TYPHOID FEVER

 TYPHOID FEVER

{Etiology,Pathogenesis, Symptoms, diagnosis, treatment & prevention}                      

By: ALI MANSOOR MALIK

                      

                         Chapter 1:

The organism, the disease and transmission

The organism

Typhoid fever is caused by Salmonella typhi, a Gram-negative bacterium. A very similar but often less severe disease is caused by Salmonella serotype paratyphi A. The nomenclature for these bacteria is confused because the criteria for designating bacteria as individual species are not clear.S.typhi has several unique features, the genetic basis of many of which is known as a result of early genetic studies and the recent sequencing of the whole genome. Although many genes are shared with E. coli and at least 90% with S. typhimurium, there are several unique clusters of genes known as pathogenicity islands and many more single genes that seem to have been acquired by S. typhi during evolution. S. typhi can be identified in the laboratory by several biochemical and serological tests.

The disease

During an acute infection, S. typhi multiplies in mononuclear phagocytic cells before being released into the bloodstream. After ingestion in food or water, typhoid organisms pass through the pylorus and reach the small intestine. They rapidly penetrate the mucosal epithelium via either microfold cells or enterocytes and arrive in the lamina propria, where they rapidly elicit an influx of macrophages (Mp) that ingest the bacilli but do not generally kill them. Some bacilli remain within Mp of the small intestinal lymphoid tissue. Other typhoid bacilli are drained into mesenteric lymph nodes where there is further multiplication and ingestion by Mp. It is believed that typhoid bacilli reach the bloodstream principally by lymph drainage from mesenteric nodes, after which they enter the thoracic duct and then the general circulation. As a result of this silent primary bacteraemia the pathogen reaches an intracellular haven within 24 hours after ingestion throughout the organs of the reticuloendothelial system (spleen, liver, bone marrow, etc.), where it resides during the incubation period, usually of 8 to 14 days. The incubation period in a particular individual depends on the quantity of inoculum, i.e. it decreases as the quantity of inoculum increases, and on host factors. Incubation periods ranging from 3 days to more than 60 days have been reported.Clinical illness is accompanied by a fairly sustained but low level of secondary bacteraemia (~1 10 bacteria per ml of blood).

SYMPTOMS

The clinical presentation of typhoid fever varies from a mild illness with low-grade fever, malaise, and slight dry cough to a severe clinical picture with abdominal discomfort and multiple complications. Many factors influence the severity and overall clinical outcome of the infection. They include the duration of illness before the initiation of appropriate therapy, the choice of antimicrobial treatment, age, the previous exposure or vaccination history, the virulence of the bacterial strain, the quantity of inoculum ingested, host factors (e.g. HLA type, AIDS or other immunosuppression) and whether the individual was taking other medications such as H2 blockers or antacids to diminish gastric acid. Patients who are infected with HIV are at significantly increased risk of clinical infection with S. typhi and S. paratyphi . Evidence of Helicobacter pylori infection also represents an increased risk of acquiring typhoid fever.

 Acute non-complicated disease: Acute typhoid fever is characterized by prolonged fever, disturbances of bowel function (constipation in adults, diarrhoea in children), headache, malaise and anorexia. Bronchitic cough is common in the early stage of the illness. During the period of fever, up to 25% of patients show exanthem (rose spots), on the chest, abdomen and back.  

Complicated disease: Acute typhoid fever may be severe. Depending on the clinical setting and the quality of available medical care, up to 10% of typhoid patients may develop serious complications. Since the gut-associated lymphoid tissue exhibits prominent pathology, the presence of occult blood is a common finding in the stool of 10-20% of patients, and up to 3% may have melena. Intestinal perforation has also been reported in up to 3% of hospitalized cases. Abdominal discomfort develops and increases. It is often restricted to the right lower quadrant but may be diffuse. The symptoms and signs of intestinal perforation and peritonitis sometimes follow, accompanied by a sudden rise in pulse rate, hypotension, marked abdominal tenderness, rebound tenderness and guarding, and subsequent abdominal rigidity. A rising white blood cell count with a left shift and free air on abdominal radiographs are usually seen. Altered mental status in typhoid patients has been associated with a high case-fatality rate. Such patients generally have delirium or obtundation, rarely with coma. Typhoid meningitis, encephalomyelitis, Guillain-Barré syndrome, cranial or peripheral neuritis, and psychotic symptoms, although rare, have been reported. Other serious complications documented with typhoid fever include haemorrhages (causing rapid death in some patients), hepatitis, myocarditis, pneumonia, disseminated intravascular coagulation, thrombocytopenia and haemolytic uraemic syndrome. In the pre-antibiotic era, which had a different clinical picture, if patients did not die with peritonitis or intestinal haemorrhage, 15% of typhoid fever cases died with prolonged persistent fever and diseases for no clear reason. Patients may also experience genitourinary tract manifestations or relapse, and/or a chronic carrier state may develop.
Carrier state: 15% of patients, depending on age, become chronic carriers harbouring S.typhi in the gallbladder.

                                      Case definition
Confirmed case of typhoid fever
A patient with fever (38°C and above) that has lasted for at least three days, with a laboratory-confirmed positive culture (blood, bone marrow, bowel fluid) of S. typhi.

Probable case of typhoid fever
A patient with fever (38°C and above) that has lasted for at least three days, with a positive serodiagnosis or antigen detection test but without S. typhi isolation.

Chronic carrier

Excretion of S. typhi in stools or urine (or repeated positive bile or duodenal string cultures) for longer than one year after the onset of acute typhoid fever. Short-term carriers also exist but their epidemiological role is not as important as that of chronic carriers. Some patients excreting S. typhi have no history of typhoid fever.

                      Contamination and transmission

Humans are the only natural host and reservoir. The infection is transmitted by ingestion of food or water contaminated with faeces. Ice cream is recognized as a significant risk factor for the transmission of typhoid fever. Shellfish taken from contaminated water, and raw fruit and vegetables fertilized with sewage, have been sources of past outbreaks. The highest incidence occurs where water supplies serving large populations are contaminated with faeces. Epidemiological data suggest that waterborne transmission of S. typhi usually involves small inocula, whereas foodborne transmission is associated with large inocula and high attack rates over short periods. The inoculum size and the type of vehicle in which the organisms are ingested greatly influence both the attack rate and the incubation period. In volunteers who ingested 109 and 108 pathogenic S. typhi in 45 ml of skimmed milk, clinical illness appeared in 98% and 89% respectively.Doses of 105 caused typhoid fever in 28% to 55% of volunteers, whereas none of 14 persons who ingested 103 organisms developed clinical illness. Although it is widely believed that Salmonella is transmitted via the oral route, the transmission of S. typhimurium via the respiratory route has been demonstrated in a mouse model.                 

                     Chapter:2

         Diagnosis of typhoid fever

The definitive diagnosis of typhoid fever depends on the isolation of S. typhi from blood, bone marrow or a specific anatomical lesion. The presence of clinical symptoms characteristic of typhoid fever or the detection of a specific antibody response is suggestive of typhoid fever but not definitive. Blood culture is the mainstay of the diagnosis of this disease.

Specimens for diagnosis

Blood

The volume of blood cultured is one of the most important factors in the isolation of S. typhi from typhoid patients: 10 15 ml should be taken from schoolchildren and adults in order to achieve optimal isolation rates; 2 4 ml are required from toddlers and preschool children . This is because children have higher levels of bacteraemia than adults. In some regions it may be impossible to collect such large volumes of blood and so alternative diagnostic methods may be necessary for cases in which blood cultures are negative. Because reducing the blood volume reduces the sensitivity of the blood culture, however, an effort should be made to draw sufficient blood if at all possible. Blood should be drawn by means of a sterile technique of venous puncture and should be inoculated immediately into a blood culture bottle with the syringe that has been used for collection.

Serum

For serological purposes, 1-3 ml of blood should be inoculated into a tube without anticoagulant. A second sample, if possible, should be collected at the convalescent stage, at least 5 days later. After clotting has occurred the serum should be separated and stored in aliquots of 200 ml at +4°C. Testing can take place immediately or storage can continue for a week without affecting the antibody titre. The serum should be frozen at -20°C if longer-term storage is required.

Stool samples.
Stools can be collected from acute patients and they are especially useful for the diagnosis of typhoid carriers. The isolation of S. typhi from stools is suggestive of typhoid fever. However, the clinical condition of the patient should be considered. Stool specimens should be collected in a sterile wide-mouthed plastic container. The likelihood of obtaining positive results increases with the quantity of stools collected. Specimens should preferably be processed within two hours after collection.          

Colony characteristics

Blood agar
On blood agar, S. typhi and S. paratyphi usually produce non-haemolytic smooth white colonies.
MacConkey agar
On MacConkey agar, salmonellae produce lactose non-fermenting smooth colonies.      

SS agar
On SS agar, salmonellae usually produce lactose non-fermenting colonies with black centres (except S. paratyphi A, whose colonies do not have black centres).
Desoxycholate agar
On desoxycholate agar, salmonellae produce lactose non-fermenting colonies with black centres (except S. paratyphi A, whose colonies do not have black centres).
Xylose-lysine-desoxycholate agar
On xylose-desoxycholate agar, salmonellae produce transparent red colonies with black centres (except S. paratyphi A, whose colonies do not have black centres).
Hektoen enteric agar
On hektoen enteric agar, salmonellae produce transparent green colonies with black centres (except S. paratyphi A, whose colonies do not have black centres).
Bismuth sulfite agar
On this medium, salmonellae produce black colonies.

Felix-Widal test

This test measures agglutinating antibody levels against O and H antigens. The levels are measured by using doubling dilutions of sera in large test tubes. Usually, O antibodies appear on days 6-8 and H antibodies on days 10-12 after the onset of the disease. The test is usually performed on an acute serum (at first contact with the patient). A convalescent serum should preferably also be collected so that paired titrations can be performed. In practice, however, this is often difficult. At least 1 ml of blood should be collected each time in order to have a sufficient amount of serum. In exceptional circumstances the test can be performed on plasma without any adverse effect on the result. The test has only moderate sensitivity and specificity. It can be negative in up to 30% of culture-proven cases of typhoid fever. This may be because of prior antibiotic therapy that has blunted the antibody response. On the other hand, S. typhi shares O and H antigens with other Salmonella serotypes and has cross-reacting epitopes with other Enterobacteriacae, and this can lead to false-positive results. Such results may also occur in other clinical conditions, e.g. malaria, typhus, bacteraemia caused by other organisms, and cirrhosis. In areas of endemicity there is often a low background level of antibodies in the normal population. Determining an appropriate cut-off for a positive result can be difficult since it varies between areas and between times in given areas. It is therefore important to establish the antibody level in the normal population in a particular locality in order to determine a threshold above which the antibody titre is considered significant. This is particularly important if, as usually happens, a single acute sample is available for testing. If paired sera are available a fourfold rise in the antibody titre between convalescent and acute sera is diagnostic. Quality control of the test is achieved by running a standard serum with a known  antibody titre in parallel in each batch of assays. The variations in the standard serum should not exceed one tube, i.e. double dilution. Despite these limitations the test may be useful, particularly in areas that cannot afford the more expensive diagnostic methods . This is acceptable so long as the results are  interpreted with care in accordance with appropriate local cut-off values for the determination of positivity. This test is unnecessary if the diagnosis has already been confirmed by the isolation of S. typhi from a sterile site. New diagnostic tests are being developed.

Widal Test Sample Report

Patient Name:   ALI MANSOOR MALIK                   Date:23/4/15                        

Age:     21 Yr                             Test: Widal

Sex:    Male                               Sample was collected at lab

Sample collected by: Qaiser Abbas

………………………………………………………………………………………………………………………………………………………….…    

                                                              WIDAL TEST

……………………………………………………………………………………………………………………………………………………………..    

     ANTIGEN                            AGGLUTINATION TITRE

S.Typhi Antigen O                      Agglutination Seen in 1 : 40
S.Typhi Antigen H                      Agglutination Seen in 1 : 80
S.Paratyphi A (H)                     Agglutination Seen in 1 : 320
S.Paratyphi B (H)                       No Agglutination Seen

Recent in fection of typhoid pathogen is indicated by the above clinical examination of the patient.

IgM dipstick test
The typhoid IgM dipstick assay is designed for the serodiagnosis of typhoid fever through the detection of S. typhi-specific IgM antibodies in serum or whole blood samples.

Typhidot® test
 This test makes use of the 50 kD antigen to detect specific IgM and IgG antibodies to S. typhi . It has.undergone full-scale multinational clinical evaluation of its diagnostic value. This dot EIA test offers simplicity, speed, specificity (75%), economy, early diagnosis, sensitivity (95%) and high negative and positive predictive values. The detection of IgM reveals acute typhoid in the early phase of infection, while the detection of both IgG and IgM suggests acute typhoid in the middle phase of infection  

                                                                  Chapter 3:
            Treatment of typhoid fever        

General management

Supportive measures are important in the management of typhoid fever, such as oral orintravenous hydration, the use of antipyretics, and appropriate nutrition and bloodtransfusions if indicated. More than 90% of patients can be managed at home with oralantibiotics, reliable care and close medical follow-up for complications or failure to respond to therapy. However, patients with persistent vomiting, severe diarrhoea and abdominal distension may require hospitalization and parenteral antibiotic therapy.

Antimicrobial therapy

Efficacy, availability and cost are important criteria for the selection of first-lineantibiotics to be used in developing countries. This section reviews the therapeutic guidelines for the treatment of typhoid fever across all age groups. It should be noted, however, that therapeutic strategies for children, e.g. the choice of antibiotics, the dosage regimen and the duration of therapy, may differ from those for adults. The fluoroquinolones are widely regarded as optimal for the treatment of typhoid fever in adults . They are relatively inexpensive, well tolerated and more rapidly and reliably effective than the former first-line drugs, viz. chloramphenicol, ampicillin, amoxicillin and trimethoprim-sulfamethoxazole . The majority of isolates are still sensitive. The fluoroquinolones attain excellent tissue penetration, kill S. typhi in
its intracellular stationary stage in monocytes/macrophages and achieve higher active drug levels in the gall bladder than other drugs. They produce a rapid therapeutic response, i.e. clearance of fever and symptoms in three to five days, and very low rates of post-treatment carriage . Evidence from various settings in Asia indicates that the fluoroquinolones are equally effective in the treatment of typhoid fever in children. However, the emergence of MDR strains has reduced the choice of antibiotics in many
areas. There are two categories of drug resistance: resistance to antibiotics such aschloramphenicol, ampicillin and trimethoprim-sulfamethoxazole (MDR strains) and resistance to the fluoroquinolone drugs. Resistance to the fluoroquinolones maybe total or partial. The so-called nalidixic-acid-resistant S. typhi (NARST) is a marker of reduced susceptibility to fluoroquinolones compared with nalidixic-acid-sensitive strains. Nalidixic acid itself is never used for the treatment of typhoid. These isolates are susceptible to fluoroquinolones in disc sensitivity testing according to current guidelines. However, the clinical response to treatment with fluoroquinolones of nalidixic-acid-resistant strains is significantly worse than with nalidixic-acid-senstive strains. There is a significant number of MDR strains from the Indian subcontinent and some other Asian countries (not Indonesia). S. typhi has recently emerged as a problem in Kenya. Nalidixic-acid-resistant strains are now endemic in many areas of Viet Nam and have also been reported from the Indian subcontinent and Tajikistan. There are disturbing recent reports of the emergence of fluorquinolone-resistant isolates in various parts of Asia and there have been a few reports of resistance to third-generation cephalopsorins in the same region. Reassuringly, however, many of these reports are coupled with evidence of the re-emergence of sensitive isolates in the same regions. Table 1 outlines the treatment strategies for uncomplicated typhoid.

 The fluoroquinolone drugs are generally very well tolerated. However, in some countries the use of fluoroquinolones is relatively contraindicated in children because of concerns that they may cause articular damage. These agents are not registered for routine use in children. The concerns have arisen because of evidence of articular damage in growing, weight-bearing joints in beagles . There is now extensive experience in the use of these drugs in large numbers of children with a variety of conditions, often with longterm follow-up (cystic fibrosis, typhoid), and in the extensive use of short courses of fluoroquinolones in children for the treatment of both typhoid fever and bacillary dysentery . Their considerable benefits, particularly in areas where there are no affordable oral alternatives, outweigh the putative risk. The only known articular sideeffect is Achilles tendon rupture in patients who are also taking corticosteroids, and this has been reported only rarely. Ciprofloxacin, ofloxacin, perfloxacin and fleroxacin have generally proved effective. In recent years, however, there have been many reports of reduced susceptibility and treatment failure for ciprofloxacin . No evidence of toxicity and impact on growth has been described in children with typhoid who have received ciprofloxacin. There is no    evidence of the superiority of any particular fluoroquinolone. Nalidixic acid and norfloxacin do not achieve adequate blood concentrations after oraladministration and should not be used. For nalidixic-acid-sensitive S. typhi, seven-day regimens have proved highly effective. Courses of treatment of three and five days have also proved highly effective against nalidixic-acid-sensitive strains. These very short courses are best reserved for outbreaks when antibiotics are in short supply.For nalidixic-acid-resistant infections a minimum of seven days of treatment at the maximum permitted dosage is necessary and 10-14 days are usually required. Courses shorter than seven days are unsatisfactory.
Chloramphenicol, despite the risk of agranulocytosis in 1 per 10 000 patients, is still widely prescribed in  developing countries for the treatment of typhoid fever. S. typhi strains from many areas of the world, e.g. most countries in Africa and Asia, remain sensitive to this drug and it is widely available in most primary care settings in developing countries for the treatment of pneumonia. The disadvantages of using chloramphenicol include a relatively high rate of relapse (5-7%), long treatment courses (14 days) and the frequent development of a carrier state in adults. The recommended dosage is 50-75 mg per kg per day for 14 days divided into four doses per day, or for at least five to seven days after defervescence. The usual adult dose is 500 mg given four times a day. Oral administration gives slightly greater bioavailability than intramuscular (i.m.) or intravenous (i.v.) administration of the succinate salt.
Ampicillin and amoxicillin are used at 50 to 100 mg per kg per day orally, i.m. or i.v., divided into three or four doses. No benefit has been reported to result from the addition of clavulanic acid to amoxicillin.
Trimethoprim-sulfamethoxazole, (TMP SMZ) can be used orally or i.v. in adults at a dose of 160 mg TMP plus 800 mg SMZ twice daily or in children at 4 mg TMP per kg and 20 mg SMZ per kg for 14 days. Of the third-generation cephalosporins, oral cefixime (15 20 mg per kg per day for
adults, 100 200 mg twice daily) has been widely used in children in a variety of geographical settings and found to be satisfactory . However, a trial of cefixime in MDR typhoid in Viet Nam indicated significantly higher treatment failure rates than with ofloxacin . Other agents, e.g. cefodoxime, have proved successful against typhoid fever . Because of the rising rates of quinolone resistance
there is a clear need to identify improved strategies for treating MDR typhoid in childhood. Recent data on the use of azithromycin in children indicate that it may be safely given as an alternative agent for the treatment of uncomplicated typhoid fever . Azithromycin in a dose of 500 mg (10 mg/kg) given once daily for seven days has proved effective in the treatment of typhoid fever in adults and children with defervescence times similar to those reported for chloramphenicol. A dose of 1 g per day for five days was also effective in adults . If intravenous antibiotics are required, i.v. cephalosporins can be given in the following doses: ceftriaxone, 50 75 mg per kg per day (2 4 g per day for adults) in one or two doses; cefotaxime, 40 80 mg per kg per day (2 4 g per day for adults) in two or three doses; and cefoperazone, 50-100 mg per kg per day (2 4 g per day for adults) in two doses. Ciprofloxacin, ofloxacin and pefloxacin are also available for i.v. use. There are few data on the treatment of typhoid in pregnancy. The beta-lactams are considered safe . There have been several case reports of the successful use of fluoroquinolones but these have generally not been recommended in pregnancy because of safety concerns . Ampicillin is safe in pregnant or nursing women, as is ceftriaxone in such women with severe or MDR disease. Although there are no data indicating that azithromycin is unsafe for pregnant or nursing women, alternatives should be used if available. Most of the data from randomized controlled trials relate to patients treated in regions of endemicity. There are few data from such trials relating to patients treated in regions where the disease is not endemic or to returning travellers. Knowledge of the antibiotic sensitivity of the infecting strain is crucial in determining drug choice. If no culture is available a knowledge of likely sensitivity as indicated by the available global data may be useful. The evidence suggests that the fluoroquinolones are the optimal choice for the treatment of typhoid fever in adults and that they may also be used in children. The recent emergence of resistance to fluoroquinolones, however, suggests that their widespread and indiscriminate use in primary care settings should be restricted. In areas of the world where the fluoroquinolones are not available or not registered for public health use and where the bacterium is still fully sensitive to traditonal first-line drugs (chloramphenicol, amoxicillin or trimethoprim-sulfamethoxazole), these remain appropriate for the treatment of typhoid fever. They are inexpensive, widely available and rarely associated with side-effects.                                                 

                                       Management of complications

Both outpatients and inpatients with typhoid fever should be closely monitored for the development of complications. Timely intervention can prevent or reduce morbidity and mortality. The parenteral fluoroquinolones are probably the antibiotics of choice for severe infections but there have been no randomized antibiotic trials . In severe typhoid the fluoroquinolones are given for a minimum of 10 days (Table 2). Typhoid fever patients with changes in mental status, characterized by delirium, obtundation and stupor, should be immediately evaluated for meningitis by examination of the cerebrospinal fluid. If the findings are normal and typhoid meningitis is suspected, adults and children should immediately be treated with high-dose intravenous dexamethasone in addition to antimicrobials . If dexamethasone is given in an initial dose of 3 mg/kg by slow i.v. infusion over 30 minutes and if, after six hours, 1 mg/kg is administered and subsequently repeated at six-hourly intervals on seven further occasions, mortality can be reduced by some 80 90% in these high-risk patients. Hydrocortisone in a lower dose is not effective . High-dose steroid treatment can be given before the results of typhoid blood cultures are available if other causes of severe disease are unlikely.

Patients with intestinal haemorrhage need intensive care, monitoring and blood transfusion. Intervention is not needed unless there is significant blood loss. Surgical consultation for suspected intestinal perforation is indicated. If perforation is confirmed, surgical repair should not be delayed longer than six hours. Metronidazole and gentamicin or ceftriazone should be administered before and after surgery if a fluoroquinolone is not being used to treat leakage of intestinal bacteria into the abdominal cavity. Early intervention is crucial, and mortality rates increase as the delay between perforation and surgery lengthens. Mortality rates vary between 10% and 32% . Relapses involving acute illness occur in 5 20% of typhoid fever cases that have apparently been treated successfully. A relapse is heralded by the return of fever soon after the completion of antibiotic treatment. The clinical manifestation is frequently milder than the initial illness. Cultures should be obtained and standard treatment should be administered. In the event of a relapse the absence of schistosomiasis shouldn be confirmed.

Management of carriers

An individual is considered to be a chronic carrier if he or she is asymptomatic and continues to have positive stool or rectal swab cultures for S. typhi a year following recovery from acute illness. Overall, some 1-5% of typhoid fever patients become chronic carriers. The rate of carriage is slightly higher among female patients, patients older than 50 years, and patients with cholelithiasis or schistosomiasis. If cholelithiasis or schistosomiasis is present the patient probably requires cholecystectomy or antiparasitic medication in addition to antibiotics in order to achieve bacteriological cure. In order to eradicate S. typhi carriage, amoxicillin or ampicillin (100 mg per kg per day) plus probenecid (Benemid®) (1 g orally or 23 mg per kg for children)or TMP-SMZ (160 to 800 mg twice daily) is administered for six weeks; about 60% of persons treated with either regimen can be expected to have negative cultures on follow-up. Clearance of up to 80% of chronic carriers can be achieved with the administration of 750 mg of ciprofloxacin twice daily for 28 days or 400 mg of norfloxacin. Other quinolone drugs may yield similar results .

Carriers should be excluded from any activities involving food preparation and serving, as should convalescent patients and any persons with possible symptoms of typhoid fever. Although it would be difficult for typhoid carriers in developing countries to follow this recommendation, food handlers should not resume their duties until they have had three negative stool cultures at least one month apart. Vi antibody determination has been used as a screening technique to identify carriers among food handlers and in outbreak investigations. Vi antibodies are very high in chronic S. typhi carriers

                     Chapter:4

         Prevention of typhoid fever

The major routes of transmission of typhoid fever are through drinking water or eating food contaminated with Salmonella typhi. Prevention is based on ensuring access to safe water and by promoting safe food handling practices. Health education is paramount to raise public awareness and induce behaviour change.

4.1 Safe water

Typhoid fever is a waterborne disease and the main preventive measure is to ensure access to safe water. The water needs to be of good quality and must be sufficient to supply all the community with enough drinking water as well as for all other domestic purposes such as cooking and washing. During outbreaks the following control measures are of particular interest:

 In urban areas, control and treatment of the water supply systems must be strengthened from catchment to consumer. Safe drinking water should be made available to the population trough a piped system or from tanker trucks.

 In rural areas, wells must be checked for pathogens and treated if necessary.

 At home, a particular attention must be paid to the disinfection and the storage of the water however safe its source. Drinking-water can be made safe by boiling it for one minute or by adding a chlorine-releasing chemical. Narrow-mouthed pots with covers for storing water are helpful in reducing secondary transmission of typhoid fever. Chlorine is ineffective when water is stored in metallic containers.

 In some situations, such as poor rural areas in developing countries or refugee camps, fuel for boiling water and storage containers may have to be supplied.

4.2 Food safety

Contaminated food is another important vehicle for typhoid fever transmission. Appropriate food handling and processing is paramount and the following basic hygiene measures must be implemented or reinforced during epidemics:  washing hands with soap before preparing or eating food; avoiding raw food, shellfish, ice;  eating only cooked and still hot food or re-heating it.

During outbreaks, food safety inspections must be reinforced in restaurants and for street food vendors activities .

Typhoid can be transmitted by chronic carriers who do not apply satisfactory food-related hygiene practices. These carriers should be excluded from any activities involving food preparation and serving. They should not resume their duties until they have had three negative stool cultures at least one month apart.

4.3 Sanitation

Proper sanitation contributes to reducing the risk of transmission of all diarrhoeal pathogens including Salmonella typhi. Appropriate facilities for human waste disposal must be available for all the community. In an emergency, pit latrines can be quickly built.  Collection and treatment of sewage, especially during the rainy season, must be implemented  In areas where typhoid fever is known to be present, the use of human excreta as fertilizers must be discouraged.

4.4 Health education

Health education is paramount to raise public awareness on all the above mentioned prevention measures. Health education messages for the vulnerable communities need to be adapted to local conditions and translated into local languages. In order to reach communities, all possible means of communication (e.g. media, schools, women’s groups, religious groups) must be applied. Community involvement is the cornerstone of behaviour change with regard to hygiene and for setting up and maintenance of the needed

infrastructures. In health facilities, all staff must be repeatedly educated about the need for : excellent personal hygiene at work;  isolation measures for the patient; disinfection measure.

4.5 Vaccination
4.5.1 Currently available vaccines
The old parenteral killed whole-cell vaccine was effective but produced strong side-effects because of LPS. Two safe and effective vaccines are now licensed and available. One is based on defined subunit antigens, the other on whole-cell live attenuated bacteria.                                                                    

Recommendations on vaccine use
The occurrence of S. typhi strains that are resistant to fluoroquinolones emphasizes the need to use safe and effective vaccines to prevent typhoid fever. WHO recommends vaccination for people travelling in high-risk areas where the disease is endemic. People living in such areas, people in refugee camps, microbiologists, sewage workers and children should be the target groups for vaccination.

Routine immunization

During the 1980s, typhoid fever was successfully controlled in Bangkok by annual routine immunization of school-age children . The disease reappeared few years after immunization was stopped. Routine immunization is conducted in several areas of Uzbekistan, resulting in a low incidence of the disease.

WHO recommends that“the immunization of school-age children be undertaken wherever the control of the disease is a priority”.

 School-based typhoid immunization programmes should be limited to geographical areas where typhoid fever is a recognized public health problem and to areas where antibiotic-resistant S. typhi strains are particularly prevalent. The use of typhoid vaccines in schoolchildren should be harmonized with the school-based administration of Td. The Vi vaccine is recommended for use in immunocompromised hosts. Because some countries, e.g. Bangladesh and India, are reporting typhoid fever cases among the very young, immunization should be started in nursery school children.

In routine immunization, therefore, the use of the available typhoid vaccines should be considered in areas where typhoid fever is endemic in children aged over two years. Either Vi or Ty21a vaccine should be used.

Immunization in outbreak situations

During 1998 in Tajikistan the vaccination of 18 000 persons with one i.m. dose of Vi polysaccharide proved effective (72% protection) in preventing the spread of typhoid fever in an immunized community

facing an outbreak situation because of the presence of a multidrug-resistant strain of S. typhi . In China’s Xing-An county  a locally produced Vi vaccine provided 70% protection in school-age children immunized either before or during an outbreak.

 Vaccination against typhoid fever before or during an outbreak situation should therefore be seriously considered as an effective tool. If the community in question cannot be fully immunized, persons aged 2-19 years should be the target group for vaccination, in addition to children in nursery schools.

                     Conclusions

Infection caused by S. typhi remains an important public health problem, particularly in developing countries. Morbidity and mortality attributable to typhoid fever are once again increasing with the emergence and worldwide spread of S. typhi strains that are resistant to most previously useful antibiotics. As a consequence there is renewed interest in understanding the epidemiology, diagnosis and treatment of typhoid fever and some specific aspects of its pathogenesis. More importantly, perhaps, there is much interest in the possibility of expanded roles for typhoid vaccines. Public health authorities should now devise ways of using the two currently available improved typhoid vaccines, parenteral Vi polysaccharide and oral Ty21a, in large-scale nursery-based and school-based immunization programmes, and should monitor their public health impact.

Referrence

Background document:The diagnosis, treatment and prevention of typhoid fever

WHO/V&B/03.07
ORIGINAL: ENGLISH

                                                 

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                          ALI MANSOOR MALIK