Traveler's diarrhea

　　There are many causes of traveler's diarrhea (DT), and it is currently believed that DT is not caused by factors such as climate, food, or water and soil. The vast majority of DT is infectious, with pathogens including bacteria, viruses, parasites, and fungi. Occasional protozoal and helminthic infections are seen. In recent years, with the development and application of microbiological identification techniques and molecular biology, many new enteric pathogens have been discovered in clinical practice. However, 20% to 35% of diarrhea patients have not been able to detect the cause and are referred to as 'non-specific acute gastroenteritis'. The following lists the main known pathogens of DT.

　　The reports on etiology vary in different regions, mainly depending on the pathogenic bacteria spectrum, prevalent strains of pathogenic bacteria (viruses), and the immune status of the local population. Globally, enterotoxigenic Escherichia coli (ETEC) is considered the most common pathogen, accounting for 40% to 70% of cases, with particularly high detection rates in Africa and Central America. Recent reports indicate that attaching and effacing Escherichia coli (EAEC) is the second most common pathogen causing traveler's diarrhea worldwide, after ETEC. Shigella species are also quite common globally, while Campylobacter jejuni is more prevalent among travelers to Asia. Although cholera is an important diarrheal disease in the Indian subcontinent and Latin America, it rarely affects travelers. The Aeromonas genus is particularly common in Thailand. In coastal areas of Southeast Asia, Vibrio parahaemolyticus is more prevalent. Travelers may occasionally experience diarrhea due to viral, protozoal, and helminthic invasions, but together they account for only 10% to 15% of the causes of traveler's diarrhea. Chinese scholars have conducted an etiological and infection factor survey on 237 cases of traveler's diarrhea patients from 18 provinces, municipalities, and autonomous regions across the country, detecting 14 species of enterotoxigenic bacteria in 118 strains, with a detection rate of 49.79%, mainly including pathogenic vibrios, enterotoxigenic Escherichia coli, and proteobacteria.

　　Diarrhea caused by mixed infection of multiple pathogens accounts for 10% to 33%, in 35 cases of DT, 33% of the cases were detected with 2 to 4 types of pathogens, and its significance is yet to be determined. In addition, 10% to 30% of the cases were not detected with pathogens, and the cause of diarrhea may be changes in dietary habits and non-pathogenic factors.

　　The complications of traveler's diarrhea often vary depending on the cause of the disease.

　　1, Occasionally, infectious colitis can have an explosive onset, accompanied by toxic megacolon.

　　2, Associated arthritis or Reiter syndrome (non-gonococcal arthritis, conjunctivitis, urethritis) can be complicated by invasive diarrhea, especially when the cause is Campylobacter jejuni or Yersinia enterocolitica.

　　3, Systemic invasion of Salmonella can lead to focal infections of bone, joint, meninges, and gallbladder.

　　4, Guillain-Barré syndrome (acute infectious polyradiculoneuritis) is a complication of Campylobacter infection.

　　5, EHEC infection can be complicated by hemolytic uremic syndrome and thrombotic thrombocytopenic purpura.

　　6, A small number of patients may develop bacteremia or metastatic infection. Some patients may experience persistent malabsorption for several months after diarrhea.

　　Pathogens causing traveler's diarrhea can be divided into non-invasive and invasive types. Cholera, ETEC, EAEC, viruses, and most bacteria causing food poisoning belong to non-invasive pathogens. Since the pathogens are non-invasive, there are usually no histological changes, and their infection mainly occurs in the small intestine. Therefore, their clinical features are not obvious systemic toxic symptoms, without fever or marked abdominal pain, diarrhea is watery and abundant, without tenesmus, prone to dehydration and acidosis, no inflammatory cells in the stool, and the course of the disease is generally short. Diarrhea caused by invasive pathogens has obvious intestinal lesions, can excrete inflammatory exudates, mainly affecting the colon. The clinical features are more obvious systemic toxic symptoms, with fever, abdominal pain, and tenesmus, diarrhea is mostly mucous or bloody stool, or bloody watery stool, frequent defecation but small amount. During stool microscopy, there are a large number of pus cells and red blood cells, and sigmoidoscopy can show diffuse hyperemic inflammation and superficial ulcers, etc. Shigella, Salmonella, EIEC, Clostridium perfringens, Yersinia, Campylobacter jejuni, and some special viral diarrhea all belong to this type. The same pathogen can be involved in various pathogenic mechanisms of diarrhea, so the clinical manifestations can appear simultaneously or sequentially.

　　To prevent traveler's diarrhea, it is necessary to improve the health awareness of travelers, maintain good personal hygiene habits when traveling, and ensure the hygiene of food and drinking water. Drink water and beverages that meet hygiene standards, do not drink unboiled water, do not eat raw and cold food, and wash, peel, or disinfect fruits before eating. Utensils, toothbrushes, and drinking utensils should be cleaned or disinfected regularly. Wash hands before meals, after using the toilet, and after touching dirty objects. Avoid overheating or catching a cold during changes in weather. There is currently no specific drug for preventing diarrhea. It has been reported that taking a large dose of bismuth subsalicylate daily can significantly reduce the incidence of DT, and the mechanism may be that the drug can prevent pathogens from adhering to the intestinal mucosa. The efficacy of using the drug in small doses is unclear. However, in view of the fact that 8-12 tablets of aspirin equivalent amount of salicylic acid needs to be ingested daily, patients with hemorrhagic diseases should avoid using it.

　　The concept of using harmless microorganisms (such as Lactobacillus, Bifidobacterium) to colonize the intestines to inhibit the growth of pathogenic microorganisms has existed for decades. It has been proven that this method is feasible, but it is difficult for the existing lactobacilli to colonize for a long time. Molecular genetic methods are currently being used to generate strains with longer colonization ability (and perhaps better therapeutic efficacy). There is now an oral cholera live vaccine, the most successful live vaccine of which is derived from Vibrio cholerae 01, with the genes that produce cholera toxin and other Vibrio cholerae toxins (blocking toxins and paracolera enterotoxin) knocked out. Currently, oral vaccines under development include rotavirus, ETEC, Shigella, and Salmonella.

　　The clinical examination of traveler's diarrhea is mainly aimed at the identification of the infecting pathogen.
　　First, laboratory examination
　　1. Fecal leukocyte classification:Two drops of methylene blue are dripped under the slide, and the fecal specimen is spread evenly in it. After covering the slide for 2-3 minutes, examine it under the microscope. The exudative lesions are mainly polymorphonuclear leukocytes, while typhoid and allergic reactions are mostly monocytes.
　　2. Fecal culture pathogenic bacteria:Three consecutive routine fecal cultures can be repeated if necessary. The conventional detection of Shigella and Salmonella is no longer sufficient. In addition to using thiosulfate and blood agar media, selective media and culture conditions should be selected according to the suspected pathogenic bacteria, including anaerobic culture (such as Campylobacter, Bacteroides fragilis, Clostridium perfringens, etc.), selective media containing antibiotics (such as Campylobacter), alkaline or salt-containing media (such as Vibrio cholerae and other Vibrio species), as well as the cold enrichment and alkalization treatment followed by thiosulfate plate detection of Yersinia proposed by China. Select the pus and mucus parts from the feces and inoculate them in time; it is best to take samples before the patient takes antibacterial drugs. Cultivate with a variety of special media under different oxygen conditions; pick multiple colonies for various identifications, which is the key to improving positive culture results. Rotavirus can be successfully isolated, but the procedure is繁琐, requires high conditions, takes a long time to detect, and cannot be completed by general laboratories.
　　3, Determination of circulating antibodies:Most antibody detection systems (including hemagglutination inhibition method, ELISA method, etc.) are specific for viruses and bacteria. The changes in serum antibody titer have been used to determine the prevalence of Norwalk-like viruses, the identification of rotavirus and enterotoxigenic Escherichia coli (ETEC). However, immunofluorescence is prone to cross-react with Giardia lamblia antibodies.
　　4, Detection of enterotoxins:
　　(1) Biological identification: The guinea pig gavage method is used to identify ST toxin (due to its small molecular weight, other immunodiagnosis is difficult), Aeromonas hydrophila enterotoxin, etc. The secretion test of the rabbit ileal loop can also be used to detect ST and LT enterotoxins.
　　(2) Tissue culture method: It has been able to use Y1 adrenal cells, Chinese hamster ovary cells (CHO), and other tissue culture cells to classify cytotoxins and LT enterotoxins.
　　(3) Biken test: It is composed of the principles of Elek and Ouchterlony tests. LT clones are produced on agar plates, which can form precipitation lines with anticholera serum to distinguish enterotoxins.
　　5, Virus RNA gel electrophoresis:It can directly extract virus RNA from fecal specimens, use polyacrylamide gel electrophoresis and silver staining method, and classify and rapidly diagnose rotavirus according to the characteristic RNA electrophoresis pattern.
　　Second, other auxiliary examinations
　　1, Electron microscopy and immunoelectron microscopy examination:It can directly observe the morphology of viruses and the detection of specific antigen particles. Although the detection of rotavirus by ELISA has greatly exceeded that by electron microscopy, electron microscopy is still needed for other diarrhea-causing viruses such as adenovirus, coronavirus, etc. The structure and life cycle of Cryptosporidium can be observed, and electron microscopy scanning can obtain special images of intestinal microorganisms, but the procedure is too complicated.
　　2, Immunological examination:It includes ELISA, solid-phase radioimmunoassay, and reverse passive hemagglutination method. It is used to detect bacterial and viral antigens in feces and specific antibodies in serum. Especially since the application of monoclonal antibodies as diagnostic reagents, it has greatly improved sensitivity and accuracy and has been used for the identification of Escherichia coli LT enterotoxin, rotavirus, infantile diarrhea virus, and the detection of amebae, Giardia lamblia flagellate antigens, and antibodies, etc.
　　3, Gas Chromatography:It has been widely used in the identification of anaerobic bacteria, such as for the rapid diagnosis of Clostridium difficile.
　　4, Polymerase Chain Reaction (PCR):Specific amplification of pathogen target genes is simple, fast, and sensitive, and can be used directly for fecal detection without culture, which is an ideal technology for the diagnosis of infectious diarrhea, especially viral diarrhea pathogens.
　　5, Chip technology:DNA chip technology or gene chip refers to the technology of simultaneously fixing an extremely large number of probe molecules to a solid-phase support (glass slide or silicon wafer), and using the characteristic of nucleic acid molecule hybridization pairing to decode and analyze the sequence information of DNA samples in a high-throughput and efficient manner.

　　After the patient's diarrhea subsides, they still need to pay more attention to their diet.

　　1. Choose easily digestible liquid foods such as vegetable soup, thin porridge, egg soup, egg custard, milk, etc.

　　2. Diet should be light and non-greasy, meeting the nutritional needs while also increasing appetite. White rice porridge, millet porridge, adzuki bean porridge, and small dishes such as sweet preserved vegetables, turnips, pickled radishes, or tofu sauce can be provided, with a preference for light and refreshing flavors.

　　3. Ensure adequate water intake, and drink more acidic fruit juices such as hawthorn juice, kiwi juice, jujube juice, fresh orange juice, watermelon juice, etc., to promote the secretion of gastric juice and increase appetite.

　　4. Eat more foods rich in vitamin C, E, and red foods such as tomatoes, apples, grapes, jujube, strawberries, beets, oranges, watermelons, and milk, eggs, etc.

　　Traveler's diarrhea (DT) is usually a self-limiting disease that does not require special treatment and can heal spontaneously. However, oral rehydration and intravenous fluid administration help to replenish the lost water and electrolytes. Most patients do not become rapidly dehydrated, so mineral water (hypotonic liquid containing glucose) is usually sufficient to meet the needs for water and electrolytes. The following is a simple electrolyte solution recipe: 1000ml of water plus 1 tablespoon of salt, 1 tablespoon of baking soda, and 4 tablespoons of sugar; 1000ml of water plus 1 tablespoon of salt and 8 tablespoons of sugar. Both formulas can be added with a small amount of apple juice, orange juice, or honey for seasoning. When travelers have diarrhea, they should fast for 8-12 hours (if infants or young children, they should still try to feed simple food), and replenish electrolyte solution, do not drink milk, and after symptoms improve, they can drink clear meat soup, light food, avoiding vegetables and fruits; after that, they can increase lean meat, boiled eggs, and other foods; if there is gastrointestinal cramping, a hot water bottle can be applied to the abdomen to improve the cramping condition. Many patients do not need other treatments.
　　Severe cases should be hospitalized for treatment. During treatment, attention should be given to the type of diarrhea, with emphasis on the treatment. Secretory diarrhea is mainly treated with fluid replacement therapy, with etiological treatment as a supplement; for invasive diarrhea, in addition to fluid replacement, active etiological treatment is also required.
　　1. For bacterial diarrhea, fluoroquinolone antibiotics are commonly used. Microecological therapy helps restore the ecological balance of the normal intestinal flora, inhibit the colonization and invasion of pathogenic bacteria, and is conducive to controlling diarrhea, commonly using bifidobacteria, lactic acid bacteria, and streptococcus faecalis preparations. Intestinal mucosal protective agents can adsorb pathogens and toxins, maintain the absorption and secretion function of intestinal cells, and interact with intestinal mucus glycoproteins to enhance their barrier function, preventing attacks by pathogenic microorganisms, such as octahedral montmorillonite (Smecta). Antidiarrheal drugs include intestinal motility inhibitors, opiate drugs (such as loperamide) acting on the opiate receptors of the intestinal wall, blocking the release of acetylcholine and prostaglandins, thereby inhibiting intestinal motility. Through the indirect effect of enhancing Na+-Cl- cotransport or the direct effect of inhibiting secretion induced by calcium-dependent secretagogues, it reduces the loss of water and electrolytes. This drug has strict indications and contraindications and should be taken under the guidance of a doctor. In addition, there are astringents (such as bismuth subsalicylate, activated carbon) and antiserous secretion drugs, etc.
　　2. For DT caused by cryptosporidium, cyclospora, isospora, etc., if the patient's immune function is intact, the symptoms are usually mild, and it is generally not necessary to take chemical drugs. Supportive and symptomatic treatment is sufficient.
　　3. For DT caused by fungi, active antibacterial treatment should be carried out in addition to supportive and symptomatic treatment.
　　For all travelers who are about to enter high-risk diarrhea areas, it is necessary to provide them with guidance on self-medication. Special medication should be determined according to the region, season, and age of the traveler. In areas where resistance to trimethoprim (TMP) by enteric pathogens is uncommon, sulfamethoxazole/trimethoprim tablets should be the first choice for treatment. If traveling in areas where resistance to trimethoprim (TMP) by enteric pathogens is very common (such as South America and South Asia, etc.), it is necessary to carry fluoroquinolone antibacterial drugs, any of which is a fluoroquinolone. If travelers expect to receive the most satisfactory self-treatment, they should also carry loperamide (chlorophenylpiperazine), bismuth subsalicylate, and a thermometer in their portable medicine kit. In special cases, two other drugs used are furazolidone and metronidazole (灭滴灵). Furazolidone has antibacterial effects on many enteric pathogens (such as Shigella, Salmonella, enterotoxic Escherichia coli, bacteria resistant to trimethoprim, etc.) and Giardia lamblia, and can be replaced by suspension for infants who cannot take tablets.