Typhoid fever, caused by Salmonella typhi and Salmonella paratyphi, is a significant health concern, especially in overcrowded and unsanitary conditions, leading to millions of cases and deaths annually. The disease presents with a varied course of symptoms, including gastrointestinal distress and systemic illness, and can lead to severe complications, particularly in immunocompromised individuals. Diagnosis relies on blood cultures and serological tests, while management involves antibiotics, supportive care, and preventive measures such as improved sanitation.

1. TYPHOID

2. • Typhoid fever is also called enteric fever.
• It is caused by Salmonella typhi and Salmonella paratyphi.
• Enteric fever is a cumulative term that illustrates both typhoid and paratyphoid
fever.
• Paratyphoid is clinically indistinct from typhoid fever; thus, enteric and typhoid
fever are used mutually.
• Typhoid fever is one of the major causes of mortality and morbidity in
overcrowded and unhygienic areas
• The disease course ranges from early gastrointestinal distress to nonspecific
systemic illness but ultimately may lead to multiple complications.
• Salmonella is said to spread by the 'four Fs" (flies, fingers, feces, fomites).
• Fever characteristically comes in a step-wise pattern (i.e., rises and falls
alternatively) followed by headache and abdominal pain.

3. • ETIOLOGY :-
• The main causative agent of typhoid fever is Salmonella typhi and Salmonella
paratyphi, both are members of the Enterobacteriaceae family.
• Salmonella is a genus that has 2 species
• Salmonella enterica serovar and enteritidis classified through extensive analysis
by multiplex quantitative polymerase chain reaction (PCR).
• Both Salmonella typhi and Salmonella paratyphi (A, B, C)
are Salmonella enterica serotypes.
• Nontyphoidal salmonella (NTS) is more typical in children and is mostly limited to
gastroenteritis.

4. • Salmonella is transmitted by the fecal-oral route through contaminated water,
undercooked foods, fomites of infected patients,
• and is more common in areas with overcrowding, social chaos, and poor
sanitation.
• It is only transmitted from an infected person to another person, as humans are its
only host.
• Normal flora of the gut is protective against the infection.
• The use of antibiotics such as streptomycin destroys the normal flora, which
heightens its invasion.
• Malnutrition decreases normal gut flora and thus increases the susceptibility to this
infection as well.

5. EPIDEMIOLOGY
• A cases each year since 2008, enteric fever remains an important cause of
illness worldwide. Approximately 215,000 deaths result from over 26 million
cases of typhoid fever and 5 million cases of paratyphoid infection each year
worldwide.
• Salmonella typhi is more common than Salmonella paratyphi, and Salmonella
paratyphi A is more prevalent than Salmonella paratyphi B infections.
• Up to 4% of patients with typhoid fever go on to become chronic carriers.
• These patients remain asymptomatic after their acute treatment, but they
may excrete Salmonella for up to 1 year in their stool, or less frequently their
urine.

6. • PATHOGENESIS
• The pathogenesis of typhoid fever depends upon a number of factors,
including infectious species, virulence, host's immunity, and infectious dose.
The larger the infectious dose, the shorter the incubation period, and the
higher the attack rate. Typhoid fever is more severe in debilitated and
immunocompromised patients.
• Salmonella is an acid-sensitive bacteria except for a few resistant strains, so
typically it is destroyed in the stomach by gastric acid unless a large dose is
ingested.
• In patients with achlorhydria, intake of antacids and antihistamines,
colonization of Salmonella occurs even with smaller doses.
• Food and beverages also act as buffers against gastric acid that facilitates
bacteria reaching the small gut.

7. • The virulence of Salmonella is determined by typhoid toxin, Vi antigen
(polysaccharide capsule), liposaccharide O antigen, and flagellar H antigen.
• Strains positive for Vi antigen have an attack rate twice that of Vi negative strains,
even for the same dose of micro-organisms.
• One of the main differences between Salmonella typhi and non-typhoidal
salmonella (NTS) is the presence of Vi antigen in Salmonella typhi but absent in
NTS.
• The main role of the Vi antigen is to act as an antiphagocytic agent preventing the
action of macrophages,
• thus shielding the O antigen from antibodies that confer the serum resistance.
• The flagellar H antigen provides bacterial mobility and adherence upon the gut
wall mucosa. Invasion of the gut wall is assisted by flagella.

8. • Salmonella also produces a molecule that stimulates the epithelial release of
chemoattractant eicosanoid, which sequesters neutrophils into the lumen and
potentiates mucosal damage.
• Bacteria induce proliferation of Payer patches via recruitment of lymphocytes and
mononuclear cells and induce necrosis and eventually, ulceration that complicates
the symptoms.
• Pathogens reach the reticuloendothelial system via both lymphatic system and
bloodstream, including other multiple organs, most commonly gallbladder in
almost all cases.
• The early bacteremic phase (24 hours to 72 hours) is asymptomatic and transient
as these bacteria are phagocytosed by macrophages and monocytes in the
reticuloendothelial system called primary bacteremia.

9. • The capacity of pathogens to grow in these immune cells makes them
characteristic, and intracellular multiplication of bacteria in the reticuloendothelial
system enforces them to re-enter the bloodstream causing continuous
bacteremia for several days and weeks known as secondary bacteremia.
• Secondary bacteremia is the phase in which disease symptoms manifest.
• Like in other gram-negative bacteria, an endotoxin has an important role in the
pathogenesis.
• The lipopolysaccharide induces the shock-like reaction, and endotoxemia leads
to vascular hyperactivity and catecholamine release, which causes focal necrosis
and hemorrhage.
•

10. • HISTORY & PHYSICAL EXAMINATION:-
• Clinical presentations of both Salmonella typhoid and Salmonella paratyphoid are
similar, though arthralgia is more common with typhoid.
• Incubation :- 10-14 days.
• Insidious onset
• Typhoid is an infectious disease that presents with nonspecific symptoms.
• Patients complain of enterocolitis after 12 hours to 48 hours of inoculation.
• Often, they initially present with nausea, vomiting that progresses to diffuse
abdominal pain, bloating, anorexia, and diarrhea , which can vary from mild to
severe diarrhea with or without blood, followed by a short asymptomatic phase that
gives way to bacteremia and fever with flu-like symptoms.
• Enterocolitis is more prominent in Salmonella typhi.

11. • Immunocompromised patients with HIV, particularly those with low CD4
counts, more commonly present with severe diarrhea and tend to have more
serious metastatic infections.
• Classic typhoid fever starts about one week after the ingestion of the organism.
Fever follows a “step-ladder” pattern (i.e., fever rises one day, falls the
subsequent morning, and continues to form peaks and troughs with insidious
onset).
• Drowsiness, headache, malaise and aching in limbs.
• Abdominal distress is frequently seen in typhoid fever.
• Due to the hypertrophy of Payer patches, nd swelling of lymphoid tissue around
ileocecal region, constipation may predominate over diarrhea in some cases.

12. • PHYSICAL EXAMINATION
• In the first week, a documented fever may be accompanied by a decreased heart
rate.
• In the second week, findings are more common, including abdominal distention.
When typhoid is complicated by ileal perforation, tenderness, rigidity, and
guarding of the abdomen may be present.
• Visible rose spots (rose-colored macules on the abdomen) are associated with
typhoid fever but occur only rarely.
• The patient looks pale, mildly distressed, and dehydrated with sunken eyes, dry
skin, and lethargy.
• Some patients have jaundice with yellowish skin and sclera, pale stool, and dark
urine when the patient has associated gallstones and other biliary pathology.
• Enlarged spleen on palpation may also be present.

13. • If the diagnosis is delayed until the third week, the patient is more toxic,
anorexic, and with notable weight loss.
COMPLICATIONS:-
• Chances of bowel perforation increase with time, which worsens abdominal
distension and peritonitis.
• The patient becomes tachypneic with crackles over the lung base on
auscultation. Signs of metastatic complications appear.
• Dry cough due to pneumonia can also be present as well as neck rigidity due to
meningitis, or rarely, chest pain due to myocarditis and pericarditis.

14. •FIRST WEEK •END OF FIRST WEEK •END OF 2ND WEEK
•FEVER •ROSE SPOTS ON TRUNK •DELIRIUM
•HEADACHE •SPLENOMEGALY •COMPLICATIONS, COMA &
DEATH
•MYALGIA •COUGH
•RELATIVE BRADYCARDIA •ABDOMINAL DISTENSION
•CONSTIPATION •DIARRHOEA
•DIARRHOEA & VOMITING IN
CHILDREN
SYMPTOMS

15. • PARATYPHOID FEVER:-
• Course tends to be shorter and milder than typhoid.
• Onset is often more with acute enteritis.
• Rash is more abundant and less GI symptoms.

16. • EVALUATION
• The approach to typhoid patients should be clinical.
• Patients residing in areas with poor sanitation or impure drinking water or history
of travel from endemic areas presenting with febrile illness for more than three
days along with gastrointestinal manifestations (pain, constipation, or diarrhea)
are highly suspicious.
• Diagnosis in the first week is difficult, but a variety of laboratory studies assist in
making the diagnosis.
• NEUTROPENIA IN FIRST WEEK
• Blood culture: Blood culture remains the primary mechanism of confirmation of
a typhoid fever diagnosis.
• Blood cultures done during secondary bacteremia (i.e., clinical manifestations)
are more reliable though 30% to 50% of cultures may be falsely negative
depending on the technique and time series.

17. • Stool culture: Stool culture is less effective in the bacteremic phase of the
disease. Stool culture is diagnostic in the second and third weeks.
• The sensitivity of stool culture depends upon the amount of stool sample taken
and the duration of illness.
• Chronic carriers intermittently pass pathogens in the fecal matter for a long time
so, several samples should be taken.
• Widal test: The Widal test is a serological test for enteric fever, which detects
antibodies against O (surface) and H (flagellar) antigens. An antibody titer of
greater than 1:160 and greater than 1:80 for anti-H antigen and anti-O antigen
respectively are considered as cut off levels to predict recent infection of typhoid
fever.
• When the convalescent titer is four times greater than the acute titer, the study is
considered positive.

18. • Polymerase chain reaction (PCR) Assay:
• Polymerase Chain Reaction (PCR) can provide DNA-based gene identification of
several serotypes such as the H antigen gene and O antigen gene.
• Enzyme-Linked Immunosorbent Assay (ELISA):
• ELISA identifies antibodies to the capsular polysaccharide Vi antigens that may
be helpful in identifying carriers but is rarely useful in acute illness.

19. • MANAGEMENT:-
• Antibiotics
• Vaccine prophylaxis
• Miscellaneous treatment: Symptomatic and supportive care is essential.
Maintaining adequate hydration during diarrhea, as well as appropriate ventilation
and oxygenation for pulmonary complications, should be provided along with
analgesics and antipyretics as supportive care for metastatic complications.
Corticosteroids have been suggested for severe cases with encephalitis.
• Surgery: When gallstones accompany a carrier state, cholecystectomy can be
curative. Surgical repair is indicated for complications, including peritonitis and
ileal perforation.
• Prevention through sanitation: Epidemiological data reveals that typhoid is more
prevalent in low and middle-income countries, in areas with poor drinking water,
and lack of sanitation. Safe drinking water, sanitation, and avoidance of
overcrowding contribute remarkably to the reduction in the number of cases.

20. • HOMOEOPATHIC THERAPUTICS:-
1. BAPTISIA
2. BRYONIA
3. COLCHICUM
4. RHUS TOX
5. PHOSPHROUS
6. SULPHURIC ACID
7. MURATIC ACID
8. OPIUM