SALMONELLOSIS / MedUrgent
SALMONELLOSIS
The Salmonellae are gram negative aerobic rods with flagella that grow rapidly on simple culture media. They are primarily pathogens of animal but can be transmitted to humans leading to disease. Contaminated food meat, eggs can transmit the disease to man and domestic animals like cattle and sheep are important reservoirs. Other animals can also transmit the disease like rats causing S. typhymurium. Over 3,000 species have been reported that can cause acute watery diarrhea in humans with a particular reference to children who may be infected either accidentally or through close contact with animals or due to poor hygiene. S. Typhi or S. para-typhi differ from other salmonellae in that they do not normally infect animals and are primarily human pathogens.
S. Typhi is much commoner in developing countries while S. paratyphi tend to occur mostly in developed countries, but there is no barrier to the extent of infection in most parts of the world.
Salmonella typhi: This causes the classical form of the disease and this form is common in Africa and other developing countries.
Salmonella paratyphi which has three strains A, B & C. These cause paratyphoid fever, which is generally mild in nature and is not associated with the usual complications of typhoid fever. It is common in Europe, America and Australia. S. paratyphi type A and B have similar presenting features; however, type C leads to acute septicemia with abscess formation. It can also lead to a short illness due to bacteraemia with fever, rigors and loss of appetite.
S. Cholera & S. Suis: are known to cause paratyphoid like fever.
Salmonella infections present in 6 different clinical syndromes including:
1. Typhoid and paratyphoid fever (enteric fever)
2. Gastroenteritis (food poisoning)
3. Enterocolitis
4. Septicemia
5. Metastasis lesions such as osteomyelitis, septic arthritis, liver or brain abscess.
6. Asymptomatic carrier state.
TYPHOID FEVER
Salmonella typhi are primarily pathogens of humans. S. typhi is endemic in the tropics due to poor nygienic situation. The source of infection is chronic a patient or chronic carrier due to che uue to gall bladder infection who may excrete the pathogen for several months. Patients excrete the organisms
in their stool or urine for several weeks which can survive in water, dust or dried sewage for weeks The disease is water and food born which can be transmitted directly from person to person contact or indirectly through the 5 Fs (feaces, flies, food, fingers, and fomites). Major outbreaks may occur due to contamination of the food and water.
The infected dose is lower in patients with achlorohydria or gastrostomy.
PATHOLOGY
The infection depends on the infected dose of the organism. Although, the larger infecting dose can shorten the incubation period, yet, it will not affect the severity of the disease. S. Typhi can be detected in the payer's patches and lymphatics of the small intestine soon after entry into the gastrointestinal tract, where it multiplies and then invades the blood-stream and settles in the reticulo-endothelial system. They multiply in these sites and are discharged into the blood causing bacteraemia.
The second stage (the phase of bacteraemia) coincides with clinical symptoms that become apparent following the preceding period of 10-12 days which constitutes the incubation period of the disease. The organs which are heavily infected are the liver, gall bladder, splen, bone marrow, respiratory secretions and urine.
Gallbladder plays an important role in re-infecting the intestine and regional lymph-nodes and tissues; particularly Payer's patches. This causes tissue hypertrophy and enlargement of the organs like the liver and splen which become palpable.
When the payer patches of the terminal ileum, which extends to an area 25cm from the ileo-caecal valve, become infected, organisms multiply rapidly. The intestine may in certain regions become very thin, thus leading to ulceration, perforation or hemorrhage. Other organs that can be affected include the heart, lungs, CNS and bones where osteomyelitis and abscess formation may occur.
PATHOGENESIS
The organism excretes an exotoxin which acts on the macrophages leading to a production of monokines and these bring about cellular necrosis, fever and other changes. Another mechanism is immunocomplex formation, which leads to proteinuria and glomerulonephritis.
IMMUNITY
if acquired naturally, typhoid can lead to a considerable degree of immunity. A second attack of the disease is unusual in endemic areas. Immunity is through IgA in the intestine or via cell-mediated immunity.
CLINICAL PICTURE
Typhoid Fever in Children
The disease in children has become less frequent than previously recorded in the Sudan. The disease is more likely to occur in children with sickle cell disease, those with liver cirrhosis, SLE, leukemia, lymphoma and schistosomiasis
The disease is characterized by four phases:
1. Flu-like illness with or without gastroenteritis 2–3 weeks after the infection.
2. Multisystem involvement eg bronchitis, high fever with relative bradycardia, encephalitis, hepatosplenomegaly, lymphadenopathy, hemorrhage or perforation.
3.Metastatic phenomena eg myocarditis
4.Carrier state may present with gallbladder disease or complete recovery.
CLINICAL PICTURE
• In the majority of cases, the patient is usually toxic, apathetic, has dry tongue and mouth and may have signs of meningism. The patient may have mild jaundice which tends to occur especially in severe cases due to typhoid hepatitis. Some degree of haemolysis may also contribute to the jaundice.
• Patients have a characteristic pulse and although they have tachycardia, it is usually slower relative to the degree of fever and the pulse is dicrotic in nature, (Fagit's sign).
• Spleen is enlarged in 20 - 70'% of patients, and is palpable around the 10th day of infection. The increase in size is slight to moderate, and the splen is soft, tender and may easily rupture. The liver is also enlarged and rose spots are seen over the patient's trunk between days 7 - 10.
• Mental state is usually affected. Apathy and psychosis are not uncommon and some patients may present with frank catatonic schizophrenia during the period of illness or shortly after. Meningism is common, and during the third week, a bad prognostic sign is loss of consciousness.
• Stools are loose and pale.
• Symptoms and signs of bronchitis may develop.
COMPLICATIONS
The common complications are:
1) Perforation: These tends to occur in the third week, in those with severe disease (3 -4%).
Perforation is seen in the region of the terminal ileum where it gives rise to an acute or insidious presentation. The patient's condition worsening during the third week, develops vomiting and ascites and gas may accumulate under the diaphragm. Treatment is surgical
2) Hemorrhage: This is seen in 2-8% of patients in the third week It is due to necrosis of the blood vessels in the region of the affected intestinal lymphoid tissue.
3) Acute cholecystitis: This is more common in females than males and can be the only presenting feature. In males, orchitis may occur.
4) The bones may be affected, although to a lesser degree than that seen in Brucellosis. Osteomyelitis may occur in the ribs, vertebrae, and the discs. This is rare, but may lead to paraplegia. Osteosclerotic changes of vertebral bodies may also be seen, and can be differentiated from Pott's disease where osteolytic lesions are usually found.
5) Arthritis due to infection of the ankle and hip joints may be noted but to a lesser degree
6) Genitourinary tract complications include orchitis during convalescence and pyelitis is of common occurrence.
7) Typhoid abscesses may be seen in the breast and spleen.
Uncommon or rare complications:
- Typhoid lobar pneumonia which may lead to death due to hemorrhage, pleural effusion and empyema in 1-2% of the patients.
- Venous thrombosis may occur in the recumbent patient especially when dehydrated. - Acute pyelonephritis, acute renal failure or rarely nephrotic syndrome. - The meninges can be infected by the bacilli causing Typhoid meningitis.
- The nerves when affected show subjective symptoms. Of these, is the 'burning foot syndrome', in which the patient develops a burning sensation in his feet.
- Involvement of the cornea can-lead to keratitis and optic neuritis. IT18th nerve may be affected and the patient may end up deaf.
- Schisto-salmonelosis is the complication of schistosomiasis by typhoid bacilli invading the adult worm. It can either be due to S. mansoni or haematobium. This may become manifested by the development of prolonged low grade recurrent fever, bloody diarrhea, abdominal pain and aches. The bacilli live and multiply within the worm's gut from where they are released in the circulation causing intermittent bacteraemia. Treatment requires antibilharzial drugs initially to destroy infection worms.
- The causes of death in typhoid are mainly due to perforation, hemorrhage or toxemia.
DIAGNOSIS
The diagnosis can be suspected from the clinical picture of continued fever of more than 4 days associated with splenomegaly. The patient is usually toxic and apathetic. Other signs include a slow dicrotic pulse and roseolar spots on the trunk. These appear in the second week, and therefore diagnosis in the first week is usually difficult. Other symptoms or signs that may be seen in the later stages include epistaxis, loose stools, abdominal distension and hemorrhage.
The differential diagnosis includes:
-Malaria, Visceral leishmaniasis, Brucellosis, Amoebic liver abscess, Tuberculosis, Viral infection (viral hepatitis), Infective endocarditic and Abscess (hidden pus).
Laboratory tests:
- Complete blood count: Leucopenia, neutropoenia and relative lymphocytosis. A normal WBC count may be found in mild cases. Leukocytosis is against the diagnosis unless there is perforation or hemorrhage. Most patients have a normochromic normocytic anemia.
- A definite diagnosis may only be done by the isolation of the bacilli; Therefore culture of stools, urine and blood in the first 10 days is important. In the severely ill, a blood culture may be positive at any stage of the disease.
• A blood culture has more of a chance of being positive in the first 10 days.
• A urine culture has more of a chance of being positive from the 2nd week.
• A stool! culture has more of a chance being positive during the 2nd_3rd weeks. • Bile obtained by a duodenal tube from carriers is positive in 70% of cases.
- Endoscopy also has a high percentage of positive results.
• Culture of organisms by aspiration of the rose spots is positive in 40% of patients.
WIDL TEST:
This is an agglutination reaction. It is positive during the second and third weeks. A rising titer is highly significant in endemic areas where the test is not of great significance as most individuals may have an increased titer due to recurrent subclinical infections. Two antibodies are produced in response to the infection. These are: lgM and IgG, 1GM is produced in response to the somatic "O" antigen; IgG is in response to the flagellar 'H' antigen. An increase in IgM indicates recent infection and is thus quite reliable; Whereas IgG is a sign of previous vaccination or infection. The significant diagnostic titers for these are 1460 for 1gM and 1/320 for 1gG.Lesser titers are either considered insignificant or suggestive.
Patients on treatment for typhoid fever may give false negative results and similarly among those who are immunologically depressed.
TREATMENT
The patient is admitted to hospital with isolation facilities. IV fluids are required for rehydration and antibiotic treatment is given in addition to the general management of the patients. Patients should be given soft food and fluids to prevent perforation. The excreta should be carefully handled and the fever treated by analgesics and tipid sponging. Those who have mild disease can be treated on an out-patients basis. Specific treatment consists of: 1) Chloramphenicol is the drug of choice with a cure rate of 98%. It is a bacteriostatic drug and adequate doses are required to prevent relapses and the prolonged carrier states.The dose is 3g daily, (0.5g every 4 hrs) until the fever subsides, when it is reduced to 2g daily (0.5g every 6 hrs), until a total dose of 22g is reached. Another regimen is 1gm 6-hourty until the fever subsides and then 0.
For those who cannot tolerate chloramphenicol orally, it is given intravenously. The IM route is avoided due to poor absorption. The response to the drug is usually good, and the patient's condition is seen to improve within 2-3 days. The fever subsides by the 4th to 5th day. Occasionally, chloramphenicol' accident can occur in severe cases, and is due to the massive killing of the bacteria (Herxheimer reaction). The patient becomes toxic and shocked, and mental changes may get worse.
Pregnant ladies should not be given chloramphenicol as it may cause the gray baby syndrome.
Resistance to chloramphenicol has been reported in Nigeria and the Far Fast: but fortunately not in the Sudan. Cure rate is 97% but it is associated with serious side-effects. It can cause bone marrow depression and aplastic anemia in those previously exposed to the drug and unless treated by bone marrow transplantation, it is commonly fatal.
2) The second line drug is Co-trimoxazole which is given as 80mg is composed of Trimethoprim and Sulphamethoxazole. Two tablets are given three times daily until the fever subsides and then twice daily for ten days. The drug has few side-effects and its cure rate is approximately 80%. Resistance to it has been reported and in such cases chloramphenicol must be used.
3) Amoxicillin compares well with chloramphenicol. Doses of 4g (Igm every 6 hrs) are given for 14 days. This may be continued for up to 6 weeks if found necessary
4) Ampicillin is given concurrently with chloramphenicol. Large doses are required to be given intravenously (1gm every 6 hrs) until the fever subsides. This is followed by 0.75g every 6 hrs for another 7 - 10 days. The use of Ampicillin is mainly for pregnant women who cannot take chloramphenicol, and for the treatment of carriers.
5) Ciprofloxacin is very effective against salmonella and Shigella organisms at a dose of 400mg twice daily for two weeks. It is, however, very expensive. 6) Cefriaxone 60mg/kg IV once daily for 7-14 days or IV 50mg/kg/day for 7 days.
7) Azithromycin 500mg orally once daily for 7 days (not in severe disease).
Relapses of typhoid fever may occur after chloramphenicol treatment. It appears approximately 10-14 days after the end of treatment, and is milder than the initial attack. The dose of treatment should be similar to doses used for the initial treatment.
Steroids have been given to the very ill and toxic patients who are in the dangerous period. A short course used for five days is given and consists of 60mg of Prednisolone. It should not be given in the third week of illness for fear of perforation.
Faecal and gall-bladder carriers are treated with ampicillin at very massive doses of 6 grams per day for 4 weeks. In some, cholecystectomy has been advocated, especially in patients with gall-stones and for food handlers. Urinary carriers are also given ampicillin at the same dose. However, should calculus disease or urinary schistosomiasis be present, then this renal should be treated as well.
A patient may not be considered fully recovered or non-infective until three consecutive stools and urines are found to be negative on culture following completion of treatment
Treatment of typhoid fever in children
Salmonella gastroenteritis is not usually treated with antibiotics as they are not very effective in this stage as well as they may lead to prolonged excretion of the organism. Indications for the use of antibiotics in these cases include toxic or severe disease, infants under 3 months of age, immunodeficient patients or patients on immunosuppresant medications.
Drugs of choice used in treatment of typhoid fever in children.
1. Ampicillin 100mg/kg/day oral or iv in 4 divided doses for 5 – 7 days
2. Amoxicillin 40mg/kg/day oral or iv in 3 divided doses for 5-7 days
3. Trimethoprim (TMP) 10mg/kg/day + Sulfamethoxazole (SMX) 50mg/kg/ day oral in 2 divided doses for 5–7 days.
4. Chloramphenicol 80 – 100mg/kg/day oral or iv in 4 divided doses for 14 days.
5. Ceftriaxone 50 - 100mg/kg/day iv in 4 divided doses for 14 days
6. Cefotaxime 200mg/kg/day iv in 2 divided doses for 14 days.
Prevention
• For those traveling to endemic countries, a monovalent typhoid vaccine should be given at least for 2 weeks before the time of intended travel. Food handlers should also be vaccinated.
• Early diagnosis and isolation of patients for elimination of source of infection
• Prevention is through: proper disposal of excreta, safe water supply and treatment of carriers particularly, if they are food handlers
• Typhoid fever is a reportable disease and the Communicable Diseases Unit in the MOH should be immediately informed.
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