Artemether-lumefantrine, mefloquine and atovaquone-proguanil in the treatment of uncomplicated Plasmodium falciparum malaria in travellers: A retrospective comparative study of efficacy and treatment failures.

BACKGROUND: The aim of this study was to evaluate the rates of parasitaemia clearance and the prevalence of treatment failure in patients with uncomplicated Plasmodium falciparum malaria treated with artemether-lumefantrine (AL), mefloquine (MQ), and atovaquone-proguanil (AP). METHOD: The retrospective descriptive study included adult patients with uncomplicated P. falciparum malaria treated at the University Hospital Bulovka in Prague from 2006 to 2019. Parasitaemia clearance was estimated using a linear regression model. RESULTS: The study included 72 patients with a median age of 33 years (IQR 27-45) and a male to female ratio of 3.2:1. Thirty-six patients (50.0%) were treated with AL, 27 (37.5%) with MQ and 9 (12.5%) with AP. The proportion of VFR and migrants was 22.2% with no significant differences among the three groups. The median time to the parasitaemia clearance was two days (IQR 2-3) in patients treated with AL versus four days in the MQ (IQR 3-4) and AP (IQR 3-4) groups, p < 0.001. The clearance rate constant was 3.3/hour (IQR 2.5-4.0) for AL, 1.6/hour (IQR 1.3-1.9) for MQ, and 1.9/hour (IQR 1.3-2.4) for AP, p < 0.001. Malaria recrudescence occurred in 5/36 (13.9%) patients treated with AL and in no patients treated with MQ or AP. CONCLUSIONS: The findings demonstrate the superior efficacy of AL compared to other oral antimalarials in early malaria treatment. However, we observed a higher rate of late treatment failure in patients treated with AL than previously reported. This issue warrants further investigation of possible dose adjustments, extended regimens, or alternative artemisinin-based combinations.

Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae co-infections among patients with newly diagnosed syphilis: a single-centre, cross-sectional study.

OBJECTIVES: The aim of the study was to determine the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae co-infections among patients with newly diagnosed syphilis. METHODS: In patients with any stage of newly diagnosed syphilis swabs were performed from urethra, rectum, pharynx and cervix according to the gender and type of sexual intercourse. From these smears standard validated nucleic acid amplification tests (NAATs) for Chlamydia trachomatis and Neisseria gonorrhoeae infections were done. RESULTS: From 548 (488 men, 60 women) screened patients co-infection was detected in 15.9% of the cases. The majority of the co-infections (86.2%) were asymptomatic. The overall prevalence of chlamydial infection was 11.1% and 8.8% for gonococcal infections. In men who have sex with men (MSM) the prevalence of co-infections was significantly higher (20.0%) than in heterosexual men and women (4.2%) (p < 0.001). In MSM patients the presence of co-infection was significantly associated with HIV infection (p < 0.001). Among MSM 9.6% of the tests detected infection in anorectal site, while prevalence in urethral (2.8%) and pharyngeal (2.4%) localization was significantly lower. In heterosexual patients prevalence was less than 2.0% in all anatomic sites. CONCLUSIONS: The implementation of screening tests in case of sexually transmitted infections in patients with newly diagnosed syphilis is an important part in the management of this disease. These results suggest that screening of asymptomatic heterosexual patients leads to detection of minimum co-infections, but in MSM (especially HIV positive) should always be performed at least in anorectal site, where asymptomatic co-infections are common.

[Guidelines for treating HIV-infected adults and post-exposure prophylaxis for HIV infection].

Antiretroviral therapy represents an essential element in the approach to treatment and prevention of human immunodeficiency virus (HIV). It has changed the fatal disease to a manageable chronic condition and is the most effective prevention of its human-to-human transmission. Knowledge regarding biological characteristics of the virus, its behavior in a human host and our understanding of these phenomena have been extended by clinical experience, new clinical data and recent scientific progress. The development of new drugs becomes a modifier for the existing therapeutic strategy and preference. Certain points are more specific than in the previous guidelines. Definitions of certain clinical and laboratory conditions have been specified more accurately. The indications of specific antiretroviral agents and pitfalls of their use in lifelong antiretroviral treatment are also described more in detail. The document is a result of a general consensus among infectious disease specialists working with HIV patients in the Czech Republic. It should serve as a basic instrument for clinicians recommending treatment of HIV infection as well as a foundation for the society when dealing with both state authorities and health care payers.

[Guidelines for caring for HIV-infected adults and post-exposure prophylaxis of HIV infection].

Presented are general principles of care for HIV-infected persons following their admission to an AIDS care center, initiation of antiretroviral therapy and follow-up. Scientific research, drug development and new clinical data in recent years have led to a change in certain therapeutic perspectives and preferences for the treatment of HIV infection. Certain conditions are better specified, which affect the choice of antiretroviral regimens. Procedures and criteria for monitoring the effect of treatment and indication of post-exposure prophylaxis are specified. The development of this document was based on the latest updates of the most prominent international and European recommendations. It also reflects some of the new scientific information published in recent months. However, general recommendations cannot fully cover all the possible alternatives. They only state basic principles based on current clinical studies, clinical observation and practice. The present document should be the basic source of information for physicians involved in the treatment of patients with HIV infection and should provide a quick reference when selecting treatment regimens in terms of modern pharmacotherapy as well as information on the pitfalls of this treatment. Finally, it should be a support for negotiations between the professional society, state authorities and health care payers.This updated version of the guidelines follows the 2012 edition; once again, they are supplemented by a modified tabular overview.

The Effect of Latent Toxoplasma gondii Infection on the Immune Response in HIV-Infected Patients.

A relationship between latent toxoplasmosis and the immune system during HIV disease is poorly understood. Therefore, the aim of this follow-up study was to characterize immunological parameters in HIV-infected patients with latent toxoplasmosis and noninfected individuals. A total of 101 HIV-infected patients were enrolled in the study. The patients were classified into two groups based on anti-Toxoplasma gondii antibodies: a group of 55 toxoplasma-positive persons (TP) and a group of 46 toxoplasma-negative persons (TN). Absolute counts of several lymphocyte subsets decreased in the TP group, namely, T cells (p = 0.007), B cells (p = 0.002), NK cells (p = 0.009), CD4 T cells (p = 0.028), and CD8 T cells (p = 0.004). On the other hand, the percentage of CD8 T cells expressing CD38 and HLA-DR significantly increased during the follow-up in the TP group (p = 0.003, p = 0.042, resp.) as well as the intensity of CD38 and HLA-DR expression (MFI) on CD8 T cells (p = 0.001, p = 0.057, resp.). In the TN group, analysis of the kinetics of immunological parameters revealed no significant changes over time. In conclusion, the results suggest that latent T. gondii infection modulates the immune response during HIV infection.

Listeria monocytogenes meningitis in adults: the Czech Republic experience.

BACKGROUND: Listeria monocytogenes (LM) is currently the third most frequent pathogen of bacterial meningitis in adults. METHODS: A prospective study of patients with LM meningitis in a Czech tertiary care hospital, carried out from 1997 to 2012. RESULTS: Thirty-one patients were diagnosed with LM meningitis, which was 7% of a total of 440 adult patients with acute bacterial meningitis (ABM) over a 16-year period. Their median age was 63 years, range 26-80 years. Nineteen patients (61%) had underlying immunocompromising comorbidity; 15 patients (48%) were older than 65 years. Fourteen patients (45%) had arterial hypertension. The typical triad of fever, neck stiffness, and altered mental status was present in 21 patients (68%). The median count of cerebrospinal fluid (CSF) leukocytes was 680/µL, protein level 2.6 g/L, and glucose ratio 0.28. Four patients (13%) died, and nine (29%) survived with moderate to severe sequelae. CONCLUSION: LM meningitis is known to affect immunosuppressed and elderly patients. Arterial hypertension seems to be another important predisposing factor. Clinical symptoms, CSF findings, and disease outcomes, did not significantly differ from other community-acquired ABM in our study, although the CSF leukocyte count was lower. Ampicillin showed good clinical and bacteriological efficacy in the majority of patients.

Toxic shock syndrome and persistent immune activation in an HIV-positive patient.

The case of an HIV-positive treatment-naive male with toxic shock syndrome (TSS) is presented herein. The course of TSS was favorable; however, the patient had extremely high plasma levels of MCP-1 and CD38 and HLA-DR expression on CD8+ T cells during the acute illness. Furthermore, the numbers of CD8+ T cells were reduced and CD4+ T cells remained stable during acute illness in comparison to baseline values. MCP-1 and HLA-DR gradually decreased, but they were still elevated after a month, whereas the number of circulating CD8+ T cells increased more than fivefold. CD38 expression remained stable during this period. A further decrease in CD38, HLA-DR and MCP-1 was noted five months after the initiation of antiretroviral therapy.

Prevalence of human leukocyte antigen HLA-B*57:01 in HIV-infected subjects in the Czech Republic.

The HLA-B*57:01 allele is associated with a hypersensitivity reaction to abacavir, and its prevalence varies in different populations. The aim of the study was to investigate HLA-B*57:01 prevalence in the Czech HIV-infected population. HLA-B*57:01 prevalence in our cohort was 5.33%, which is similar to the situation in other Central European countries.

[Exogenous Cushing's syndrome as a serious side-effect of therapy with ritonavir an inhaled fluticasone]. / Exogenni Gushinguv syndrom jako zavazny nezadouci ucinek lecby ritonavirem a inhalacnim flutikazonem.

Inhalation of fluticasone is usually devoid of systemic side-effects. The authors describe a case of a young HIV positive woman treated concomitantly with fluticasone and inhibitors of HIV protease ritonavir and lopinavir in which developed a serious endocrine side-effect - an iatrogenic Cushing's syndrome. Plasma concentration of cortisol < 5.5 nmol/l was very low (norm 250-650 nmol/l) and plasmatic ACTH was even not detectable. The administration of fluticasone and both inhibitors of HIV protease was stopped and substitution therapy with decreasing dose of hydrocortisone was initiated. Twenty weeks later resolved both clinical and laboratory symptoms of Cushing's syndrome, and the substitution therapy with hydrocortisone was terminated. Two years later became the patient pregnant and gave birth to a healthy child.

Antiretroviral treatment of HIV infection does not influence HIV-specific immunity but has an impact on non-specific immune activation.

HIV-specific and non-specific immune responses are crucial in the immunopathogenesis of HIV infection. Therefore, the objective of our study was to analyse the frequency and functional status of HIV-specific CD8+ T cells and the expression of non-specific activation markers on CD8+ T cells in HIV+ patients, and to assess the effects of combined antiretroviral treatment (cART). We examined 28 HIV+ patients, including 13 patients not receiving therapy and 15 patients on cART therapy using ELISpot assay and flow cytometry with intracellular and MHC tetramer staining. MHC tetramers detected HIV-specific CD8+ T cells in 6 HIV+ patients on cART and in 7 untreated individuals; the ELISpot method detected these cells in 5 untreated HIV+ individuals only. Reduced intracellular IFN-γ and IL-2 production by HIV-specific CD8+ T cells was detected in both treated and untreated HIV+ patients, and multifunctional CD8+ T cells simultaneously producing these cytokines were not found in any patient. In contrary to these findings, the percentage of CD8+ T cells expressing CD38 and HLA-DR was significantly higher in untreated patients as compared to HIV+ patients on cART. Together, these results suggest that the alterations of HIV-specific immunity are not influenced by the therapy of HIV infection; whereas, the non-specific chronic immune activation is down-regulated by cART.

Bilateral Holmes-Adie syndrome as an early manifestation of the HIV neuropathy.

A 38-year-old HIV-1 infected woman affected with bilateral tonic pupils. Ophthalmologic examination confirmed Holmes-Adie syndrome (HAS), and peripheral distal polyneuropathy, orthostatic hypotension and leg hyperhidrosis were detected on further workup. The HAS can be either idiopathic or associated with neuropathy of various etiology (autoimmune, paraneoplastic and infectious). In our patient, the pupillotonia was the first and early symptom of hitherto unrecognized HIV neuropathy. HAS has been previously observed in association with syphilis, Lyme borreliosis, herpes simplex and parvovirus B19 infection. Our case is the first report of HAS in a case of HIV infection.

Acute appendicitis as a manifestation of the immune reconstitution inflammatory syndrome.

Acute appendicitis as a manifestation of the immune reconstitution inflammatory syndrome is repeatedly discussed in the literature, but only a few cases of acute appendicitis associated with the initiation of cART have been published as yet. We describe a case of a young HIV-infected man who suffered from acute appendicitis early after the successful switch of a failing cART regimen.

[Two types of CMV ocular complications in patients with HIV infection]. / Dva typy cytomegalovirového postizení oka u pacientu s HIV infekcí.

CMV retinitis is the most serious ocular complication of AIDS. Introduction of the combination antiretroviral therapy markedly reduced the occurrence of CMV retinitis, on the other hand it brought a new ocular complication - CMV uveitis. CMV uveitis is an immunopathological inflammatory reaction associated with the immune reconstitution inflammatory syndrome, which is a side effect of successfully initiated cART. These two forms of CMV ocular complications differ in pathogenesis, symptomatology and therapy. The CMV retinitis is treated with anti-CMV virostatics whereas the therapy of CMV uveitis is based on attenuation of the inflammatory reaction by administration of corticosteroids. The optimal prevention of both complications is an early initiation of cART before the CD4+ T lymphocytes drop below 200/microl.

[HIV retinopathy]. / HIV retinopatie.

HIV retinopathy is an ocular affection occurring especially in HIV positive patients with deep immunodeficiency. Because of benign character the HIV retinopathy does not require any specific therapy, but it must be carefully distinguished from other ocular diseases, which can seriously damage sight, e.g. CMV retinitis. The presence of HIV retinopathy can also be a symptom of progression of HIV infection and should be perceived as a signal for considering the initiation of antiretroviral therapy in treatment naive patients.

Acute bacterial meningitis in adults: predictors of outcome.

Case fatality ratio and permanent sequelae of acute bacterial meningitis remain high in recent decades. A prospective longitudinal study of adult patients admitted with community acquired acute bacterial meningitis at a tertiary infectious diseases unit aimed to identify predictors of unfavourable outcome - death and sequelae. Anamnestic, clinical and laboratory data and clinical outcome were recorded. From 1997 to 2006, 279 adults (122F, 157M) with a median age of 51 y were admitted with acute bacterial meningitis. Predisposing condition and comorbidity were recorded in 42% and 38% of patients, respectively. Time between symptoms onset and antibiotic treatment ranged from 6 to 160 h. An aetiological agent was identified in 77% of patients: Streptococcus pneumoniae (29%) and Neisseria meningitidis (27%) were the most frequent. 55 patients (20%) died and 63 (23%) had neurological sequelae 6 months after discharge. In multivariate analysis, 7 independent predictors of unfavourable outcome were identified: internal comorbidity, time to treatment >48 h, coma, hypotension, high CSF protein, low glucose ratio, and non-meningococcal aetiology. The results suggest that acute bacterial meningitis remains associated with significant morbidity and mortality. Maintaining a high clinical suspicion and initiating appropriate diagnostic testing and therapeutic interventions promptly are essential for an optimal clinical outcome.

[Proposals for guidelines for vaccination of adults infected with HIV-1 in the Czech Republic]. / Návrh doporuceného postupu ockování u dospelých osob infikovaných virem HIV-1.

HIV positive patients are in a higher risk of many infections, including the preventable ones. The vaccination is thus a very important part of health-care offered to those patients. Effectiveness of vaccination correlates strongly with the actual immunological status. Vaccination is safe, including some live vaccines, in persons with CD4+ T cells > 500/ml. In patients with CD4+ T cells > 200/ml the efficacy of vaccination is uncertain and live vaccines are strictly contraindicated. A good knowledge of all aspects of vaccination and HIV-infection is necessary, hence we recommend that vaccination of all HIV-positive persons should be realized exclusively by experts in specialized AIDS centers. In the following text we present the proposals for guidelines for vaccination of adult patients infected with HIV-1.

[Procalcitonin: a reliable marker for the diagnosis and monitoring of the course of bacterial infection]. / Prokalcitonin: spolehlivý ukazatel pro diagnostiku a monitorování prubehu bakteriální infekce.

The review is aimed at the importance of determining procalcitonin serum levels (S-PCT) in numerous infectious and non-infectious diseases. Detecting increased S-PCT is particularly important for differential diagnosis of systemic bacterial as well as fungal infections. High S-PCT concentrations are also of predictive value in severe sepsis and septic shock. S-PCT kinetics may be used for monitoring the effect of antibiotic therapy. When compared to the other routinely used markers of bacterial infection (i.e. C-reactive protein, white blood cell count and neutrophil percentage), S-PCT has higher sensitivity and specificity in predicting bacterial infection.