Search

It is not yet entirely clear what is the relevance of skin symptoms and what clinical implications are related to their appearance in COVID‐19 patients. We describe two cases of COVID‐19‐associated pneumonia, which presented skin manifestations in advanced stage of illness, when nasopharyngeal swabs became negative for SARS‐CoV‐2. The first case presented erythematous, maculopapular lesions; the second developed petechial, vesicular and blood‐encrusted lesions on the limbs. Histopathology documented perivascular lymphocytic infiltrates, with prevalent CD4+ T‐cells in both patients. The research of SARS‐CoV‐2 in tissues with real time RT‐PCR was negative. Basal keratinocytes displayed C4d deposits in one case, who developed laboratory signs indicative of a procoagulative condition at the same time as the skin rash. Skin manifestations during SARS‐CoV‐2 infection seem to be clinically relevant and further studies are necessary to assess if they are linked to systemic complications, lack of viral clearance or cascades of immune responses induced by the virus, even in patients affected by mild pneumonia.

Background Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective. Cases presentation In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB. Conclusions We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.

Background Few data about predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS) are available. Methods Retrospective study including all patients admitted with COVID-19 in an Italian reference hospital for infectious diseases between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between duration of VS and probability of clinical outcomes was evaluated through inverse probability weighted Cox model. Results 536 subjects were included. Median duration of VS from symptoms onset was 18 days (IQR 12-26). The estimated 30-day probability of VC was 70.2% (95%CI:65-75). At multivariable analysis, patients with comorbidities (aIRR = 0.88, p = 0.004), lymphopenia at hospital admission (aIRR = 0.75, p = 0.032) and with moderate/severe respiratory disease (aIRR = 0.42, p 1000 ng/mL at admission (aOR = 1.76, p = 0.035) independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery (aHR = 2.17, p

Background Surgical site infections are a leading cause of morbidity and mortality after caesarean section, especially in Low and Middle Income Countries. We hypothesized that a combined infection prevention and control with antimicrobial stewardship joint program would decrease the rate of post- caesarean section surgical site infections at the Obstetrics & Gynaecology Department of a Tanzanian tertiary hospital. Methods The intervention included: 1. formal and on-job trainings on infection prevention and control; 2. evidence-based education on antimicrobial resistance and good antimicrobial prescribing practice. A second survey was performed to determine the impact of the intervention. The primary outcome of the study was post-caesarean section surgical site infections prevalence and secondary outcome the determinant factors of surgical site infections before/after the intervention and overall. The microbiological characteristics and patterns of antimicrobial resistance were ascertained. Results Total 464 and 573 women were surveyed before and after the intervention, respectively. After the intervention, the antibiotic prophylaxis was administered to a significantly higher number of patients (98% vs 2%, p p = 0.001), with higher rates of Pfannenstiel skin incisions (29% vs 18%, p p p Staphylococus aureus was detected in the post-intervention survey. Conclusions Further researches are needed to better understand the potential of a hospital-based multidisciplinary approach to surgical site infections and antimicrobial resistance prevention in resource-constrained settings.

On 31 August, a veterinarian and a farmworker were hospitalised for skin lesions. Both had been exposed to a dead cow on 19 August on a farm near Rome, where eight further cattle died of confirmed anthrax later the same month. At admission, the first case showed a black depressed eschar and another smaller lesion on one hand. The second case presented deep infection of the skin, with involvement of both arms. Anthrax diagnosis was confirmed by detection of B. anthracis DNA in eschar fragments from both patients. T-cell specific immunity was studied by flow cytometry and Elispot assay after stimulation with B. anthracis secretome in blood samples collected from Case 1. Immunoglobulin production was detected by complement fixation assay. In Case 1, specific CD4+ T-cell activation was detected, without antibody production. Specific antibodies were detected only in the second patient with severe cutaneous illness. Both patients recovered. The two human anthrax cases were epidemiologically linked, but anthrax was not suspected at admission in either case. The veterinarian had initially unrecognised professional exposure and the exposed farmworker did initially not report exposure to affected animals. A One Health strategy integrating human and animal investigations was essential to confirm the diagnosis.

Objective: To make an informed viewpoint on the usefulness of Tuberculin Skin test (TST) compared to Interferon Gamma Release Assays (IGRAs) for diagnosis of Latent TB Infection (LTBI) in different geographical settings. Methods: We reviewed the current literature on TST compared to IGRA, including national implementation of WHO LTBI recommendations and retrospective data over the past 7 years at the National Institute for Infectious Diseases “L. Spallanzani” as indirect indicator of usage of both tests under actual programmatic conditions. Results: Current national guidelines vary considerably, reflecting the uncertainty and rapidly evolving evidence about the potential use of these tests. Data from Institute “L. Spallanzani” showed IGRA concordance in TST positive subjects only in 54.74% of subjects, while there was strong concordance between two tests in TST negative subjects (93.78%). Conclusion: Neither IGRAs nor TST can distinguish active TB from LTBI. TST will continue to be clinically useful in low and high TB endemic areas until more accurate and predictive tests will become available. Clinical judgment remains fundamental in choosing between IGRA/TST tests and interpreting their results. Keywords: Tuberculin skin test, TST, Interferon-γ release assays, IGRA, Tuberculosis, Quantiferon, TB, Latent TB, LTBI

The diagnosis of sarcoidosis in a patient living with HIV infection is an uncommon event and a challenge for clinicians. Clinical manifestations are variable and fluctuating depending to adherence to ARV therapy and to the level of CD4 count. We analyze here one chronic case in which sarcoidosis appeared clinically two years after pulmonary tuberculosis. The course of the disease was influenced and prolonged by frequent interruptions of antiretroviral therapy. Moreover the diagnosis and the decision to treat have been delayed by the need of exclusion of other pathologies, principally tuberculosis reactivation/reinfection, other mycobacterial diseases, hematologic malignancies. We propose a simplified flowchart for diagnosis and follow up of sarcoidosis, which may also be applied to patients with HIV infection. Diagnosis of latent tuberculosis infection (LTBI) may be difficult in these patients, because the immunological paradox of sarcoidosis. For this reason, following exclusion of active tuberculosis, we advise to submit all sarcoidosis patients to IPT (isoniazid preventive therapy), when immunosuppressive therapy is started.

In endemic countries with a high level of chloroquine resistance, Plasmodium vivax malaria is associated with high morbidity and mortality. In these areas, the dihydroartemisinin–piperaquine combination resulted in clinical response, a more rapid clearance of parasitaemia, compared to chloroquine therapies, and reduction of recrudescence or reinfection. We describe five cases of Plasmodium vivax malaria in returning travelers treated with dihydroartemisinin–piperaquine. All patients showed the early parasite clearance and no side effects. Our preliminary results suggest that the dihydroartemisinin–piperaquine combination is effective and safe even in imported cases. A unified treatment policy using the artemisinin combination therapy should be adopted even in non-endemic countries and larger studies are underway to support this strategy.

Objectives Cases of undiagnosed severe febrile rhabdomyolysis in refugees coming from West Africa, mainly from Nigeria, has been observed since May 2014. The aim of this study was to describe this phenomenon. Methods This was a multicentre retrospective observational study of cases of febrile rhabdomyolysis reported from May 2014 to December 2016 in 12 Italian centres. Results A total of 48 cases were observed, mainly in young males. The mean time interval between the day of departure from Libya and symptom onset was 26.2 days. An average 8.3 further days elapsed before medical care was sought. All patients were hospitalized with fever and very intense muscle aches. Creatine phosphokinase, aspartate aminotransferase, and lactate dehydrogenase values were abnormal in all cases. The rhabdomyolysis was ascribed to an infective agent in 16 (33.3%) cases. In the remaining cases, the aetiology was undefined. Four out of seven patients tested had sickle cell trait. No alcohol abuse or drug intake was reported, apart from a single reported case of khat ingestion. Conclusions The long incubation period does not support a mechanical cause of rhabdomyolysis. Furthermore, viral infections such as those caused by coxsackievirus are rarely associated with such a severe clinical presentation. It is hypothesized that other predisposing conditions like genetic factors, unknown infections, or unreported non-conventional remedies may be involved. Targeted surveillance of rhabdomyolysis cases is warranted.

RationaleTreatment of multi-drug resistant Tuberculosis (MDR-TB) is challenging because it mostly relies on drugs with lower efficacy and greater toxicity than those used for drug-susceptible TB.ObjectivesAim of the study was to describe the frequency and type of adverse drug reactions in a cohort of MDR-TB patients and their potential impact on treatment outcome.MethodsWe conducted a retrospective study in a cohort of MDR-TB patients enrolled at a tertiary referral hospital in Italy from January 2008 to December 2016. The records of patients were reviewed for epidemiological, clinical, microbiological and adverse drug reactions data.ResultsSeventy-four MDR-TB patients (mean age 32 years, 58.1% males, 2 XDR, 12 pre-XDR TB) were extracted from the Institute data base and included in the retrospective study cohort in the evaluation period (January 2008-December 2016). Median length of treatment duration was 20 months (IQR 14-24). Treatment outcome was successful in 57 patients (77%; 51 cured, 6 treatment completed); one patient died and one failed (2.7% overall); 15 patients were lost to follow-up (20.3%). Sixty-six (89.2%) presented adverse drug reactions during the whole treatment period. Total number of adverse drug reactions registered was 409. Three hundred forty-six (84.6%) were classified as adverse events (AEs) and 63 (15.4%) were serious AEs (SAEs). One third of the total adverse drug reactions (134/409; 32.8%) was of gastrointestinal origin, followed by 47/409 (11.5%) ototoxic drug reactions, thirty-five (8.6%) regarded central nervous system and 33 (8.1%) affected the liver. All 63 SAEs required treatment suspension with 61 SAEs out of 63 (96.8%) occurring during the first six months of treatment. Factors associated with unsuccessful treatment outcome were smoking (p = 0.039), alcohol abuse (p = 0.005) and homeless condition (p = 0.044). Neither the number of antitubercular drugs used in different combinations nor the number of AEs showed significant impact on outcome. Patients who completed the treatment experienced a greater number of AEs and SAEs (p < 0.001) if compared to lost to follow-up patients.ConclusionsOur data demonstrate that, despite the high frequency of adverse drug reactions and long term therapy, the clinical management of MDR-TB patients in a referral center could reach successful treatment according to WHO target, by implementing active and systematic clinical and laboratory assessment to detect, report and manage suspected and confirmed adverse drug reactions.

Background Surgical site infection (SSI) is a common post-operative complication causing significant morbidity and mortality. Many SSI occur after discharge from hospital. Post-discharge SSI surveillance in low and middle income countries needs to be improved. Methodology We conducted an observational cohort study in Dodoma, Tanzania to examine the sensitivity and specificity of telephone calls to detect SSI after discharge from hospital in comparison to a gold standard of clinician review. Women undergoing caesarean section were enrolled and followed up for 30 days. Women providing a telephone number were interviewed using a structured questionnaire at approximately days 5, 12 and 28 post-surgery. Women were then invited for out-patient review by a clinician blinded to the findings of telephone interview. Results A total of 374 women were enrolled and an overall SSI rate of 12% (n = 45) was observed. Three hundred and sixteen (84%) women provided a telephone number, of which 202 had at least one telephone interview followed by a clinical review within 48 h, generating a total of 484 paired observations. From the clinical reviews, 25 SSI were diagnosed, of which telephone interview had correctly identified 18 infections; telephone calls did not incorrectly identify SSI in any patients. The overall sensitivity and specificity of telephone interviews as compared to clinician evaluation was 72 and 100%, respectively. Conclusion The use of telephone interview as a diagnostic tool for post-discharge surveillance of SSI had moderate sensitivity and high specificity in Tanzania. Telephone-based detection may be a useful method for SSI surveillance in low-income settings with high penetration of mobile telephones.

Coccidioidomycosis is a fungal infection caused by the Coccidioides species, which is endemic in the deserts of the southwestern region of the United States, northern Mexico, and in some areas of Central and South America. We describe a case of pulmonary coccidioidomycosis in a 49-year-old Italian man who came to our hospital with fever and joint and muscle pain 10 days after his return to Italy from Venezuela. Computer Tomography revealed multiple bilateral pulmonary nodules with mediastinal lymphadenopathy. Pulmonary coccidioidomycosis was diagnosed by a serological test, and fluconazole was immediately started. The patient improved within 2 weeks, with complete clinical recovery after 6 months of therapy. This case appears to be part of a large serologically unconfirmed outbreak. In order to provide early diagnosis and treatment, healthcare providers should be aware of coccidioidomycosis, even in travellers returning home from short trips to endemic areas.

Resume Pour obtenir plus d'informations sur l'epidemiologie de l'infection par Pneumocystis carinii sp. f. hominis, nous avons analyse les regions intercalaires internes transcrites du noyau de l'operon de l'ARNr du microorganisme, a partir d'echantillons respiratoires obtenus de cinq patients sideens italiens ayant eu deux atteintes de pneumocystose. Le procede nous a permis d'identifier 8 types de P. carinii, et parmi ceux-ci trois types nouveaux: A4a1 , B1b5 et B1c2. Le type B1a3 apparait comme le genotype italien le plus representatif de cette etude. Nos resultats suggerent que les reinfections sont exogenes de facon predominante plutot que dues a la reactivation d'une infection prealable.

DNA amplification using dihydrofolate reductase (DHFR) primers in bronchoalveolar lavage fluids (BALFs) from patients with Pneumocystis carinii (PC) pneumonia yielded low sensitivity and specificity. Amplified products of BALFs from an AIDS patient without PC pneumonia and five patients with PC pneumonia were cloned and sequenced. All samples showed the same sequence without any homology with DHFR cDNA of rat PC, or with any DHFR sequences in databases at the DNA or amino acid level. The data demonstrate that these DHFR primers amplify a non-specific region of DNA with a sequence unrelated to the human PC DHFR gene both in PC positive and in PC negative samples. This finding precludes the use of these DHFR primers for the diagnosis of PC pneumonia in respiratory specimens.

Artemisinin and its derivatives are essential components of artemisinin-based combination therapies for treating severe falciparum malaria. In this paper, we describe the occurrence of haemolysis after oral artemether–lumefantrine treatment. To the best of our knowledge, this is the second reported case of a patient affected by severe falciparum malaria with haemolytic anaemia that is likely associated with oral artemether–lumefantrine treatment.

By using a recently developed PCR-solution hybridization enzyme-linked assay (PCR-SHELA), we investigated Pneumocystis carinii in bronchoalveolar lavage fluid samples and induced sputa of patients with pneumocystosis. In detecting P. carinii, PCR-SHELA proved more sensitive than immunofluorescence staining or a single PCR and significantly more diagnostically specific than a nested PCR. Our data suggest that PCR-SHELA could be used to detect P. carinii organisms in respiratory samples, particularly in patients with uncertain diagnoses.

The purpose of this study was to determine whether dihydropteroate synthase gene (DHPS) mutations were associated with the failure of sulpha/sulphone drugs used as prophylaxis agents in HIV infected patients. Results suggested that DHPS mutations were significantly associated with failure of anti-Pneumocystis carinii sulphone prophylaxis (P=0.031). An increasing number of mutant P. carinii strains have been isolated from patients no longer having prophylaxis. There was no statistically significant difference in severity or outcome of the pneumonia caused by wild-type or mutant DHPS. Moreover, two of the three patients with mutant P. carinii pneumonia (PCP) were successfully treated with sulpha drugs. We think that P. carinii drug-resistance could be an emerging problem for immunocompromised patients including those with HIV infection.

The aim of this study was to determine the kinetics, the dissemination of the infection and the immunological response to Pneumocystis carinii primary infection in a non-immunosuppressed rabbit model. For this purpose, we developed a nested PCR that amplified a portion of the mitochondrial large-subunit rRNA gene of rabbit-derived P. carinii. The PCR detected P. carinii DNA in lung and bronchoalveolar lavage fluids from 14- to 45-day-old rabbits but not in their serum. No P. carinii DNA was detected in extrapulmonary organs from 28-day-old rabbits with P. carinii pneumonia. ELISA and immunoblotting analysis showed that 5-day-old pups had elevated specific IgG. The IgG concentration sharply decreased, reaching a trough on day 21, and from then onwards progressively increased as the infection cleared. Conversely, the specific IgM concentration increased during the infection and peaked on day 28. IgG mainly recognized a 50-kDa subunit of P. carinii organisms; IgM recognized first a 45-kDa subunit on day 21, whereas from day 28 onwards it also recognized the 50-kDa subunit. A P. carinii-specific splenocyte proliferative response was observed on day 45. These findings suggest that P. carinii primary infection is a time-limited and a lung-limited event and contribute new information on the relationship between the kinetics of primary P. carinii infection and the immunological response in a model that mimics the primary infections in humans.

Our aim was to evaluate if genetic diversity of Pneumocystis carinii could influence the detection by molecular techniques in bronchoalveolar lavage (BAL) fluids and in non-invasive specimens (induced sputum, oropharyngeal washing and serum/blood). P. carinii is morphologically similar in different hosts although several strains have been identified by biomolecular techniques. Variations of mt-LSU and ITSs sequences could determine a lack of hybridization of some clinical samples and could have diagnostic consequences with loss in sensitivity and specificity of available molecular tests, but at the moment no data support a significant impact of genetic diversity in these sequences on molecular detection of P. carinii for clinical purposes.

Detection and quantification of different Pneumocystis carinii (PC) life cycle forms were performed by polymerase chain reaction (PCR) and by morphological stains on bronchoalveolar lavage fluids (BALF) from HIV-infected patients with P. carinii pneumonia (PCP). The number of PC trophozoites was higher in patients with PCP who were receiving prophylaxis than in those not receiving prophylaxis. Also the cyst: trophozoite ratio was lower in the first group. No difference was observed between patients receiving different prophylactic medications. The imbalance between PC forms in BALF from patients with PCP receiving anti-PC prophylaxis may hamper the sensitivity of cyst stains. Multiple stains or PCR examination should be performed on BALF from patients with clinically suspected PCP who are receiving prophylaxis.

The efficiency of three different primer pairs, complementary to different Pneumocystis carinii DNA regions, was compared in the polymerase chain reaction (PCR) for the diagnosis of Pneumocystis carinii pneumonia (PCP) on bronchoalveolar fluid (BALF) from patients with AIDS. PCR coupled with dot-blot hybridization (BLOT) using primers and probe from the mitochondrial 23SrDNA region showed the highest sensitivity, with a lower detection limit of 0·5–1 organisms μl −1 . When testing 47 BALF, PCR plus BLOT if the mitochondrial 23SrDNA region showed also the best diagnostic efficiency (97% sensitivity, 100% specificity). Sensitivity was significantly higher than with PCR and BLOT of the 5SrDNA region (81·5% sensitivity; P = 0.025 , McNemar test); and of the dehydrofolate reductase (DHFR) gene region (75·6% sensitivity; P = 0·019 ). Sensitivity was also significantly higher than indirect immunofluorescence (75·8% sensitivity; P = 0·008 ). Using DHFR primers and probe, specificity was also reduced. The diagnostic sensitivity in clinical specimens paralleled the detection limit in the standard dilutions. The use of repeated DNA sequences of proven specificity as target of PCR amplification favourably influences sensitivity and specificity. This comparative study demonstrates that primer selection plays a significant role in the diagnosis of PCP by PCR.

Oropharyngeal washings (Ophs) from 27 HIV infected patients (18 with P. carinii pneumonia, PCP, and 9 without PCP) were examined for P. carinii using morphological staining and DNA amplification with PCR-SHELA and nested PCR methods. The comparison of these techniques shows that 1. the amplification of P. carinii DNA is more sensitive than (and as specific as) morphological staining; 2. PCR-SHELA is less sensitive than (and as specific as) nested PCR.

To understand the way of reinfection of Pneumocystis carinii we have analyzed the genetic variation at the internal transcribed spacer (ITS) in DNA samples from bronchoalveolar lavage fluid of Italian HIV patients who had multiple episodes of P.carinii pneumonia. The presence of the same and/or a new type in both episodes suggest the possible occurrence of both reactivation of a previously acquired infection and reinfection from an exogenous source. Furthermore the occurrence of two different types in the same episode indicate that a mixed infection is common.

Summary. DNA amplification by the polymerase chain reaction (PCR) is a promising method for the detection of Pneumocystis carinii in immunosuppressed patients. The sensitivity and specificity of the PCR technique has been assessed in comparison with the immunofluoresence method (IF) on bronchoalveolar lavage fluid (BALF). Results correlated in 43 (78·8%) of 52 cases studied. P. carinii PCR gave positive results with BALF from all 32 patients found to have P. carinii pneumonia (PCP); IF gave positive results with 26 of them. PCR was more sensitive and as specific as IF. However, at the present time, we do not believe that it is clinically useful for detection of P. carinii in BALF samples. P. carinii DNA amplification by PCR should be reserved for testing IF-negative BALF samples from patients judged clinically to have PCP.

Data reported by Dr. Sing et al. ([3][1]) about Pneumocystis carinii carriage in immunocompetent adults with primary pulmonary disorders differ partially from our results. We have analyzed 81 bronchoalveolar lavage fluid samples (BALs) from 78 patients (37 male and 41 female; mean age, 57.8 years

A nested PCR which amplified a portion of the mitochondrial large-subunit rRNA gene of Pneumocystis carinii was used to detect P. carinii DNA in blood from patients with P. carinii pneumonia. P. carinii DNA was not detected in serum and was detected at low levels of blood cells.