ABSTRACT BACKGROUND: Syphilis is a major public health issue worldwide. In people living with human immunodeficiency virus (PLHIV), there are higher incidences of both syphilis and neurosyphilis. The criteria for referring PLHIV with syphilis for lumbar puncture is controversial, and the diagnosis of neurosyphilis is challenging. OBJECTIVE: To describe the knowledge, attitudes, and practices of infectious disease specialists and residents in the context of care for asymptomatic HIV-syphilis coinfection using close-ended questions and case vignettes. DESIGN AND SETTING: Cross-sectional study conducted in three public health institutions in São Paulo (SP), Brazil. METHODS: In this cross-sectional study, we invited infectious disease specialists and residents at three academic healthcare institutions to answer a self-completion questionnaire available online or in paper form. RESULTS: Of 98 participants, only 23.5% provided answers that were in line with the current Brazilian recommendation. Most participants believed that the criteria for lumbar puncture should be extended for people living with HIV with low CD4+ cell counts (52.0%); in addition, participants also believed that late latent syphilis (29.6%) and Venereal Disease Research Laboratory (VDRL) titers ≥ 1:32 (22.4%) should be conditions for lumbar puncture in PLHIV with no neurologic symptoms. CONCLUSION: This study highlights heterogeneities in the clinical management of HIV-syphilis coinfection. Most infectious disease specialists still consider syphilis stage, VDRL titers and CD4+ cell counts as important parameters when deciding which patients need lumbar puncture for investigating neurosyphilis.

Abstract Rapid Diagnostic Tests (RDT) are useful to identify syphilis cases, particularly for hard-to-reach populations and if laboratory services are scarce. However, RDT performance may be suboptimal. We aimed to assess the sensitivity and specificity of a syphilis RDT using well-characterized blood donors’ samples. We categorized samples from 811 blood donors into five groups: 1 - Samples with reactive Chemiluminescence (QML), FTA-Abs, and VDRL; 2 - Samples with reactive QML and FTA-Abs, and nonreactive VDRL; 3 - Samples with reactive QML, and nonreactive for other markers (false-positives); 4 - Controls with nonreactive QML; and 5 - Samples reactive for HIV, with nonreactive QML. Sensitivity was tested in groups 1 (overall and according to VDRL titers) and 2; specificity was tested in groups 3‒5. The RDT had high specificity, even in samples reactive for HIV. The sensitivity was high (91.9%) in samples with reactive VDRL but varied between 75.0%‒100% according to VDRL titers. The overall sensitivity was lower (81.3%) in samples with reactive FTA-Abs and nonreactive VDRL. The RDT is a useful tool to detect active syphilis but may be more limited for cases with very early or remote infection, or those with prior treatment. When higher sensitivity is needed, additional strategies including recurrent testing or laboratory-based tests may be required.

ABSTRACT Vaccination coverage has been dropping in Brazil and other countries. In addition, immune responses after vaccination may not be homogeneous, varying according to sociodemographic and clinical factors. Understanding the determinants of incomplete vaccination and negative antibody test results may contribute to the development of strategies to improve vaccination effectiveness. In this study, we aimed to investigate the frequency of vaccine adherence, factors associated with incomplete vaccination for measles, mumps, rubella (MMR) and hepatitis A, and factors associated with the seronegative test results for measles, mumps and hepatitis A at 2 years of age. This was a population-based cohort that addressed health conditions and mother/infant nutrition in Cruzeiro do Sul city, Brazil. Vaccination data were obtained from official certificates of immunization. The children underwent blood collection at the two-year-old follow-up visit; the samples were analyzed using commercially available kits to measure seropositivity for measles, mumps, and hepatitis A. We used modified Poisson regression models adjusted for covariates to identify factors associated with incomplete vaccination and negative serology after vaccination. Out of the 825 children included in the study, adherence to the vaccine was 90.6% for MMR, 76.7% for the MMRV (MMR + varicella), and 74.9% for the hepatitis A vaccine. For MMR, after the adjustment for covariates, factors associated with incomplete vaccination included: white-skinned mother; paid maternity leave; raising more than one child; lower number of antenatal consultations; and attending childcare. For hepatitis A, the factors included: white-skinned mother and not having a cohabiting partner. The factors with statistically significant association with a negative antibody test result included: receiving Bolsa Familia allowance for measles and mumps; incomplete vaccination for measles; and vitamin A deficiency for mumps. Strategies to improve the efficiency of vaccine programs are urgently needed. These include improvements in communication about vaccine safety and efficacy, and amplification of access to primary care facilities, prioritizing children exposed to the sociodemographic factors identified in this study. Additionally, sociodemographic factors and vitamin A deficiency may impact the immune responses to vaccines, leading to an increased risk of potentially severe and preventable diseases.

Abstract Introduction: Optimized allocation of medical resources to patients with COVID-19 has been a critical concern since the onset of the pandemic. Methods: In this retrospective cohort study, the authors used data from a Brazilian tertiary university hospital to explore predictors of Intensive Care Unit (ICU) admission and hospital mortality in patients admitted for COVID-19. Our primary aim was to create and validate prediction scores for use in hospitals and emergency departments to aid clinical decisions and resource allocation. Results: The study cohort included 3,022 participants, of whom 2,485 were admitted to the ICU; 1968 survived, and 1054 died in the hospital. From the complete cohort, 1,496 patients were randomly assigned to the derivation sample and 1,526 to the validation sample. The final scores included age, comorbidities, and baseline laboratory data. The areas under the receiver operating characteristic curves were very similar for the derivation and validation samples. Scores for ICU admission had a 75% accuracy in the validation sample, whereas scores for death had a 77% accuracy in the validation sample. The authors found that including baseline flu-like symptoms in the scores added no significant benefit to their accuracy. Furthermore, our scores were more accurate than the previously published NEWS-2 and 4C Mortality Scores. Discussion and conclusions: The authors developed and validated prognostic scores that use readily available clinical and laboratory information to predict ICU admission and mortality in COVID-19. These scores can become valuable tools to support clinical decisions and improve the allocation of limited health resources.

Abstract Background In the initial phases of the COVID-19 pandemic, strategies adopted to reduce the dissemination of SARS-CoV-2 relied on non-pharmacological interventions, including physical distancing. Mobility restrictions affected the availability and quality of care for many health conditions, including sexually transmitted infections. Objective To investigate the impact of the COVID-19 pandemic mobility restriction on syphilis and HIV testing in outpatient settings. Methods In this study, we collected the weekly number of syphilis and HIV tests performed in a referent laboratory in São Paulo, Brazil, as well as the percentage of positive tests between January 2019 and December 2021. We also retrieved data on retail and recreation mobility in São Paulo city using Google COVID-19 Community Mobility Reports. We explored the association between populational mobility and the number of weekly tests and the association between the number of weekly tests and the percentage of positive results during the pandemic period. The analyses were conducted separately for syphilis and HIV tests. Results We found that mobility restrictions during the COVID-19 pandemic have been associated with a significant decrease in both syphilis and HIV tests performed in outpatient settings. We also observed that the number of tests performed was inversely associated with the percentage of positive results for syphilis; this association was also apparent for HIV tests in the first wave of the pandemic in the graphic analysis. Conclusion Taken together, our findings suggest an indirect impact of COVID-19 pandemic-related mobility restrictions on the uptake of diagnostic tests for HIV and syphilis and the potential adoption of targeted-testing strategies. Understanding the extent and complexity of COVID-19 aftermaths on specific conditions and communities is essential to build strategies to mitigate the long-term consequences of COVID-19.

ABSTRACT Cycle threshold (Ct) values in COVID-19 reverse-transcription polymerase chain reaction (RT-PCR) tests estimate the viral load in biological samples. Studies have investigated variables associated with SARS-CoV-2 viral load, aiming to identify factors associated with higher transmissibility. Using the results from tests performed between May/2020-July/2022 obtained from the database of a referent hospital in Sao Paulo, Brazil, we investigated associations between Ct values and patient’s age, gender, sample collection setting and pandemic period according to the predominant SARS-CoV-2 variant locally. We also examined variations in Ct values, COVID-19 incidence, mortality, and vaccination coverage over time. The study sample included 42,741 tests. Gender was not significantly associated with Ct values. Age, sample collection setting and the pandemic period were significantly associated with Ct values even after adjustment to the multivariable model. Results showed lower Ct values in older groups, during the Gamma and Delta periods, and in samples collected in emergency units; and higher Ct values in children under 10 years old, home-based tests, during the Omicron period. We found evidence of a linear trend in the association between age and Ct values, with Ct values decreasing as age increases. We found no clear temporal associations between Ct values and local indicators of COVID-19 incidence, mortality, or vaccination between February/2020-November/2022. Our findings suggest that SARS-CoV-2 Ct values, a proxy for viral load and transmissibility, can be influenced by demographic and epidemiological variables.

ABSTRACT PrEP users are under high risk for bacterial sexually transmitted infections (STI), including those caused by Treponema pallidum (Tp), Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (Ng). Ct and Ng screening at multiple anatomic sites may improve the diagnostic sensitivity among high-risk populations. We analyzed the prevalence and incidence of Ct, Ng, and Tp and investigated predictors of bacterial STI occurrence between January 2018 and November 2019 in a retrospective cohort of PrEP users in Sao Paulo, Brazil. We describe the frequency and percentage of Ct/Ng per anatomical site and calculate the percentage of missed diagnosis if molecular testing were applied only in symptomatic patients, or only in urine samples. Patients underwent syphilis testing every 3-4 months and Ct/Ng testing every 6 months. We included 413 PrEP users with a median age of 31 years. At baseline, 25% had a positive treponemal test and 7% had active syphilis; Ct and Ng were more frequently detected in the oropharynx and anus (6.4-6.9%) than in urine samples (0.7-2.6%). Twelve months after the onset of PrEP, the incidence of Tp, Ct and Ng was, respectively, 13.4%, 11.4% and 8.9%. During follow-up, 23 out of 33 Ct/Ng cases (69%, 95% CI 51-84) would have been missed if oropharynx and anus samples had not been tested. In addition, if only symptomatic cases had been tested, 30 out of 33 Ct/Ng cases (90%, 95% CI 75-98) would have been missed. Participants with incident STI had a higher baseline number of sexual partners and a longer follow-up. Our study reinforces that active and frequent screening for STI is a powerful strategy to improve the diagnostic sensitivity.

ABSTRACT Blood transfusion is still an irreplaceable therapeutic modality, widely applied to medical care. Clinical interviews and laboratory testing for transfusion-transmitted infections (TTI) are routinely performed to prevent TTI among the recipients. However, there is still a residual risk of TTI, and some blood banks have adopted the confidential unit exclusion (CUE) as an additional safety strategy. In this study, we investigated the demographic characteristics and laboratory results of the screening of TTI among blood donors who opted for the CUE, compared to blood donors who did not opt for the CUE. In this study, we included 32,261 blood donations collected in a single blood bank in Sao Paulo, Brazil. A very small proportion of donors (0.25%) opted for the CUE. They were mainly single males and were more likely to have HBV, syphilis, and other positive results in the combined screening for TTI, in comparison with those who did not opt for the CUE. This difference was statistically significant in both the univariable and the multivariable analysis adjusted for age, gender , marital status and years of schooling. Our findings highlight that CUE may be a useful tool to improve the safety for blood recipients, but its efficiency is context-dependent.

ABSTRACT Background Mobility restrictions and overloaded health services during the COVID-19 pandemic compromised services dedicated to the prevention and care of HIV and other sexually transmitted infections (STI). In this study, we present client’s responses to standardized questionnaires applied during the COVID-19 pandemic period as part of the strategy to measure impacts on social and sexual vulnerability, access to STI prevention services, and access to STI care. Methods: The questionnaires included variables on sociodemographics, behavior, risk perception, prevention attitudes, barriers to service-based HIV rapid test, reasons for taking an HIV self-test, and access to health services for STI diagnosis and treatment. We explored demographic variables associated with income reduction, reduced access to HIV/STI testing/treatment and increased vulnerability to HIV/STI. Results: 847 participants responded to the study questionnaire between May 2020 and January 2021. Most were young, cisgender male, and 63% self-reported as men who have sex with men. Income reductions were reported by 50%, with 30% reporting a decline over 50% of total income. An increase in heavy episodic drinking (>5 doses) was reported by 18%; 7% reported more sexual partners and 6% reported using condoms less often. Difficulties in obtaining HIV tests, tests for other STI and treatment for STI were reported by 5%, 6% and 6%, respectively. Lower schooling was significantly associated with income reduction (p = 0.004) and with reduced access to HIV/STI testing or STI treatment (p = 0.024); employment status was associated with income reduction (p < 0.001) and increased vulnerability to HIV/STI (p = 0.027). Having access to an expedite test result, avoiding physical attendance in health units during the pandemic, and undertaking the test with privacy with a trusted person were reported as motivators for HIV self-test. Conclusions: Our findings are relevant to promote service improvements tailored to subgroups more likely to struggle with detrimental effects during and after the COVID-19 pandemic.

ABSTRACT Background The recognition of the causal association between Zika virus (ZIKV) infection during pregnancy and congenital abnormalities including microcephaly underlines the importance of preventing this disease in pregnant women (PW) and women of childbearing age (WCA). Although Brazil and other Latin American countries reported a significant reduction in the number of ZIKV infections in recent years, epidemic waves can recur in settings with previous outbreaks as conditions for transmission remain optimal and susceptible populations are continuously replenished. Methods: In this cross-sectional study, we enrolled 64 PW and 260 non-pregnant WCA attending routine medical appointments in two primary care units in São Paulo, Brazil, and assessed knowledge and attitudes about ZIKV infection and prevention. Results: Most women reported knowing that ZIKV is transmitted through the bite of Aedes mosquitos, and most knew that acute symptoms are similar to those seen in Dengue infection. Furthermore, most participants correctly described that ZIKV infection during pregnancy may cause detrimental outcomes for the newborn. However, most ignored that ZIKV infection can be asymptomatic, and only 15% knew about the risk of ZIKV sexual transmission. We found no statistically significant differences between PW and WCA regarding knowledge about ZIKV sexual transmission. Knowledge about ZIKV sexual transmission was significantly associated with education; among participants with ≤12 schooling years, only 9.0% (95%CI 3.4-18.5%) correctly answered that ZIKV can be sexually transmitted, compared to 12.9% (95%CI 8.2-18.8%) among participants with 12-14 schooling years, and to 24.4% (95%CI 15.9-34.9%) of participants with ≥15 schooling years (p = 0.015). Education remained independently associated with knowledge about sexual transmission of ZIKV in a multivariate logistic regression model adjusted for age, race and pregnancy status (p = 0.022). Conclusion: Our findings underscore the urgent need of educational and family planning programs that may help prevent detrimental outcomes of ZIKV infection in an endemic area of Brazil.

Resumo: Introdução: Uma extensa literatura demonstra os benefícios do ensino ativo na educação médica e a necessidade de atualização das metodologias de ensino. As estratégias de aprendizagem ativa consolidam o conhecimento teórico e estimulam as habilidades conceituais do aluno. No entanto, reformar a prática pedagógica é desafiador. Existem diversas estratégias de aprendizagem ativa que sugerem uma adaptação do formato de entrega do conteúdo, de modo a adequá-las a diversos contextos. Neste artigo, discutimos a experiência da aplicação da técnica Four Corners no ensino de doenças infecciosas em nossa instituição. Relato de experiência: A estratégia Four Corners foi implementada da seguinte maneira: 1. preparação: os estudantes recebem material de estudo para análise prévia; 2. preparação da sala: cada um dos quatro cantos recebe cartelas com os casos clínicos escolhidos; 3. divisão de tarefas: as tarefas são divididas entre os estudantes; 4. atividade: os estudantes leem e discutem cada um dos casos propostos com mínima interferência do moderador; 5. finalização: discussão final com todos os participantes liderados pelo moderador. A duração de toda a tarefa varia de duas horas e meia a três horas. Discussão: O processo educacional emerge da experiência do aprendiz. Muitos professores do ensino superior acreditam que promovem o pensamento crítico por meio do ensino ativo em suas aulas, entretanto a porcentagem dos que aplicam essas técnicas ainda é baixa. Existe uma ampla variedade de técnicas ativas de ensino, e muitas delas se adaptam a diferentes cenários. A técnica Four Corners é uma estratégia de aprendizagem ativa que promove debate e troca de conceitos entre os estudantes. Conclusão: Este relato de experiência descreve uma estratégia de aprendizagem ativa para o ensino de doenças infecciosas para estudantes de Medicina. O aprimoramento da educação médica passa por entender o papel do professor como mediador do processo de aprendizagem. Propor novas estratégias de ensino é desafiador e requer ajustes frequentes. A estratégia Four Corners melhora o envolvimento do aluno com o processo de aprendizagem e é eficiente para compreender um conteúdo teórico extenso em um tempo de discussão relativamente curto.

Abstract: Introduction: An extensive literature has demonstrated the benefits of active learning in medical education and has revealed the need for updating the teaching methodologies. Active learning strategies consolidate the theoretical knowledge, while simultaneously encouraging the student´s concrete abilities. Nonetheless, remodeling the pedagogical practice is challenging. Several active learning strategies are available and selecting the most suitable one is often a matter of format, not of content. In this article, we discuss the experience of the ‘Four Corners’ technique in the teaching of Infectious Diseases during the internship at our institution. Experience report: The four corners strategy can be adapted to different topics and should be implemented as follows: 1. pre-activity learning: students receive the supportive material for previous analysis; 2. Preparation of the room: each of the four corners is labeled with a different case vignette; 3. Dividing tasks: the specific assignments are divided among the students; 4. Activity: the students read the case vignette and discuss the questions, while the mediator has an observer’s role, and 5. Debriefing: final discussion with all participants led by the mediator. The entire process takes from 2h30 to 3 hours. Discussion: The educational process emerges from the learner´s experience. Many instructors working in higher education believe they promote critical thinking and active teaching during their classes; however, the percentage of teachers who regularly use active teaching strategies is still low. A range of different active learning strategies have been described and many can be adapted to different scenarios; most approaches change the nature of the learning experience but do not always require a change in the given subject. The Four Corners technique is an active learning strategy that promotes debate and exchange of ideas among students. Conclusion: This experience report describes an active learning strategy for the teaching of Infectious Diseases to medical students. The medical education improvement goes through highlighting the teacher’s role as a mediator of the learning process; proposing new teaching strategies is challenging and requires frequent adjustments. The Four Corners strategy improves student’s engagement with the learning process, and it is an efficient strategy to comprise an extensive theoretical content in a relatively short discussion time.

ABSTRACT The study aimed to analyze the impact of health interventions carried out in the city of Palmas, Brazil, on the epidemiological and operational indicators of leprosy between 2007 and 2017. The intervention consisted of training healthcare personnel on the diagnosis and follow-up of patients and organizing the referral of patients to health units. Estimates of the impact were calculated by taking the differences between indicators reported in two equal periods of 1.5 years pre- and post-intervention, with a transition period of six months. During the study period, the database contained 1,875 notifications, with 66% of cases diagnosed in the post-intervention period. There was a predominance of males (52%); aged 50 years or more (34.9%); with mixed ethnicity (63.5%). The low level of education was noticeable, with more than half of the cases (51.7%) reporting illiteracy or ≤ 7 years of education. The intervention resulted in an increase in both, epidemiological and operational indicators, suggesting a positive impact of the intervention on leprosy detection and treatment. Our results also emphasize the need for further studies addressing the impact of pragmatic health interventions aiming at controlling and eliminating the disease.

ABSTRACT Tuberculosis (TB) is still a leading cause of morbidity and mortality among people living with HIV (PLHIV). The diagnosis of latent TB is required for the implementation of prophylactic therapy with isoniazid (PTI). However, low access to diagnosis of latent TB and non-adherence to PTI may hinder potential benefits of this essential intervention. In this study, we addressed the access and adherence to PTI in a cohort of PLHIV with positive tuberculin skin test (TST) in a reference HIV clinic in Sao Paulo, Brazil. We have also analyzed the occurrence of active TB over a median of 131 months after a positive TST among study participants. Our findings revealed that 88.3% of the 238 TST-positive patients had access to PTI, and 196 (93.3%) of those with access adhered to PTI. Active tuberculosis was diagnosed in three of the 196 TST-positive patients who adhered to PTI (1.5%; 95% confidence interval [CI] 0.3-4.4%), whereas seven cases were detected among 42 patients without access or who did not adhere to PTI (16.6%; 95% CI 7.0-31.3%). The apparent beneficial effect of PTI in our cohort is consistent with previous studies including PLHIV, and highlights the importance of reliably delivering each of the steps between screening for latent TB and provision of PTI.

ABSTRACT Background: HIV-infected children surviving until adulthood have been transitioning to adult outpatient health care service in Brazil since the late 2000's. Deterioration of clinical condition is expected during this period, as reported among youths with non-communicable chronic diseases. Despite their young age, they are long-term hosts of the virus, have prolonged exposure to antiretroviral therapy and have suffered from the social determinants and stigma of HIV infection since early childhood. Objectives: This study aimed to 1) describe demographic and clinical characteristics at the first appointment at adult care service following pediatric care of a cohort of Brazilian youths living with HIV since childhood; and 2) retrospectively address adherence and clinical variables in the last two years of pediatric follow-up. Methods: Descriptive study. Results: 41 consecutive patients referred to adult outpatient care from a pediatric HIV unit were enrolled, median age 19 years, and median lifetime CD4 + nadir 117 cell/mm3; 89% reported previous AIDS-defining conditions. At first laboratory assessment in adult care, only 46% had undetectable (<400 copies/ml) HIV viral load and the median CD4 + count was 250 cell/mm3. Conclusion: Youths living with HIV at the transition from pediatric to adult care had poor treatment adherence, low lifetime CD4 + cell nadir, low CD4 cell count and detectable HIV viral load. Health care providers should closely monitor these adolescents in a youth friendly environment, prepared for open communication about all aspects of their health.