| BackgroundAcquired immunodeficiency syndrome(AIDS)caused by human immunodeficiency virus(HIV)infection is a major infectious disease that threatens the lives and public health safety of people worldwide.Up to the end of October 2019,about 958 thousand living HIV/AIDS patients were reported in China,of which about1/3 were AIDS patients.A total of 20,999 AIDS deaths were reported in 2019,accounting for about 83%of notifiable disease deaths reported in last year.HIV mainly invade CD4+T lymphocytes,causing impaired immune function and secondary opportunistic infections(OIs)or tumors.Aspergillus spp.,Talaromyces marneffei,and Mucor are important opportunistic pathogenic filamentous fungi in patients with HIV/AIDS,and their resulting invasive fungal infection(IFI)is one of the main causes of hospitalization and death.The incidence of OIs among HIV/AIDS patients has been greatly reduced over the last 20 years due to the implementation and promotion of highly active antiretroviral therapy(HAART).However,invasive filamentous fungal infections still have a higher incidence among the HIV positive population.According to many previously studies,the biological type of oral Candida isolate from the HIV positive population was more diverse than the healthy population and was also highly related to the immune status and the implementation of HAART.However,do nasopharynx and oropharynx of HIV positive populations carry invasive filamentous fungi?What factors influence its carrier state?Does the invasive filamentous fungus cause IFI?Little is known about these issues.Based on the above questions,a prospective cohort study was conducted to provide a basis for effective prevention and treatment of invasive filamentous fungal infection in HIV positive population.ObjectiveTo study the prevalence and influencing factors of naso-and oropharyngeal invasive filamentous fungi(including pathogenic Aspergillus spp.,Talaromyces marneffei,and Mucors)in HIV positive populations,to observe their effect on the later stage of developing IFI,and to explore effective strategies to prevent opportunistic filamentous fungal infection.Methods1.Design and study subjects:To be a prospective cohort study,the HIV-positive population of Guangzhou Eighth People's Hospital Infection Outpatient Clinic from May 1,2017 to August 31,2017 was included in the criteria(Infection Group).HIV-negative people who took part in the physical examination at the same time in a physical examination center in Guangzhou were taken as the control group.All subjects collected nasopharyngeal and oropharyngeal swabs for fungal culture and collected personal information by questionnaire.2.Identification of Fungi:Fungi cultured from naso-or oropharynx identified yeast-like fungi and filamentous fungi by morphology.Filamentous fungi often identified invasive filamentous fungi(pathogenic Aspergillus spp.,Talaromyces marneffei and Mucors).At the same time,about 40%of the strains of filamentous fungi cultured in infection group and control group were randomly selected for rDNA-ITS sequencing and identified to the genus.3.Research contents:(1)Comparison of naso-and oropharyngeal yeast-like fungi,filamentous fungi and common invasive filamentous fungi carrying in infected and control groups;(2)Comparison of the pathogenic profiles of filamentous fungi carried by naso-and oropharyngeal in the infected and control groups;(3)univariate and multivariate logistic regression was used to analyze the influencing factors of naso-and oropharynx carrying invasive filamentous fungi in HIV positive population;(4)To observe the late IFI occurrence of HIV positive population(observation endpoint:31 December 2019)carrying invasive filamentous fungi in naso-and oropharynx.Results1.General information:The infection group included 716 HIV positive cases,aged 18?73,with a median of 34(27,42)years,of which 602 males(84.08%)and 114females(15.92%),male to female ratio 5.28:1.Control group included 293 cases,age18?66 years old,median 28(22,45)years old,of which 246 men(83.96%),47 women(16.04%),male to female ratio 5.23:1.The age and sex ratio of the two groups were comparable,and there was no statistical difference(?2=0.002,P=0.963;?2=3.879,P=0.144).2.Infection group and control group naso-and oropharyngeal yeast-like fungi,filamentous fungi,common invasive filamentous fungi carrier state:Compared the positive rates of naso-and oropharyngeal fungi(90.22%vs 80.89%),yeast-like fungi(41.90%vs 30.38%),filamentous fungi(80.54%vs 73.72%),yeast-like and filamentous fungi(32.12%vs 23.21%)of the two groups,the rates of the infection group were significantly higher than those of the control group(?~2=16.583,P<0.001;?~2=11.656,P=0.001;?~2=5.573,P=0.018;?~2=7.940,P=0.005).But there was no significant difference in the proportion of pathogenic filamentous fungi,pathogenic Aspergillus spp.(?~2=1.049,P=0.306;?~2=0.309,P=0.578).3.Pathogenic spectrum of filamentous fungi in infected group and control group:777 strains and 261 strains of filamentous fungi were cultured in the infected group and control group,respectively,and 40%were randomly sampled.304 and 103 strains from the infection group and control group were successfully resuscitated and took PCR sequencing,respectively,and 89 strains(29.28%)and 35 strains(33.98%)of invasive filamentous fungi were identified.The first three invasive filamentous fungi:in infection group were P.citrinum(36 strains,11.84%),A.fumigatus(13 strains,4.28%),A.sydowii(9 strains,2.96%);in control group were P.citrinum(8 strains,7.77%),A.fumigatus(8 strains,7.77%),A.niger(6 strains,5.83%),A.versicolor(4strains)and A.sydowii(3 strains).2 strains of T.marneffei and 1 strain of Rhizomucor variabilis were identified in infection group.4.Influencing factors of naso-and oropharyngeal invasive filamentous fungi in HIV positive population:A total of 119 patients with nasopharyngeal and oropharyngeal invasive filamentous fungi.After regression analysis of 12 factors(sex,age,exposure to rodents and their secretion history,exposure to hay or husks for nearly 6 months,respiratory tract infection,other transmission disease,curable opportunistic infection,smoking history,alcoholism history,HAART history,CD4~+count,HIV-1-RNA load,etc.),we found that smoking and previously cured OIs may be risk factors of HIV positive population carrying invasive filamentous fungi in naso-and oropharynx(OR=1.547,P=0.035;OR=1.965,P=0.004).5.Late IFI of nasopharynx and oropharynx of HIV positive population carrying invasive filamentous fungi:119 patients with nasopharyngeal/oropharyngeal invasive filamentous fungi were followed up until December 31,2019.All patients survived.At the starting of the follow-up,111(93.28%)patients have received HAART for25(11,46)months.Until the end of the follow-up,all(100%)of the patients have received HAART for 52(35,73)months.At the end of the follow-up,the median CD4~+count was 477(312,611),and the median ratio of CD4~+/CD8~+was 0.66(0.48,0.96).The CD4~+count,CD4~+/CD8~+ratio was significantly higher than the baseline(F=9.706,P=0.002;F=8.126,P=0.005).No antifungal prophylaxis was used during the follow-up,but none suffered from IFI.Conclusion1.HIV positive people have higher carrying rate of filamentous fungi but not invasive filamentous fungi in nasopharynx/oropharynx than HIV negative one.The history of previously cured OIs and smoking may be the risk factors of carrying invasive filamentous fungi in nasopharynx/oropharynx of HIV positive people.2.Despite carrying invasive filamentous fungi in nasopharynx/oropharynx,few HIV positive people develop IFI if they acquire well immunological reconstruction and virological inhibition after HAART. |
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