Table 4.

Laboratory Diagnostics for Organisms Associated With Infectious Diarrhea

Etiologic AgentDiagnostic ProceduresOptimal Specimen
Clostridium difficileNAATStool
GDH antigen with or without toxin detection followed by cytotoxin or Clostridium difficile toxin or toxigenic C. difficile strain
Salmonella enterica, Shigella spp, Campylobacter sppRoutine stool enteric pathogen culturea or NAATStool
Salmonella enterica serovars Typhi and Paratyphi (enteric fever)Routine cultureStool, blood, bone marrow, and duodenal fluid
Shiga toxin–producing Escherichia coliCulture for E. coli O157:H7b
and Shiga toxin immunoassay or NAAT for Shiga toxin genes
Stool
Yersinia spp, Plesiomonas spp, Edwardsiella tarda, Staphylococcus aureus, E. coli (enterotoxigenic, enteroinvasive, enteropathogenic, enteroaggregative)Specialized stool culture or molecular assaysc or NAATStool
Clostridium perfringensSpecialized procedure for toxin detectiondStool
Bacillus cereus, S. aureusSpecialized procedure for toxin detectiondFood
Clostridium botulinumMouse lethality assay (performed at a state public health laboratory, or CDC) e,f,gSerum, stool, gastric contents, vomitus
Entamoeba  histolytica; Blastocystis hominih;
Dientamoeba fragilish; Balantidium coli; Giardia lamblia; nematodes (generally not associated with diarrhea) including Ascaris lumbricoides, Strongyloides stercoralisi, Trichuris trichiura, hookworms; cestodes (tapeworms); trematodes (flukes)
Ova and parasite examination including permanent stained smeari or NAATStool
Duodenal fluid for Giardia and Strongyloides
E. histolyticaE. histolytica species-specific
immunoassay or NAAT
Stool
G. lamblia  jEIA or NAATStool
Cryptosporidium spp [11]jDirect fluorescent immunoassay, EIA, or NAATStool
Cyclospora cayetanensis, Cystoisospora bellikModified acid-fast staink performed on
concentrated specimen, ultraviolet fluorescence microscopy, or NAAT
Stool
Microsporidia (now classified as a fungus)Modified trichrome staink performed on
concentrated specimen
Stool
Histologic examination with electron microscopic confirmationSmall bowel biopsy
Calicivirus (norovirus, sapovirus)k; enteric adenovirus; enterovirus/ parechovirusk; rotavirusNAATStool
Rotavirus, enteric adenovirusEIAStool
Enteric adenovirusl; enterovirus/parechovirusViral cultureStool
CytomegalovirusHistopathological examinationBiopsy
Cytomegalovirus cultureBiopsy
Etiologic AgentDiagnostic ProceduresOptimal Specimen
Clostridium difficileNAATStool
GDH antigen with or without toxin detection followed by cytotoxin or Clostridium difficile toxin or toxigenic C. difficile strain
Salmonella enterica, Shigella spp, Campylobacter sppRoutine stool enteric pathogen culturea or NAATStool
Salmonella enterica serovars Typhi and Paratyphi (enteric fever)Routine cultureStool, blood, bone marrow, and duodenal fluid
Shiga toxin–producing Escherichia coliCulture for E. coli O157:H7b
and Shiga toxin immunoassay or NAAT for Shiga toxin genes
Stool
Yersinia spp, Plesiomonas spp, Edwardsiella tarda, Staphylococcus aureus, E. coli (enterotoxigenic, enteroinvasive, enteropathogenic, enteroaggregative)Specialized stool culture or molecular assaysc or NAATStool
Clostridium perfringensSpecialized procedure for toxin detectiondStool
Bacillus cereus, S. aureusSpecialized procedure for toxin detectiondFood
Clostridium botulinumMouse lethality assay (performed at a state public health laboratory, or CDC) e,f,gSerum, stool, gastric contents, vomitus
Entamoeba  histolytica; Blastocystis hominih;
Dientamoeba fragilish; Balantidium coli; Giardia lamblia; nematodes (generally not associated with diarrhea) including Ascaris lumbricoides, Strongyloides stercoralisi, Trichuris trichiura, hookworms; cestodes (tapeworms); trematodes (flukes)
Ova and parasite examination including permanent stained smeari or NAATStool
Duodenal fluid for Giardia and Strongyloides
E. histolyticaE. histolytica species-specific
immunoassay or NAAT
Stool
G. lamblia  jEIA or NAATStool
Cryptosporidium spp [11]jDirect fluorescent immunoassay, EIA, or NAATStool
Cyclospora cayetanensis, Cystoisospora bellikModified acid-fast staink performed on
concentrated specimen, ultraviolet fluorescence microscopy, or NAAT
Stool
Microsporidia (now classified as a fungus)Modified trichrome staink performed on
concentrated specimen
Stool
Histologic examination with electron microscopic confirmationSmall bowel biopsy
Calicivirus (norovirus, sapovirus)k; enteric adenovirus; enterovirus/ parechovirusk; rotavirusNAATStool
Rotavirus, enteric adenovirusEIAStool
Enteric adenovirusl; enterovirus/parechovirusViral cultureStool
CytomegalovirusHistopathological examinationBiopsy
Cytomegalovirus cultureBiopsy

The field of rapid diagnostic testing is rapidly expanding. We expect that additional diagnostic assays will become available following publication of these guidelines, specifically panel-based molecular diagnostics, including NAAT. Contact the laboratory for instructions regarding container, temperature, and transport guidelines to optimize results.

Abbreviations: CDC, Centers for Disease Control and Prevention; EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; NAAT, nucleic acid amplification test.

aRoutine stool culture in most laboratories is designed to detect Salmonella spp, Shigella spp, Campylobacter spp, and E. coli O157 or Shiga toxin–producing E. coli, but this should be confirmed with the testing laboratory.

bIt is recommended that laboratories routinely process all stool specimens submitted for bacterial culture for the presence of Shiga toxin–producing strains of E. coli including O157:H7. However, in some laboratories, O157:H7 testing is performed only by specific request.

cSpecialized cultures or molecular assays may be required to detect these organisms in stool specimens. The laboratory should be notified whenever there is a suspicion of infection due to one of these pathogens.

d  Bacillus cereus, Clostridium perfringens, and Staphylococcus aureus are associated with diarrheal syndromes that are toxin mediated. An etiologic diagnosis is made by demonstration of toxin in stool for C. perfringens and demonstration of toxin in food for B. cereus and S. aureus.

eToxin assays are either performed in public health laboratories or referred to laboratories specializing in such assays.

fTesting for Clostridium botulinum toxin is either performed in public health laboratories or referred to laboratories specializing in such testing. The toxin is lethal and special precautions are required for handling. Class A bioterrorism agent and rapid sentinel laboratory reporting schemes must be followed. Immediate notification of a suspected infection to the state health department is mandated.

gImplicated food materials may also be examined for C. botulinum toxin, but most hospital laboratories are not equipped for food analysis.

hThe pathogenicity of Blastocystis hominis and Dientamoeba fragilis remains controversial. In the absence of other pathogens, they may be clinically relevant if symptoms persist. Reporting semiquantitative results (rare, few, many) may help determine significance and is a College of American Pathologists accreditation requirement for participating laboratories.

iDetection of Strongyloides in stool may require the use of Baermann technique or agar plate culture.

j  Cryptosporidium and Giardia lamblia testing is often offered and performed together as the primary parasitology examination. Further studies should follow if the epidemiologic setting or clinical manifestations suggest parasitic disease.

kThese stains may not be routinely available.

lEnteric adenoviruses may not be recovered in routine viral culture.

Table 4.

Laboratory Diagnostics for Organisms Associated With Infectious Diarrhea

Etiologic AgentDiagnostic ProceduresOptimal Specimen
Clostridium difficileNAATStool
GDH antigen with or without toxin detection followed by cytotoxin or Clostridium difficile toxin or toxigenic C. difficile strain
Salmonella enterica, Shigella spp, Campylobacter sppRoutine stool enteric pathogen culturea or NAATStool
Salmonella enterica serovars Typhi and Paratyphi (enteric fever)Routine cultureStool, blood, bone marrow, and duodenal fluid
Shiga toxin–producing Escherichia coliCulture for E. coli O157:H7b
and Shiga toxin immunoassay or NAAT for Shiga toxin genes
Stool
Yersinia spp, Plesiomonas spp, Edwardsiella tarda, Staphylococcus aureus, E. coli (enterotoxigenic, enteroinvasive, enteropathogenic, enteroaggregative)Specialized stool culture or molecular assaysc or NAATStool
Clostridium perfringensSpecialized procedure for toxin detectiondStool
Bacillus cereus, S. aureusSpecialized procedure for toxin detectiondFood
Clostridium botulinumMouse lethality assay (performed at a state public health laboratory, or CDC) e,f,gSerum, stool, gastric contents, vomitus
Entamoeba  histolytica; Blastocystis hominih;
Dientamoeba fragilish; Balantidium coli; Giardia lamblia; nematodes (generally not associated with diarrhea) including Ascaris lumbricoides, Strongyloides stercoralisi, Trichuris trichiura, hookworms; cestodes (tapeworms); trematodes (flukes)
Ova and parasite examination including permanent stained smeari or NAATStool
Duodenal fluid for Giardia and Strongyloides
E. histolyticaE. histolytica species-specific
immunoassay or NAAT
Stool
G. lamblia  jEIA or NAATStool
Cryptosporidium spp [11]jDirect fluorescent immunoassay, EIA, or NAATStool
Cyclospora cayetanensis, Cystoisospora bellikModified acid-fast staink performed on
concentrated specimen, ultraviolet fluorescence microscopy, or NAAT
Stool
Microsporidia (now classified as a fungus)Modified trichrome staink performed on
concentrated specimen
Stool
Histologic examination with electron microscopic confirmationSmall bowel biopsy
Calicivirus (norovirus, sapovirus)k; enteric adenovirus; enterovirus/ parechovirusk; rotavirusNAATStool
Rotavirus, enteric adenovirusEIAStool
Enteric adenovirusl; enterovirus/parechovirusViral cultureStool
CytomegalovirusHistopathological examinationBiopsy
Cytomegalovirus cultureBiopsy
Etiologic AgentDiagnostic ProceduresOptimal Specimen
Clostridium difficileNAATStool
GDH antigen with or without toxin detection followed by cytotoxin or Clostridium difficile toxin or toxigenic C. difficile strain
Salmonella enterica, Shigella spp, Campylobacter sppRoutine stool enteric pathogen culturea or NAATStool
Salmonella enterica serovars Typhi and Paratyphi (enteric fever)Routine cultureStool, blood, bone marrow, and duodenal fluid
Shiga toxin–producing Escherichia coliCulture for E. coli O157:H7b
and Shiga toxin immunoassay or NAAT for Shiga toxin genes
Stool
Yersinia spp, Plesiomonas spp, Edwardsiella tarda, Staphylococcus aureus, E. coli (enterotoxigenic, enteroinvasive, enteropathogenic, enteroaggregative)Specialized stool culture or molecular assaysc or NAATStool
Clostridium perfringensSpecialized procedure for toxin detectiondStool
Bacillus cereus, S. aureusSpecialized procedure for toxin detectiondFood
Clostridium botulinumMouse lethality assay (performed at a state public health laboratory, or CDC) e,f,gSerum, stool, gastric contents, vomitus
Entamoeba  histolytica; Blastocystis hominih;
Dientamoeba fragilish; Balantidium coli; Giardia lamblia; nematodes (generally not associated with diarrhea) including Ascaris lumbricoides, Strongyloides stercoralisi, Trichuris trichiura, hookworms; cestodes (tapeworms); trematodes (flukes)
Ova and parasite examination including permanent stained smeari or NAATStool
Duodenal fluid for Giardia and Strongyloides
E. histolyticaE. histolytica species-specific
immunoassay or NAAT
Stool
G. lamblia  jEIA or NAATStool
Cryptosporidium spp [11]jDirect fluorescent immunoassay, EIA, or NAATStool
Cyclospora cayetanensis, Cystoisospora bellikModified acid-fast staink performed on
concentrated specimen, ultraviolet fluorescence microscopy, or NAAT
Stool
Microsporidia (now classified as a fungus)Modified trichrome staink performed on
concentrated specimen
Stool
Histologic examination with electron microscopic confirmationSmall bowel biopsy
Calicivirus (norovirus, sapovirus)k; enteric adenovirus; enterovirus/ parechovirusk; rotavirusNAATStool
Rotavirus, enteric adenovirusEIAStool
Enteric adenovirusl; enterovirus/parechovirusViral cultureStool
CytomegalovirusHistopathological examinationBiopsy
Cytomegalovirus cultureBiopsy

The field of rapid diagnostic testing is rapidly expanding. We expect that additional diagnostic assays will become available following publication of these guidelines, specifically panel-based molecular diagnostics, including NAAT. Contact the laboratory for instructions regarding container, temperature, and transport guidelines to optimize results.

Abbreviations: CDC, Centers for Disease Control and Prevention; EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; NAAT, nucleic acid amplification test.

aRoutine stool culture in most laboratories is designed to detect Salmonella spp, Shigella spp, Campylobacter spp, and E. coli O157 or Shiga toxin–producing E. coli, but this should be confirmed with the testing laboratory.

bIt is recommended that laboratories routinely process all stool specimens submitted for bacterial culture for the presence of Shiga toxin–producing strains of E. coli including O157:H7. However, in some laboratories, O157:H7 testing is performed only by specific request.

cSpecialized cultures or molecular assays may be required to detect these organisms in stool specimens. The laboratory should be notified whenever there is a suspicion of infection due to one of these pathogens.

d  Bacillus cereus, Clostridium perfringens, and Staphylococcus aureus are associated with diarrheal syndromes that are toxin mediated. An etiologic diagnosis is made by demonstration of toxin in stool for C. perfringens and demonstration of toxin in food for B. cereus and S. aureus.

eToxin assays are either performed in public health laboratories or referred to laboratories specializing in such assays.

fTesting for Clostridium botulinum toxin is either performed in public health laboratories or referred to laboratories specializing in such testing. The toxin is lethal and special precautions are required for handling. Class A bioterrorism agent and rapid sentinel laboratory reporting schemes must be followed. Immediate notification of a suspected infection to the state health department is mandated.

gImplicated food materials may also be examined for C. botulinum toxin, but most hospital laboratories are not equipped for food analysis.

hThe pathogenicity of Blastocystis hominis and Dientamoeba fragilis remains controversial. In the absence of other pathogens, they may be clinically relevant if symptoms persist. Reporting semiquantitative results (rare, few, many) may help determine significance and is a College of American Pathologists accreditation requirement for participating laboratories.

iDetection of Strongyloides in stool may require the use of Baermann technique or agar plate culture.

j  Cryptosporidium and Giardia lamblia testing is often offered and performed together as the primary parasitology examination. Further studies should follow if the epidemiologic setting or clinical manifestations suggest parasitic disease.

kThese stains may not be routinely available.

lEnteric adenoviruses may not be recovered in routine viral culture.

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