Clostridial necrotizing enteritis (CNE) is a severe and potentially fatal type of

food poisoning Foodborne illness (also known as foodborne disease and food poisoning) is any illness resulting from the contamination of food by pathogenic bacteria, viruses, or parasites, as well as prions (the agents of mad cow disease), and toxins such ...

caused by a

β-toxin ''Clostridium perfringens'' beta toxin is one of the four major lethal protein toxins produced by ''Clostridium perfringens'' Type B and Type C strains. It is a necrotizing agent and it induces hypertension by release of catecholamine. It has be ...

of ''

Clostridium perfringens ''Clostridium perfringens'' (formerly known as ''C. welchii'', or ''Bacillus welchii'') is a Gram-positive, bacillus (rod-shaped), anaerobic, spore-forming pathogenic bacterium of the genus '' Clostridium''. ''C. perfringens'' is ever-present ...

'', Type C. It occurs in some developing regions, particularly in

New Guinea New Guinea (; Hiri Motu: ''Niu Gini''; , fossilized , also known as Papua or historically ) is the List of islands by area, world's second-largest island, with an area of . Located in Melanesia in the southwestern Pacific Ocean, the island is ...

, where it is known as pig-bel. The disease was also documented in

Germany Germany, officially the Federal Republic of Germany, is a country in Central Europe. It lies between the Baltic Sea and the North Sea to the north and the Alps to the south. Its sixteen States of Germany, constituent states have a total popu ...

following

World War II World War II or the Second World War (1 September 1939 – 2 September 1945) was a World war, global conflict between two coalitions: the Allies of World War II, Allies and the Axis powers. World War II by country, Nearly all of the wo ...

, where it was called ''Darmbrand'' (literally translated as "bowel fire"). The toxin is normally inactivated by certain proteolytic enzymes and by normal cooking, but when these protections are impeded by diverse factors, and high protein is consumed, the disease can emerge. Sporadic and extremely rare cases occur in diabetics. In New Guinea, where people generally have low-protein diets apart from tribal feasts, a number of factors—diet and endemic

helminth Parasitic worms, also known as helminths, are a polyphyletic group of large macroparasites; adults can generally be seen with the naked eye. Many are intestinal worms that are soil-transmitted and infect the gastrointestinal tract. Other par ...

infections among them—compound to result in pig-bel.

Preterm infants

The majority of preterm infants who develop NEC are generally healthy, feeding well, and growing prior to developing NEC. The most frequent sign of NEC is a sudden change in feeding tolerance, which can be manifest by numerous clinical signs listed below. While gastric residuals are often seen in early NEC, there is no evidence that routine measurement of gastric residual volumes in asymptomatic infants is a useful guide to prevent or detect the onset of NEC, or help to advance feeds. The timing of the onset of symptoms varies and appears to be inversely related to gestational age (GA). There appears to be a bimodal distribution (early versus late onset) based on GA. For example, the median age at onset of NEC in infants with a GA of less than 26 weeks was 23 days (late), and for those with a GA of greater than 31 weeks, the median age at onset was 11 days (early). Laboratory findings of infants presenting with NEC often include anemia, thrombocytopenia, evidence of disseminated intravascular coagulopathy (DIC), and in 20 percent of cases a positive blood culture.

Signs and symptoms

CNE is a necrotizing inflammation of the small bowel (especially the jejunum but also the ileum). Clinical results may vary from mild diarrhea to a life-threatening sequence of severe abdominal pain, vomiting (often bloody), bloody stool, ulceration of the small intestine with leakage (perforation) into the

peritoneal cavity The peritoneal cavity is a potential space located between the two layers of the peritoneum—the parietal peritoneum, the serous membrane that lines the abdominal wall, and visceral peritoneum, which surrounds the internal organs. While situated ...

and possible death within a single day due to

peritonitis Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and covering of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One pa ...

. Many patients exhibit meteorism (swelling of the abdomen due to excess gas) and fever. Fluid can enter the peritoneum. Sepsis can occur, with one case having 28,500 white blood cells per cubic milliliter.

Causes

All the factors collectively causing CNE are generally only present in the hinterlands of

and parts of

Africa Africa is the world's second-largest and second-most populous continent after Asia. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 20% of Earth's land area and 6% of its total surfac ...

Latin America Latin America is the cultural region of the Americas where Romance languages are predominantly spoken, primarily Spanish language, Spanish and Portuguese language, Portuguese. Latin America is defined according to cultural identity, not geogr ...

, and

Asia Asia ( , ) is the largest continent in the world by both land area and population. It covers an area of more than 44 million square kilometres, about 30% of Earth's total land area and 8% of Earth's total surface area. The continent, which ...

. These factors include protein deprivation (causing inadequate synthesis of the enzyme trypsin protease, to which the toxin is very sensitive), poor food hygiene, episodic meat feasting, staple diets containing

trypsin Trypsin is an enzyme in the first section of the small intestine that starts the digestion of protein molecules by cutting long chains of amino acids into smaller pieces. It is a serine protease from the PA clan superfamily, found in the dig ...

inhibitors (

sweet potatoes The sweet potato or sweetpotato (''Ipomoea batatas'') is a dicotyledonous plant in the morning glory family, Convolvulaceae. Its sizeable, starchy, sweet-tasting tuberous roots are used as a root vegetable, which is a staple food in parts of the ...

), and infection by ''

Ascaris ''Ascaris'' is a nematode genus of parasitic worms known as the "small intestinal roundworms". One species, ''Ascaris lumbricoides'', affects humans and causes the disease ascariasis. Another species, ''Ascaris suum'', typically infects pigs. O ...

'' parasites, which secrete a trypsin inhibitor. In New Guinea (origin of the term "pig-bel"), the disease is usually spread through contaminated meat (especially pork) and perhaps by peanuts. CNE was also diagnosed in post-World War II Germany, where it was known as ''Darmbrand'' or "bowel fire," and reached epidemic proportions. The causative agents of these CNE cases have since been described as Type C isolates of ''C. perfringens'', which possessed genes for β-toxins and enterotoxins. In developed countries, CNE can also occur in people with

diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

, including children. This form of CNE is extremely rare: to demonstrate its scope, only three such cases have been reported in the United States up to 2002.

Diagnosis

An abdominal x-ray shows multiple dilated loops of small bowel and gas. The abdomen can be tender, distended, and soft. A differential diagnosis can be an intussusception.

Treatment

Treatment involves suppressing the toxin-producing organisms with antibiotics such as penicillin G or

metronidazole Metronidazole, sold under the brand name Flagyl and Metrogyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vagino ...

. About half of seriously ill patients require surgery for perforation, persistent intestinal obstruction, or failure to respond to the antibiotics. An investigational toxoid vaccine has been used successfully in some developing countries but is not available outside of research. Antibiotic therapy: For all infants with suspected or established NEC, initiating broad-spectrum antibiotics after obtaining appropriate specimens for culture is a suggested treatment. The empiric antibiotic regimen should provide broad-spectrum coverage, including coverage for common causes of late-onset neonatal sepsis. The choice is also guided by the local susceptibility patterns (i.e., the local antibiogram in a particular neonatal intensive care unit ICU. Acceptable empiric regimens include the following: *Ampicillin plus gentamicin (or amikacin) plus metronidazole *Ampicillin plus gentamicin (or amikacin) plus clindamycin *Ampicillin plus an expanded-spectrum cephalosporin (e.g., cefotaxime here available ceftazidime, or cefepime) plus metronidazole *Monotherapy with piperacillin-tazobactam *Monotherapy with meropenem Vancomycin should be included in the regimen (i.e., replacing ampicillin or added to monotherapy) in centers where there is a high prevalence of methicillin-resistant ''Staphylococcus aureus'' (MRSA) or ampicillin-resistant enterococcal infections. Centers with significant gentamicin resistance patterns should consider amikacin in place of gentamicin. The use of oral aminoglycosides is not recommended because it can result in the development of resistant bacterial strains, and has not been shown to be more beneficial than standard care.

Other clostridial toxemias

Leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...

patients, cancer

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

recipients and others suffering from suppressed

white blood cells White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

(

neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ...

) can be afflicted by a similar syndrome, neutropenic enterocolitis, in which the

cecum The cecum ( caecum, ; plural ceca or caeca, ) is a pouch within the peritoneum that is considered to be the beginning of the large intestine. It is typically located on the right side of the body (the same side of the body as the appendix (a ...

is targeted by '' Clostridium septicum'' in much the same way. * In neonatal

intensive-care unit An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensive care medicine. An inten ...

s, the syndrome of neonatal necrotizing enterocolitis may be caused in a similar way by '' C. perfringens'', '' C. butyricum'', and ''

C. difficile ''Clostridioides difficile'' ( syn. ''Clostridium difficile'') is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as ''C. difficile'', or ''C. diff'' (), and is a Gram-positive spec ...

'', but this has not been proved.

References

External links

{{Digestive system diseases Foodborne illnesses Clostridial infections