Organism Salmonella enterica serovar Typhi.

Clinical features Although transmitted by the faecal-oral route, typhoid manifests mainly as a systemic infection, generally presenting as a fever. The fever starts gradually, increasing in a stepwise fashion over the first 1-2 weeks, with a progressive malaise, disorientation and drowsiness. At the end of the first week, a rash of characteristic rose spots may appear (not seen in black skins).

The stools are normally constipated at first, but may later change to diarrhoea. If the organism localizes in the Peyers patches of the small intestine, ulceration, haemorrhage and perforation may occur.

Diagnosis is difficult and depends upon finding the organism in blood, stool or urine. A blood culture (3-5 ml) taken in the first week is the most satisfactory. Culture from the stools can be obtained if repeated examinations are made from the start of the illness, with a greater likelihood of becoming positive as the illness progresses, provided antibiotics have not been used. Finding the organism from urine, in which it is excreted spasmodically, is more difficult. Where the diagnosis has still not been made and further investigation considered necessary, S. enterica can be cultured from the bone marrow or bile (by duodenal string test). Bone marrow culture has the advantage of occasionally being positive even if the patient has received antibiotics. Sewage culture can be used in the investigation of epidemics.

The Widal test on the patient's serum can indicate infection, but a search for S. enterica must also be made to confirm the diagnosis. The Widal test has three components, the H (flagella) the O (somatic) and Vi antigens. The H antibody titre can be raised by any Salmonella infection and remain raised (giving an estimate of previous exposure), whereas the O antibody indicates recent infection. However, both H and O levels will be raised by a recent typhoid immunization, negating any value of the test. A titre of 1/40 or higher is required. Added weight is given to the diagnosis by making a series of tests and demonstrating a rising titre. The Vi antibody is produced during the acute stage of the disease and persists while the organism is present and, therefore, has a value in detecting the carrier state.

Transmission The main method of transmission is water, contaminated by faecal material from a carrier. These water-borne outbreaks may not always be explosive and where low-grade infection of the water source is taking place, groups of cases, spread over time, may occur.

S. enterica has been found to survive periods of 4 weeks in fresh water, but if the water is stored in bright sunlight (as in a reservoir), then the number of organisms rapidly dies off. It can survive in aerobic conditions with organic nutrient present, as found in contaminated streams. If the stream is polluted with raw sewage, then the organism can survive over 5 weeks and within solid faecal material for considerable periods of time. Seawater is bactericidal, but where a sewage outfall is near a shellfish bed, then the organism is filtered and concentrated providing a potent source of infection if the shellfish are eaten raw.

Milk and dairy products provide ideal culture media and can become infected during handling by a carrier, or rinsing of containers with polluted water. Contaminated ice cream has been responsible for several outbreaks. Pasteurization of milk at 60°C is effective in killing S. enterica. Infection of meat products and canned foods is less common, but can occur in the cooling process (if carried out in polluted water).

Flies can transmit the organism from faeces to food, whereas person-to-person infection is uncommon. Secondary cases form a very small proportion of an epidemic; so serial transmission in an unhygienic environment is not a feature.

Carriers The carrier state is the most important epidemiological feature, with persistence of the organism in some individuals for periods in excess of 50 years. Three per cent of typhoid cases are found to still be excreting organisms after 1 year. People become more prone to act as carriers if they have a chronic irritational process, such as cholecystitis, and especially the presence of gallstones (in which S. enterica are able to survive). Opisthorchis sinensis has also been associated with the development of faecal carriers. Urinary carriers often suffer from an abnormality of the urinary tract such as calculus and Schistosoma haematobium is a predisposing cause.

Incubation period is 3-30 days, with a mean of 8-14 days. The length of the incubation period is inversely proportional to the infecting dose.

Period of communicability From 1 week after the start of illness for a period of 3 months, except in the chronic carrier where it continues for years.

Occurrence and distribution In most tropical areas, the disease is endemic with seasonal outbreaks. Water is probably the main vehicle of transmission, but may be more related to the gathering of people at scarce water sources (as occurs in the dry season), rather than epidemics occurring with the early rains. Endemic typhoid is maintained by sub-clinical infections, especially in un-diagnosed children, who obtain a degree of immunity. It has been suggested that these sub-clinical infections result from persons swallowing lower bacterial doses than the critical threshold. In endemic areas, the peak of infection is in children between 5 and 12 years of age.

Typhoid is a worldwide disease and serious outbreaks, generally epidemic in nature, have occurred in developed countries from contamination of the water supply or food produce. Repair work on water supplies or an accidental interruption of chlor-ination has led to epidemics. Typhoid organisms have persisted in canned meat cooled in infected water thousands of miles away from the outbreak. Many well-known outbreaks have been due to ice cream. The movement of carriers can be followed from the outbreaks they produce as they travel around.

Control and prevention Control relies on the protection of water supplies and the sanitary disposal of faeces. Placing latrines too close to wells, fractures in water mains and accidental contamination by sewage are ways in which outbreaks occur. Drinking water taken from polluted streams can be boiled, chlorinated or left to stand (the three-pot system in Fig. 3.7). Reservoirs and settling tanks can reduce the level of organisms below the infecting dose.

Where the outbreak can be traced to a food source, a search for carriers can be made. Stool specimens should be obtained from persons involved in the preparation of the food. If a carrier is discovered, they should be prohibited from preparing food. This cannot always be applied to domestic catering, so careful instruction in personal hygiene should be tried. The organism can persist under the nails, so these should be kept short. Food must be protected from flies and stored only for limited periods. All shellfish must be properly cooked.

An infecting dose of at least 103 organisms is required (except in persons suffering from achlorhydria), but may need to be as high as 109. The main effect of vaccination appears to be to offer protection against lower dose infecting inocula (less than 105 organisms).

Typhoid vaccine has a variable effect, offering protection to persons who receive a low infecting dose, but none to those who ingest a high dose of organisms. It may, therefore, be useful for individual protection, but is limited on a mass immunization basis, except to selected groups such as school children. The live oral vaccine (Ty 21a) gives protection for at least 3 years and may also give cross-immunity against S. enterica Paratyphi B. It is administered in three capsules taken orally on days 1, 3 and 5. A vaccine containing the polysaccharide Vi antigen is administered parenterally by a single injection. Both of these methods produce less reaction than the whole-bacteria vaccine. A booster dose is required every 3 years in travellers or persons from non-endemic areas living in countries where typhoid is common. The oral vaccine is probably more effective in young children and in mass programmes, given as a liquid formulation rather than in capsules, but pro-guanil, mefloquine and antibiotics should be stopped 3 days before administration.

Treatment is with ampicillin or co-tri-moxazole, but multiple resistant organisms have meant that more expensive antibiotics, such as the quinalones (e.g. ciprofloxocin and ofloxacin) and third-generation cepha-losporins, are now required. Prolonged treatment of the carrier with ampicillin, 1 g three times a day for 11 weeks has been successful, or if available, one of the quinalones can be used. Relapse occurs in about 5% of treated acute cases.

Surveillance Once a carrier has been identified they should be warned of the danger they pose to others and told to report their condition to any medical people they come in contact with. Carriers are sometimes registered by health authorities.

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