Perception and Awareness about Monkeypox and Vaccination Acceptance in an At-Risk Population in Brescia, Italy: An Investigative Survey.

Before 2022, monkeypox virus (Mpox) infection in humans was seldom reported outside Africa. During the May 2022 outbreak, most cases were detected among men who have sex with men (MSM). Since Mpox is largely unknown to the general population, through a self-completion questionnaire, we investigated the behaviours and knowledge of our at-risk population belonging to the sexually transmitted infection (STI) outpatient clinic of the Infectious Diseases Unit of the ASST Spedali Civili of Brescia, Italy, between August and October 2022. Most patients that took part in the compilation are HIV positive MSM. The other participants were HIV-seronegative patients with other STIs. Overall, 144 questionnaires were compiled. Most of the participants were Italians (130;90%) and males (139;96.5%) between 30 and 60 years (118;82%). Almost all (136;94%) reported having heard about Mpox and more than half (80;56%) received information about the transmission. Twenty-four respondents (16%) received information from health professionals and 14 (10%) believed that the information received was complete. Although 41% of respondents thought they were at risk of getting the infection and 62% were afraid to get it, the majority (56%) did not increase the precautions taken. When asked if they would accept a vaccine to prevent the disease, more than a third (32%) of respondents expressed hesitation or complete refusal to be vaccinated. Based on our results, what emerges is that there is still a lack of knowledge and awareness about Mpox. To address this issue, targeted health promotion and education strategies that provide the necessary resources to reduce risk behaviours and enhance connections with healthcare professionals are needed.

Use of nebulized liposomal amphotericin B and posaconazole as antifungal prophylaxis in patients with severe SARS-CoV2 infection in intensive care unit.

PURPOSE: COVID-19 associated pulmonary aspergillosis (CAPA) is common and linked with high fatality rates. To assess the impact on the incidence and outcome of CAPA of an antifungal prophylaxis (AFP) we compared two cohorts of COVID-19 patients admitted to intensive care units (ICU) in Brescia, Italy, from January to August 2021. METHODS: The study cohort included all mechanically ventilated patients observed between April 2021 and August 2021 with SARS-CoV-2-pneumonia, who received AFP with oral posaconazole (200 mg every 6 h) and nebulized liposomal amphotericin B (50 mg every 2 weeks) from ICU admission to 7 days after discharge or, if applicable, until tracheostomy removal. The control cohort included COVID-19 patients admitted to the same ICU between January and March 2021 who did not receive any AFP. Subjects with CAPA at ICU admission were excluded. RESULTS: We included 270 patients, of whom 64 (23.7%) received AFP. In patients in the study group, CAPA-related mortality was significantly reduced (29% vs. 48% p = 0.04), as well as the incidence of CAPA (3.1% vs 12.1%, p = 0.03). Patients who developed CAPA were older (mean of 70-y-old vs 63-y-old, p < 0.001). One subject discontinued posaconazole due to an adverse reaction. Among the 46 patients who received it, only one patient reached an effective plasma concentration of posaconazole. CONCLUSION: AFP was associated with reduced incidence and mortality from CAPA and was well tolerated in patients with severe COVID-19. Posaconazole concentrations below the efficacy threshold in almost all patients may be attributable to drug interactions and prompt further studies to define its clinical significance.

PPE59 antibodies in tuberculous patients and potential use for diagnosis when assayed with other rapid biomarkers.

BACKGROUND: PPE 59, which is absent from bacillus Calmette Guérin (BCG) strains, seems to induce a humoral immune response in patients with tuberculosis (TB). Additional studies are needed to better evaluate this protein in immune response to tuberculosis. OBJECTIVES: To evaluate the response of antibodies to PPE59 in TB individuals, its combination with IgG response to other, previously tested mycobacterial antigens (Ag) and with sputum smear microbiology (SM) results. METHODS: We have cloned and expressed the rv3429 gene that encodes PPE59, then IgG, IgM, and IgA against PPE59 antigens measured by enzyme-linked immunosorbent assay (ELISA) in 212 sera samples obtained from the following subject cohorts: TB residents from Italy (79) and in Brazil (52); and an all-Brazilian cohort of 55 patients with other respiratory disorders; 10 patients infected with non-tuberculous mycobacteria, and 16 asymptomatic subjects. Drawing on results from a previous study(17) of serum samples from Brazilian subjects tested for IgG by ELISA against mycobacterial antigens ESAT-6, 16kDa, MT10.3, MPT-64 and 38kDa, the results were analysed in combination with those of the PPE59 and SM tests. FINDINGS: Keeping the specificity rate at 97%, the overall PPE59 IgA sensitivity was 42.7%, while IgG and IgM showed lower performance (p < 0.0001). Combining PPE59 IgA/16kDa IgG results increased sensitivity to 71%, and even higher rates when the results were combined with SM results (86.5%, p = 0.001), at 88.9% specificity. Positive IgA was associated with pulmonary image alterations of high TB probability (p < 0.05). MAIN CONCLUSIONS: Tests with TB patients found a moderate frequency of positivity for PPE59 IgA. However, the higher level of sensitivity attained in combination with PPE59 IgA/16kDa IgG/SM results unheard of before, although imperfect, suggests that this may be a potential additional tool for rapid detection of TB in low-resource areas.

Drivers determining tuberculosis disease screening yield in four European screening programmes: a comparative analysis.

BACKGROUND: The World Health Organization End TB Strategy emphasises screening for early diagnosis of tuberculosis (TB) in high-risk groups, including migrants. We analysed key drivers of TB yield differences in four large migrant TB screening programmes to inform TB control planning and feasibility of a European approach. METHODS: We pooled individual TB screening episode data from Italy, the Netherlands, Sweden and the UK, and analysed predictors and interactions for TB case yield using multivariable logistic regression models. RESULTS: Between 2005 and 2018 in 2 302 260 screening episodes among 2 107 016 migrants to four countries, the programmes identified 1658 TB cases (yield 72.0 (95% CI 68.6-75.6) per 100 000). In logistic regression analysis, we found associations between TB screening yield and age (≥55 years: OR 2.91 (95% CI 2.24-3.78)), being an asylum seeker (OR 3.19 (95% CI 1.03-9.83)) or on a settlement visa (OR 1.78 (95% CI 1.57-2.01)), close TB contact (OR 12.25 (95% CI 11.73-12.79)) and higher TB incidence in the country of origin. We demonstrated interactions between migrant typology and age, as well as country of origin. For asylum seekers, the elevated TB risk remained similar above country of origin incidence thresholds of 100 per 100 000. CONCLUSIONS: Key determinants of TB yield included close contact, increasing age, incidence in country of origin and specific migrant groups, including asylum seekers and refugees. For most migrants such as UK students and workers, TB yield significantly increased with levels of incidence in the country of origin. The high, country of origin-independent TB risk in asylum seekers above a 100 per 100 000 threshold could reflect higher transmission and re-activation risk of migration routes, with implications for selecting populations for TB screening.

Atypical monkeypox presentation in a previously vaccinated MSM HIV-positive adult.

The outbreak of monkeypox virus (MPXV) in non-endemic countries is an international public health emergency, and the diversity in manifestations poses challenges for early diagnosis and isolation. We describe an atypical case of monkeypox (MPX) in a 46-year-old homosexual male living with HIV. He reported 1-day duration fever, a lesion on his chin that, over a period of 18 days, had gradually enlarged and ulcerated. Biopsy examination performed at an external centre revealed pyoderma gangrenosum, unconfirmed at a subsequent biopsy. When he reported to our hospital outpatients' clinic the chin lesion had a diameter of 5 × 5 cm, necrotic margins and ulcerated base and signs of superinfection. He was admitted for further investigations. Three swabs collected from pharynx, skin and chin lesion resulted positive for MPXV. He had a favourable clinical course and was discharged soon after. Pending the achievement of optimal vaccination coverage in at-risk groups, early identification and isolation of infectious patients represent the cornerstones of the containment strategy. Atypical cases of MPX manifestations are not uncommon, particularly in patients with HIV infection. A high level of suspicion should be maintained to identify infectious cases at an early stage and avoid further spread of the infection.

Strongyloides stercoralis infection: an underlying cause of invasive bacterial infections of enteric origin. Results from a prospective cross-sectional study of a northern Italian tertiary hospital.

PURPOSE OF THE STUDY: We assessed the prevalence of S. stercoralis in a cohort of inpatients with invasive bacterial infections of enteric origin to investigate whether the parasite may facilitate these bacterial infections even in the absence of larval hyperproliferation. METHODS: We performed a prospective cross-sectional study in a hospital in northern Italy. Subjects admitted due to invasive bacterial infection of enteric origin and potential previous exposure to S. stercoralis were systematically enrolled over a period of 10 months. S. stercoralis infection was investigated with an in-house PCR on a single stool sample and with at least one serological method (in-house IFAT and/or ELISA Bordier). Univariate, bi-variate and logistic regression analyses were performed. RESULTS: Strongyloidiasis was diagnosed in 14/57 patients (24.6%; 95% confidence interval 14.1-37.8%) of which 10 were Italians (10/49, 20.4%) and 4 were migrants (4/8, 50.0%). Stool PCR was performed in 43/57 patients (75.4%) and no positive results were obtained. Strongyloidiasis was found to be significantly associated (p ≤ 0.05) with male gender, long international travels to areas at higher endemicity, deep extra-intestinal infectious localization and solid tumors. In the logistic regression model, increased risk remained for the variables deep extra-intestinal infectious localization and oncologic malignancy. CONCLUSIONS: Our findings suggest a new role of chronic strongyloidiasis in favoring invasive bacterial infections of enteric origin even in the absence of evident larval dissemination outside the intestinal lumen. Further well-designed studies should be conducted to confirm our results, and possibly establish the underlying mechanisms.

Mycobacterial skin infection.

PURPOSE OF REVIEW: The aim of this article is to review the most recent evidences concerning mycobacterial skin infections, limiting the period of literature research to 2020--2021. RECENT FINDINGS: Mycobacterial skin infections include a heterogeneous group of cutaneous diseases.Cutaneous tuberculosis is usually the result of hematogenous dissemination or spread from underlying foci and it must be distinguished from tuberculids, resulting from the immunological reaction to Mycobacterium tuberculosis antigens. Leprosy prevalence was drastically reduced after introduction of multidrug therapy in the 1980 s, but cases are still reported due to underdiagnosis, and animal and environmental reservoirs. Recent advances concentrate in the diagnostic field. Specific guidelines for the treatment of nontuberculous mycobacteria skin infections are missing and surgical procedures may be required. Prognosis is better as compared to nontuberculous mycobacteria lung disease. Rapid laboratory-confirmed diagnosis of Buruli ulcer may be achieved by the IS2404 PCR. Among new drugs, telacebec is promising in terms of potency, shorter duration and tolerability in animal studies. A clinical trial in humans is planned. SUMMARY: Mycobacterial cutaneous lesions are nonpathognomonic and clinical suspicion must be confirmed by culture or molecular detection. Long-course multidrug treatment is required based on susceptibility tests. Surgical intervention may also be required. Rehabilitation and psychosocial support reduce long-term physical and mental consequences mostly in Buruli ulcer and leprosy.

Adapting teaching and learning in times of COVID-19: a comparative assessment among higher education institutions in a global health network in 2020.

BACKGROUND: This research examines the ways in which higher education institutions (HEIs) across the tropEd Network for Education in International Health (tropEd) began to adapt their teaching and learning approaches in response to the COVID-19 pandemic in 2020. Already during this early phase of the pandemic HEIs' responses demonstrate global health approaches emphasising cooperation and communication, rather than national health driven strategies that emphasise quarantine and control. Key lessons learnt for multiple dimensions of teaching and learning in global health are thus identified, and challenges and opportunities discussed. METHODS: Data collection includes a cross-sectional online survey among tropEd member institutions (n = 19) in mid-2020, and a complementary set of open-ended questions generating free-text responses (n = 9). Quantitative data were analysed using descriptive statistics, textual data were analysed using a Framework Analysis approach. RESULTS: While early on in the pandemic the focus was on a quick emergency switch to online teaching formats to ensure short-term continuity, and developing the administrative and didactic competence and confidence in digital teaching, there is already recognition among HEIs of the necessity for more fundamental quality and longer-term reforms in higher education in global health. Alongside practical concerns about the limitations of digital teaching, and declines in student numbers, there is a growing awareness of opportunities in terms of inclusivity, the necessity of cross-border cooperation, and a global health approach. The extent to which the lack of physical mobility impacts HEI programmes in global health is debated. CONCLUSION: The COVID-19 pandemic has brought about preventive measures that have had a considerable impact on various dimensions of academic teaching in global health. Going forward, international HEIs' experiences and response strategies can help generate important lessons for academic institutions across different settings worldwide.

Tests for tuberculosis infection: landscape analysis.

BACKGROUND: Only the tuberculin skin test (TST) and two interferon-γ release assays (IGRAs), QuantiFERON-TB Gold In-Tube and T-SPOT.TB, are currently endorsed by the World Health Organization as tests for tuberculosis (TB) infection. While IGRAs are more specific than the TST, they require sophisticated laboratory infrastructure and are costly to perform. However, both types of tests have limited performance to predict development of active TB. Tests with improved predictive performance and operational characteristics are needed. METHODS: We reviewed the current landscape of tests for TB infection identified through a web-based survey targeting diagnostic manufacturers globally. RESULTS: We identified 20 tests for TB infection: 15 in vitro tests and five skin tests. 13 of the in vitro tests are whole-blood IGRAs and 14 use early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), with or without additional antigens. 10 of the tests are based on assays other than an ELISA, such as a fluorescent lateral flow assay that requires less manual operation and shorter assay time and hence is more suitable for decentralisation compared with the existing IGRAs. Four of the five skin tests use ESAT-6 and CFP-10 proteins, while the remaining test uses a new antigen that is specific to Mycobacterium tuberculosis complex. CONCLUSIONS: New tests have the potential to improve accuracy, operational characteristics and end-user access to tests for TB infection. However, published data in various populations and settings are limited for most new tests. Evaluation of these new tests in a standardised design would facilitate their endorsement and programmatic scale-up.

Framework for the evaluation of new tests for tuberculosis infection.

The scale-up of tuberculosis (TB) preventive treatment (TPT) must be accelerated to achieve the targets set by the United Nations High-level Meeting on TB and the End TB Strategy. The scale-up of effective TPT is hampered by concerns about operational challenges to implement the existing tests for TB infection. New simpler tests could facilitate the scale-up of testing for TB infection. We present a framework for evaluation of new immunodiagnostic tests for the detection of TB infection, with an aim to facilitate their standardised evaluation and accelerate adoption into global and national policies and subsequent scale-up. The framework describes the principles to be considered when evaluating new tests for TB infection and provides guidance to manufacturers, researchers, regulators and other users on study designs, populations, reference standards, sample size calculation and data analysis and it is also aligned with the Global Strategy for TB Research and Innovation adopted by the World Health Assembly in 2020. In addition, we briefly describe technical issues that should be considered when evaluating new tests, including the safety for skin tests, costs incurred by patients and the health system, and operational characteristics.

Strongyloides infection manifested during immunosuppressive therapy for SARS-CoV-2 pneumonia.

BACKGROUND: SARS-CoV-2 pandemic has posed formidable public health and clinical challenges. The use of immunosuppressive agents, such as high dose corticosteroids and cytokine inhibitors (e.g., Tocilizumab) has been suggested to contrast the hyperinflammatory process involved in the pathogenesis of the severe disease, with conflicting evidence. Among the drawbacks of immunosuppressive therapy, the risk of reactivation of latent infections, including parasitic infestations, is to be considered. CASE PRESENTATION: We report a case of a 59-year-old Italian patient treated with high dose intravenous dexamethasone and two intravenous doses of Tocilizumab for interstitial bilateral pneumonia associated with SARS-CoV-2 infection who developed itching, abdominal pain, and an increased eosinophil count. Stool examination confirmed the presence of S. stercoralis larvae. The patient was treated with a 4-day course of Ivermectin with full recovery. DISCUSSION: We report the first case of S. stercoralis infection following an 11-day treatment with high-dose steroids and Tocilizumab for severe COVID-19. Clinicians should be aware of the risk of strongyloidiasis as a complication of the treatment for severe COVID-19.

Importance of mitigation measures for hospital transmission of SARS-CoV-2 at the onset of the epidemic: the experience of Brescia, Northern Italy.

PURPOSE: Since the first Italian case of SARS-CoV-2 was detected in Lombardy (Northern Italy)  Italy quickly became one of the worst-affected European countries, with a severe impact on health-care workers (HCWs). In the first epidemic, HCWs accounted for 12% of all national COVID-19 cases. We evaluated the burden of COVID-19 among HCWs and other non-health-care workers (nHCWs) in a large Italian hospital. METHODS: From March 1st to May 31st 2020, we performed a retrospective study at ASST Civil Hospital, in the Province of Brescia, Lombardy. The study population included all hospital personnel (n = 9265), categorized by professional status. RESULTS: A SARS-CoV-2 test was performed in 3572 workers (38.5%), with a positive result in 552 (5.9% of all hospital personnel). The temporal trend of SARS-CoV-2 cases in hospital staff broadly reflected that in the community, with a great majority of infections occurred during March 2020 (87.7%). From April onward, a steep decrease of positive cases was observed among hospital personnel, while in the community the decrease was much slower. Medical doctors (8.9%) and nurses (8.5%) were the most affected professional categories with a significantly higher risk of SARS-CoV-2 infection (OR 1.436 and OR 1.410, respectively p < 0.0001). HCWs in COVID-19 units presented a significantly higher risk of infection compared to HCWs in non-COVID units (p < 0.001). CONCLUSION: HCWs were severely affected by the COVID-19 epidemic, probably associated with an overwhelming burden of work and lack of preparedness in prevention of nosocomial transmission of the infection. The rapid decrease of COVID-19 spread in the hospital, registered before the one in the community, suggests that the adopted preventive measures were effective.

Factors associated with unfavourable treatment outcomes in people with HIV-associated tuberculosis in Armenia, 2015 to 2019.

To evaluate factors associated with tuberculosis (TB) treatment outcomes in human Immunodeficiency Virus-Associated (HIV) TB patients in Armenia, we conducted a nation-wide cohort study using routine programmatic data of all HIV-associated TB patients receiving TB treatment with first- or second-line drugs from 2015 to 2019. Data were obtained from the TB and HIV electronic databases. We analysed occurrence of the combined unfavourable outcome (failure, lost to follow-up, death and not evaluated) and death separately, and factors associated with both outcomes using Cox regression. There were 320 HIV-associated TB patients who contributed a total of 351 episodes of TB treatment. An unfavourable TB treatment outcome was registered in 155 (44.2%) episodes, including 85 (24.2%) due to death, 38 (10.8%) lost to follow up, 13 (3.7%) failure and 19 (5.4%) not evaluated. Multivariable analysis showed that receipt of Antiretroviral Treatment (ART) [ART start before TB treatment: adjusted hazard ratio (aHR)=0.3, 95% confidence interval (CI): 0.2-0.5, aHR=, 95% CI:, 95% CI:, 95% CI:TB meningitis (aHR=4.4, 95% CI: 1.6-11.9) increased the risk. The risk of death was affected by the same factors as above in addition to the low BMI (aHR=2.5, 95% CI: 1.3-4.5) and drug resistance (aHR=2.3, 95% CI: 1.0-5.4). In the subsample of episodes receiving ART, history of interruption of ART during TB treatment increased the risk of unfavourable outcome (aHR=2.1 95% CI: 1.2-3.9), while ART start during TB treatment was associated with lower risk of both unfavourable outcome (within first 8 weeks: aHR: 0.5, 95% CI: 0.3-0.9; after 8 weeks: aHR: 0.4, 95% CI: 0.2-1.0) and death (within first 8 weeks: aHR: 0.2, 95% CI: 0.1-0.4; after 8 weeks: aHR: 0.1, 95% CI: 0.01-0.3). The rates of unfavourable TB treatment outcomes, and death in particular, among HIV-associated TB patients in Armenia are high. Our findings emphasize the protective effect of ART and the importance of proper management of cases complicated by drug resistance or meningitis.

Factors associated with unfavourable treatment outcomes among people with rifampicin-resistant tuberculosis in Armenia, 2014-2017.

Rifampicin-Resistant/Multidrug-Resistant Tuberculosis (RR/MDR-TB) is recognized as a major public health concern globally. In Armenia, the proportion of RR/MDR-TB is increasing among all people affected with TB. We conducted a nationwide cohort study involving analysis of programmatic data to investigate the rates of and factors associated with unfavourable treatment outcomes among patients with RR/MDR-TB registered by the national TB programme from 2014 to 2017 in Armenia. We used Cox regression to identify factors associated with the outcome. Among 451 RR/MDR-TB patients, 80% were men and median age was 46 years. Of them, 53 (11.8%) had Extensively Drug-Resistant Tuberculosis (XDR-TB) and 132 (29.3%) had pre-XDR-TB. Almost half (224, 49.7%) of the patients had unfavourable treatment outcome, which included 26.8% Loss To Follow-Up (LTFU), 13.3% failures and 9.5% deaths. In multivariable analysis, people with pre-XDR-TB [adjusted Hazard Ratio [aHR] 3.13, 95% confidence intervals [CI] 2.16-4.55] and XDR-TB (aHR 4.08, 95% CI 2.45-6.79) had a higher risk of unfavourable outcomes. Patients receiving home-based treatment (71/451, 15.7%) and treatment with new drugs (172/451, 38.1%) had significantly lower risk (aHR 0.45, 95% CI 0.28-0.72 and aHR 0.26, 95% CI 0.18-0.39) of unfavourable treatment outcome.  The proportion of MDR-TB patients reaching favourable treatment outcome in Armenia was substantially lower than the recommended level (75%). The most common treatment outcome was LTFU indicating the need for further assessment of underlying determinants. Home-based treatment looks promising and future studies are required to see if expanding it to all RR/MDR-TB patients is feasible and cost-effective.

Pharmacokinetic study of two different rifabutin doses co-administered with lopinavir/ritonavir in African HIV and tuberculosis co-infected adult patients.

BACKGROUND: This study aimed to assess the pharmacokinetic profile of 150 mg rifabutin (RBT) taken every other day (every 48 h) versus 300 mg RBT taken every other day (E.O.D), both in combination with lopinavir/ritonavir (LPV/r), in adult patients with human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection. METHODS: This is a two-arm, open-label, pharmacokinetic, randomised study conducted in Burkina Faso between May 2013 and December 2015. Enrolled patients were randomised to receive either 150 mg RBT EOD (arm A, 9 subjects) or 300 mg RBT EOD (arm B, 7 subjects), both associated with LPV/r taken twice daily. RBT plasma concentrations were evaluated after 2 weeks of combined HIV and TB treatment. Samples were collected just before drug ingestion and at 1, 2, 3, 4, 6, 8, and 12 h after drug ingestion to measure plasma drug concentration using an HPLC-MS/MS assay. RESULTS: The Cmax and AUC0-12h medians in arm A (Cmax = 296 ng/mL, IQR: 205-45; AUC0-12h = 2528 ng.h/mL, IQR: 1684-2735) were lower than those in arm B (Cmax = 600 ng/mL, IQR: 403-717; AUC0-12h = 4042.5 ng.h/mL, IQR: 3469-5761), with a statistically significant difference in AUC0-12h (p = 0.044) but not in Cmax (p = 0.313). No significant differences were observed in Tmax (3 h versus 4 h). Five patients had a Cmax below the plasma therapeutic limit (< 300 ng/mL) in the 150 mg RBT arm, while the Cmax was above this threshold for all patients in the 300 mg RBT arm. Additionally, at 48 h after drug ingestion, all patients had a mycobacterial minimum inhibitory concentration (MIC) above the limit (> 64 ng/mL) in the 300 mg RBT arm, while 4/9 patients had such values in the 150 mg RBT arm. CONCLUSION: This study confirmed that the 150 mg dose of rifabutin ingested EOD in combination with LPV/r is inadequate and could lead to selection of rifamycin-resistant mycobacteria. TRIAL REGISTRATION: PACTR201310000629390, 28th October 2013.

Pharmacokinetics of plasma lopinavir and ritonavir in tuberculosis-HIV co-infected African adult patients also receiving rifabutin 150 or 300 mg three times per week.

BACKGROUND: To evaluate the pharmacokinetic of plasma lopinavir (LPV) and ritonavir (RTV) when co-administered with three times weekly (TPW) rifabutin (RBT) at a dose of either 150 or 300 mg in African tuberculosis (TB) and HIV co-infected adult patients. METHODS: This is a pharmacokinetic study conducted in Ouagadougou among patients treated with a standard dosage of LPV/RTV 400/100 mg twice daily and RBT 150 mg TPW (arm A = 9 patients) or rifabutin 300 mg TPW (arm B = 7 patients) based regimens. Patients were recruited from the Bogodogo and Kossodo district hospitals in Ouagadougou from May 2013 to December 2015. Study inclusion criteria were that the patients were between 18 and 60 years of age, HIV-1 infected with pulmonary tuberculosis confirmed or suspected. Subsequent blood samples for pharmacokinetic monitoring were collected at 1, 2, 3, 4, 6, 8 and 12 h after combined drug ingestion for plasma drug monitoring using HPLC/MS assays. RESULTS: The medians LPV Cmax and Tmax were respectively, 20 µg/mL and 4 h for the RBT 150 mg group (arm A) and 7.7 µg/mL and 3 h for the RBT 300 mg group (arm B). The AUC0-12 of LPV was 111.8 µg h/mL in patients belonging to arm A versus 69.9 µg/mL for those in arm B (p = 0.313). The C0 of LPV was lower than 4 µg/mL in three patients receiving RBT 300 mg. Of note, the RTV plasma concentrations were nearly halved among patients on RBT 300 mg compared to those on lower RBT doses. The AUC0-12 of RTV in arm A was 12.7 µg h/mL versus 6.6 µg h/ml in arm B (p = 0.313). CONCLUSION: In our study, the pharmacokinetic of LPV and RTV was found to be highly variable when coadministrated with RBT 150 mg or 300 mg three times per week. There is a need for specific large study to verify clinical and virological effects of this variation, especially when coadministrated with RBT of 300 mg TPW, and to prevent viral resistance in response to under-dosing of LPV. Trial registration PACTR201310000629390. Registered 28 October 2013, http://www.pactr.org/.

Multidisciplinary approach to prostatitis.

The modern clinical research on prostatitis started with the work of Stamey and coworkers who developed the basic principles we are still using. They established the segmented culture technique for localizing the infections in the males to the urethra, the bladder, or the prostate and to differentiate the main categories of prostatitis. Such categories with slight modifications are still used according to the NIH classification: acute bacterial prostatitis, chronic bacterial prostatitis, Chronic Pelvic Pain Syndrome (CPPS) and asymptomatic prostatitis. Prostatic inflammation is considered an important factor in influencing both prostatic growth and progression of symptoms of benign prostatic hyperplasia and prostatitis. Chronic inflammation/neuroinflammation is a result of a deregulated acute phase response of the innate immune system affecting surrounding neural tissue at molecular, structural and functional levels. Clinical observations suggest that chronic inflammation correlates with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH) and an history of clinical chronic prostatitis significantly increases the odds for prostate cancer. The NIHNIDDK classification based on the use of the microbiological 4- glasses localization test or simplified 2-glasses test, is currently accepted worldwide. The UPOINT system identifies groups of clinicians with homogeneous clinical presentation and is used to recognize phenotypes to be submitted to specific treatments. The UPOINTS algorithm implemented the original UPOINT adding to the urinary domains (U), psycho-social (P), organspecific (O), infection (I), neurological (N), muscle tension and tenderness (T) a further domain related to sexuality (S). In fact sexual dysfunction (erectile, ejaculatory, libido loss) has been described in 46-92% of cases with a high impact on the quality of life of patients with CP/CPPS. Prostatic ultrasound represents the most popular imaging test in the work-up of either acute and chronic prostatitis although no specific hypo-hyperechoic pattern has been clearly associated with chronic bacterial prostatitis and CPPS. Use of a digital-processing software to calculate the extension of prostatic calcification area at ultrasound demonstrated a higher percentage of prostatic calcification in patients with chronic bacterial prostatitis. Multiparametric Magnetic Resonance Imaging (mpMRI) is the current state-of-the art imaging modality in the assessment of patients with prostate cancer although a variety of benign conditions, including inflammation, may mimic prostate cancer and act as confounding factors in the discrimination between neoplastic and non-neoplastic lesions. Bacteria can infect prostate gland by: ascending the urethra, reflux of urine into the prostatic ducts, direct inoculation of bacteria through inserted biopsy needles or hematogenous seeding. Enterobacteriaceae are the predominant pathogens in acute and chronic bacterial prostatitis, but an increasing role of Enterococci has been reported. Many strains of these uropathogens exhibit the ability to form biofilm and multidrug- resistance. Sexually Transmitted Infections (STI) agents, in particular Chlamydia trachomatis and Mycoplasma genitalium, have been also considered as causative pathogens of chronic bacterial prostatitis. On the contrary the effective role in genital diseases of other "genital mycoplasmas" is still a much debated issue. Sexually Transmitted Infections agents should be investigated by molecular methods in both patient and sexual partner. "Next generation" investigations, such as cytokine analysis, cytological typing of immune cells could help stratifying the immune response. Epigenetic dysregulation of inflammatory factors should be investigated according to systemic and compartment-specific signals. The search for biomarkers should also include evaluation of hormonal pathways, as measurement of estrogen levels in semen. Antimicrobials are the first line agents for the treatment of bacterial prostatitis. The success of antimicrobial treatment depends on the antibacterial activity and the pharmacokinetic characteristics of the drug which must reach high concentrations in prostate secretion and prostate tissue. Acute bacterial prostatitis can be a serious infection with a potential risk for urosepsis For iInitial treatment of severely ill patients, intravenous administration of high doses of bactericidal antimicrobials, such as broad-spectrum penicillins, third-generation cephalosporins or fluoroquinolones, is recommended in combination with an aminoglycoside. Use of piperacillin-tazobactam and meropenem is justified in presence of multiresistant gramnegative pathogens. The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. For the treatment of Chlamydial prostatitis macrolides were shown to be more effective than fluoroquinolones, whereas no differences were observed in microbiological and clinical efficacy between macrolides and tetracyclines for the treatment of infections caused by intracellular pathogens. Aminoglycosides and fosfomycin could be considered as a therapeutic alternative for the treatment of quinolone resistant prostatitis. Use of alpha-blockers in CP/CPPS patients with urinary symptoms and analgesics +/- non steroidal anti-inflammatory drugs (NSAID), in presence of pain demonstrated a reduction of symptoms reduction and an improvement of quality of life, although long term use of NSAID is limited by side effect profile. However, the multimodal therapeutic regimen by contemporary use of alphablockers, antibiotics and anti-inflammatory showed a better control of prostatitis symptoms than single drug treatment. Novel therapeutic substances for the treatment of pain, such as the cannabinoid anandamide would be highly interesting to test. An alternative for the treatment of chronic prostatitis/chronic pelvic pain syndrome is phytotherapy, as primary therapy or in association with other drugs. Quercetin, pollen extract, extract of Serenoa repens and other mixtures of herbal extracts showed a positive effect on symptoms and quality of life without side effects. The association of CP/CPPS with alterations of intestinal function has been described. Diet has its effects on inflammation by regulation of the composition of intestinal flora and direct action on the intestinal cells (sterile inflammation). Intestinal bacteria (microbiota) interacts with food influencing the metabolic, immune and inflammatory response of the organism. The intestinal microbiota has protective function against pathogenic bacteria, metabolic function by synthesis of vitamins, decomposition of bile acids and production of trophic factors (butyrate), and modulation of the intestinal immune system. The alteration of the microbiota is called "dysbiosis" causing invasive intestinal diseases pathologies (leaky gut syndrome and food intolerances, irritable bowel syndrome or chronic inflammatory bowel diseases) and correlating with numerous systemic diseases including acute and chronic prostatitis. Administration of live probiotics bacteria can be used to regulate the balance if intestinal flora. Sessions of hydrocolontherapy can represent an integration to this therapeutic approach. Finally, microbiological examination of sexual partners can offer supplementary information for treatment.

An evaluation framework for new tests that predict progression from tuberculosis infection to clinical disease.

Novel accurate tests are needed that identify individuals infected with Mycobacterium tuberculosis who have incipient disease and are likely to develop clinical tuberculosis (TB) in the near future to allow for targeted preventive treatment beyond the current risk groups. Recently, a target product profile was developed that outlines the minimal and optimal characteristics for such an incipient TB test. We describe an evaluation framework for generating evidence to inform the development of policy guidance for the use of such a new test by the World Health Organization. Two research objectives are addressed. 1) The predictive ability of an incipient TB test should be assessed in clinical evaluation studies that include the intended target population and follow-up of sufficient duration to observe whether individuals do or do not progress to clinical TB disease. 2) Studies are needed to evaluate the test under routine programmatic conditions and measure its impact on patient- or health-system-important outcomes. For both research objectives, study designs, methods and analysis are described, with the intent to inform the clinical development plans of test manufacturers, researchers and funders.

Implementation of tuberculosis prevention for exposed children, Burkina Faso.

OBJECTIVE: To develop and test a simple system for recording and reporting the diagnosis and treatment of latent tuberculosis infection and to compare the effects of passive and active tracing of child contacts on indicators of such infection. METHODS: We revised Burkina Faso's latent tuberculosis infection register and quarterly tuberculosis reporting form. Subsequently, coverage of the routine screening of contacts, who were younger than five years, for active tuberculosis and the corresponding percentages of such contacts who, if eligible, initiated preventive therapy were measured, nationwide, between 1 April 2016 and 31 March 2017. In 2016, we evaluated indicators of latent tuberculosis infection in the Hauts-Bassins region before and after community health workers had begun the active tracing of contacts who were younger than five years. FINDINGS: In Burkina Faso, during our study period, 3717 cases of pulmonary tuberculosis and 1166 corresponding contacts who were younger than five years were reported as the result of routine screening and passive contact tracing. The overall contact:index ratio was 0.31 and corresponding screening coverage was 82.0% (956/1166) and proportion of children starting on preventive treatment was 90.5% (852/941). Active tracing in Hauts-Bassins led to a substantially higher contact/index ratio (1.83) and screening coverage (99.3%; 145/146). CONCLUSION: The newly established recording and reporting system proved feasible and user-friendly and allowed measurement of global indicators of latent tuberculosis infection. Compared with active tracing, passive tracing led to much lower estimates of the numbers of child contacts.

Mycobacterium decipiens sp. nov., a new species closely related to the Mycobacterium tuberculosis complex.

Two mycobacterial strains with close similarity to the Mycobacterium tuberculosis complex (MTBC) were isolated from cutaneous lesions of patients in the USA and Italy. At the phenotypic level, similarities to the MTBC included slow growth rate, rough morphotype of the unpigmented colonies and nearly identical high-performance liquid chromatography profiles of mycolic acids. In contrast to the MTBC, the strains were niacin- and nitrate-negative, and catalase-positive both at 68 °C and in semi-quantitative tests. The clinical isolates were more closely related to M. tuberculosis than to any other known mycobacterium and scored positive with commercial DNA probes (Hologic AccuProbe M. tuberculosis). Both average nucleotide identity and genome-to-genome distance suggested the strains are different from the MTBC. Therefore, given the distinguishing phenotypic and genomic-scale differences, we submit that the strains belong to a new species we have named Mycobacteriumdecipiens with type strain TBL 1200985T (=ATCC TSD-117T=DSM 105360T).