Background

Typhoid fever also known as enteric fever is a widespread disease. It is a major public health challenge in developing countries. It is caused by Salmonella paratyphi and Salmonella typhi. Enteric fever is used for thyroid and parathyroid fever. 

Typhoid fever is a major cause of death and morbidity in densely populated and unhygienic areas. Progression of this disease starts from gastrointestinal symptoms and leads to various complications. 

Salmonella bacteria are mostly transmitted by the four Fs: fingers, feces, flies, and fomites. Typhoid fever is a disease marked by a progressive pattern of fever. Temperatures rises and falls leads to symptoms like headache and abdominal pain. 

Epidemiology

Typhoid and paratyphoid fever is a major worldwide health problem. In united state the cases are relatively low since 2008. There are 26 million cases of typhoid fever and 5 million cases of paratyphoid fever each year. The deaths are around 215,000. Enteric fever is also a major worldwide health problem. Low- and middle-income countries in southern Africa and south-central Asia have a higher typhoid fever incidence than developed countries.  

In developed countries, most of the cases are seen in travellers who are return from the pandemic area. They are exposed to the contaminated food and water. Typhoid fever is common in areas with tropical and climate changes area. It is directly connected to poor sanitation, a lack of effective sewer systems, and poor water treatment facilities. 

Salmonella typhi is most common than Salmonella paratyphi. It is a most widespread subtype. Advanced research, different treatment approaches, and development in drug have led to a decrease rate in mortality. Only a small number of cases show splenomegaly and rose patches in United States. Around 4% of typhoid fever patients become chronic transporters because of the release of Salmonella in their feces or urine for 1 year. 

Anatomy

Pathophysiology

Salmonella toxicity is affected by typhoid toxin, Vi antigen, lipopolysaccharide O antigen, and flagellar H antigen. Strains with Vi positive antigen have a greater attack rate than Vi-negative strains. The presence of Salmonella typhi differs from non-typhoidal Salmonella. Vi antigen acts as an antiphagocytic agent. It prevents macrophages from consuming bacteria. Flagellar H antigen increases bacterial movement and binding to the gut wall. 

Bacteria with M cells and cytoplasm containing bacteria discharged into the luminal space. It destroys M cells and basal lamina. The cystic fibrosis transmembrane conductance regulator (CFTR) affects Salmonella absorption. People with inadequate CFTR proteins are more resistant to typhoid. 

Salmonella can survive into immune system of host is because of the Rho GTPases. Salmonella produces a molecule that stimulates the release of chemoattractant eicosanoids. It attracts neutrophils into intestinal lumen and enhance mucosal damage. 

Peyer’s patches or proliferation of the mononuclear cells and lymphocytes can cause necrosis and ulcer. This can increase the symptoms. Pathogen can travel to reticuloendothelial system via lymphatic system and blood. It affects multiple organs and specifically gallbladder. Endotoxin and lipopolysaccharide play a important role in secondary bacteremia. 

Etiology

Salmonella paratyphi and Salmonella typhi is a species of the Enterobacteriaceae family. They cause typhoid fever. The transmission of Salmonella occurs through fecal-oral routes. The primary reason is contaminated water, undercooked food, and fomites.  

The disease is common in areas with over populations, social instability, and poor sanitation. Other sources include like chickens, eggs, and turtles. In China around 57% of chicken slaughterhouse tests were positive for Salmonella bacteria. The normal gut flora provides a protective barrier against infection. Antibiotics like streptomycin disrupt it. Salmonella can easily pass through it. Malnutrition can also reduce the normal gut flora. It increases the penetration of infection.  

Genetics

Prognostic Factors

Typhoid fever is a global health problem. The greater effects are in Africa and south Asia. There is an advancement in antibiotics and treatment. The overall mortality rate is deceased around 1%. Earlier I was 12.75% in 1940. Early diagnosis and treatment plays an important role in preventing the disease. Untreated patients can lead to conditions like relapses and chronic infection.  

Clinical History

Salmonella typhoid and salmonella paratyphoid has the same clinical characteristics. The diagnosis of this disease requires the history of patient, residency, travel history, immunization status, factors related to socioeconomic status, lifestyle, disease duration and drug history. Other history includes like drinking water, animal contact, insect bites, accommodations, and undercooked food. This can improve with the diagnosis by removing the other infectious disease. 

Physical Examination

Typhoid fever is a severe condition. It causes high fever and temperature goes unt0 103 to 104 °F. The other symptoms are like headache, cough, abdominal discomfort, small, pink, or red spots on trunk and abdomen, weakness, fatigue.  

It can also lead to changes in bowel movements and diseases like constipation, diarrhea. Patients with jaundice can have yellow skin, pale stools and dark urine, gallstones, and other biliary pathology. Tachypnea is present. It examination may indicate crackles across the lung base and an enlarged spleen. 

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

• Malaria  
• Dengue Fever  
• Brucellosis  
• Tuberculosis  
• Leptospirosis  

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

The common antibiotics used for the treatment of this disease includes fluoroquinolones, cephalosporins, and azithromycin. The choice of the treatment depends on the patient age, severity of disease and antibiotic susceptibility. Early antibiotic treatment is necessary to prevent complications and reduce the duration of disease. Care which includes hydration, a diet and rest is necessary for treatment.  

In severe cases, surgical intervention is necessary. Vaccination is required for those who are traveller to typhoid endemic areas. Lifestyle changes like good hygiene, normal food and water and medical advice is the key management to treat the typhoid fever. Regular follow up is important with healthcare providers for the proper recovery. 

Lifestyle Modifications 

To prevent dehydration and diarrhea, it is essential to take sufficient amount of fluids and electrolytes. A diet which includes soup, boiled vegetables and rice is recommended in the acute phase. To prevent the spread of bacteria, avoid contact with other people and crowded places. If you are travelling to high infectious places then issue of taking the vaccination to prevent it.  

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

role-of-antibiotics

Ciprofloxacin 

Antibiotic treatment is necessary to prevent the severe complications. It is an initial choice of the treatment option. Fluoroquinolones like ciprofloxacin and levofloxacin are the most effective medicines for the many areas. In extreme cases, they might be used empirically based on clinical suspicion. Fluoroquinolones can be given orally for mild cases. For severe cases, it can be given intravenously. It depends on the severity of infection. 

Amoxicillin 

Amoxicillin is a widespread penicillin type antibiotic. It is rarely used to treat the typhoid fever. The resistance of these bacteria to amoxicillin has limited its efficacy in treating typhoid fever. It is used if specific strains of Salmonella is sensitive to amoxicillin. 

Trimethoprim-sulfamethoxazole  

Trimethoprim-sulfamethoxazole is used for complicated cases of typhoid fever. It is an alternative treatment for fluoroquinolone resistance. Trimethoprim-sulfamethoxazole is used as a prophylactic. It is used in the areas where high rate of incidence occur. It prevents the development of the infection.

In cases of multi-drug resistance   

Typhoid fever strains that are multidrug-resistant or very drug-resistant are becoming more common in endemic areas. Extracellular antibiotics are not effective against these bacteria. Treatment for multidrug resistance include third generation cephalosporins like ceftriaxone, cefotaxime, and oral cefixime, along with azithromycin. Ciprofloxacin is an alternative. This method tries to target drug-resistant strains. 

role-of-vaccination

Typhoid vaccination is suggested for those who are visiting the country with typhoid fever or poor sanitation and water hygiene. The countries include Asia, Africa and Latin America. Healthcare workers and laboratory people who are dealing with Salmonella typhi ae at high risk of infection. The intramuscular Vi capsular polysaccharide vaccine is suggested for people who are 2 years older. The live attenuated oral vaccine uses the Ty21a strain of serotype Typhi. It boosts the immunity and stimulates the production of endogenous antibiotics. This vaccine is suggested for those who are 6 years old and travels to infected areas. The prescription consists of taking 4 capsules every other day and take capsule on an empty stomach. 

Medication

Future Trends

Media Gallary

References