Evolutionary Profile of Opportunistic Infections in People Living with Human Immunodeficiency Virus during Six Months of Dolutegravir Based Antiretroviral Treatment in Kinshasa, Democratic Republic of Congo

Background: Opportunistic infections (OI), which are still a major problem in the care of People Living with HIV (PLHIV), occur in situations of immunosuppression. The AntiRetroViral Treatments (ART) used allow a spectacular reduction in the frequency of Opportunistic Infections. Objective: The objective of this study is to present the evolution of Opportunistic Infections in People Living with HIV under AntiRetroViral Treatment in Kinshasa in the era of Dolutegravir. Methods: The present study is a prospective cohort to present the evolutionary profile of OIs in PLHIV on ART for 6 months in Outpatient Treatment Centers (OTC) in Kinshasa. Sixteen OTCs had been included. The population of the present work was patients over 18 years of age at inclusion, infected with HIV-1 and initiating ART in the selected OTC. Results: On inclusion, 119 patients were included of which 56.3% were women. Malaria (45.4%), tuberculosis (29.4%) and cutaneous pruritus (23.5%) were the most common Opportunistic Infections (OIs). In the third month of ART, 37 patients came for the consultation of which 70.3% were women. Non-specific STIs (97.3%), skin pruritus (37.8%) and malaria (24.3%) were the dominant OIs among patients. At the sixth month of ART, 62 patients came for the medical consultation of which 61.3% were women. Skin pruritus (25.8%), dermatitis (22.6%) and rash (21%) were the most common OIs. Conclusion: The evolutionary profile is marked by the conservation of Opportunistic Infections such as dermatitis (pruritus and rashes) and malaria.

Role of upper endoscopy in diagnosing opportunistic infections in human immunodeficiency virus-infected patients

Highly active antiretroviral therapy (HAART) has dramatically decreased opportunistic infections (OIs) in human immunodef iciency virus (HIV)-infected patients. However,gastrointestinal disease continues to account for a high proportion of presenting symptoms in these patients. Gastrointestinal symptoms in treated patients who respond to therapy are more likely to the result of drug-induced complications than OI. Endoscopic evaluation of the gastrointestinal tract remains a cornerstone of diagnosis,especially in patients with advanced immunodeficiency,who are at risk for OI. The peripheral blood CD4 lymphocyte count helps to predict the risk of an OI,with the highest risk seen in HIV-infected patients with low CD4 count (< 200 cells/mm3). This review provides an update of the role of endoscopy in diagnosing OI in the upper gastrointestinal tract in HIV-infected patients in the era of HAART.

Distribution Characteristics of Drug Susceptibility Test Results of Tuberculosis and Non-Tuberculous Bacilli in Patients with Opportunistic Infections of AIDS

Objective: To understand the distribution of drug susceptibility test results of opportunistic infections of tuberculosis and non-tuberculous bacilli in AIDS patients. Methods: The AIDS patients who were hospitalized in our hospital from January 2016 to June 2019 were collected as the research objects, and patients with opportunistic tuberculosis and non-tuberculous bacilli from AIDS patients were screened for drug susceptibility tests, and the distribution characteristics of drug susceptibility were analyzed. Results: 179 strains of tuberculosis and non-tuberculous mycobacteria were isolated from the specimens of AIDS patients, including 135 cases of tuberculosis mycobacteria and 44 cases of non-tuberculous mycobacteria. In the results of the drug susceptibility test, most strains of Mycobacterium tuberculosis showed sensitivity to commonly used drugs, and a few strains showed resistance;most strains of non-tuberculous mycobacteria showed resistance, and a few strains showed sensitivity. Conclusion: AIDS opportunistic infection of Mycobacterium tuberculosis and non-tuberculous mycobacteria have significant differences in drug sensitivity test results. Timely detection and analysis are of great significance to the diagnosis and treatment of the disease.

Viral infections in inflammatory bowel disease:Tips and tricks for correct management

Over the past decades,the treatment of inflammatory bowel diseases(IBD)has become more targeted,anticipating the use of immune-modifying therapies at an earlier stage.This top-down approach has been correlated with favorable short and long-term outcomes,but it has also brought with it concerns regarding potential infectious complications.This large IBD population treated with immunemodifying therapies,especially if combined,has an increased risk of severe infections,including opportunistic infections that are sustained by viral,bacterial,parasitic,and fungal agents.Viral infections have emerged as a focal safety concern in patients with IBD,representing a challenge for the clinician:they are often difficult to diagnose and are associated with significant morbidity and mortality.The first step is to improve effective preventive strategies,such as applying vaccination protocols,adopt adequate prophylaxis and educate patients about potential risk factors.Since viral infections in immunosuppressed patients may present atypical signs and symptoms,the challenges for the gastroenterologist are to suspect,recognize and diagnose such complications.Appropriate treatment of common viral infections allows us to minimize their impact on disease outcomes and patients’lives.This practical review supports this standard of care to improve knowledge in this subject area.

Obligate aerobic, gram-positive, weak acid-fast, nonmotile bacilli, Tsukamurella tyrosinosolvens: Minireview of a rare opportunistic pathogen

Tsukamurella species are obligate aerobic,gram-positive,weak acid-fast,nonmotile bacilli.They are found in various environments,such as soil,water,sludge,and petroleum reservoir wastewater,and belong to the order Actinomycetales.In 2016,there was a reclassification of species within the genus Tsukamurella,merging the species Tsukamurella tyrosinosolvens(T.tyrosinosolvens)and Tsukamurella carboxydivorans.Tsukamurella species are clinically considered to be a rare opportunistic pathogen,because most reported cases have been related to bacteremia and intravascular prosthetic devices and immunosuppression.To date,it has been isolated only from human specimens,and has always been associated with clinical disease;human infections are very rare.Reported infections have included pneumonia,brain abscesses,catheter-related bloodstream infections,ocular infections,bacteremia,and sepsis presenting with septic pulmonary emboli in patients who are immunocompromised.To date,there is no commercially available test for identification.On the other hand,sequence-based identification,including matrix-assisted laser desorption ionization time-of-flight mass spectrometry,is an alternative method for identifying clinical isolates that are either slow growers or difficult to identify through biochemical profiling.The golden standards for diagnosis and optimal management still remain to be determined.However,newer molecular biological techniques can provide accurate identification,and contribute to the appropriate selection of definitive therapy for infections caused by this organism.Combinations of several antimicrobial agents have been proposed for treatment,though the length of treatment for infections has yet to be determined,and should be individualized according to clinical response.Immunocompromised patients often experience severe cases due to infection,and life-threatening T.tyrosinosolvens events associated with dissemination and/or failure of source control have occurred.Favorable prognoses can be achieved through earlier identification of the cause of infection,as well as successful management,including appropriate antibiotic therapy together with source control.Further analyses of similar cases are required to establish the most adequate diagnostic methods and treatment regimens for infections.

Pulmonary cryptococcosis after immunomodulator treatment in patients with Crohn’s disease:Three case reports

BACKGROUND Corticosteroids and anti-tumor necrosis factorαmAbs are widely used to treat Crohn's disease(CD).However,one disadvantage of this treatment is impairment of normal immune function,leading to an increased risk of infection.Cryptococcus infection is an opportunistic infection that occurs mainly in immunocompromised patients and poses a significant diagnostic challenge in patients with CD.CASE SUMMARY Here,we report three cases of pulmonary cryptococcosis in patients with CD after receiving immunomodulatory treatment.The patients presented with no or mild respiratory symptoms.Chest computed tomography scans revealed pulmonary nodules in the unilateral or bilateral lobes.Diagnoses were made using pathological examination and metagenomic sequencing.The patients were treated with fluconazole 400 mg once daily for 1 to 6 mo,and symptoms were resolved.Literature searches were conducted in PubMed,Web of Science,and Embase to retrieve previously reported cases and summarize patient characteristics.CONCLUSION The incidence of cryptococcus infection has increased along with immunomodulator use.Clinical vigilance is required for early identification and standardized treatment.

In vitro intracellular IFNγ, IL-17 and IL-10 producing T cells correlates with the occurrence of post-transplant opportunistic infection in liver and kidney recipients

AIM To validate intracellular cytokine production functional assay as means of cell-mediated immunity monitoring of post-transplant patients with opportunistic infection(OI).METHODS Intracellular cytokine-producing CD4^+ and CD8^+ T-cell monitoring was carried out in 30 liver transplant(LTr) and 31 kidney transplant(KTr) recipients from 2010 to 2012. Patients were assessed in our Department of Immunology at the Clinical University ‘Hospital Virgen de la Arrixaca-IMIB' in Murcia, Spain for one year following transplantation. FACS Canto Ⅱ flow cytometer was employed to quantify the intracellular production of IL-17, IFNγ and IL-10 cytokines on stimulated CD4^+CD69^+ and CD8^+CD69^+ T cells and BD FACS DIVA v.6 software was used to analysed the data. Statistical analysis was carried out using SPSS 22.0.RESULTS LTr with OI had significantly lower % of CD8^+CD69^+IFNγ^+T cells at 60(7.95 ± 0.77 vs 26.25 ± 2.09, P < 0.001), 90(7.47 ± 1.05 vs 30.34 ± 3.52, P < 0.001) and 180(15.31 ± 3.24 vs 24.59 ± 3.28, P = 0.01) d posttransplantation. Higher % of CD4^+CD69^+IL-10^+ as well as CD4^+CD69^+IL-17^+ T cells were yet reported at 30(14.06 ± 1.65 vs 6.09 ± 0.53, P = 0.0007 and 4.23 ± 0.56 vs 0.81 ± 0.14, P = 0.005; respectively), 60(11.46 ± 1.42 vs 4.54 ± 0.91, P = 0.001 and 4.21 ± 0.59 vs 1.43 ± 0.42, P = 0.03; respectively) and 90 d(16.85 ± 1.60 vs 4.07 ± 0.63, P < 0.001 and 3.97 ± 0.43 vs 0.96 ± 0.17, P = 0.001). Yet, KTr with OI had significantly lower percentage of CD4^+CD69^+IFNγ^+ at 30(11.80 ± 1.59 vs 20.64 ± 3.26, P = 0.035), 60(11.19 ± 1.35 vs 15.85 ± 1.58, P = 0.02), 90(11.37 ± 1.42 vs 22.99 ± 4.12, P = 0.028) and 180(13.63 ± 2.21 vs 21.93 ± 3.88, P = 0.008) d post-transplantation as opposed to CD4^+CD69^+IL-10^+ and CD8^+CD69^+IL-10^+ T cells which percentages were higher at 30(25.21 ± 2.74 vs 8.54 ± 1.64, P < 0.001 and 22.37 ± 1.35 vs 17.18 ± 3.54, P = 0.032; respectively), 90(16.85 ± 1.60 vs 4.07 ± 0.63, P < 0.001 and 23.06 ± 2.89 vs 10.19 ± 1.98, P = 0.002) and 180(21.81 ± 1.72 vs 6.07 ± 0.98, P < 0.001 and 19.68 ± 2.27 vs 10.59 ± 3.17, P = 0.016) d posttransplantation. The au ROC curve model determined the most accurate cut-off values to stratify LTr and KTr at high risk of OI and Cox Regression model confirmed these biomarkers as the most significant risk factors to opportunistic infection.CONCLUSION Post-transplant percentages of T-cell subsets differed significantly amongst infected-and non-infected-LTr and-KTr and yet this imbalance was found to contribute towards a worst clinical outcome.

Pathological and immunohistochemical findings of lungs,heart,liver,and kidneys,and unexpected findings of fungi and parasites in lungs of deceased COVID-19 patients:A case series

Objective:To define histopathologic and immunohistochemical features of the lungs,heart,liver,and kidneys in patients who died from coronavirus disease 2019(COVID-19),and to determine the presence of SARS-CoV-2 in all tissues,as well as the presence of fungi and parasites in lung tissues.Methods:This retrospective case study was conducted in the intensive care units of Dokuz Eylül University Hospital,and patients(≥18 years)who died due to COVID-19 between October 2020 and April 2021 were included.The biopsy samples of the patient’s lung,heart,liver,and kidney tissues were studied.Results:In the study,we enrolled 12 patients(mean age:70 years;50%male).Alveolar epithelial cell damage and diffuse alveolar damage were predominant in lung tissues.Lobular lymphocyte infiltration,centrilobular sinusoidal dilatation,and microvesicular steatosis in the liver,together with pigmented cast,non-isometric vacuolar degeneration,and capillary plugging in the kidneys,were commonly found among the patients.SARS-CoV-2 nucleocapsid protein antibodies were detected in three lung and two kidney tissues,and so did angiotensin-converting enzyme 2 receptor positivity in one lung and more than half of the kidney tissues.The RT-PCR tests were positive in three lungs and one kidney tissue.After DNA isolation from lung tissues,Pneumocystis jirovecii was detected in nine patients,Aspergillus fumigatus in two,Microsporidia in three,and Cryptosporidium in two.Conclusions:SARS-CoV-2 is a multisystemic disease.Fungi and parasites should be investigated in critically ill COVID-19 patients prescribed corticosteroids.

Inflammatory bowel disease in travelers:Choosing the right vaccines and check-ups

The majority of patients with inflammatory bowel disease (IBD) achieve good control of the inflammatory activity using available therapies. When remission is achieved and quality of life recovered, a considerable proportion of IBD patients express their desire to travel abroad, be it for business, academic or leisure purposes. Their physicians should help and encourage them whenever possible. However, preventive measures are warranted to minimize the risk, since IBD patients are exposed to the same infections affecting the general population, plus opportunistic infections (OI) related to the immunosuppression. There are a large number of potential OI that might affect patients with IBD. The true prevalence of these infections is unknown, and can vary from country to country. Therefore, reactivation or de novo acquisition of infections such as tuberculosis, malaria, and viral hepatitis will be much more frequent in endemic areas. Therefore, physicians should beaware of these aspects when planning specific preventive measures for patients traveling to a particular country. This includes good control of environmental exposure, chemoprophylaxis when indicated, and the use of a specific vaccination program to prevent endemic infections. In addition, it should be noted that, though the risk of acquiring an infectious disease is probably greater for IBD patients traveling from a developed to a developing country, the inverse situation can also occur; it depends on the previous acquired immunity of the host against infections in any particular environment.

Epidemiology of opportunistic invasive fungal infections in China： review of literature

Objective To summarize the recent findings on the epidemiology of medically important, opportunistic invasive fungal infections （IFIs） in China and discuss the relevant social, economical reasons and medical factors. Data sources We performed a comprehensive search of both English and Chinese literatures of opportunistic IFIs from China up to April 2012. Study selection Relevant literatures involving researches and cases/case sedes were identified, retrieved and reviewed. Results The incidence of opportunistic IFIs in China was steadily increasing. The incidence and mortality of IFIs were different in patients with various underlying conditions/diseases, from 4.12% to 41.18% and 9.8% to 60.0%, respectively. Candida species, Aspergillus species and Cryptococcus neoformans species complex were the most frequent isolated pathogens. Other uncommon opportunistic IFIs were also been reported, including trichosporonosis, mucormycosis, hyalohyphomycosis （hyaline hyphomycetes） and phaeohyphomycosis （dematiaceous hyphomycetes）. Reports of Chinese patients differed from those of many other countries as there were a higher number of patients without identifiable underlying diseases/conditions. Conclusions Because of the rapid economic development, changing population structure and a growing number of immunocompromised hosts with risk factors, today opportunistic IFIs in China have a significant impact on public health, associated with high morbidity/mortality and higher care costs. Now information related to the epidemiology of opportunistic IFIs in China is still sparse, so we need more organized groups of clinical scientists performing related researches to help the clinicians to obtain more accurate epidemiological characteristics.

A Serratia marcesens Strains Involved in Cotton (<i>Gossypium hirsutum</i>) Boll Infection by a Prokaryote

A boll infection caused by non-traditional cotton pathogens was first reported to occur in the southeastern U.S. Cotton Belt (year 2000) and has since spread to Texas causing significant yield losses. This study was aimed towards investigating the verde plant bug (Creontiades signatus) link between interior boll disease in Texas, USA. Using glasshouse grown bolls, bacteria recovered from locules with disease symptoms from field-grown cotton bolls caged with the piercing-sucking C. signatus were analyzed for the capacity to inflict the disease. For pathogenicity testing, spontaneously generated rifampicin resistant (Rifr) variants were utilized to track the antibiotic resistant bacterium and deter growth of endophytic and contaminating bacteria. To simulate C. signatus feeding, a needle (31 gauge) was employed to inoculate bolls at 13 - 15 days after flower bloom. Bacterial suspensions ranged from 101 - 106 colony forming units/ml. Field infection symptoms were duplicated after two weeks of bacterial exposure. Infectious strains were best categorized as Serratia marcescens based on traditional carbon utilization and enzyme production testing, and a 99% nucleotide sequence identity of 16S ribosomal DNA. Putative S. marcescens representatives isolated from rotted bolls exposed to C. signatus were shown to reproduce field infection symptoms upon inoculation into greenhouse grown fruit. Serratia spp. can inflict disease in alfalfa, cucurbits, and sunflower. The presented data are the first to definitively show that a Serratia sp. has the capacity to infect cotton.

Fungi between extremotolerance and opportunistic pathogenicity on humans

Numerous agents of infections in humans and other mammals are found among fungi that are able to survive extreme environmental conditions and to quickly adapt to novel habitats.Nevertheless,the relationship between opportunistic potential and polyextremotolerance was not yet studied systematically in fungi.Here,the link between polyextremotolerance and opportunistic pathogenicity is shown in a kingdom-wide phylogenetic analysis as a statistically significant co-occurrence of extremotolerance(e.g.osmotolerance and psychrotolerance)and opportunism at the level of fungal orders.In addition to extremotolerance,fungal opportunists share another characteristic—an apparent lack of specialised virulence traits.This is illustrated by a comparative genomic analysis of 20 dothideomycetous and eurotiomycetous black fungi.While the genomes of specialised fungal plant pathogens were significantly enriched in known virulence-associated genes that encode secreted proteases,carbohydrate active enzyme families,polyketide synthases,and non-ribosomal peptide synthetases,no such signatures were observed in human opportunists.Together the presented results have several implications.If infection of human hosts is a side effect of fungal stress tolerance and adaptability,the human body is most likely neither the preferred habitat of such species,nor important for their evolutionary success.This defines opportunism as opposed to pathogenicity,where infection is advantageous for the species’fitness.Since opportunists are generally incapable of the host-to-host transmission,any host-specific adaptations are likely to be lost with the resolution of the infection,explaining the observed lack of specialised virulence traits.In this scenario opportunistic infections should be seen as an evolutionary dead end and unlikely to lead to true pathogenicity.

A Case Report of Methylobacterium radiotolerans Bacteremia and Brain Abscesses

Methylobacterium radiotolerans is a ubiquitous organism found in the environment and is considered an opportunistic pathogen of low virulence in humans.Most human infections from M.radiotolerans have been reported in immunocompromised hosts and have been reported mainly as bloodstream infections related to central venous catheters.We present the first known case of M.radiotolerans as a causative agent of multiple brain abscesses in an immunocompromised host.

Current epidemiological and etiological characteristics and treatment of seizures or epilepsy in patients with HIV infection

Seizures or epilepsy is one of the common serious complications in patients with advanced human immunodeficiency virus(HIV)infection or diagnosed with immune deficiency syndrome,with higher incidence and prevalence than in the general population.Generalized seizures are the most common type in the patients.Opportunistic infections are a stereotypical predisposing factor for seizures in HIV patients,but a variety of pathogenic factors can also be found in these patients,such as metabolic perturbation and drug-drug interactions.The diagnostic criteria for seizures in these patients are the same as those in the general population.As HIV patients with seizures need to take both antivirals and antiepileptic drugs,the risk of drug-drug interactions is greatly increased,and the side effects of drugs may also become more prominent.At present,most experience in antiepileptic drug usage has come from the general population,and there is still a lack of guidance of antiepileptic drug use in special groups such as the HIV-infected people.Unlike the old-generation drugs that involve metabolisms through CYP450,the first-line antiepileptic drugs usually bypass CYP450,thus having less drug-drug interactions.In this review,we summarize the recent research progress on the above-mentioned widely discussed topics and make a prospect on future research direction.