TYPHOID FEVER
 |
| TYPHOID FEVER: TRANSMISSION AND PATHOLOGIC LESIONS |
In popular culture, the potential devastation of typhoid fever has been best illustrated by the story of Typhoid Mary, also known as Mary Mallon, the personal chef to numerous affluent families in the greater New York City area in the early 20th century. She was an asymptomatic chronic carrier of the Salmonella enterica serotype typhi (previously, S. typhi) and caused approximately 50 deaths as she moved between families, rejecting the notion that she had a role in their demise. She spent the bulk of her last 30 years of life in and out of quarantine.
Indeed,
S. enterica serotype typhi is uncommon in the United States, with only
200 to 300 cases reported annually. Most of these cases occur in travelers
returning from endemic countries, such as those in southern Africa, southern
and central Asia, southeast Asia, Latin America, and the Caribbean region.
Globally, approxi-mately 6 million annual cases are reported. Because human
beings are the sole vector for S. enterica typhi, it is not surprising
that the highest frequency of illnesses and outbreaks occurs in the endemic
areas, in which people are often underprivileged, populations are dense, and
public sanitation programs are suboptimal. Salmonella enterica serotype
paratyphi A, B, and C cause similar illnesses. Discernment between S.
typhi and S. paratyphi is of little clinical practicality because
both are identically managed.
In
various interviews, Typhoid Mary related that she did not wash her hands
because she did not believe she was a risk to others. Unfortunately, the
organism is spread via the fecal-oral route and optimal hygiene is paramount to
preventing transmission. The organism must survive the caustic gastric
environment before invading the small bowel, where it is spread systemically
via hematogenous and lymphatic routes. The higher the infectious load, the
greater the symptoms.
A
characteristic temporal pattern of illness ensues. The incubation period may
range from 5 days to 3 weeks initially, manifesting with fever due to
bacteremia, bradycardia, and chills. During the second week of disease,
submucosal tissue hypertrophy manifests as diffuse abdominal pain. Also,
characteristic rose spots, described as salmon-colored macules, are distributed
across the abdomen and upper torso. Dissemination during the third
week manifests with hepatosplenomegaly. At this stage, progressive submucosal
and lymphatic tissue hyperplasia may advance to tissue necrosis, presenting
with intestinal bleeding and ileal perforation. The latter is more common in
adults than children and can be potentially fatal if prompt medical and
surgical inter-ventions are not established. Though headache is a frequently
reported symptom, nausea and vomiting, interestingly, are not. Also,
individuals may experience either
diarrhea or constipation with equal frequency, though this dichotomy is not
clearly understood. In some individuals, patients may develop delirium (typhoid
encephalopathy). Other extraintestinal manifestations of disease are
infrequent but may include disease of the cardiovascular, respiratory,
musculoskeletal, hepatobiliary, and central nervous systems and genitourinary
tract. Even with treatment, symptoms may last for weeks to months, with 1% to
5% of individuals developing a chronic
carrier state. This is defined as identification of
S.
enterica typhi within urine or stool more than 12 months after
established acute infection. Notably, the gallbladder is a known nidus for
chronic colonization; this development may be an independent risk factor for
gallbladder carcinoma. Hence, individuals with recurrent infection may warrant
cholecystectomy. Interestingly, Schistosoma bladder infection increases
the risk of an S. enterica typhi chronic carrier state, suggesting a
synergistic parasite-bacteria relationship. Mechanical defects in the
genitourinary tree due to prostatic hyperplasia, urolithiasis, or stricture are
also associated with a chronic carrier state. Notably, individuals with C282Y
homozygous hemochromatosis are resistant to Salmonella infection, but of
course are very susceptible to infection with Vibrio species.
The
diagnostic value of the Widal test, a serologic agglutination test commonly
performed in endemic countries, suggests previous exposure and does not
equivocate to active infection. The Tubex test has not demonstrated superiority
to the Widal test. Diagnostic blood cultures may take several days to become
positive. Hence, the clinical history and physical examination are key to the
initiation of life-saving antibiotics. Nevertheless, successful culture does remain
the cornerstone of both successful diagnosis and guidance of antibiotic
selection, especially if there is antibiotic resistance afoot. Urine, stool,
and even rose spots may be cultured. The most sensitive tissue source for
diagnosis remains the bone marrow. Whereas blood cultures may return with
negative results after several days of infection, bone marrow culture may be
positive in up to 50% of cases.
Other
diagnostic clues include the presence of leukopenia or anemia. Leukocytosis
during the third week of disease may herald ileal perforation. Elevated liver
enzymes can often be high enough to suggest viral hepatitis, making the
diagnosis challenging. Cerebrospinal fluid assays in those with mental status
changes are often frustratingly normal.
In
individuals who are thought to have contracted the organism in a nonendemic
area, fluoroquinolones given for 7 to 10 days are a reasonable option. For
individuals thought to have acquired infection from an endemic source, the
culture isolates should be screened for
nalidixic acid resistance, which has been associated with reduced
fluoroquinolone susceptibility. In these individuals, azithromycin,
beta-lactams, and chloramphenicol have demonstrated good clinical efficacy.
Remarkably, relapse can occur even in healthy, nonimmunocompromised patients 2
to 3 weeks following acute infection. Patients should be monitored closely even
after they have demonstrated signs of improvement.
 |
| TYPHOID FEVER: PARATYPHOID FEVER, ENTERIC FEVER |
Two
live vaccines exist, one oral and one parenteral, but neither provides protection
against S. paratyphi A or B. Also, neither is completely
effective at preventing
S. enterica serotype typhi infection. Travelers to endemic regions are strongly encouraged to be vaccinated unless they are pregnant or immunocompromised. As Typhoid Mary has demonstrated, hand washing and good hygiene and sanitation methods are essential to preventing deadly outbreaks of infection.
