Helicobacter pylori infection in children

Introduction to Helicobacter pylori infection in children Since Australian scholars Marshall and Warren successfully isolated and cultured Helicobacter pylori (Hp) from the gastric mucosa of patients with chronic gastritis in 1982, a large number of studies from adults have confirmed that Hp is associated with many upper gastrointestinal diseases, and Hp is chronic activity. The main pathogenic factor of gastritis is an important factor in the pathogenesis of peptic ulcer. The long-term infection of Hp is also associated with the occurrence of gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Clinical studies have found that eradication of Hp can significantly reduce the recurrence rate of peptic ulcer disease, and can also reverse or even disappear the course of gastric MALT lymphoma. It can also improve the symptoms of refractory dyspepsia in some patients with chronic gastritis. It can be said that the discovery and research of Hp has pushed the diagnosis and treatment level of gastrointestinal diseases to a new level. basic knowledge The proportion of illness: 0.005% Susceptible people: children Mode of infection: non-infectious Complications: anemia, peptic ulcer, atrophic gastritis, gastric cancer, gastric ulcer, duodenal ulcer, abdominal pain, bloating

Causes of Helicobacter pylori infection in children

Cause:

A large amount of data currently supports Hp as a pathogen of chronic gastritis. Since Hp enters the body and mainly settles in the gastric mucosa, the detection rate of Hp in patients with chronic gastritis is high, and almost no Hp is detected in normal gastric mucus. In addition, gastric mucus is found. The number of Hp colonization is directly proportional to the number of leukocyte infiltration in the gastric mucosa, and is positively correlated with the degree of inflammation. The main component of inflammatory activity in adult gastritis is neutrophils. The source of infection and the route of transmission of Hp are still unclear. There is no established host in nature. Except for human beings, there are natural infections only in non-human primates. More evidence proves that Hp is a transmission from person to person. However, so far, no positive conclusions have been made on the source and route of transmission of Hp.

Pathogenesis:

The exact pathogenesis of Hp is still unclear. In addition to the virulence factors of bacteria, the host's immune response and environmental effects also play a role. In recent years, studies have found that the pathogenic mechanism of Hp depends on the virulence of bacteria ( Colonization factors and pathogenic factors, the spiral and motility of Hp, the ability to adapt to enzymes and proteins, and adhesion to cells and mucous membranes, allowing them to survive in the stomach cavity, their secreted toxins and induced inflammatory mediators, Directly destroy the gastric mucosal barrier, leading to gastric mucosal damage.

Virulence factor

Among the virulence factors, the motility is one of the most basic factors for Hp colonization on the surface of gastric mucus. There are 2 to 6 flagella at one end of Hp cells, making Hp active, penetrating the mucus layer, and a special kind of Hp. Adhesin can adhere Hp to the epithelial cells of the stomach or duodenum, causing the surface deformation of these cells, the cytoskeleton changes, and the adhesion of Hp to the gastric mucosa is a mucus that prevents bacteria from flowing during food transportation and continues to flow. It is necessary to lose the layer to maintain its infection. Since Hp is specifically colonized in gastric tissue, it is speculated that there are specific receptors on the surface of gastric epithelial cells, such as lewisb blood group antigen.

Urease is the main colonization factor of Hp. The amount of urease synthesized by Hp is very large. The ammonia produced by urease decomposing urea can neutralize hydrochloric acid. This transient low acid and high pH enable bacteria to pass through gastric mucus smoothly. The layer reaches the mucosal surface and colonizes and survives in this alkaline microenvironment; at the same time, the increase in ammonia produced by urease is also toxic to the gastric mucosa.

2. Pathogenic factors

Among the pathogenic factors, the role of cytotoxin is of concern. 60% Hp strains are reported in adults, and 40% to 70% Hp strains in children are found to have cytotoxin associated gene A (cagA). 120-140kD protein (cytotoxin-associated protein A, cagA), cagA protein has a very high detection rate in patients with peptic ulcer and moderate to severe gastritis, cagA has no cell vacuolar activity, but it is associated with cellular vacuolating toxin Related to the expression, vaculating cytotoxin (vacA), encoded by the vacA gene, was first discovered by Leunk et al., the culture medium of Hp contains a substance, and the culture filtrate of the bacterium is cultured together with different cells. Some cells, such as Hela cells, are vacuolar-like degeneration, so they are called cell vacuolating toxins. vacA is strongly activated at pH<6 to pH 1.5, and has strong resistance to pepsin at pH 2.0. In the intestine, the activated vacA causes vacuolization of the duodenal epithelial cells before it is digested by some proteases in the intestine, thus causing duodenal ulceration in the absence of Hp in the duodenum. Ulcer, which forms the leaking roof hypothesis of duodenal ulcer formation, for cagA, vacA detection and Hp virulence gene analysis in children with partial gastroduodenal diseases, the results are also related to the literature. According to the report, 68.18% of the children with Hp-infected gastritis can detect CagA antibody, but 68.96% of children with duodenal ulcer can measure both cagA and vacA, indicating that vacA is associated with pediatric peptic ulcer.

Prevention of Helicobacter pylori infection in children

In view of the fact that the source of infection and the route of transmission of Hp infection are not well understood, it has brought difficulties in preventing Hp infection. Since the 1990s, the research on Hp vaccine has made great progress, and it is expected that in the near future, the vaccine will be adopted. Prevention and treatment of Hp infection will become a reality, and may also be an important measure for the prevention and treatment of Hp-related diseases in the future.

Complications of Helicobacter pylori infection in children Complications anemia peptic ulcer atrophic gastritis gastric cancer gastric ulcer duodenal ulcer abdominal pain bloating

Often until the child is thin, lack of nutrition, and anemia; can be complicated by peptic ulcer, can cause gastrointestinal bleeding, a small to atrophic gastritis and gastric cancer.

1. Bleeding: The complications of bleeding can sometimes be the first symptom of ulcers without any prodromal performance. Hematemesis is usually seen in gastric ulcers. The spit is coffee-like, while melena is more common in duodenal ulcers. For a long time, any kind of ulcer can simultaneously show hematemesis and melena. In children's stomach, blood drainage is more suggestive of gastric bleeding, but those with negative drainage can not rule out the possibility of duodenal ulcer combined with bleeding (because blood can not pass pylorus Reverse into the stomach).

2. Perforation: Perforation is much less common than bleeding, ulcer perforation often occurs suddenly, without any aura symptoms, a small number of children can have no history of ulcers, perforation complications as the first symptom, confirmed by surgery as duodenal ulcer with perforation, In the early neonatal period, perforation of stress gastric ulcer can also be seen, showing abdominal pain and bloating.

Symptoms of Helicobacter pylori infection in children Common symptoms Hernia irritability, abdominal distension, fatigue, dyspepsia, nausea, peptic ulcer, anorexia, abdominal pain, abdominal discomfort

Hp is a chronic source of infection. After entering the body, it mainly settles in the gastric mucosa, resulting in a series of pathological changes, leading to different clinical consequences. The common Hp-related diseases in children are mainly chronic active gastritis, duodenal ulcer and stomach. Ulcers, rare gastric MALT lymphoma, rare gastric adenocarcinoma, so the clinical manifestations of infection after Hp are the symptoms of these diseases, such as abdominal pain, fullness, early satiety, anorexia or upper gastrointestinal bleeding.

1. Children with chronic gastritis

There are different degrees of dyspeptic symptoms, the severity of clinical manifestations vary, and the course of disease is prolonged. The main manifestation is repeated abdominal pain, no obvious regularity, usually worsened after eating, the pain is not exact, mostly in the umbilical cord, and the child's abdominal pain can be Only manifestations of uneasiness and normal eating behavior changes, older children with symptoms like adults, often complained of abdominal pain, followed by hernia, early satiety, nausea, upper abdominal discomfort, acid reflux, eating hard, cold, spicy food or cold, temperature drop When it can cause or aggravate symptoms, some children may have loss of appetite, fatigue, weight loss and dizziness. Those with stomach erosion may have black stools, and the signs are not obvious. The tenderness can be in the upper abdomen or the umbilicus. widely.

2. Pediatric peptic ulcer

The clinical manifestations are various, and the symptoms of different ages are quite different.

(1) Neonatal period: the main features of sudden upper gastrointestinal bleeding or perforation, often acute onset, mainly due to hematemesis, blood in the stool, abdominal distension and peritonitis, easily misdiagnosed, this period is mostly acute stress Ulcer, the mortality rate is higher, the most common incidence 24 to 48 hours after birth.

(2) Infant and child: In this period, children with more acute onset, irritability, poor appetite, sudden hematemesis, melena, may have loss of appetite in the early stage, repeated vomiting and abdominal pain, growth retardation.

(3) Preschool age: The symptoms of abdominal pain in this period are obvious, mostly located in the umbilical cord, with intermittent seizures, and the relationship with diet is not clear, nausea, vomiting, acid reflux, anemia and upper gastrointestinal bleeding are also more common.

(4) School age: With increasing age, clinical manifestations are close to adults, abdominal pain above symptoms, mainly abdominal pain in the umbilical cord, sometimes night pain, or acid reflux, hernia or chronic anemia, and a few people show painless black stools. Fainting, even shock.

Examination of Helicobacter pylori infection in children

There are many diagnostic methods for Hp, which are mainly divided into two categories: direct method and indirect method.

1. Direct inspection of bacteria

Hp in the gastric mucosa was directly detected by culture, PCR, and histology.

(1) Culture method: Hp culture by gastroscopic forceps for Hp culture is the most accurate diagnostic method, which can be used as a gold standard for verifying other diagnostic tests. In addition, it can also provide drug sensitivity test for bacteria to guide clinical selection of drugs. Especially in treatment failures or in countries and regions where Hp resistance is high, Hp culture method is characterized by high specificity, but sensitivity is middle, operation technology is difficult, and it takes a long time, and cultivation takes 3-6 days, even if It is an experienced experimenter, and the success rate of culture is only 75%~95%, which affects the growth of Hp. There are many factors that cause false negative results, such as culture specimens without Hp; swallowing surface anesthetic during gastroscopy; biopsy forceps contamination Or recently used antibiotics or tinctures, which can inhibit bacterial growth, and the time of specimen inoculation is also related to whether the culture medium is fresh.

It has recently been reported that Hp can also be cultured from human feces, but it needs to be centrifuged in a micro-oxygen environment to obtain bacteria, since it can only be detected in the feces of 50% Hp colonized patients, so this non-invasive method Further research is needed.

(2) Tissue sectioning method: Another direct examination method of Hp can provide information on histomorphology, because Hp settles in the mucous layer of human gastric mucus, on the surface of epithelial cells, under normal circumstances, there are no other bacteria in this part, so According to the morphological characteristics and distribution characteristics of the tissue sections (the presence of Helicobacter in the gastric mucus and the gastric cavity), it is a reliable method to diagnose Hp infection. The histological examination is characterized by high sensitivity and simultaneous Do pathological examination, and can save data permanently. There are many staining methods, including HE staining, Gram staining, red carbonate staining, WS (Warthin-Starry) staining, Giemsa staining, Gram staining, detection rate. Low is almost useless; standard HE staining can detect Hp, but it is not a reliable method. WS silver staining is a good technology. Although the price and technical requirements are high, because of the effective detection, the clinical application is more common, and the cost of Giemsa dyeing is higher. Less, some authors believe that this method is equal in quality to WS silver.

In addition to routine histological examinations, there are immunochemical and immunofluorescence methods, but the use of immunofluorescence and immunological antibodies makes inspections more expensive and does not provide information beyond routine histological findings, and thus cannot be routinely used. , mostly used in laboratory research.

(3) Direct smear staining: Hp was directly examined by a phase contrast microscope for gastric mucus applied to the slide, stained with acridine orange, Gram stained, and Giemsa stained.

(4) PCR (polymerase chain reaction): PCR is another method for detecting the presence or absence of Hp. It is characterized by rapid detection of Hp in fresh gastric mucus specimens, as well as detection of paraffin-embedded biopsy samples, PCR primers. It is specific to all Hp strains and is highly specific. Compared with rapid urease, culture and histology, PCR is highly sensitive, but some hidden factors can affect this high sensitivity and specificity, such as Endoscopy and biopsy forceps cleaning, lack of disinfection leads to DNA contamination, so that the specificity is reduced, the factors that reduce the sensitivity are the presence of bacterial colonization or PCR inhibitory factors in the gastric mucosa. PCR can be used for the clinical diagnosis of Hp infection. , Epidemiological investigation, molecular genetics research of Hp.

2. Indirect examination of bacteria

Using the biological characteristics of bacteria, especially the ability of Hp to hydrolyze urea to produce a breath test, urease test, serological factors can not provide the basis for the existence of bacteria, it can not be used for the diagnosis of current infection, mainly for screening or popular In the case of clinicians, it is important for clinicians to choose the appropriate method for the patient according to the conditions of the hospital. At present, the joint method is mainly used for diagnosis.

(1) Rapid urease test: Since Hp is the only bacteria in the human stomach that can produce a large amount of urease, Hp infection can be diagnosed by detecting urease. Urease decomposes urea in the stomach to produce ammonia and carbon dioxide, which reduces the urea concentration. The ammonia concentration is increased, and based on this principle, various detection methods have been developed.

The rapid urease test of gastric mucosa biopsy is the most widely used method in clinical practice. It has the advantages of simplicity, practicality, rapidness and sensitivity. However, due to the number of bacteria, when the number of Hp in biopsy tissue is small, it is prone to false negative. After treatment with tincture, ampicillin, and even H2 receptor antagonists, the sensitivity of the urease test is significantly reduced. Therefore, this method is mainly used for the initial detection of Hp infection. Currently, there are two methods.

1pH indicator method: the reagent contains urea and pH indicator (such as yellow color when phenol red pH 6.8, pink when pH 8.4), the sample taken from the stomach is usually acidic (pH <6.0), under normal circumstances The color of the reagent is unchanged. If there is Hp infection in the stomach, when the mucosa specimen is placed in the reagent, the urease produced by Hp decomposes urea to produce ammonia, so that the pH value rises and the reagent turns pink.

2 Analytical Chemistry: The final product of Hp urease is detected by analytical chemistry. Since the positive color reaction does not depend on the pH change in the reagent, some false negatives caused by pH factors can be avoided. Fujian Sanqiang Biochemical Co., Ltd. produces The CPUT kit belongs to this method and can semi-quantitatively indicate the extent of Hp infection.

(2) Breath test: labeling urea with radionuclide, measuring the amount of CO2 in exhaled after oral administration, can indirectly reflect the amount of urease, is a non-invasive test, and the breath test is fast, reliable, safe, and painless. The advantages are suitable for large-scale epidemiological investigations, indicating whether there is Hp infection at present, rather than having had an infection, so it is superior to serological examination. Some studies have found that after taking gelatin-based bismuth citrate for 2 hours, you can see The amount of 14CO2 is significantly reduced, so it is a sensitive indicator for therapeutic observation. It is also an ideal method for follow-up. The breath test is divided into 13C-urea breath test and 14C- according to the different markers. Urea breath test.

(3) 13C-urea breath test: the subject took oral 13C-urea 5mg/kg, then collected a breath sample every 10min for 3h, if there is Hp infection in the stomach, the oral 13C-urea solution in urease Under the action, it is decomposed into 13CO2, exhaled by absorption through the gastrointestinal tract, and the collected gas specimens are analyzed by mass spectrometer to calculate the content of 13CO2. In the case of Hp infection, the 13CO2 rises 20 minutes after the oral test solution, and continues to rise within 100 minutes. In the absence of Hp infection, there is no 13CO2 exhalation, 13C is a stable nuclides, no radioactivity, and can be repeatedly checked, but the 13CO2 measurement is more complicated, and the mass spectrometer is required, which is expensive, and most hospitals cannot carry out.

(4) 14C-urea breath test: In order to overcome the disadvantages of complicated operation and high cost of 13C-urea breath test, 14C-urea is used to replace 13C-urea, and the same satisfactory effect is obtained. The liquid scintillation counter for 14C can be detected. Therefore, it is more practical. The disadvantage is that 14C has a certain radioactivity and is not suitable for pregnant women and children.

Factors affecting the accuracy of breath test: The most common cause of false negative results is a breath test with antibiotics, expectorants or omeprazole (not normally required at least 1 month after the end of treatment); followed by urea The emptying of the stomach is too fast or the sample collection is too late. The false positive result is the presence of bacteria with urease activity in the body or in the oral cavity.

However, the breath test can only provide the information of Hp, but can not distinguish the digestive tract disease, can not replace the gastroscopy, can not be used as the initial evaluation method for children with upper gastrointestinal symptoms.

(5) Serological examination: Serological diagnosis of Hp is a non-invasive and indirect method, mainly used for epidemiology or screening, and can not be used as the initial diagnostic tool for Hp infection, unless it is combined with other methods, the basis of serological examination Hp has the ability to induce local and systemic immune responses. Hp antibody can be detected by bacterial agglutination, complement binding and ELISA. The ELISA is simple because of simple operation, rapid diagnosis, low price and high sensitivity. More.

There are two types of ELISA methods:

1 Qualitative test: expressed in yin or positive, not only for serum, but also for saliva, gingival secretions, especially for children. The disadvantage is that the false positive rate is high, so the positive result often needs to be supplemented with another positive method.

2 Quantitative test: It is tested by machine and the result is more accurate. It can also be used for follow-up examination after treatment.

Serological tests are an ideal screening test because they are non-invasive and simple to use in children. In children, because Hp infection is less than that of adults, positive findings are more helpful for diagnosis than adults. The IgG antibody content in children is reported in the literature. There is a certain correlation with the number of bacteria or the severity of gastritis histology, but serology cannot be used as a single diagnostic test, and because of the slow decline of antibodies after Hp eradication, it can not be used for immediate follow-up after antibacterial therapy.

Blood Hp immunoblotting: Hp-IgG antibody, cagA, vacA protein antibody, can be used to distinguish the type of infected strain, but it is expensive.

X-ray examination and B-ultrasound examination are routinely performed, except for certain chronic diseases such as tuberculosis and hepatitis.

Diagnosis and diagnosis of Helicobacter pylori infection in children

diagnosis

The clinical manifestations of chronic gastritis and ulcers are characteristic, mainly relying on laboratory examination and diagnosis. In July 1999, the second conference on pediatric digestive endoscopy and digestive diseases was held in Kunming, and the diagnosis of Hp infection was discussed. And the cure criteria are as follows:

Diagnostic criteria for Hp infection:

1. Culture positive.

2. Slice staining saw a large number of typical bacteria.

3. The section saw a small amount of bacteria, urease test, 13C-urea breath test, serological Hp-IgG, Hp nucleic acid any two positive.

4. Those who take antibiotics within the above test may be false negative.

Hp eradication criteria: withdrawal for more than 1 month for review, the above-mentioned examination turned negative for radical treatment.

Differential diagnosis

Different from chronic gastritis, duodenal inflammation and ulcers, it is mainly determined by laboratory test results. Hp has high urease activity, can decompose urea to produce NH+4, and indirectly judge whether there is Hp infection by measuring the presence or absence of NH+4. The patient was orally administered with 14C urea. If there was Hp infection, the patient exhaled gas with 14 CO2 after 20 minutes, and no 14CO2 exhaled without Hp infection. Anti-Hp IgG or anti-Hp IgA in serum or saliva was detected by ELISA for specificity and sensitivity.

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