Clinical Perspective on Human Immunodeficiency Virus Care of Ukrainian War Refugees in Poland.

BACKGROUND: The Russian invasion of Ukraine forced migration for safety, protection, and assistance. Poland is the primary sheltering country for Ukrainian refugees, providing support including medical care, which resulted in the rapid ∼15% increase in the number of followed-up people with human immunodeficiency virus (HIV) (PWH) in the country. Here, we present the national experience on HIV care provided for refugees from Ukraine. METHODS: Clinical, antiretroviral, immunological, and virologic data from 955 Ukrainian PWH entering care in Poland since February 2022 were analyzed. The dataset included both antiretroviral-treated (n = 851) and newly diagnosed (n = 104) patients. In 76 cases, protease/reverse transcriptase/integrase sequencing was performed to identify drug resistance and subtype. RESULTS: Most (70.05%) of the patients were female, with a predominance of heterosexual (70.3%) transmissions. Anti-hepatitis C antibody and hepatitis B antigen were present in 28.7% and 2.9% of the patients, respectively. A history of tuberculosis was reported in 10.1% of cases. Among previously treated patients, the viral suppression rate was 89.6%; 77.3% of newly HIV diagnosed cases were diagnosed late (with lymphocyte CD4 count <350 cells/µL or AIDS). The A6 variant was observed in 89.0% of sequences. Transmitted mutations in the reverse transcriptase were found in 15.4% treatment-naive cases. Two patients with treatment failure exhibited multiclass drug resistance. CONCLUSIONS: Migration from Ukraine influences the characteristics of HIV epidemics in Europe, with an increase in the proportion of women and hepatitis C coinfected patients. Antiretroviral treatment efficacy among previously treated refugees was high, with new HIV cases frequently diagnosed late. The A6 subtype was the most common variant.

Management of bacterial skin and soft tissue infections.

Skin and soft tissue infections (SSTIs) are a group of diseases usually caused by bacteria, and connected with different clinical picture, course, and prognosis. The increasing incidence of SSTIs is associated mainly with aging of the population, the increasing number of metabolic diseases, especially diabetes mellitus, as well as cardiovascular diseases. Although SSTIs are often benign and usually does not require medical consultations, some of them may cause a systemic infection. In this situation, knowledge of the principles of diagnostic work-up and therapy is essential. The principles of recognition and treatment of skin and soft tissue infections, including new biocidal drugs, are presented.

[The risk of malaria during travel, observations in the department of infectious diseases in Cracow from 1996 to 2010]. / Ryzyko zarazenia malaria w czasie podrózy w swietle danych kliniki chorob zakaznych w krakowie z lat 1996-2010.

UNLABELLED: Actually in Poland malaria is not present as an endemic disease, but is one of the most common "imported" diseases. In its mild form it is an awkward illness with recurring fever, whereas the more severe form, which is caused by Plasmodium falciparum can be life-threatening. AIM OF THE STUDY: Epidemiological and clinical analysis on malaria-infected patients hospitalized in the Department of Infectious Diseases in Cracow from 1996 to 2010. METHODS: Interview, physical examination, laboratory tests and usg of the abdomen were performed among all patients. Diagnosis was performed by malaria parasites detection in direct microscopic observation of thick and thin blood films. Patients were treated with antimalarial drugs according to parasites species and previously used prophylaxis. RESULTS: 33 people with malaria, 26 men (79%) and 7 women (21%), aged 24-71 years were hospitalized. Annually 1 to 4 patients were treated, but in year 2008 - 7 patients. 18 persons (54%) were travelling as a tourists to the endemic regions, including 15 persons on short trips (up to 1 month). 15 persons (46%) were involved in business-trips and missions with over 2 years stay. Most patients visited Africa (25 persons), 4 travelled to Oceania, 3 to Asia and 1 to South America. Only 3 patients (9%) used recommended antimalarial prophylaxis. Symptoms of malaria usually appeared a few days after returning to Poland, 1 woman presented the symptoms after 1 year, 4 patients were presenting the symptoms already in the tropics. 25 persons (76%) had malaria for the first time. Clinical symptoms among patients were: fever preceded by shivering (100%), sweating (94%), muscles and joints pain (84%), nausea and vomiting (24%), diarrhoea (12%), jaundice (12%), cough (6%), coma (6%), multiorgan failure (6%). 12 persons were diagnosed with hepatomegaly, 21 with splenomegaly, 9 with hemolytic anaemia, 18 with thrombocytopenia and 14 with elevation of liver enzymes. P. falciparum infection was proven in 15 patients (46%), P. vivax in 11 patients (33%), P. ovale in 1 patient (3%), mixed infection (P. falciparum and P. ovale) in 6 patients (18%). In the treatment of P. falciparum infection quinine with doxycycline (18 patients) or mefloquine (2 patients) were used, in other cases chloroquine with following primaquine. 32 patients recovered, 1 patient with cerebral malaria died. CONCLUSIONS: Malaria was most commonly diagnosed among tourists staying for short period of time in an endemic area. Travelers did not use accurate antimalarial prophylaxis. Malaria must be excluded as a potential diagnosis among all fever suffering persons returning from the tropics.

Molecular epidemiology and HIV-1 variant evolution in Poland between 2015 and 2019.

The occurrence of HIV-1 subtypes differs worldwide and within Europe, with non-B variants mainly found across different exposure groups. In this study, we investigated the distribution and temporal trends in HIV-1 subtype variability across Poland between 2015 and 2019. Sequences of the pol gene fragment from 2518 individuals were used for the analysis of subtype prevalence. Subtype B was dominant (n = 2163, 85.90%). The proportion of subtype B-infected individuals decreased significantly, from 89.3% in 2015 to 80.3% in 2019. This was related to the increasing number of subtype A infections. In 355 (14.10%) sequences, non-B variants were identified. In 65 (2.58%) samples, recombinant forms (RFs) were noted. Unique recombinant forms (URFs) were found in 30 (1.19%) sequences. Three A/B recombinant clusters were identified of which two were A6/B mosaic viruses not previously described. Non-B clades were significantly more common among females (n = 81, 22.8%, p = 0.001) and heterosexually infected individuals (n = 45, 32.4%, p = 0.0031). The predominance of subtype B is evident, but the variability of HIV-1 in Poland is notable. Almost half of RFs (n = 65, 2.58%) was comprised of URFs (n = 30, 1.19%); thus those forms were common in the analyzed population. Hence, molecular surveillance of identified variants ensures recognition of HIV-1 evolution in Poland.

[Lipodystrophy and metabolic disturbances as complications of antiretroviral therapy]. / Lipodystrofia i zaburzenia metaboliczne jako powiklanie terapii antyretrowirusowej.

Effective treatment of HIV infection with antiretroviral drugs significantly improve prognosis. Reduction of mortality and life prolongations in patients receiving such therapy have been also connected with the risk of side effects development. Among these complications metabolic disturbances such as lipodystrophy, dyslipidaemia, and insulin resistance which are present according some authors in up to 50% of patients receiving HAART play an important role. In spite of different investigations molecular basis of lipodystrophy development during HAART have not be fully understood, and the latest research revealed a lot of new aspects connected w adipocyte tissue pathophysiology, which were not taken up to know into consideration. In the presented publication the most important information about pathogenesis of lipodystrophy development in HIV infected patients treated with ARV drugs have been presented.

[Brain abscess--modern diagnostics and therapeutic treatment]. / Ropnie mózgu--wspólczesne postepowanie diagnostyczno-terapeutyczne.

Brain abscess is one of the most serious diseases of the central nervous system. This condition is more common among men--twice to three times, and morbidity rate is highest in fourth decade of the life. Etiologic agents of brain abscess are bacteria, fungus, protozoa and parasites. The development of the brain abscess can resulted from the spread of infection from local sites or bloodborne from distal sites. In 10-15% of cases multiple abscesses develop. Headache is the most common syndrome. The radiologic tests: computed tomography or magnetic resonance are tests of choice in diagnosis and monitoring of treatment. Treatment of brains abscesses required cooperation of different specialists: infectious diseases, neuroradiologist, neurologists and neurosurgeon. Decision about therapeutic methods depends on number, size and localization of lesions, and patient's condition. In conservative treatment empiric antibiotic therapy and supportive treatment are used. Actually two methods of surgical treatment are used: CT- guided stereotactic aspiration and incision of the brain abscess by craniotomy. Actually mortality rate is 6 to 24%. Among 30-56% patients permanent neurological complications are reported.

Acute Hepatitis A Outbreak Among Men Who Have Sex With Men in Krakow, Poland; February 2017-February 2018.

Since February 2017 in Poland, an increasing number of acute hepatitis A (AHA) cases have been reported; a noteworthy increase to 3,072 cases of AHA in 2017 compared to 35 cases in 2016 was reported by the National Institute of Public Health (NIPH). The aim of this study was to evaluate the demographic features, clinical manifestations, laboratory results, and sexually transmitted coinfections. All cases of AHA diagnosed between February 2017 and February 2018 at the University Hospital in Krakow were analyzed. A total of 119 cases of hepatitis A virus (HAV) were reported; 105 (88%) were males and 14 (12%) were females, with a mean age 31 years (range 19-62). In 84 patients (71%), the HAV was transmitted by oral-anal sexual contact between men. Six women were infected by close house contact with men infected with HAV. The route of transmission was not identified for 29 cases, and 88 patients (74%) required hospitalization. Among the cases, the following coinfections were already diagnosed: HIV 36 patients (30%), chronic hepatitis C virus (HCV) 4 patients (3%), and chronic hepatitis B virus (HBV) 2 patients (1.5%). During AHA diagnosis, some new sexually transmitted infections (STIs) were detected; syphilis eight patients (6.7%), HIV/syphilis seven patients (6%), HIV//HCV/syphilis one patient, and acute retroviral syndrome/Shigella flexneri one patient. Overall, AHA outbreak in Poland in 2017 affected primarily men who have sex with men (MSM) and was connected with oral-anal sexual contacts, and the majority of patients did not have HAV vaccination. These results show a clear need for routinely offering HAV vaccination to at-risk populations and that awareness among health-care workers about HAV sexual transmission may help introduce prevention methods.

[Invasive meningococcal disease--management and treatment]. / Inwazyjna choroba meningokokowa--postepowanie i leczenie.

Invasive meningococcal disease is life threatening disease and in fulminant cases mortality rate may be as high as 70%. Rapid introduction of treatment and monitoring on intensive care unit is crucial for prognosis. The understanding of patomechanism responsible for sepsis development allow to introduce supportive treatment including glicocorticoids and recombinant human activated protein C. Very important is suitable prophylaxis among risk groups with, additional considering vaccination in the case of infection caused by A, C, Y, W-135 serogroups.

[Efficacy of vaccination against hepatitis B in adult with HIV infection]. / Skutecznosc szczepienia przeciwko wirusowemu zapaleniu watroby typu B u doroslych osób zakazonych HIV.

OBJECTIVES: The aim of the study was to evaluate the efficacy of vaccination against hepatitis B in HIV infected individuals and the influence of the stage of HIV infection and antiretroviral therapy (HAART). Response for additional doses of hepatitis B vaccine among the patients who do not develop protective anti-HBs level after routine vaccination schedule was analysed. METHODS: Fifty-four HIV infected individuals, 20 women (37%) and 34 men (63%), 20 to 64 years old (mean age 32 years) were analysed. 32 patients (59.6%), 22 men and 10 women were treated with antiretroviral drugs. Stage of HIV infection was assessed on the basis of data derived from medical records (lowest CD4 cells count, highest viral load), and immunological status at the moment of introduction of vaccination (CD4 cells count, viral load). Efficacy of vaccination was compared with control group, which consisted of 56 healthy volunteers. In both groups hepatitis B virus infection was excluded by serologic tests. HBvaxPro vaccine produced by Merck Sharp & Dohme Company, dose registered for adults (10 ug) was injected at month 0-1-6. Patients with anti-HBs <10 IU/l have received booster doses of vaccine month intervals, no more then three. RESULTS: Protective level of antibodies was found in 52 (92.9%) persons from control group and 32 (63%) HIV infected individuals. Anti-HBs > 100 IU/l was twice more common in control group (80%) than in investigated group (46.3%) (p < 0.001). Protective level of anti-HBs had 14.3% patients with CD4 below 200 cells/pl, none of them had anti-HBs > 100 IU/l. Patients with higher CD4 cell count had better response for vaccination (p = 0.015). Differences between patients with high and low viral load were not statistically significant (p = 0.015). Patients with viral load below 10,000 copies/ml had slightly better response then those with higher viral load. Efficacy of vaccination was also associated with the level of distraction of immunological system before introduction of HAART. Patients with CD4 < 200 cells/microl or HIV-RNA > 50,000 copies/ml had worst immunological response for vaccination. After the fist additional dose of vaccine anti-HBs >10 IU/l had 79.7% patients, 87.1% after the second dose and 90.7% after the third dose. Anti-HBs >100 IU/l had subsequently 57.4%, 66.7%, 79.6% patients. CONCLUSIONS: We concluded that efficacy of the routine vaccination schedule was lower among HIV individuals in comparison with healthy volunteers. Influence of the progression of HIV infection on the response for vaccination was detected. Additional vaccine's doses have improved efficacy of immunisation which was comparable with general population.

[Toxoplasmosis--epidemiology, clinical manifestation and infection in pregnant women]. / Toksoplazmoza--epidemiologia, obraz kliniczny i zakazenie w czasie ciazy.

Toxoplasma gondii infection is one of the most popular human zoonosis. Presented is the epidemiology and clinical symptoms of toxoplasmosis with particular attention to infection during pregnancy. The paper presents the life cycle of Toxoplasma gondii, routes of transmission and clinical manifectations. The scheme of diagnostic and terapeutic procedures in case of infection during pregnancy is discussed. Congenital infection, serologic diagnostics and clinical symptoms have been described. Treatment of congenital toxoplasmosis is also presented.

Distribution and time trends of HIV-1 variants in Poland: Characteristics of non-B clades and recombinant viruses.

The spread of HIV-1 subtypes varies considerably both worldwide and within Europe, with non-B variants commonly found across various exposure groups. This study aimed to analyse the distribution and temporal trends in HIV-1 subtype variability across Poland. For analysis of the subtype distribution, 1219 partial pol sequences obtained from patients followed up in 9 of 17 Polish HIV treatment centres were used. Subtyping was inferred using the maximum likelihood method; recombination was assessed using the bootscanning and jumping profile hidden Markov model methods. Subtype B dominated in the studied group (n=1059, 86.9%); in 160 (13.1%) sequences, non-B variants were present [A1 (n=63, 5.2%), D (n=43, 3.5%), C (n=22, 1.8%), and F1 (n=2, 0.2%)]. In 25 (2.1%) cases circulating recombinant forms (CRFs) were found. Five A1 variants (0.4%) were unique AB recombinant forms (URF) not previously identified in Poland. Non-B clades were notably more common among females (n=73, 45.6%, p<0.001) and heterosexual individuals (n=103, 66.5%, p<0.001) and less frequent among men who have sex with men (MSM) (n=27, 17.42%, p<0.001). HIV-1 viral load at diagnosis was higher among non-B cases [median: 5.0 (IQR: 4.4-5.6)] vs. [median: 4.8 (IQR: 4.3-5.4) log copies/ml for subtype B (p<0.001)] with a lower CD4(+) lymphocyte count at baseline [median: 248 (IQR: 75-503) for non-B vs. median: 320 (IQR: 125-497) cells/µl for subtype B; p<0.001]. The frequency of the non-B subtypes proved stable from 2008 (11.5%) to 2014 (8.0%) [OR: 0.95 (95% CI: 0.84-1.07), p=0.4], with no temporal differences for exposure groups, gender, age and AIDS. Despite the predominance of subtype B, the variability of HIV in Poland is notable; both CRFs and URFs are present in the analysed population. Non-B variants are associated with heterosexual transmission, more advanced HIV disease and have stable temporal frequencies.

[Tuberculous meningoencephalitis--own observations]. / Gruzlicze zapalenie opon mózgowo-rdzeniowych i mózgu--obserwacje wlasne.

Nine cases of the tuberculous meningoencephalitis in adult men and women treated in years 1993-2000 have been presented. The diagnosis was established on the basis of clinical picture and examination of the cerebrospinal fluid (CSF). Routine analysis of CSF was done, as well as the microscopic examination, biological assay, and culture on the Lowenstein-Jensena medium and using Bactec 460 TB system. Only in one case Mycobacterium tuberculosis was found in the smear of CSF stained by Ziehl-Nielsen method. In one case the biologic assay was positive and Mycobacterium tuberculosis was cultured on Lowenstein-Jensen medium. In another 4 cases the pathogen was detected by Bactec 460 TB technique. In 4 cases Mycobacterium tuberculosis was also cultured from the secretion of the respiratory tract, and in one patient urine. On chest X-ray characteristic changes for pulmonary tuberculosis were observed in 5 cases (56%). Seven patients (78%) had hydrocephalus detected on CT scan of the head. One patient died, one (11%) developed persistent complication in form of spastic paralysis of lower extremities and sphincters dysfunction. Seven patients (78%) recovered completely after the 12 months therapy with standard chemotherapeutic regimen for tuberculosis.

[Concentration of proinflammatory cytokines (TNF-alpha, IL-8) in the cerebrospinal fluid and the course of bacterial meningitis]. / Stezenie cytokin prozapalnych (TNF-alpha, IL-1 beta, IL-8) w plynie mózgowo-rdzeniowym a przebieg bakteryjnego zapalenia opon.

Bacterial meningitis is still associated with high mortality rate and severe neurological sequels. The aim of the study was to assess correlation between concentration of proinflammatory cytokines (TNF-alpha, IL-1 beta, IL-8) in the cerebrospinal fluid (CSF) and patient condition described on the basis of Glasgow Coma Scale (GCS), changes in the CSF (pleocytosis, protein and glucose level), mortality rate and occurrence of neurological complications. 42 patients with bacterial meningitis have been analysed. Control group consisted of 25 patients with viral meningitis and 23 patients without meningitis. In analysed group with bacterial meningitis the correlation between number of scores aggregated by patients in GCS and outcome has been observed. Concentration of TNF-alpha, IL-1 beta, IL-8 in CSF of patient with bacterial meningitis was significantly higher (mean value; 705.2 pg/ml, 401.1 pg/ml and 1696.0 pg/ml) than in control group (viral meningitis: 7.93 pg/ml, 31.89 pg/ml, 405.28 pg/ml, without meningitis: 0.38 pg/ml, 2.55 pg/ml, 32.56 pg/ml). Negative correlation between concentration of investigated cytokines in the CSF of patient with bacterial meningitis and GCS has been observed. Furthermore TNF-alpha and IL-8 levels correlated with pleocytosis, and protein and glucose levels, whereas IL-1 beta correlated with pleocytosis and protein level in CSF. Connection between TNF-alpha and IL-1 beta but not IL-8 level and outcome of bacterial meningitis has been observed. High TNF-alpha in the CSF (median value 953 pg/ml) was associated with significant risk of patient death. IL-1 beta has been better prognostic indicator. Patients who developed neurological sequels had median value of IL-1 beta level 401.3 pg/ml, and those who died had 585.9 pg/ml vs 244.7 pg/ml in the group who survived without any complications. Analysis of the ROC curve-revealed, that concentration of IL-1 beta > or = 289.9 pg/ml with 88.9% sensitivity and 67.7% specifity differentiate cases who at risk for death. For TNF-alpha the cut-off was > or = 538.9 pg/ml. The sensitivity for determined critical point was 77%, and specificity was 68.7%. Our investigation confirm that TNF alpha, IL-1 beta, IL-8 are useful in differential diagnosis of neuroinfections. Assessment of patients with bacterial meningitis on the basis of GCS is helpful to establish prognosis, and CGS seems to correlate with the intensity of inflammation in the CSF. High concentration of TNF-alpha, and IL-1 beta in the CSF are associated with the risk of patient death during the course of bacterial meningitis, but IL-1 beta has been the better prognostic marker.

[The effect of antiinflammatory therapy with dexamethasone and dexamethasone with pentoxifylline on the course of bacterial meningitis]. / Wplyw leczenia przeciwzapalnego z zastosowaniem deksametazonu i deksametazonu z pentoksyfilina na przebieg bakteryjnego zapalenia opon mózgowordzeniowych.

Despite of antimicrobial therapy mortality rate in the bacterial meningitis (BM) is high. The aim of the study was to assess the influence of anti-inflammatory treatment with dexamethasone and dexamethasone with pentoxifylline on the course of this disease and concentration of proinflammatory cytokines TNF-alpha, IL-1 beta, II-8 in the cerebrospinal fluid (CSF). 42 patients with the BM were analysed. They were divided into three groups on the basis of applied therapy: A--treated only with antibiotics, A+D--treated with antibiotics and dexamethasone, A+D+P--treated with antibiotics, dexamethasone and pentoxifylline. Anti-inflammatory therapy did not have impact on the resolution of inflammation (pleocytosis, protein and glucose level) in the CSF. However, it was established that adjuvant treatment with dexa-methasone and pentoxifylline has beneficial effect on the course of the BM. In this group 61.5% of patients recovered, in comparison with 28.6% in the group A+D and 26.7% in the group A. Mortality rate was: in the group A--33%, A+D--21.4%, A+D+P--7.7% (p = 0.01). Correlation between the outcome of the BM in the investigated groups and cytokines concentration in CSF was observed. In the group A+D+P all patients responded to the therapy with decrease of cytokine concentration, and coefficients of variation were low (TNF-alpha--1%, IL-1 beta--23.6%, IL-8--18.9%). Also in the group A+D decrease of cytokines concentration in the CSF was observed, however was not such significant in all cases. In the group of patients treated only with antibiotics concentration of cytokines in the CSF varied, even increased in some of them. Our investigation indicates that inhibition of cytokines production in central nervous system (CNS) with dexamethasone and pentoxifylline improves the outcome of BM and is associated with the reduction of neurological sequels and deaths.

[Calcifications of basal ganglia and cerebellum in patient with pseudohypoparathyroidism--case report]. / Zwapnienia jader podstawy mózgu i mózdzku u chorego z rzekoma niedoczynnoscia przytarczyc--opis przypadku.

Presented is the case report of symmetrical calcifications of basal ganglia, cerebellum and subcortical white matter of cerebral hemispheres (Fahr's syndrome) in a 34 year old man with pseudohypoparathyroidism. Attention has been put on characteristic features of Fahr's syndrome and differential diagnosis of this rare disease.

Role of IL-6 and neopterin in the pathogenesis of herpetic encephalitis.

Herpetic encephalitis (HSE) is one of the most severe infection of the central nervous system (CNS), connected with high mortality rate, even when appropriate therapy has been introduced. Better understanding of pathomechanisms responsible for neuronal injury during the course of the disease can be useful in the assessment of the risk of the occurrence of severe complications, as well as in potential introduction of additional therapeutic methods. The purpose of this study is to assess the correlation between concentration of neopterin and IL-6 in the CSF and serum, and the course of HSE. In this study, 36 patients with HSE were investigated, and the control group consisted of 32 patients in whom the infection of the CNS was excluded. We observed significantly higher concentration of neopterin and IL-6 in the CSF of patients with HSV as compared with the control group. Neopterin and IL-6 levels in the CSF correlated with the course of HSE. Higher values were connected with the risk of respiratory failure, development of permanent neurologic complications and patient death. Negative correlations between concentration of IL-6 and neopterin and patient condition assessed by Glasgow Coma Scale (GCS) were observed. Neopterin with high sensitivity and specificity allowed to predict the risk of death or severe neurological complications. Increased concentration of neopterin and IL-6 in the CSF and serum revealed reciprocal positive correlation. Assessment of the concentration of IL-6 and neopterin in the serum was not useful to predict the course of HSE.