1. Typhoid fever

2. Introduction ● Typhoid fever is a severe multisystem illness
characterized by the classic
prolonged fever, sustained bacteremia, and bacterial invasion and multiplication within the mononuclear phagocytic cells of the liver, spleen, lymph nodes, and Peyer patches.

3. Introduction ● Occurs only in humans ● Potentially fatal if untreated.
● Typhoid fever is most prevalent in underdeveloped countries

4. Epidemiology
● Typhoid infection is encountered worldwide but is primarily found in those countries of the developing world where sanitary conditions are poor.
● Indian subcontinent, Southeast and Far East Asia, the Middle East, Africa, Central America, and South America.

5. Epidemiology
● In endemic areas, children aged 1-5 years are at the highest risk because of waning passively acquired maternal antibody and a lack of acquired immunity.

6. The causes of typhoid fever:
Typhoid fever is caused by a type
of bacteria called Salmonella typhi.
Typhoid fever is contracted by
Drinking or eating the bacteria in
contaminated food or water.
People with acute illness can contaminate the surrounding water supply through stool, which contains a high concentration of the bacteria.
Contamination of the water supply can, in turn, taint the food supply.
The bacteria can survive for weeks in water or dried sewage.

7. After the ingestion of contaminated food or water, the Salmonella bacteria invade the small intestine and enter the bloodstream temporarily.
The bacteria are carried by white blood cells to the liver, spleen, and bone marrow.
The bacteria then multiply in the cells of these organs and reenter the bloodstream.

8. About 3%-5% of people become carriers of the bacteria after the acute illness.
Others suffer a very mild illness that goes unrecognized.
These people may become long-term carriers of the bacteria , even though they have no symptoms .

9. Other ways typhoid fever can be contracted include:
eating seafood from a water source contaminated by infected faeces or urine
eating raw vegetables that have been fertilized with human waste
contaminated milk products

10. Clinical manifestations

11. Clinical manifestation
Typhoid fever begins 7-14 days after ingestion of the organism . The fever pattern is stepwise, characterized by a rising temperature over the course of each day that drops by the subsequent morning. The peaks and troughs rise progressively over time.
Over the course of the first week of illness, the gastrointestinal manifestations of the disease develop. These include diffuse abdominal pain and tenderness .
Monocytic infiltration causes inflammation and narrows the bowel lumen, causing constipation that lasts the duration of the illness. The individual then develops a dry cough, frontal headache, delirium, and malaise.
At approximately the end of the first week of illness,
the fever reaches °F (39-40°C).
The patient develops rose spots which are salmon-colored,
pale, truncal, maculopapules usually 1-4 cm wide
and fewer than 5 in number; these generally resolve
within 2-5 days.
These are bacterial emboli to the dermis and occasionally develop in persons with shigellosis or nontyphoidal salmonellosis.

12. During the second week of illness, the signs and symptoms progress
During the second week of illness, the signs and symptoms progress. The abdomen becomes distended, and soft splenomegaly is common. Relative bradycardia and dicrotic pulse (double beat, the second beat weaker than the first) may develop.
In the third week, the still feverish(febrile) individual grows more toxic and anorexic with significant weight loss. The conjunctivae are infected, and the patient is tachypneic .
Abdominal distension is severe. Some patients experience foul, green-yellow, liquid diarrhea .

13. The individual may descend into the typhoid state, which is characterized by apathy, confusion, and even psychosis. bowel perforation and peritonitis may also happen
At this point, strong toxemia, myocarditis, or intestinal hemorrhage may cause death.
If the individual survives to the fourth week, the fever, mental state, and abdominal distension slowly improve over a few days. Intestinal and neurologic complications may still occur in surviving untreated individuals. Weight loss and debilitating weakness last months.

14. The timing of the symptoms and host response may vary based on geographic region, race factors, and the infecting bacterial strain.
Young children, individuals with AIDS, and one third of immunocompetent adults who develop typhoid fever develop diarrhea rather than constipation.
In addition, in some localities, typhoid fever is generally more appropriate to cause diarrhea than constipation.

15. Diagnosis
Diagnosis is often challenging because many signs and symptoms are non specific
For example; redness of the skin (erythema)by it is self is a sign of many disorders
And thus does not tell the health care professional what's wrong
Thus differential diagnosis in which several possible explanations are compared and contrasted must be performed
Your doctor is likely to suspect typhoid fever based on your symptoms and your medical and travel history. But the diagnosis is usually confirmed by identifying S. typhi in a culture of your blood or other body fluid or tissue.

16. 1.Body fluid or tissue culture
For the culture, a small sample of your blood, stool, urine or bone marrow is placed on a special medium that encourages the growth of bacteria. The culture is checked under a microscope for the presence of typhoid bacteria.
. Cultures are widely considered 100% specific.
Culture of bone marrow aspirate is 90% sensitive until at least 5 days after starting of antibiotics. However, this technique is extremely painful, which may outweigh its benefit
Blood, intestinal secretions (vomitus or duodenal aspirate), and stool culture results are positive for S typhi in approximately 85%-90% of patients with typhoid fever who present within the first week of onset.
. Cultures of punch-biopsy samples of rose spots reportedly yield a sensitivity of 63% and may show positive results even after administration of antibiotics.

17. 3.Specific serologic tests
2.Polymerase chain reaction
Combining assays of blood and urine, this technique has achieved a sensitivity of 82.7% and reported specificity of 100%. However, no type of PCR is widely available for the clinical diagnosis of typhoid fever.
3.Specific serologic tests
Assays that identify Salmonella antibodies or antigens support the diagnosis of typhoid fever, but these results should be confirmed with cultures or DNA evidence.
The Widal test was the mainstay of typhoid fever diagnosis for decades. It is used to measure agglutinating antibodies against H and O antigens of S typhi.
Neither sensitive nor specific, the Widal test is no longer an acceptable clinical method.

18. 4.Other nonspecific laboratory studies
Typhidot is a medical test consisting of a dot ELISA kit that detects IgM and IgG antibodies against the outer membrane protein (OMP) of the Salmonella typhi. The typhidot test becomes positive within 2–3 days of infection and separately identifies IgM and IgG antibodies.
The most important limitation of this test is that it is not quantitative and result is only positive or negative. Whereas a detailed Widal test can tell the titres of specific antibodies. However both tests lack sensitivity and specificity.
4.Other nonspecific laboratory studies
Most patients with typhoid fever are moderately anemic, have an elevated erythrocyte sedimentation rate (ESR), thrombocytopenia, and relative lymphopenia.
Most also have a slightly elevated prothrombin time (PT)) and decreased fibrinogen levels.
Circulating fibrin degradation products commonly rise
Liver transaminase and serum bilirubin values usually rise to twice the reference range.
Mild hyponatremia and hypokalemia are common.

19. TREATMENT (Pharmacological Treatment)
Typhoid fever is treated with antibiotics wich kill the Salmonella bacteria .
Cloramphenicol was the original drug of choice for many years .Because of rare serious side effects,cloramphenicol has been replaced by other effective antibiotics
Commonly prescribed antibiotics;
Ciprofloxacin (cipro) . In the united states,doctors often prescribe this for nonpregnant adults.
Ceftriaxone (rocephin) . This injectable antibiotic is an alternative for people who may not be candidates for ciprofloxacin,such as childeren.

20. The third-generation fluoroquinolone gatifloxacin appears to be highly effective against all known clinical strains of S typhi both in vitro and in vivo.
due to its unique interface with gyrA.It achieves better results than cephalosporins even among strains that are considered fluoroquinoloe resistant.
Other treatment include;
Drinking fluids
This helps prevent the dehydration that results from a prolonged fever and diarrhea,if the patient severly dehydrated,may need to receive fluids through a vein intravenously.
Surgery
If patientes intestine become perforated,they will need surgery to repair the hole.

21. Non-pharmacological treatment
Wash your hands.
Frequent hand-washing in hot,soapy water is the best way to control infection.
Avoid drinking untreated water.
Avoid raw fruits and vegetables.
Choose hot foods.

22. Fluid and electrolytes should be monitored and replaced diligently.
Oral nutrition with a soft digestible diet is preferable in the absence of abdominal distention or ileus.
No specific limitation on activity are indicated for patients with typhoid fever.As with most systemic diseases,rest is helpful,but mobility should be maintained if tolerable.
The patient should be encouraged to stay home from work until recovery.
To help decrease rate of typhoid fever in developing nations,the World Health Organization endorsed the use of a vaccination program starting in 1999.
Two typhoid vaccines are licensed for use for the prevention of typhoid;
the live,oral Ty21a vaccine
the injectable typhoid polysaccharide vaccine.
Both are efficacious and recommended for travellers to areas where typhoid is endemic.

23. Thank you