Higher intraindividual variability of body mass index is associated with elevated risk of COVID-19 related hospitalization and post-COVID conditions.

BACKGROUND: Cardiometabolic diseases are risk factors for COVID-19 severity. The extent that cardiometabolic health represents a modifiable factor to mitigate the short- and long-term consequences from SARS-CoV-2 remains unclear. Our objective was to evaluate the associations between intraindividual variability of cardiometabolic health indicators and COVID-19 related hospitalizations and post-COVID conditions (PCC) among a relatively healthy population. METHODS: This retrospective, multi-site cohort study was a post-hoc analysis among individuals with cardiometabolic health data collected during routine blood donation visits in 24 US states (2009-2018) and who responded to COVID-19 questionnaires (2021-2023). Intraindividual variability of blood pressure (systolic, diastolic), total circulating cholesterol, and body mass index (BMI) were defined as the coefficient of variation (CV) across all available donation timepoints (ranging from 3 to 74); participants were categorized into CV quartiles. Associations were evaluated by multivariable binomial regressions. RESULTS: Overall, 3344 participants provided 42,090 donations (median 9 [IQR 5, 17]). The median age was 48 years (38, 56) at the first study donation. 1.2% (N = 40) were hospitalized due to COVID-19 and 15.5% (N = 519) had PCC. Higher BMI variability was associated with greater risk of COVID-19 hospitalization (4th quartile aRR 4.15 [95% CI 1.31, 13.11], p = 0.02; 3rd quartile aRR 3.41 [95% CI 1.09, 10.69], p = 0.04). Participants with higher variability of BMI had greater risk of PCC (4th quartile aRR 1.29 [95% CI 1.02, 1.64]; p = 0.04). Intraindividual variability of blood pressure (systolic, diastolic) and total circulating cholesterol were not associated with COVID-19 hospitalization or PCC risk (all p > 0.05). From causal mediation analysis, the association between the highest quartiles of BMI variability and PCC was not mediated by hospitalization (p > 0.05). CONCLUSIONS: Higher intraindividual variability of BMI was associated with COVID-19 hospitalization and PCC risk. Our findings underscore the need for further elucidating mechanisms that explain these associations and importance for consistent maintenance of body weight.

Heterogeneities of the impact of public health policies on HIV/AIDS indicators in Brazil according to sociodemographic factors: A real-life study.

INTRODUCTION: The impact of specific policies on HIV care has been scarcely investigated. In this study we aimed to analyze the impact of the Treatment For All policy (TFA-2013) and the adoption of integrase strand transfer inhibitors (INSTIs-2017) as first-line therapy on clinical indicators of people living with HIV (PLHIV) in Brazil. METHODS: We assessed the public database of Brazil's Ministry of Health and extracted data from 2009 to 2019. We investigated the impact of TFA and INSTIs with a time-series analysis of four health indicators in PLHIV: antiretroviral treatment (ART) initiation with a CD4+ count >500/mm3 ; ART initiation <1 month after the first CD4+ measurement; viral load suppression (VLS); and treatment adherence. We explored trends over time by gender, age, macroregion of residency and municipal-level social vulnerability index. RESULTS: We included 753 316 PLHIV in 2019. Most were males (64.81%) in the 30-49 years age category (50.86%). We observed an overall improvement in all HIV clinical indicators, with notable impact of TFA on timely ART initiation and VLS, and mild impact of INSTIs on treatment adherence. Such improvements were heterogeneous, with remarkable gaps in gender, age and socioeconomic groups that have persisted over time. Indicators point to inferior outcomes among children, older adults, women and people living in socially vulnerable locations. CONCLUSIONS: Recent Brazilian public policies have had positive impacts on key HIV clinical indicators. However, our results highlight the need for specific policies to improve HIV care for children, older adults, women and socially vulnerable groups.

Hookworm infection as a model for deepen knowledge of iron metabolism and erythropoiesis in anemia.

Over the years, there has been progress in understanding the molecular aspects of iron metabolism and erythropoiesis. However, despite research conducted both in laboratories and living organisms, there are still unanswered questions due to the complex nature of these fields. In this study we investigated the effects of hookworm infection on iron metabolism and how the hosts response to anemia is affected using hamsters infected with Ancylostoma ceylanicum as a model. Our data revealed interesting relationships between infection-induced anemia, erythropoiesis, iron metabolism, and immune modulation, such that the elevated production of erythropoietin (EPO) in renal tissue indicated intensified erythropoiesis in response to anemia. Additionally, the increased expression of the erythroferrone (ERFE) gene in the spleen suggested its involvement in iron regulation and erythropoiesis. Gene expression patterns of genes related to iron metabolism varied in different tissues, indicating tissue-specific adaptations to hypoxia. The modulation of pro-inflammatory and anti-inflammatory cytokines highlighted the delicate balance between immune response and erythropoiesis. Data derived from the investigation of changes induced in iron metabolism and stress erythropoiesis following anemia aid in our understanding of mechanisms related to blood spoliation and anemia, which could potentially be extrapolated or compared to other types or causes of anemia. These findings also contribute to our understanding of the pathophysiology of erythropoiesis in the context of blood loss.

SARS-CoV-2 antibody levels and long COVID occurrence in blood donors.

BACKGROUND: Long COVID is a common condition lacking consensus definition; determinants remain incompletely understood. Characterizing immune profiles associated with long COVID could support the development of preventive and therapeutic strategies. METHODS: We used a survey to investigate blood donors' infection/vaccination history and acute/persistent symptoms following COVID-19. The prevalence of long COVID was evaluated using self-report and an adapted definition from the RECOVER study. We evaluated factors associated with long COVID, focusing on anti-spike and anti-nucleocapsid SARS-CoV-2 antibodies. Lastly, we investigated long COVID clinical subphenotypes using hierarchical clustering. RESULTS: Of 33,610 participants, 16,003 (48%) reported having had COVID-19; 1853 (12%) had self-reported long COVID, 685 (4%) met an adapted RECOVER definition, and 2050 (13%) met at least one definition. Higher anti-nucleocapsid levels measured 12-24 weeks post-infection were associated with higher risk of self-reported and RECOVER long COVID. Higher anti-spike IgG levels measured 12-24 weeks post-infection were associated with lower risk of self-reported long COVID. Higher total anti-spike measured 24-48 weeks post-infection was associated with lower risk of RECOVER long COVID. Cluster analysis identified four clinical subphenotypes; patterns included neurological and psychiatric for cluster 1; neurological and respiratory for cluster 2; multi-systemic for cluster 3; and neurological for cluster 4. DISCUSSION: Long COVID prevalence in blood donors varies depending on the adopted definition. Anti-SARS-CoV-2 antibodies were time-dependently associated with long COVID; higher anti-nucleocapsid levels were associated with higher risk; and higher anti-spike levels were associated with lower risk of long COVID. Different underlying pathophysiologic mechanisms may be associated with distinct clinical subphenotypes.

Viral Kinetics in Sylvatic Yellow Fever Cases.

BACKGROUND: Yellow fever is a mosquito-borne zoonotic disease caused by yellow fever virus (YFV). Between 2017 and 2019, more than 504 human cases and 176 deaths were confirmed in the outskirts of São Paulo city. Throughout this outbreak, studies suggested a potential association between YFV viremia and mortality. METHODS: Viral ribonucleic acid was measured using reverse-transcription quantitative polymerase chain reaction in plasma samples collected at up to 5 time points, between 3 and 120 days after symptoms onset. RESULTS: Eighty-four patients with confirmed YFV infection were included. Most were males, median age was 42, and 30 (36%) died. Deceased patients were older than survivors (P = .003) and had a higher viremia across all time points (P = .0006). Mean values of viremia had a positive, statistically significant correlation with peak values of neutrophils, indirect bilirubin, aspartate transaminase, international normalized ratio, and creatinine. Finally, a Cox proportional hazards model adjusted for age and laboratory variables showed that viremia is independently associated with death, with a mean 1.84-fold increase (84%) in the hazard of death (P < .001) for each unit increase in mean log10 viremia. CONCLUSIONS: Our results raise the importance of monitoring YFV viremia and suggest a potential benefit of antiviral drugs or neutralizing monoclonal antibodies early in the course of this infection to improve disease outcomes.

Disparities in HIV continuum of care in the paediatric population: A real-life study in Brazil.

INTRODUCTION: Paediatric HIV follow-up is challenging, and treatment indicators are markedly far from Joint United Nations Programme on HIV/AIDS (UNAIDS) goals. In this study, we describe the 2019 Brazilian HIV cascade according to age categories and sociodemographic variables and address temporal trends between 2009 and 2019. METHODS: We obtained data from the Brazilian Ministry of Health monitoring database. Cascade outcomes included retention in care, antiretroviral use, and viral suppression. We assessed the effect of age on timely initiation of antiretroviral treatment (ART; initiation with CD4+ T-cell count ≥350 cells/mm3 or a first ART dispensation ≤30 days after the first CD4+ T-cell measurement) and detectable HIV viral load (>50 copies/mL) in univariable and multivariable analysis adjusted for sex, race, and social vulnerability index (SVI). Temporal trends in timely ART initiation and viral suppression were evaluated graphically. RESULTS: Among 771 774 people living with HIV, those in the youngest age categories had poorer indicators in the care cascade. Those in younger age groups, those with higher SVI, and those declaring Black and native Brazilian race/ethnicity had higher odds of having detectable viral load and delayed ART initiation. Although children living with HIV tend to start ART with higher CD4+ T-cell counts, time-series analysis suggests that improvements in treatment indicators seen in the adult population are not observed in the paediatric population. CONCLUSION: Our results highlight the challenges faced by children and adolescents living with HIV in achieving UNAIDS goals. Lower access to ART among children is a central barrier to improved paediatric care.

The pervasive association between political ideology and COVID-19 vaccine uptake in Brazil: an ecologic study.

BACKGROUND: Despite the unequivocal benefits of vaccination, vaccine coverage has been falling in several countries in the past few years. Studies suggest that vaccine hesitancy is an increasingly significant phenomenon affecting adherence to vaccines. More recently, during the COVID-19 pandemic, political views have emerged as an additional influencing factor for vaccine hesitancy. METHODS: In this ecologic study, we used information from publicly available databases to investigate the association between political ideology, depicted by the percentage of votes for the right-wing candidate Jair Bolsonaro in the presidential elections of 2018 and 2022, and COVID-19 vaccination in Brazilian municipalities. The primary endpoint was the COVID-19 vaccination index, calculated as the number of COVID-19 vaccine doses administered up to September 2022 divided by the number of inhabitants in each municipality. The analysis was conducted using Pearson correlation coefficients and linear regression models adjusted for HDI, the percentage of male voters, the percentage of voters who were older than 50 years old, and the percentage of voters with a middle school education or less. In addition, we explored whether the effect of the percentage of Bolsonaro voters on the COVID-19 vaccination index was modified in different quartiles of HDI using an interaction term. RESULTS: Five thousand five hundred sixty-three Brazilian municipalities were included in the analysis. For both the 2018 and 2022 elections, the percentage of votes for Jair Bolsonaro was significantly and inversely associated with COVID-19 vaccine uptake after adjustment for the sociodemographic characteristics of the voters (change in mean vaccination index in 2018 for each 1% increase in Bolsonaro voters -0.11, 95% confidence interval [CI] -0.13 to -0.08, p < 0.001; change in mean vaccination index in 2022 for each 1% increase in Bolsonaro voters -0.09, 95% CI -0.11 to -0.07, p < 0.001). We also found a statistically significant interaction between the primary predictor of interest and HDI scores, with a more significantly detrimental effect of the right-wing political stance in municipalities in the lower HDI quartiles (interaction p < 0.001 for the first HDI quartile; p = 0.001 for the second HDI quartile). CONCLUSION: Our findings suggest that political ideologies have influenced COVID-19 vaccine hesitancy in Brazilian municipalities, affecting communities inequitably. The politicization of vaccines is a new challenge for vaccine programs. Strategies to face these challenges should include joint efforts from governments and civil society for a common public health goal.

Say it right: measuring the impact of different communication strategies on the decision to get vaccinated.

BACKGROUND: Vaccine hesitancy is a concerning menace to the control of vaccine-preventable diseases. Effective health communication could promote an overall understanding of the importance, risks, and benefits of vaccination and reduce vaccine hesitancy. METHODS: In this survey, four fictitious newspaper articles addressing an emerging bogus disease and its vaccine were randomly assigned to participants. The first version focused on information about the disease; the second was akin to the first, including a case description and image. The third version focused on vaccine safety/efficacy; the fourth version was like the third, including a case description and image. After reading a single version of the article, participants responded if they would take the vaccine and if they would vaccinate their children. We used chi-squared tests for comparisons and investigated interactions with vaccine-hesitant attitudes. RESULTS: We included 5233 participants between August/2021 and January/2022; 790 were caregivers of a child ≤ 5 years old, and 15% had prior vaccine hesitancy. Although most declared intention to take the vaccine, the percentage was highest among those exposed to the newspaper article focusing on the vaccine safety/efficacy with the case description and picture (91%; 95% confidence interval 89-92%), and lowest among participants exposed to the article focusing on the disease with no case description (84%; 95% confidence interval 82-86%). Similar trends were observed in the intention of offspring vaccination. We found evidence of effect modification by vaccine-hesitant attitudes, with a higher impact of communication focusing on vaccine safety/efficacy compared to that focusing on disease characteristics among hesitant participants. CONCLUSION: Communication strategies focusing on different aspects of the disease-vaccine duet may impact vaccine hesitancy, and storytelling/emotive imagery descriptions may improve risk perception and vaccine uptake. Moreover, the effect of message framing strategies may differ according to previous vaccine hesitant attitudes.

Structure of the protective nematode protease complex H-gal-GP and its conservation across roundworm parasites.

Roundworm parasite infections are a major cause of human and livestock disease worldwide and a threat to global food security. Disease control currently relies on anthelmintic drugs to which roundworms are becoming increasingly resistant. An alternative approach is control by vaccination and 'hidden antigens', components of the worm gut not encountered by the infected host, have been exploited to produce Barbervax, the first commercial vaccine for a gut dwelling nematode of any host. Here we present the structure of H-gal-GP, a hidden antigen from Haemonchus contortus, the Barber's Pole worm, and a major component of Barbervax. We demonstrate its novel architecture, subunit composition and topology, flexibility and heterogeneity using cryo-electron microscopy, mass spectrometry, and modelling. Importantly, we demonstrate that complexes with the same architecture are present in other Strongylid roundworm parasites including human hookworm. This suggests a common ancestry and the potential for development of a unified hidden antigen vaccine.

Impact of coronavirus disease (COVID-19) on HIV testing and care provision across four continents.

OBJECTIVES: The coronavirus disease (COVID-19) pandemic has been associated with severe disruptions in health care services, and nonpharmacological measures such as social distancing also have an impact on access to screening tests and on the long-term care of patients with chronic conditions globally. We aimed to describe the impact of the COVID-19 pandemic on HIV testing and treatment and to describe strategies employed to mitigate the impact of COVID-19 on HIV care. METHODS: In this retrospective cohort study, we used secondary data from the AIDS Healthcare Foundation (AHF) Global Quality Program from 44 countries in four continents (Asia, Latin America and the Caribbean, Europe and Africa), and compared information on HIV testing, percentage of positive results, number of in-person appointments, and number of new enrolments in HIV care from 1 January 2020 to 31 August 2020 with the equivalent period in 2019. RESULTS: Despite marked inter-country heterogeneities, we found that COVID-19 was associated with a significant reduction in HIV testing, an increase in the percentage of positive tests, a reduction in the number of in-person consultations and a reduction in the number of new enrolments in care, despite the implementation of several mitigation strategies. The impact of COVID-19 differed across continents and key populations. CONCLUSIONS: Our findings suggest that, in the years to come, health care services must be prepared to respond to the impact of COVID-19 on HIV testing and care. Providers and facilities should build on the lessons learned so far to further improve mitigation strategies and establish care priorities for both the pandemic and the post-pandemic periods.

Clinical outcomes of HIV-syphilis coinfection among patients with no neurological symptoms: a retrospective cohort study.

OBJECTIVE: Our objective was to describe and compare the occurrence of neurological outcomes and neurosyphilis in people living with HIV with incident syphilis and no neurological symptoms who underwent early screening for asymptomatic neurosyphilis (ANS) or regular clinical management without a lumbar puncture. METHODS: This was a retrospective cohort study in a single referral centre of Sao Paulo, Brazil. Patients with incident syphilis diagnosed between January 2000 and August 2016 and meeting the adapted criteria for ANS investigation suggested by Marra et al. (CD4+ T-cell counts ≤350 cells/mm³ and/or venereal disease research laboratory test results ≥1:16) were identified. Those with no neurological symptoms and immediately referred for lumbar puncture were categorized as group 1, and those not referred for cerebrospinal fluid collection were categorized as group 2. We compared the occurrence of neurological symptoms and neurosyphilis diagnoses between the groups using incidence rates and Kaplan-Meier curves. RESULTS: We included 425 participants with a median follow-up of 6 years. The incidence rate of neurological symptoms was 36.5/1000 person-years in group 1 and 40.6/1000 person-years in group 2 (incidence rate ratio [IRR] 0.90; 95% confidence interval [CI] 0.57-1.39; p = 0.62). The incidence rate of neurosyphilis was 15.0 cases/1000 person-years in group 1 and 6.7 cases/1000 person-years in group 2 (IRR 2.26; 95% CI 0.93-5.68; p = 0.05). CONCLUSIONS: We found no statistically significant differences between groups in the incidence rates of neurological symptoms and neurosyphilis. Our findings support the current guidelines, which suggest a less invasive approach regarding ANS investigation among people living with HIV with incident syphilis.

Predictors of knowledge of and access to biomedical prevention among MSM and transgender men in Latin America: Results from the Latin American internet survey.

INTRODUCTION: HIV is still a central public health issue in Latin America, disproportionally affecting key populations. Knowledge and access to biomedical prevention strategies, including treatment as prevention (TASP) or undetectable = untransmissible (U=U), pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), are the first steps to increasing uptake. We used data from the Latin American MSM Internet Survey (LAMIS) to describe knowledge and access to biomedical HIV prevention strategies among gay, bisexual, transgender and other men who have sex with men (MSM) living in 18 Latin American countries. METHODS: We compared LAMIS data across countries and according to age categories using frequencies and percentages. We also used multivariable models to explore whether age, gender identity, sexual identity, steady partnership, HIV status and education were independently associated with outcomes. RESULTS: In all, 55 924 participants were included. Most were cisgender (99%) and identified as gay/homosexual (77%) or bisexual (17%). Schooling levels were very high, with 89% reporting highest attained education as tertiary level, university or post-graduation. In total, 16% had been previously diagnosed with HIV; of those, rates of undetectable viral load varied from 60% in Venezuela to 83% in Brazil. Overall, 54%, 54% and 52% of participants already knew about PEP, PrEP and U=U, respectively. Participants from Brazil and those aged between 26 and 55 years, living with diagnosed HIV and having a gay/homosexual identity had greater levels of awareness about biomedical prevention strategies. CONCLUSIONS: Our study highlights gaps in HIV prevention campaigns directed to MSM in Latin America resulting in low uptake of biomedical prevention methods.

HIV self-test: a tool to expand test uptake among men who have sex with men who have never been tested for HIV in São Paulo, Brazil.

OBJECTIVES: HIV self-testing is an effective tool to improve diagnostic coverage in key populations, enabling linkage to care and access to antiretroviral therapy. Its implementation requires better understanding of patients' perspectives on this novel strategy. The aim of the study was to investigate the perception of men who have sex with men (MSM) regarding the HIV oral fluid self-test (HIVST) in São Paulo, Brazil, and to analyse the sociodemographic characteristics and testing strategy preferences of individuals registered to undertake HIVST. METHODS: Preceding the implementation of HIVST use as public policy in 2019, we recruited MSM living in São Paulo to undertake HIVST using a digital platform, and investigated their sociodemographic profiles, testing experiences and testing preferences. Results were compared according to reported lifetime HIV testing. RESULTS: A total of 6477 MSM (median age 28 years) were recruited to the study from April 9th to December 31st, 2018. Seventy-eight per cent reported previous HIV testing. The opening hours of health facilities (53%), concern about disclosing intimate personal information to health care providers (34%) and fear of stigma (21%) were reported as the main barriers to testing. Older age, higher education, illicit drug use and self-identifying as gay were associated with prior HIV testing (P < 0.001). Most participants (67%) were unaware that HIVST was available before enrolling in the study. Preference for HIVST over other testing technologies was higher among those never tested (71%) than among participants with previous HIV testing (61%; P < 0.001). CONCLUSIONS: HIVST was found to be an effective tool to improve testing uptake among MSM, particularly those who had never been tested before. Characterization of the most likely users of HIVST among MSM will help to inform implementation and scaling up of this novel testing method in the Brazilian public health system.

Covid-19 Social Distancing, Lifestyle and Health Outcomes Among Persons Living with HIV (PLWH): A Web-based Survey.

We investigated changes in lifestyle, depressive symptoms, self-perception of health, and body weight changes of persons living with HIV (PLWH) during the COVID-19 social distancing (SD). In a Web-based cross-sectional survey, participants (n = 406) were questioned about lifestyle and health status before and during SD. Most responders were men, 50 + years old, high education level; 49.8% had their income reduced during SD. About 9% were diagnosed with COVID-19, of whom 13.5% required hospitalization. During SD: - most participants did not change their food intake, although 25% replaced healthy foods with unhealthy ones; -more than half mentioned poor sleep quality; -about 50% increased their sedentary behavior. Depressive symptoms (reported by 70.9%) were associated with sedentary behavior, poor sleep quality, and reduced income. About one-third had a negative perception of their health status, which was inversely associated with practicing physical exercises and positively associated with sedentarism and poor sleep quality. More than half increased their body weight, which was associated with a lower intake of vegetables. The older age reduced the odds of the three outcomes. Carefully monitoring PLWH regarding SD will enable early interventions toward health.

RESUMEN: En este trabajo investigamos los cambios en el estilo de vida, síntomas depresivos, autopercepción de salud y cambios en el peso corporal de las personas que viven con el VIH (PVCV) durante el distanciamiento social (DS) de COVID-19. En una encuesta transversal en línea, se preguntó a los participantes (n = 406) sobre el estilo de vida y el estado de salud antes y durante el DS. La mayoría de los encuestados eran hombres, mayores de 50 años, con alto nivel educativo. El 49,8% tuvo una disminución en sus ingresos durante el DS. El 9,1% fue diagnosticados con COVID-19, de los cuales 13,5% requirió hospitalización. Durante el DS: - la mayoría de los participantes no cambió su ingesta de alimentos, aunque el 25% reemplazó los alimentos saludables por los no saludables; más de la mitad mencionó mala calidad del sueño; cerca del 50% aumentó su comportamiento sedentario. Los síntomas depresivos (referidos por el 70,9%), fueron incrementados por el sedentarismo, la mala calidad del sueño y reducción de la renta. Cerca de un tercio tenía una percepción negativa de su estado de salud, que se redujo con la práctica de ejercicio físico y aumentó con el sedentarismo y la mala calidad del sueño. Más de la mitad aumentó su peso corporal, lo que se asoció con una menor ingesta de vegetales. Una edad más avanzada redujo las probabilidades de los tres desenlaces. El monitoreo cuidadoso de las PVCV con respecto al DS permitirá intervenciones tempranas para la salud.

Adherence to antiretroviral treatment and quality of life among transgender women living with HIV/AIDS in São Paulo, Brazil.

This study focused on factors associated with antiretroviral therapy (ART) adherence and quality of life among transgenderwomen in Sao Paulo, Brazil, using univariable and adjusted analysis. Adherence was evaluated with a self-report tool and with HIV viral load (VL) measurement. PROQOL-HIV was used to assess quality of life. 106 TGW with median 41 years old were included; most were white (56%) and had >10 years of education (57%). Median time since HIV/AIDS diagnosis was 10 years. Overall, participants had high T CD4+ counts (median 659 cells/mm3) and most (75%) had undetectable HIV VL. 85% were considered adherent using self-report (95%CI 77-91), whereas 72% (95%CI 62-80) were considered adherent when self-report and undetectable HIV VL were analyzed jointly. Older age was associated with higher ART adherence; each year increase in age was associated with 5% higher odds of adherence (p = 0.021). Quality of life ranged from good-excellent in 5 of 8 domains. Younger age, lower education, higher time since HIV diagnosis, comorbidities, illicit drugs use and depression were associated with lower PROQOL scores in specific domains in univariable analysis, while depression was also associated with lower total PROQOL score even after adjustment for age, comorbidities and time since HIV diagnosis (p = 0.048).

Diabetes mellitus hospitalization and mortality rate according to a national database in Brazil: a longitudinal study.

BACKGROUND: Diabetes mellitus (DM) is an important public health problem worldwide. In addition to the impairment in functionality, the large number of complications which lead to hospitalizations results in high treatment costs. The aim of this study was to analyze the incidence of hospitalizations, mortality rate and hospital costs, as well as to observe the temporal trend of hospitalizations and length of hospital stay due to DM between 2008 and 2019 in Brazil. METHODS: This is a longitudinal descriptive study in which all data regarding hospital admissions registered in the Brazilian system of Hospital Information of "Sistema Único de Saúde" (SIH/SUS; http://datasus.saude.gov.br ) due to DM (ICD-10) were included. Comparisons among the groups were performed by an unpaired Student's t-test, two-way ANOVA with a Tukey post hoc test (p < 0.05). RESULTS: An increased hospitalization of 1.83% due to DM was observed between 2008 and 2019 in Brazil. The Southeastern region had the highest incidence (34.6%) and mortality rate when compared to the other regions (p < 0.05). We also found that females were more likely to be hospitalized in comparison to males, without a statistically significant difference. Finally, a progressive increase of hospitalizations and mortality rate were observed according to age groups, as well as increased spending due to DM hospitalizations over the years. CONCLUSION: Hospitalizations due to DM in Brazil showed an expressive increase over the last 12 years, and there is a need for primary healthcare interventions to help reduce this situation.

Use of polyclonal IgY antibodies to detect serum immune complexes in patients with active hookworm infection.

Definitive diagnosis of hookworm infection is usually based on the microscopic detection of eggs in a stool sample; however, several cases display a low or irregular egg output. Serodiagnosis can be a useful tool to identify these cases, but conventional tests do not differentiate past from active infections. The aim of this study was to obtain and apply egg yolk polyclonal immunoglobulin (IgY) antibodies to detect immune complexes (ICs) in serum samples from patients infected with hookworm. Hens were immunized with Ancylostoma ceylanicum saline extract, their eggs were collected and then IgY antibodies were extracted and purified. Antibody purity was tested by 12% sodium dodecyl sulphate polyacrylamide gel electrophoresis and specificity was assessed by immunoblotting and immunofluorescence. IgY production was evaluated by kinetics enzyme-linked immunosorbent assay (ELISA). Sandwich ELISA tested the ability of IgY to detect ICs in serum samples, from which diagnostic parameters were calculated. Antibody responses increased steadily from day 7 to 42. In the immunoblotting assay, IgY recognized two protein complexes. The immunofluorescence assay showed no staining in control samples. The sandwich ELISA presented a very high diagnostic value, with a sensitivity of 90% and a specificity of 86.7%. Our pioneer strategy highlights the potential use of egg yolk IgY as a diagnostic test to detect active hookworm infection.

Untold stories of the Zika virus epidemic in Brazil.

The Zika virus infection outbreak in Brazil in 2014 to 2015 resulted in the identification of previously unknown consequences of the disease, including the notorious microcephaly among many defects in fetuses born to women infected during pregnancy. A number of individuals were involved in this remarkable discovery, from the detection of viral circulation in the country to the studies on the causal link with congenital abnormalities and the provision of awareness and social support to families affected by the disease. In this article, we review the background to this experience, describing aspects of the epidemiology, medical research, and scientific response to the Zika virus outbreak in Brazil.

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium.

BACKGROUND: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. METHODS: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies. DISCUSSION: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV. STUDY REGISTRATIONS: clinicaltrials.gov NCT03188731 (PW cohort), June 15, 2017; clinicaltrials.gov NCT03393286 (CH cohort), January 8, 2018; clinicaltrials.gov NCT03204409 (NH cohort), July 2, 2017.

Albendazole resistance induced in Ancylostoma ceylanicum is not due to single-nucleotide polymorphisms (SNPs) at codons 167, 198, or 200 of the beta-tubulin gene, indicating another resistance mechanism.

Mass drug administration has been implicated as the major cause of drug resistance in nematodes of ruminants. Single-nucleotide polymorphisms (SNPs) at codons 167, 198, and 200 of the beta-tubulin isotype 1 gene are associated with albendazole resistance mechanisms. Although drug resistance is suspected to occur in nematodes of the same order, at present, there is no evidence of a strong correlation between these canonical SNPs and albendazole resistance in hookworms. In the absence of a hookworm strain that is naturally resistant to albendazole, we produced an albendazole-resistant Ancylostoma ceylanicum strain by selective drug pressure. Restriction fragment length polymorphism-PCR (RFLP-PCR) was employed to identify the presence of SNPs previously associated with drug resistance in other nematodes. However, none of the benzimidazole resistance-associated SNPs known in other nematodes were found. A beta-tubulin isotype 1 gene mini-cDNA library was constructed to obtain the complete cDNA gene sequence for the analysis of the entire gene to identify distinct SNPs associated with resistance. Some SNPs were found, but the resulting sequences were not reproducibly detected among the different clones, preventing their association with the resistance mechanism. The parasitological and hematological parameters of the albendazole-resistant strain were characterized and compared to those of the sensitive strain. Although the albendazole-resistant strain was less adapted to its host, with fewer worms recovered, all other parameters analyzed were similar between both strains. The results of the present study indicate that the mechanism of albendazole resistance of the resistant strain described herein must differ from those that have previously been characterized. Thus, new mechanistic studies are needed in the future.