ALTERATIONS IN SELECTED HEMATOLOGICAL PARAMETERS DURING OP-PORTUNISTIC INFECTIONS

Danish Scientific Journal No102, 2025 31 MEDICAL SCIENCES ALTERATIONS IN SELECTED HEMATOLOGICAL PARAMETERS DURING OPPORTUNISTIC INFECTIONS Nurieva Kh. The Scientific-Research Institute of Medical Prophylaxis named after V.Y.Akhundov https://doi.org/10.5281/zenodo.17740984 Abstract Opportunistic infections (OIs) predominantly occur in individuals with compromised immune systems—particularly those living with Human Immunodeficiency Virus (HIV), organ transplant recipients, or patients receiving immunosuppressive therapy due to chronic illnesses. These infections lead to various alterations in the hematological system. This article scientifically analyzes the changes in key blood parameters during OIs, including hemoglobin, leukocytes, lymphocytes, platelets, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Such hematological changes are of diagnostic and prognostic importance and play a critical role in monitoring the effectiveness of treatment. Keywords: Opportunistic infections, hematological alterations, HIV, anemia, lymphopenia, thrombocytopeni. Methodology This article was prepared based on a systematic review of scientific literature published between 2020 and 2025. Data were collected from the PubMed, Scopus, ScienceDirect, and World Health Organization (WHO) databases using the keywords “opportunistic infections,” “hematological changes,” “HIV,” “anemia,” “thrombocytopenia,” and “CRP.” Inclusion criteria comprised studies published in English, conducted on human subjects, and reporting hematological parameters in the context of opportunistic infections. Duplicate studies and articles not directly related to the topic were excluded. The collected data were classified and analyzed thematically to assess alterations in hematological and biochemical markers. Findings were supported by relevant scientific references and supplemented with regional statistics from Azerbaijan, Armenia, and Georgia. Introduction Opportunistic infections (OIs) develop when the normal function of the immune system is compromised, particularly with a decrease in the number of CD4+ Tlymphocytes. In such conditions, the immune response of the organism is weakened, allowing latent or widely distributed environmental microorganisms to cause infection. OIs are accompanied not only by clinical manifestations but also by hematological alterations, which are of significant importance for diagnosis and treatment planning. (1,2) Hemoglobin, as the primary component of red blood cells, plays a crucial role in oxygen transport to tissues. A decrease in its level—known as anemia—is a common clinical problem frequently observed in chronic diseases and infections. The development of anemia in these contexts is explained by multiple mechanisms, and it significantly impacts clinical progression, quality of life, and survival outcomes. (1) The development of anemia during opportunistic infections involves several key mechanisms: • Inflammatory cytokines (IL-1, IL-6, TNFalpha) increase the synthesis of hepcidin, thereby reducing iron utilization. • Bone marrow suppression due to the cytotoxic effects of the infection itself or medications such as zidovudine and chemotherapeutic agents. • Nutritional deficiencies, including deficits in vitamin B12, folate, and iron. • Hemolysis caused by autoimmune processes triggered by certain infections or drugs. Research indicates that Human Immunodeficiency Virus (HIV) belongs to the genus Lentivirus within the family Retroviridae. The virus primarily targets CD4+ T-helper lymphocytes, leading to progressive depletion of these cells and resulting in excessive immunosuppression. This suppression weakens the immune system and causes a wide range of clinical manifestations. Untreated HIV infection ultimately progresses to Acquired Immunodeficiency Syndrome (AIDS), at which stage the immune system fails to prevent infections, leading to opportunistic infections that can be fatal. HIV is classified into two major types: HIV-1 and HIV-2. Although their genomes are structurally similar, they differ significantly at the amino acid level. These two viruses emerged from separate zoonotic transmissions of simian immunodeficiency viruses and differ substantially in terms of virulence, transmission, and prognosis. Notably, HIV-1 and HIV-2 share only approximately 60% amino acid sequence homology and 48% nucleotide sequence identity. Anemia is observed in 30–70% of patients with HIV infection, with the risk increasing as CD4+ cell counts decline. (3) Opportunistic infections such as Pneumocystis jirovecii pneumonia, cytomegalovirus (CMV), Mycobacterium tuberculosis, and others can further exacerbate this process. Clinically, this is manifested by symptoms including fatigue, dizziness, tachycardia, impaired concentration, dyspnea, and decreased functional capacity. The presence of anemia predicts disease severity, reduces survival rates, increases the risk of developing 32 Danish Scientific Journal No102, 2025 opportunistic infections, and diminishes the efficacy of antiretroviral therapy (ART). (3) This graph illustrates the prevalence (%) of anemia and the average hemoglobin levels (g/dL) observed in various opportunistic infections. • The highest anemia prevalence is observed in the HIV/AIDS stage (70%), with an average hemoglobin level of approximately 9.2 g/dL. • Anemia is less common during CMV and Pneumocystis jirovecii infections, and hemoglobin levels remain more stable. • In Cryptococcus neoformans infection, hemoglobin levels are slightly elevated, with anemia prevalence around 55%. This article examines the leukocyte changes observed during different opportunistic infection agents, their role in pathogenesis, and their clinical significance. Leukocytes provide defense against various microorganisms. In opportunistic infections, particularly with the reduction of CD4+ T-lymphocyte levels, the number, subsets, and functions of leukocytes change. These alterations not only reflect the immunosuppressive state but also provide valuable information about disease progression and prognosis. (2) The above graph presents percentage changes in leukocyte fractions (lymphocytes, neutrophils, monocytes) observed during various opportunistic infections. Different leukocyte types and their functional alterations are discussed below. Lymphocytes, particularly CD4+ and CD8+ Tcells, play critical roles in immune defense. HIV infection leads to depletion of CD4+ T-lymphocytes, which weakens resistance against opportunistic infections (4). Although reactive CD8+ T-lymphocytosis (increase in CD8+ cells) can be observed as a compensatory response, it is insufficient to fully prevent infections (5). CD4+ T lymphocytes coordinate the immune response by stimulating other immune cells such as macrophages, B lymphocytes (B cells), and CD8+ T lymphocytes to combat infections. HIV destroys CD4+ cells, thereby impairing the immune system. Neutrophils and neutropenia are especially common in patients undergoing antiretroviral therapy (ART) or chemotherapy. Neutrophil activity may also Danish Scientific Journal No102, 2025 33 be diminished during infections caused by Mycobacterium avium complex and Pneumocystis jirovecii (6,7). Monocytes – Pathogens such as Mycobacterium tuberculosis and Histoplasma capsulatum activate monocytes, leading to increased secretion of inflammatory mediators. During chronic infections, an increase in monocyte count (monocytosis) may be observed (8). Eosinophils and basophils – Eosinophilia is commonly observed in parasitic infections, such as Toxoplasma gondii. Although information regarding basophil function is limited, they may play a role in allergic and hypersensitivity reactions (9). B lymphocytes and natural killer (NK) cells also play crucial roles in the immune response. Changes in the function and number of these cells can be observed during opportunistic infections. Thrombocytopenia is one of the common hematological abnormalities frequently encountered in HIV infection. A systematic review and meta-analysis conducted in 2021 determined the overall prevalence of thrombocytopenia among HIV-infected adults to be 17.9% (10). The prevalence of thrombocytopenia was observed to be 21% before HAART therapy and decreased to 11.64% after treatment (11). Antiretroviral therapy (ART) plays a critical role in the restoration of hematological parameters in patients with HIV infection. • Following initiation of ART, CD4+ cell counts gradually increase, and the CD8/CD4 ratio tends to normalize. • Most cases of anemia and thrombocytopenia regress within 6–12 months of treatment. • A study published in BMC Hematology (2023) demonstrated that patients receiving ART exhibited a mean increase of 1.4 g/dL in hemoglobin levels, while the prevalence of thrombocytopenia declined from 21% to 11%(19). • A reduction in C-reactive protein (CRP) levels and stabilization of ferritin have been proposed as indicators of treatment effectiveness (21). HIV infection can induce the production of antibodies against platelets. Additionally, HIV can impair megakaryocyte function, leading to reduced platelet production in the bone marrow. Opportunistic infections, particularly tuberculosis and cytomegalovirus (CMV), can affect the bone marrow and cause thrombocytopenia. Some antiretroviral drugs, such as zidovudine (part of ART), may also contribute to this condition (12). In opportunistic infections, the increase in Creactive protein (CRP) levels is generally lower compared to typical bacterial infections. This suggests that CRP is less sensitive in viral or nonbacterial infections. Normalization of CRP levels following treatment in patients with Mycobacterium avium complex (MAC) infection has been associated with improved survival (13). The above graph illustrates the average C-reactive protein (CRP) levels (mg/L) observed during various opportunistic infections. The data were derived from relevant studies and visually depict how CRP levels correlate with the severity of infection. An inverse relationship has been observed between elevated CRP levels and decreased CD4 cell counts in HIV-infected patients. This suggests that CRP may serve as a marker of immunosuppression (14). Hematological biomarkers—CRP, ESR, ferritin, D-dimer, IL-6, and TNF-α—are widely utilized to evaluate the intensity of inflammation, the extent of tissue injury, and the therapeutic response in opportunistic infections. • CRP levels reflect the activity of opportunistic bacterial infections in HIV-infected individuals, whereas increases are generally less pronounced in viral opportunistic infections. • ESR is typically elevated in chronic infections and often parallels the presence and severity of anemia. • Ferritin serves as a marker of both iron metabolism and systemic inflammation; elevated levels may indicate active infection and ongoing inflammatory responses. • IL-6 and TNF-α cytokines suppress hematopoiesis within the bone marrow, thereby contributing to the development and progression of anemia and thrombocytopenia. According to a 2024 PLOS ONE study, levels of IL-6 and TNF-α were found to be 3–5 times higher than normal among ART-naïve HIV-infected patients, demonstrating a strong association with hematological imbalance and immune dysregulation (22). In HIV-positive patients with Toxoplasma gondii infection, increased CRP levels have been reported. Following antiretroviral therapy (ART), a decrease in 34 Danish Scientific Journal No102, 2025 CRP levels was observed in these patients, indicating the effectiveness of the treatment. The above graph visually presents changes in CD4+ and CD8+ lymphocytes, as well as decreases in the CD4/CD8 ratio, observed during various opportunistic infections. Cytokines act not only as key mediators of the immune response against infections but also affect other body systems, including bone metabolism. Some studies have demonstrated that in osteoporosis developed against the background of estrogen deficiency, levels of cytokines such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factoralpha (TNF-α) increase. However, no significant differences were observed in other cytokines like IFN-γ, GM-CSF, and LIF. The systemic effects of elevated proinflammatory cytokines during infections extend beyond immune responses and may negatively impact bone metabolism. These findings are important for understanding the complex systemic consequences of cytokine activity in opportunistic infections (15). These findings indicate that the increase in proinflammatory cytokines affects not only the immune system but also the skeletal system. During opportunistic infections, such systemic inflammatory changes may lead to disruptions in bone metabolism. Azerbaijan and Regional Context The HIV prevalence in Azerbaijan in 2022 among the population aged 15–49 was 0.1%, which is below the global average. Neighboring countries in the region, such as Armenia and Georgia, exhibit relatively similar figures. For instance, in Armenia in 2019, approximately 66% of newly diagnosed individuals had a CD4 count below 350 cells/mm³, indicating a more advanced stage of opportunistic infections. In people living with HIV, a decrease in CD4+ cells correlates with an increased risk of anemia, and delayed initiation of antiretroviral therapy (ART) in the region exacerbates these conditions. The prevalence of thrombocytopenia among treatment-naïve patients ranges between 20– 22%, and this rate rises to 25–35% when the CD4+ count is below 200 cells/mm³. CRP and ESR levels are elevated during tuberculosis and other coinfections, serving important diagnostic roles. (16,17) Danish Scientific Journal No102, 2025 35 The above graph presents the estimated prevalence rates of certain hematological parameters in Azerbaijan and neighboring regional countries: CD4+ cell counts below 350 cells/mm³, thrombocytopenia, and anemia. The data is based on available regional statistics and scientific sources. Data on the hematological aspects of HIV and opportunistic infections in the Caucasus region remain limited; however, available statistics indicate several notable differences: • Azerbaijan – HIV prevalence is approximately 0.1%, with ART coverage around 70%. The prevalence of anemia among patients with CD4+ counts below 350 cells/mm³ ranges from 42% to 45%. • Armenia – HIV prevalence is estimated at 0.2%, and the initiation rate of ART is relatively lower (62%), with hematological complications observed more frequently (16). • Georgia – ART coverage approaches 80%, yet opportunistic infections—particularly tuberculosis (TB) and cytomegalovirus (CMV)—remain major causes of morbidity. These findings suggest that comprehensive ART coverage and strengthened hematological monitoring continue to represent priority areas for improving patient outcomes in the region (17,20). Conclusion Changes in hematological parameters during opportunistic infections play a crucial role in the diagnosis, assessment of disease progression, and monitoring of treatment. Hematological indicators—particularly alterations in leukocyte, lymphocyte, neutrophil, erythrocyte, and hemoglobin levels—reflect the body’s immune response and immunological status against infections. Additionally, biochemical and immunological markers such as C-reactive protein (CRP), ferritin, erythrocyte sedimentation rate (ESR), interleukins, and tumor necrosis factoralpha (TNF-α) provide valuable information about the degree of inflammation, tissue damage, and systemic immune activation. Comprehensive analysis of these parameters serves as a reliable tool for the early detection of opportunistic infections, evaluation of disease severity, and individualization of therapeutic interventions in immunodeficient patients. References: 1. Weiss, G., & Goodnough, L. T. (2005). Anemia of chronic disease. New England Journal of Medicine, 352(10), 1011– 1023. https://doi.org/10.1056/NEJMra041809 2. Hoffbrand, A. V., & Moss, P. A. H. (2019). Hoffbrand’s Essential Haematology (8th ed.). 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