Typhoid disease overview¶
IDM is committed to utilizing modeling approaches and quantitative analysis to explore how interventions can act to reduce the burden and transmission of typhoid fever. This page provides information about typhoid itself: the biology, symptoms, treatment, and prevention. See Typhoid model overview for information about the Epidemiological MODeling software (EMOD) TYPHOID_SIM simulation type developed by IDM to aid in typhoid elimination.
Typhoid is caused by Salmonella enterica typhi (hereafter referred to as S. Typhi), a gram- negative enteric bacillus that is a motile, facultative anaerobe. There are many different strains of S. Typhi that have varying virulence and susceptibility to antibiotics.
S. Typhi is transmitted via the fecal-oral route, either by person-to-person contact or environmental exposure through contaminated food or water. An inoculum size of approximately 100,000 bacteria is required for infection. S. Typhi has several qualities that make it an effective pathogen; it contains an endotoxin typical of gram- negative organisms, excretes a protein that enables it to live intracellularly in non-phagocytic cells, and inhibits the activity of leukocytes which makes the innate immune response ineffective.
After the initial acute infection, 2-5% of people remain asymptomatic carriers of the infection, which lives in the gallbladder and is shed through the stool. Unlike other Salmonella species, S. Typhi has no animal carriers, so these asymptomatic carriers are a crucial disease reservoir. The most famous typhoid carrier was “Typhoid Mary” Mallon, a cook responsible for infecting at least 78 and killing 5 in the early 20th century.
For more information on how the EMOD typhoid model simulates transmission, see Disease transmission. The seasonality of transmission via contact vs. environmental exposure is described in Seasonality.
Once ingested, the bacteria multiply in the small intestine over the course of the next one to three weeks, after which they pass through the intestinal wall and into other organs and tissues. The patient’s immune system has little ability to fight the infection due to its effect on leukocytes.
Early in the infection, people commonly experience fever, headache, and cough. They may also have a bloody nose or abdominal pain. The severity of the illness progresses quickly and then causes extreme fatigue, high fever, delirium, slow heartbeat, and diarrhea or constipation. Some patients may also experience red spots on the chest and abdomen and enlarged liver or spleen. More severe symptoms may occur in the third week, such as severe dehydration, respiratory distress, intestinal hemorrhage, and neuropsychiatric symptoms such as confusion and motor problems. The fever generally begins to subside after three weeks.
The EMOD typhoid model represents the progression of typhoid through a series of state changes. For more information, see Disease progression.
Without treatment, case fatality is approximately 20%, with the highest fatality rate among children under four years of age.
Diagnosis & treatment¶
Accurate and timely diagnosis and treatment of typhoid is essential for improving the health of those who are sick and preventing additional infections. However, there are a number of challenges involved due to both the nature of the illness and the available tools. The parameters you can use to simulate various diagnostic tests and treatments are described in Individual-level interventions.
Diagnostic tests fall into two categories: bacterial cultures or serologic assays for detecting antibodies. According to the World Health Organization (WHO), a definitive diagnosis of typhoid requires isolation of S. Typhi using blood or bone marrow culture. However, cultures have considerable practical limitations in that the tests are expensive, require trained medical providers and specialized laboratory facilities, and take several days to return results.
Additionally, bacterial levels in the blood are highest before symptoms develop and drop after the illness develops, so many blood cultures fail to diagnose active infections. Bone marrow cultures are more sensitive, but sampling bone marrow is a painful and challenging procedure rarely undertaken in low- and middle-income countries. Urine and stool cultures are easier but do not provide reliable results.
Serologic assays detect antibodies that the immune system produces in response to a typhoid infection. The older Widal test detects antibodies to the O and H antigens of Salmonella; though it is prone to false positives due to cross-reactivity with other infectious agents, it is still used in some areas due to its low cost. Several newer serological assays that aim to provide cost- effective and rapid results are in development, though they still need to be evaluated in larger trials.
Therefore, in low-resource and high-burden settings, most typhoid diagnoses are made based on clinical criteria. Because typhoid symptoms are similar to many other febrile illnesses, this can lead to frequent misdiagnoses. Generally, the clinician will attempt to rule out malaria, dysentery, and pneumonia before treating with chloramphenicol while awaiting blood or stool culture results.
Prevention & treatment¶
Safe water, sanitation, and hygiene (WASH) interventions are critical to prevent transmission of typhoid. For example, water treatment or filtration, toilets and other sanitation systems, and education campaigns regarding the importance of hand washing and proper food handling practices.
In many high-burden settings, progress on the infrastructure required for WASH interventions can be slow and typhoid vaccines also play an important role in preventing the disease. There are two vaccines available to prevent typhoid. One is an inactivated vaccine administered as an injection. A booster dose is needed every two years and it can be given to younger children (age two and older). The other is a live oral vaccine that provides immunity for up to five years and can be given to school-age children.
Treatment for typhoid involves oral rehydration and antibiotics to kill S. Typhi bacteria. With proper care, mortality can be reduced to 1%-3%. However, some patients can remain chronic carriers even after treatment. Recent studies have shown chronic carriers can be cured of their infection with long-term courses of antibiotics.
Global typhoid burden¶
School-age children are most vulnerable to typhoid infection. There are approximately 10 million new cases each year across the globe, causing 150,000 deaths. It is especially common in India.