Laboratory diagnostics
Since bacteriological methods are not used in practical healthcare, the leading role is assigned to serological reactions and the detection of genetic markers using molecular biology methods (PCR).
Main serological tests:
- IHA (indirect hemagglutination assay): detects antibodies at the peak and in the convalescent period (up to 6–7 months after the end of the disease). The diagnostic titer is 1:1000 and higher. The study must be performed using paired sera.
- CFT (complement fixation test): antibodies to Rickettsia prowazekii antigens appear slightly later, from the 7th–8th day of illness. The diagnostic titer is 1:160 with subsequent dynamic rise.
- TA (agglutination test): strictly specific, agglutinins are detected from the 5th–7th day (titer 1:200), but today it is not widely used.
- Modern alternatives: ELISA (enzyme-linked immunosorbent assay) and IFA (indirect immunofluorescence assay) are increasingly used at the present stage.
The hemogram during the peak period has a characteristic profile: moderate leukocytosis with neutrophilia and a band cell shift, thrombocytopenia, lymphopenia, and eosinopenia. The appearance of plasma cells, a slight decrease in the erythrocyte count, and a moderate increase in ESR are also noted.
Differential diagnosis in the initial period
Before the appearance of the rash, epidemic typhus must be differentiated from influenza, generalized forms of meningococcal infection, and hemorrhagic fevers.
Influenza is characterized by a sharp temperature rise up to 39–40°C in the very first hours. The fever stays at its maximum for no more than 2–3 days, then gives way to subfebrile temperature. From the second day, catarrhal syndrome joins (acute tracheobronchitis, pronounced hyperemic oropharyngeal mucosa, and granularity of the posterior pharyngeal wall). Neurological status without gross disorders: consciousness is preserved, the patient prefers to lie down, the tongue is protruded freely (without tremor and deviation), and the Chiari-Avtsyn symptom is negative. The liver and spleen are not enlarged.
Meningococcal infection (meningitis, meningococcemia) begins with chills. In meningitis, the headache becomes unbearable and bursting within a few hours, accompanied by vomiting. The patient assumes a "meningeal posture" (head hyperextended, legs drawn up to the abdomen). Cerebrospinal fluid shows cell-protein dissociation and high neutrophilic pleocytosis. In meningococcemia, by days 1–2, a stellate hemorrhagic rash with central necrosis appears on the distal extremities and buttocks. Blood tests reveal hyperleukocytosis.
HFRS (hemorrhagic fever with renal syndrome) is characterized by strict cyclicity. On the 5th day (the onset of the oliguric period), the temperature normalizes, but the condition worsens: lower back pain increases, diuresis decreases, severe thirst, hiccups, vomiting, and focal petechial rash appear (in the armpits, areas of clothing pressure). Blood urea and creatinine levels rise, and hematuria and proteinuria are detected in the urine.
Differential diagnosis in the peak period
At the peak of the illness, differential diagnosis is carried out with typhoid-paratyphoid diseases, leptospirosis, and trichinosis.
Typhoid fever and paratyphoid fevers have a gradual onset. Patients are lethargic; the skin is pale and dry. A thickened tongue with tooth impressions, coated along the spine (while the tip and edges remain free of coating), is characteristic. Relative bradycardia, pulse dicrotism, pronounced flatulence, and a positive Padalka's sign are noted. Unlike epidemic typhus, a sparse roseolous rash on the anterior abdominal wall appears only from the 8th–10th day of illness (the "successive eruption" phenomenon is characteristic). Leukopenia and aneosinophilia are present in the blood.
Leptospirosis proceeds with intense muscle pain (especially in the calves) upon palpation and movement. The fever is often biphasic, with the possible development of icteric, hemorrhagic, and renal syndromes. The hemogram reveals a high ESR and neutrophil leukocytosis.
In trichinosis, puffiness of the face and eyelids, conjunctivitis, and pain upon eye movement come to the forefront. Muscular pain syndrome is moderately expressed and localized predominantly in the masticatory muscles.
Briefly: answers to topical questions
How does the rash in meningococcemia differ from the exanthem in epidemic typhus?
The rash in meningococcemia and the exanthem in epidemic typhus differ in the timing of appearance and morphology.
| Characteristic | Meningococcemia | Epidemic typhus |
|---|---|---|
| Time of appearance | On the 1st–2nd day of illness | On the 4th–5th day of fever / from the 5th day of fever |
| Morphology | Hemorrhagic rash: from petechial to large star-shaped elements; irregular elements, dense to the touch, with rapid formation of central necrosis | Abundant roseolous-petechial exanthem |
| Background and localization | Against a pale skin background; predominantly distal extremities, buttocks, pressure areas | The cited sources indicate a roseolous-petechial skin exanthem; specific predominant localization is not specified |
Which immunoglobulin classes (IgM, IgG) are determined by ELISA for the differential diagnosis of primary typhus and Brill-Zinsser disease?
For the differential diagnosis of primary epidemic typhus and Brill-Zinsser disease, specific serum antibodies of IgM and IgG classes are determined dynamically.
- Primary epidemic typhus — specific IgM are detected in a diagnostic titer on the 5th–7th day of illness, and IgG antibodies are detected in high titers during the convalescent period.
In the presented sources, the description of antibodies for Brill-Zinsser disease is cut off. At the same time, enzyme-linked immunosorbent assay (ELISA) is mentioned in the context of detecting rickettsial antigens rather than antibody classes.
The "rule of five and ten" will help distinguish epidemic typhus from typhoid fever by the timing of the rash: in epidemic typhus, we expect the diagnosis (and rash) by the 5th day, whereas in typhoid fever, the rash is delayed until the 8th–10th day.
Class and exam questions
Why is a bacterial culture not performed in the diagnosis of typhus?
Bacteriological methods are not used in practical healthcare due to the high technical difficulty of cultivating rickettsiae.
What happens to blood parameters at the peak of epidemic typhus?
The hemogram reveals thrombocytopenia, moderate leukocytosis with neutrophilia and a band cell shift, a decrease in eosinophils and lymphocytes, as well as the appearance of plasma cells.
How long do antibodies persist in the blood after an infection?
IgG class antibodies in low titers (detected by CFT) can be determined in the blood serum of convalescents for 20–50 years.
What else to study on this topic
- Neuropsychiatric manifestations and typhus encephalitis (coma vigile)
- Infectious-toxic shock as the main cause of death
- Brill-Zinsser disease (long-term consequences)
- Specific complications of mixed genesis (gangrene, destructive vasculitis)
- Mild and atypical forms of typhus
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