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PURPOSE: To report a rare non-endemic case of Leishmania aethiopica in Washington DC. CASE REPORT: A 68-year-old female presented for a routine examination with a complaint of right upper eyelid lesions for the past 5 months. On examination, a cluster of elevated and erythematous lesions extending from the medial canthus to the brow area of the right eye were seen. Initial treatment with Valtrex based on a suspected viral etiology failed. Although a biopsy was recommended at this time, the patient declined, and subsequent workup included nasolacrimal duct irrigation, blood work to rule out autoimmune etiology, a course of doxycycline, and an MRI, which yielded no improvement. Upon progression of the lesions into persistent plaques on the eyelids, a punch biopsy was performed, confirming leishmaniasis. The patient was then started on a 28-day course of oral miltefosine which led to complete resolution of her symptoms. CONCLUSION: This case underlines the importance of a broad differential including non-endemic diseases, particularly in urban areas with frequent patient travel. Furthermore, the delayed punch biopsy in this case highlights the importance of patient counseling to ensure prompt diagnosis and treatment.
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Detailed characterization of transmitted HIV-1 variants in Uganda is fundamentally important to inform vaccine design, yet studies on the transmitted full-length strains of subtype D viruses are limited. Here, we amplified single genomes and characterized viruses, some of which were previously classified as subtype D by sub-genomic pol sequencing that were transmitted in Uganda between December 2006 to June 2011. Analysis of 5' and 3' half genome sequences showed 73% (19/26) of infections involved single virus transmissions, whereas 27% (7/26) of infections involved multiple variant transmissions based on predictions of a model of random virus evolution. Subtype analysis of inferred transmitted/founder viruses showed a high transmission rate of inter-subtype recombinants (69%, 20/29) involving mainly A1/D, while pure subtype D variants accounted for one-third of infections (31%, 9/29). Recombination patterns included a predominance of subtype D in the gag/pol region and a highly recombinogenic envelope gene. The signal peptide-C1 region and gp41 transmembrane domain (Tat2/Rev2 flanking region) were hotspots for A1/D recombination events. Analysis of a panel of 14 transmitted/founder molecular clones showed no difference in replication capacity between subtype D viruses (n = 3) and inter-subtype mosaic recombinants (n = 11). However, individuals infected with high replication capacity viruses had a faster CD4 T cell loss. The high transmission rate of unique inter-subtype recombinants is striking and emphasizes the extraordinary challenge for vaccine design and, in particular, for the highly variable and recombinogenic envelope gene, which is targeted by rational designs aimed to elicit broadly neutralizing antibodies.
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Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/genética , Heterosexualidad/estadística & datos numéricos , Adulto , Linfocitos T CD4-Positivos/citología , Femenino , Variación Genética , Genoma Viral/genética , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , VIH-1/clasificación , VIH-1/aislamiento & purificación , VIH-1/fisiología , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Recombinación Genética , Uganda/epidemiología , Carga Viral , Replicación Viral , Adulto JovenRESUMEN
Most studies of HIV-1 transmission have focused on subtypes B and C. In this study, we determined the genomic sequences of the transmitted founder (TF) viruses from acutely infected individuals enrolled between 2005 and 2011 into IAVI protocol C in Rwanda and have compared these isolates to viruses from more recent (2016-2019) acute/early infections in three at risk populations - MSM, high risk women (HRW), and discordant couples (DC). For the Protocol C samples, we utilized near full-length single genome (NFLG) amplification to generate 288 HIV-1 amplicons from 26 acutely infected seroconverters (SC), while for the 21 recent seroconverter samples (13 from HRW, two from DC, and six from MSM), we PCR amplified overlapping half-genomes. Using PacBio SMRT technology combined with the MDPseq workflow, we performed multiplex sequencing to obtain high accuracy sequences for each amplicon. Phylogenetic analyses indicated that the majority of recent transmitted viruses from DC and HRW clustered within those of the earlier Protocol C cohort. However, five of six sequences from the MSM cohort branched together and were greater than 97% identical. Recombination analyses revealed a high frequency (6/26; 23%) of unique inter-subtype recombination in Protocol C with 19% AC and 4% CD recombinant viruses, which contrasted with only 6.5% of recombinants defined by sequencing of the pol gene previously. The frequency of recombinants was significantly higher (12/21; 57%) in the more recent isolates, although, the five related viruses from the MSM cohort had identical recombination break points. While major drug resistance mutations were absent from Protocol C viruses, 4/21 of recent isolates exhibited transmitted nevirapine resistance. These results demonstrate the ongoing evolution and increased prevalence of recombinant and drug resistant transmitted viruses in Rwanda and highlight the importance of defining NFLG sequences to fully understand the nature of TF viruses and in particular the prevalence of unique recombinant forms (URFs) in transmission cohorts.
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Basaloid squamous cell carcinoma (BSCC) is a poorly differentiated variant of squamous cell carcinoma (SCC) with distinct morphologic characteristics. Yet, there are no clearly defined guidelines established for management. BSCC in the esophagus is a very rare entity, with the proportion of esophageal BSCC ranging from 0.068% to 11%. This wide range is thought to be secondary to difficulty making the diagnosis on small biopsy specimens and the lack of a universally defined proportion of BSCC components necessary to make the diagnosis. We present the case of a 57-year-old African American female, who underwent esophagogastroduodenoscopy (EGD) after an abnormal barium swallow in the setting of two months history of dysphagia and weight loss and was diagnosed with BSCC of the esophagus on histopathology.
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HIV-1 transmission is associated with a severe bottleneck in which a limited number of variants from a pool of genetically diverse quasispecies establishes infection. The IAVI protocol C cohort of discordant couples, female sex workers, other heterosexuals and men who have sex with men (MSM) present varying risks of HIV infection, diverse HIV-1 subtypes and represent a unique opportunity to characterize transmitted/founder viruses (TF) where disease outcome is known. To identify the TF, the HIV-1 repertoire of 38 MSM participants' samples was sequenced close to transmission (median 21 days post infection, IQR 18-41) and assessment of multivariant infection done. Patient derived gag genes were cloned into an NL4.3 provirus to generate chimeric viruses which were characterized for replicative capacity (RC). Finally, an evaluation of how the TF virus predicted disease progression and modified the immune response at both acute and chronic HIV-1 infection was done. There was higher prevalence of multivariant infection compared with previously described heterosexual cohorts. A link was identified between multivariant infection and replicative capacity conferred by gag, whereby TF gag tended to be of lower replicative capacity in multivariant infection (p = 0.02) suggesting an overall lowering of fitness requirements during infection with multiple variants. Notwithstanding, multivariant infection was associated with rapid CD4+ T cell decline and perturbances in the CD4+ T cell and B cell compartments compared to single variant infection, which were reversible upon control of viremia. Strategies aimed at identifying and mitigating multivariant infection could contribute toward improving HIV-1 prognosis and this may involve strategies that tighten the stringency of the transmission bottleneck such as treatment of STI. Furthermore, the sequences and chimeric viruses help with TF based experimental vaccine immunogen design and can be used in functional assays to probe effective immune responses against TF.
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Linfocitos T CD4-Positivos/inmunología , Efecto Fundador , Infecciones por VIH , VIH-1/fisiología , Replicación Viral , Productos del Gen gag del Virus de la Inmunodeficiencia Humana , Enfermedad Aguda , Adolescente , Adulto , Linfocitos B/inmunología , Linfocitos B/patología , Linfocitos T CD4-Positivos/patología , Linfocitos T CD4-Positivos/virología , Femenino , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Infecciones por VIH/patología , Humanos , Masculino , Persona de Mediana Edad , Viremia/genética , Viremia/inmunología , Viremia/patología , Replicación Viral/genética , Replicación Viral/inmunología , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/inmunologíaRESUMEN
Serrated polyposis syndrome (SPS) was formerly considered a rare condition. In the past decade, it has gained increasing recognition due to its close association with colorectal cancer (CRC). Diagnosis is made based on the updated World Health Organization (WHO) criteria of having serrated polyps (SPs) proximal to the rectum, all being ≥5 mm in size, with at least two being ≥10 mm in size (criterion I), and a more distal phenotype that presents with greater than 20 SPs of any size throughout the large bowel with five being proximal to the rectum (criterion II). There are three subtypes of SP: hyperplastic polyp (HP), sessile serrated lesion (SSL), and traditional serrated adenoma (TSA). We present a 61-year-old Caucasian male who was referred for surveillance colonoscopy due to a history of colon polyps. A total of 28 polyps were completely removed, 21 of which were found to be SPs, three of which were >10 mm in size, meeting the WHO criteria for SPS. A follow-up colonoscopy was recommended in one year. It is now recognized that SPS are significant contributors to the development of CRC. The United States Multi-Society Preventive Task Force recently updated their consensus statement in 2020 with specific guidance for surveillance of SPs. It is important to emphasize that the diagnostic criteria apply to cumulative polyp count over the individual's lifetime. The optimal surveillance for SPS remains unclear.