Association between HTLV-1/2 infection and COVID-19 severity in a migrant Shipibo-Konibo population in Lima, Peru.

OBJECTIVES: The migrant community of the Shipibo-Konibo indigenous people in Lima, Peru were extremely vulnerable during the COVID-19 pandemic. Additionally, infection with human T-cell lymphotropic virus type 1 and 2 (HTLV-1/2) is endemic in this population causing immunosuppression. The aim of the study was to describe the association between HTLV-1/2 infection and the clinical severity of COVID-19. METHODS: This was a cross-sectional descriptive study involving a survey of adult Shipibo-Konibo indigenous migrants residing in Cantagallo-Rímac who were identified as suspected or confirmed cases of COVID-19. Blood samples were collected for SARS-CoV-2 antibody and HTLV-1/2 ELISA testing. A confirmatory Western Blot test was performed for those with a positive ELISA test. RESULTS: A total of 182 individuals were surveyed and sampled. No significant association was found between HTLV-1/2 infection and the clinical severity of COVID-19. The prevalence of HTLV-1/2 was 8.8% (95%CI: 5.0-14.1) with Western Blot. Age was the only statistically significant risk factor for developing a more severe form of COVID-19 (OR: 1.03; 95%CI: 1.00-1.06; p = 0.032). CONCLUSIONS: There was no association found between HTLV-1/2 infection and the clinical severity of COVID-19. The prevalence of HTLV-1/2 infection in the Shipibo-Konibo population is high and warrants continuous monitoring in the advent of other infectious disease outbreaks and the development of HTLV-associated comorbidities.

Overlooked, dismissed, and downplayed: reversion of Mycobacterium tuberculosis immunoreactivity.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb). Following infection, immune responses to Mtb antigens can be measured using the tuberculin skin test or an interferon-γ release assay. The gain of Mtb immunoreactivity, a change from a negative to a positive tuberculin skin test or interferon-γ release assay result, is called conversion and has long been used as a measure of Mtb exposure. However, the loss of immunoreactivity (reversion; a positive followed by a negative result) has often been overlooked. Instead, in clinical and epidemiological circles, Mtb immunoreactivity is commonly considered to persist lifelong and confer a lifetime of disease risk. We present a critical review, describing the evidence for reversion from cohort studies, ecological studies and studies of TB progression risk. We outline the inconsistent reasons why reversion has been dismissed from common understanding and present evidence demonstrating that, just as conversion predominantly indicates prior exposure to Mtb antigens, so its opposite, reversion, suggests the reduction or absence of exposure (endogenous or exogenous). Mtb immunoreactivity is dynamic in both individuals and populations and this is why it is useful for stratifying short-term TB progression risk. The neglect of reversion has shaped TB research and policy at all levels, influencing clinical management and skewing Mtb infection risk estimation and transmission modelling, leading to an underestimation of the contribution of re-exposure to the burden of TB, a serious oversight for an infectious disease. More than a century after it was first demonstrated, it is time to incorporate reversion into our understanding of the natural history of TB.

Recent Travel and Tuberculosis in Migrants: Data From a Low-Incidence Country.

Tuberculosis (TB) incidence rates among migrants are higher than those in low-incidence countries. We evaluated smear-positive, pulmonary TB notifications of foreign-born individuals, comparing time since arrival and time since last return travel to the country of origin. TB incidence suggests a time course consistent with recent infection during travel.

Impact of micro- and macronutrient status on the incidence of tuberculosis: An examination of an African cohort initiating antiretroviral therapy.

Macronutrient and micronutrient deficiencies are associated with tuberculosis (TB) incidence. However, evidence is limited on the impact of micronutrient (vitamins and minerals) supplementation among underweight individuals. We conducted a secondary data analysis of a randomised controlled trial of lipid nutritional supplements with and without high-dose vitamin and mineral supplementation (LNS-VM vs LNS) for underweight (Body Mass Index [BMI] <18.5 kg/m2) adults with human immunodeficiency virus (HIV) initiating antiretroviral therapy (ART) in Tanzania and Zambia (2011-2013). Incident TB disease diagnoses were extracted from trial records. We used multivariable Cox regression to estimate hazard ratios (HR) for the impact of receiving LNS-VM on TB incidence, and the dose-response relationship between baseline BMI and TB incidence. Overall, 263 (17%) of 1506 participants developed TB disease. After adjusting for age, sex, CD4 count, haemoglobin, and C-reactive protein, receiving LNS-VM was not associated with TB incidence (aHR [95%CI] = 0.93 [0.72-1.20]; p = 0.57) compared to LNS alone. There was strong evidence for an association between lower BMI and incident TB (aHR [95%CI]: 16-16.9kg/m2 = 1.15 [0.82-1.62] and <16kg/m2 = 1.70 [1.26-2.30] compared to 17-18.5kg/m2; linear trend p<0.01). There was strong evidence that the rate of developing TB was lower after initiating ART (p<0.01). In conclusion, the addition of micronutrient supplementation to LNS was not associated with lower TB incidence in this underweight ART-naive population.

Hydroxychloroquine to prevent SARS-CoV-2 infection among healthcare workers: early termination of a phase 3, randomised, open-label, controlled clinical trial.

OBJECTIVE: To assess the effectiveness and safety of hydroxychloroquine (HCQ) prophylaxis for the prevention of SARS-CoV-2 infection in healthcare workers (HCW) on duty during the COVID-19 pandemic. RESULTS: A total of 68 HCWs met the eligibility criteria were randomly allocated to receive HCQ (n = 36) or not (n = 32). There were no significant differences between groups in respects to age, gender, or medical history. Eight participants met the primary efficacy endpoint of SAR-CoV-2 infection during the study period; there was no difference in incidence of SARS-CoV-2 infections between both study arms (HCQ: 5 vs Control: 3, p = 0.538). The relative risk of SARS-CoV-2 infection in the HCQ arm was 1.69 compared to the control group (95%CI 0.41-7.11, p = 0.463); due to poor participant accrual, the resulting statistical power of the primary efficacy outcome was 11.54%. No serious adverse events occurred; however, two (2/36, 5.6%) participants no longer wished to participate in the study and withdrew consent due to recurring grade 1 and 2 adverse events. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04414241. (Registered on June 4, 2020).

Impact of Reversion of Mycobacterium tuberculosis Immunoreactivity Tests on the Estimated Annual Risk of Tuberculosis Infection.

A key metric in tuberculosis epidemiology is the annual risk of infection (ARI), which is usually derived from tuberculin skin test (TST) and interferon-γ release assay (IGRA) prevalence surveys carried out in children. Derivation of the ARI assumes that immunoreactivity is persistent over time; however, reversion of immunoreactivity has long been documented. We used a deterministic, compartmental model of Mycobacterium tuberculosis (Mtb) infection to explore the impact of reversion on ARI estimation using age-specific reversion probabilities for the TST and IGRA. Using empirical data on TST reversion (22.2%/year for persons aged ≤19 years), the true ARI was 2-5 times higher than that estimated from immunoreactivity studies in children aged 8-12 years. Applying empirical reversion probabilities for the IGRA (9.9%/year for youths aged 12-18 years) showed a 1.5- to 2-fold underestimation. ARIs are increasingly underestimated in older populations, due to the cumulative impact of reversion on population reactivity over time. Declines in annual risk did not largely affect the results. Ignoring reversion leads to a stark underestimation of the true ARI in populations and our interpretation of Mtb transmission intensity. In future surveys, researchers should adjust for the reversion probability and its cumulative effect with increasing age to obtain a more accurate reflection of the burden and dynamics of Mtb infection.

COVID-19 in Latin America and the Caribbean: Two years of the pandemic.

Worldwide, nations have struggled during the coronavirus disease 2019 (COVID-19) pandemic. However, Latin America and the Caribbean faced an unmatched catastrophic toll. As of March 2022, the region has reported approximately 15% of cases and 28% of deaths worldwide. Considering the relatively late arrival of SARS-CoV-2, several factors in the region were determinants of the humanitarian crisis that ensued. Pandemic unpreparedness, fragile healthcare systems, forthright inequalities, and poor governmental support facilitated the spread of the virus throughout the region. Moreover, reliance on repurposed and ineffective drugs such as hydroxychloroquine and ivermectin-to treat or prevent COVID-19-was publicised through misinformation and created a false sense of security and poor adherence to social distancing measures. While there were hopes that herd immunity could be achieved after the region's disastrous first peak, the emergence of the Gamma, Lambda, and Mu variants made this unattainable. This review explores how Latin America and the Caribbean fared during the first 2 years of the pandemic, and how, despite all the challenges, the region became a global leader in COVID-19 vaccination, with 63% of its population fully vaccinated.

Know your tuberculosis epidemic-Is it time to add Mycobacterium tuberculosis immunoreactivity back into global surveillance?

Tuberculosis (TB) still causes 1.5 million deaths globally each year. Over recent decades, slow and uneven declines in TB incidence have resulted in a falling prevalence of TB disease, which increasingly concentrates in vulnerable populations. Falling prevalence, while welcome, poses new challenges for TB surveillance. Cross-sectional disease surveys require very large sample sizes to accurately estimate disease burden, and even more participants to detect trends over time or identify high-risk areas or populations, making them prohibitively resource-intensive. In the past, tuberculin skin surveys measuring Mycobacterium tuberculosis (Mtb) immunoreactivity were widely used to monitor TB epidemiology in high-incidence settings, but were limited by challenges with both delivering and interpreting the test. Here we argue that the shifting epidemiology of tuberculosis, and the development of new tests for Mtb infection, make it timely and important to revisit the strategy of TB surveillance based on infection or immunoreactivity. Mtb infection surveys carry their own operational challenges and fundamental questions, for example: around survey design and frequency; which groups should be included; how the prevalence of immunoreactivity in a population should be used to estimate force of infection; how individual results should be interpreted and managed; and how surveillance can be delivered efficiently and ethically. However, if these knowledge gaps are addressed, the relative feasibility and lower costs of Mtb infection surveillance offer a powerful and affordable opportunity to better "know your TB epidemic", understand trends, identify high-risk and underserved communities, and tailor public health responses to dynamic epidemiology.

High SARS-CoV-2 Seroprevalence in Rural Peru, 2021: a Cross-Sectional Population-Based Study.

Latin America has been severely affected by the COVID-19 pandemic. The COVID-19 burden in rural settings in Latin America is unclear. We performed a cross-sectional, population-based, random-selection SARS-CoV-2 serologic study during March 2021 in the rural population of San Martin region, northern Peru. In total, 563 persons from 288 houses across 10 provinces were enrolled, reaching 0.2% of the total rural population of San Martin. Screening for SARS-CoV-2 IgG antibodies was done using a chemiluminescence immunoassay (CLIA), and reactive sera were confirmed using a SARS-CoV-2 surrogate virus neutralization test (sVNT). Validation of the testing algorithm using prepandemic sera from two regions of Peru showed false-positive results in the CLIA (23/84 sera; 27%) but not in the sVNT, highlighting the pitfalls of SARS-CoV-2 antibody testing in tropical regions and the high specificity of the two-step algorithm used in this study. An overall 59.0% seroprevalence (95% confidence interval [CI], 55 to 63%) corroborated intense SARS-CoV-2 spread in San Martin. Seroprevalence rates between the 10 provinces varied from 41.3 to 74.0% (95% CI, 30 to 84%). Higher seroprevalence was not associated with population size, population density, surface area, mean altitude, or poverty index in Spearman correlations. Seroprevalence and reported incidence diverged substantially between provinces, suggesting regional biases of COVID-19 surveillance data. Potentially, limited health care access due to environmental, economic, and cultural factors might lead to undetected infections in rural populations. Additionally, test avoidance to evade mandatory quarantine might affect rural regions more than urban regions. Serologic diagnostics should be pursued in resource-limited settings to inform country-level surveillance and vaccination strategies and to support control measures for COVID-19. IMPORTANCE Latin America is a global hot spot of the COVID-19 pandemic. Serologic studies in Latin America have been mostly performed in urban settings. Rural populations comprise 20% of the total Latin American population. Nevertheless, information on COVID-19 spread in rural settings is scarce. Using a representative population-based seroprevalence study, we detected a high seroprevalence in rural populations in San Martin, northern Peru, in 2021, reaching 41 to 74%. However, seroprevalence and reported incidence diverged substantially between regions, potentially due to limited health care access or test avoidance due to mandatory quarantine. Our results suggest that rural populations are highly affected by SARS-CoV-2 even though they are sociodemographically distinct from urban populations and that highly specific serological diagnostics should be performed in resource-limited settings to support public health strategies of COVID-19 control.

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.

The COVID-19 Pandemic in Peru: What Went Wrong?

Despite the early adoption of a national lockdown and other restrictions, Peru has been severely impacted by the COVID-19 pandemic. Having reached a milestone of more than 1,200 deaths per one million inhabitants by February 2021, important messages can be learned from how the pandemic was handled. Possible explanations for poor outcomes are a fragmented and already overwhelmed public health sector, lack of infrastructure and specialized personnel to tackle the pandemic, and deficient leadership from health authorities.

Oxygen saturation as a predictor of mortality in hospitalized adult patients with COVID-19 in a public hospital in Lima, Peru.

INTRODUCTION: Peru is among the top ten countries with the highest number of coronavirus disease 2019 (COVID-19) cases worldwide. The aim of the study was to describe the clinical features of hospitalized adult patients with COVID-19 and to determine the prognostic factors associated with in-hospital mortality. METHODS: We conducted a retrospective cohort study among adult patients with COVID-19 admitted to Hospital Cayetano Heredia; a tertiary care hospital in Lima, Peru. The primary outcome was in-hospital mortality. Multivariate Cox proportional hazards regression was used to identify factors independently associated with in-hospital mortality. RESULTS: A total of 369 patients (median age 59 years [IQR:49-68]; 241 (65.31%) male) were included. Most patients (68.56%) reported at least one comorbidity; more frequently: obesity (42.55%), diabetes mellitus (21.95%), and hypertension (21.68%). The median duration of symptoms prior to hospital admission was 7 days (IQR: 5-10). Reported in-hospital mortality was 49.59%. By multiple Cox regression, oxygen saturation (SaO2) values of less than 90% on admission correlated with mortality, presenting 1.86 (95%CI: 1.02-3.39), 4.44 (95%CI: 2.46-8.02) and 7.74 (95%CI: 4.54-13.19) times greater risk of death for SaO2 of 89-85%, 84-80% and <80%, respectively, when compared to patients with SaO2 >90%. Additionally, age >60 years was associated with 1.88 times greater mortality. CONCLUSIONS: Oxygen saturation below 90% on admission is a strong predictor of in-hospital mortality in patients with COVID-19. In settings with limited resources, efforts to reduce mortality in COVID-19 should focus on early identification of hypoxemia and timely access to hospital care.

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.