Typhoid is an acute infectious disease caused by a specific serotype of the bacterium Salmonella typhi. The bacterium usually enters the body through the mouth by the ingestion of contaminated food or water, penetrates the intestinal wall, and multiplies in lymphoid tissue. After an average 10–14-day incubation period, the early symptoms of typhoid appear: headache, malaise, generalized aching, fever, and restlessness that may interfere with sleep. There may be loss of appetite, nosebleeds, cough, and diarrhea or constipation. Persistent fever develops and gradually rises, usually in a stepwise fashion, reaching a peak of 39 or 40 °C (103 or 104 °F) after 7–10 days and continuing with only slight morning remissions for another 10–14 days. During about the second week of fever, when typhoid bacilli are present in great numbers in the bloodstream, a rash of small, rose-colored spots appears on the trunk, lasts four or five days, and then fades away. The lymph follicle along the intestinal wall in which the typhoid bacilli have multiplied become inflamed and necrotic and may slough off, leaving ulcers in the walls of the intestine. The dead fragments of intestinal tissue may erode blood vessels, causing hemorrhage, or they may perforate the intestinal wall, allowing the intestine's contents to enter the peritoneal cavity. Other complications can include acute inflammation of the gallbladder and heart failures with a continued high fever the symptoms usually increase in intensity and mental confusion may appear. By the end of the third week the patient is emaciated, abdominal symptoms are marked, and mental disturbance is prominent. In favorable cases, during about the beginning of the fourth week, the fever begins to decline, the symptoms begin to abate, and the temperature gradually returns to normal. If untreated, typhoid fever proves fatal in up to 25 percent of all cases. Patients with such diseases as cancer or sickle cell anemia are particularly prone to develop serious and prolonged infection with Salmonella. Most major typhoid fever has been caused by the pollution of public water supplies. Food and milk may be contaminated, however, by the disease who is employed in handling and processing them; by flies; or by the use of polluted water for cleaning purposes. Shellfish, particularly oysters, grown in polluted water and fresh vegetables grown on soil fertilized or contaminated by untreated sewage are possible causes. The prevention of typhoid fever depends mainly on proper sewage treatment, filtration and chlorination of water, and the exclusion of carriers from employment in food industries and restaurants. In the early part of the 20th century, prophylactic vaccination using killed typhoid organisms was introduced, mainly in military forces and institutions, and contributed to a lowering of the incidence of the disease. Diagnosis of typhoid fever is made by blood culture, stool culture, and serological testing. The treatment of typhoid fever is with antibiotics, particularly Chloramphenicol begins to lower the patient's fever within three or four days after beginning therapy, and there is progressive improvement thereafter. The drug treatment is continued for several weeks in order to prevent relapses.