1. typhoid fever follow-up.pdf

6/19/2014 Typhoid Fever Follow-up

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Typhoid Fever Follow-up

Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD more...

Updated: Apr 1, 2014

Further Inpatient Care

If treated with well-selected antibiotics, patients with typhoid fever (enteric fever) should defervesce within 3-5 days. However, patients with complicated typhoid fever should finish their course intravenously and shouldremain in the hospital if unable to manage this at home.Patients with complicated typhoid fever should be admitted through the acute phase of the illness.Uncomplicated cases are generally treated on an outpatient basis unless the patient is a public health riskor cannot be fully monitored outside the home.

Further Outpatient Care

After discharge, patients should be monitored for relapse or complications for 3 months after treatment hascommenced.Five percent to 10% of patients treated with antibiotics experience relapse of typhoid fever after initialrecovery. Relapses typically occur approximately 1 week after therapy is discontinued, but relapse after 70days has been reported. In these cases, the blood culture results are again positive, and high serum levelsof H, O, and Vi antibodies and rose spots may reappear.

A relapse of typhoid fever is generally milder and of shorter duration than the initial illness. In rarecases, second or even third relapses occur. Notably, the relapse rate is much lower followingtreatment with the new quinolone drugs, which have effective intracellular penetration.S typhi and S paratyphi rarely develop antibiotic resistance during treatment. If an antibiotic has beenchosen according to sensitivities, relapse should dictate a search for anatomic, pathologic, orgenetic predispositions rather than for an alternate antibiotic.Previous infection does not confer immunity. In any suspected relapse, infection with a differentstrain should be ruled out.

Depending on the antibiotic used, between 0% and 5.9% of treated patients become chronic carriers. Insome cases, the organism evades antibiotics by sequestering itself within gallstones or Schistosomahaematobium organisms that are infecting the bladder. From there, it is shed in stool or urine, respectively.If present, these diseases must be cured before the bacterium can be eliminated.Untreated survivors of typhoid fever may shed the bacterium in the feces for up to 3 months. Therefore, afterdisease resolution, 3 stool cultures in one-month intervals should be performed to rule out a carrier state.Concurrent urinary cultures should be considered.

Deterrence/Prevention

Travelers to endemic countries should avoid raw unpeeled fruits or vegetables since they may have beenprepared with contaminated water and should not buy food from street vendors; in addition, they shoulddrink only boiled water.In endemic countries, the most cost-effective strategy for reducing the incidence of typhoid fever is theinstitution of public health measures to ensure safe drinking water and sanitary disposal of excreta. Theeffects of these measures are long-term and reduce the incidence of other enteric infections, which are a

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major cause of morbidity and mortality in those areas.

Vaccines

In endemic areas, mass immunization with typhoid vaccines at regular intervals considerably reduces theincidence of infections. Routine typhoid vaccination is not recommended in the United States but is indicated fortravelers to endemic areas, persons with intimate exposure to a documented S typhi carrier (eg, householdcontact), and microbiology laboratory personnel who frequently work with S typhi. Vaccines are not approved foruse children younger than 2 years. The efficacy of typhoid fever vaccinations against paratyphi serovars has not

been firmly established, but is markedly less than their efficacy against typhi.[62]

Travelers should be vaccinated at least one week prior to departing for an endemic area. Because typhoidvaccines lose effectiveness after several years, consultation with a specialist in travel medicine is advised ifthe individual is traveling several years after vaccination.The only absolute contraindication to vaccination is a history of severe local or systemic reactions followinga previous dose. The typhoid vaccines available in the United States have not been studied in pregnantwomen.Currently, the 3 typhoid fever vaccines include injected Vi capsular polysaccharide (ViCPS; Typhim Vi,Pasteur Merieux) antigen, enteric Ty21a (Vivotif Berna, Swiss Serum and Vaccine Institute) live-attenuatedvaccine, and an acetone-inactivated parenteral vaccine (used only in members of the armed forces). Theefficacy of both vaccines available to the general public approaches 50%.

Vi capsular polysaccharide antigen vaccine is composed of purified Vi antigen, the capsularpolysaccharide elaborated by S typhi isolated from blood cultures. The Vi antigen is absent in Sparatyphi A, but this vaccine does provide some in vitro immunogenicity against S paratyphi A. This

may be due to trace amounts of other, common antigens in the preparation.[63]

Primary vaccination with ViCPS consists of a single parenteral dose of 0.5 mL (25 g IM) oneweek before travel. The vaccine manufacturer does not recommend the vaccine for childrenyounger than 2 years. Booster doses are needed every 2 years to maintain protection ifcontinued or renewed exposure is expected.Adverse effects include fever, headache, erythema, and/or induration of 1 cm or greater. In astudy conducted in Nepal, the ViCPS vaccine produced fewer local and systemic reactions

than the control (the 23-valent pneumococcal vaccine).[64] Among school children in SouthAfrica, ViCPS produced less erythema and induration than the control (bivalent vaccine).A systemic review and meta-analysis of 5 randomized controlled trials on the efficacy andsafety of ViCPS versus placebo or nontyphoid vaccine found a cumulative efficacy of 55%(95% CI, 30%-70%).The efficacy of vaccination with ViCPS has not been studied among persons from areaswithout endemic disease who travel to endemic regions or among children younger than 5years. ViCPS has not been given to children younger than 1 year.Questions concerning Vi typhoid vaccine effectiveness in young children (ie, < 5 y) haveinhibited its use in developing countries. Whether the vaccine is effective under programmaticconditions is also unclear.Sur et al conducted a phase IV effectiveness trial in slum-dwelling residents aged 2 years orolder in India to determine vaccine protection. Participants (n=37,673) were randomlyassigned to receive a single dose of either Vi vaccine or inactivated hepatitis A vaccine,according to geographic clusters. The mean rate of Vi vaccine coverage was 61% and 60%for the hepatitis A vaccine.Typhoid fever was diagnosed in 96 subjects in the hepatitis A vaccine group compared with34 in the Vi vaccine group (no more than 1 episode was reported per individual). Protectiveeffect for typhoid with the Vi vaccine was 61% (P < 0.001) compared with the hepatitis Avaccine group. Children vaccinated while aged 2-5 years had an 80% protection level.Unvaccinated members of the Vi vaccine clusters showed a protection level of 44%. Theoverall protection level with all Vi vaccine cluster residents was 57%. The authors concludedthat the Vi vaccine was effective in young children and protected unvaccinated neighbors of Vi

vaccinees.[65]

Ty21a is an oral vaccine that contains live attenuated S typhi Ty21a strains in an enteric-coatedcapsule. The vaccine elicits both serum and intestinal antibodies and cell-mediated immuneresponses.

In the United States, primary vaccination with Ty21a consists of one enteric-coated capsuletaken on alternate days to a total of 4 capsules. The capsules must be refrigerated (not



frozen), and all 4 doses must be taken to achieve maximum efficacy.The optimal booster schedule has not been determined; however, the longest reported follow-up study of vaccine trial subjects indicated that efficacy continued for 5 years aftervaccination. The manufacturer recommends revaccination with the entire 4-dose series every5 years if continued or renewed exposure to S typhi is expected. This vaccine may beinactivated if given within 3 days of antibiotics.Adverse effects are rare. They include abdominal discomfort, nausea, vomiting, fever,headache, and rash or urticaria.The vaccine manufacturer of Ty21a recommends against use in children younger than 6years. It should not be administered to immunocompromised persons; the parenteralvaccines present theoretically safer alternatives for this group.A systemic review and meta-analysis of 4 randomized controlled trials on the efficacy andsafety of Ty21a versus placebo or nontyphoid vaccine found a cumulative efficacy of 51%(95% CI, 36%-62%).The efficacy of Ty21a has not been studied among persons from areas without endemicdisease who travel to disease-endemic regions.

Acetone-inactivated parenteral vaccine is currently available only to members of the US Armed Forces.Efficacy rates for this vaccine range from 75%-94%. Booster doses should be administered every 3 years ifcontinued or renewed exposure is expected.

The parenteral heat-phenolinactivated vaccine (Wyeth-Ayerst) has been discontinued.No information has been reported concerning the use of one vaccine as a booster after primaryvaccination with a different vaccine. However, using either the series of 4 doses of Ty21a or 1 dose ofViCPS for persons previously vaccinated with parenteral vaccine is a reasonable alternative toadministration of a booster dose of parenteral inactivated vaccine.A more effective vaccine may be on the horizon. An investigational vaccine using ViCPS conjugatedto the nontoxic recombinant pseudomonas exotoxin A (Vi-rEPA) has been studied in a randomizedcontrolled trial. The vaccine was given to children aged 2-5 years and showed an efficacy of 89%(95% CI, 76%-97%) after 3.8 years. Vi-rEPA has not been approved for use in the United States.

Complications

Neuropsychiatric manifestations (In the past 2 decades, reports from disease-endemic areas havedocumented a wide spectrum of neuropsychiatric manifestations of typhoid fever.)

A toxic confusional state, characterized by disorientation, delirium, and restlessness, ischaracteristic of late-stage typhoid fever. In some cases, these and other neuropsychiatric featuresdominate the clinical picture at an early stage.Facial twitching or convulsions may be the presenting feature. Meningismus is not uncommon, butfrank meningitis is rare. Encephalomyelitis may develop, and the underlying pathology may be thatof demyelinating leukoencephalopathy. In rare cases, transverse myelitis, polyneuropathy, or cranialmononeuropathy develops.Stupor, obtundation, or coma indicates severe disease.

Focal intracranial infections are uncommon, but multiple brain abscesses have been reported.[66]

Other less-common neuropsychiatric manifestations events have included spastic paraplegia,peripheral or cranial neuritis, Guillain-Barr syndrome, schizophrenialike illness, mania, anddepression.

RespiratoryCoughUlceration of posterior pharynxOccasional presentation as acute lobar pneumonia (pneumotyphoid)

CardiovascularNonspecific electrocardiographic changes occur in 10%-15% of patients with typhoid fever.Toxic myocarditis occurs in 1%-5% of persons with typhoid fever and is a significant cause of deathin endemic countries. Toxic myocarditis occurs in patients who are severely ill and toxemic and ischaracterized by tachycardia, weak pulse and heart sounds, hypotension, and electrocardiographicabnormalities.Pericarditis is rare, but peripheral vascular collapse without other cardiac findings is increasingly

described. Pulmonary manifestations have also been reported in patients with typhoid fever.[67]

HepatobiliaryMild elevation of transaminases without symptoms is common in persons with typhoid fever.Jaundice may occur in persons with typhoid fever and may be due to hepatitis, cholangitis,



cholecystitis, or hemolysis.Pancreatitis and accompanying acute renal failure and hepatitis with hepatomegaly have been

reported.[68]

Intestinal manifestationsThe 2 most common complications of typhoid fever include intestinal hemorrhage (12% in one Britishseries) and perforation (3%-4.6% of hospitalized patients).From 1884-1909 (ie, preantibiotic era), the mortality rate in patients with intestinal perforation due totyphoid fever was 66%-90% but is now significantly lower. Approximately 75% of patients haveguarding, rebound tenderness, and rigidity, particularly in the right lower quadrant.Diagnosis is particularly difficult in the approximately 25% of patients with perforation and peritonitiswho do not have the classic physical findings. In many cases, the discovery of free intra-abdominalfluid is the only sign of perforation.

Genitourinary manifestationsApproximately 25% of patients with typhoid fever excrete S typhi in their urine at some point duringtheir illness.

Immune complex glomerulitis[69] and proteinuria have been reported, and IgM, C3 antigen, and Styphi antigen can be demonstrated in the glomerular capillary wall.Nephritic syndrome may complicate chronic S typhi bacteremia associated with urinaryschistosomiasis.Nephrotic syndrome may occur transiently in patients with glucose-6-phosphate dehydrogenasedeficiency.Cystitis: Typhoid cystitis is very rare. Retention of urine in the typhoid state may facilitate infectionwith coliforms or other contaminants.

Hematologic manifestationsSubclinical disseminated intravascular coagulation is common in persons with typhoid fever.

Hemolytic-uremic syndrome is rare.[70]

Hemolysis may also be associated with glucose-6-phosphate dehydrogenase deficiency.Musculoskeletal and joint manifestations

Skeletal muscle characteristically shows Zenker degeneration, particularly affecting the abdominalwall and thigh muscles.

Clinically evident polymyositis may occur.[71]

Arthritis is very rare and most often affects the hip, knee, or ankle.Late sequelae (rare in untreated patients and exceedingly rare in treated patients)

Neurologic - Polyneuritis, paranoid psychosis, or catatonia[72]

Cardiovascular - Thrombophlebitis of lower-extremity veinsGenitourinary -OrchitisMusculoskeletal

Periostitis, often abscesses of the tibia and ribsSpinal abscess (typhoid spine; very rare)

Prognosis

The prognosis among persons with typhoid fever depends primarily on the speed of diagnosis and initiationof correct treatment. Generally, untreated typhoid fever carries a mortality rate of 10%-20%. In properlytreated disease, the mortality rate is less than 1%.An unspecified number of patients experience long-term or permanent complications, includingneuropsychiatric symptoms and high rates of gastrointestinal cancers.

Patient Education

Because vigilant hand hygiene, vaccination, and the avoidance of risky foods and beverages are mainstaysof prevention, educating travelers before they enter a disease-endemic region is important.Because the protection offered by vaccination is at best partial, close attention to personal, food, and waterhygiene should be maintained. The US Centers for Disease Control and Prevention dictum to "boil it, cookit, peel it, or forget it" is a good rule in any circumstance. If disease occurs while abroad despite theseprecautions, one can usually call the US consulate for a list of recommended doctors.For excellent patient education resources, see eMedicineHealth's patient education article Foreign Travel.Case study

A wealthy middle-aged man presented to his physician a few days after the onset of flulike



symptoms, including fever, myalgias, chills, severe abdominal pain, and a cough, in addition tosevere abdominal pain. Over the next 2 weeks, he lost a great deal of weight. He had intermittent butever-increasing fevers. About 3 weeks after the onset of symptoms, he developed a few pale,salmon-colored macules on his trunk. His cough became much more frequent and severe. Hebecame delirious, listlessly wandering around the house fiddling with doorknobs. During the fourthweek of his illness, he rapidly declined with increasing somnolence. After nearly 4 weeks of illness,he died surrounded by his loving family.The patient was Prince Albert, the Consort to Queen Victoria. He was diagnosed with typhoid fever.His personal physician, Sir William Jenner, a leading expert on the disease, diagnosed typhoid fever.Prince Albert received the best therapy of the day.

For the most up-to-date information, visit the Centers for Disease Control and Prevention Travelers' HealthTyphoid resource (www.cdc.gov/travel) or call the Travelers' Health automated information line at 877-FYI-TRIP. The World Health Organizations site (www.who.int/ith), International Society of Travel Medicine site(www.istm.org), and Travel Doctor (www.traveldoctor.co.uk/diseases.htm) contain useful information as well,though the authors disagree with some of the WHOs antibiotic guidelines.

Contributor Information and DisclosuresAuthorJohn L Brusch, MD, FACP Assistant Professor of Medicine, Harvard Medical School; Consulting Staff,Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians andInfectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)Thomas Garvey, MD, JD Primary Care Physician, Burlington Medical Associates; Co-chair, Medical AdvisoryCommittee for the Elimination of Tuberculosis

Thomas Garvey, MD, JD is a member of the following medical societies: American College of Legal Medicine,American College of Physicians, and American Society of Law, Medicine & Ethics


Roberto Corales, DO Vice President, Chief Medical Officer and Principal Investigator, AIDS Care

Roberto Corales, DO is a member of the following medical societies: American Medical Association, AmericanOsteopathic Association, and International AIDS Society


Steven K Schmitt, MD Staff Physician, Department of Infectious Disease, Cleveland Clinic

Steven K Schmitt, MD is a member of the following medical societies: Infectious Diseases Society of America


Specialty Editor BoardFrancisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical CenterCollege of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Richard B Brown, MD, FACP Chief, Division of Infectious Diseases, Baystate Medical Center; Professor,Department of Internal Medicine, Tufts University School of Medicine

Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, AmericanCollege of Chest Physicians, American College of Physicians, American Medical Association, AmericanSociety for Microbiology, Infectious Diseases Society of America, and Massachusetts Medical Society




Chief EditorMichael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart GWolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health ScienceCenter

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, AmericanCollege of Physicians, American Medical Association, Association of Professors of Medicine, InfectiousDiseases Society of America, Oklahoma State Medical Association, and Southern Society for ClinicalInvestigation


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