Decisions about the administration of blood products are an integral aspect of caring for the injured patient. The per-spective on transfusion of homologous blood, once viewed as a routine and low-risk procedure, has shifted dramatically as a result of increased recognition and awareness of its poten¬tial risks, including transfusion-transmitted diseases (TID). Consideration of the specific indications for and potential benefits of transfusion, weighed against its potential risks, is essential in each individual decision about the type and quantity of blood products to be administered. A Consensus Development Conference sponsored by the U.S. National Institutes of Health in 1988 suggested that transfusions be administered for clearly defined indications, including the restoration of intravascular volume, restoration of oxygen carrying capacity, correction of coagulation abnormalities, and correction of granulocyte deficiencies. 1
Blood products remain a vital and limited resource. In¬creased awareness of the potential risks of TID has not re¬duced the number of transfused units of blood, which has re¬mained steady at over 14-million units of blood components
per year since 1986.2 Responsible utilization of this limited commodity is an additional factor mandating judicious trans-fusion therapy.
In this chapter we will discuss the types of blood prod¬ucts available and their characteristics. We will then outline a strategy for matching appropriate products with their spe¬cific indications.
AVAILABLE BLOOD PRODUCTS
The majority of blood is collected with anticoagulant and is rapidly separated into components, including packed red blood cells (PRBCs), platelets, plasma, cryoprecipitate, leukocytes, and more concentrated clotting factors. (Figure 12-1. Table 12-1). The separation of blood into components and improvements in the anticoagulant/preservation solu¬tions have significantly increased the storage life of blood and its products and the efficiency of utilization of these important resources.
Robert G. Mackersie, MO, FAGS
,Ideally, the therapeutic goals of allogeneic and autologous blood transfusions should represent an extension of the gen¬eral goals of resuscitation for the trauma patient: (1) restora¬tion of circulating blood volume, (2) restoration of oxygen¬carrying capacity and tissue perfusion, and (3) prevention of metabolic disturbances and complications (such as coagulopa¬thy, acidosis, and hypothermia) and the post-resuscitation in¬flammatory response syndromes. Blood transfusions continue to be an important adjunct to the treatment of both major injury and a variety of critical illnesses. In the last several years, however, largely because of ch_ in. hl.aod _1>;i.Wb and transfusion practices resulting from the acquired immuno-deficiency syndrome (AIDS) epidemic, transfusions of red cell mass and blood components (platelets and plasma) continue to decline. Despite these recent trends and improvements in plasma and blood substitutes (see Chapter 26), allogeneic and autologous blood and blood products continue to provide the best means of improving oxygen-carrying capacity and correcting deficits and coagulation.
STORED BLOOD PRODUCTS
The earliest reported attempt at blood transfusion was in 1667, when whole animal blood was transfused into a patient. The result was a dramatic hemolytic transfusion reaction, caus¬ing the practice to be abandoned until the early 1800s, when transfusion of women hemorrhaging as a result of childbirth was again attempted. Similar incompatibility problems fore¬stalled further progress until the discovery of ABO blood group types (fable 25-1). The subsequent development of anticoagulants, around the turn of the 20th century, permitted blood matching and preservation of donated blood for the first time. Further changes in transfusion therapy became possible when technologic developments allowed the separa¬tion of whole blood into cellular and noncellular components. The emphasis on component therapy, the most common form of transfusion today, started with several publications by the Office of Medical Applications of Research and the National Institutes of Health. The majority of donor blood collected in the United States is now separated into the red cell mass (with varying amounts of donor plasma), the platelet component, and the plasma component.
A unit of full donor blood typically contains approximately 500 mL (450 mL of blood plus 50 to 60 mL of an anticoagulant preservative). Whole blood is most commonly separated into various components. Packed red blood cells (RBCs), with a
TABLE 12-1. SUMMARY CHART OF BLOOD COMPONENTS
Component Major Indications Action Special Precautions Rate of Infusion
Whole blood Symptomatic anemia with Restoration of Must be ABO indentical For massive loss, fast as
large volume deficit oxygen-carrying Labile coagulation factors patient can tolerate
capacity, restoration deteriorate within
of blood volume 24 hours after collection
Red blood cells (RBCs) Symptomatic anemia Restoration of Must be ABO compatible As patient can tolerate
oxygen-carrying but less than 4 hours
Red blood cells (RBCs), Symptomatic anemia, Restoration of Must be ABO compatible As patient can tolerate
leukocytes removed febrile reactions from oxygen-carrying but less than 4 hours
leukocyte antibodies capacity
Fresh frozen plasma (FFP) Deficit of labile and Source of labile and Should be ABO compatible Less than 4 hours
stable plasma stable plasma
coagulation factors factors
Cryoprecipitated Hemophilia A, Provides Factor VIII, Frequent repeat doses Less than 4 hours
anti hemophilia von Willebrand's disease, fibrinogen, may be necessary
factor (AHF) hypofibrinogenemia, von Willebrand factor,
Factor XIII deficiency Factor XIII
Platelets Bleeding from Improves hemostasis Should not use some micro- Less than 4 hours
(pheresis) thrombocytopenia or aggregate filters (check
platelet-function manufacturer's instruction)
Granulocytes Neutropenia with infection Provides granulocytes Must be ABO compatible, One unit over 2-4 hour
(pheresis) do not use depth-type period; observe
microaggregate filters closely for reactions
What World Health Organisation says about Safety in Blood Transfusion
Blood transfusion is an essential part of modern health care. Used
correctly, it can save life and improve health. However, as with any
therapeutic intervention, it may result in acute or delayed
complications and carries the risk of transmission of infectious
agents, such as HIV, hepatitis viruses, syphilis and Chagas disease.
The inappropriate use of blood and blood products, coupled with the
transfusion of unscreened or improperly screened units, particularly
in countries with poor blood programmes, increases the risk of TTIs
to recipients. It also widen the gaps between supply and demands and
contributes to shortages of blood and blood products for patient
requiring transfusion. Thus, it is necessary to reduce the
unnecessary transfusions. This can be achieved through the
appropriate clinical use of blood, avoiding the needs for
transfusion and use of alternatives to transfusion. The transfusion
is deemed appropriate when it is used to treat condition leading to
significant morbidity and mortality that cannot be prevented or
managed effectively by other means. The commitment of the health
authorities, health care providers and clinicians are important in
prevention, early diagnosis and treatment of diseases/ conditions
that could lead to the need for blood transfusion.
Key elements of effective clinical use of blood
Consistently effective clinical transfusion practice cannot be
achieved unless the following elements are in place:
well organized blood programme, coordinated at national level to
guarantee safe, adequate and timely supply;
a national blood policy that addresses the clinical use of blood,
with appropriate supportive legal frameworks;
a national committee on the clinical use of blood and hospital
transfusion committees at local level to implement, regularly
review and update the national policy and guidelines;
national guidelines on the clinical use of blood to aid
prescribers of blood in their clinical decisions about
transfusion, based on systematic reviews of evidence on clinical
effectiveness. The development of these guidelines requires
involvement of blood prescribers from different clinical
disciplines working together with the blood transfusion services.
These guidelines should suit local situation;
the availability of simple alternatives for transfusion
(crystalloids and colloids) for the correction of hypovolaemia,
and pharmaceuticals and medical devices to reduce blood loss;
the education and training of clinician, nurses and blood
transfusion service staff involved in the transfusion process;
monitoring and evaluation of the implementation of the national
policy and guidelines and the use of monitoring data in quality
improvement and education programme to assist clinicians to
improve their practice.
In order to support Member States in developing systems for
appropriate use of blood and to reduce unnecessary transfusion, WHO
has produced a series of recommendations, guidelines and learning
materials, including Recommendations on Developing a National Policy
and Guidelines on the Clinical Use of Blood and a module of
interactive learning material, The Clinical Use of Blood.
The recommendations provide assistance to Member States in
developing and implementing national policies and guidelines and
ensuring active collaboration between the blood transfusion service
and clinicians throughout the management of patients who may require
transfusion. They emphasize the importance of education and training
in the clinical use of blood for all clinical and blood bank staff
involved in the transfusion process.
The learning material includes a comprehensive module that can be
used in undergraduate and postgraduate programmes, in-service
training and continuing medical education programmes or for
independent study by individual clinicians and blood transfusion
specialists, as well as a pocket handbook which summarizes the
information contained in the module and has been produced for quick
reference by clinicians who need to make urgent decisions on
The WHO- HQ in collaboration with the regional offices also has
carried out global and regional workshops on promotion of
appropriate clinical use of blood in the African, American, Eastern
Mediterranean and South East Asian Region as well as national
workshops in China and India. These promoted the development of
national policies and guidelines on transfusion, the establishment
of hospital transfusion committees and haemovigilance systems, the
incorporation of transfusion medicine into medical and nursing
school curricula and the development of education and training
programmes for physicians, nurses and other prescribers of blood.
WHO also provides country support in the development and
implementation of transfusion guidelines, the establishment of
hospital transfusion committees and the training of clinicians.
:: Aide-Memoire on Clinical Use of Blood in English [pdf 144kb]
:: Aide-Memoire on Clinical Use of Blood in French [pdf 92kb]
:: The Clinical Use of Blood Handbook in English [pdf 717kb]
:: The Clinical Use of Blood Handbook in Portuguese [pdf 7.20Mb]
:: The Clinical Use of Blood Handbook in Spanish [pdf 5.91Mb]
:: The Clinical Use of Blood in Obstetrics, Paediatrics, Surgery &
Anaesthesia, Trauma & Burns. Module in English [pdf 1.62Mb]
:: The Clinical Use of Blood in Obstetrics, Paediatrics, Surgery &
Anaesthesia, Trauma & Burns. Module in Portuguese [pdf 12.53Mb]
:: The Clinical Use of Blood in Obstetrics, Paediatrics, Surgery &
Anaesthesia, Trauma & Burns. Module in Spanish [pdf 11.25Mb]
:: Recommendations on Developing a National Policy and Guidelines on
the Clinical Use of Blood in English [pdf 739kb]
:: Recommendations on Developing a National Policy and Guidelines on
the Clinical Use of Blood in Spanish [pdf 2.24Mb]
Recommendations on Developing a National Policy and Guidelines on
the Clinical Use of Blood
French [pdf 245kb]
World Health Organization
Department of Essential Health Technologies
20 Avenue Appia
1211, Geneva 27
Tel: +41 22 791 4660
Fax: +41 22 791 4836
Typhoid or enteric fever is an ancient disease, which has afflicted mankind since human populations grew large enough to contaminate their water and food supplies. It is caused by Salmonella enterica serovar typhi (previously known as salmonella typhi), a pathogen specific only to humans, as well as by certain non-typhoid salmonella (NTS), particularly Paratyphoid strains A, B, C. These waterborne gram negative aerobes are associated with poor sanitation and fecal contamination of water and food supplies. The syndrome needs to be distinguished from that caused by many other organisms. Today there are as many as 16-30 million cases per year, almost exclusively in the developing world, with a mortality rate of 10%. Recent developments in the mapping of the Salmonella genome have provided insights into its pathogenicity and how antibiotic resistance and human immunity develop. Typhoid fever is important surgically because abdominal complications such as intestinal perforation, bleeding, cholecystitis and pancreatitis represent the most serious complications of the illness. Typhoid perforation of the ileum is one of the most common causes of bowel perforation in the developing world. (1) Excellent reviews are available for both adult (2-6) as well as pediatric disease. (7) This Review will focus on recent developments in our understanding of this disease.
Typhoid fever was not well understood in the ancient world, probably because its symptoms are not primarily diarrheal, but rather systemic and non-specific. It was only in the mid-19th century that physicians began to distinguish it from typhus and malaria. (8) Sir William Osler’s clinical description remains unsurpassed. Typhoid fever was frequently associated with military campaigns and was a significant cause of death in the American Civil War and Boer War where deaths from typhoid exceeded those from combat. (9) With recognition that fecal contamination of food and water supplies was the main mode of transmission of the illness and measures taken to prevent these (10;11), typhoid fever has been restricted, in industrialized countries, to localized epidemics (12;13) and infections in travelers returning from endemic areas. (14)
In contrast to that seen in the rich countries, typhoid fever remains an important cause of illness in the developing world where annual incidences in Papua New Guinea and Indonesia may reach 1200/100,000 population. A recent epidemiologic study showed that south-east and south-central Asia are the regions of highest endemicity with rates greater than 100/100,000 cases per year; the rest of Asia, Africa, Latin America, the Caribbean and Oceania (except Australia and New Zealand) are the next highest with incidence rates of 10-100/100,000 and Europe, North America and the rest of the developed world have low rates of disease. (15) Typhoid fever represents the 4th most common cause of death in Pakistan. (16)
The majority of patients, 60-90%, are treated as outpatients and, therefore, hospital based studies will underestimate true incidence. Two hospital based case-control studies from Vietnam found that risk of infection was related to recent contact with an infected person, lack of education and drinking untreated water. (17;18) S. paratyphi A, which normally causes about 15-20% of cases of typhoid fever in Asia, increasingly is becoming a pathogen in India (19) and China (20), possibly due to vaccination against S. typhi. Recent epidemiologic studies also show the rise of multi-drug resistant (MDR) organisms. (21) In a study of 1100 hospitalized children in Pakistan, the mortality rate of 1.6% was found to be related to younger age and MDR infection. (22)
Traditionally the age range considered to be at greatest risk was 5-25 years. However this has been questioned in a study from a private laboratory in Bangladesh, which found that the 57% of S. typhi isolates were in children less than 5 years of age and 27% less than 2 years. (23) This has significant implications for vaccination policies.
In 2001 the entire genome of a MDR isolate of S. typhi was sequenced. (24) This showed that Salmonella share more than 70-80% of genes with other enteric bacteria, like E. coli. Another feature of S. typhi genome is the presence of over 200 inactivated genes which are felt to be related to the adaptation of the bacteria to the human host and possibly its ability to invade human tissue. Drug resistance is encoded in a transmissible plasmid. The development of additional horizontal genes in the salmonella pathogenicity islands (SPI) represented the separation of the E. Coli and Salmonella lineages and allows for the targeting of intestinal epithelial cells by Salmonella. (25)
Much of the genetic and cellular studies on the pathophysiology of invasive Salmonella infection have been carried out in the murine model using S. typhimurium, which causes invasive disease in mice but not in humans. As opposed to the Salmonella spp. associated with human diarrheal illness, S. typhi and those strains that cause typhoid fever are able to achieve cellular invasion.
The pathophysiology of typhoid fever is a complex process which proceeds through several stages. (24;26;27) The disease begins with an asymptomatic incubation period of 7-14 days, (inversely related to the size of the infecting dose), during which bacteria invade macrophages and spread throughout the reticuloendothelial system. The first week of symptomatic disease is characterized by progressive elevation of the temperature followed by bacteremia. The second week begins with the development of rose spots, abdominal pain and splenomegaly. The third week is marked by a more intense intestinal inflammatory response particularly in the Peyer’s patches with associated necrosis which can result in perforation and hemorrhage. These clinical stages are associated with complex cellular events just now being understood.
First, ingested bacteria must survive the acidic environment of the stomach. The known increased risk of typhoid fever with concomitant Helicobacter pylori infection (28) may express itself via the hypochlorhydria associated with chronic H.pylori infection. (29) Invading organisms pass through the intestinal epithelial cells and come into contact with phagocytic cells in the Peyer’s patches of the intestinal wall. However the macrophages do not kill the bacteria. Thence, bacterial replication is primarily intracellular. Salmonella avoids encapsulation in lysosomes by diverting normal cellular mechanisms. (30) Bacteria inject effector proteins into the cells of the innate immune system (macrophages and natural killer cells) though a type III protein secretion system (TTSS) which stimulate both pro and anti-inflammatory responses. (31)
Over the asymptomatic incubation period of 7-14 days the bacteria proliferate and spread through the blood stream to other cells in the reticuloendothelial system in the liver, spleen, bone marrow and gall bladder. As replication inside phagocytic cells continues, bacteria are shed into the blood stream in sustained but low concentrations and the clinical syndrome of fever, headache and abdominal pain begins. The gallbladder is felt to be a significant site (32) for ongoing exposure of intestinal epithelial cells to the pathogen. The inflammatory response to this process of repeated exposure is felt to give rise to the necrosis which is a prominent feature of the disease. (33) This occurs in areas of greatest macrophage concentration such as the Peyer’s patches and explains why intestinal bleeding and perforation are the most frequent complications. Elsewhere typhoid nodules, foci of macrophages and lymphocytes proliferate. As the infection progresses the typical changes of sepsis accumulate in the heart, brain and kidneys. If not interrupted this process may lead to circulatory failure and death from overwhelming sepsis.
Infected or asymptomatic carrier humans represent the reservoir for S. typhi. Therefore identification and treatment of these individuals represents one strategy for interruption of transmission.
Food and water sanitation
There is no doubt that lack of clean drinking water and unsanitary conditions for the production and preparation of food represent the main reasons for the ongoing endemicity of typhoid fever in the developing world. Poor water quality, sanitation and hygiene account for some 1.7 million deaths a year world-wide (3.1% of all deaths and 3.7% of all DALY's), mainly through infectious diarrhea. Nine out of 10 such deaths are in children. (34) Poverty, uncontrolled urbanization and inadequate infrastructure all contribute to the contamination of water supplies. (35) Filtration and chlorination together are effective methods of interrupting the transmission of water-borne diseases. (36;37)
The other approach to the control and eradication of typhoid fever has been through vaccination. Acquired immunity to S. typhi infection is both humoral and cellular but is incomplete, allowing for subsequent infections and restricting the efficacy of vaccines. (38;39) Older, parenteral whole-cell vaccines resulted in significant local and systemic reactions. (40) Two new vaccines are in current use: a parenteral capsule polysaccharide vaccine based on the Vi antigen and an oral live attenuated vaccine containing strain Ty21a. The first, while resulting in local pain in 86% of children, requires 1 injection with a booster in 3 years and confers protection within 7-10 days of inoculation. On the other hand the Ty21a vaccine requires several doses, is only moderately immunogenic and its efficacy is reduced by simultaneous anti-malarial therapy, (although a report from Gabon showed that simultaneous anti-malarial prophylaxis with atovaquone/proguanil does not have this effect (41)). A systematic review for the Cochrane Database showed these two vaccines had significantly reduced efficacy (efficacy rates approx.50%) in comparison to the older whole-cell vaccines, but fewer side effects.(42) Current vaccines do not afford protection against Paratyphoid strains. The search for better vaccines continues. (43)
The use of vaccines for travelers to endemic areas has been recommended for some time; (44) even if the travel is for short periods. (45) Malaria remains the most common febrile disease of returning travelers to Italy requiring hospital admission. (46)
Mass vaccination campaigns have been used to lower the risk of disease in India and Thailand, but their use in the rest of the developing world is otherwise limited. A report from the ongoing epidemic in Tajikistan advocated mass vaccination. (47) A recent report from an urban slum community in Delhi, India showed the high costs of typhoid fever and recommended more widespread vaccination. (48) The current Vi and Ty21a vaccines are not licensed for use in children less than 2 years, in whom its efficacy is unproven, and therefore are deemed unsuitable for expanded immunization programs which target infants in their first year of life. (49) They are also costly. All these factors have restricted mass vaccination for typhoid in endemic countries.
The World Health Organization appears to advocate mass vaccination in endemic areas. (50;51) However this is seldom implemented. The Diseases of the Most Impoverished (DOMI) project is undertaking a randomized cluster vaccination program in Asia which should help to clarify the effects of mass typhoid vaccination. (52)
Traditionally the age range considered at greatest risk is 5-25 years of age, although young children and infants may also be infected. In these the disease may present as a non-specific febrile illness until diagnostic tests are positive. Akpede from Nigeria provides an excellent review of the management of these cases, including those with HIV. (53)
After the initial 7-14 day asymptomatic phase, the clinical features of typhoid fever begin with the onset of a remitting diurnal fever, anorexia, headache, lethargy, confusion, cough and abdominal pain. (54) Constipation is considered a feature, although diarrhea and vomiting is recognized, particularly with young children and those infected with HIV. Relative bradycardia is said to be a feature; increased heart rate is correlated with later stages and with mortality. (55) The clinical signs are few: rose spots (pink macules which blanch on pressure, are present on the thorax and abdomen of 60% of light-skinned patients but are considerably more difficult to detect in dark-skinned patients); abdominal tenderness (acute abdomen if perforation); splenomegaly more common than hepatomegaly; rales (with a normal chest xray); conjunctivitis and apathy. Assessment of hemodynamic and mental status is important and correlates with severity of illness. In contrast to other investigators Haq et al. found clinical factors strongly correlated with diagnostic accuracy. (56)
Thielman gives a very good differential diagnosis of other infectious which may mimic typhoid fever. (3) In Africa, malaria is probably the most important disease from which typhoid must be distinguished. (57;58)
Non resolution gives rise to complications which are discussed below. Typhoid fever patients suffer a relapse rate of 5-10% and 1-3% will become asymptomatic carriers, potentially infecting others. Relapses take the form of a milder disease and are less common after quinolone therapy. Carriers excrete S. typhi in the stool more than 3 months after treatment. In Egypt, carrier state is associated with urinary pathology such as Schistosomiasis and may be evidenced by urinary excretion. (6) Carriers require treatment with high dose quinolones (ciprofloxacin 750mg q12h) for 4 weeks. Carrier state associated with cholelithiasis is a risk for gall bladder cancer and requires cholecystectomy. (59)
The lack of specificity of the clinical spectrum, added to the difficulty of achieving a definitive bacteriologic or serologic diagnosis, frustrates clinicians managing typhoid fever.(60;61) Laboratory tests are non-specific but haemoglobin, white cell and platelet counts are usually reduced. Liver function tests are mildly elevated.
Culture of the infectious agent may be obtained from stool, urine, blood, bone marrow or bile. Bone marrow is the most sensitive source (80-95%) and positive blood cultures (60-80%) are facilitated by increasing the volume sampled. (62) Detection of S. typhi DNA by polymerase chain reaction (PCR) has recently been shown to be a very sensitive index of infection. (63)
Serologic tests have a long but limited history of use in typhoid fever. The Widal test, useful only for infection with S. typhi, detects O (surface) and H (flagellar) antigens. However, baseline titers in the general population must be determined for each geographic region. (64-66) When used as a single test in endemic areas, it lacks sensitivity and specificity. (67) A 4 fold rise in O, H or Vi titers provides support for the diagnosis of typhoid fever, but is not useful in the acute situation. As a result, numerous other serologic tests are being developed (2): ELISA; (68-70) salivary IgA;(71) a modified Widal test to detect IgM; (72) and dipstick assay.(73)
It is recommended that treatment of typhoid fever begin on the basis of clinical findings prior to definitive diagnosis. Sadly in endemic regions, facilities for definitive diagnosis, based on blood or bone marrow culture or serologic tests may be entirely lacking. Supportive measures such as oral or intravenous rehydration, antipyretics, appropriate nutrition and blood transfusion are important.
Mortality from typhoid fever showed a marked decline from 20% to 1% after the introduction of chloramphenicol in 1948. (74) Chloramphenicol however does not prevent relapse unless given for 2-3 weeks; the carrier state is not eradicated; nor is it useful against MDR strains. (75) Ampicillin and sulfonamides, co-trimazole, became the next antibiotics to be used, but multi-drug resistant MDR organisms developed.(76-78) In some regions with high MDR prevalence, sensitivity to chloramphenicol has re-emerged. (79) MDR strains are noted to be more virulent and associated with increased mortality and complications.
The flouroquinolones - ofloxacin and ciprofloxacin, the third generation cephalosporins -ceftriazone and cefixime, and azithromycin, a macrolide antibiotic, are the drugs of choice for MDR typhoid fever. Flouroquinolones achieve excellent penetration in macrophages and bile, important sites of infection. In the developed countries they have been used infrequently in patients less than 18 years of age, because of potential arthropathy. However there is increased evidence for their safety in this population. However, resistance to flouroquinolones has also developed and represents a significant threat to the treatment of typhoid fever. (80) The presence of nalidixic acid resistance is a marker for decreased susceptibility to flouroquinolones and should be tested for when dealing with MDR strains.(81-83) Nalidixic acid resistant strains may show a slower response to flouroquinolones and require higher doses (ciprofloxacin 1500mg/d instead of 1000mg/d). Switching to ceftriaxone or azithromycin may be preferable in these patients. (84) These agents should be given for at least 7 days.
The standard duration of treatment has been for 10-14 days, but uncomplicated typhoid fever has been shown to respond to shorter courses of flouroquinolones, ie. 2-3 days of treatment.(85) Thaver (75), in a systematic review for the Cochrane database comparing flouroquinolones with other antibiotics, concluded that the scientific data derived from RCTs was poor, and that there was little to recommend flouroquinolones over 1st line drugs, (chloramphenicol, ampicillin and co-trimazole). Flouroquinolones reduced failure rates when compared to third generation cephalosporins. The study recommended large multi-center outpatient trials comparing flouroquinolones and 1st line therapy in children to settle this question. Thaver et al admit their conclusions differ from those of Parry (5) and standard textbooks which recommend flouroquinolones as modern 1st line therapy. (3;4)
Since there is great regional variability with regard to antibiotic sensitivity and the presence of MDR strains and because misuse of antibiotics is a potent cause of the development of MDR strains (86), it is essential that physicians working in regions where typhoid fever is endemic, ascertain the nature and prevalence of the different strains and base appropriate recommendations for first and second line therapy on this information.
The WHO recommends the following regimes for uncomplicated typhoid fever.
Table 1 page 20 (2)
In severe disease the following regimes are recommended. Table 2 page 23 (2)
Complications occur in 10-15% of patients, particularly those who have been ill for more than 2 weeks. Gastrointestinal hemorrhage, perforation and encephalopathy are the most important. GI hemorrhage is most common but usually resolves without surgery. Severe typhoid may be defined as occurring in those patients with hypotension despite rehydration and mental confusion or altered state of consciousness. These patients may benefit from high dose dexamethasone therapy (3mg/kg followed by 8 doses of 1mg/kg q6h) with a marked reduction in mortality. (87) This is one of the few instances where high dose steroids are of value in sepsis. (88)
The surgeon is typically consulted in typhoid fever when perforation is suspected. It may present suddenly as an acute abdomen or more commonly as worsening in an already sick patient with increasing abdominal signs, rising pulse and falling blood pressure. (89) The presence of free air on abdominal xrays is pathognomonic.
These are very sick patients who require vigorous resuscitation and the addition of metronidazole to combat gram-negative anaerobes and gentamycin for aerobes. Conservative therapy has been abandoned with improved mortality rates. (90) Mortality increased when time to presentation is delayed and also with delayed time to surgery after perforation. (91) Mortality rates vary from 14% in Nigeria (89) to 34% in Cote d’Ivoire. (92) Single perforations are most common (70%) and in the terminal ileum, but multiple perforations may occur.(93)
At operation the entire small bowel and proximal colon should be carefully examined for perforation. Debate exists as to the various methods of closure from simple suture, to wedge resection and closure to segmental resection and primary anastomosis. (94;95) It is not clear to me that any conclusion can be drawn from the evidence. Obviously multiple perforations lend themselves to segmental resection.
Numerous other complications are seen with typhoid fever. (4) see Table 163-1 The most important surgical ones being: hepatic or splenic abscess(96), splenic rupture (97) and pancreatitis. Encephalomyelitis (98), osteomyelitis (99), glomerulonephritis and renal failure (100) may all occur. Myocarditis is a common cause of circulatory collapse.
Despite intensive scrutiny and major advances in genetic research and understanding the details of cellular inflammation, typhoid fever remains a major cause of death and disease in the developing world. Its eradication awaits the provision of sanitary water supplies and proper disposal of human sewage. Its eradication would probably be accelerated by programs of mass vaccination in endemic regions. Appropriate antibiotic therapy may postpone the further development of MDR strains. In the meantime, surgeons will continue to be asked to care for desperately sick typhoid patients with intestinal perforations and other complications.
1. Typhoid fever should be suspected in young children and infants with fevers of unknown origins in endemic regions.
2. Filtration and chlorination are the two important steps in ensuring a safe water supply. In urban areas safe drinking water should be made available though piped systems or trucked tankers.
3. Appropriate food handling is essential: washing hands with soap before preparing and handling food; eating only cooked or still hot food; avoiding raw food, shellfish, ice.
4. Appropriate systems for human waste disposal must be available for the entire community.
5. Countries with high rates of typhoid fever should consider mass immunization programs using new Vi and Ty21a vaccines for those more than 2 years of age.
6. In hospitals where microbiological facilities are available for the culture of salmonella spp., bone marrow samples, as well as blood and stool should be obtained in patients when typhoid fever is suspected.
7. Testing should include stools of recovering patients at 3 months or urine in regions where schistosomiasis is common, to detect the carrier state.
8. The Widal test cannot be used in the diagnosis without assessing background antibody levels in the population. Better serologic tests should be available soon.
9. Antibiotic therapy should be based on the sensitivity spectrum of local S. typhi strains. Chloramphenicol, ampicillin or co-trimazole may be adequate agents if strains are susceptible.
10. In regions where MDR strains are known to exist, fluroquinolones are the agents of choice.
11. In regions where MDR strains exist and where quinolone use has been extensive, testing for relative flouroquinolone resistance with nalidixic acid discs should be undertaken.
12. Patients, with “severe typhoid” manifested by hypotension and/or altered state of consciousness, should receive short term high dose steroid therapy.
13. The treatment of typhoid perforation is aggressive resuscitation using broad spectrum antibiotics against enteric organisms, prompt surgery with examination of the entire small bowel and right colon with resection (local or segmental) of all full thickness ulcers and perforations.
Brian Ostrow MD, FRCS(C)
Guelph, Ontario, Canada
Save review as .PDF
1. McConkey SJ, McConkey SJ. Case series of acute abdominal surgery in rural Sierra Leone. World Journal of Surgery 2002; 26(4):509-513. (84 kb)
2. anon. Background document: the diagnosis, treatment and prevention of typhoid fever. 2003. Geneva, World Health Organization. (225 kb)
Ref Type: Pamphlet
3. Thielman NM&GRL. Enteric Fever. In: Mandell GLBJE&DR, editor. Mandell, Bennett & Dolin: Principles and Practice of Infectious Diseases. Philadelphia: Churchill Livingstone, 2005: 1273-1279. (295 kb)
4. Richens J. Typhoid Fever. In: Cohen J&PWG, editor. Cohen & Powderly: Infectious Diseases. Edinburgh: Mosby Inc., 2004: 1561-1565. (141 kb)
5. Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ, Parry CM et al. Typhoid fever. New England Journal of Medicine 2002; 347(22):1770-1782. (248 kb)
6. Kamel R&WM. Salmonellosis. In: Kamel R&LJ, editor. Textbook of Tropical Surgery. London: Westminster Publishing Ltd., 2004: 908-912. (615 kb)
7. Graham SM, Graham SM. Salmonellosis in children in developing and developed countries and populations. Current Opinion in Infectious Diseases 2002; 15(5):507-512. (84 kb)
8. Cunha BA, Cunha BA. Osler on typhoid fever: differentiating typhoid from typhus and malaria. Infectious Disease Clinics of North America 2004; 18(1):111-125. (226 kb)
9. Lim ML, Wallace MR, Lim ML, Wallace MR. Infectious diarrhea in history. Infectious Disease Clinics of North America 2004; 18(2):261-274. (218 kb)
10. Casner N, Casner N. "Do It Now!" Yakima, Wash, and the campaign against rural typhoid. American Journal of Public Health 2001; 91(11):1768-1775. (711 kb)
11. Scuderi G, Scuderi G. A review of the Salmonellosis surveillance systems in Italy: evolution during the course of time within the international framework.[erratum appears in Eur J Epidemiol 2000;16(12):1187 Note: Gabriella S [corrected to Scuderi G]]. European Journal of Epidemiology 2000; 16(9):861-868. (16 kb) Abstract only
12. Yoon J, Segal-Maurer S, Rahal JJ, Yoon J, Segal-Maurer S, Rahal JJ. An outbreak of domestically acquired typhoid fever in Queens, NY. Archives of Internal Medicine 2004; 164(5):565-567. (64 kb)
13. Katz DJ, Cruz MA, Trepka MJ, Suarez JA, Fiorella PD, Hammond RM et al. An outbreak of typhoid Fever in Florida associated with an imported frozen fruit. Journal of Infectious Diseases 2002; 186(2):234-239. (187 kb)
14. Mermin JH, Townes JM, Gerber M, Dolan N, Mintz ED, Tauxe RV et al. Typhoid fever in the United States, 1985-1994: changing risks of international travel and increasing antimicrobial resistance. Archives of Internal Medicine 1998; 158(6):633-638. (189 kb)
15. Crump JA, Luby S, Mintz E. The global burden of typhoid disease. Bulletin of the World Health Organization 2004; 82:346-353. (218 kb)
16. World Health Organization. 6th International Conference on Typhoid Feve and other Salmonelloses. 2006. Geneva, WHO.
Ref Type: Pamphlet (69 kb)
17. Tran HH, Bjune G, Nguyen BM, Rottingen JA, Grais RF, Guerin PJ et al. Risk factors associated with typhoid fever in Son La province, northern Vietnam. Transactions of the Royal Society of Tropical Medicine & Hygiene 2005; 99(11):819-826. (213 kb)
18. Luxemburger C, Chau MC, Mai NL, Wain J, Tran TH, Simpson JA et al. Risk factors for typhoid fever in the Mekong delta, southern Viet Nam: a case-control study. Transactions of the Royal Society of Tropical Medicine & Hygiene 2001; 95(1):19-23. (622 kb)
19. Tankhiwale SS, Agrawal G, Jalgaonkar SV, Tankhiwale SS, Agrawal G, Jalgaonkar SV. An unusually high occurrence of Salmonella enterica serotype paratyphi A in patients with enteric fever. Indian Journal of Medical Research 2003; 117:10-12. (17 kb) Abstract only
20. Ochiai RL, Wang X, von Seidlein L, Yang J, Bhutta ZA, Bhattacharya SK et al. Salmonella paratyphi A rates, Asia. Emerging Infectious Diseases 2005; 11(11):1764-1766. (1 199 kb)
21. Walia M, Gaind R, Mehta R, Paul P, Aggarwal P, Kalaivani M et al. Current perspectives of enteric fever: a hospital-based study from India. Annals of Tropical Paediatrics 2005; 25(3):161-174. (19 kb) Abstract only
22. Bhutta ZA, Bhutta ZA. Impact of age and drug resistance on mortality in typhoid fever. Archives of Disease in Childhood 1996; 75(3):214-217. (232 kb)
23. Saha SK, Baqui AH, Hanif M, Darmstadt GL, Ruhulamin M, Nagatake T et al. Typhoid fever in Bangladesh: implications for vaccination policy. Pediatric Infectious Disease Journal 2001; 20(5):521-524. (267 kb)
24. Wain J, House D, Parkhill J, Parry C, Dougan G, Wain J et al. Unlocking the genome of the human typhoid bacillus. The Lancet Infectious Diseases 2002; 2(3):163-170. (1 316 kb)
25. Fierer J, Guiney DG, Fierer J, Guiney DG. Diverse virulence traits underlying different clinical outcomes of Salmonella infection. Journal of Clinical Investigation 2001; 107(7):775-780. (387 kb)
26. de Andrade DR, Andrade Junior DR, de Andrade DR, de Andrade Junior DR. Typhoid fever as cellular microbiological model. Revista do Instituto de Medicina Tropical de Sao Paulo 2003; 45(4):185-191. (107 kb)
27. House D, Bishop A, Parry C, Dougan G, Wain J, House D et al. Typhoid fever: pathogenesis and disease. Current Opinion in Infectious Diseases 2001; 14(5):573-578. (108 kb)
28. Bhan MK, Bahl R, Sazawal S, Sinha A, Kumar R, Mahalanabis D et al. Association between Helicobacter pylori infection and increased risk of typhoid fever. Journal of Infectious Diseases 2002; 186(12):1857-1860. (68 kb)
29. Frenck RW, Jr., Clemens J, Frenck RWJ, Clemens J. Helicobacter in the developing world. Microbes & Infection 2003; 5(8):705-713. (105 kb)
30. Patel JC, Rossanese OW, Galan JE, Patel JC, Rossanese OW, Galan JE. The functional interface between Salmonella and its host cell: opportunities for therapeutic intervention. Trends in Pharmacological Sciences 2005; 26(11):564-570. (182 kb)
31. Hensel M, Hensel M. Salmonella pathogenicity island 2. Molecular Microbiology 2000; 36(5):1015-1023. (214 kb)
32. Shetty PB, Broome DR, Shetty PB, Broome DR. Sonographic analysis of gallbladder findings in Salmonella enteric fever. Journal of Ultrasound in Medicine 1998; 17(4):231-237. (186 kb)
33. Everest P, Wain J, Roberts M, Rook G, Dougan G, Everest P et al. The molecular mechanisms of severe typhoid fever. Trends in Microbiology 2001; 9(7):316-320. (134 kb)
34. Ashbolt NJ, Ashbolt NJ. Microbial contamination of drinking water and disease outcomes in developing regions. Toxicology 2004; 198(1-3):229-238. (152 kb)
35. Kumar KS, Harada H, Kumar Karn S, Harada H. Field survey on water supply, sanitation and associated health impacts in urban poor communities--a case from Mumbai City, India. Water Science & Technology 2002; 46(11-12):269-275. (55 kb)
36. Schoenen D, Schoenen D. Role of disinfection in suppressing the spread of pathogens with drinking water: possibilities and limitations. Water Research 2002; 36(15):3874-3888. (599 kb)
37. Tulchinsky TH, Burla E, Clayman M, Sadik C, Brown A, Goldberger S et al. Safety of community drinking-water and outbreaks of waterborne enteric disease: Israel, 1976-97. Bulletin of the World Health Organization 2000; 78(12):1466-1473. (309 kb)
38. Levine MM, Tacket CO, Sztein MB, Levine MM, Tacket CO, Sztein MB. Host-Salmonella interaction: human trials. Microbes & Infection 2001; 3(14-15):1271-1279. (145 kb)
39. Mastroeni P, Menager N, Mastroeni P, Menager N. Development of acquired immunity to Salmonella. Journal of Medical Microbiology 2003; 52(Pt 6):453-459. (130 kb)
40. Garmory HS, Brown KA, Titball RW, Garmory HS, Brown KA, Titball RW. Salmonella vaccines for use in humans: present and future perspectives. FEMS Microbiology Reviews 2002; 26(4):339-353. (299 kb)
41. Faucher JF, Binder R, Missinou MA, Matsiegui PB, Gruss H, Neubauer R et al. Efficacy of atovaquone/proguanil for malaria prophylaxis in children and its effect on the immunogenicity of live oral typhoid and cholera vaccines. Clinical Infectious Diseases 2002; 35(10):1147-1154. (125 kb)
42. Engels EA, Lau J, Engels EA, Lau J. Vaccines for preventing typhoid fever. Cochrane Database of Systematic Reviews 2000;(2):CD001261. (203 kb)
43. Kirkpatrick BD, Tenney KM, Larsson CJ, O'Neill JP, Ventrone C, Bentley M et al. The novel oral typhoid vaccine M01ZH09 is well tolerated and highly immunogenic in 2 vaccine presentations. Journal of Infectious Diseases 2005; 192(3):360-366. (227 kb)
44. Connor BA, Schwartz E, Connor BA, Schwartz E. Typhoid and paratyphoid fever in travellers. The Lancet Infectious Diseases 2005; 5(10):623-628. (598 kb)
45. Steinberg EB, Bishop R, Haber P, Dempsey AF, Hoekstra RM, Nelson JM et al. Typhoid fever in travelers: who should be targeted for prevention? Clinical Infectious Diseases 2004; 39(2):186-191. (94 kb)
46. Antinori S, Galimberti L, Gianelli E, Calattini S, Piazza M, Morelli P et al. Prospective observational study of fever in hospitalized returning travelers and migrants from tropical areas, 1997-2001. Journal of Travel Medicine 2004; 11(3):135-142. (22 kb) Abstract only
47. Tarr PE, Kuppens L, Jones TC, Ivanoff B, Aparin PG, Heymann DL et al. Considerations regarding mass vaccination against typhoid fever as an adjunct to sanitation and public health measures: potential use in an epidemic in Tajikistan. American Journal of Tropical Medicine & Hygiene 1999; 61(1):163-170. (146 kb)
48. Bahl R, Sinha A, Poulos C, Whittington D, Sazawal S, Kumar R et al. Costs of illness due to typhoid fever in an Indian urban slum community: implications for vaccination policy. Journal of Health, Population & Nutrition 2004; 22(3):304-310. (140 kb)
49. Levine MM, Levine MM. Immunization against bacterial diseases of the intestine. Journal of Pediatric Gastroenterology & Nutrition 2000; 31(4):336-355. (172 kb)
50. anon. Joint WHO/Unicef Statement for Typhoid Vaccine use in Tsunami-Affected areas. 2006. World Health Organization. (100 kb)
Ref Type: Report
51. anon. Typhoid Vaccine. 2003. Geneva, World Health Organization. Immunization, Vaccines and Biologicals. (171 kb)
Ref Type: Report
52. Acosta CJ, Galindo CM, Ali M, Elyazeed RA, Ochiai RL, Danovaro-Holliday MC et al. A multi-country cluster randomized controlled effectiveness evaluation to accelerate the introduction of Vi polysaccharide typhoid vaccine in developing countries in Asia: rationale and design. Tropical Medicine & International Health 2005; 10(12):1219-1228. (124 kb)
53. Akpede GO, Akenzua GI, Akpede GO, Akenzua GI. Management of children with prolonged fever of unknown origin and difficulties in the management of fever of unknown origin in children in developing countries. Paediatric Drugs 2001; 3(4):247-262. (185 kb)
54. Caumes E, Ehya N, Nguyen J, Bricaire F, Caumes E, Ehya N et al. Typhoid and paratyphoid fever: a 10-year retrospective study of 41 cases in a Parisian hospital. Journal of Travel Medicine 2001; 8(6):293-297. (554 kb)
55. Otegbayo JA, Daramola OO, Onyegbutulem HC, Balogun WF, Oguntoye OO, Otegbayo JA et al. Retrospective analysis of typhoid fever in a tropical tertiary health facility.[erratum appears in Trop Gastroenterol. 2002 Apr-Jun;23(2):p3 Note: Daramola, O O O [corrected to Daramola, O O M]]. Tropical Gastroenterology 2002; 23(1):9-12. (19 kb) Abstract only
56. Haq SA, Alam MN, Hossain SM, Ahmed T, Tahir M, Haq SA et al. Value of clinical features in the diagnosis of enteric fever. Bangladesh Medical Research Council Bulletin 1997; 23(2):42-46. (19 kb) Abstract only
57. Cunha BA, Cunha BA. Typhoid fever: the temporal relations of key clinical diagnostic points. The Lancet Infectious Diseases 2006; 6(6):318-320. (49 kb)
58. Nsutebu EF, Martins P, Adiogo D, Nsutebu EF, Martins P, Adiogo D. Prevalence of typhoid fever in febrile patients with symptoms clinically compatible with typhoid fever in Cameroon. Tropical Medicine & International Health 2003; 8(6):575-578. (57 kb)
59. Dutta U, Garg PK, Kumar R, Tandon RK, Dutta U, Garg PK et al. Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder. American Journal of Gastroenterology 2000; 95(3):784-787. (48 kb)
60. Vollaard AM, Ali S, Widjaja S, Asten HA, Visser LG, Surjadi C et al. Identification of typhoid fever and paratyphoid fever cases at presentation in outpatient clinics in Jakarta, Indonesia. Transactions of the Royal Society of Tropical Medicine & Hygiene 2005; 99(6):440-450. (222 kb)
61. Ngwu BA, Agbo JA, Ngwu BA, Agbo JA. Typhoid fever: clinical diagnosis versus laboratory confirmation. Nigerian Journal of Medicine: Journal of the National Association of Resident Doctors of Nigeria 2003; 12(4):187-192. (16 kb) Abstract only
62. Wain J, Pham VB, Ha V, Nguyen NM, To SD, Walsh AL et al. Quantitation of bacteria in bone marrow from patients with typhoid fever: relationship between counts and clinical features. Journal of Clinical Microbiology 2001; 39(4):1571-1576. (89 kb)
63. Massi MN, Shirakawa T, Gotoh A, Bishnu A, Hatta M, Kawabata M et al. Rapid diagnosis of typhoid fever by PCR assay using one pair of primers from flagellin gene of Salmonella typhi. Journal of Infection & Chemotherapy 2003; 9(3):233-237. (226 kb)
64. Shukla S, Patel B, Chitnis DS, Shukla S, Patel B, Chitnis DS. 100 years of Widal test & its reappraisal in an endemic area. Indian Journal of Medical Research 1997; 105:53-57. (13 kb) Abstract only
65. Ibadin MO, Ogbimi AO, Ibadin MO, Ogbimi AO. Anti-typhoid agglutinins in school aged African children. East African Medical Journal 2002; 79(2):92-95. (13 kb) Abstract only
66. Frimpong EH, Feglo P, Essel-Ahun M, Addy PA, Frimpong EH, Feglo P et al. Determination of diagnostic Widal titres in Kumasi, Ghana. West African Journal of Medicine 2000; 19(1):34-38. (12 kb) Abstract only
67. Parry CM, Hoa NT, Diep TS, Wain J, Chinh NT, Vinh H et al. Value of a single-tube widal test in diagnosis of typhoid fever in Vietnam. Journal of Clinical Microbiology 1999; 37(9):2882-2886. (74 kb)
68. House D, Chinh NT, Diep TS, Parry CM, Wain J, Dougan G et al. Use of paired serum samples for serodiagnosis of typhoid fever. Journal of Clinical Microbiology 2005; 43(9):4889-4890. (50 kb)
69. Jesudason MV, Sridharan G, Arulselvan R, Babu PG, John TJ, Jesudason MV et al. Diagnosis of typhoid fever by the detection of anti-LPS & anti-flagellin antibodies by ELISA. Indian Journal of Medical Research 1998; 107:204-207. (12 kb) Abstract only
70. Nguyen NQ, Tapchaisri P, Chongsa-nguan M, Cao VV, Doan TT, Sakolvaree Y et al. Diagnosis of enteric fever caused by Salmonella spp. in Vietnam by a monoclonal antibody-based dot-blot ELISA. Asian Pacific Journal of Allergy & Immunology 1997; 15(4):205-212. (479 kb)
71. Herath HM, Herath HMTU. Early diagnosis of typhoid fever by the detection of salivary IgA. Journal of Clinical Pathology 2003; 56(9):694-698. (177 kb)
72. Pai AP, Koppikar GV, Deshpande S, Pai AP, Koppikar GV, Deshpande S. Role of modified Widal test in the diagnosis of enteric fever. Journal of the Association of Physicians of India 2003; 51:9-11. (72 kb)
73. Hatta M, Goris MG, Heerkens E, Gooskens J, Smits HL, Hatta M et al. Simple dipstick assay for the detection of Salmonella typhi-specific IgM antibodies and the evolution of the immune response in patients with typhoid fever. American Journal of Tropical Medicine & Hygiene 2002; 66(4):416-421. (64 kb)
74. Lakshmi V, Ashok R, Susmita J, Shailaja VV, Lakshmi V, Ashok R et al. Changing trends in the antibiograms of Salmonella isolates at a tertiary care hospital in Hyderabad. Indian Journal of Medical Microbiology 2006; 24(1):45-48. (101 kb)
75. Thaver Deal. Fluoroquinolones for treating typhoid and paratyphoid fevers (enteric fevers). Cochrane Database of Systematic Reviews 2006; 1. (363 kb)
76. Wain J, Kidgell C, Wain J, Kidgell C. The emergence of multidrug resistance to antimicrobial agents for the treatment of typhoid fever. Transactions of the Royal Society of Tropical Medicine & Hygiene 2004; 98(7):423-430. (313 kb)
77. Kariuki S, Revathi G, Muyodi J, Mwituria J, Munyalo A, Mirza S et al. Characterization of multidrug-resistant typhoid outbreaks in Kenya. Journal of Clinical Microbiology 2004; 42(4):1477-1482. (124 kb)
78. Mills-Robertson F, Addy ME, Mensah P, Crupper SS, Mills-Robertson F, Addy ME et al. Molecular characterization of antibiotic resistance in clinical Salmonella typhi isolated in Ghana. FEMS Microbiology Letters 2002; 215(2):249-253. (188 kb)
79. Wasfy MO, Frenck R, Ismail TF, Mansour H, Malone JL, Mahoney FJ et al. Trends of multiple-drug resistance among Salmonella serotype Typhi isolates during a 14-year period in Egypt. Clinical Infectious Diseases 2002; 35(10):1265-1268. (85 kb)
80. Renuka K, Kapil A, Kabra SK, Wig N, Das BK, Prasad VV et al. Reduced susceptibility to ciprofloxacin and gyra gene mutation in North Indian strains of Salmonella enterica serotype Typhi and serotype Paratyphi A. Microbial Drug Resistance-Mechanisms Epidemiology & Disease 2004; 10(2):146-153. (109 kb)
81. Parry CM, Parry CM. The treatment of multidrug-resistant and nalidixic acid-resistant typhoid fever in Viet Nam. Transactions of the Royal Society of Tropical Medicine & Hygiene 2004; 98(7):413-422. (159 kb)
82. Slinger R, Desjardins M, McCarthy AE, Ramotar K, Jessamine P, Guibord C et al. Suboptimal clinical response to ciprofloxacin in patients with enteric fever due to Salmonella spp. with reduced fluoroquinolone susceptibility: a case series. BMC Infectious Diseases 2004; 4:36. (141 kb)
83. Crump JA, Barrett TJ, Nelson JT, Angulo FJ, Crump JA, Barrett TJ et al. Reevaluating fluoroquinolone breakpoints for Salmonella enterica serotype Typhi and for non-Typhi salmonellae. Clinical Infectious Diseases 2003; 37(1):75-81. (109 kb)
84. Chinh NT PCLNHHTMDTW. A randomized controlled comparison of azithromycin and ofloxacin for treatment of multidrug-resistant or nalidixic acid-resistant enteric fever. Antimicrobial agents and chemotherapy 2000; 44(7):1855-1859. (78 kb)
85. Vinh H, Duong NM, Phuong lT, Truong NT, Bay PV, Wain J et al. Comparative trial of short-course ofloxacin for uncomplicated typhoid fever in Vietnamese children. Annals of Tropical Paediatrics 2005; 25(1):17-22. (70 kb)
86. Hart CA, Kariuki S, Hart CA, Kariuki S. Antimicrobial resistance in developing countries. BMJ 1998; 317(7159):647-650. (217 kb)
87. Ajao OG AA. Methylprednisolone sodium succinate (Solu-Medrol) in the treatment of typhoid perforation (a preliminary report). Transactions of the Royal Society of Tropical Medicine and Hygiene 1984; 78(5):573-576. (367 kb)
88. Annane D, Annane D. Glucocorticoids in the treatment of severe sepsis and septic shock. Current Opinion in Critical Care 2005; 11(5):449-453. (76 kb)
89. Ugwu BT, Yiltok SJ, Kidmas AT, Opaluwa AS, Ugwu BT, Yiltok SJ et al. Typhoid intestinal perforation in north central Nigeria. West African Journal of Medicine 2005; 24(1):1-6. (14 kb) Abstract only
90. Chatterjee H, Jagdish S, Pai D, Satish N, Jayadev D, Reddy PS et al. Changing trends in outcome of typhoid ileal perforations over three decades in Pondicherry. Tropical Gastroenterology 2001; 22(3):155-158. (13 kb) Abstract only
91. Aziz M, Qadir A, Aziz M, Faizullah., Aziz M, Qadir A et al. Prognostic factors in typhoid perforation. Jcpsp, Journal of the College of Physicians & Surgeons - Pakistan 2005; 15(11):704-707. (13 kb) Abstract only
92. Kouame J, Kouadio L, Turquin HT, Kouame J, Kouadio L, Turquin HT. Typhoid ileal perforation: surgical experience of 64 cases. Acta Chirurgica Belgica 2004; 104(4):445-447. (13 kb) Abstract only
93. Agbakwuru EA, Adesunkanmi AR, Fadiora SO, Olayinka OS, Aderonmu AO, Ogundoyin OO et al. A review of typhoid perforation in a rural African hospital. West African Journal of Medicine 2003; 22(1):22-25. (13 kb) Abstract only
94. Ameh EA, Dogo PM, Attah MM, Nmadu PT, Ameh EA, Dogo PM et al. Comparison of three operations for typhoid perforation. British Journal of Surgery 1997; 84(4):558-559. (166 kb)
95. Pal DK, Pal DK. Evaluation of best surgical procedures in typhoid perforation--an experience of 60 cases. Tropical Doctor 1998; 28(1):16-18. (13 kb) Abstract only
96. Chaudhry R, Mahajan RK, Diwan A, Khan S, Singhal R, Chandel DS et al. Unusual presentation of enteric fever: three cases of splenic and liver abscesses due to Salmonella typhi and Salmonella paratyphi A. Tropical Gastroenterology 2003; 24(4):198-199. (12 kb) Abstract only
97. Julia J, Canet JJ, Lacasa XM, Gonzalez G, Garau J, Julia J et al. Spontaneous spleen rupture during typhoid fever. International Journal of Infectious Diseases 2000; 4(2):108-109. (12 kb) Abstract only
98. Krishna KK, Mitra DK, Diwan AG, Bamnikar AA, Krishna KK, Mitra DK et al. Acute disseminated encehalomyelitis with typhoid fever. Journal of the Association of Physicians of India 1999; 47(10):1017-1019. (12 kb) Abstract only
99. Laloum E, Zeller V, Graff W, Aerts J, Chazerain P, Mamoudy P et al. Salmonella typhi osteitis can mimic tuberculosis. A report of three cases. Joint, Bone, Spine: Revue du Rhumatisme 2005; 72(2):171-174. (203 kb)
100. Khan M, Coovadia Y, Sturm AW, Khan M, Coovadia Y, Sturm AW. Typhoid fever complicated by acute renal failure and hepatitis: case reports and review. American Journal of Gastroenterology 1998; 93(6):1001-10. (13 kb)