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Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modeling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged β-sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles.

Bacterial-fungal interactions have important physiologic and medical ramifications, but the mechanisms of these interactions are poorly understood. The gut is host to trillions of microorganisms, and bacterial-fungal interactions are likely to be important. Using a neutropenic mouse model of microbial gastrointestinal colonization and dissemination, we show that the fungus Candida albicans inhibits the virulence of the bacterium Pseudomonas aeruginosa by inhibiting P. aeruginosa pyochelin and pyoverdine gene expression, which plays a critical role in iron acquisition and virulence. Accordingly, deletion of both P. aeruginosa pyochelin and pyoverdine genes attenuates P. aeruginosa virulence. Heat-killed C. albicans has no effect on P. aeruginosa, whereas C. albicans secreted proteins directly suppress P. aeruginosa pyoverdine and pyochelin expression and inhibit P. aeruginosa virulence in mice. Interestingly, suppression or deletion of pyochelin and pyoverdine genes has no effect on P. aeruginosa's ability to colonize the GI tract but does decrease P. aeruginosa's cytotoxic effect on cultured colonocytes. Finally, oral iron supplementation restores P. aeruginosa virulence in P. aeruginosa and C. albicans colonized mice. Together, our findings provide insight into how a bacterial-fungal interaction can modulate bacterial virulence in the intestine. Previously described bacterial-fungal antagonistic interactions have focused on growth inhibition or colonization inhibition/modulation, yet here we describe a novel observation of fungal-inhibition of bacterial effectors critical for virulence but not important for colonization. These findings validate the use of a mammalian model system to explore the complexities of polymicrobial, polykingdom infections in order to identify new therapeutic targets for preventing microbial disease.

Dengue cases rose to record levels during 2023–2024. We investigated dengue in Valle del Cauca, Colombia, to determine if specific virus serotypes or lineages caused its large outbreak. We detected all 4 serotypes and multiple lineages, suggesting that factors such as climatic conditions were likely responsible for increased dengue in Colombia.

BackgroundDengue is hyperendemic in Colombia. It imposes a substantial economic burden on patients, caregivers, society, and the national health system. We intend to identify and synthesize the evidence regarding the economic burden of dengue in Colombia.MethodsA systematic review (PROSPERO CRD42021257985) of economic studies was performed. A comprehensive search was completed in PubMed, EMBASE, the Cochrane Library, the LILACS, and SciELO databases. Study selection and data extraction was made by two researchers.Results160 records were identified. Of these, 14 studies were selected for data extraction. Direct medical cost of dengue is mainly represented by hospitalization (USD 823 to 1,754). The annual aggregated cost is near to USD 159.6 million, with ambulatory care (USD 90.1 million) and fatal cases (USD 30.7 million) representing 75% of the total cost. The aggregate indirect cost (due to loss in income while sick or as a caretaker) was USD 92.8 million. Vaccination seems to reduce the economic cost of dengue.ConclusionsDengue financial burden could be challenging for low-income communities as those affected in Colombia. An integrated approach including vector control and the introduction of a vaccine for dengue has the potential to reduce the economic burden of the disease.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children around the world. The post-pandemic era has resulted in a notable increase in reported cases of RSV infections, co-circulation of other respiratory viruses, shifts in epidemiology, altered respiratory season timing, and increased healthcare demand. Low- and middle-income countries are responsible for the highest burden of RSV disease, contributing significantly to health expenses during respiratory seasons and RSV-associated mortality in children. Until recently, supportive measures were the only intervention to treat or prevent RSV-infection, since preventive strategies like palivizumab are limited for high-risk populations. Advances in new available strategies, such as long-acting monoclonal antibodies during the neonatal period and vaccination of pregnant women, are now a reality. As the Regional Expert Group of the Latin American Pediatric Infectious Diseases Society (SLIPE), we sought to evaluate the burden of RSV infection in Latin America and the Caribbean (LAC) region, analyze current strategies to prevent RSV infection in children, and provide recommendations for implementing new strategies for preventing RSV infection in children in LAC region.

BackgroundStaphylococcus aureus infections are a significant cause of morbidity and mortality in pediatric populations worldwide. The Staphylo Research Network conducted an extensive study on pediatric patients across Colombia from 2018 to 2021. The aim of this study was to describe the epidemiological and microbiological characteristics of S. aureus in this patient group.MethodsWe analyzed S. aureus isolates from WHONET-reporting centers. An “event” was a positive culture isolation in a previously negative individual after 2 weeks. We studied center characteristics, age distribution, infection type, and antibiotic susceptibilities, comparing methicillin sensitive (MSSA) and resistant S. aureus (MRSA) isolates.ResultsIsolates from 20 centers across 7 Colombian cities were included. Most centers (80%) served both adults and children, with 55% offering oncology services and 85% having a PICU. We registered 8,157 S. aureus culture isolations from 5,384 events (3,345 MSSA and 1,961 MRSA) in 4,821 patients, with a median age of 5 years. Blood (26.2%) and skin/soft tissue (18.6%) were the most common infection sources. Most isolates per event remained susceptible to oxacillin (63.2%), clindamycin (94.3%), and TMP-SMX (98.3%). MRSA prevalence varied by city (

IntroductionInvasive Pneumococcal Disease (IPD) causes significant morbidity and mortality in children under 5 y. Colombia introduced PCV10 vaccination in 2012, and the Neumocolombia network has been monitoring IPD in pediatric patients since 2008.Materials and methodsThis study is a secondary analysis of a prospective cohort involving pediatric patients with IPD admitted to 17 hospitals in Colombia, from January 1st, 2017, to December 31st, 2022. We present data on serotypes (Spn), clinical characteristics, and resistance patterns.ResultsWe report 530 patients, 215 (40.5%) were younger than 24 months. Among these, 344 cases (64.7%) presented with pneumonia, 95 (17.9%) with primary bacteremia, 53 (10%) with meningitis, 6 (1.1%) had pneumonia and meningitis, and 32 (6%) had other IPD diagnosis. The median hospital stay was 12 days (RIQ 8–14 days), and 268 (50.6%) were admitted to the ICU, of whom 60 (11.3%) died. Serotyping was performed in 298 (56.1%). The most frequent serotypes were Spn19A (51.3%), Spn6C (7.7%), Spn3 (6.7%), Spn6A (3.6%), and Spn14 (3.6%). Of 495 (93%) isolates with known susceptibility, 46 (9.2%) were meningeal (M) and 449 (90.7%) non-meningeal (NM). Among M isolates, 41.3% showed resistance to penicillin, and 21.7% decreased susceptibility to ceftriaxone. For NM isolates, 28.2% had decreased susceptibility to penicilin, and 24.2% decreased susceptibility to ceftriaxone. Spn19A showed the highest resistant to penicillin at 47% and was linked to multiresistance.ConclusionThe prevalence of PCV10-included serotypes decreased, while serotypes 19A and 6C increased, with Spn19A being associated with multiresistance. These findings had played a crucial role in the decision made by Colombia to modify its immunization schedule by switching to PCV13 in July 2022.

BackgroundVenereal 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 findingsWe 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.ConclusionsThis 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.

While the first 1,000 days of life are a critical period in child's development, limited information on the main determinants affecting this period in the Latin America and the Caribbean (LAC) region is available. Therefore, the Latin American Pediatric Infectious Diseases Society (SLIPE) held an ad hoc workshop in May 2022 with an expert panel designed to analyze the main factors impacting the development of childhood in the region during this period and the main causes of maternal infant morbimortality. The aim was to identify priorities, generate recommendations, and advise practical actions to improve this situation. Considerations were made about the challenges involved in bridging the gap that separates the region from more developed countries regarding an optimal early childhood and maternal care. Extensive discussion was conducted to reach consensus recommendations on general strategies intended to reduce maternal and infant mortality associated with infections and immune-preventable diseases during the first 1,000 days of life in LAC.

Introduction The WHO 2030 Immunization Agenda (IA-2030) harmonizes immunization activity plans at community, national, regional and global levels. Additionally, medical societies play an important role. The Latin American Group of Experts on Infant Immunization, established in 2018, advises on the harmonization, update, and optimization of infant vaccination programs in Latin America and the Caribbean (LAC). In September 2021, 41 such experts from 13 LAC countries met to develop recommendations for increasing regional vaccination coverage to avoid the reemergence of vaccine-preventable diseases and/or the occurrence of outbreaks. Areas covered The following items were evaluated: (i) immunization challenges before and during the COVID-19 pandemic; (ii) the status of current immunization programs, particularly infant pertussis and polio vaccination; (iii) possible solutions for overcoming vaccination challenges and achieving regional vaccination coverage targets. Expert opinion/commentary Medical societies provide valuable recommendations to guide and update vaccination schedules. In the LAC region, possible strategies to achieve target vaccination rates include the use of combination vaccines, strengthening surveillance systems, improving school attendance, advancing vaccine education and confidence, striving for vaccination equity, widening operational capacity, creating strategic alliances, and strengthening the role of medical groups. It is hoped that these recommendations will be implemented in the LAC region.

We conducted a dose-finding phase 2 study of the HilleVax bivalent virus-like particle (VLP) vaccine candidate (HIL-214) in two cohorts of children, 6–≤12 months and 1–≤4 years of age (N = 120 per cohort), in Panama and Colombia (ClinicalTrials.gov, identifier NCT02153112). On Day 1, children randomized to one of the four equal groups received intramuscular injections of four different HIL-214 formulations containing 15/15, 15/50, 50/50, or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)3. On Day 29, half the children in each group received a second vaccination (N = 60), while the other half received saline placebo injections to maintain the blind. VLP-specific ELISA Pan-Ig and histo-blood group binding antigen-blocking antibodies (HBGA) were measured on Days 1, 29, 57 and 210. On Day 29, after one dose, there were large Pan-Ig and HBGA responses in both age cohorts with some indication of dose-dependence, and higher geometric mean titers (GMT) in the older children. A further increase in titers was observed 28 days after a second dose in the 6–≤12-month-old groups, but less so in the 1–≤4-year-old groups; GMTs at Day 57 were broadly similar across doses and in both age groups. GMTs of Pan-Ig and HBGA persisted above baseline up to Day 210. All formulations were well tolerated with mostly mild-to-moderate transient solicited adverse events reported by parents/guardians, and no vaccine-related serious adverse events occurred. Further development of HIL-214 is warranted to protect the most susceptible young children against norovirus.

IntroductionAcute bacterial meningitis (ABM) is a public health problem. The disease has reemerged after the introduction of pneumococcal conjugate vaccines (PCVs) due to an increase in serotypes that are not covered. The objective was to determine the changes in the disease incidence before and after the introduction of the 10-valent vaccine (PCV10) in Colombia.MethodsThis multicenter study was conducted in 17 hospitals in Colombia. Data were collected from January 2008 to December 2019 in 10 hospitals in Bogotá and from January 2017 to December 2019 in seven hospitals in Cali, Medellín and Cartagena. The data were grouped into three periods: 2008–2011, 2012–2015, and 2016-2019.ResultsOf the 706 cases of invasive pneumococcal disease, 81 (11.4%) corresponded to meningitis. The relative incidence in Bogotá in the first period was 0.6 per 100,000 patients ≤ 5 years, decreased to 0.4 per 100,000 patients ≤ 5 years in the second period and increased in the third period to 0.7 per 100,000 patients ≤ 5 years. Serotypes covered by PCV10 decreased from 75 to 9.1%, with Spn19A (31.8%) and Spn34 (13.6%) emerging in the third period. Increased resistance to penicillin (13 to 37%) and to ceftriaxone (5.9 to 16%) was due to the emergence of multidrug-resistant Spn19A. The total mortality rate was 23.5% and increased from 12 to 33%.ConclusionsABM due to pneumococcus has high morbidity and mortality rates. Reemergence of the disease has been observed due to the inclusion of polymerase chain reaction (PCR) for diagnosis and replacement of circulating serotypes after the introduction of PCV10, with an increase in Spn19A, which causes death and exhibits antimicrobial resistance. Continued surveillance is needed.

BackgroundLimited data is available from low-middle and upper-middle income countries of the factors associated with hospitalization or admission to pediatric intensive care unit (PICU) for children with COVID-19.ObjectiveTo describe the factors associated with hospitalization or PICU admission of children with COVID-19 in Latin America.MethodMulticenter, analytical, retrospective study of children reported from 10 different Latin American countries to the Latin-American Society of Pediatric Infectious Diseases (SLIPE-COVID) research network from June 1, 2020, and February 28, 2021. Outpatient or hospitalized children

Objective: To characterize the use of adjunctive therapy in Kawasaki disease (KD) in Latin America.Methods: The study included 1,418 patients from the Latin American KD Network (REKAMLATINA) treated for KD between January 1, 2009, and May 31, 2017.Results: Of these patients, 1,152 received only a single dose of IVIG, and 266 received additional treatment. Age at onset was similar in both groups (median 2 vs. 2.2 years, respectively). The majority of patients were male (58 vs. 63.9%) and were hospitalized with the first 10 days of fever (85.1 vs. 84.2%). The most common adjunctive therapy administered was steroids for IVIG-resistance, followed by additional doses of IVIG. The use of biologics such as infliximab was limited. KD patients who received adjunctive therapy were more likely to have a lower platelet count and albumin level as well as a higher Z score of the coronary arteries.Conclusion: This is the first report of adjunctive therapies for KD across Latin America. IVIG continues to be the initial and resistance treatment, however, steroids are also used and to a lesser extent, biological therapy such as infliximab. Future studies should address the barriers to therapy in children with acute KD throughout Latin America.

Objective: To characterize the clinical presentation and outcomes of Kawasaki disease (KD) in infants 10 days (50 vs. 7.4%, P = 0.043)].Conclusion: Our data show that despite treatment in the first 10 days of illness, infants

As infants suffer significant morbidity and mortality due to norovirus-related acute gastroenteritis (AGE), we assessed four formulations of the bivalent virus-like particle (VLP) vaccine candidate (HIL-214) in Panamanian and Colombian infants. 360 infants aged 6 weeks to 5 months were randomly allocated to 8 groups to receive three doses of HIL-214 or two doses of HIL-214 and one dose of placebo (Days 1, 56 and 112), where HIL-214 doses contained 15/15, 15/50, 50/50 or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)3. Solicited injection-site and systemic adverse events (AE) were collected within 7 days after each dose, unsolicited AEs were collected within 28 days after each, and serious AEs throughout the study. Pan-Ig and histoblood group antigen-blocking antibodies (HBGA) were measured on Days 1, 56, 84, and 140. All formulations were well-tolerated causing mainly mild-to-moderate transient solicited AEs, most frequently local pain and irritability/fussiness, but no vaccine-related serious AEs. Two doses of each formulation induced high titers of high avidity Pan-Ig and also HBGA antibodies; a third dose increased titers against both antigens and the avidity of Pan-Ig antibodies against GII.4c but not against GI.1. Two and three doses of HIL-214 were well-tolerated and induced potent immune responses at 4–6 months of age supporting further clinical assessment to protect against norovirus-related AGE.

Antecedentes : Poco se sabe sobre la neumonitis intersticial linfoidea (NIL) en niños con infección por el virus de inmunodeficiencia humana-1 (VIH-1) Objetivos: Describir las características clínicas y patológicas de NIL en niños infectados por VIH-1 en un centro de referencia para VIH pediátrico en Cali (Colombia). Métodos: Se llevó a cabo una descripción de serie de casos de NIL basados en revisión retrospectiva de historias clínicas de todos los casos de niños con enfermedad pulmonar crónica y LIP confirmada por biopsia entre los años 2001 y 2012. Resultados y conclusiones: Diez de 12 casos con NIL fueron confirmados por biopsia pulmonar. Se observó una respuesta clínica y de función respiratoria luego del tratamiento con prednisona, excepto en un caso que presentó tos persistente. No se encontraron casos de tuberculosis pulmonar (TP) en nuestra serie y el papel de la biopsia pulmonar fue crítico para alcanzar un diagnóstico preciso.

La criptococosis puede afectar niños de todas las edades, especialmente aquellos inmunocomprometidos. Usualmente se adquiere a través de la inhalación de esporas del medio ambiente, aunque existen otras formas de transmisión. Describimos un caso de criptococosis congénita adquirido de una madre con síndrome de inmunodeficiencia adquirida (SIDA) y tratado en forma exitosa con combinación de antimicoticos.