Prolonged subfebrile condition, pyretic fever and febrile attacks of unknown genesis: new approach to diagnosis and treatment. Part 2. Diagnostics and treatment


  • I.S. Markov Vitacell Clinic, Kyiv, Ukraine; Markov Clinic, Kyiv, Ukraine, Ukraine
  • A.I. Markov Vitacell Clinic, Kyiv, Ukraine; Markov Clinic, Kyiv, Ukraine; Bogomolets National Medical University, Kyiv, Ukraine, Ukraine



prolonged subfebrile fever, febrile attack, fever of unknown genesis, nephrodysbacteriosis, chronic bacterial intoxication syndrome, bacterial autovaccines


Background. The study was aimed to establish the true etiological cause of such pathological conditions as prolonged low-grade fever, fever of unknown genesis, and cases of rapid short-term febrile increase of temperature of unknown origin. Materials and methods. The design of the study was clinical-diagnostic and included the search for ways to diagnose and treat such pathological conditions as prolonged subfebrile fever, fever of unknown genesis, and cases of rapid short-term febrile increase of temperature of unknown origin. The studies were prospective-retrospective and were longitudinal with long-term periodic follow-up of a certain part of the same patients during 1–10 years after diagnosis of CBIS (chronic bacterial intoxication syndrome) and appropriate treatment. According to the effectiveness of the obtained results, the study was direct, because it undoubtedly led to the recovery of the patient with the improvement of his/her state and life. All patients (infants and adults aged till 80 years) who went to the hospital during 2009–2020 with complaints about violation of the temperature regime (subfebrile or febrile increase). Results. During 2009–2020, 3999 patients (adults — 2047/3999, 51.2 %, children — 1952/3999, 48.8 %) with a fever of unknown origin, namely 1578/2047 (77.1 %) adults and 1206/1952 (61.8 %) children with prolonged subfebrile fever, 70/2047 (3.4 %) and 25/1952 (1.3 %), respectively — with febrile fever and 399/2047 (19.5 %) and 721/1952 (36.9 %) — with febrile attacks (FA), were observed by the authors. In all 3999 (100 %) patients, there was detected a focus of chronic bacterial infection in the kidneys. Herewith in more than 2/3 cases (2780/3999 patients, 69.5 %), there was diagnosed the locally asymptomatic nephrodysbacteriosis without clinical, general laboratory (inclu­ding almost normal general analysis of urine) and instrumental signs of the inflammatory process in the kidneys. In 960/3999 (24.0 %) ca­ses, there was first established the latent form of delayed clinically asymptomatic chronic pyelonephritis. 259/3999 (6.5 %) patients were diagnosed with chronic pyelonephritis at the stage of clinical exacerbation. As a consequence of the formation of a focus of chronic bacterial infection in the kidneys, the patients developed monosymptomatic (only with temperature increase) or full-symptom CBIS, namely: 2024/2784 (72.7 %) children and adults with prolonged subfebrile fever there presented with typical clinical manifestations of CBIS in various combinations, but in 760/2784 (27.3 %) cases, the subfebrile temperature was monosymptoma­tic without other complaints and clinical symptoms. The diagnosis was confirmed by bacteriological examination of warm urine (three times, for three days running) and toxicological blood examination using the diagnostic system Toxicon. Urine cultures of various bacteria were isolated from urine in all 3999 (100 %) patients. Herewith in 2205/3999 (55.1 %) cases, there were isolated one culture of bacteria in each case, in 1608/3999 (40.2 %) patients — simultaneously two cultures of different bacteria, i.e. another 3216 strains, in 186/3999 (4,7 %) — three cultures (558 strains). That is, in general, there were isolated 5979 strains of different bacteria, which were considered as diagnostic confirmation of the presence of a focus of chronic bacterial infection in the kidneys in all 3999 patients with prolonged subfebrile fever, fever of unknown genesis, or febrile attacks. The main factors of the occurrence of temperature regime disorders on the background of CBIS were Enterococci (2471/3999 strains from 61.8 % of patients), Escherichia coli — 1495/3999 strains (from 37.4 % of patients) and Staphylococci (Staphylococcus aureus and Staphylococcus haemolyticus) and Streptococci (Streptococcus pyogenes): a total of 696/3999 strains (from 17.4 % of patients). In 818 (100 %) patients who were examined using the Toxi­con system, all, without exception, the indicators of cytolytic activity of toxic proteomes, which were tested, significantly exceeded the norm (p < 0.001). In the vast majority of patients (in 664/818 or 81.17 % of cases), there was detected severe toxemia, in 140/818 (17.11 %) — moderate and only in 14 (1.71 %) — mild. All 3999 patients with prolonged subfebrile fever, fever of unknown genesis, and FA were treated with bacterial autovaccines made from strains, isolated during the bacteriological examination. One cycle consisted of 2–3 courses of immunization with bacterial vaccines. One course included 10 or 12 subcutaneous injections in increasing dosage during 19–21 days. Between courses, there was maintained an interval of 3 to 4 weeks. The treatment cycle generally lasted from 70 to 110 days, depending on the number of courses. Intervals between treatment cycles were usually maintained for 3 months. The effectiveness of such treatment was 71.2 % after the first cycle, 92.8 % — after the second, and 99.2 % — after the third with full recovery of the ability to work, lost during the illness, and the emotional level of personal life. Conclusions. It has been established that the etiological cause of the occurrence of prolonged subfebrile fever, febrile fevers of unknown genesis, and febrile attacks is such a clinically and nosologically separate disease as chronic bacterial intoxication syndrome, which develops on the background of a chronic bacterial focus, usually locally asymptomatic infection in the kidneys, called nephrodysbacteriosis, and is usually associated with severe bacterial endotoxicosis that was confirmed by appropriate toxicological examination of the blood. The use of bacterial autovaccines was proved to be an effective method of treatment (up to 99.2 %) of patients with increased temperature of bacterial-toxic origin.


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