus is often absent. Proteus mirabilis growth can be seen in the bacterial culture with the stools and leftover foods.

Bacterial dysentery

The incubation period is long, usually 1 - 2 days. Patients often present with systemic poisoning symptoms, such as fever, headache, abdominal pain, diarrhea, and general malaise. Vomiting is less common. Repeated defecations are often more than 10 times a day, but a small amount of feces is present in every bowel movement. The stools include mucus, pus, and blood, and obvious rectal tenesmus is present. Shigella can be found in the stool culture.

Cholera

The incubation period is generally 1 - 3 days. Epidemiological clues can often be found. Typical symptoms are diarrhea followed by vomiting. Rice water stools and obvious dehydration are present. Generally fever and abdominal pain are absent in cholera caused by Vibrio cholerae O1, whereas in cholera caused by non-O group 1 Vibrio cholerae, fever, abdominal pain, and bacteremia can often occur, resulting in extraintestinal lesions. Vibrio cholerae can be found in the bacterial culture with the stools.

Chemical food poisoning and gastroenteritis caused by biological toxins

Gastroenteritis caused by chemical poisons such as arsenic, mercury, and organic phosphorus, or biological toxins such as poisonous mushrooms, fish bile, and globefish has a short incubation period, usually several hours. In addition to gastrointestinal symptoms, patients also have clinical manifestations of multiple organ dysfunction syndromes. The toxicant can be detected from the vomitus or stools.


Treatment

Supportive treatment is necessary.

Ciprofloxacin, azithromycin, ceftriaxone, and trimethoprim/sulfamethoxazole (TMP/SMX) are only used in high risk patients and patients with systemic or focal infections

Gastroenteritis caused by salmonella requires symptomatic treatment with oral or intravenous rehydration.

Antibiotics do not accelerate the recovery of the disease and may prolong the elimination time of the bacteria, so patients without complications do not need antibiotics. However, old patients in nursing homes, infants, and HIV-infected patients have a high mortality rate and should be treated with antibiotics.

Antibiotic treatment options include:

  • TMP-SMX 5mg/kg orally once every 12 hours in children
  • Ciprofloxacin 500mg orally once every 12 hours
  • Azithromycin 500mg loading dose followed by 250mg maintenance dose orally once a day for 4 days
  • Ceftriaxone 2g once a day intravenously for 7 - 10 days

Patients without immunodeficiency should be treated for 3 - 5 days, but AIDS patients need long term inhibitory treatment to prevent recurrence.

Systemic or focal infection should be given antibiotics at the same dose as typhoid fever. Persistent bacteremia usually requires treatment for 4 - 6 weeks.

Incision and drainage are required for the treatment of abscess, and at least 4 weeks of antibiotic treatment should be given after surgery.

Infected aneurysms, heart valves, and bone or joint usually require surgical treatment and long term antibiotic treatment.

Asymptomatic carriers are usually self-limiting and seldom require antibiotics. Few patients such as food processors or health care workers can be treated with ciprofloxacin 500mg once every 12 hours for 1 month.


Prognosis

The prognosis of this disease depends on the clinical manifestations, the general condition of the patient, and the serovars of the bacteria. The prognosis of gastroenteritis is generally good, and the mortality rate rarely exceeds 1%, with an average of about 0.3%. Deaths occur mostly in infants, old adults, and patients with severe chronic diseases. Severe systemic infections have a high mortality rate. The mortality rate of sepsis caused by salmonella enterica can be as high as 20%. Patients with meningitis caused by salmonella, especially infants and young children, have a high mortality rate. Endocarditis caused by salmonella enterica has a poor prognosis.


Prevention

It is most important to prevent foods and drink from contamination by infected humans or animals. Undercooked meat should be avoided.