Review Article

Typhoid Fever
Current Concepts
Zulfiqar A. Bhutta, MB, BS, FRCP, FRCPCH, PhD
Abstract: Infectious diseases account for most of the 10 million
annual deaths globally in children younger than 5 years. In recent
years, data indicating that typhoid fever is a major cause of morbidity
among the urban and periurban populations and the single most
important cause of febrile bacteremia in febrile children has emerged.
In several community-based studies from south Asia, the incidence
rate seems to be especially high among young children, with rates
exceeding 500 to 1000 cases per 100,000 population. In contrast,
nontyphoidal salmonella infections in Africa seem to be an important
cause of community-acquired bacteremia, especially among HIVinfected populations.
Although isolated cases of chloramphenicol resistance in
Salmonella typhi have been known for a long time, the mid 1980s saw
the emergence of strains of S. typhi resistant to all the 3 primary oral
antibiotics. In recent years, there has also been a marked increase in
quinolone-resistant isolates. Although the exact determinants and factors
associated with endemic disease and outbreaks of drug-resistant cases of
typhoid are uncertain, there does seem to be an association with
crowding, lack of sanitation and hygiene, and access to street foods.
The appropriate and rapid diagnosis of typhoid remains a
challenge with a variety of serological diagnostic tests and polymerase
chain reactionbased techniques. Given the limited resources
available for case management, appropriate antimicrobial therapy of
multidrug- and quinolone-resistant typhoid poses particular problems
in developing countries, especially because of the rapid emergence of
resistant strains in recent years. Therefore, it is imperative that the
focus clearly remain on preventive strategies for typhoid, including
safe water, hygiene, and appropriate vaccination strategies.
(Infect Dis Clin Pract 2006;14:266 272)

espite the vast advances in public health and hygiene in

much of the developed world, enteric fever (more
commonly termed typhoid fever) remains endemic in many
developing countries. Typhoid fever is caused by Salmonella
enterica serovar Typhi (S. typhi), a Gram-negative bacterium. A very similar but often less severe disease is caused
by S. paratyphi A and, less commonly, by S. paratyphi B
(Schotmulleri) and S. paratyphi C (Hirschfeldii).

Department of Pediatrics and Child Health, The Aga Khan University,

Karachi, Pakistan.
Address correspondence and reprint requests to Zulfiqar A. Bhutta, MB, BS,
FRCP, FRCPCH, PhD, Chairman, Department of Paediatrics and Child
Health, The Aga Khan University, Stadium Road, P.O. Box 3500,
Karachi 74800, Pakistan. E-mail: [Link]@[Link].
Copyright n 2006 by Lippincott Williams & Wilkins
ISSN: 1056-9103/06/1405-0266

266

PATHOGENESIS
Human volunteer experiments established an infecting
dose of about 105 to 109 organisms with an incubation period
ranging from 4 to 14 days, depending on the inoculating dose
of viable bacteria.1 After ingestion, S. typhi are thought to
invade the body through the gut mucosa in the terminal ileum,
possibly through specialized antigen-sampling cells, known as
M cells, which overlie gut-associated lymphoid tissues,
through enterocytes, or via a paracellular route. After
attachment to the microvilli, S. typhi crosses the intestinal
mucosal barrier by an intricate mechanism involving
membrane ruffling, actin rearrangement, and internalization
in an intracellular vacuole. After passing through the intestinal
mucosa, S. typhi enters the mesenteric lymphoid system, and
then passes into the bloodstream via the lymphatics. This
primary bacteremia is usually symptomless, and blood
cultures are frequently negative at this stage of the disease.
The blood-borne bacteria are disseminated throughout the
body and are thought to colonize the organs of the
reticuloendothelial system, where they may replicate within
macrophages. After a period of bacterial replication, S. typhi
are shed back into the blood, causing a secondary bacteremia,
which coincides with the onset of clinical symptoms and
marks the end of the incubation period (Fig. 1).
In addition to the virulence of the infecting organisms,
host factors and immunity may also play an important role in
predisposition to infection. Similar to studies in murine
models, a recent study has indicated an association between
susceptibility to typhoid fever and genes within the major
histocompatibility complex class II and class III loci.2 To
illustrate, carriers pass a large number of virulent bacilli into
the intestine daily, which are then excreted in the stool,
without entering the epithelium of the host. Patients who are
infected with HIV are at significantly increased risk of
clinical infection with S. typhi and S. paratyphi.3 Similarly,
patients with Helicobacter pylori infection also have
increased risk of acquiring typhoid.4

EPIDEMIOLOGY AND RECENT BURDEN

ESTIMATES
There are few established surveillance systems for
typhoid in the developing world, especially in community
settings; as a result, the true problem is difficult to estimate.
Recent estimates indicate that there may be at least 21.7
million typhoid cases annually (with an estimated 5.4 million
cases due to paratyphoid). However, the global mortality
estimates of about 200,000 deaths have been revised 3-fold
downward from previous estimates.5,6 The incidence rate of

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Typhoid Fever: Current Concepts

FIGURE 1. Pathogenesis of typhoid fever.

typhoid fever in developed countries is lower than 15 cases

per 100,000 population, with most cases occurring among
travelers. In contrast, the incidence varies considerably in the
developing world, with estimated incidence rates ranging
from 100 to 1000 cases per 100,000 population. Several
population-based studies from south Asia7 9 also indicate
that, contrary to previous views, the age-specific incidence of
typhoid may be highest in children younger than 5 years,
with comparatively higher rates of complications and
hospitalization. In contrast with previous studies in Latin
America10 and Africa11 suggesting that S. typhi infection
may cause either a benign bacteremia or mild disease in
infancy and childhood, the consistency of data between the
south Asian studies may reflect the risk of early exposure to
relatively large infecting dose of the organisms in these
populations.
There may be other factors that affect the changing
epidemiology of typhoid. Although the overall ratio of
disease caused by S. typhi to that caused by S. paratyphi is
about 10:1, the proportion of S. paratyphi infections is
increasing in some parts of the world12 (Dong Mei Tan
personal communication, 2005). In addition, in contrast with
the Asian situation, the HIV and AIDS epidemic in Africa
has also been associated with a concomitant increase in
community-acquired bacteremia caused by nontyphoidal
salmonellae, such as S. typhimurium,3,13 and an illness that
may be clinically indistinguishable from typhoid. The exact
reasons for these differences in the spectrum of salmonella
infections between Asia and Africa remain unclear.

Another worrying development in typhoid has been the

emergence of drug-resistant typhoid. After the sporadic
outbreaks of chloramphenicol-resistant typhoid between
1970 and 1985, many strains of S. typhi developed
plasmid-mediated multidrug resistance (MDR) to all the 3
primary antimicrobials (ampicillin, chloramphenicol, and
trimethoprim-sulfamethoxazole).14 Although this was countered by the availability and advent of oral quinolones, the
chromosomally acquired quinolone resistance in S. typhi has
been recently described in recent years from various parts of
Asia15 and may be related to the widespread and indiscriminate use of these agents in population settings.16

CLINICAL FEATURES
The incubation period is usually 7 to 14 days but is
also dependent on the infecting dose (range, 3 30 days). The
clinical presentation of typhoid fever varies from a mild
illness with low-grade fever, malaise, and slight dry cough to
a severe clinical condition with abdominal discomfort and
multiple complications. The advent and availability of
antibiotic therapy has changed the presentation of typhoid
fever; the classic mode of presentation with a slow and
stepladder rise in fever and toxicity is now rare.17
Many factors influence the severity and overall clinical
outcome of the infection. These include the duration of
illness before the initiation of appropriate therapy, the choice
of antimicrobial treatment, age, exposure or vaccination

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267

Infectious Diseases in Clinical Practice
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Bhutta

history, the virulence of the bacterial strain, the quantity of

inoculum ingested, and several host factors affecting the
immune status.
The presentation of typhoid fever may also differ
according to age. Although previous data from South
America and other parts of Africa suggested that typhoid
may present as a mild illness in young children,10,11 this may
vary in different parts of the world. There is emerging
evidence from south Asia that the presentation of typhoid
may be more dramatic in children younger than 5 years, with
comparatively higher rates of complications and hospitalization.7 9 Diarrhea, toxicity, and complications, such as
disseminated intravascular complications, are also more
common in infancy, with higher case fatality rates. However,
some of the other features and complications of typhoid
fever observed in adults, such as relative bradycardia,
neurological manifestations, and gastrointestinal bleeding,
are relatively rare in childhood.
Typhoid fever usually presents with high-grade fever
with a wide variety of associated features, such as generalized
myalgia, abdominal pain, hepatosplenomegaly, abdominal
pain, and anorexia. In younger children, diarrhea may be a
more common presentation in the earlier stages of the illness
and may be followed by constipation. In the absence of
localizing signs, the early stage of the disease may be difficult
to differentiate from other endemic diseases, such as malaria
or dengue fever. In about 25% of cases, a macular or
maculopapular rash (rose spots) may be visible around the 7th
to the 10th day of the illness, and lesions may appear in crops
of 10 to 15 on the lower chest and abdomen and may last 2 to 3
days. These lesions may be difficult to see in dark-skinned
children. Table 1 shows some of the common clinical features
observed among children with typhoid fever in south Asia

TABLE 1. Common Clinical Features of Typhoid Fever

in Childhood in Hospital and Community Settings in
Karachi, Pakistan
Hospital-based
Patients,18 No., %
(n = 1158)
High grade fever
Anorexia
Vomiting
Hepatomegaly
Diarrhea
Toxicity
Abdominal pain
Splenomegaly
Constipation
Headache
Jaundice
Obtundation
Ileus
Intestinal perforation
Myalgia

268

1044
811
451
471
406
377
320
226
127
138
23
23
12
58
174

(95%)
(70%)
(39%)
(41%)
(35%)
(33%)
(28%)
(20%)
(11%)
(12%)
(2%)
(2%)
(1%)
(0.5%)
(15%)

Community-based
Cohort,9 No., %
(n = 340)
338 (99%)
11 (3%)
43 (13%)
68 (20%)
26 (8%)
1 (0.3%)
65 (19%)
17 (5%)
1 (0.3%)
26 (8%)
0 (0%)
1 (0.3%)
1 (0.3%)
1 (0.3%)
15 (4.4%)

based on a longitudinal series of culture-proven cases

presenting to ambulatory settings in either community or
hospital settings.9,18 These data highlight the fact that
hospital-based series may represent more severe disease than
that presenting in community settings.
The presentation of typhoid fever may be tampered by
coexisting morbidities and early administration of antibiotics. In malaria-endemic areas and in parts of the world
where schistosomiasis is common, the presentation of
typhoid may also be atypical.19,20 It is also recognized that
MDR typhoid is a more severe clinical illness with higher
rates of toxicity, complications, and case fatality rates.21 This
may be related to the increased virulence of MDR S. typhi
and to the higher number of circulating bacteria.22 These
findings may have implications for treatment algorithms,
especially in endemic areas with high rates of MDR typhoid.
If no complications occur, the symptoms and physical
findings gradually resolve within 2 to 4 weeks; however, the
illness may be associated with malnutrition in a number of
affected children. Although the enteric fever caused by S.
paratyphi organisms (paratyphoid) has been classically
regarded as a milder illness, recent reports of infections with
drug-resistant isolates indicate that paratyphoid fever may
also be severe with significant morbidity and complications.23

COMPLICATIONS
Although altered liver function is found in many
patients with enteric fever, clinically significant hepatitis,
jaundice, and cholecystitis are relatively rare and may be
associated with higher rates of adverse outcome.
Intestinal perforation may be preceded by marked
increase in abdominal pain (usually in the right lower
quadrant), tenderness, vomiting, and features of peritonitis.
Intestinal perforation and peritonitis may be accompanied by
a sudden rise in pulse rate, hypotension, marked abdominal
tenderness and guarding, and subsequent abdominal rigidity.
A rising white blood cell count with a left shift and free air
on abdominal radiographs may be seen in such cases. The
relatively infrequent gastrointestinal perforations and hemorrhage in childhood compared with adults may be related to
the higher frequency of intestinal lymphoid hyperplasia.24,25
Rarer complications include toxic myocarditis (which
may be manifested by arrhythmias, sinoatrial block, or
cardiogenic shock). Neurological complications are also
relatively uncommon among children and may include
delirium, psychosis, increased intracranial pressure, acute
cerebellar ataxia, chorea, deafness, and Guillain Barre
syndrome. Although case fatality rates may be higher with
neurological manifestations, recovery usually occurs with no
sequelae. Other reported complications include fatal bone
marrow necrosis, disseminated intravascular coagulation,
hemolytic uremic syndrome, pyelonephritis, nephrotic syndrome, meningitis, endocarditis, parotitis, orchitis, and
suppurative lymphadenitis.
The propensity to become a carrier follows the
epidemiology of gallbladder disease, increasing with age
and antibiotic resistance of the prevalent strains. Although
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Typhoid Fever: Current Concepts

TABLE 2. Treatment of Uncomplicated Typhoid Fever

Optimal Therapy

Alternative Effective Drugs

Daily Dose in
Children
(mg/kg)

Adult
Daily
Dose

Duration
(days)

Fully sensitive Fluoroquinolone

(eg, ofloxacin or
ciprofloxacin)

15

400 mg

5 7*

Multidrug
resistance

Fluoroquinolone
or cefixime

15

400 mg

Quinolone
resistancey

Azithromycin or
ceftriaxone

15 20
8 10
75

Susceptibility

Antibiotic

Antibiotic

Daily
Dose
(mg/kg)

Adult
Daily
Dose

5 7

Chloramphenicol
Amoxicillin
TMP-SMZ
Azithromycin

50 75
75 100
8 40
8 10

2g
36 g
320 1600 mg
500 mg

0.8 1.6 g
500 mg

7 14
7

Cefixime
Cefixime

15 20
20

0.8 1.6 g
0.8 1.6 g

24 g

10 14

Duration
(days)
14 21
14
14
7
7 14
7 14

*Three-day courses are also effective and are particularly so in epidemic containment.
y
The optimum treatment for quinolone-resistant typhoid fever has not been determined. Azithromycin, the third-generation cephalosporins, or a 10- to
14-day course of high-dose fluoroquinolones is effective. Combinations of these are now being evaluated.
TMP-SMZ indicates trimethoprim-sulfamethoxazole.
Adapted from World Health Organization.34

limited data is available, the rates of chronic carriage are

generally lower in children than in adults.26

DIAGNOSIS OF TYPHOID
The basis of the diagnosis of typhoid fever is a positive
culture from the blood or another anatomical site. Results of
blood cultures are positive in 40 60% of the patients seen
early in the course of the disease, and stool and urine cultures
become positive after the 1st week. The stool culture result is
also occasionally positive during the incubation period.
However, the sensitivity of blood cultures in diagnosing
typhoid fever in many parts of the developing world is
limited as widespread antibiotic prescribing may render
bacteriological confirmation difficult. Although bone marrow cultures may increase the likelihood of bacteriological
confirmation of typhoid, these are difficult to obtain and
relatively invasive. In recent years, the development of
sensitive nested PCR diagnostic techniques have made it
possible to detect typhoid fever with greater sensitivity than
blood cultures, thus raising questions as to whether blood
cultures can be regarded as the gold-standard for its
diagnosis.27
Other laboratory investigations are nonspecific. Although blood leukocyte counts are frequently low in relation
to the fever and toxicity, there is a wide range in counts; in
younger children, leukocytosis is a common association and
may reach 20,000 to 25,000 cells per cubic millimeter.18,28
Thrombocytopenia may be a marker of severe illness and
may accompany disseminated intravascular coagulation.
Although liver function test results may be deranged,
significant hepatic dysfunction is rare.
The classic Widal test measures antibodies against the
O and the H antigens of S. typhi but lacks sensitivity and
specificity in endemic areas. Because many false-positive
and false-negative results occur, diagnosis of typhoid fever

by Widal test alone is prone to error. Other relatively newer

diagnostic tests using monoclonal antibodies have been
developed, directly detecting S. typhi-specific antigens in the
serum or S. typhi Vi antigen in the urine.29,30 However, only
a few have proved sufficiently robust in large-scale evaluations. A nested polymerase chain reaction using H1-d
primers has been used to amplify specific genes of S. typhi in
the blood of patients; given the low level of bacteremia in
enteric fever, it is a promising means of making a rapid
diagnosis.28 Despite these new developments in most of
the developing world, the basis of diagnosis of typhoid
remains clinical, and several diagnostic algorithms have
been evaluated in endemic areas.
In endemic areas, typhoid fever may mimic many
common febrile illnesses without localizing signs. In children with multisystem features, the early stages of enteric
fever may be confused with alternative conditions, such
as acute gastroenteritis, bronchitis, or bronchopneumonia.
Subsequently, the differential diagnosis includes malaria,
sepsis with other bacterial pathogens, infections caused by
intracellular microorganisms, such as tuberculosis, brucellosis, tularemia, leptospirosis, and rickettsial diseases, and viral
infections, such as dengue fever, acute hepatitis, and infectious mononucleosis. There are preliminary efforts underway
to develop diagnostic tests, such as a fever stick, that may
allow the rapid diagnosis of a variety of febrile illnesses in
developing countries.31

TREATMENT STRATEGIES
Early diagnosis of typhoid fever and institution of
appropriate treatment are essential for optimal management
and outcome, especially in children. The vast majority of
cases can be managed at home with oral antibiotics and close
medical follow-up for complications or failure to respond to
therapy. However, patients with persistent vomiting, severe

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Bhutta

TABLE 3. Treatment of Severe Typhoid Fever

Optimal Therapy
Daily Dose
in Children (mg/kg)

Alternative Effective Drugs

Adult
Daily
Dose

Duration
(days)

Susceptibility

Antibiotic

Fully sensitive

Fluoroquinolone
(eg, ofloxacin or
ciprofloxacin)

15

400 mg

10 14

Multidrug
resistant

Fluoroquinolone
(eg, ofloxacin or
ciprofloxacin)
Ceftriaxone or
cefotaxime

15

400 mg

10 14

6080

24 g

10 14

Quinolone
resistant

Antibiotic

Daily
Dose
(mg/kg)

Adult
Daily
Dose

Duration
(days)

Chloramphenicol
Ampicillin
TMP-SMZ
Ceftriaxone or
cefotaxime

100
100
8/40
60
80

2g
36 g
0.3 1.6 g
24 g

14 21
14
14
10 14

Fluoroquinolone

20

800 mg

14

TMP-SMZ indicates trimethoprim-sulfamethoxazole.

Adapted from World Health Organization.34

diarrhea, and abdominal distension may require hospitalization and parenteral antibiotic therapy. The general principles
of management of typhoid include (1) general nursing and
supportive care, and (2) antibiotic therapy.

General Nursing and Supportive Care

Close attention must be given to adequate rest, hydration,
and correction of fluid-electrolyte imbalance. Soft, easily digestible diet should be continued unless the patient has abdominal distension or ileus. This is especially important in children
because inadequate nutrition and dietary restrictions can trigger
acute malnutrition and increased risk of complications.
Antipyretics (acetaminophen, 120 750 mg every 4 to
6 hours PO) should be administered as required, recognizing
that despite clinical improvement, defervescence may take
several days. Given the importance of overall clinical
improvement, a composite typhoid morbidity score has been
recommended for monitoring recovery in typhoid.32

Antibiotic Therapy
Antibiotic therapy (the right choice, dosage, and duration) is critical to curing typhoid with minimal complications
and has made an enormous contribution to the reduction of
morbidity and mortality.33 Traditional therapy with either
chloramphenicol or amoxicillin is associated with relapse rates
of 5% to 15% and 4% to 8%, respectively, whereas the newer
quinolones and third-generation cephalosporins are associated
with higher cure rates. The antibiotic treatment of typhoid
fever in children is also influenced by the prevalence of
antimicrobial resistance. Over the last 2 decades, the emergence
of MDR strains of S. typhi (ie, isolates fully resistant to
amoxicillin, trimethoprim-sulfamethoxazole, and chloramphenicol) has necessitated treatment with second-line agents,
such as fluoroquinolones or cephalosporins. In recent years,
the emergence of resistance to quinolones has placed tremendous pressure on public health systems because therapeutic
options are limited.
Tables 2 and 3 indicate the recommended therapy for
typhoid fever in uncomplicated and severe cases based on
current recommendations by the World Health Organiza-

270

tion.34 A number of additional studies have evaluated the

potential of short-course treatment with newer antibiotics for
the treatment of typhoid fever,35 37 although this may not
succeed in MDR typhoid.38 Although it has been recommended that children with typhoid, like adults, should also
be treated with fluoroquinolones, some have questioned this
approach on the bases of the potential development of further
resistance to fluoroquinolones after widespread use in
community settings and of the fact that quinolones are still
not approved by the Food and Drug Administration for use in
children.39 A recent systematic review of the treatment of
typhoid fever also indicates that there is little evidence to
support the carte blanche administration of fluoroquinolones
to all cases of typhoid;40 thus, as much as possible, treatment
regimen that restricts the use of second- and third-line
antibiotics for the treatment of typhoid in primary care
settings must be devised.
In addition to antibiotics, the importance of supportive
treatment and maintenance of appropriate nutrition and
hydration must be underscored. Although additional treatment with dexamethasone (dosage, 3 mg/kg for the initial
dose, followed by 1 mg/kg every 6 hours for 48 hours) has
been recommended among severely ill patients with shock,
obtundation, stupor, or coma,41 this must only be done under
strict, controlled conditions and supervision, and signs of
abdominal complications may be masked.

PROGNOSIS
The prognosis for a patient with enteric fever depends
on the rapidity of diagnosis and institution of appropriate
antibiotic therapy. Other factors include the age of the patient,
the general state of health and nutrition, the causative salmonella serotype, and the appearance of complications. Infants
and children with underlying malnutrition and those infected
with MDR isolates are at higher risk of adverse outcomes.
Despite appropriate therapy, between 2% and 4% of
infected children can relapse after initial clinical response to
treatment. Individuals who excrete S. typhi for 6 months or
longer after infection are regarded as long-term carriers. The
risk of becoming a carrier is low in children and increases with
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Typhoid Fever: Current Concepts

TABLE 4. Risk Factors for Typhoid Fever from Recent Studies

Location and Year
Dyarbakir, Turkey (2001 2003)
Son La, Vietnam (2002)42
Mandalay, Myanmar (2000)43

Type of Disease
41

Jakarta, Indonesia (2001 2003)44

Semarang, Indonesia (2000)45
Mekong Delta, Vietnam (2000)46
Dushanbe, Tajikistan (1997)47
Karachi, Pakistan (1994)48
Ujung Pandang, Indonesia (1991)49

Risk Factors Identified

Community endemic disease

Hospital-based endemic disease
Village outbreak

Overcrowding; eating raw vegetables.

Lack of education; drinking of untreated water.
Drinking unboiled river water; history of contact
with other patients; not washing of hand with
soap after defecation.
Hospital cases and community controls, Contact with typhoid; nonavailability of toilet;
endemic disease
not washing of hand with soap; eating of street
foods associated with paratyphoid.
Community-based endemic disease
Lack of water supply and open sewers; never or
rare washing of hands with soap before eating.
Hospital cases and hospital and
Recent contact with a patient with typhoid fever.
community controls, endemic disease
Epidemic investigation
Drinking of unboiled water; failure of chlorination
of municipal water supply; previous antibiotic use.
Hospital cases and community controls Eating of street foods and ice cream; drinking of unboiled
water at work; previous antibiotic use.
Hospital-based case-control study,
Eating from food stalls (street foods); infrequent use of
endemic disease
soap for hand washing.

age but, generally, is in less than 2% of all infected children.

However, it must be emphasized that there is little recent
epidemiological information on the true burden of typhoid
carriers in developing countries. According to recent World
Health Organization recommendations,34 proven carriers can
be treated with amoxicillin or ampicillin (dosage, 100 mg/kg
per day) plus probenecid (dose, 1 g orally or 23 mg/kg
for children) or trimethoprim-sulfamethoxazole (dosage,
160 800 mg twice a day) for 6 weeks, with clearance rates
of about 60%. Higher clearance of long-term carriers can be
achieved with the administration of 750 mg of ciprofloxacin
twice a day for 28 days or other quinolones.
Children with schistosomiasis can develop a chronic
urinary carrier state. If cholelithiasis or schistosomiasis is
present, then additional cholecystectomy or antiparasitic
medication may also be required for eradication.

PREVENTIVE STRATEGIES

and has been largely withdrawn from public health use.

Globally, 2 vaccines are currently available for potential use
in children. An oral, live-attenuated preparation of the Ty21a
strain of S. typhi has been shown to have good efficacy
(range, 67% 82%) for up to 5 years.5 Significant adverse
effects are rare. The Vi capsular polysaccharide can be used
in people aged 2 years or older. It is administered as a single
intramuscular dose, with a booster every 2 years, and has a
protective efficacy of 70% to 80%. The vaccines are
currently recommended for traveling into endemic areas,
but a few countries have introduced large-scale vaccination
strategies. Given the age spectrum and the distribution of
cases in south Asia, it is important that the strategies for
vaccinating preschool children be explored. The recent Viconjugate vaccine has been shown to have a protective
efficacy exceeding 90% in younger children and may offer
protection in parts of the world where a large proportion of
preschool children are at risk of the disease.53

Of the major risk factors for outbreaks of typhoid,

contamination of water supplies with sewage is the most
important. Therefore, a combination of central chlorination
and domestic water purification is important during outbreaks. In endemic situations, consumption of street foods,
especially ice cream and cut fruits, and lack of proper hand
washing have been recognized as important risk factors
(Table 4).42 50 The human-to-human spread of the organisms by the long-term carriers is also an important risk
factor, and attempts should therefore be made to target food
handlers and high-risk groups for S. typhi carriage screening.
Once identified, long-term carriers must be counseled
regarding the risk of disease transmission and given advice
on hand washing and preventive strategies. Recent studies on
community-based strategies for hand washing promotion
indicate that these can be effective in reducing the problem
on diarrheal diseases and acute respiratory infections.51,52
The classic heat-inactivated whole cell vaccine is
associated with an unacceptably high rate of adverse effects

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