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Despite use of tecovirimat since the beginning of the 2022 outbreak, few data have been published on its antiviral effect in humans. We here predict tecovirimat efficacy using a unique set of data in nonhuman primates (NHPs) and humans. We analyzed tecovirimat antiviral activity on viral kinetics in NHP to characterize its concentration–effect relationship in vivo. Next, we used a pharmacological model developed in healthy volunteers to project its antiviral efficacy in humans. Finally, a viral dynamic model was applied to characterize mpox kinetics in skin lesions from 54 untreated patients, and we used this modeling framework to predict the impact of tecovirimat on viral clearance in skin lesions. At human-recommended doses, tecovirimat could inhibit viral replication from infected cells by more than 90% after 3 to 5 days of drug administration and achieved over 97% efficacy at drug steady state. With an estimated mpox within-host basic reproduction number, R0, equal to 5.6, tecovirimat could therefore shorten the time to viral clearance if given before viral peak. We predicted that initiating treatment at symptom onset, which on average occurred 2 days before viral peak, could reduce the time to viral clearance by about 6 days. Immediate postexposure prophylaxis could not only reduce time to clearance but also lower peak viral load by more than 1.0 log10 copies/mL and shorten the duration of positive viral culture by about 7 to 10 days. These findings support the early administration of tecovirimat against mpox infection, ideally starting from the infection day as a postexposure prophylaxis. Despite its use since the beginning of the 2022 mpox outbreak, few data have been published on the antiviral effect of tecovirimat in humans. This study predicts the impact of early tecovirimat administration on the time to viral clearance in patients with mpox infection, using an integrative modeling approach that combines pre-clinical and clinical data. [ABSTRACT FROM AUTHOR]

We evaluated the accuracy of patient-collected skin lesions, oropharyngeal, and rectal swabs among 50 individuals enrolled in a study of mpox viral dynamics. We found that the performance of self-collected samples was similar to that of physician-collected samples, suggesting that self-sampling is a reliable strategy for diagnosing mpox. [ABSTRACT FROM AUTHOR]

The Chembio DPP (Dual Path Platform) Syphilis Screen & Confirm kit (https://chembio.com) is a rapid serologic test that can be used to diagnose yaws. We evaluated its capacity to detect patients with ulcers that tested PCR positive for Treponema pallidum subsp. pertenue. DPP detected 84% of ulcers that were positive by PCR. [ABSTRACT FROM AUTHOR]

Background: Evidence on the determinants of the magnitude of humoral responses and neutralizing titers in individuals with mild COVID-19 is scarce. Methods: In this cohort study of mild COVID-19 patients, we assessed viral load (VL) by RT-qPCR at two/three time points during acute infection, and anti-SARS-CoV-2 antibodies by ELISA and plasma neutralizing responses using a pseudovirus assay at day 60. Results: Seventy-one individuals (65% female, median 42 years old) were recruited and grouped into high viral load (VL) >7.5 Log10 copies/mL (n=20), low, VL ≤7.5 Log10 copies/mL (n=22), or as Non-early seroconverters with a positive PCR (n=20), and healthy individuals with a negative PCR (n=9). Individuals with high or low VL showed similar titers of total neutralizing antibodies at day 60, irrespective of maximal VL or viral dynamics. Non-early seroconverters had lower antibody titers on day 60, albeit similar neutralizing activity as the groups with high or low VL. Longer symptom duration and older age were independently associated with increased humoral responses. Conclusions: In mild SARS-CoV-2-infected individuals, the duration of symptoms and age (but not VL) contribute to higher humoral responses. [ABSTRACT FROM AUTHOR]

Background: In yaws-endemic areas, children with Treponema pallidum subsp. pertenue infection may suffer recurrent episodes due to either reinfection or relapse. However, the possibility of infection with other cutaneous ulcer causative agents and difficulties in interpreting standard laboratory results challenges the estimation of yaws recurrence rates. Methods: We estimated the rates of yaws recurrences in the Lihir Island (Papua New Guinea) using two approaches: passive surveillance based on a retrospective screening of electronic medical records of cutaneous ulcers diagnosed using serological testing between 2005 and 2016, and active surveillance conducted during a cross-sectional prevalence study which included PCR analyses of ulcers of all suspected cases of yaws. The risk of recurrent infection was assessed based on data from the passive surveillance analysis and using two Cox regression models (crude and multivariate), stratified by year of index episode. Data gathered from the active surveillance was used to characterize the recurrences and no hypothesis testing was performed. Results: The electronic medical records included 6,125 patients (7,889 ulcer episodes) with documented serological results of cutaneous ulcers of which1,486 were diagnosed with yaws. Overall, 1,246/6,125 patients (20.3%) presented more than once with a cutaneous ulcer, and 103/1,486 (6.7%) patients had multiple episodes of yaws. The risk of yaws recurrence significantly increased with age and was higher in patients with ≥3 recurrent episodes. In the active surveillance, we identified 50 individuals with recurrent cutaneous ulcer that had PCR results available for both the index and recurrent episode. Of 12 individuals with T. pallidum in the index ulcer, 8 (66%) had T. pallidum in subsequent assessments, relapse related to macrolide-resistance was identified in two of these cases. Conclusions: Our results confirm the need for active follow-up of yaws patients after treatment, particularly children and individuals with a history of recurrence. Author summary: Yaws is a neglected tropical disease produced by Treponema pallidum pertenue that causes skin ulcers in children living in remote rural areas of the South Pacific and West Africa. Children aged 5–15 and individuals with a history of recurrence are at higher risk of reinfection. Although yaws can be treated with single-dose azithromycin, some children present with recurrent cutaneous ulcers; however, the prevalence and risk factors for yaws recurrence are poorly known. Our analysis of skin ulcers in Papua New Guinea revealed that up to 20% of patients who presented to a health care facility in the Lihir island of Papua New Guinea with a cutaneous ulcer experienced a recurrent episode within the 6–36 months following treatment. Nearly all individuals with recurrent yaws were children aged 15 years or younger. Besides age, the number of previous ulcers was associated with a higher risk of recurrence. The molecular analysis revealed that among cases with T. pallidum at baseline that had a recurrence, this was often related to reinfection with the same microorganism. Our results confirm the need for active follow-up of young children diagnosed with cutaneous ulcers, with particular attention to those with younger age and previous history of recurrences. [ABSTRACT FROM AUTHOR]

Background No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19. Methods Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. Results A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (−1.41 vs −1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (−3.37 vs −3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported. Conclusions In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis is a neglected disease caused by different species of the protozoa Leishmania spp. Cutaneous lesions are the most common clinical manifestation. This disease is prevalent in tropical and subtropical areas, including the Mediterranean basin. In Spain, Leishmania (L.) infantum is the only endemic species, but imported cases are often diagnosed. Different classical parasitological methods can be performed for cutaneous leishmaniasis (CL) diagnosis; but currently molecular techniques serve as a relevant tool for the detection and characterization of Leishmania parasites. We aimed to evaluate clinical and epidemiological characteristics of CL diagnosed patients by real-time PCR in a tertiary hospital over a six-year period. Methodology/Principal findings: Clinical, epidemiological and microbiological data were retrospectively collected and analyzed. In our study, CL was confirmed in 59 (31.4%) out of 188 patients by real-time PCR, showing an increase over recent years: 11 cases of CL between 2014 and 2016 and 48 between 2017 and 2019. Real-time PCR was performed on skin swabs and/or biopsies samples, with a positivity of 38.5% and 26.5%, respectively. Results were 100% concordant when biopsy and skin swab were performed simultaneously. L. (L.) infantum was the most frequent species detected (50%), followed by L. (L.) major (45%) and Viannia subgenus (5%), which were detected only in imported cases. L. (L.) major was almost entirely detected in travelers/migrants from Morocco. Multiple and atypical skin lesions were more common in imported cases than in autochthonous cases (44.4% vs. 21.8%). Conclusions/Significance: An increase in both autochthonous and imported CL cases has been observed in past years in our hospital. Molecular techniques assist in improving CL diagnosis and characterization of the Leishmania species, mainly in imported cases. Author summary: Leishmaniasis is a neglected disease caused by different species of the genus Leishmania. This disease is prevalent in tropical and subtropical areas, including the Mediterranean basin. In Spain, the only endemic species is L. (L) infantum, although there are cases of imported leishmaniasis due to travel and migration of people from other endemic areas. Cutaneous lesions are the most common clinical form, but L. (L) infantum can also cause mucosal or visceral involvement. Although microscopic diagnosis and skin biopsy specimens are still used in routine diagnosis for cutaneous leishmaniasis, they are time-consuming and invasive, respectively. Currently, molecular techniques, such as real-time PCR, are very sensitive tools for the detection and identification of Leishmania parasites. In addition, the skin swab sample seems to be a non-invasive alternative for the diagnosis of cutaneous leishmaniasis. In the present work, we describe the clinical characteristics of 59 patients diagnosed by real-time PCR of cutaneous leishmaniasis, as well as the molecular epidemiology of the causative species. We show that there has been an increase in cutaneous leishmaniasis cases, both autochthonous and imported cases, over the study period. The presence of Leishmania species other than L. (L) infantum is also highlighted. [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis factor alpha (TNF-α) blockers are recognized as a risk factor for reactivation of granulomatous infections. Leishmaniasis has been associated with the use of these drugs, although few cases have been reported. Methodology: We performed a retrospective observational study including patients with confirmed leishmaniasis acquired in the Mediterranean basin that were under TNF-α blockers therapy at the moment of the diagnosis. Patients diagnosed in our hospital from 2008 to 2018 were included. Moreover, a systematic review of the literature was performed and cases fulfilling the inclusion criteria were also included. Principal findings: Forty-nine patients were analyzed including nine cases from our series. Twenty-seven (55.1%) cases were male and median age was 55 years. Twenty-five (51%) patients were under infliximab treatment, 20 (40.8%) were receiving adalimumab, 2 (4.1%) etanercept, one (2%) golimumab and one (2%) a non-specified TNF-α blocker. Regarding clinical presentation, 28 (57.1%) presented as cutaneous leishmaniasis (CL), 16 (32.6%) as visceral leishmaniasis (VL) and 5 (10.2%) as mucocutaneous leishmaniasis (MCL). All VL and MCL patients were treated with systemic therapies. Among CL patients, 13 (46.4%) were treated with a systemic drug (11 received L-AmB, one intramuscular antimonials and one miltefosine) while 14 (50%) patients were given local treatment (13 received intralesional pentavalent antimonials, and one excisional surgery). TNF-α blockers were interrupted in 32 patients (65.3%). After treatment 5 patients (10.2%) relapsed. Four patients with a CL (3 initially treated with local therapy maintaining TNF-α blockers and one treated with miltefosine) and one patient with VL treated with L-AmB maintaining TNF-α blockers. Conclusions: This data supports the assumption that the blockage of TNF-α modifies clinical expression of leishmaniasis in endemic population modulating the expression of the disease leading to atypical presentations. According to the cases reported, the best treatment strategy would be a systemic drug and the discontinuation of the TNF-α blockers therapy until clinical resolution. [ABSTRACT FROM AUTHOR]

Background Treponema pallidum subsp pertenue and Haemophilus ducreyi are causative agents of cutaneous ulcer (CU) in yaws-endemic regions in the tropics. However, a significant proportion of CU patients remain polymerase chain reaction (PCR) negative for both bacterial agents. We aimed to identify potential additional etiological agents of CU in a yaws-endemic region. Methods This population-based cohort study included children in Lihir Island (Papua New Guinea) examined during a yaws eradication campaign in October 2013–October 2014. All consenting patients with atraumatic exudative ulcers of >1 cm diameter were enrolled. Lesional swabs were collected for real-time PCR testing for T. pallidum subsp pertenue and H. ducreyi. We then performed shotgun whole DNA metagenomics sequencing on extracted DNA and taxonomically assigned shotgun sequences using a human microbiome reference. Results Sequence data were available for 122 samples. Shotgun sequencing showed high classification agreement relative to PCR testing (area under the curve for T. pallidum/H. ducreyi was 0.92/0.85, respectively). Clustering analysis of shotgun data revealed compositional clusters where the dominant species (median relative abundance ranged from 32% to 66%) was H. ducreyi (23% of specimens), T. pallidum subsp pertenue (16%), Streptococcus dysgalactiae (12%), Arcanobacterium haemolyticum (8%), and Corynebacterium diphtheriae (8%). Sample clustering derived from ulcer microbial composition did not show geographical patterns. Conclusions These data suggest a diverse etiology of skin ulcers in yaws-endemic areas, which may help design more accurate diagnostic tools and more effective antimicrobial treatment approaches to the cutaneous ulcer syndrome. [ABSTRACT FROM AUTHOR]

Background: There is no consensus for the best treatment of complex cutaneous leishmaniasis (CL). We aimed to describe a cohort of CL, focusing on liposomal amphotericin B (L-AmB) treatment outcome. Methods: We performed a retrospective study in Vall d'Hebron University Hospital (Barcelona, Spain). All patients with parasitologically proven CL diagnosed from 2012 to 2018 were included. Results: The analysis included 41 patients with CL. The median age was 39 years (IQR 12- 66); 12 (29%) were children, and 29 (71%) were men. Regarding treatment, 24 (59%) received local treatment, whereas 17 (41%) had complex CL and were offered intravenous systemic treatment. Sixteen patients received L-AmB; eight (50%) had adverse events, and three (19%) discontinued treatment for safety reasons. All cases were considered cured within the first year post-treatment. Conclusions: L-AmB for complex CL showed no treatment failures, offering an alternative treatment option for patients with complex CL. Clinicians should pay close attention to the potential adverse events of L-AmB and adopt an active drug safety surveillance scheme to rapidly detect reversible side effects. [ABSTRACT FROM AUTHOR]