Specimen sharing for epidemic preparedness: Building a virtual biorepository system from local governance to global partnerships.

We present a framework for a federated, virtual biorepository system (VBS) with locally collected and managed specimens, as a 'global public good' model based on principles of equitable access and benefit sharing. The VBS is intended to facilitate timely access to biological specimens and associated data for outbreak-prone infectious diseases to accelerate the development and evaluation of diagnostics, assess vaccine efficacy, and to support surveillance and research needs. The VBS is aimed to be aligned with the WHO BioHub and other specimen sharing efforts as a force multiplier to meet the needs of strengthening global tools for countering epidemics. The purpose of our initial research is to lay the basis of the collaboration, management and principles of equitable sharing focused on low- and middle-income country partners. Here we report on surveys and interviews undertaken with biorepository-interested parties to better understand needs and barriers for specimen access and share examples from the ZIKAlliance partnership on the governance and operations of locally organized biorepositories.

Long-term impact on cardiopulmonary function and quality of life among patients recovered from SARS-CoV-2 infection in a 6-month follow-up period in Lima, Peru: FUNCTION cohort study protocol.

INTRODUCTION: The sequelae of COVID-19 have been described as a multisystemic condition, with a great impact on the cardiovascular and pulmonary systems with abnormalities in pulmonary function tests, such as lower diffusing capacity of the lung for carbon monoxide (DLco) levels and pathological patterns in spirometry; persistence of radiological lesions; cardiac involvement such as myocarditis and pericarditis; and an increase in mental disorders such as anxiety and depression. Several factors, such as infection severity during the acute phase as well as vaccination status, have shown some variable effects on these post-COVID-19 conditions, mainly at a clinical level such as symptoms persistence. Longitudinal assessments and reversibility of changes across the spectrum of disease severity are required to understand the long-term impact of COVID-19. METHODS AND ANALYSIS: A prospective cohort study aims to assess the impact of SARS-CoV-2 infection on cardiopulmonary function and quality of life after the acute phase of the disease over a 6-month follow-up period. Sample size was calculated to recruit 200 participants with confirmatory COVID-19 tests who will be subsequently classified according to infection severity. Four follow-up visits at baseline, month 1, month 3 and month 6 after discharge from the acute phase of the infection will be scheduled as well as procedures such as spirometry, DLco test, 6-minute walk test, chest CT scan, echocardiogram, ECG, N-terminal pro-B-type natriuretic peptide measurement and RAND-36 scale. Primary outcomes are defined as abnormal pulmonary function test considered as DLco <80%, abnormal cardiovascular function considered as left ventricular ejection fraction <50% and abnormal quality of life considered as a <40 score for each sphere in the RAND-36-Item Short Form Health Survey. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Ethics Committee of the Universidad Peruana Cayetano Heredia (SIDISI 203725) and the Ethics Committee of the Hospital Cayetano Heredia (042-2021). Protocol details were uploaded in ClinicalTrials.gov. Findings will be disseminated through peer-reviewed journals, scientific conferences and open-access social media platforms. TRIAL REGISTRATION NUMBER: NCT05386485.

Zika Virus Seroprevalence in Two Districts of Chincha, Ica, Peru: A Cross-Sectional Study.

In 2017, a major outbreak of Zika virus (ZIKV) infection took place in Chincha Province, Peru, where arboviral circulation had never been reported before. We conducted a cross-sectional survey (March-May 2019) in two districts of Chincha Province: Pueblo Nuevo and Chincha Baja. We included residents who were 20 to 40 years old and who had lived in these districts for at least 1 year. Serological testing combined screening with a commercial NS1 protein-based Zika IgG ELISA, and confirmation by a cytopathic effect-based virus neutralization test (VNT). Prevalence ratios (PRs) were calculated using Poisson regression with robust error variance. Four hundred participants, divided equally among districts, were enrolled. Anti-ZIKV IgG ELISA was positive for 42 participants (10.5%) and borderline for 12 (3%). Fifty-two of these 54 samples were confirmed positive by ZIKV VNT (13% of the total population). The Pueblo Nuevo district exhibited a greater ZIKV seroprevalence based on VNT results than the Chincha Baja district (23.5% versus 2.5%), with participants from the Pueblo Nuevo district being 9.4 times more likely to have a positive ZIKV VNT result. Average monthly income greater than the minimum wage and adequate water storage were found to be protective factors (PR, 0.29 and 0.24, respectively). In multivariate analysis, living in the Pueblo Nuevo district and a personal history of fever and rash were strong predictors of ZIKV positivity by VNT. The low ZIKV seroprevalence should prompt health authorities to stimulate interventions to prevent potential future outbreaks. In the Pueblo Nuevo district, the seroprevalence was greater but presumably not sufficient to ensure protective herd immunity.

Fluoroquinolone susceptibility in first-line drug-susceptible M. tuberculosis isolates in Lima, Peru.

OBJECTIVE: To determine at two distinct time points the prevalence of resistance to ofloxacin (OFX), the representative class drug of fluoroquinolones (FQs), in M. tuberculosis isolates susceptible to first-line drugs. RESULTS: There were 279 M. tuberculosis isolates from the two cohorts (2004-2005: 238 isolates; 2017: 41 isolates) that underwent OFX drug-susceptibility testing (critical concentration: 2 µg/ml). Of 238 isolates in Cohort 1, no resistance to OFX was detected (95% CI 0-0.016); likewise, in Cohort 2, no resistance to OFX was detected in 41 isolates (95% CI 0-0.086). Our findings suggest that FQ use remains a viable option for the treatment of first-line drug-susceptible TB in Peru.

Clinical, Radiological and Functional Characteristics of Pulmonary Diseases among HTLV-1 Infected Patients without Prior Active Tuberculosis Infection.

The lifelong infection with the human T lymphotropic virus type 1 (HTLV-1) has been associated with a variety of clinical manifestations; one of the less-explored is HTLV-1-associated pulmonary disease. Imaging of lung damage caused by the HTLV-1 hyperinflammatory cascade can be similar to sequelae from TB infection. Our study aims to describe the pulmonary lesions of HTLV-1-positive patients without past or current active TB and evaluate pulmonary function. We found that nine out of fourteen patients with no known TB disease history presented bronchiectasis, mainly found bilaterally while five presented pulmonary fibrosis. A normal pattern was found in most patients with a pulmonary functional test. Furthermore, there was no association between the PVL and the chest-CT scan findings, nor with spirometry results. However, the sample size was insufficient to conclude it.

Tuberculosis Scientific Conferences in Peru: Sharing local evidence for local decisions.

INTRODUCTION: International conferences on tuberculosis (TB) have been held since the 19th century. In Peru, the TB Scientific Conferences have been held annually in Lima since 2013 as a means of developing a national TB research network and setting the stage for researchers and institutions to present and share new findings from studies conducted in Peru. METHODS: Systematization of information on speakers and presentations from TB Scientific Conferences in Peru. Presentation files and official agendas for the conferences from 2013 to 2019 were obtained from the Tuberculosis Prevention and Control Directorate's website. RESULTS: A total of 426 scientific presentations have been delivered by 230 speakers, with a steady annual increase. 37.1% of the talks were given by female speakers. To date, 61.4% of the research presented has been published. Out of all the studies, 10.9% (30/275) were part of international, multicentric research projects. Main research lines were epidemiology (40.1%), drug-resistance (29.6%) and treatment (22.1%). CONCLUSIONS: TB Scientific Conferences serve as a platform to share region-specific TB evidence between local stakeholders (health officials, academics, and others) who aim to facilitate the implementation of measures with the goal of reducing the national gaps towards the End TB Strategy goals.

Impact of fractures and orthopedic surgeries in patients with HTLV-1 associated myelopathy/tropical spastic paraparesis.

INTRODUCTION: In patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) gait disturbance is a predominant feature that leads to falls and fractures, which can further aggravate disability. We sought to evaluate the impact of fractures and orthopedic surgeries in patients with HAM/TSP. METHODS: We retrieved the medical records of HAM/TSP patients enrolled in our study center's HTLV-1 clinical cohort between 1989-2018. The selection criteria included: (1) diagnosis of HTLV-1 infection using two enzyme-linked immunosorbent assays and/or a confirmatory test, (2) clinical diagnosis of HAM/TSP by neurological assessment, and (3) fractures associated with HAM/TSP. RESULTS: We identified 24 cases of fractures, 70% of which were females. The median age at the time of fracture was 60 years (IQR=24). Six cases reported fractures in patients under 45 years old. Ten patients (42%) had hip/coccyx fractures, seven (29%) were in the lower extremities, and four (17%) in the upper extremities. Half of these patients reported the use of wheelchairs. Five patients who had previously used canes required the use of wheelchairs after the reported fracture. Eight patients underwent corrective orthopedic surgery as a result of the fracture. CONCLUSIONS: For HAM/TSP patients, fractures are a complication that can exacerbate their severe impairment.

Case Report: Multiorgan Involvement with Congenital Zika Syndrome.

We report the case of an infant born with congenital Zika syndrome (CZS). During the largest Zika virus (ZIKV) outbreak in Peru, the mother presented with fever and rash that were confirmed to be due to ZIKV by real-time PCR. The infant was born with severe microcephaly. Imaging revealed corpus callosum dysgenesis, lissencephaly, ventriculomegaly, and calcifications. Mild hypertrophic cardiomyopathy with diastolic dysfunction was reported in the echocardiogram. Valgus deviation of the lower extremities and a left clubfoot were diagnosed at birth. The hip ultrasound showed incipient signs of Graf type II dysplasia. The findings confirm that CZS is a multiorgan phenotype in which microcephaly is merely the tip of the iceberg. A multidisciplinary approach is needed for the evaluation of these children.

Adherence to standards of care and mortality in the management of Staphylococcus aureus bacteraemia in Peru: A prospective cohort study.

BACKGROUND: Despite high mortality rates, physicians can alter the course of the Staphylococcus aureus bacteraemia (SAB) by following recommended standards of care. We aim to assess the adherence of these guidelines and their impact on mortality. METHODS: Substudy from a prospective cohort of hospitalized patients with SAB from three hospitals from Peru. Hazard ratios were calculated using Cox proportional regression to evaluate the association between 30-day mortality and the performance of standards of care: removal of central venous catheters (CVC), follow-up blood cultures, echocardiography, correct duration, and appropriate definitive antibiotic therapy. RESULTS: 150 cases of SAB were evaluated; 61.33% were MRSA. 30-day attributable mortality was 22.39%. CVC removal was done in 42.86% of patients. Follow-up blood cultures and echocardiograms were performed in 8% and 29.33% of cases, respectively. 81.33% of cases had appropriate empirical treatment, however, only 22.41% of MSSA cases were given appropriate definitive treatment, compared to 93.47% of MRSA. The adjusted regression for all-cause mortality found a substantial decrease in hazards when removing CVC (aHR 0.28, 95% CI: 0.10 - 0.74) and instituting appropriate definitive treatment (aHR 0.27, 95% CI: 0.08 - 0.86), while adjusting for standards of care, qPitt bacteraemia score, comorbidities, and methicillin susceptibility; similar results were found in the attributable mortality model (aHR 0.24, 95% CI: 0.08 - 0.70 and aHR 0.21, 95% CI: 0.06 - 0.71, respectively). CONCLUSIONS: Deficient adherence to standards of care was observed, especially definitive treatment for MSSA. CVC removal and the use of appropriate definitive antibiotic therapy reduced the hazard mortality of SAB.

Early-Onset HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis.

BACKGROUND: Vertical transmission of HTLV-1 could lead to the early development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This significantly affects quality of life and increases morbimortality. OBJECTIVE: To describe the epidemiological and clinical characteristics of patients with early-onset HAM/TSP, defined as disease onset before 20 years of age. METHODS: This is a retrospective study from an HTLV-1 clinical cohort between 1989 and 2019. We searched for medical records of patients with (1) diagnosis of HTLV-1 infection using two ELISA and/or one Western blot, (2) clinical diagnosis of HAM/TSP by neurological assessment, and (3) HAM/TSP symptom-onset before 20 years of age. RESULTS: A total of 38 cases were identified in the cohort; 25 were female (66%). The median age of onset was 14 years old. 31 (82%) cases had HTLV-1 testing done among family members; 22 out of 25 tested mothers (88%) were HTLV-1 positive. Most patients (27/34) were breastfed for more than one year. Disease progression measured through EDSS and IPEC-1 showed an upward trend towards worsening spasticity with 18 patients (47%) eventually requiring mobility aids. CONCLUSIONS: Cases of early-onset HAM/TSP are not of rare occurrence, which translates into many more years of dependency, the use of mobility aids, and increased overall morbidity.

Prevalence of positive TST among healthcare workers in high-burden TB setting in Peru.

BACKGROUND: Tuberculosis (TB) transmission has long been recognized as an important occupational hazard for healthcare workers (HCWs). HCWs have a 5.8% annual risk of exposure and three times greater risk of developing active TB than the general population. METHODS: We conducted an observational cross-sectional study between September 2014 and March 2015 among HCWs in a high-burden TB setting in Lima to estimate the prevalence of positive Tuberculin Skin Test (TST) and to investigate factors associated with a positive TST. RESULTS: Two hundred forty participants were included in the analysis; TST was administered to 190 (79.2%) while the rest were exempt due to a previous positive TST result, history of TB, or test refusal. A positive TST result was found among 56.2% of participants to whom the TST was applied (95% CI: 49.22-63.55%). When considering those who had a previous positive TST result and those with a history of TB, the prevalence of a positive TST result was 64.3% (95% CI: 57.8-70.3%). No significant differences were observed between clinical/paramedical and administrative staff in the health center. The use of N95 masks during work hours was reported by 142 (69.9%) participants. Prevalence ratios (PR) show that workers with more than 120 months as a HCW were 1.44 times more likely to be TST positive. The multivariate analysis found that HCWs with over 10 years of service were 1.52 times more likely to be TST positive. CONCLUSION: This study supports previous reports that TB infection is an occupational hazard for HCWs. Prevention of TB transmission through control measures, as well as timely diagnosis of LTBI in this particular high-risk group, is critical for individual and public health.

Association between tuberculosis and depression on negative outcomes of tuberculosis treatment: A systematic review and meta-analysis.

BACKGROUND: Depression is a common comorbidity of tuberculosis (TB) and is associated with poor adherence to treatment of multiple disorders. We conducted a systematic review to synthesize the existing evidence on the relationship between depression and negative outcomes of TB treatment. METHODS: We systematically reviewed studies that evaluated depressive symptoms (DS) directly or indirectly through psychological distress (PD) and measured negative treatment outcomes of drug-sensitive pulmonary TB, defined as death, loss to follow-up, or non-adherence. Sources included PubMed, Global Health Library, Embase, Scopus and Web of Science from inception to August 2019. RESULTS: Of the 2,970 studies initially identified, eight articles were eligible for inclusion and two were used for the primary outcome meta-analysis. We found a strong association between DS and negative TB treatment outcomes (OR = 4.26; CI95%:2.33-7.79; I2 = 0%). DS were also associated with loss to follow-up (OR = 8.70; CI95%:6.50-11.64; I2 = 0%) and death (OR = 2.85; CI95%:1.52-5.36; I2 = 0%). Non-adherence was not associated with DS and PD (OR = 1.34; CI95%:0.70-2.72; I2 = 94.36) or PD alone (OR = 0.92; CI95%:0.81-1.05; I2 = 0%). CONCLUSIONS: DS are associated with the negative TB treatment outcomes of death and loss to follow-up. Considerable heterogeneity exists in the definition of depression and outcomes such as non-adherence across the limited number of studies on this topic.

Impact of fractures and orthopedic surgeries in patients with HTLV-1 associated myelopathy/tropical spastic paraparesis

Abstract INTRODUCTION In patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) gait disturbance is a predominant feature that leads to falls and fractures, which can further aggravate disability. We sought to evaluate the impact of fractures and orthopedic surgeries in patients with HAM/TSP. METHODS: We retrieved the medical records of HAM/TSP patients enrolled in our study center's HTLV-1 clinical cohort between 1989-2018. The selection criteria included: (1) diagnosis of HTLV-1 infection using two enzyme-linked immunosorbent assays and/or a confirmatory test, (2) clinical diagnosis of HAM/TSP by neurological assessment, and (3) fractures associated with HAM/TSP. RESULTS: We identified 24 cases of fractures, 70% of which were females. The median age at the time of fracture was 60 years (IQR=24). Six cases reported fractures in patients under 45 years old. Ten patients (42%) had hip/coccyx fractures, seven (29%) were in the lower extremities, and four (17%) in the upper extremities. Half of these patients reported the use of wheelchairs. Five patients who had previously used canes required the use of wheelchairs after the reported fracture. Eight patients underwent corrective orthopedic surgery as a result of the fracture. CONCLUSIONS: For HAM/TSP patients, fractures are a complication that can exacerbate their severe impairment.