• Nu S-Au Găsit Rezultate

View of Features of the Clinical Course of Invasive Candidiasis in HIV-Infected Patients

N/A
N/A
Protected

Academic year: 2022

Share "View of Features of the Clinical Course of Invasive Candidiasis in HIV-Infected Patients"

Copied!
6
0
0

Text complet

(1)

Features of the Clinical Course of Invasive Candidiasis in HIV-Infected Patients

Alisa Aldamova*1, Zarui Ovsepian1

1Peoples' Friendship University of Russia (RUDN University), Moscow, Russia

*Corresponding Author: [email protected]

ABSTRACT

The article presents the results of follow-up of 30 patients with invasive candidiasis who developed against the background of HIV infection during the period 2019-2021. The features of the clinical course of the disease and the risk factors for its occurrence are described. The clinical picture of invasive candidiasis in HIV-infected patients is similar to that of bacterial sepsis, characterized by a severe course and high mortality. Risk factors are severe immunodeficiency, lack of antiretroviral therapy, and the presence of 2 or more foci of superficial candidiasis. The diagnosis of hematogenic dissemination should be performed in all HIV-infected patients in the presence of supporting symptoms.

Keywords:Candida pathogen, invasive candidiasis, HIV infection, sepsis, risk factors.

INTRODUCTION

Candidiasis is the most common opportunistic mycosis caused by fungi of the genus Candida. To date, about 160 species of this genus are known, 10 of which are pathogenic to humans. Fungi of the genus Candida are widely distributedin the external environment: air, soil, water [1]. Some of them are inhabitants of the human body and are detected by mycological studies of the mucous membranes of the oral cavity and gastrointestinal tract in 30-50% of practically healthypeople. When reducing the resistance of the bodyCandida spp.

they can cause diseases, and clinical manifestations range from a relatively minor superficial pathological process to a highly lethal invasive lesion of various organs and tissues [2]. The prevalence of candidiasis has increased due to the widespread use of antibiotics, glucocorticosteroids, immunosuppressants, and the pandemic HIV infection. Fungi of the genus Candida spp. affect 90% of HIV-infected patients [3].

In recent years, there has been a significant increase in the incidence of invasive candidiasis worldwide. Its rate in economically developed countries is about 200 cases per 1 million populationannually. In Europe, Candida spp. is 3rd most common pathogens of nosocomial sepsis. The main etiological agents of invasive candidiasis are C. albicans (51- 62%), C. glabrata (18%), C. parapsilosis (13%), C. tropicalis (10%), and C. krusei (3%). At the same time, the shift towards Candida non-albicans resistant to antimycotics increases [4,10]. In patients with risk factors, invasive candidiasis can occur as an intra-hospital infection, characterized by severe clinical manifestations and high mortality (among certain groups of patients, it reaches 80%). Timely and adequate use of antimycotics largely determines the outcome of the disease. However, it still remains so only in 15-40% of patients with invasive candidiasis. This is due to the difficulties of diagnosis, since the clinical signs of

(2)

the disease are often non-specific, and candida fungemia is intermittent and has a low level [5-8]. In addition, there is insufficient data in the literature on the manifestations of invasive candidiasis in HIV-infected patients.

Objective: to conduct detailed microbiological research on the study of invasive candidiasis in HIV-infected patients.

MATERIALS AND METHODS

In the Moscow region Infectious Diseases Hospital from 2019 to 2021, 30 patients were observedwith invasive candidiasis: 20 men and 10women aged 18 to 42 years. The diseasedeveloped against the background of 4 B - Stage HIV infection withoutantiretroviral therapy (according to the clinical classification of V. I. Pokrovsky, 2001). From the epidemiological history, it was found that 18 patients were drug users who were infected by parenteral route. 12 patients were infected during heterosexual and homosexual contacts.

Duration HIV infection without treatment ranged from 1 to 10 years. The majority of patients (20 people) were sent to the hospital with primary diagnoses: "pneumonia" and "sepsis". On the basis of a complex of clinical, laboratory and mycological methods, including isolation and identification of candida culture, the diagnosis of acute disseminated candidiasis was established in vivo in 23 and postmortem in 7 patients. Concomitant diseases were chronic hepatitis B and C, type 1 diabetes mellitus, and pulmonary tuberculosis. In 13 cases the genus Candida was isolated alone, in 17 cases - with bacteria Esherichiacoli, Staphylococcus spp., Klebsiella pneumonia P. aeruginosa, P. multocida and others[11-18].

RESULTS AND DISCUSSION

All patients complained of weakness, myalgia, fever, cough, shortness of breath. Chest pain was observed in 9 patients, headache- 6, dyspeptic phenomena- 2. 17 patients had fever up to 38-41oC with the wrong type of temperature curve. In 5cases, normothermia and low body temperature were registered. The patients were admitted in an extremely serious condition, the disease was fatal in the first day of their stay in the hospital. A serious condition was recorded in 17 patients, a moderate condition – in 5. The severity of the condition was caused by intoxication, respiratory failure, and hemodynamic disorders. Most of the patients were underweight or emaciated (19 people), the skin was pale, and 3 people had jaundice.

Hemorrhagic rash in the distalextremities was observed in 3 patients. The peripheral lymph nodes in all the examined patients were enlarged from 0.5 to 1.5 cm, dense, painless, and the skin above them was not changed. When examining the oropharynx, the mucous membrane of 18 people was moderately hyperemic, edematous, and covered with grayish-yellow spots, curd- like deposits with predominantlocalization on the tongue, the inner surface of the cheeks, and thesoft palate. In 23 patients, hyperkeratosis is expressed on the skin of the feet, cracks in the interdigital spaces, the nails are thickened, with uneven nail plates. When examining the cardiovascular system, all patients had deafness of heart tones, tachycardia (heart rate 86-110 per minute), instability of blood pressure (from 50/30 to 140/80 mm Hg). In 9 cases, a systolic murmur was heard at the top of the heart.

On the part of the lungs, 21 patients had dry and wet wheezing, weakening of breathing in the lesion. Dyspnea was observed in 11 people (BH 22-42 per minute). Three patients required respiratory support (extended ventilator). All patients showed a significant increase in the size of the liver, and 12 patients had splenomegaly. One third of the patients had meningeal

(3)

symptoms (rigidity of the muscles of the back of the neck, symptoms of Kernig, Brudzinsky), one-insufficiency of the 7thpair of cranial nerves.

The number of CD4-lymphocytes in the blood varied from 3 to 660 cells/µl (on average, 168 cells /µl). The viral load was 80 000-300 000 copies HIV RNA in 1 ml of blood.

In the hemogram of the vast majority patients were found to have hypochromic anemia, left shift of the formula, lymphopenia, and high COE. Leukocytosis was observed in 14 patients (9,0–35,8·109/l), leukopenia-in 4 (1,1–3,3 · 109/l). In general analysis in the urine of all the observed patients, proteinuria occurred (up to 0.794 g/l), in one third – leukocyturia and erythrocyturia.

The study of biochemical blood analysis in 15 patients revealed an increase in the levels of bilirubin (25-150mmol/L), urea (8.8–36.6 mmol/l) and creatinine (up to 0.68). A third of the patients were diagnosed with cytolysis syndrome (transaminase indices from 49 up to 135 units), 7 people have hyperglycemia (6.3-20.9 mmol/l).

For diagnostic purposes, 10 patients underwent spinal puncture. Meningitis was detected in 7 patients. There was an increase in the pressure of the cerebrospinal fluid, clear cerebrospinal fluid, pleocytosis from 10 to 278 cells/ml (average 120 cells/ml).

Lung radiography was performed in all 25patients, pneumonia was detected in 18 (2- sided in 10 cases). In addition, lung abscess, pneumothorax, hydrothorax, and calcified pleurisy were diagnosed. Changes in the ECG - electrocardiogram - were observed in 9 patients in the form of a decrease in the voltage of the teeth and a violation of the ventricular conduction.

Fungi of the genus Candida spp. were isolated in 19 patients during mycological examination of sputum and smears from the pharynx, of which C. albicans in 12 people, C.

glabrata in 2, and in the remaining cases Candida spp. was not identified. In 9 cases, C. albicans were detected in urine cultures.

To confirm the diagnosis of invasive candidiasis, the study material was blood, cerebrospinal fluid, as well as pieces of cadaveric material from deceased patients. In order to isolate the culture and identify the pathogen, a mycological study was conducted. Identification of fungi of the genus Candida spp. from the blood occurred in 17 human. On the Saburo medium, they formed smooth,small, shiny, cream-colored colonies. After the identification of micromycetes, the following results were obtained: C. albicans-19, C. albicans + C. glabrata-4, C. albicans + C. lusitania-1.In one case – Candida parapsilosis. In 9 cases, there was a combination of fungi of the genus Candida and various bacteria (Esherichia coli, Staphylococcus spp., Klebsiella pneumonia)[19-25].

Etiotropicantimycotic therapy according to the clinical recommendations was prescribed to all patients in the hospital. Also all patients received broad-spectrum antibiotics.

The outcomes of the disease were different. In 18 cases, positive dynamics were achieved. Despite the treatment, 7 patients died from septic shock, multiple organ failure and manifestations of DIC syndrome. Death occurred within 10 to 50 days of treatment.

The analysis of the results of the study revealed the features of the course of invasive candidiasis in patients withHIV-infected patients. The disease occurs in the form of an acute disseminated process, characterized by a severe course and highmortality. Thus, the clinical picture of systemic candidiasis is similar to that of bacterial sepsis: antibiotic-resistant fever broad spectrum of action, lung damage, multiple organ failure with a predominance of hepatic- renal and manifestations of DIC-syndrome. This causes difficulties in the diagnosis and

(4)

adequate treatment of the disease. Complicating the task is the fact that in a third of patients, the etiological cause of the disease was an association of fungi and bacteria.This led to a late diagnosis and did not allow for adequate and timely treatment.

CONCLUSION

The results of the studies indicate that invasive candidiasis in HIV-infected patients occurs as an acute disseminated process, characterized by a severe course and high mortality.

In one third of cases, the etiological cause of the disease is mixed fungal-bacterial flora. The clinical picture of invasive candidiasis is similar to bacterial sepsis, which leads to difficulties in diagnosing the disease. Risk factors for invasive candidiasis in HIV-infected patients are:

severe immunodeficiency, no antiretroviral therapy and the presence of foci of superficial candidiasis. The diagnosis of hematogenic dissemination of candidiasis should be carried out in all HIV-infected patients with supporting symptoms: fever, resistant to broad-spectrum antibiotics; acute respiratory failure and lung damage.In 13 cases the genus Candida was isolated alone, in 17 cases - with bacteria Esherichia coli, Staphylococcus spp., Klebsiella pneumonia P. aeruginosa, P. multocida and others.

Acknowledgments

This paper has been supported by the RUDN University StrategicAcademicLeadership Program.

Competing Interests

The authors declare that they have no competing interests.

REFERENCES

1. Sachivkina N, Lenchenko E, Blumenkrants D, Ibragimova A, Bazarkina O (2020). Effects of farnesol and lyticase on the formation of Candida albicans biofilm, Veterinary World, 13(6):

1030-1036.

2. Smirnova IP, Kuznetsova OM, Shek D, Ivanova-Radkevich VI, Sachivkina NP, Gushchina YS.

Investigation of the immunogenic properties of antitumor enzyme l-lysine-alpha-oxidase. FEBS Journal. 2018; 8(S1): 234.

3. Sachivkina NP, Karamyan AS, Kuznetsova OM, Byakhova VM. Development of therapeutic transdermal systems for microbial biofilm destruction. FEBS Open Bio. 2019; 9(S1): 386.

4. Kravtsov E.G., Anokhina I.V., RybasYa.A., Sachivkina N.P., Ermolaev A.V., Brodskaya S.B.

Effects of female sex hormones on adhesion of candida albicans yeast-like fungi to the buccal epithelium. Bulletin of Experimental Biology and Medicine. 2014. 157(2): 246-248.

5. Sachivkina N.P., Kravtsov E.G., Vasilyeva E.A., Anokhina I.V., Dalin M.V. Study of antimycotic activity of Lyticase. Bulletin of Experimental Biology and Medicine. 2009. 148(2): 214-216.

6. Rudenko P, Rudenko V, Vatnikov Y, Rudenko A, Kulikov E, Sachivkina N, Sotnikova E, Sturov N, Rusanova E, Mansur T, Vyalov S, Sakhno N, Drukovsky S. Biocoenotic Diagnostics of Unfavorable Factors in the Cows Infection of Farms in the Moscow Region. Sys Rev Pharm 2020;

11(5): 347-357.

7. Rudenko A, Rudenko P, Glamazdin I, Vatnikov Y, Kulikov E, Sachivkina N, Rudenko V, Sturov N, Babichev N, Romanova E, Rusanova E, Lukina D. Assessment of Respiratory Rate in Dogs during the Sleep with Mitral Valve Endocardiosis, Complicated by Congestive Heart Failure Syndrome: the Degree of Adherence for this Test by Animal Owners and its Impact on Patient Survival. Sys Rev Pharm 2020; 11(5): 358-367.

(5)

8. Lenchenko E, Blumenkrants D, Sachivkina N, Shadrova N, Ibragimova A. Morphological and adhesive properties of Klebsiellapneumoniae biofilms. Veterinary World. 2020; 13(1): 197-200.

9. Stanishevskiy YM, Sachivkina NP, Tarasov YV, Philippov YI, Sokolov SA, Shestakova MV.

Evaluation of biocompatibility of an experimental membrane for glucose sensors: the results of a prospective experimental controlled preclinical study involving laboratory animals. Problems of Endocrinology. 2017; 63(4), 219-226.

10. Sachivkina N, Lenchenko E, Strizakov A, Zimina V, Gnezdilova L, Gavrilov V, Byakhova V, Germanova S, Zharov A, Molchanova M. The evaluation of intensity of formation of biomembrane by microscopic fungi of the Candida genus. International Journal of Pharmaceutical Research. 2018; 10(4), 738-744.

11. Brigadirov Y, Engashev S, Sachivkina N, Kulikov E, Rystsova E, Notina E, Bykova I, Likhacheva I, Pavlova M, Terekhin A, Bolshakova M. The role of genital tract microflora correction and metabolic status of sows in the reproductive potential implementation. Intern. Journal of Pharmaceutical Research. 2020; 12 (2), 416-423.

12. Sereda AD, Makarov VV, Sachivkina NP, Strizhakov AA, Gnezdilova LA, Kuznetsov VI, Sturov NV, Zimina VN. Effectiveness of combined use: inactivated vaccines with immunostimulants on the in vivo model of Teschen disease. Advances in Animal and Veterinary Sciences. 2020; 8(2):

151-156.

13. Lenchenko E, Blumenkrants D, Vatnikov Y, Kulikov E, Khai V, Sachivkina N, Gnezdilova L, Sturov N, Sakhno N, Kuznetsov V, Strizhakov A, Mansur T. Poultry Salmonella sensitivity to antibiotics. Systematic Reviews in Pharmacy. 2020; 11(2): 170-175.

14. Rudenko P, Vatnikov Y, Kulikov E, Sachivkina N, Karamyan А, Rudenko A, Rudenko V, Gadzhikurbanov A, Murylev V, Elizarov P, Mansur T, Vyalov S, Troshina N. Experimental and Clinical Justification of the use of Probiotic-Sorption Drugs in Veterinary Surgery . Sys Rev Pharm. 2020; 11(4): 275-287.

15. Zhilkina, N. P. Sachivkina, A. N. Ibragimova, T. Y. Kovaleva, M. A. Molchanova, D. V. Radeva.

Methods for the identification and quantitative analysis of biologically active substances from vitamin plants raw material. FEBS Open Bio. 2019; 9(S1): 285-286.

16. Morozov I.A., Sachivkina N.P., Kravtsov E.G., Vasilyeva E.A., Anokhina I.V., Yashina N.V., Dalin M.V. Damaging effects of lyticase on Candida albicans and changes in the response of rat alveolar macrophages to the contact with yeast-like fungi. Bulletin of Experimental Biology and Medicine. 2011. 151(6): 705-708.

17. Sachivkina N.P., Kravtsov E.G., Wasileva E.A., Anokchina I.V., Dalin M.V. Efficiency of lyticase (bacterial enzyme) in experimental candidal vaginitis in mice. Bulletin of Experimental Biology and Medicine. 2010. 149(6): 727-730.

18. Vatnikov Y., Shabunin S., Kulikov E., Karamyan A., Lenchenko E., Sachivkina N., Bobkova N., Bokov D., Zhilkina V., Tokar A., Shopinskaya M., Rudenko P.. Effectiveness of biologically active substances from HypericumPerforatum L. in the complex treatment of purulent wounds.

Inter. J. of Pharm. Research. 2020; 12(4): 1108-1117.

19. Vatnikov Y., Shabunin S., Karamyan A., Kulikov E., Sachivkina N., Vasilieva E., Bobkova N., Bokov D., Rudenko P., Rudenko A.. Antimicrobial activity of HypericumPerforatum L. Inter. J. of Pharm. Research. 2020; 12(Suppl.1): 723-730.

20. Vatnikov Y., Donnik I., Kulikov E., Karamyan A., Sachivkina N., Rudenko P., Tumanyan A., Khairova N., Romanova E., Gurina R., Sotnikova E., Bondareva I. Investigation of the antibacterial and antimicotic effect of the phytopreparation Farnesol on biofilm forming microorganisms in veterinary medicine. Inter. J. of Pharm. Research. 2020; 12(Suppl.2): 1481-92.

(6)

21. Sachivkina N.P., Podoprigora I.V., Marakhova A.I. Farnesol: properties, role, and prospects for use in the regulation of film formation in fungi of the genus Candida Farmatsiya, 2020; 69 (6): 8–

12. https://doi.org/10/29296/25419218-2020-06-02

22. Khan I.I., Parfait K., Sachivkina N.P. Comparison of different methods for determining the critical micell concentration. Farmatsiya (Pharmacy), 2018; 67 (6): 35–38.

https://doi.org/10.29296/25419218-2018-06-07

23. Sachivkina N.P., Lenchenko E.M., Marakhova A.I. Study of the formation of Candida albicans and Escherichia coli biofilms. Farmatsiya (Pharmacy), 2019; 68 (7): 26–30.

https://doi.org/10/29296/25419218-2019-07-05

24. Sachivkina N.P., Lenchenko E.M., Mannapova R.T., Strizhakov А.А., Romanova E.V., Lukina D.M. Candida biofilm modeling: past and present. Farmatsiya (Pharmacy), 2019; 68 (3): 18–22.

https://doi.org/10/29296/25419218-2019-03-03

25. Rudenko P, Sachivkina N, Vatnikov Y, Shabunin S, Engashev S, Kontsevaya S, Karamyan A, Bokov D, Kuznetsova O, Vasilieva E (2021). Role of microorganisms isolated from cows with mastitis in Moscow region in biofilm formation, Veterinary World, 14(1): 40-48.

Referințe

DOCUMENTE SIMILARE

Our data also showed a moderate correlation be- tween 2D-SWE.GE and 2D-SWE.SSI (r=0.63, R 2 =0.4, p<0.0001), results which could be accountable to the nar- row range

Thus, in the present study are presented the prevalence of Rotavirus group A infection and the significance of the associated risk factors and clinical signs in

Comparison of transient elastography and acoustic radiation force impulse for non-invasive staging of liver fibrosis in patients with chronic hepatitis C.. Acoustic

The disease is observed in all patients with clinical and laboratory manifestations of kidney inflammation, renal echographic changes are noted, which can be divided

for diagnosis of suspected Ischemic chest pain presumably presenting as Chronic stable angina (CSA.) ,documented with +ve Exercise tolerance test (ETT);or

It can be concluded from the study that all the mortality and morbidity cases of the COVID-19 infection which developed severe illness post admission in hospital or COVID-19

CONCLUSIONS- Owing to many factors associated such as drain site infection , hospital psychosispersistent drain site pain , unwillingness among patients for oral diet with drain in

The results of the study of DISS in patients with allergic dermatoses, who received Fatiderm cream in external therapy, showed positive dynamics of the clinical course of