TYPHOID FEVER

Typhoid fever, otherwise known as enteric fever, is an acute illness associated with fever caused by the Salmonella typhi bacteria. S. typhosa is a short, plump, gram negative rod that is flagellated and actively motile. Contaminated food or water is the common medium of contagion. The disease follows four stages. The first stage is known as incubation period, usually 10-14 days in occurrence. In this stage generalization of the infection occurs. In the second stage, aggregation o f t h e m a c r o p h a g e a n d e d e m a i n f o c a l a r e a s i n d i c a t e s b a c t e r i a l l o c a l i z a t i o n (embolization) and resultant toxic injury which disappear after few days. The third stage of disease is dominated by effects of local bacterial injury especially in t h e i n t e s t i n a l t r a c t , mesenteric lymph nodes, spleen, and liver. The fourth stage, or the stage of lysis, is the stage wherein the infectious process is gradually overcome. Symptoms slowly disappear and the temperature gradually returns to normal. The symptoms of typhoid fever include high fever, chills, cough, muscle pain, weakness, s t o m a c h p a i n , h e a d a c h e a n d a r a s h m a d e u p o f f l a t , r o s e c o l o r e d s p o t s . D i a r r h e a i s a l e s s common symptom of a typhoid fever, although it is a gastrointestinal disease. Sometimes there are mental changes, known as typhoid psychosis. A characteristic feature of typhoid psychosis is plucking at the bed linens if patient is confined to bed. Complications of typhoid fever are secondary conditions, symptoms, or other disorders that are caused by typhoid fever. Complications include overwhelming infection, pneumonia, intestinal bleeding, and intestinal perforation which may eventually lead to death. T yp hoid fever is one of the most protean of all bacterial d i s e a s e s t h u s l a b o r a t o r y procedures are usually depended on to confirm or disprove suspicion of such disease. The place of blood culture, serologic studies and bacteriologic examination feces and urine are useful in establishing the diagnosis. Agglutination (Widal) for typhoid fever is done to determine antibody response against different antigenic fractions of organisms. T y p h o i d f e v e r i s t r e a t e d w i t h a n t i b i o t i c s w h i c h k i l l t h e Salmonella bacteria. Several antibiotics are effective for the treatment of typhoid fever. The choice of antibiotics needs to be guided by identifying the geographic region where the organism was acquired and the results of cultures once available. Two new vaccines are currently licensed and widely used worldwide, a subunit (Vi PS) vaccine administered by the intramuscular route and a live attenuated S. typhi strain (Ty21a) for oral immunization. I n m o s t c a s e s , t yp h o i d f e v e r i s m a n a g e d a t h o m e w i t h a n t i b i o t i c s a n d b e d rest. For hospitalized patients, effective

antibiotics, good nursing care, adequate nutrition, careful attention to fluid and electrolyte balance, and prompt recognition and treatment of complications are strategies to avert the possibility of death.

Pathophysiology Risk factors for acquiring typhoid fever likely include improper food handling, eating food from outside sources like carinderia, drinking contaminated water, poor sanitation and even poor hygiene practices. B o t h g e n d e r s d o h a v e equal chances on acquiring such disease. Asian, African and Americans are at greatest risks of acquiring the disease since geographical locations play a part. During an acute infection, S. typhi multiplies in mononuclear phagocytic cells before released into the bloodstream. After ingestion in food or water, typhoid organisms pass through the pylorus and reach the small intestine. They rapidly penetrate the mucosal epithelium via either microfold cells or enterocytes and arrive in the lamina propria, where they rapidly elicit an influx of macrophages (Mp) that ingest the bacilli but do not generally kill them. Some bacilli remain within Mp of the small intestinal lymphoid tissue. Other typhoid bacilli are drained into mesenteric lymph nodes where there is further multiplication and ingestion by Mp. It is believed that typhoid bacilli reach the bloodstream principally by lymph drainage from mesenteric nodes, after which they enter the thoracic duct and then the general circulation. As a result of this silent primary bacteraemia the pathogen reaches an intracellular haven within 24 hours after ingestion throughout the organs of the reticuloendothelial system (spleen, liver, bone marrow, etc.), where it resides during the incubation period, usually of 8 to 14 days. The incubation period in a particular individual depends on the quantity of inoculum, i.e. it decreases as the quantity of inoculum increases, and on host factors. Incubation periods ranging from 3 days to more than 60 days have been reported. Clinical illness is accompanied by a fairly sustained but low level of secondary bacteraemia (~1-10 bacteria per ml of blood). Diagnostics The definitive diagnosis of typhoid fever depends on the isolation of S. typhi from blood, bone marrow or a specific anatomical lesion. The presence of clinical symptoms characteristic of typhoid fever or the detection of a specific antibody response is suggestive of typhoid fever but not definitive. Blood culture is the mainstay of the diagnosis of this disease. Microbiological procedures Blood culture - A typical blood culture bottle contains 45 ml of tryptic soy broth or brain heart infusion broth. These are inoculated with 5 ml of fresh blood and

incubated at 37C. Negatives should be kept for at least seven days. Because S. typhi is not the only bacterial pathogen found 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 most bacterial pathogens. Stool or rectal swab culture This involves inoculating 1 g of stool into 10 ml of selenite F broth and incubating at 37C for 18_48 hours. Felix-Widal test This test measures agglutinating antibody levels against O and H antigens. The levels are measured by using doubling dilutions of sera in large test tubes. Usually, O antibodies appear on days 6-8 and H antibodies on days 10-12 after the onset of the disease. The test is usually performed on an acute serum (at first contact with the patient). A convalescent serum should preferably also be collected so that paired titrations can be performed. In practice, however, this is often difficult. At least 1 ml of blood should be collected each time in order to have a sufficient amount of serum. In exceptional circumstances the test can be performed on plasma without any adverse effect on the result. IDL Tubex test The Tubex test is simple (essentially a one-step test) and rapid (taking approximately two minutes). The O9 antigen used in the test is extremely specific because its immunodominant epitope is a very rare dideoxyhexose sugar that occurs in nature. This antigen has been found in serogroup D salmonellae but not in other microorganisms. The closest to it is the tyvelose antigen found in Trichinella spiralis but antibodies to these two antigens do not cross-react with each other. A positive result given by Tubex invariably suggests a Salmonella infection, although the test cannot tell which group D Salmonella is responsible. Typhidot test This test makes use of the 50 kD antigen to detect specific IgM and IgG antibodies to S. typhi (25). It has undergone full-scale multinational clinical evaluation of its diagnostic value (26, 27, 28). This dot EIA test offers simplicity, speed, specificity (75%), economy, early diagnosis, sensitivity (95%) and high negative and positive predictive values. The detection of IgM reveals acute typhoid in the early phase of infection, while the detection of both IgG and IgM suggests acute typhoid in the middle phase of infection. IgM dipstick test The typhoid IgM dipstick assay is designed for the serodiagnosis of typhoid fever through the detection of S. typhi-specific IgM antibodies in serum or whole blood samples.

Treatment Modalities

General management Supportive measures are important in the management of typhoid fever, such as oral or intravenous hydration, the use of antipyretics, and appropriate nutrition and blood transfusions if indicated. More than 90% of patients can be managed at home with oral antibiotics, reliable care and close medical follow-up for complications or failure to respond to therapy. However, patients with persistent vomiting, severe diarrhea and abdominal distension may require hospitalization and parenteral antibiotic therapy. Antimicrobial therapy Efficacy, availability and cost are important criteria for the selection of first-line antibiotics to be used in developing countries. Drug of choice The fluoroquinolones are widely regarded as optimal for the treatment of typhoid fever in adults. They are relatively inexpensive, well tolerated and more rapidly and reliably effective than the former first-line drugs, viz. chloramphenicol, ampicillin, amoxicillin and trimethoprim-sulfamethoxazole. The available fluoroquinolones (ofloxacin, ciprofloxacin, fleroxacin, perfloxacin) are highly active and equivalent in efficacy (with the exception of norfloxacin which has inadequate oral bioavailability and should not be used in typhoid fever). The evidence suggests that the fluoroquinolones are the optimal choice for the treatment of typhoid fever in adults and that they may also be used in children. Management of complications In severe typhoid the fluoroquinolones are given for a minimum of 10 days. Typhoid fever patients with changes in mental status, characterized by delirium, obtundation and stupor, should be immediately evaluated for meningitis by examination of the cerebrospinal fluid. If the findings are normal and typhoid meningitis is suspected, adults and children should immediately be treated with high-dose intravenous dexamethasone in addition to antimicrobials. Patients with intestinal haemorrhage need intensive care, monitoring and blood transfusion. Intervention is not needed unless there is significant blood loss. Surgical consultation for suspected intestinal perforation is indicated. If perforation is confirmed, surgical repair should not be delayed longer than six hours. Metronidazole and gentamicin or ceftriazone should be administered before and after surgery if a fluoroquinolone is not being used to treat leakage of intestinal bacteria into the abdominal cavity. Early intervention is crucial, and mortality rates increase as the delay between perforation and surgery lengthens. .