1. Introduction

Recent years have witnessed significant advancements in the management of various infectious diseases, including brucellosis. Collaborative efforts among healthcare providers and veterinary specialists have effectively eradicated brucellosis from numerous previously endemic regions, leading to a marked reduction in human cases. However, despite these achievements, the incidence of brucellosis remains persistently high in specific geographical areas [1,2,3,4].

Control of brucellosis continues to be a critical social concern due to its severe economic implications and health effects. Brucellosis infections can cause chronic illness, prolonged disability, and permanent impairments. While the disease has become relatively uncommon in many parts of the world, it still poses a significant health risk in Asia, particularly in endemic regions such as Central Asia and Kazakhstan [5,6,7].

In Uzbekistan, recent data indicates a substantial increase in brucellosis across all demographic groups. Annually, Uzbekistan reports around 1.5 to 2.2 new brucellosis cases per 100,000 populations, a rate notably higher—between two to five times—than that observed in other CIS countries [8,9,10].

Research conducted in Uzbekistan has shown that non-professional populations represent 81.6% of brucellosis cases, while the remaining 18.4% occur within professionally at-risk groups. Additionally, a correlation was established between clinical manifestations of brucellosis and the type of livestock farming practiced. Areas practicing mixed livestock farming demonstrated more severe disease progression, including significant organ involvement such as splenomegaly and hepatomegaly. A key factor identified was the prevalence of the highly virulent B. melitensis biovar 3 strain in these mixed farming areas. Uzbekistan also has circulating strains such as B. melitensis biovars 1 and 3, alongside B. abortus biovars 1, 3, and 6 [11].

Another notable feature of brucellosis in Uzbekistan and Kazakhstan is the dominance of chronic disease forms, affecting up to 71.2% of cases, with primary chronic cases comprising up to 48.6% [12,13].

The demographic most frequently affected by brucellosis includes individuals aged 20 to 40, typically engaged in meat and dairy production industries. Children, primarily consumers of dairy products, also exhibit a significant infection rate. Human-to-human transmission does not occur, rendering humans an epidemiological dead-end for brucellosis and other similar zoonotic infections [14,15].

Over the past 25-30 years, limited research has explored the impact of chronic brucellosis on pregnancy outcomes. Studies, including those by E.M. Gvozdikova, have revealed notable clinical and pathological changes affecting female reproductive health due to brucellosis, such as menstrual irregularities (dysmenorrhea, oligomenorrhea, menorrhagia), impaired reproductive capacity, spontaneous miscarriages, and intrauterine fetal death [16].

Our observations highlighted characteristic pathological changes in female reproductive organs caused by brucellosis, predominantly vascular alterations including sclerosis leading to significant vessel constriction or blockage. In acute brucellosis, inflammatory infiltrates and localized hemorrhages in ovaries were commonly found. Severe damage to female reproductive organs also occurs frequently in septic-metastatic forms, manifesting predominantly as menstrual irregularities, spontaneous abortions, and premature labor. Menstrual disorders, including amenorrhea, dysmenorrhea, metrorrhagia, and menorrhagia, have been extensively documented in affected individuals.

Multiple studies indicate that brucellosis-related disturbances of menstrual cycles, such as amenorrhea and heteropolymenorrhea, frequently coexist with fertility issues, including infertility, spontaneous abortions, and increased risk of premature birth.

Current immunocorrective therapies for brucellosis carry drawbacks such as high immunogenic potential and notable side effects. Therefore, enhancing therapeutic approaches for women with brucellosis is essential, emphasizing the correction of imbalanced cellular immunity, cooperative functioning of T- and B-lymphocytes and their regulatory subsets, and reduced phagocytic activity. This suggests integrating immunomodulatory agents into comprehensive brucellosis treatment regimens, which include etiotropic, anti-inflammatory, and symptomatic therapies.

The purpose of this research was to analyze epidemiological and clinical characteristics of chronic brucellosis in reproductive-aged women.

2. Materials and Methods

The base of clinical data collection is the Research Institute of Microbiology, Epidemiology and Infectious Diseases in Tashkent city. The study involved 120 female patients, aged between 19 and 39 years, diagnosed with chronic brucellosis. Diagnoses were confirmed through clinical examination, bacteriological cultures, serological tests, and statistical analysis.

3. Results and Discussion

A total of 120 female patients with chronic brucellosis were included in our study. The selected age range, 19 to 39 years, corresponds to the reproductive phase of life. The overall average age of patients across all examined groups was 26.1±0.27 years, without statistically significant variations (P>0.05). Additionally, no significant disparities in age distribution were observed among subgroups. However, women aged 30 years and older (35.1%) and those aged between 20-24 years (29.1%) represented the largest subpopulations. A detailed summary of the age distribution is presented in Figure 1.

Figure 1. Age of the patients

Epidemiologic studies established the following sources of infection: 30.5% of cases were infected from small cattle, 13.3% from cattle, and 9.5% from small and cattle simultaneously (Figure 2).

Figure 2. Source of infection

Infection was alimentary in 49 (46.6%) women, contact in 48.6% and contact-alimentary in 5 (4.8%) (Figure 3).

Figure 3. Pathways of transmission

Epidemiological data indicate that brucellosis infection is mainly associated with contact with individual sector cattle, which is consistent with literature data (Ni-azmatov B. I. 2002; Imomaliev U. N., 2005).

The duration of the disease in the patients before admission to the hospital was different: up to 1 year - in 24 (22.8%), in 68 (64.7%) - from 2 to 5 years, in 13 (12.3%) - more than 5 years (Figure 4).

Figure 4. Duration of the disease

Serological tests conducted on the examined women predominantly yielded seropositive results. Heddleson's reaction was positive in 87.0% of cases, Wright's reaction in 85.4%, and ELISA identified antibodies in 85.5% of cases and antigens in 29.7%. The geometric mean antibody titers were 1:100 using Wright’s reaction and 1:800 via ELISA.

Furthermore, reproductive health assessment revealed that chronic brucellosis significantly adversely affected pregnancy outcomes. Women with chronic brucellosis had elevated occurrences of early and late spontaneous miscarriages, preterm births, and a higher rate of perinatal mortality (Table 1).

Table 1

A detailed evaluation of the clinical features of brucellosis infection indicates that the contemporary presentation of the disease tends to be milder compared to past observations. A thorough review of disease onset and progression showed that in 60% of cases, brucellosis primarily exhibited a chronic form, developing gradually without significant temperature elevations. However, subfebrile temperatures were noted in approximately one-third (30.7%) of patients, while nearly one-fifth (19.3%) presented with elevated temperatures and chills. Mild sweating was reported in 72.7% of patients.

All patients experienced general weakness, with reduced appetite and nausea documented in 34.1% of cases. Notably, joint pain, particularly in the large joints of the limbs, emerged as the principal symptom in 52.3% of patients, while muscle pain in limbs and back pain were reported in 31.8% and 26.1%, respectively.

Comparatively, patients suffering from chronic brucellosis experienced symptoms such as fatigue (82.3±4.1%) and sweating (70.1±4.9%) at rates similar to those with acute manifestations. A similar pattern was observed for hypotonic dystonia (24.1±4.5%). Nevertheless, chronic brucellosis patients exhibited significantly higher incidences of cardiac discomfort (25.3±4.6%) and headaches (62.1±5.1%). Conversely, genitourinary system involvement was relatively rare in acute brucellosis cases (6.9±3.9%).

Musculoskeletal symptoms were frequently associated with peripheral nervous system involvement, including headache and disrupted sleep, affecting 34.1% of patients. Objective clinical examination identified moist skin in 72.0% and pale-pink mucous membranes in 80.0%. No rash or skin hemorrhages were detected. Enlargement of peripheral lymph nodes was common, especially inguinal (78.0%), axillary (70.0%), and less frequently submandibular (16.0%), with nodes being painless and movable upon palpation.

Cardiovascular examinations revealed variable heart rate abnormalities: tachycardia (38.0%), bradycardia (34.0%), muted heart tones (80.0%), and low blood pressure (50.0%). Digestive symptoms included tongue coating (46.0%), epigastric pain (12.0%), hepatomegaly (78.0%), and splenomegaly (18.0%). Liver palpation findings were modest enlargement (64.1%), moderate enlargement (20.5%), and mild sensitivity (5.1%).

In secondary chronic brucellosis, patients predominantly reported subjective symptoms such as joint pains in major limb joints, bursitis, radiculitis, neuritis, and polyneuritis. Primary chronic brucellosis primarily affected the musculoskeletal system, notably arthritis of the shoulder (40.0%), knee (36.0%), elbow (22.0%), ankle (14.0%), hip (14.0%), small joints (16.0%), wrist (12.0%), bursitis (64.0%), and myositis (48.0%). Chronic brucellosis patients experienced musculoskeletal complaints at twice the frequency compared to acute cases, with significant reports of joint pain (90.8±3.1%, P<0.05) and spinal discomfort (87.4±3.6%, P<0.05). Chronic cases notably presented with osteoarthritis confirmed by radiology (73.6±4.7%), and similar proportions had lumbar and thoracic osteochondrosis. Extra-articular manifestations differed markedly between acute and chronic forms, with synovitis (33.3±5.1%) and bursitis (9.2±3.1%) seen exclusively in chronic brucellosis.

Additional analysis of somatic health in women diagnosed with chronic brucellosis during remission found high prevalence (63.2±2.2%) of concurrent chronic extragenital diseases. Among these, anemia (90.4±3.2%), recurrent respiratory infections (85.5±3.9%), thyroid disorders (53.0±5.5%), and chronic cholecystitis (49.4±5.5%) were prevalent. Women with brucellosis demonstrated a notably higher history of childhood infectious diseases (53.0±5.5%), ENT conditions (44.6±5.5%), chronic tonsillitis (34.9±5.2%), viral hepatitis (20.5±4.4%), and pneumonia compared to controls.

Women with chronic brucellosis also showed significantly higher rates of gastrointestinal issues (gastritis, enterocolitis, biliary dyskinesia) at 34.9±5.2%, and intestinal giardiasis at 14.5±3.9%, compared to control groups. Thyroid pathologies occurred at twice the rate in affected women (53.0±5.5%) versus controls (23.3±2.6%, P<0.001).

Reproductive outcomes in women with chronic brucellosis frequently included early and late spontaneous abortions, premature labor, and increased perinatal mortality. The findings highlight the critical importance of prior infectious episodes, chronic inflammation, latent urinary tract infections, and delayed menstrual function development as risk factors. Understanding these clinical and immunological dynamics is essential for improving preventative and therapeutic strategies for chronic brucellosis (Table 2).

Table 2

4. Conclusions

Patients diagnosed with primary chronic brucellosis in 35% of cases had musculoskeletal disorders aggravated by neurological disorders. For example: headaches and sleep disorders. Patients with secondary chronic brucellosis predominantly reported subjective symptoms, including joint pain (arthralgia) in large joints of hands and feet, accompanied by bursitis and neurological issues like radiculitis, neuritis, and polyneuritis. Additionally, the presence of extragenital pathologies was notably high among the studied women. This may suggest that chronic brucellosis frequently develops in individuals with previous exposure to significant infectious events, likely due to compromised immune responses.

Reproductive outcomes in women with chronic brucellosis frequently included early and late spontaneous abortions, premature labor, and increased perinatal mortality. The findings highlight the critical importance of prior infectious episodes, chronic inflammation, latent urinary tract infections, and delayed menstrual function development as risk factors. Understanding these clinical and immunological dynamics is essential for improving preventative and therapeutic strategies for chronic brucellosis.

In conclusion, chronic brucellosis is significantly correlated with adverse reproductive outcomes, notably spontaneous miscarriages and premature births. These complications likely result from underlying inflammatory processes and immune disturbances characteristic of chronic infection, emphasizing the necessity for targeted clinical monitoring and management strategies in pregnant women with a history of brucellosis.