Typhoid fever
Typhoid fever, also known as typhoid, is a disease caused by Salmonella enterica serotype Typhi bacteria, also called Salmonella Typhi. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several days. This is commonly accompanied by weakness, abdominal pain, constipation, headaches, and mild vomiting. Some people develop a skin rash with rose colored spots. In severe cases, people may experience confusion. Without treatment, symptoms may last weeks or months. Diarrhea may be severe, but is uncommon. Other people may carry it without being affected, but are still contagious. Typhoid fever is a type of enteric fever, along with paratyphoid fever. Salmonella enterica Typhi is believed to infect and replicate only within humans.
Typhoid is caused by the bacterium Salmonella enterica subsp. enterica serovar Typhi growing in the intestines, Peyer's patches, mesenteric lymph nodes, spleen, liver, gallbladder, bone marrow and blood. Typhoid is spread by ingesting food or water contaminated with the feces of an infected person. Risk factors include limited access to clean drinking water and poor sanitation. Those who have not yet been exposed to it and ingest contaminated drinking water or food are most at risk for developing symptoms. Only humans can be infected; there are no known animal reservoirs. Salmonella typhi which causes typhoid fever is different from the other Salmonella bacteria that usually cause salmonellosis, a common type of food poisoning.
Diagnosis is performed by culturing and identifying S. typhi from patient samples or detecting an immune response to the pathogen from blood samples. Recently, new advances in large-scale data collection and analysis have allowed researchers to develop better diagnostics, such as detecting changing abundances of small molecules in the blood that may specifically indicate typhoid fever. Diagnostic tools in regions where typhoid is most prevalent are quite limited in their accuracy and specificity, and the time required for a proper diagnosis, the increasing spread of antibiotic resistance, and the cost of testing are also hardships for under-resourced healthcare systems.
A typhoid vaccine can prevent about 40–90% of cases during the first two years. The vaccine may have some effect for up to seven years. For those at high risk or people traveling to areas where it is common, vaccination is recommended. Other efforts to prevent it include providing clean drinking water, good sanitation, and handwashing. Until an infection is confirmed as cleared, the infected person should not prepare food for others. Typhoid is treated with antibiotics such as azithromycin, fluoroquinolones, or third-generation cephalosporins. Resistance to these antibiotics has been developing, which has made treatment more difficult.
In 2015, 12.5 million new typhoid cases were reported. The disease is most common in India. Children are most commonly affected. Typhoid decreased in the developed world in the 1940s as a result of improved sanitation and the use of antibiotics. Every year about 400 cases are reported in the U.S. and an estimated 6,000 people have typhoid. In 2015, it resulted in about 149,000 deaths worldwide – down from 181,000 in 1990. Without treatment, the risk of death may be as high as 20%. With treatment, it is between 1% and 4%.
Typhus is a different disease, caused by unrelated species of bacteria. Owing to their similar symptoms, they were not recognized as distinct diseases until the 1800s. "Typhoid" means "resembling typhus".
Signs and symptoms
Classically, the progression of untreated typhoid fever has three distinct stages, each lasting about a week. Over the course of these stages, the patient becomes exhausted and emaciated.- In the first week, the body temperature rises slowly, and fever fluctuations are seen with relative bradycardia, malaise, headache, and cough. A bloody nose is seen in a quarter of cases, and abdominal pain is also possible. A decrease in the number of circulating white blood cells occurs with eosinopenia and relative lymphocytosis; blood cultures are positive for S. enterica subsp. enterica serovar Typhi. The Widal test is usually negative.
- In the second week, the person is often too tired to get up, with high fever in plateau around and bradycardia, classically with a dicrotic pulse wave. Delirium can occur, where the patient is often calm, but sometimes becomes agitated. This delirium has given typhoid the nickname "nervous fever". Rose spots appear on the lower chest and abdomen in around a third of patients. Rhonchi are heard in the base of the lungs. The abdomen is distended and painful in the right lower quadrant, where a rumbling sound can be heard. Diarrhea can occur in this stage, but constipation is also common. The spleen and liver are enlarged and tender, and liver transaminases are elevated. The Widal test is strongly positive, with antiO and antiH antibodies. Blood cultures are sometimes still positive.
- In the third week of typhoid fever, possible complications include:
- * The fever is still very high and oscillates very little over 24 hours. Dehydration ensues along with malnutrition, and the patient is delirious. A third of affected people develop a macular rash on the trunk.
- * Intestinal haemorrhage due to bleeding in congested Peyer's patches occurs; this can be very serious but is usually not fatal.
- * Intestinal perforation in the distal ileum is a critical complication and often fatal. It may occur without alarming symptoms until sepsis or diffuse peritonitis sets in.
- * Respiratory diseases such as pneumonia and acute bronchitis
- * Encephalitis
- * Neuropsychiatric symptoms, with picking at bedclothes or imaginary objects.
- * Metastatic abscesses, cholecystitis, endocarditis, and osteitis.
- * Low platelet count is sometimes seen.
Causes
Bacteria
The Gram-negative bacterium that causes typhoid fever is Salmonella enterica subsp. enterica serovar Typhi. Based on the MLST subtyping scheme, the two main sequence types of the S. Typhi are ST1 and ST2, which are widespread globally. Global phylogeographical analysis showed dominance of a haplotype 58, which probably originated in India during the late 1980s and is now spreading through the world with multi-drug resistance. A more detailed genotyping scheme was reported in 2016 and is now widely used. This scheme reclassified the nomenclature of H58 to genotype 4.3.1.Transmission
Unlike other strains of Salmonella, humans are the only known typhoid carriers. S. enterica subsp. enterica serovar Typhi is spread by the fecal-oral route from people who are infected and from asymptomatic carriers of the bacterium. An asymptomatic human carrier is someone who is still excreting typhoid bacteria in stool a year after the acute stage of the infection.Diagnosis
Diagnosis is made by any blood, bone marrow, or stool cultures and with the Widal test. In epidemics and less wealthy countries, after excluding malaria, dysentery, or pneumonia, a therapeutic trial time with chloramphenicol is generally undertaken while awaiting the results of the Widal test and blood and stool cultures.Widal test
The Widal test is used to identify specific antibodies in the serum of people with typhoid by using antigen-antibody interactions.In this test, the serum is mixed with a dead bacterial suspension of Salmonella with specific antigens. If the patient's serum contains antibodies against those antigens, they get attached to them, forming clumps. If clumping does not occur, the test is negative. The Widal test is time-consuming and prone to significant false positives. It may also be falsely negative in recently infected people. But unlike the Typhidot test, the Widal test quantifies the specimen with titres.
Rapid diagnostic tests
Rapid diagnostic tests such as Tubex, Typhidot, and Test-It have shown moderate diagnostic accuracy.Typhidot
Typhidot is based on the presence of specific IgM and IgG antibodies to a specific 50Kd OMP antigen. This test is carried out on a cellulose nitrate membrane where a specific S. typhi outer membrane protein is attached as fixed test lines. It separately identifies IgM and IgG antibodies. IgM shows recent infection; IgG signifies remote infection.The sample pad of this kit contains colloidal gold-anti-human IgG or gold-anti-human IgM. If the sample contains IgG and IgM antibodies against those antigens, they will react and turn red. The typhidot test becomes positive within 2–3 days of infection.
Two colored bands indicate a positive test. A single control band indicates a negative test. A single first fixed line or no band at all indicates an invalid test. Typhidot's biggest limitation is that it is not quantitative, just positive or negative.
Tubex test
The Tubex test contains two types of particles: brown magnetic particles coated with antigen and blue indicator particles coated with O9 antibody. During the test, if antibodies are present in the serum, they will attach to the brown magnetic particles and settle at the base, while the blue indicator particles remain in the solution, producing a blue color, which means the test is positive.If the serum does not have an antibody in it, the blue particles attach to the brown particles and settle at the bottom, producing a colorless solution, which means the test is negative.