TYPHOID FEVER

​WELCOM TO MADEK ZINC HERBAL(THE USE OF LOCAL HERBS WILL MAKE YOU LAUGH)Acknowledgements ........................................................................................................ viiChapter 1: The organism, the disease and transmission ....................................... 1 1.1 The organism ............................................................................ ........................... 1 1.2 The disease ........................................................................................................... 1 1.3 Contamination and transmission ....................................................................... 4 Chapter 2: Diagnosis of typhoid fever ....................................................................... 7 2.1 Specimens ............................................................................................................. 7 2.2 Microbiological procedures ............................................................................... 9 2.3 Serological procedures...................................................................................... 11 2.4 Antimicrobial susceptibility test for typhoid fever organisms .................... 16 2.5 Storage of typhoid fever organisms ................................................................ 17 2.6 Quality control .................................................................................................. 17 Chapter 3: Treatment of typhoid fever ................................................................... 19 3.1 General management ........................................................................................ 19 3.2 Antimicrobial therapy ....................................................................................... 19 3.3 Management of complications ......................................................................... 22 3.4 Management of carriers.................................................................................... 23 Chapter 4: Prevention of typhoid fever ................................................................... 25 4.1 Safe water........................................................................................................... 25 4.2 Food safety ......................................................................................................... 25 4.3 Sanitation ............................................................................................................ ACKNOWLEDGEMENTThe author is  greatly indebted to our LORD CHRIST for all the physical and spiritual resources and feasible  provided, and by whose grace the publishing work has been possible. I also wish to express my profound gratitude to all OSSEC agricultural and General science students their contribution and also to readers whose corrective contributions has helped to shape this herbal tips.Chapter 1:The organism, the disease and transmissionTyphoid fever is caused by Salmonella typhi, a Gram-negative bacterium. A very similarbut often less severe disease is caused by Salmonella serotype paratyphi A.The nomenclature for these bacteria is confused because the criteria for designatingbacteria as individual species are not clear. Two main views on the nomenclature of thegenus Salmonella have been discussed. Le Minor and Popoff suggested that two speciesshould be recognized: Salmonella bongori and Salmonella enterica. S. enterica includedsix subspecies, of which subspecies I (one) contained all the pathogens of warm-bloodedanimals. S. typhi was a serotype within subspecies I: Salmonella enterica subspecies Iserotype typhi. This proposal was rejected by the International Judicial Commissionbecause the name was not well known to clinicians and its use might cause accidentsendangering health or life. The original rules therefore remain in force. Ezaki andcolleagues have noted in the International Journal of Systematic and EvolutionaryMicrobiology that the correct nomenclature for the causal agent of typhoid fever isSalmonella typhi and have requested that the current subspecific status of serotypeparatyphi A should be raised to specific status, i.e. Salmonella paratyphi A.S. typhi has several unique features, the genetic basis of many of which is known asa 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 manymore 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(see Chapter 2). One of the most specific is that of polysaccharide capsule Vi, which ispresent in about 90% of all freshly isolated S. typhi and has a protective effect againstthe bactericidal action of the serum of infected patients. This capsule provides the basisfor one of the commercially available vaccines (see Chapter 4). Vi antigen is present insome other bacteria (Citrobacter freundii, Salmonella paratyphi C and Salmonelladublin) but not in exactly the same genetic context. The ratio of disease caused byS. typhi to that caused by S. paratyphi is about 10 to 1 in most of the countries wherethis matter has been studied.1.2 The diseaseDuring an acute infection, S. typhi multiplies in mononuclear phagocytic cells beforebeing released into the bloodstream. After ingestion in food or water, typhoid organismspass through the pylorus and reach the small intestine. They rapidly penetrate themucosal epithelium via either microfold cells or enterocytes and arrive in the laminapropria, where they rapidly elicit an influx of macrophages (Mp) that ingest the bacillibut do not generally kill them. Some bacilli remain within Mp of the small intestinal2 The diagnosis, treatment and prevention of typhoid feverfever, disturbances of bowel function (constipation in adults, diarrhoea in children),headache, malaise and anorexia. Bronchitic cough is common in the early stage ofthe illness. During the period of fever, up to 25% of patients show exanthem (rosespots), on the chest, abdomen and back.Complicated disease: Acute typhoid fever may be severe. Depending on the clinicalsetting and the quality of available medical care, up to 10% of typhoid patientsmay develop serious complications. Since the gut-associated lymphoid tissueexhibits prominent pathology, the presence of occult blood is a common findingin the stool of 10-20% of patients, and up to 3% may have melena. Intestinalperforation has also been reported in up to 3% of hospitalized cases. Abdominaldiscomfort develops and increases. It is often restricted to the right lower quadrantbut may be diffuse. The symptoms and signs of intestinal perforation and peritonitissometimes follow, accompanied by a sudden rise in pulse rate, hypotension, markedabdominal tenderness, rebound tenderness and guarding, and subsequentabdominal rigidity. A rising white blood cell count with a left shift and free air onabdominal radiographs are usually seen.Altered mental status in typhoid patients has been associated with a high case-fatalityrate. Such patients generally have delirium or obtundation, rarely with coma. Typhoidmeningitis, encephalomyelitis, Guillain-Barré syndrome, cranial or peripheral neuritis,and psychotic symptoms, although rare, have been reported. Other seriouscomplications documented with typhoid fever include haemorrhages (causing rapiddeath in some patients), hepatitis, myocarditis, pneumonia, disseminated intravascularWHO/V&B/03.07 3coagulation, thrombocytopenia and haemolytic uraemic syndrome. In the pre-antibioticera, which had a different clinical picture, if patients did not die with peritonitis orintestinal haemorrhage, 15% of typhoid fever cases died with prolonged persistentfever and diseases for no clear reason. Patients may also experience genitourinary tractmanifestations or relapse, and/or a chronic carrier state may develop.Carrier state: 15% of patients, depending on age, become chronic carriersharbouring S.typhi in the gallbladder1.2.2 Magnitude of the problemTyphoid fever is a global health problem. Its real impact is difficult to estimate becausethe clinical picture is confused with those of many other febrile infections. Additionally,the disease is underestimated because there are no bacteriology laboratories in mostareas of developing countries. These factors are believed to result in many cases goingundiagnosed. On the basis of the literature (2, 3) and the incidence of typhoid feverrecorded in control groups in large vaccine field trials with good laboratory support ithas been estimated that approximately 17 million cases of typhoid fever and 600 000associated deaths occur annually (4). However, the estimates have been biased becausestudy populations have usually been in areas of high incidence. Furthermore, theseestimates of burden relate to the clinical syndrome of typhoid fever but not to S. typhiexposure. Since the prevalence of bacteraemia in febrile children is quite high (23%)in areas of endemicity it is suggested that exposure to the bacteria is higher than indicatedby the figures that are based solely on the clinical syndrome of typhoid fever.The incidence of the disease in areas of endemicity may resemble the incidencesobserved in control groups in large vaccine field trials, viz. between 45 per 100 000per year and over 1000 per 100 000 per year. Preliminary results from recent studiesconducted in Bangladesh by ICDDR,B show an incidence of approximately 2000 per100 000 per year. Typhoid fever also has a very high social and economic impact becauseof the hospitalization of patients with acute disease and the complications and loss ofincome attributable to the duration of the clinical illness (5). It is important to notethat reports from some provinces in China and Pakistan have indicated more cases ofparatyphoid fever caused by S. paratyphi A than by S. typhi.In areas of endemicity and in large outbreaks, most cases occur in persons aged between3 and 19 years. In 1997, for example, this age range was reported during an epidemic ofthe disease in Tajikistan. Nevertheless, clinically apparent bacteraemic S. typhi infectionin children aged under three years has been described in Bangladesh, India, Jordan,Nigeria, and elsewhere (6, 7). In Indonesia there is a mean of 900 000 cases per yearwith over 20 000 deaths. In Indonesia, people aged 319 years accounted for 91% ofcases of typhoid fever and the attack rate of blood-culture-positive typhoid fever was1026 per 100 000 per year. A similar situation was reported from Papua New Guinea.When typhoid fever was highly endemic in certain countries in South America theincidence of clinical typhoid fever in children aged under 3 years was low. In Chile,however, single blood cultures for all children aged under 24 months who presented athealth centres with fever, regardless of other clinical symptoms, showed that 3.5% hadunrecognized bacteraemic infections caused by S. typhi or S. paratyphi (8).Enteric fever had not been suspected on clinical grounds in any of the children.In South America the peak incidence occurred in school students aged 519 years andin adults aged over 35 years. This kind of study has not been conducted in other areasof endemicity.4 The diagnosis, treatment and prevention of typhoid feverBetween 1% and 5% of patients with acute typhoid infection have been reported tobecome chronic carriers of the infection in the gall bladder, depending on age, sex andtreatment regimen. The propensity to become a carrier follows the epidemiology ofgall bladder disease, increasing with age and being greater in females than in males.The propensity to become a chronic carrier may have changed with the presentavailability and selection of antibiotics as well as with the antibiotic resistance of theprevalent strains. The role of chronic carriers as a reservoir of infection was studiedin Santiago, Chile, where a crude rate of 694 carriers per 100 000 inhabitants wasfound (9)1.2.3 Case definitionConfirmed case of typhoid fever A patient with fever (38°C and above) that has lasted for at least three days, with alaboratory-confirmed positive culture (blood, bone marrow, bowel fluid) of S. typhi.Probable case of typhoid feverA patient with fever (38°C and above) that has lasted for at least three days, with apositive serodiagnosis or antigen detection test but without S. typhi isolation.Chronic carrierExcretion of S. typhi in stools or urine (or repeated positive bile or duodenal stringcultures) for longer than one year after the onset of acute typhoid fever. Short-termcarriers also exist but their epidemiological role is not as important as that of chroniccarriers. Some patients excreting S. typhi have no history of typhoid fever.1.3 Contamination and transmissionHumans are the only natural host and reservoir. The infection is transmitted by ingestionof food or water contaminated with faeces. Ice cream is recognized as a significant riskfactor 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 arecontaminated with faeces. Epidemiological data suggest that waterborne transmissionof S. typhi usually involves small inocula, whereas foodborne transmission is associatedwith large inocula and high attack rates over short periods. The inoculum size and thetype of vehicle in which the organisms are ingested greatly influence both the attackrate and the incubation period. In volunteers who ingested 109 and 108 pathogenicS. 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 of14 persons who ingested 103 organisms developed clinical illness. Although it is widelybelieved that Salmonella is transmitted via the oral route, the transmissionof S. typhimurium via the respiratory route has been demonstrated in a mousemodel (10).Family studies were conducted in Santiago, Chile, during an era of high typhoidendemicity in order to ascertain whether chronic carriers were significantly morefrequent in households where there were index cases of children with typhoid feverthan in matched control households. Other epidemiological studies investigated whetherWHO/V&B/03.07 5risk factors could be identified for persons with typhoid fever in comparison withuninfected household members. It was concluded that chronic carriers in householdsdid not play an important role in transmission. Subsequently, it was shown that theirrigation of salad with wastewater contaminated with sewage was the key factorresponsible for maintaining the high endemicity of typhoid in Santiago. In developedcountries, on the other hand, typhoid is transmitted when chronic carriers contaminatefood as a consequence of unsatisfactory food-related hygiene practices.Chapter 2:Diagnosis of typhoid feverThe definitive diagnosis of typhoid fever depends on the isolation of S. typhi fromblood, bone marrow or a specific anatomical lesion. The presence of clinical symptomscharacteristic of typhoid fever or the detection of a specific antibody response issuggestive of typhoid fever but not definitive. Blood culture is the mainstay of thediagnosis of this disease.Although ox bile medium (Oxgall) is recommended for enteric fever pathogens(S. typhi and S. paratyphi), only these pathogens can be grown on it. In a generaldiagnostic laboratory, therefore, where other pathogens are suspected, a general bloodculture medium should be used. More than 80% of patients with typhoid fever havethe causative organism in their blood. A failure to isolate the organism may be causedby several factors: (i) the limitations of laboratory media (11); (ii) the presence ofantibiotics (12); (iii) the volume of the specimen cultured (13); or (iv) the time ofcollection, patients with a history of fever for 7 to 10 days being more likely thanothers to have a positive blood culture. Bone marrow aspirate culture is the gold standardfor the diagnosis of typhoid fever (14, 15, 16) and is particularly valuable for patientswho have been previously treated, who have a long history of illness and for whomthere has been a negative blood culture with the recommended volume of blood (17).Duodenal aspirate culture has also proved highly satisfactory as a diagnostic test (18)but has not found widespread acceptance because of poor tolerance of duodenalaspiration, particularly in children (19).2.1 Specimens If a bacteriology laboratory is not available on site, clinical specimens for culture canbe transported to a main laboratory for processing. For blood culture it is essential toinoculate media at the time of drawing blood. For other specimens it is advisable tomake the time of transportation to the laboratory as short as possible. It is moreimportant to process the specimens quickly than to keep them cold. Once they havebeen inoculated, blood culture bottles should not be kept cold. They should be incubatedat 37°C or, in tropical countries, left at room temperature, before being processed inthe laboratory.2.1.1 BloodThe volume of blood cultured is one of the most important factors in the isolation ofS. typhi from typhoid patients: 1015 ml should be taken from schoolchildren andadults in order to achieve optimal isolation rates; 24 ml are required from toddlersand preschool children (13, 17). This is because children have higher levels of bacteraemiathan adults. In some regions it may be impossible to collect such large volumes of8 The diagnosis, treatment and prevention of typhoid feverblood and so alternative diagnostic methods may be necessary for cases in which bloodcultures are negative. Because reducing the blood volume reduces the sensitivity of theblood culture, however, an effort should be made to draw sufficient blood if at allpossible. Blood should be drawn by means of a sterile technique of venous punctureand should be inoculated immediately into a blood culture bottle with the syringe thathas been used for collection.Several reports of pseudobacteraemia have been associated with the reinoculation ofblood culture bottles after the collection of blood in contaminated vessels. The practiceof inoculating blood culture bottles from specimens taken for biochemicalor haematological analysis should therefore be avoided. The optimum ratio of thevolume of blood to traditional culture broth should be 1 to 10 or more (e.g. 1:12).Some commercial blood culture systems have special resins in the media which allowhigher volumes of blood to be used. The instructions with commercial blood culturesystems should always be read and the recommended amounts should not be exceeded.In general, if 5 ml of blood are drawn they should be inoculated into 45 ml or more ofbroth. If 1015 ml of blood are drawn the specimen can be divided into equal aliquotsand inoculated into two or more blood culture bottles. This allows the use of standardblood culture bottles of 50 ml. For small children the volume of blood drawn can bereduced but should still be inoculated into 45 ml of culture broth. In order to assist theinterpretation of negative results the volume of blood collected should be carefullyrecorded. The blood culture bottle should then be transported to the main laboratoryat ambient temperature (15°C to 40°C) as indicated above. Blood cultures should notbe stored or transported at low temperatures. If the ambient temperature is below15°C it is advisable to transport blood cultures in an incubator. In the laboratory, bloodculture bottles should be incubated at 37°C and checked for turbidity, gas formationand other evidence of growth after 1, 2, 3 and 7 days. For days 1, 2 and 3, only bottlesshowing signs of positive growth are cultured on agar plates. On day 7 all bottlesshould be subcultured before being discarded as negative.2.1.2 SerumFor serological purposes, 13 ml of blood should be inoculated into a tube withoutanticoagulant. A second sample, if possible, should be collected at the convalescentstage, at least 5 days later. After clotting has occurred the serum should be separatedand stored in aliquots of 200 ml at 4°C. Testing can take place immediately or storagecan continue for a week without affecting the antibody titre. The serum should befrozen at -20°C if longer-term storage is required.2.1.3 Stool samplesStools can be collected from acute patients and they are especially useful for the diagnosisof 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 specimensshould be collected in a sterile wide-mouthed plastic container. The likelihood ofobtaining positive results increases with the quantity of stools collected. Specimensshould preferably be processed within two hours after collection. If there is a delay thespecimens should be stored in a refrigerator at 4°C or in a cool box with freezer packs,and should be transported to the laboratory in a cool box. Stool culture may increasethe yield of culture-positive results by up to 5% in acute typhoid fever. If a stoolsample cannot be obtained, rectal swabs inoculated into Carry Blair transport mediumcan been used but these are less successful.WHO/V&B/03.07 92.2 Microbiological procedures2.2.1 Blood cultureA typical blood culture bottle contains 45 ml of tryptic soy broth or brain heart infusionbroth. These are inoculated with 5 ml of fresh blood and incubated at 37°C. Negativesshould be kept for at least seven days. Because S. typhi is not the only bacterial pathogenfound in blood, subculturing is performed on days 1, 2, 3 and 7 on non-selective agar.The best agar is blood agar (horse or sheep blood) as this allows the growth of mostbacterial pathogens. If blood agar is not available, nutrient agar can be used incombination with MacKonkey agar. In some laboratories the use of MacConkey agaralone is preferred as this allows the growth of only bile-tolerant bacteria such asS. typhi and does not allow the growth of many Gram-positive contaminants.The contamination of blood cultures reduces isolation rates for S. typhi and should beprevented as far as possible. It is important to identify contaminating bacteria thatcome from the skin of patients or the air of the laboratory so that measures can betaken to prevent further problems. MacKonkey agar should therefore not be used asthe only agar for the sampling of blood cultures in a diagnostic microbiology laboratory.Furthermore, because it is selective, MacKonkey agar does not permit the growth ofGram-positive pathogens or even all E. coli.For suspected tyhoid fever, subculture plates should be incubated at 37°C for1824 hours in an aerobic incubator.2.2.2 Stool or rectal swab cultureThis involves inoculating 1 g of stool into 10 ml of selenite F broth and incubating at37°C for 1848 hours. Because selenite broth is very sensitive to heat the manufacturer’sinstructions should be carefully followed during preparation and overheating of thebroth during sterilization should be avoided. Once a batch is prepared it should bestored at 4°C. Selenite broth inhibits the motility of E. coli found in stools but does notkill this bacterium. A subculture of selenite broth on a selective agar is therefore madefrom the surface of the broth without disturbing the sediment. The choice of agarmedia includes Mac Conkey agar, desoxycholate citrate agar, xylose-lysinedesoxycholate agar, and hektoen enteric agar or SS (SalmonellaShigella). The plate isincubated at 37°C for 24 hours. Different batches of agar plates can give slightly differentcolonies of S. typhi and it is therefore important to keep one strain of S. typhi for use inquality control for each batch of agar plates and selenite broth. New batches of mediaare inoculated with the control strain and the amount of growth and the appearance ofthe colonies are recorded. If S. typhi does not grow as well as usual in any batch ofmedium, discard the medium and make a fresh one.The identification of colonies as S. typhi is straightforward if reagents of satisfactoryquality are available. Colonies from solid media can be used for agglutination withspecific antisera. Several salmonellae may share the same antigenic structure.Consequently, confirmation by means of biochemical tests is always necessary.2.2.3 Colony characteristicsBlood agarOn blood agar, S. typhi and S. paratyphi usually produce non-haemolytic smooth whitecolonies.MacConkey agarOn MacConkey agar, salmonellae produce lactose non-fermenting smooth colonies.SS agarOn SS agar, salmonellae usually produce lactose non-fermenting colonies with blackcentres (except S. paratyphi A, whose colonies do not have black centres).Desoxycholate agarOn desoxycholate agar, salmonellae produce lactose non-fermenting colonies with blackcentres (except S. paratyphi A, whose colonies do not have black centres).Xylose-lysine-desoxycholate agarOn xylose-desoxycholate agar, salmonellae produce transparent red colonies with blackcentres (except S. paratyphi A, whose colonies do not have black centres).Hektoen enteric agarOn hektoen enteric agar, salmonellae produce transparent green colonies with blackcentres (except S. paratyphi A, whose colonies do not have black centres).Bismuth sulfite agarOn this medium, salmonellae produce black colonies.Chapter 3:Prevention of typhoid feverThe major routes of transmission of typhoid fever are through drinking water or eatingfood contaminated with Salmonella typhi. Prevention is based on ensuring access tosafe water and by promoting safe food handling practices. Health education isparamount to raise public awareness and induce behaviour change.THE BEST WAY OF SOLVING TYPHOID  IS TO USE THE ORGANIC/LOCAL HERBS WHICH CAN RECOVER YOUR TYPOID IN JUST 7 DAYS CONTACT:0558817226/0558460344WHATSAPP:0558817226/0558460344Gmail:millsahyia2004@gmail.comLOCATED AT KUKURANTUMI AKYEM E/R NEAR ST.PAUL TECHNICAL SCHOOL HOUSE  NUMBER KD57NOTE: JUST ONE GALLON WIL L HEAL YOUR SICKNESS4.1 Safe waterTyphoid fever is a waterborne disease and the main preventive measure is to ensureaccess to safe water. The water needs to be of good quality and must be sufficient tosupply all the community with enough drinking water as well as for all other domesticpurposes 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 bestrengthened from catchment to consumer. Safe drinking water should be madeavailable 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 ofthe water however safe its source. Drinking-water can be made safe by boiling itfor one minute or by adding a chlorine-releasing chemical. Narrow-mouthed potswith covers for storing water are helpful in reducing secondary transmission oftyphoid fever. Chlorine is ineffective when water is stored in metallic containers.In some situations, such as poor rural areas in developing countries or refugeecamps, fuel for boiling water and storage containers may have to be supplied.4.2 Food safetyContaminated food is another important vehicle for typhoid fever transmission.Appropriate food handling and processing is paramount and the following basic hygienemeasures 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.26 The diagnosis, treatment and prevention of typhoid feverDuring outbreaks, food safety inspections must be reinforced in restaurants and forstreet food vendors activities .Typhoid can be transmitted by chronic carriers who do not apply satisfactoryfood-related hygiene practices. These carriers should be excluded from any activitiesinvolving food preparation and serving. They should not resume their duties until theyhave had three negative stool cultures at least one month apart.4.3 SanitationProper sanitation contributes to reducing the risk of transmission of all diarrhoealpathogens including Salmonella typhi.Appropriate facilities for human waste disposal must be available for all thecommunity. In an emergency, pit latrines can be quickly built.Collection and treatment of sewage, especially during the rainy season, must beimplementedIn areas where typhoid fever is known to be present, the use of human excreta asfertilisers must be discouraged.4.4 Health educationHealth education is paramount to raise public awareness on all the above mentionedprevention measures. Health education messages for the vulnerable communities needto be adapted to local conditions and translated into local languages. In order to reachcommunities, 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 hygieneand 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 Vaccination4.5.1 Currently available vaccinesThe old parenteral killed whole-cell vaccine was effective but produced strongside-effects because of LPS. Two safe and effective vaccines are now licensed andavailable. One is based on defined subunit antigens, the other on whole-cell liveattenuated bacteria.WHO/V&B/03.07 27The first of these vaccines, containing Vi polysaccharide, is given in a single dosesubcutaneous (s.c.) or i.m. Protection begins seven days after injection, maximumprotection being reached 28 days after injection when the highest antibody concentrationis obtained. In field trials conducted in Nepal and South Africa, where the disease isendemic and attack rates reach 900/100 000, the protective efficacy was 72% one andhalf years after vaccination (74) and was still 55% three years after a single dose (75).The vaccine is approved for persons aged over two years. Revaccination is recommendedevery three years for travellers. In a field trial in South Africa, 10 years afterimmunization 58% of vaccinees still had over 1 ìg/ml of anti-Vi antibodies in theirblood (76), i.e. a protective level. In efficacy trials conducted in Chiang Su and Guangxi,China, in 1995 and 1997 respectively with a locally produced Vi vaccine, 72% protectionwas obtained in vaccinees (77, 78). A protective efficacy of 70% was reported in apopulation vaccinated before or during an outbreak situation in the same country (78).The Vi vaccine is licensed in Australia and in more than 92 countries in Africa, theAmericas, Asia, and Europe. It is mainly used by travellers visiting areas at high risk oftyphoid fever because of the presence of multidrug-resistant strains. There have been afew reports of Vi-negative S. typhi strains (79). However, S. typhi strains freshly isolatedfrom the blood of patients have always been Vi-positive. During laboratory storage ortransfer the Vi capsule may be lost but even if this happens through gene mutation oralteration it is quite uncommon. Moreover, this is not a major problem in relation tothe protection obtained in Asian countries where Vi-negative strains have been reportedat the low average level of 3%. The majority of the 600 000 estimated deaths per yearare in Asia. Vaccinated people with Vi can be differentiated from S. typhi carriers becauseof the higher level of Vi antibodies in the latter (see 3.4 above).The live oral vaccine Ty2la is available in enteric-coated capsule (80) or liquidformulation. It should be taken in three doses two days apart on an empty stomach.It elicits protection as from 1014 days after the third dose. It is approved for use inchildren aged at least 5 years. Travellers should be revaccinated annually. The protectiveefficacy of the enteric-coated capsule formulation seven years after the last dose is still62% in areas where the disease is endemic; the corresponding figure for the liquidformulation is 70%. Herd immunity was clearly demonstrated during field trials inChile. Antibiotics should be avoided for seven days before or after the immunizationseries. This vaccine is licensed in 56 countries in Africa, Asia, Europe, South America,and the USA. Although the package insert allows simultaneous administration ofmefloquine (Lariam®) or chloroquine (Nivaquine® or Aralen®) for malaria prophylaxis,it is recommended that an interval of three days be maintained between the completionof the immunization series and the first dose of mefloquine or proguanil.4.5.2 Future vaccinesVi-rEPAA new Vi conjugate candidate vaccine bound to non-toxic recombinant Pseudomonasaeruginosa exotoxin A (rEPA) has enhanced immunogenicity in adults and inchildren aged 514 years, and has induced a booster response in children aged24 years (81). In a double-blind randomized field trial, 11 091 Vietnamese childrenaged 25 years were given two injections of Vi-rEPA separated by six weeks (82).No serious side-reactions were observed. The efficacy after 27 months of activesurveillance was 91.2%. Passive surveillance in the 16 months since the study ended(three-and-a-half years after the first injection) showed 88% efficacy.28 The diagnosis, treatment and prevention of typhoid feverS. paratyphi A causes the second commonest enteric fever in Asia. The TAB vaccine,composed of inactivated Salmonella, caused a strong side-reaction. A new S. paratyphiA vaccine composed of the surface O-specific polysaccharide conjugated with tetanustoxoid was shown to be safe and immunogenic in Vietnamese adults, 108 teenagers and110 children aged 24 years (83). An efficacy trial is being planned.Other candidatesThree live attenuated candidate vaccines are currently being evaluated. Each isadministered as a single oral dose. CVD 908-htrA is an S. typhi strain with a mutationdeletion in the htrA gene (84, 85); a derivative strain, CVD 909, was prepared in orderto produce Vi antigen according to constitutive expression. The second candidate is anS. typhi Ty2 strain with triple mutation deletion in the cya, crp and cdt genes (86).The third is a derivative of an S. typhi Ty2 strain with a double mutation deletion ingenes phoP and phoQ (87).4.5.3 Recommendations on vaccine useThe occurrence of S. typhi strains that are resistant to fluoroquinolones emphasizesthe need to use safe and effective vaccines to prevent typhoid fever. WHO recommendsvaccination for people travelling in high-risk areas where the disease is endemic.People living in such areas, people in refugee camps, microbiologists, sewage workersand children should be the target groups for vaccination.Routine immunizationDuring the 1980s, typhoid fever was successfully controlled in Bangkok by annualroutine immunization of school-age children (88). The disease reappeared few yearsafter immunization was stopped. Routine immunization is conducted in several areasof Uzbekistan, resulting in a low incidence of the disease. WHO recommends thatthe immunization of school-age children be undertaken wherever the control ofthe disease is a priority. School-based typhoid immunization programmes shouldbe limited to geographical areas where typhoid fever is a recognized public healthproblem and to areas where antibiotic-resistant S. typhi strains are particularly prevalent.The use of typhoid vaccines in schoolchildren should be harmonized with theschool-based administration of Td (see Report of the Scientific Group of Experts (SAGE),WHO/GPV/98.06, and Strategies, policies and practices for immunization of adolescents:a global review, WHO, 1999). The Vi vaccine is recommended for use in immunocompromised hosts. Because some countries, e.g. Bangladesh and India, are reportingtyphoid fever cases among the very young, immunization should be started in nurseryschool children. In routine immunization, therefore, the use of the available typhoidvaccines should be considered in areas where typhoid fever is endemic in childrenaged over two years. Either Vi or Ty21a vaccine should be used.CONTACT:  0558460344/0558817226GMAIL:millsahyia2004@gmail.com