Introduction

If you’ve ever had food poisoning then you have a good idea of the symptoms even before visiting a hospital. These symptoms include diarrhoea, abdominal cramps, vomiting and nausea. One of the most common culprits of food poisoning is an organism called Salmonella. This organism causes salmonellosis, which is obtained through the consumption of contaminated or undercooked foods like chicken, eggs, unpasteurised milk and cheese. It can also cause typhoid and paratyphoid fever. 

Beyond the intestine, Salmonella can cause disseminated diseases (spread throughout the body) or infections. These infections can be insidious and severe, especially if this organism invades the internal organs. This article will unravel the ways in which Salmonella infections can manifest beyond the intestine.

What is Salmonella?

Salmonella are a group of gram-negative, non-spore producing, facultative anaerobic bacteria that belong to the family Enterobacteriaceae.¹ Within the Salmonella family, there are about 2600 types identified. Most of these types can adapt within a variety of animal hosts, including humans.² 

Diseases caused by this organism are grouped into typhoidal salmonellosis (enteric or typhoid fever) and non-typhoidal Salmonella associated infections (NTS).³ 

Typhoid only occurs in humans, however, NTS affects a range of host vertebrates.⁴ NTS presents a more chronic and invasive effect, particularly in immunocompromised adults, including those with human immunodeficiency virus (HIV).⁴ 

Two main species of the Salmonella family are Salmonella enterica (serotypes Typhi and Paratyphi A, B and C) and Salmonella bongori.⁵

Both typhoidal and non-typhoidal Salmonella can cause extraintestinal (outside of the gastrointestinal tract) manifestations. Unfortunately, these extraintestinal manifestations are often underdiagnosed and underreported. This is mostly because they are not suspected. Among all the Salmonella species, Salmonella typhi is the most frequent cause of extraintestinal infections.⁶

How do Salmonella infections manifest beyond the intestine?

The root cause of extraintestinal manifestations of Salmonella infection is via infectious complications that occur with Salmonella typhi infection (i.e. typhoid fever).⁷ Typhoid fever occurs more commonly in people who live in or visit developing countries where there is poor sanitation and faecal contamination of water and food.⁷

The pathogenesis (how the disease develops) of extraintestinal infectious complications of typhoid fever depends on the following:⁸

• The ingested concentration of S. typhi
• Virulence of the strain
• Immune response of the host
• Available protective factors 

S. typhi is released into the blood once a threshold is reached and this initiates a secondary bacteremia which can affect internal organs.⁸ This bacteremia (bacteria in the blood) results in the following extraintestinal manifestations: 

Central nervous system (brain and spinal cord)

S. typhi infection of the central nervous system (CNS) occurs in 3-35% of affected individuals. The manifestations in the CNS include:⁹

• Encephalopathy 
• Meningitis 
• Ataxia 
• Cerebral oedema 
• Seizures 
• Guillain-Barre Syndrome 

Risk factors that trigger nervous system involvement include:¹⁰

• Meningitis 
• Endocarditis 
• Pulmonary infections 
• Congenital heart disease

Salmonella meningitis occurs mostly in neonates and infants with high morbidity and mortality. A reported case study resulted in the death of an 18-month-old baby girl despite continued treatment with recommended antibiotics on the fourth day of admission.⁶

Cardiovascular system (the heart)

Cardiac complications caused by Salmonella infections such as myocarditis and endocarditis occur in 1-5% of those affected. Most people with infectious cardiac complications have underlying cardiac issues such as rheumatic heart disease or congenital heart defects.⁶ 

Salmonella also causes other cardiac infections such as salmonella coronary arteritis and infection of the cardiac pacemaker with Salmonella typhimurium.¹¹

Respiratory system (the lungs)

People with pulmonary manifestations due to severe typhoid fever usually have one of the below:⁷

• Underlying lung abnormalities 
• A previous history of lung infection
• Sickle cell anaemia 
• Alcohol abuse disorder
• Diabetes 
• HIV/AIDS 

The occurrence of respiratory complications is about 1-6%. Complications such as pneumonia and empyema can occur in roughly 10% of immunocompromised individuals.¹²

Musculoskeletal system (bones, joints and muscles)

Salmonella can manifest in musculoskeletal problems, such as:⁶

• Salmonella osteomyelitis: Salmonella infection in the bones
• Salmonella septic arthritis: Salmonella infection in the joints 
• Pyomyositis: Salmonella infection in the muscles

Perhaps surprisingly, the spine is a commonly affected site in salmonella osteomyelitis. This can either be by haematogenous or contiguous spread.¹³

The occurrence of osteomyelitis is less than 1% of all Salmonella infections. Three case studies were reported about three individuals who were diagnosed with salmonella osteomyelitis, salmonella septic arthritis and salmonella pyomyositis in a hospital. 

On subsequent follow-up after 2 months and 6 months after discharge, the individuals were discovered to be symptom-free.⁶

Genitourinary system (the urinary tract, kidneys, bladder and pelvic region)

S. typhi extraintestinal infection of the genitourinary system occurs rarely, even in endemic areas (less than 1%).⁷ Risk factors for genitourinary involvement include underlying functional abnormalities of the urinary tract, bladder, and pelvic organs. 

Predisposing aetiologies are:⁷ 

• Congenital abnormalities 
• Pyelonephritis 
• Chronic salpingitis 
• Dermoid cyst 
• Renal transplant 

However, upper urinary tract infections, particularly pyelonephritis, account for most of these infections.¹¹

A case study was reported about an individual who developed salmonella pyelonephritis with recurrent episodes of burning micturition (burning sensation when passing urine). 

However, subsequent follow-up revealed that the individual has been symptom-free after 6 months.⁶

What treatment options are available?

Antibiotics used for typhoid fever and its manifestations include:¹⁴

• Chloramphenicol 
• co-trimoxazole (trimethoprim-sulfamethoxazole) 
• Ampicillin 
• Azithromycin 
• Furazolidone
• Aztreonam
• Carbapenems 

The use of chloramphenicol is reserved for the treatment of serious infections caused by S. typhi when the less toxic antimicrobials are ineffective.¹⁴ 

Salmonella osteomyelitis sometimes requires thorough surgical debridement combined with 4 weeks of intravenous antibiotics.⁷ 

For those with CNS involvement caused by S. typhi, surgical procedures may be needed (such as drainage of pus) along with antibiotics that have good passage across the blood-brain barrier.⁷ 

FAQs

How does Salmonella affect animals? 

Salmonella lives in the gut of different animals such as birds, reptiles and amphibians without causing illness. Most animals infected with Salmonella do not show signs of disease. When they do, visible signs depend on the age and type of animal infected. 

The disease is usually more severe in young or pregnant animals. Signs of infection include abdominal pain, fever, foul-smelling diarrhoea and dehydration.

What are the signs and symptoms of Salmonellosis? 

Salmonellosis is a form of gastroenteritis commonly known as food poisoning. People infected with Salmonella develop symptoms 12-72 hours after infection. The symptoms include: 

• Diarrhoea 
• Fever 
• Abdominal cramps or aches
• Blood in urine or stool

How do you diagnose Salmonella infections?

Salmonella infection is diagnosed through laboratory tests that detect Salmonella in stool, body tissue or fluid samples. The test could be a microbial culture that isolates the bacteria or a culture-independent technique that can detect the genetic material of the bacteria.

Can you prevent extraintestinal manifestations of Salmonella infections? 

Prevention of extraintestinal involvement is rooted in avoiding the progression of typhoid fever. Additionally, it is recommended to follow safe food and water precautions, avoid consuming untreated water and undercooked or raw meat, eggs and dairy products. 

Practice of good hand hygiene and ensuring proper handling of pets and animals are also advised to avoid contracting Salmonella infection that can progress to extraintestinal manifestations. 

Summary

• Salmonella infection can progress to extraintestinal infections in various organs such as the joints, muscles, spine, brain, and heart, amongst others
• The primary mode of transmission for Salmonella is faecal-oral which can lead to gastroenteritis 
• Salmonella osteomyelitis is the most common extraintestinal manifestation of Salmonella, while others such as salmonella meningitis, myocarditis and endocarditis are not widely prevalent
• Salmonella meningitis is the most severe form of extraintestinal manifestation and can lead to death 
• The possibility of severe multisystem involvement when it comes to extraintestinal manifestations of Salmonella infection should be put into consideration for early diagnosis to avoid progression to severity and subsequent life-threatening complications