Typhoid Fever

Define

Typhoid is an acute infectious gastrointestinal disease caused by the bacilli Salmonella (S. typhi and S. paratyphi A, B). Clinical manifestations are systemic toxic infection syndrome, accompanied by specific pathological lesions in the gastrointestinal tract.

Research history

Typhoid has been around since ancient times, but it was not until the 18th century that the different clinical images of the disease were described.

1804: Prost was the first to detect a specific pathological lesion in the gut.

1829: Louis presents the perfect clinical and GPB synthesis of the disease.

1834: The term "Typhoid" begins to be named for the disease and to this day.

1880: Eberth (Germany) isolated the typhoid bacillus from the spleen, mesenteric lymph nodes in a typhoid patient.

1890: Schottméler isolates S. paratyphi A and B.

1890: Pfeiffer and Kalle find a preventive vaccine.

1896: Widal discovers the Widal serum reaction

1930: Reilly demonstrates the pathogenic role of typhoid endotoxin.

1948: Wood Ward applied the drug to the treatment and achieved very good results.

Epidemiology

Pathogens

Typhoid bacillus (S. typhi) and paratyphoid (S. paratyphi A, B).

Salmonella is gram-negative bacilli, size 1-3 ´0.5-0.7 mm, hairy, mobile, non-spore-forming, aerobic and anaerobic, easy to grow in pine culture. Usually, pH: 6-8, temperature between 15 °C - 41 °C (the most suitable temperature is 37.5 °C). In addition to the general chemical properties of the Enterobacteriaceae family, Salmonella also has some properties: No fermentation of Lactose, Sacaroza, Ureaza (-), Indol (-), H2S (+).

Salmonella has good vitality and resistance. In broth, in soil can survive for several months, in normal water: 2-3 weeks, in ice: 2-3 months, in feces: several weeks.

Bacilli are killed at 50 °C / 1 hour, 60 °C / 10-20 minutes, 100 °C / 5 minutes. Common disinfectants such as 3% chloramine, 5% phenol etc. kill bacteria easily.

Bacilli have 3 main types of antigens:

O-antigen: A body antigen, essentially a Lipopolysaccharide (LPS). This is the bacterial endotoxin, which is released only when the bacteria is destroyed.

H-antigen: A hairy antigen, which is essentially a protein.

Micro-antigen: It is a shell antigen, essentially a polysaccharide (PS). Micro antigens are only found in S. typhi and S. paratyphi C. Micro antigens interfere with phagocytosis and inhibit complement activity.

Inoculum

Only people, including:

Patient

Excretion of bacteria in feces (mainly), in addition to urine, sputum, vomit. Bacillus discharged in batches. Excreted in feces at all stages of the disease, including the incubation period, is most discharged in the 2-3 weeks of the disease.

Carriers of bacteria, including:

Carriers after recovering from the disease: The patient recovers clinically but 3-5% continues to carry the bacteria after a few months and years (due to bacteria residing in the gallbladder, intestinal tract).

The carrier has no clinical manifestations. This is an important source of infection.

Infection

Gastrointestinal tract transmission, there are 2 ways of transmission.

Due to eating and drinking food, water contaminated with bacteria, not cooked. Waterborne transmission is an important and easy way to cause large epidemics.

Due to direct contact with patients, carriers through waste, limbs, utensils etc. often causes small and dispersed fluids.

The body is aware and immune

All ages and sexes can suffer.

Immunity: Long after infection or vaccination. There is no cross immunity between strains.

Mechanism of pathogenesis and pathology

Mechanism of pathogenesis

Endotoxin mechanism

According to Reilly, the mechanism of causing typhoid disease through 3 stages:

State 1:

Typhoid bacteria pass from the digestive tract to the stomach. Here some bacteria are destroyed by acidity of gastric juice. The remainder descended into the intestine after 24-72 hours to pass through the intestinal mucosa into the mesenteric lymph nodes, the Payer plaque follows the lymphatic pathway and grow there for about 15 days. It was the incubation period.

Phase 2:

After a period of development in the mesenteric lymph nodes, bacteria enter the blood for the first time. Here typhoid bacteria only exist for 24-72 hours, do not cause clinical symptoms and are destroyed by endothelial retinal system cells in the liver, spleen, bone marrow ... but some bacteria have spread. throughout the body, proliferates in the gallbladder and many other organs, then re-enters the bloodstream a second time and begins to cause clinical symptoms, corresponding to the onset.

Stage 3:

The destroyed bacteria release endotoxins. It is the endotoxin of typhoid bacteria that plays a decisive role in clinical signs such as: Li, temperature disturbance, heart failure and some intestinal damage ...

Bacterial mechanism

According to Hornick et al 1970, when injecting typhoid endotoxins to volunteers, it was not found to cause TH disease. But if you give oral VK TH, it can cause a clinical picture. therefore, according to these authors, the mechanism of disease is caused by typhoid bacteria

Immune mechanism - role of macrophages (Bacterial factor + Toxin)

The pathogenesis of typhoid has the role of both VK and NDE, they affect   

to the macrophage leukocytes release cytokines and induce symptoms

clinical symptoms of the disease.

Pathology

Typhoid causes damage to many organs, especially the digestive system.

Small intestine: Lesions mainly in the ileum, 30 cm from the Bouhin van on the free bank opposite the mesenteric mesenter. Payer plaques have congestive inflammation, edema leading to necrosis, ulcers. The ulcer can go deep into the muscle layer and serosa and can cause perforation of the intestine. In the 3rd - 4th week of the disease, if it heals, the ulcer will heal, leaving no scars.

Endothelial retinal system (liver, spleen, lymph nodes) proliferation, local necrosis in each region.

clinical

Divide the clinical form

According to the clinical picture

Hidden.

Typical conventional form.

Atypical form.

According to the degree of disease

Light form.

Can fit.

Heavy form.

According to geography

Children.

Old people.

Pregnant.

People who have been vaccinated.

According to progress

Acute form.

Recurrence form.

According to the pathogen

Typhoid caused by Sal. Typhi.

Deputy typhoid by Sal. paratyphi A, B.

Symptoms study according to each clinical form

Hidden

There is no clinical manifestation, but the test contains typhoid bacteria.

Typical conventional form

Incubation period:

Average 7-15 days, can vary from 3-60 days. There are usually no symptoms.

Onset period:

Usually progresses slowly over 1 week with symptoms:

Fever: The temperature increases gradually, often with cold spines at first, rarely chills. By day 7 of the illness the temperature rises to 39-41 ° C.

Headache, fatigue, poor appetite, tinnitus, and confusion.

Full-play period:

Lasts 2 weeks.

Fever.

Is the most important and constant symptom. Constant high fever of 39-40 ° C, high fever shape. Hot fever is essential.

Neurotoxicity: Is a prominent symptom, manifested by headache, insomnia, nightmares, tinnitus, lisp, shaking hands. Typically, the state of typhos (the patient lies motionless, his expression is indifferent though he is still aware of stimuli from the surrounding environment, and his eyes are blank). More severe than patient’s lethargy, delirium, coma is less common.

Rubella (or erythema).

The rash is small 2-3 mm, pink in color, usually in the abdomen, chest, and ribs. The number of rash is less than a dozen, appearing in the 7th to 12th day of the disease (with paratyphoid often more often and growing later).

Gastrointestinal: Image of "rotating tongue": dry tongue, red edge of tongue, a layer of white or gray moss between the tongue.

Going outside the stool is loose, yellow-brown color, very puffy, about 5-6 times / day.

Bloating, mild pain spreading to the right pelvic fossa. Signs of Padalka (perforated right pelvis) positive, right pelvic aortic brain positive.

Liver, spleen enlarged 1-3 cm below the ribs, soft density.

Cardiovascular: The pulse is slow relative to temperature, called the pulse and dissociation temperature. Blurred heart sound, low blood pressure.

Respiratory: Bronchitis and pneumonia may be encountered.

Recovery period:

Usually 1 week.

The temperature fluctuated drastically and then slowly dropped. The patient is less tired, has better eating and sleeping, and has no digestive disorders. The disease recovers gradually.

Atypical form

Today due to the widespread use of KS and vaccines. The clinical picture is no longer typical as described. The main common symptoms and diagnostic values ​​are:

Prolonged fever, normal BC, decreased.

Gastrointestinal disturbances.

Enlarged liver, spleen ...

Implementing the quadrants

Clinical basis

Prolonged fever.

There are digestive disorders.

Enlarged liver, spleen.

Test basis

CBC

Leukocytes are normal or decreased, polymorphonuclear neutrophils (N) decreased, eosinophils (E) decreased or lost. Red blood cells and blood sedimentation rate less changed.

Blood cultures

Is a test with definitive diagnostic value. Should take blood before using antibiotics and sufficient quantity. The rate of blood transplants (+) is high at week 1 (90%), in week 3, 4, it decreases to about 30%. It is necessary to make an antibiotic to monitor the resistance of the typhoid bacteria.

Bone marrow transplantation

The rate (+) is high, it should be done when clinically suspected of typhoid but 2-3 times negative for blood cultures.

Fecal culture, bile culture, urine culture

The positive rate is lower.

Serum diagnosis

Widal reaction: A specific antigen-antibody agglutination reaction. However, there are still false positives and false negatives, so the reaction has a certain value. Reaction using antigens of 3 strains: S. typhi, S. paratyphi A and B, test done 2 times, time 1: weekend 1, time 2 times 1: 7-14 days. The result (+) when the titre of the second antibody is 4 times higher than that of the 1. If it can only be done once, the dilution of antibody titer (for people who have not been vaccinated) TO ³ 1/100, TH ³ 1/200. For those who have been vaccinated, TO ³ 1/200, TH ³ 1/400.

Currently, there are many quick and accurate serological diagnosis methods such as IFA test (indirect fluorescent antibody), ELISA, PCR ..., find antibodies in the urine.

Epidemiological basis: it may happen oddly or into an epidemic

Differential diagnosis

Gram-negative sepsis

Two diseases have the same symptoms: prolonged fever, digestive disorder, enlarged liver and spleen. But in sepsis often fever has a lot of chills, temperature fluctuates strongly, rapid pulse, red blood cells decrease clearly. If there is a rash often macular rash - measles-like papules. There are primary and secondary drives. The decisive factor for differential diagnosis is blood culture for pathogenic bacteria.

Primary malaria

There are also symptoms of prolonged fever, enlarged liver and spleen. But in primary malaria, the fever is usually constant at first, but then gradually enters the typical malaria. Red blood cell test is reduced clearly, there are malaria parasites in the blood. Epidemiology: Patients in malaria endemic areas.

Symptoms

Typhoid disease can cause many complications, increasing the mortality rate of the disease, especially before antibiotics are available. Complications of typhoid can be caused by many reasons: toxins, typhoid bacteria, other bacterial superinfection and antibiotic complications. Currently, complications of typhoid fever have decreased, but there are still complications such as:

Gastrointestinal complications

Gastrointestinal bleeding

Meet rate of about 15%. Usually on 2 and 3 weeks of illness. Depending on the severity of appearance, heavy bleeding manifests itself: rapid, small pulse, drop in blood pressure, sudden drop in temperature. Patients with perspiration, green mucous skin, anaemia, black stools, decreased red blood cells, decreased haemoglobin.

Perforation of the intestine

The rate of 1-3% usually occurs in week 2, 3 of the disease or in the recovery phase due to eating "fake meals". Patients with severe abdominal pain in the right pelvic fossa or spread throughout the abdomen. There are signs of dizziness: small strength, low temperature, low blood pressure, cold limbs, sweating. Bloating, abdominal wall reaction, knocking echoes in front of liver. X-ray images of sickle gas, water level.

Cardiovascular complications

Myocarditis

Chest pain, blurred heartbeat, arrhythmia, low blood pressure. On electrocardiogram: flat, negative T waves, inverted ST.

Cardiomyopathy

Symptoms of endotoxin dizziness: Small tachycardia, low blood pressure, sweating, cold limbs, etc.

Complications of the liver and bile

Cholecystitis

Meet the rate of 1-2%. Manifestations: Pain in the lower right rib, jaundice. Painful gallbladder score, Murphi (+) sign.

Hepatitis

Jaundice, enlarged liver, increased SGOT, SGPT test.

Other complications are rare

They don't come, they don't come.

Inflammation of veins and arteries.

Glomerulonephritis, pyelonephritis, cystitis ...

Antibiotic complications (allergies, intoxication ...)

Treatment

The principles of treatment

Treatment to kill the pathogen.

Symptomatic treatment, according to the pathogenetic mechanism.

Resistance enhancement.

Treat the cause

Chloramphenicol was the first antibiotic used by Woodward to treat typhoid since 1948. Antibiotics have changed clinical course and disease prognosis. Dosage 0.03-0.05g / kg / day used continuously until the fever is gone for 10 days.

Side effects: The drug causes bone marrow suppression, leukopenia. Therefore, when the white blood cell count is £ 3000 / mm3, no other drugs should be used or switched. In recent years in our country and the world there have been many reports that the typhoid bacillus is resistant to this antibiotic.

Ampicillin, Amoxicillin: Fever reduction effect is slower than that of Chloramphenicol, now there is a report of drug resistance. Dosage: 50-80mg / kg / day for continuous use until the fever is gone for 10 days.

Bactrim: Dose of 60 mg / kg / day. There has been a resistance phenomenon.

Currently, a number of new drugs of the class of Cephalosporin 3rd generation and Fluoroquinolone are based on the treatment of typhoid, especially in areas with high rates of resistance to Chloramphenicol and some other classical drugs. The drug has brought good results: rapid fever reduction, less recurrence and few side effects.

Ceftriaxone (Rocefin): 2-3 g / day ´ 5-7 days.

Cefotaxime (Claforan): 2-3 g / day ´ 5-7 days.

Pefloxacin (Peflacin): 400 mg ' 2 capsules / day ' 5- 7 days.

Ofloxacin (Oflocet): 200 mg '2 capsules / day '5- 7 days.

Ciprofloxacin (Ciprobay): 500 - 1000 mg / day ´5- 7ngay vv.

Treatment according to the pathogenetic mechanism

Electrolyte water compensation.

Cardiovascular support.

Sedative.

Smoothie.

Nutrition: A liquid, soft, nutritious diet.

Complicated treatment

When complications stop or reduce chlorosis dose, switch to a new group of antibiotics.

Use corticosteroids in case of endotoxin shock.

Gastrointestinal bleeding: Motionless, cold compresses, haemostatic drugs, fresh blood transfusion.

Intestinal perforation: Anti-shock, surgical treatment.

Prevention

General prevention

Improve environmental sanitation, control water, waste, sewers, disinfect water sources.

Isolation of the patient, and waste treatment of the patient.

Treatment of healthy carriers.

Specific disease prevention 

Typhoid vaccine: TAB vaccine or oral live vaccine.