Treponema pallidum genetic diversity and its implications for targeted vaccine development: A cross-sectional study of early syphilis cases in Southwestern Colombia.

BACKGROUND: Venereal syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (TPA), is surging worldwide, underscoring the need for a vaccine with global efficacy. Vaccine development requires an understanding of syphilis epidemiology and clinical presentation as well as genomic characterization of TPA strains circulating within at-risk populations. The aim of this study was to describe the clinical, demographic, and molecular features of early syphilis cases in Cali, Colombia. METHODS AND FINDINGS: We conducted a cross-sectional study to identify individuals with early syphilis (ES) in Cali, Colombia through a city-wide network of public health centers, private sector HIV clinics and laboratory databases from public health institutions. Whole blood (WB), skin biopsies (SB), and genital and oral lesion swabs were obtained for measurement of treponemal burdens by polA quantitative polymerase chain reaction (qPCR) and for whole-genome sequencing (WGS). Among 1,966 individuals screened, 128 participants met enrollment criteria: 112 (87%) with secondary (SS), 15 (12%) with primary (PS) and one with early latent syphilis; 66/128 (52%) self-reported as heterosexual, while 48 (38%) were men who have sex with men (MSM). Genital ulcer swabs had the highest polA copy numbers (67 copies/µl) by qPCR with a positivity rate (PR) of 73%, while SS lesions had 42 polA copies/µl with PR of 62%. WB polA positivity was more frequent in SS than PS (42% vs 7%, respectively; p = 0.009). Isolation of TPA from WB by rabbit infectivity testing (RIT) was achieved in 5 (56%) of 9 ES WB samples tested. WGS from 33 Cali patient samples, along with 10 other genomic sequences from South America (9 from Peru, 1 from Argentina) used as comparators, confirmed that SS14 was the predominant clade, and that half of all samples had mutations associated with macrolide (i.e., azithromycin) resistance. Variability in the outer membrane protein (OMP) and vaccine candidate BamA (TP0326) was mapped onto the protein's predicted structure from AlphaFold. Despite the presence of mutations in several extracellular loops (ECLs), ECL4, an immunodominant loop and proven opsonic target, was highly conserved in this group of Colombian and South American TPA isolates. CONCLUSIONS: This study offers new insights into the sociodemographic and clinical features of venereal syphilis in a highly endemic area of Colombia and illustrates how genomic sequencing of regionally prevalent TPA strains can inform vaccine development.

Applying implementation science frameworks to identify factors that influence the intention of healthcare providers to offer PrEP care and advocate for PrEP in HIV clinics in Colombia: a cross-sectional study.

BACKGROUND: Few studies have used implementation science frameworks to identify determinants of PrEP prescription by healthcare providers. In this work, we developed and psychometrically examined a questionnaire using the theoretical domains framework (TDF) and the consolidated framework for implementation research (CFIR). We used this questionnaire to investigate what factors influence the intention of healthcare providers to offer PrEP care and advocate for PrEP. METHODS: We conducted a cross-sectional study in 16 HIV healthcare organizations in Colombia. A 98-item questionnaire was administered online to 129 healthcare professionals. One hundred had complete data for this analysis. We used exploratory factor analysis to assess the psychometric properties of both frameworks, and multinomial regression analysis to evaluate the associations of the frameworks' domains with two outcomes: (1) intention to offer PrEP care and (2) intention to advocate for PrEP impmentation. RESULTS: We found support for nine indices with good internal consistency, reflecting PrEP characteristics, attitudes towards population needs, concerns about the use of PrEP, concerns about the role of the healthcare systems, knowledge, beliefs about capabilities, professional role, social influence, and beliefs about consequences. Notably, only 57% of the participants were likely to have a plan to care for people in PrEP and 66.7% were likely to advocate for PrEP. The perception of the need for PrEP in populations, the value of PrEP as a practice, the influence of colleagues, and seeing PrEP care as a priority was related to being less likely to be unwilling to provide or advocate for PrEP care. CONCLUSION: Our findings suggested the importance of multilevel strategies to increase the provision of PrEP care by healthcare providers including adquisition of new skills, training of PrEP champions, and strength the capacity of the health system.

Synthetic bovine lactoferrin peptide Lfampin kills Entamoeba histolytica trophozoites by necrosis and resolves amoebic intracecal infection in mice.

Amoebiasis caused by the protozoan parasite Entamoeba histolytica remains a public health problem in developing countries, making the identification of new anti-amoebic compounds a continuing priority. Previously, we have shown that lactoferrin (Lf) and several Lf-derived peptides exhibit in vitro anti-amoebic activity independently of their iron-binding activity. Here, we evaluated the amoebicidal effect of synthetic Lf-derived peptides Lfcin-B, Lfcin 17-30, and Lfampin, analyzed the mechanism of death induced by the peptides and determined their therapeutic effects on murine intestinal amoebiasis. MTT assays in trophozoite cultures of E. histolytica exposed to each peptide (1-1000 µM) showed that Lfampin is far more amoebicidal than Lfcins. Lfampin killed 80% of trophozoites at doses higher than 100 µM in 24 h, and FACs analysis using Annexin V/propidium iodide showed that death occurred mainly by necrosis. In contrast, Lfcin-B and Lfcin 17-30 appeared to have no significant effect on amoebic viability. FACs and confocal microscopy analysis using FITC-labeled peptides showed that all three peptides are internalized by the amoeba mainly using receptor (PI3K signaling) and actin-dependent pathways but independent of clathrin. Docking studies identified cholesterol in the amoeba's plasma membrane as a possible target of Lfampin. Oral treatment of intracecally infected mice with the abovementioned peptides at 10 mg/kg for 4 days showed that Lfampin resolved 100% of the cases of intestinal amoebiasis, whereas Lfcin 17-30 and Lfcin-B were effective in resolving infection in 80 and 70% of cases, respectively. These data show that although synthetic bovine Lf-derived peptides exhibit varying amoebicidal potentials in vitro, they do resolve murine intestinal amoebiasis efficiently, suggesting that they may be useful as a therapeutic treatment.

Prevalencia y caracterización de las neoplasias malignas en personas viviendo con VIH en Colombia / Prevalence and characterization of cancer in people living with HIV in Colombia

INTRODUCCIÓN: En el síndrome de inmunodeficiencia adquirida las neoplasias han jugado un papel preponderante, y con el advenimiento del tratamiento antirretroviral (TAR), la infección por VIH se ha transformado en una enfermedad crónica, siendo los tumores malignos una causa importante de morbilidad y mortalidad. OBJETIVO: Describir las características demográficas, clínicas y de laboratorio de las personas que viven con VIH (PVVIH) y han sido diagnosticadas con cáncer en Colombia y comparar los grupos de neoplasias definitorias y no definitorias de Sida. MÉTODOS: Revisión multicéntrica retrospectiva, en la que se recolectó y analizó datos relacionados con la infección por VIH y de diagnóstico de cáncer y tipo. Incluyó PVVIH diagnosticadas con neoplasias malignas atendidas en 23 centros de atención de pacientes con VIH en 11 ciudades de Colombia desde 1986 hasta 2018. RESULTADOS: En 23.189 pacientes, se identificaron 650 casos de malignidad (prevalencia de 2,8 % [IC de 95%: 2,6-2,9]). La neoplasia definitoria de Sida (NDS) sigue siendo el tipo de cáncer prevalente (71,1%), las neoplasias malignas más frecuentes fueron sarcoma de Kaposi (n: 330; 50,8%), linfoma no Hodgkin (n: 110; 16,9%), cáncer de piel (n: 48; 7,4%) y linfoma de Hodgkin (n: 25; 3,8%). Los pacientes con NDS tenían más probabilidades de ser HSH y estar en un estadio CDC 3, un recuento de linfocitos T CD4 < 200/μL y una carga viral del VIH ≥ 50 copias/mL al momento del diagnóstico de malignidad. Las personas con neoplasias no definitorias de Sida (NNDS) eran significativamente mayores y tenían más probabilidades de ser fumadores. CONCLUSIONES: Estos hallazgos son relevantes considerando la creciente carga de cáncer en las PVVIH que envejecen y las causas cambiantes de morbilidad y mortalidad. La presentación tardía a la atención del VIH y el retraso en el inicio del TAR son probablemente factores que contribuyen al cambio más lento hacia NNDS en comparación con las regiones de altos ingresos donde hay un acceso más rápido y temprano al TAR. El conocimiento de las tendencias epidemiológicas actuales y el perfil del cáncer en las PVVIH es fundamental para mejorar los esfuerzos de prevención y tratamiento del cáncer en el contexto de la atención integral del VIH.

BACKGROUND: In the acquired immunodeficiency syndrome, neoplasms have played a preponderant role, and with the advent of antiretroviral treatment (ART), HIV has become a chronic disease, with malignant tumors being an important cause of morbidity and mortality. AIM: To describe the demographic, clinical, and laboratory characteristics of people living with HIV (PLHIV) who have been diagnosed with cancer in Colombia and to compare the groups of AIDS-defining (ADC) and non-AIDS-defining neoplasms (NADC). METHODS: Retrospective, multicenter study that included people living with HIV/AIDS (PLHIV) diagnosed with malignancies treated at 23 HIV care centers located in 11 Colombian cities from 1986 to 2018. Data related to HIV infection and cancer diagnosis were collected and analyzed. RESULTS: Among 23,189 patients, 650 malignancy cases were identified (prevalence of 2.8% [95% CI 2.6-2.9]). AIDS-defining neoplasm remains the most prevalent type of cancer (71.1%), The most frequent individual malignancies were Kaposi sarcoma (n: 330; 50.8%), non-Hodgkin lymphoma (n: 110; 16.9%), skin cancer (n: 48; 7.4%), and Hodgkin lymphoma (n: 25; 3.8%). Compared people with NADC, with ADC were more likely to be MSM and have a CDC HIV stage 3, CD4 T cell count < 200/μL, and HIV viral load ≥ 50 copies/mL at the time of malignancy diagnosis. PLHIV and with NADC were significantly older and were more likely to be smokers. CONCLUSIONS: These findings are relevant considering the increasing burden of cancer in the aging PLHIV and the changing causes of morbidity and mortality. Late presentation to HIV care and delayed ART initiation are likely factors contributing to the slower shift toward NADCs compared with high-income regions where access to ART is better. Knowledge of the current epidemiological trends and profile of cancer in PLWHA is critical to improve cancer prevention and treatment efforts in the context of comprehensive HIV care.