Traveler's diarrhea

Traveler's diarrhea Traveler diarrhea (travelersdiarrhea) is defined as three or more unformed feces per day during or after travel, or unformed feces with fever, abdominal pain or vomiting, and even more minor But it is enough to affect the intestinal disorder of the business schedule or travel plan. basic knowledge The proportion of illness: 0.089% Susceptible people: no special people Mode of infection: non-infectious Complications: Reiter syndrome Urethritis Conjunctivitis Thrombotic thrombocytopenic purpura Bacteremia

Traveler's cause of diarrhea

(1) Causes of the disease

There are many causes of DT. It is currently believed that DT is not caused by factors such as climate, food or soil and water. Most of DT is infectious, and its pathogens are bacteria, viruses, parasites, fungi, etc. Occasionally, protozoa and helminth infections have occurred in recent years. With the development and application of microbial identification technology and molecular biology, many new intestinal pathogens have been discovered in the clinic, but 20% to 35% of diarrhea patients still fail to detect the cause, but it is called non-special Heterogenous acute gastroenteritis, the main pathogens of known DT are listed below.

There are different reports on the pathogens, mainly depending on the local pathogenic spectrum, the epidemic bacteria (virus) strain and the immune status of the local population. Worldwide, the production of toxic Escherichia coli (ETEC) is considered to be The most common pathogens account for 40% to 70% (Figure 1), and their high detection rates are particularly high in Africa and Central America. Recently, it has been reported that adhesion-accumulation E. coli (EAEC) is the only one in the world. For ETEC's pathogens of traveller's diarrhea, Shigella is also common worldwide, and Campylobacter jejuni is more common in travelers to Asia, although cholera is an important diarrheal disease in the Indian subcontinent and Latin America. However, it rarely invades travelers. The genus Aeromonas in Thailand is particularly common. In the coastal areas of Southeast Asia, Vibrio parahaemolyticus is more common. Travellers may develop diarrhea due to invasion of viruses, protozoa and worms. Add up to only 10% to 15% of the cause of traveller's diarrhea. Domestic scholars have investigated the pathogens and infection factors of 237 travellers from 18 provinces, municipalities and autonomous regions in China, and detected diarrhea. Species 11 8 strains, the detection rate was 49.79%, causing pathogenic Vibrio, diarrhea-causing Escherichia coli and Proteus, accounting for 52.54% (62/118), 16.95% (20/118) and 13.56%, respectively. (16/118), from 1999 to 2001, a hospital in Barcelona, Spain investigated 863 patients with diarrhea, and 18 (2%) of Aeromonas were detected in 18 patients, which should be paid attention to. The DT caused by the virus has attracted people's attention, especially the DT of children and infants. It is estimated that about 70% of the virus infection is caused. Dupont reports that the pathogen rotavirus of DT in the US to Mexico is 10%.

Mixed infections of various pathogens ranged from 10% to 33%. In Thailand, 33% of 35 cases of DT detected 2 to 4 pathogens, and its significance is still difficult to determine. In addition, 10% to 30% of cases have not been detected. Out of the pathogen, the cause of diarrhea may be changes in eating habits and non-pathogenic factors.

(two) pathogenesis

Bacteria invade intestinal mucosal epithelial cells, causing intestinal mucosal damage, intestinal dysfunction, resulting in diarrhea and water, electrolyte imbalance, TDH and TRH produced by Vibrio parahaemolyticus, heat-resistant enterotoxin and fungi of Yarrowia Toxins cause a series of pathological changes through their target organs, some stimulate the intestinal wall nerve receptors, reflexively cause vomiting, and some cause fever, shock, nervous system symptoms and systemic toxicity.

Most of the pathological changes are seen in the small intestine. The mucosa is hyperemia, edema, inflammatory exudation, necrosis, erosion, but Escherichia coli can invade the colon, causing mucosal congestion, edema, hemorrhage, necrosis, and even ulceration.

Traveler diarrhea prevention

Improve the health awareness of tourists, travel abroad to maintain good personal hygiene habits, ensure that food, drinking water, drinking water and beverages that meet health standards, do not drink raw water, do not eat cold food, fruit should be washed before eating, peeled or Disinfection, utensils, toothbrushes and drinking utensils should be cleaned or disinfected frequently. Wash hands before and after meals and after touching the soil. Avoid overheating or cold when the climate changes. There is no specific medicine to prevent diarrhea. It is reported that large doses are taken every day. Bismuth subsalicylate can significantly reduce the incidence of DT. The mechanism may be that the drug can prevent the pathogens from being adsorbed to the intestinal mucosa. The effect of using the drug solution and tablets in small doses is unknown, but the daily intake is equivalent to 8-12. The amount of aspirin is salicylic, so patients with bleeding disorders should be banned.

Antibiotic prophylaxis is currently a controversial issue. Many well-controlled clinical trials have shown that antibiotics have a good protective effect on travelers' diarrhea; in recent studies, the effective rate is 80% to 90%, but it is generally not recommended. Every passenger uses antibiotics to prevent the growth of pathogenic microorganisms by killing the normal intestinal flora, and the antibiotics are very serious, even fatal adverse reactions, including photosensitivity, antibiotic-associated diarrhea and colitis. Even occasionally, Stevens-Johnson syndrome (type 1 of erosive erythema) can occur, and in addition, the use of these antibiotics on a larger scale can increase drug resistance and reduce the effectiveness of these agents in the treatment of other more serious diseases. Precautionary measures should be taken according to individual circumstances, antibiotic prevention should be used for:

1. Short-term (3 to 5 days) travellers' chances of preventing success will be greatly reduced after 12 to 24 hours of delay.

2. Travelers who participate in official visits who do not strictly follow dietary guidelines for entertainment.

3. Patients with medical conditions Due to acute diarrheal diseases associated with dehydration and acidosis, the overall health of these people will be worse.

4. Patients with lower acid secretion have a poorer gastric acid bactericidal function.

5. Patients with low immunity.

6. Patients with inflammatory bowel disease (such as Crohn's disease, ulcerative colitis) are known.

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, and the facts show that this method is feasible, but Long-term colonization is difficult for existing lactobacilli, and molecular genetics is currently being used to generate strains with longer colonization capabilities (perhaps better therapeutic efficacy), and oral cholera vaccines are now available, the most successful of which The live vaccine is derived from Vibrio cholerae 01, and its gene for the production of cholera toxin and other Vibrio cholera toxin (closed toxin band and paracholinergic toxin) has been knocked out. The oral vaccine currently under development is rotavirus, ETEC, Hemonia and Salmonella.

Traveler diarrhea complications Complication Reiter syndrome urethritis conjunctivitis thrombotic thrombocytopenic purpura bacteremia

1. Occasionally, infectious colitis can be violent and accompanied by a toxic megacolon.

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

3. Systemic invasion of Salmonella can lead to focal infections of bones, joints, meninges and gallbladder.

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

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

6. Very few patients may have bacteremia or metastatic infection, and some patients have malabsorption after several months of diarrhea.

Traveler's diarrhea symptoms Common symptoms Abdominal pain, loose stools, watery stools, disease, toxic diarrhea, dehydration, urgency, heavy mucus, loss of water, bowel

The pathogens causing traveller's diarrhea can be divided into non-invasive and invasive types. Cholera, ETEC, EAEC, viruses and most bacteria causing food poisoning are mostly non-invasive pathogens. Because pathogens are non-invasive, many are not organized. Learning changes, the infection is mainly in the small intestine, so its clinical features are not obvious symptoms of systemic poisoning, no fever or obvious abdominal pain, diarrhea is watery stool, the amount is large, not accompanied by urgency and heavy, easy to lead to water loss and acidosis, within the stool Non-inflammatory cells, the course of disease is generally short, diarrhea caused by invasive pathogens, intestinal lesions are obvious, inflammatory exudate can be discharged, mainly involving the colon, its clinical features are obvious symptoms of systemic toxic blood, fever, abdominal pain and After urgency and urgency, diarrhea is mostly mucus and bloody stools, or bloody watery stools. It is less and less, there are a lot of pus cells and red blood cells during stool examination, and diffuse congestive inflammation and superficial ulcers can be seen by sigmoidoscopy. Shigella, Salmonella, EIEC, Clostridium perfringens, Yersinia, Campylobacter jejuni and certain special viral diarrhea are all of this type.

The same pathogen can have multiple pathogenesis of diarrhea, so its clinical manifestations may overlap or appear successively.

Tourist diarrhea often occurs in the early stages of staying outside, and in the tropics, 62% of patients occur within 1 week and have the highest incidence on day 3.

Tourists' diarrhea is mostly self-limiting. The diarrhea period is usually short-lived. 55% of patients with diarrhea in the tropics and 65% of patients in North America stop diarrhea within 48 hours, while in the subtropical zone, they fluctuate between 42% and 61%. The average diarrhea period was (3.6 ± 0.1) days (median value was 2.3 days), while the average period of thin stools was (2.9 ± 0.3) days (median 2 days). There was no significant difference between different regions in North America. The average diarrhea period was (2.9 ± 0.5) days (median 1.8 days). The above values refer to the results of various treatments. Of the 3,554 patients with diarrhea in the tropics, 918 (26%) were untreated. The average duration of disease was (4.1 ± 0.2) days (median value was 2.4 days). The diarrhea period was significantly shorter in older patients, 4.0 to 4.2 days in patients aged 30 years and younger, and 3.6 days in age from 30 to 39 years old, 39 years old. The above cases ranged from 2.9 to 3.2 days, and mainly in the tropics. The shorter course of the disease was later, and the gender or previous history of tropical tourism had no significant effect on it.

Clinically, if the severity of diarrhea is used to measure the severity of the diarrhea, the diarrhea is usually lighter. More than 75% of tropical diarrhea patients do not have diarrhea more than 5 times a day, and 4.6±0.1 times in the tropics. There were (3.6±0.2) times in North America, no difference in age, and slightly more women than men. The number of trips and the nature of tourism in the same area had no significant effect on the number of diarrhea, and there was no significant correlation between the number of diarrhea and the length of the disease in the tropics. Sexuality, watery stools and non-formation only suggest that the latter often occurs in mild patients. The incidence of abdominal cramps is higher in women with diarrhea in higher incidence areas, when expedition travelers have diarrhea. With more fever symptoms.

Clinically, the thinning stool is not simply a functional disorder. It is similar to the diarrhea of light tourists in terms of symptoms and disease. It is impossible to distinguish between the incidence of diarrhea, the time of onset and the length of the disease. And accompanying symptoms are related to their specific pathogens.

Bloody diarrhea is seen in 10% to 15% of travellers with diarrhea. Fever and abdominal pain are often accompanied by dysentery, but the guidance for the diagnosis of the cause is not significant, the stool is small, the amount is small, and there is mucus and blood, which is mainly invading the colon. Typical manifestations of dysentery microorganisms in the distal ileum, although bloody diarrhea strongly suggests the presence of invasive microorganisms (such as Campylobacter jejuni, Salmonella and Shigella, etc.), but not in this type of infection, so different causes The clinical difference is not reliable.

Persistent diarrhea (Table 4) is rare in travellers. If it occurs, consider Giardia lamblia, cryptosporidiosis, cyclosporosis, possibly roundworm disease, persistent diarrhea. If the intestinal pathogen has not been detected after thorough examination, it may be caused by tropical stomatitis and diarrhea, which is commonly found in the Indian subcontinent, traveled in parts of Southeast Asia and the Caribbean, and is extremely rare in Africa. It is confirmed that irritable bowel syndrome can occur after infection and can persist for several months after an infectious event, most of which is acute, but may last for a long time.

According to the epidemiological history of the tourist destination, the onset season, clinical manifestations and stool characteristics are easy to make a clinical diagnosis, and at the same time, it is necessary to determine whether there is dehydration (degree and nature), electrolyte imbalance and acid-base imbalance, etc., pay attention to find the cause.

Traveler's diarrhea check

1. Fecal white blood cell sorting slide drops 2 drops of methylene blue, the fecal specimens are evenly spread in it, and covered with slides for 2 ~ 3 minutes, microscopic examination, exudative lesions are mainly multinucleated white blood cells, typhoid, allergic reactions are mostly Monocytes.

2. The fecal culture of pathogens for 3 consecutive routine fecal cultures can be repeated if necessary. In the past, the routine detection of Shigella and Salmonella was not enough. Except for the use of disulfide and blood agar medium, it should be based on suspiciousness. The pathogenic bacteria are selected from the corresponding selective medium and culture conditions, anaerobic culture (such as Campylobacter, Clostridium difficile, Clostridium perfringens, etc.), selective medium containing antibiotics (such as Campylobacter), alkaline Or salt-containing medium (such as Vibrio cholerae and other Vibrio), as well as domestically proposed cold-enriched bacteria and alkalized treatment, the disulfide plate is used to detect Yersinia, etc., and the pus and mucus in the feces are selected and inoculated in time. It is best for patients to take antibiotics before sampling, using a variety of special media, culture under different oxygen conditions; picking multiple colonies for various identification is the key to improve the positive culture results, although rotavirus can already Successful separation, but the procedures are cumbersome, the requirements are high, and the detection time is long, which can be done by non-general laboratories.

3. Determination of circulating antibodies Most antibody detection systems (including hemagglutination inhibition, ELISA, etc.) are specific for viruses and bacteria. The changes in serum antibody titers have been used to determine the prevalence of Norwalk-like viruses. Identification of rotavirus and ETEC, but immunofluorescence is prone to cross-reactivity to Giardia lamblia antibodies.

4. Detection of enterotoxin

(1) Biological identification: Identification of ST toxins by intragastric administration of suckling mice (due to its too small molecular weight, other immunodiagnosis is difficult), Aeromonas hydrophila enterotoxin, etc., can also be used in rabbit intestinal secretion test (secretion) In rabbit intestinal loops test) detects ST and LT enterotoxin.

(2) Tissue culture method: It is possible to culture cells with tissue such as Y1 adrenal cells and Chinese voles (CHO) to classify cytotoxin and LT enterotoxin.

(3) Biken test: consisting of the principle of Elek and Ouchtertory experiments, producing LT clones on agar plates, which can form a sedimentation line with anti-cholera antiserum to distinguish enterotoxin.

5. Viral RNA gel electrophoresis can directly extract viral RNA from fecal samples, and use polyacrylamide gel electrophoresis and silver staining to classify and rapidly diagnose rotavirus according to characteristic RNA electrophoresis map.

6. DNA Molecular Hybridization Test The autoradiography radionuclide labeling method was used for the detection of rotavirus, the detection of homologous DNA encoding genes of EIEC enterotoxin, and the like.

7. DNA homology examination Genetic engineering techniques were used to identify pathogenic Vibrio, Escherichia coli enterotoxin-producing plasmids.

8. Electron microscopy and immunoelectron microscopy can directly observe the detection of virus morphology and specific antigen particles. The detection of rotavirus by ELISA has greatly exceeded the electron microscope, but electron microscopy to other diarrhea-causing viruses such as adenovirus, coronavirus, etc. It is still necessary to observe the structure and life cycle of Cryptosporidium. Electron microscopy can obtain a special image for intestinal microbes, but the procedures are too complicated.

9. Immunological examination including ELISA, solid phase radioimmunoassay and reverse passive hemagglutination, for the detection of bacteria, viral antigens, specific antibodies in serum, especially after the application of monoclonal antibodies as diagnostic reagents, greatly improved Sensitivity and accuracy have been used for the detection of Escherichia coli LT enterotoxin, rotavirus, infant diarrhea virus and detection of amoeba, Giardia lamblia antigen, antibodies, etc.

10. Gas chromatographs have been widely used for the identification of anaerobic bacteria, such as for rapid diagnosis of Clostridium difficile.

11. Polymerase chain reaction (PCR) The specific amplification of the target gene of the pathogen is simple, rapid, sensitive, and can be directly used for fecal detection without culture. It is an ideal technique for the diagnosis of infectious diarrhea, especially the pathogen of viral diarrhea. .

12. Chip technology DNA chip technology or gene chip refers to the simultaneous immobilization of an extremely large number of probe molecules onto a solid phase (glass plate or silicon wafer) support, and the sequence information of the DNA sample is made high by virtue of the hybridization pairing characteristics of the nucleic acid molecules. Flux, efficient interpretation and analysis techniques.

(1) The characteristics of DNA chip technology are:

1 Trace (the minimum amount of loading is 0.25~1nl).

2 Large scale, large information reserves (already short arrays of more than 1 million oligonucleotide probes).

3 Parallelization (for example, 300,000 microarray-arranged probes simultaneously hybridize with 10,000 DNAs to be tested to complete hybridization).

4 High efficiency and high degree of automation (due to large information capacity, matrix arrangement, simultaneous detection), operation and operation are fully automated, so the efficiency is extremely high.

(2) The application of DNA chip technology is very extensive, with broad prospects and rapid progress, mainly used in:

1 DNA sequence analysis.

2 gene mutations, gene polymorphism analysis and tumor diagnosis.

3 new drug development and component screening.

4 differential gene expression and analysis of gene expression profiles.

5 experimental diagnosis of pathogenic microorganisms and infectious diseases.

13. T7 ribonuclease-enhanced immunoassay system (IDAT) IDAT (immuno-detection amplified by T RNA polymerase), an immunoassay technology amplified by T7 ribonucleic acid polymerase, by immobilizing a target protein (using a signal It is shown to bind to the antibody and then excite the cocatalyst, which can reactivate T7 ribonuclease polymerase activation, transcribe specific ribonucleic acid molecules (signal molecules) as an indicator system, and the sensitivity of the IDAT method is extremely high (detectable single protein) Molecular), easy to operate (automated), further improved the use of universal probe molecules, it is possible to detect an unlimited number of proteins and lipids, sugar and other cellular molecules, IDAT technology and protein chip technology will push biochip technology to new Levels, early detection of cancer, potential applications for screening important areas such as new drugs and molecular samples.

14. Selective Capture Transcription Sequence Analysis System (SCOTS) SCOTS technology was established in 1999 by Graham and Clark-Curtiss. They jointly studied the reaction of Mycobacterium tuberculosis in human macrophages, and found that DNA repair, nutrient metabolism, and transcription Many genes involved in regulation and virulence production have been transcribed, and Morrow et al. have combined SCOTS and genomic differential hybridization methods to detect some operons and transcriptional regulators in the genome of macrophages. Using SCOTS technology or in line with contemporary new experimental methods, gene expression can be recognized from the genomic level, revealing pathogens such as bacteria entering the body, interaction and infection mechanisms, which will greatly enrich the research content and improve the level of experimental diagnosis.

Traveler Diarrhea Diagnosis

Diagnostic criteria

1.DT diagnostic program

(1) Accurate collection of epidemiological data:

1 Ask the patient about diarrhea before eating, drinking, living and medication.

2 Understand the patient's past illness, bowel habits, work and environmental conditions.

3 to find out the location of the patient, the epidemiological history of diarrhea in the same diet.

4 Understand the pathogenic spectrum of the local circulation, the epidemic strain (virus) strain and the population immune status.

(2) Objective understanding of clinical signs: Focus on the following clinical data:

1 The onset and duration of diarrhea.

2 frequency, traits and time of diarrhea.

3 accompanying symptoms and signs of diarrhea.

4 Abdominal signs include tenderness, rebound tenderness, and bowel sounds.

5 patients' general condition includes consciousness, blood pressure, pulse and skin elasticity.

(3) Reasonable selection of auxiliary laboratory tests: clinicians must personally and carefully observe the fecal traits and changes of patients with diarrhea, rather than relying on laboratory reports, in order to make a correct judgment, such as fecal traits can determine the lesions : watery stool, no urgency, heavy, lesions in the small intestine; mucus, lesions in the colon; mucus with jam-colored blood, lesions in the upper colon; peach red pus and bloody stools, lesions in the lower colon; fecal surface with blood or With obvious urgency and weight, the lesions are mostly in the rectum or the terminal colon. Fecal traits can also determine the nature of the lesion: watery stool, no inflammatory cells, mostly non-invasive lesions; mucus pus and blood, many inflammatory cells, lesions are mostly invasive .

Differential diagnosis

Dysentery: Bacterial dysentery is an intestinal infectious disease caused by dysentery bacilli. Generally, abdominal pain is in the left lower abdomen. It is often followed by urgency and pus and bloody stools. The stool culture is positive. The amoebic trophozoites can be found in the amoebic dysentery.

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