Laboratory Diagnosis of Typhoid fever (for Healthcare practitioners).

The laboratory diagnosis of typhoid fever is made by detecting S. Typhi species from bone marrow or a blood sample. Bone marrow samples are the most accurate methods for laboratory diagnosis of Typhoid fever.

This article is aimed at health care practitioners (doctors and nurses); however, we simplified the information for general use for informational purposes by non-medical personnel interested in the laboratory diagnosis of typhoid fever.

1. When to suspect typhoid fever:

The laboratory diagnosis of typhoid fever is only indicated after clinical suspicion of the disease. Therefore, it would be best if you considered typhoid fever based on the following:

• The history of traveling to endemic areas (traveler’s diarrhea).
• Living in an endemic area.
• A combination of fever and abdominal symptoms for more than three days.
• The presence of typical symptoms of typhoid fever (discussed in the next section)

2. Thy Typical symptoms (and their frequencies) in typhoid fever.

• At first, the symptoms often start with nausea and vomiting.
• Then, it progresses to diffuse abdominal pain.
• Bloating.
• Anorexia (lost appetite).
• Fever (rising over days in a step-ladder pattern): present in 96% of cases.
• Diarrhea or constipation.
• Rose skin spots (in only 1.5%).
• Dry cough ( in about 22% of cases).
• Atypical symptoms such as Shortness of breath, dizziness, chest pain, and others.

3. The first laboratory diagnosis of typhoid fever to order.

The laboratory diagnosis of typhoid fever is made by detecting S. Typhi species from bone marrow or a blood sample. Bone marrow samples are the most accurate methods for laboratory diagnosis of Typhoid fever.

With the exception of bone marrow cultures, cultures from other specimens are often less sensitive. Moreover, other laboratory diagnostic methods such as antibody testing (Widal test) and culture-independent methods) are also of limited accuracy (reference).

A. What is the first laboratory test to order for typhoid fever?

When typhoid fever is suspected on a clinical basis, the most practical clinical approach is to order blood and stool culture for typhoid (reference).

You should note that the blood culture samples should be large in volume to get the best results.

Two or three blood samples (each of them is 20 mL) will bring the best results (reference).

Bone marrow culture is the most sensitive method for laboratory diagnosis of typhoid fever. However, it is an invasive procedure and not available most of the time.

Antibody testing (serology) as the Widal test is of limited use, especially in endemic areas, as it couldn’t differentiate between current and past infections.

B. Culture (blood, stool, or bone marrow).

Culture and isolation of the organism is the best diagnostic method for typhoid fever.

The sensitivity varies according to the type of sample cultured:

• Bone marrow culture: is positive in more than 90%.
• Blood cultures are positive only in 50% to 70% of cases.
• Stool cultures are positive in only about 37% of patients with antibiotic therapy (reference).

Blood remains the primary laboratory diagnostic test due to the combination of relatively higher sensitivity and the non-invasive advantage over BM culture.

Blood culture is best performed during the flare-up of symptoms (during fever). This improves the sensitivity of the test.

C. Serology or antibody testing (as Widal Test).

Widal test detects the antibodies against antigens of the salmonella bacteria. However, it is of limited use, especially in the endemic areas of typhoid fever.

The test can be positive for both the current and past infections of typhoid fever. In addition, rising test levels on follow-up testing can aid in the diagnosis.

Widal test is not as accurate and sensitive as culture methods for the laboratory diagnosis of typhoid fever.

D. Culture-independent methods.

New rapid antibody tests also exist, For example (reference):

• Enzyme-linked immunosorbent assay (ELISA) for the Vi antigen.
• Polymerase chain reaction (PCR)-based tests for salmonella.
• Immunoglobulin A (IgA) anti-hemolysin E antibodies: a new and promising tests.

However, These tests are not as accurate as culture tests. Therefore, blood, stool, and bone marrow cultures are still the best method for laboratory diagnosis of typhoid fever.