Toxoplasmosis in immunocompromised patients is associated with a high mortality rate. Molecular techniques are important tools to diagnose acute disease in immunocompromised patients, but there are ...various methods with variable efficiency. Some of them have been validated for the diagnosis of congenital toxoplasmosis, but the impact of their use has not been evaluated in immunocompromised patients.
Toxoplasmosis is of increasing importance in non-HIV immunocompromised patients. In addition, the picture of disease shows greater severity in South America, both in immunocompetent study participants and in congenitally infected infants. These epidemiological differences could influence the sensitivity of diagnostic methods. This review analyzes recent data on molecular diagnosis and compares them with older ones, in light of progress gained in molecular techniques and of recent epidemiological findings. Most recent studies were conducted in South America and used PCR targeting the B1 gene. PCR on blood could allow diagnosing a significant proportion of patients with ocular toxoplasmosis in Brazil.
Quantitative PCR methods with specific probes should be used to improve sensitivity and warrant specificity. Performance of quantitative PCR targeting the repeated 529 bp sequence for the diagnosis of toxoplasmosis in immunocompromised patients needs evaluation in field studies in South America and in western countries.
Toxoplasmosis is a worldwide parasitic disease infecting about one third of humans, with possible severe outcomes in neonates and immunocompromised patients. Despite continuous and successful efforts ...to improve diagnosis, therapeutic schemes have barely evolved since many years. This article aims at reviewing the main clinical trials and current treatment practices, and at addressing future perspectives in the light of ongoing researches.
•Toxoplasmosis is a widespread zoonosis, which may have an important impact on human and animal health worldwide•Treatment schemes remain unchanged since 20 years, as no new drug has been put recently on the market•Among the few drugs currently available for treatment of toxoplasmosis, none of them is efficient on cysts•Active research to discover new therapeutic targets is ongoing, and promising pathways have been identified, thus paving the way for future drug combinations to eradicate the parasite•Immunomodulatory approaches could add value to prevent relapses in immunocompromised patients, but are still underdeveloped
Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection in immunocompromised patients. Quantitative real-time PCR (qPCR) is more sensitive than microscopic examination for the ...detection of P. jirovecii but also detects colonized patients. Hence, its positive predictive value (PPV) needs evaluation. In this 4-year prospective observational study, all immunocompromised patients with acute respiratory symptoms who were investigated for PCP were included, totaling 659 patients (814 bronchoalveolar lavage fluid samples). Patients with negative microscopy but positive qPCR were classified through medical chart review as having retained PCP, possible PCP, or colonization, and their clinical outcomes were compared to those of patients with microscopically proven PCP. Overall, 119 patients were included for analysis, of whom 35, 41, and 43 were classified as having retained PCP, possible PCP, and colonization, respectively. The 35 patients with retained PCP had clinical findings similar to those with microscopically proven PCP but lower fungal loads (P < 0.001) and were mainly non-HIV-infected patients (P < 0.05). Although the mean amplification threshold was higher in colonized patients, it was not possible to determine a discriminant qPCR cutoff. The PPV of qPCR in patients with negative microscopy were 29.4% and 63.8% when considering retained PCP and retained plus possible PCP, respectively. Patients with possible PCP had a higher mortality rate than patients with retained PCP or colonization (63% versus 3% and 16%, respectively); patients who died had not received co-trimoxazole. In conclusion, qPCR is a useful tool to diagnose PCP in non-HIV patients, and treatment might be better targeted through a multicomponent algorithm including both clinical/radiological parameters and qPCR results.
Although microscopic examination of stool samples remains the reference method for the diagnosis of intestinal protozoal infections, these techniques are time-consuming and require operators who are ...experienced and well trained. Molecular biology seems to offer performances at least equivalent in terms of sensitivity and specificity for certain parasites. This study aimed to compare three multiplex PCR assays on 93 prospectively collected positive stools (prospective cohort) and a panel of 12 more Cryptosporidium-positive samples (Cryptosporidium panel). On the prospective cohort, the sensitivity was 89%, 64% and 41% for Giardia sp. detection for BD Max
, G-DiaPara
and RIDA
GENE, respectively and 75%, 100% and 100% for C. parvum/hominis detection. The sensitivity of the RIDA
GENE assay for all Cryptosporidium species was 100%, and for D. fragilis 71%. All the techniques obtained the same results for E. histolytica detection, with one positive sample. All species in the Cryptosporidium panel were identified by the RIDA
GENE PCR. The BD Max
and G-DiaPara
assays detected only C. parvum/hominis with the exception of one positive sample for C. meleagridis. No assay showed satisfactory results for all parasites simultaneously, and the DNA extraction seems to be the critical step. More studies are needed to standardize this procedure.
Diphyllobothriosis is an intestinal cestodosis caused by tapeworms of the family Diphyllobothriidae. In France, endemic cases are limited to south-east and due to Dibothriocephalus latus. In this ...paper, we investigate a series of seven cases of diphyllobothriosis in the non-endemic French region of Brittany. All have been diagnosed between 2016 and 2018 at the University Hospital of Rennes.
Parasites were identified by their morphological features and by phylogenetic analysis of the cox1 gene. Phylogenetic tree was built using maximum likelihood criterion under the GTR+G+I model and 2000 bootstrap replicates. A form was sent to all patients to collect data concerning clinical signs and possible sources of infection.
All cases were due to Dibothriocephalus nihonkaiensis, a species strictly distributed in the North Pacific. Epidemiological investigation showed that the parasite was probably acquired in France, after consumption of Japanese food containing raw salmon. All patients presented with at least abdominal pain and fatigue except for one patient who had no symptoms.
To our knowledge, this case series is the most important cohort of allochthonous diphyllobothriosis described in Europe. This sudden emergence raises concern about foodborne infections, highlighting (i) risky food habits in absence of adequate sanitary control; and (ii) the breaking of the rule of geographical restriction due to globalization and worldwide trades.
(1) Background: The diagnosis of invasive aspergillosis (IA) in an intensive care unit (ICU) remains a challenge and the COVID-19 epidemic makes it even harder. Here, we evaluated Aspergillus PCR ...input to help classifying IA in SARS-CoV-2-infected patients. (2) Methods: 45 COVID-19 patients were prospectively monitored twice weekly for Aspergillus markers and anti-Aspergillus serology. We evaluated the concordance between (I) Aspergillus PCR and culture in respiratory samples, and (II) blood PCR and serum galactomannan. Patients were classified as putative/proven/colonized using AspICU algorithm and two other methods. (3) Results: The concordance of techniques applied on respiratory and blood samples was moderate (kappa = 0.58 and kappa = 0.63, respectively), with a higher sensitivity of PCR. According to AspICU, 9/45 patients were classified as putative IA. When incorporating PCR results, 15 were putative IA because they met all criteria, probably with a lack of specificity in the context of COVID-19. Using a modified AspICU algorithm, eight patients were classified as colonized and seven as putative IA. (4) Conclusion: An appreciation of the fungal burden using PCR and Aspergillus serology was added to propose a modified AspICU algorithm. This proof of concept seemed relevant, as it was in agreement with the outcome of patients, but will need validation in larger cohorts.
Although leishmaniasis has been studied for over a century, the fight against cutaneous, mucocutaneous and visceral forms of the disease remains a hot topic. This review refers to the parasitic cell ...wall and more particularly to the constitutive glycoconjugates. The structures of the main glycolipids and glycoproteins, which are species-dependent, are described. The focus is on the disturbance of the lipid membrane by existing drugs and possible new ones, in order to develop future therapeutic agents.
Strongyloides stercoralis serology is a sensitive method for strongyloidiasis diagnosis, but it is prone to cross-reactions with other helminthiases. This four-year retrospective study aimed at ...estimating the performance of the Bordier IVD
Strongyloides ratti ELISA assay in a non-endemic country (France). The study included all patients tested for strongyloidiasis in our center between 2015 and 2019, by both serology and stool examination. Cases were defined using an algorithm considering serological results, microscopic examination of stools, and other biological, clinical or epidemiological data. The study included 805 stools from 341 patients (70% migrants, 20% travelers, 10% without travel to a highly endemic area). Thirty patients (8.8%) had positive serology, 9 had microscopically proven strongyloidiasis, and 11 and 10 were classified as probable and possible strongyloidiasis, respectively. Performances of microscopy and serology were compared, considering proven and probable strongyloidiasis as true infections. The sensitivity, specificity, positive predictive value and negative predictive value of serology were 100%, 97%, 67% and 100%, respectively, and those of microscopic examination of stools were 45% (p < 0.01), 100% (p < 0.01), 100% (p = 0.079) and 96% (p < 0.001), respectively. Eosinophilia did not help in discriminating true-positive from false-positive results. Overall, these results underline the high value of the S. stercoralis serologic assay, compared to stool examination. The systematic use of this technique for screening purposes in travelers or migrants, or before onset of immunosuppressive therapy, could help to improve patient management and epidemiological knowledge.
Invasive pulmonary aspergillosis (IPA) in intensive care unit patients is a major concern. Influenza-associated acute respiratory distress syndrome (ARDS) and severe COVID-19 patients are both at ...risk of developing invasive fungal diseases. We used the new international definitions of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) to compare the demographic, clinical, biological, and radiological aspects of IAPA and CAPA in a monocentric retrospective study. A total of 120 patients were included, 71 with influenza and 49 with COVID-19-associated ARDS. Among them, 27 fulfilled the newly published criteria of IPA: 17/71 IAPA (23.9%) and 10/49 CAPA (20.4%). Kaplan–Meier curves showed significantly higher 90-day mortality for IPA patients overall (p = 0.032), whereas mortality did not differ between CAPA and IAPA patients. Radiological findings showed differences between IAPA and CAPA, with a higher proportion of features suggestive of IPA during IAPA. Lastly, a wide proportion of IPA patients had low plasma voriconazole concentrations with a higher delay to reach concentrations > 2 mg/L in CAPA vs. IAPA patients (p = 0.045). Severe COVID-19 and influenza patients appeared very similar in terms of prevalence of IPA and outcome. The dramatic consequences on the patients’ prognosis emphasize the need for a better awareness in these particular populations.
The chemotherapeutic arsenal available to treat visceral leishmaniasis is currently limited, in view of many drawbacks such as high cost, toxicity or emerging resistance. New therapeutic strategies ...are particularly needed to improve the management and the outcome in immunosuppressed patients. The combination of an immunomodulatory drug to a conventional anti-Leishmania treatment is an emerging concept to reverse the immune bias from Th2 to Th1 response to boost healing and prevent relapses.
Here, immunostimulating and leishmanicidal properties of octyl-β-D-galactofuranose (Galf) were assessed in human monocyte-derived macrophages (HM) and in a murine model, after challenge with Leishmania donovani promastigotes. We recorded parasite loads and expression of various cytokines and immune effectors in HM and mouse organs (liver, spleen, bone marrow), following treatment with free (Galf) and liposomal (L-Galf) formulations.
Both treatments significantly reduced parasite proliferation in HM, as well as liver parasite burden in vivo (Galf, P < 0.05). Consistent with in vitro results, we showed that Galf- and L-Galf-treated mice displayed an enhanced Th1 immune response, particularly in the spleen where pro-inflammatory cytokines TNF-α, IL-1β and IL-12 were significantly overexpressed compared to control group. The hepatic recruitment of myeloid cells was also favored by L-Galf treatment as evidenced by the five-fold increase of myeloperoxidase (MPO) induction, which was associated with a higher number of MPO-positive cells within granulomas. By contrast, the systemic level of various cytokines such as IL-1β, IL-6, IL-17A or IL-27 was drastically reduced at the end of treatment.
Overall, these results suggest that Galf could be tested as an adjuvant in combination with current anti-parasitic drugs, to restore an efficient immune response against infection in a model of immunosuppressed mice.
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