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Clostridial necrotizing enteritis (CNE) is a severe and potentially fatal type of
food poisoning Foodborne illness (also foodborne disease and food poisoning) is any illness resulting from the spoilage of contaminated food by pathogenic bacteria, viruses, or parasites that contaminate food, as well as prions (the agents of mad cow disea ...
caused by a β-toxin of ''
Clostridium perfringens ''Clostridium perfringens'' (formerly known as ''C. welchii'', or ''Bacillus welchii'') is a Gram-positive, rod-shaped, anaerobic, spore-forming pathogenic bacterium of the genus '' Clostridium''. ''C. perfringens'' is ever-present in nature an ...
'', Type C. It occurs in some developing regions, particularly in
New Guinea New Guinea (; Hiri Motu: ''Niu Gini''; id, Papua, or , historically ) is the world's second-largest island with an area of . Located in Oceania in the southwestern Pacific Ocean, the island is separated from Australia by the wide Torr ...
, where it is known as pig-bel. The disease was also documented in
Germany Germany, officially the Federal Republic of Germany (FRG),, is a country in Central Europe. It is the most populous member state of the European Union. Germany lies between the Baltic and North Sea to the north and the Alps to the sou ...
following
World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the World War II by country, vast majority of the world's countries—including all of the great power ...
, where it was called ''Darmbrand'' (literally "bowel fire," or bowel necrosis). 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 large macroparasites Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adap ...
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 between the parietal peritoneum (the peritoneum that surrounds the abdominal wall) and visceral peritoneum (the peritoneum that surrounds the internal organs). The parietal and visceral peritonea are lay ...
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 cover of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One part or ...
. Many patients exhibit
meteorism Tympany or tympanites (sometimes tympanism or tympania), also known as meteorism (especially in humans), is a medical condition in which excess gas accumulates in the gastrointestinal tract and causes abdominal distension. The term is from the ...
(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
New Guinea New Guinea (; Hiri Motu: ''Niu Gini''; id, Papua, or , historically ) is the world's second-largest island with an area of . Located in Oceania in the southwestern Pacific Ocean, the island is separated from Australia by the wide Torr ...
and parts of
Africa Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...
,
Latin America Latin America or * french: Amérique Latine, link=no * ht, Amerik Latin, link=no * pt, América Latina, link=no, name=a, sometimes referred to as LatAm is a large cultural region in the Americas where Romance languages — languages derived ...
, and
Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an ...
. 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 these long chains of amino acids into smaller pieces. It is a serine protease from the PA clan superfamily, found in the d ...
inhibitors (
sweet potatoes The sweet potato or sweetpotato (''Ipomoea batatas'') is a dicotyledonous plant that belongs to the bindweed or morning glory family, Convolvulaceae. Its large, starchy, sweet-tasting tuberous roots are used as a root vegetable. The young sho ...
), and infection by ''
Ascaris ''Ascaris'' is a genus of parasitic nematode worms known as the "small intestinal roundworms", which is a type of parasitic worm. One species, ''Ascaris lumbricoides'', affects humans and causes the disease ascariasis. Another species, ''Ascari ...
'' 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, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
, 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 Intussusception may refer to: * Intussusception (medical disorder) Intussusception is a medical condition in which a part of the intestine folds into the section immediately ahead of it. It typically involves the small bowel and less commonly t ...
.


Treatment

Treatment involves suppressing the toxin-producing organisms with antibiotics such as penicillin G or
metronidazole Metronidazole, sold under the brand name Flagyl 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 vaginosis. It is e ...
. 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 (ie, the local antibiogram in a particular neonatal intensive care unit
ICU ICU commonly refers to: * Intensive care unit, a special department of a hospital ICU may also refer to: Organisations Universities * Information and Communications University, South Korea *Istanbul Commerce University, Istanbul, Turkey * Intern ...
. Acceptable empiric regimens include, but are not limited to, the following: •Ampicillin plus gentamicin (or amikacin) plus metronidazole •Ampicillin plus gentamicin (or amikacin) plus clindamycin •Ampicillin plus an expanded-spectrum cephalosporin (eg, cefotaxime
here available Here is an adverb that means "in, on, or at this place". It may also refer to: Software * Here Technologies, a mapping company * Here WeGo (formerly Here Maps), a mobile app and map website by Here Television * Here TV (formerly "here!"), a ...
ceftazidime, or cefepime) plus metronidazole •Monotherapy with piperacillin-tazobactam •Monotherapy with meropenem Vancomycin should be included in the regimen (ie, 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 and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
patients, cancer
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
recipients and others suffering from suppressed
white blood cells White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
(
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 bacteri ...
) can be afflicted by a similar syndrome,
neutropenic enterocolitis Neutropenic enterocolitis is inflammation of the cecum (part of the large intestine) that may be associated with infection. It is particularly associated with neutropenia, a low level of neutrophil granulocytes (the most common form of white blood ...
, in which the
cecum The cecum or caecum 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, to which it is joined). The w ...
is targeted by '' Clostridium septicum'' in much the same way. * In neonatal intensive-care units, the syndrome of
neonatal necrotizing enterocolitis Necrotizing enterocolitis (NEC) is a devastating intestinal disease that affects premature or very low birth weight infants.Gephart S.M., Quinn M. A call to action to fight for equity and end necrotizing enterocolitis disparities. ''Adv. Neonata ...
may be caused in a similar way by '' C. perfringens'', '' C. butyricum'', and ''
C. difficile ''Clostridioides difficile'' ( syn. ''Clostridium difficile'') is a bacterium that is well known for causing serious diarrheal infections, and may also cause colon cancer. Also known as ''C. difficile'', or ''C. diff'' (), is Gram-positive spe ...
'', but this has not been proved.


See also

* Protein poisoning refers to a different diet-induced phenomenon.


References

* * * * Nuland, Sherwin B., “The Beast in the Belly”, ''
Discover Discover may refer to: Art, entertainment, and media * ''Discover'' (album), a Cactus Jack album * ''Discover'' (magazine), an American science magazine Businesses and brands * DISCover, the ''Digital Interactive Systems Corporation'' * ...
'', Vol. 16 No. 02 (February 1995).


External links

{{Digestive system diseases Foodborne illnesses Clostridial infections