Aetiological molecular identification of sexually transmitted infections that cause urethral discharge syndrome and genital ulcer disease in Brazilian men: a nationwide study.

BACKGROUND: Little is known about the aetiology of urethral discharge syndrome (UDS) and genital ulcer disease (GUD) in Brazil due to limited access to laboratory tests and treatment based mainly on the syndromic approach. OBJECTIVES: To update Brazilian treatment guidelines according to the current scenario, the first nationwide aetiological study for UDS and GUD was performed. METHODS: Male participants with urethral discharge (UD) and/or genital ulcer (GU) reports were enrolled. Sample collection was performed by 12 sentinel sites located in the five Brazilian regions. Between 2018 and 2020, 1141 UD and 208 GU samples were collected in a Universal Transport Medium-RT (Copan). A multiplex quantitative PCR kit (Seegene) was used to detect UD: Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), M. hominis (MH), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), Ureaplasma parvum (UP), U. urealyticum (UU) and another kit to detect GU: cytomegalovirus (CMV), Haemophilus ducreyi (HD), herpes simplex virus type 1 (HSV1), herpes simplex virus type 2 (HSV2), lymphogranuloma venereum (LGV), Treponema pallidum (TP) and varicella-zoster virus (VZV). RESULTS: In UD samples, the frequency of pathogen detection was NG: 78.38%, CT: 25.6%, MG: 8.3%, UU: 10.4%, UP: 3.5%, MH: 3.5% and TV: 0.9%. Coinfection was assessed in 30.9% of samples, with 14.3% of NG/CT coinfection. The most frequent pathogen identified in GU was HSV2, present in 40.8% of the samples, followed by TP at 24.8%, LGV and CMV at 1%, and HSV1 at 0.4%. Coinfection of TP/HSV2 was detected in 4.4% of samples. VZV and HD were not detected. In 27.7% of the GU samples, no pathogen was detected. CONCLUSION: This study provided the acquisition of unprecedented data on the aetiology of UDS and GUD in Brazil, demonstrated the presence of a variety of pathogens in both sample types and reaffirmed the aetiologies known to be most prevalent globally.

Brazilian Clinical Practice Guidelines for Sexually Transmitted Infections That Cause Urethral Discharge: Assessment According to the AGREE II and Critical Analysis Based on the WHO Recommendations.

BACKGROUND: Sexually transmitted infections (STI) can have severe consequences. In Brazil, case management is recommended by the Clinical Protocol and Therapeutical Guidelines for Comprehensive Care for People with STIs (PCDT-IST). This study assessed the quality of PCDT-IST (2021) and reviewed the main recommendations for the management of STI that cause urethral discharge compared with the World Health Organization (WHO) STI Guidelines. METHODS: The PCDT-IST (2021) quality was independently assessed by 4 appraisers using the Appraisal of Guidelines Research and Evaluation instrument, version II (AGREE II). The PCDT-IST (2021) and the WHO Guidelines for the Management of Symptomatic STI (2021) were compared considering 14 different assessment domains. RESULTS: The PCDT-IST (2021) scores in the AGREE II domains were: Rigor of Development (58%), Applicability (35%), Editorial Independence (38%), Scope and Purpose (78%), Stakeholder Involvement (74%), and Clarity and Presentation (82%). The overall score was 67%, and all appraisers recommended the Brazilian guideline. Regarding the PCDT-IST (2021) and the WHO STI Guidelines (2021) comparation, 10 domains would be relevant for further reviewing the Brazilian recommendations: Diagnostic tests; Etiological approach; Treatment for recurrent urethral discharge; Treatment for urethritis without etiological agent identification; Treatment for gonococcal urethritis; Treatment for chlamydial urethritis; Retreatment for gonococcal infections; Treatment for Mycoplasma genitalium urethritis; Treatment for Trichomonas vaginalis urethritis; 10. Flowcharts. CONCLUSIONS: The PCDT-IST (2021) has a reasonable degree of quality. However, the domains of Applicability, Rigor of Development, and Editorial Independence must be better ensured. The guidelines comparison will help to select key topics that should be addressed with priority in the following national STI guidelines updates.

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.

Impact of a culturally tailored informative video on cervical cancer: a pilot study with Amazonian women in treatment for cervical cancer.

The present study is a randomised pilot study that evaluated a culturally tailored video promoting information about cervical cancer (CC), developed with Amazonian women in treatment for CC. The sample included 63 patients in treatment for CC who were randomly assigned to three groups of 21 patients. The experimental group watched an informative video about CC. The active control group watched a video on healthy habits and the passive control group received no intervention. The groups were compared in terms of change in knowledge and illness perceptions, over time. The results showed that the experimental group was the only one with a significant increase in knowledge (ß = .166; p = .03) that was not maintained over time (ß = -.195; p = .04). Threatening illness perceptions about the disease increased in all groups over time (ß = .105; p = .001). Future studies should replicate the results testing the efficacy of an audiovisual strategy in a larger sample, in health services that serve populations with similar social and cultural characteristics. This study emphasises the importance of interprofessional oncology teams providing clear information regarding CC, during all stages of the disease, and patients' treatment.Impact StatementWhat is already known on this subject? Latin American countries, such as Brazil, the low coverage of screening for CC can be related to the low education of women and their difficulty of access to health care. Hence, educational interventions may be a good strategy to reinforce the importance of screening and increase knowledge about illness prevention and treatment.What the results of this study add? An audiovisual informational intervention on CC was developed, addressing prevention, causes, control, consequences and treatment while respecting the patients' cultural and social reality through an approach that is simple and easy to understand. The group that watched the informative video was the only one that increased knowledge, revealing that it was a good CC informational strategy.What are the implications of these findings for clinical practice and/or further research? This study confirmed the importance of developing informational and educational strategies that are appropriate to patients' social and cultural reality. The video is now available to health teams in primary, secondary and tertiary care units, as a strategy for health promotion and CC prevention.

Modeling the epidemiological impact of the UNAIDS 2025 targets to end AIDS as a public health threat by 2030.

BACKGROUND: UNAIDS has established new program targets for 2025 to achieve the goal of eliminating AIDS as a public health threat by 2030. This study reports on efforts to use mathematical models to estimate the impact of achieving those targets. METHODS AND FINDINGS: We simulated the impact of achieving the targets at country level using the Goals model, a mathematical simulation model of HIV epidemic dynamics that includes the impact of prevention and treatment interventions. For 77 high-burden countries, we fit the model to surveillance and survey data for 1970 to 2020 and then projected the impact of achieving the targets for the period 2019 to 2030. Results from these 77 countries were extrapolated to produce estimates for 96 others. Goals model results were checked by comparing against projections done with the Optima HIV model and the AIDS Epidemic Model (AEM) for selected countries. We included estimates of the impact of societal enablers (access to justice and law reform, stigma and discrimination elimination, and gender equality) and the impact of Coronavirus Disease 2019 (COVID-19). Results show that achieving the 2025 targets would reduce new annual infections by 83% (71% to 86% across regions) and AIDS-related deaths by 78% (67% to 81% across regions) by 2025 compared to 2010. Lack of progress on societal enablers could endanger these achievements and result in as many as 2.6 million (44%) cumulative additional new HIV infections and 440,000 (54%) more AIDS-related deaths between 2020 and 2030 compared to full achievement of all targets. COVID-19-related disruptions could increase new HIV infections and AIDS-related deaths by 10% in the next 2 years, but targets could still be achieved by 2025. Study limitations include the reliance on self-reports for most data on behaviors, the use of intervention effect sizes from published studies that may overstate intervention impacts outside of controlled study settings, and the use of proxy countries to estimate the impact in countries with fewer than 4,000 annual HIV infections. CONCLUSIONS: The new targets for 2025 build on the progress made since 2010 and represent ambitious short-term goals. Achieving these targets would bring us close to the goals of reducing new HIV infections and AIDS-related deaths by 90% between 2010 and 2030. By 2025, global new infections and AIDS deaths would drop to 4.4 and 3.9 per 100,000 population, and the number of people living with HIV (PLHIV) would be declining. There would be 32 million people on treatment, and they would need continuing support for their lifetime. Incidence for the total global population would be below 0.15% everywhere. The number of PLHIV would start declining by 2023.

Ending AIDS as a public health threat by 2030: Time to reset targets for 2025.

Paul De Lay and co-authors introduce a Collection on the design of targets for ending the AIDS epidemic.

Behavioral factors associated with multiple-type HPV genital infections: data from a cross-sectional study in young women in Brazil.

OBJECTIVES: To investigate the pattern of multiple human papillomavirus (HPV) infections and associated factors in young women who access the Brazilian public health care system to better understand the characteristics of multiple HPV infections, a critical issue in this era of multivalent vaccines. METHODS: This was a cross-sectional, multicenter study with sexually active unvaccinated women (16-25 years old) from 119 primary Brazilian healthcare centers between September 2016 and November 2017. Cervical samples were collected by trained health professionals, and HPV detection was performed in a central laboratory by Linear Array. RESULTS: Of the 5268 women, 33.00% (95% CI 31.07-34.92) had multiple infections. At least one type of high-risk HPV was present in 85.50% of all multiple infections. All HPV types were detected more frequently in association with other types than alone. Young individuals who were single or in a casual relationship and those who had more than one sexual partner in the past year were more likely to have multiple infections. CONCLUSIONS: In this work, a high rate of multiple HPV infections among unvaccinated young adults tended to increase due to certain risk factors. Such data can provide insight for decision makers in the development of public policies regarding HPV prevention.

Understanding the characteristics of multiple infections is critical in the era of HPV multivalent vaccines for the prevention of cervical carcinomas. Therefore, in this cross-sectional study, we aimed to investigate the pattern of multiple HPV infections and associated factors in 5,268 sexually active unvaccinated women (16­25 years old) who access the Brazilian public health care system. Cervical samples were collected by trained health professionals, and HPV detection was performed in a central laboratory by Linear Array. A total of 33.00% (95% CI 31.07­34.92) had multiple infections (60.43% of the HPV-positive sample). The number of HPV types in a multiple infection ranged from 2 to 14 different types. The viral types more frequently identified were HPV 16 and 52. All HPV types were detected more frequently in association with other types than alone. The incidence of multiple infections was 1.29 times higher in single than in married or cohabitating participants. Women who had two or more partners in the last year also had higher rates of multiple infections than those who had fewer than two sexual partners. In conclusion, a high prevalence of multiple infections prior to the national HPV immunization program was observed, especially with the increase in less safe behavior factors.

Genomic epidemiology of Neisseria gonorrhoeae elucidating the gonococcal antimicrobial resistance and lineages/sublineages across Brazil, 2015-16.

OBJECTIVES: Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance is imperative internationally, but only eight (22.9%) countries in the WHO Region of the Americas reported complete AMR data to the WHO Global Gonococcal Antimicrobial Surveillance Program (WHO GASP) in 2016. Genomic studies are ideal for enhanced understanding of gonococcal populations, including the spread of AMR strains. To elucidate the circulating gonococcal lineages/sublineages, including their AMR determinants, and the baseline genomic diversity among gonococcal strains in Brazil, we conducted WGS on 548 isolates obtained in 2015-16 across all five macroregions in Brazil. METHODS: A total of 548 gonococcal isolates cultured across Brazil in 2015-16 were genome sequenced. AMR was determined using agar dilution and/or Etest. Genome sequences of isolates from Argentina (n = 158) and the 2016 WHO reference strains (n = 14) were included in the analysis. RESULTS: We found 302, 68 and 214 different NG-MAST, MLST and NG-STAR STs, respectively. The phylogenomic analysis identified one main antimicrobial-susceptible lineage and one AMR lineage, which was divided into two sublineages with different AMR profiles. Determination of NG-STAR networks of clonal complexes was shown as a new and valuable molecular epidemiological analysis. Several novel mosaic mtrD (and mtrR and mtrE) variants associated with azithromycin resistance were identified. CONCLUSIONS: We describe the first genomic baseline data to support the Brazilian GASP. The high prevalence of resistance to ciprofloxacin, tetracycline and benzylpenicillin, and the high number of isolates with mosaic penA and azithromycin resistance mutations, should prompt continued and strengthened AMR surveillance, including WGS, of N. gonorrhoeae in Brazil.

The case for a universal hepatitis C vaccine to achieve hepatitis C elimination.

BACKGROUND: The introduction of highly effective direct-acting antiviral (DAA) therapy for hepatitis C has led to calls to eliminate it as a public health threat through treatment-as-prevention. Recent studies suggest it is possible to develop a vaccine to prevent hepatitis C. Using a mathematical model, we examined the potential impact of a hepatitis C vaccine on the feasibility and cost of achieving the global WHO elimination target of an 80% reduction in incidence by 2030 in the era of DAA treatment. METHODS: The model was calibrated to 167 countries and included two population groups (people who inject drugs (PWID) and the general community), features of the care cascade, and the coverage of health systems to deliver services. Projections were made for 2018-2030. RESULTS: The optimal incidence reduction strategy was to implement test and treat programmes among PWID, and in settings with high levels of community transmission undertake screening and treatment of the general population. With a vaccine available, the optimal strategy was to include vaccination within test and treat programmes, in addition to vaccinating adolescents in settings with high levels of community transmission. Of the 167 countries modelled, between 0 and 48 could achieve an 80% reduction in incidence without a vaccine. This increased to 15-113 countries if a 75% efficacious vaccine with a 10-year duration of protection were available. If a vaccination course cost US$200, vaccine use reduced the cost of elimination for 66 countries (40%) by an aggregate of US$7.4 (US$6.6-8.2) billion. For a US$50 per course vaccine, this increased to a US$9.8 (US$8.7-10.8) billion cost reduction across 78 countries (47%). CONCLUSIONS: These findings strongly support the case for hepatitis C vaccine development as an urgent public health need, to ensure hepatitis C elimination is achievable and at substantially reduced costs for a majority of countries.

Decline in reported AIDS cases in Brazil after implementation of the test and treat initiative.

BACKGROUND: To evaluate the trends in AIDS detection and the AIDS-attributed death rate in Brazil between 2007 and 2015 and to determine the population characteristics associated with AIDS detection. METHODS: Surveillance data including demographics, mode of HIV transmission, AIDS cases, and AIDS-attributed deaths were analysed. A logistic regression model was fitted to assess the trends in AIDS cases by mode of HIV transmission throughout the study period. A segmented Poisson regression model was used to assess changes in the trends of AIDS detection and mortality rates before (2007-2014) and after (2015) the introduction of the Test and Treat Initiative. RESULTS: In the segmented Poisson regression, the decline in the AIDS detection rate from 2007 to 2014 was 2.0% annually (i.e., the odds ratio (OR) for annual decline was 0.98 (95% [CI: 0.98-1.00, p-value < 0.001). The observed AIDS detection rate in 2015 was 7.7 cases per 100,000, which was 60% lower than the regression estimate of 19.8 for the hypothetical absence of the Test and Treat Initiative. The reduction in AIDS-attributed deaths from 2007 to 2014 was 8.0% annually (i.e., the OR for annual decline was 0.92 (95% [CI: 0.91-0.95, p-value < 0.001). The observed AIDS mortality rate in 2015 was 0.49 cases per 100,000, which was 73% lower than the regression estimate of 2.1 for the hypothetical absence of the Test and Treat Initiative in 2015. CONCLUSIONS: Our results reveal a fairly stable AIDS detection rate from 2007 to 2014, with a sudden significant drop in 2015. This drop may be related to the increasing trends in rapid testing, the number of new HIV diagnoses, the number of patients on antiretroviral therapy (ART), and a median CD4 count at ART enrolment. Further evaluation of the effects of the Test and Treat Initiative on AIDS diagnosis and mortality is needed and must be strengthened with additional data from subsequent years.

Determinants of survival of people living with HIV/AIDS on antiretroviral therapy in Brazil 2006-2015.

BACKGROUND: We compared AIDS-related mortality rates in people living with HIV (PLHIV) starting antiretroviral therapy (ART) in Brazil during 2006-2015 and examined associated risk factors . METHODS: Data on ART use in PLHIV and AIDS mortality in Brazil was analysed with piecewise constant exponential models. Mortality rates and hazard ratios were estimated for 0-6, 6-12, 13-24, 25-36 and > 36 months of ART use and adjusted for region, age, sex, baseline CD4 cell count and calendar year of ART initiation. An additional analysis restricted to those with data on risk group was also performed. RESULTS: 269,076 individuals were included in the analysis, 165,643 (62%) males and 103,433 (38%) females, with 1,783,305 person-years of follow-up time. 21,749 AIDS deaths were reported and 8898 deaths occurred in the first year of ART. The risk of death in the first six months decreased with early ART initiation; those starting treatment early with CD4 > 500 cells per µL had a hazard ratio of 0.06 (95% CI 0.05-0.07) compared with CD4 < 200 cells per µL. Older age, male sex, intravenous drug use and starting treatment in earlier calendar years were associated with higher mortality rates. People living in the North, Northeast and South of Brazil experienced significantly higher AIDS mortality rates than those in the Southeast (HR 1.44, [95% CI 1.35-1.54], 1.10 [1.05-1.16] and 1.22 [1.17-1.28] respectively). CONCLUSIONS: Early treatment is likely to have contributed to the improved survival in PLHIV on ART, with the greatest benefits observed in women, younger age-groups and those living in the North.

Antiretroviral treatment, government policy and economy of HIV/AIDS in Brazil: is it time for HIV cure in the country?

Brazil is a low-and-middle income country (LMIC) that, despite having a large population and continental dimensions, has been able to successfully fight HIV/AIDS through a number of governmental and societal measures. These included an early response to the epidemic, the development of a universal and free public health system, incisive discussions with pharmaceutical companies to reduce antiretroviral (ARV) drug prices, investments towards the development of generic drugs and compulsory licensing of ARVs. Through such measures, Brazil is among the leading LMIC towards achieving the 90-90-90 UNAIDS goals in the years to come. In this review, we analyze Brazil's progress throughout the HIV/AIDS epidemic to achieve state-of-the-art ARV treatment and to reduce AIDS mortality in the country. The top-quality HIV/AIDS research in Brazil towards HIV prophylactic and functional cure, the next step towards the economic sustainability of the battle against HIV, is also discussed.

HIV/AIDS health services in Manaus, Brazil: patient perception of quality and its influence on adherence to antiretroviral treatment.

BACKGROUND: Patient satisfaction is an important factor for both assessing the quality of healthcare and predicting positive health outcomes. This study assesses the influence of HIV/AIDS patients' perception of the quality of health services on adherence to antiretroviral treatment using the decentralized care model in Manaus, Brazil. METHODS: We conducted a non-randomized, cross-sectional analysis to explore the relationship between patient satisfaction and adherence to antiretroviral treatment (ART) in Manaus, Amazonas, Brazil. We also compared patient satisfaction levels at the city's main hospital with those at smaller health units established to decentralize HIV/AIDS healthcare. Using survey responses from 812 patients and health data from 713 patients, we conducted descriptive and regression analyses to identify health center characteristics associated with higher patient satisfaction and higher adherence to treatment. RESULTS: We found a clear and positive relationship between patient satisfaction with the quality of health services and adherence to ART. Patients who had better access to their health center and its services -mainly in the form of convenient location, shorter commute times, and shorter wait times- tended to rate the quality of services higher and were also more likely to adhere to ART. We also found higher levels of patient satisfaction and adherence to ART among patients served at decentralized health units than among patients served at the main hospital. CONCLUSIONS: The study's results emphasize the importance of patients' experience at the health center for improved health outcomes. While many of the factors that play a role in whether a patient adheres to ART or not are beyond the control of the health center, our findings highlight that health centers can importantly contribute to increased ART adherence by improving such experience. The study also showcases the potential benefits of decentralizing HIV care to increase patient satisfaction and, with it, adherence to ART.

High risk human papillomavirus prevalence and genotype distribution among women infected with HIV in Manaus, Amazonas.

BACKGROUND: Human immunodeficiency virus (HIV)-positive women have a high prevalence of human papillomavirus (HPV), and are infected with a broader range of HPV types than HIV-negative women. We aimed to determine the prevalence of cervical cytologic abnormalities, high-risk (HR)-HPV prevalence, type distribution according to the severity of cervical lesions and CD4 cell count and identify factors associated with HR-HPV infection among women living with HIV in Manaus, Amazonas. METHODS: We enrolled 325 women living with HIV that attended an infectious diseases referral hospital. Each woman underwent a gynecological exam, cervical cytology, HR-HPV detection by Polymerase chain Reaction (PCR) using the BD Onclarity™ HPV Assay, colposcopy and biopsy, when necessary. We assessed the associations between potential risk factors and HR-HPV infection. RESULTS: Overall, 299 (92.0%) women had a PCR result. The prevalence of HR-HPV- infection was 31.1%. The most prevalent HR-HPV types were: 56/59/66 (32.2%), 35/39/68 (28.0%), 52 (21.5%), 16 (19.4%), and 45 (12.9%). Among the women with HR-HPV infection (n = 93), 43.0% had multiple infections. Women with HPV infection showed higher prevalence of cervical abnormalities than that HPV-negative (LSIL: 22.6% vs. 1.5%; HSIL: 10.8% vs. 0.0%). The prevalence of HR-HPV among women with cytological abnormalities was 87.5% for LSIL and 100.0% for HSIL. Women with CD4 < 200 cell/mm3 showed the highest HR-HPV prevalence (59.3%) although this trend was not statistically significant (p-value = 0.62). The mean CD4 cell count decreased with increasing severity of cervical lesions (p-value = 0.001). The multivariable analysis showed that increasing age was associated with a decreased risk of HR-HPV infection with an adjusted prevalence odds ratio of 0.9 (95.0% CI: 0.9-1.0, p-value: 0.03) for each additional year. The only factor statistically significant associated with HR-HPV infection was CD4 cell count. CONCLUSIONS: HR-HPV and abnormal cytology prevalence are high among women in the Amazonas. The low CD4 cell count was an important determinant of HPV infection and abnormal cytological findings. HPV quadrivalent vaccination used in Brazil might not offer protection for an important fraction of HPV-related disease burden in women living with HIV. This is partly explained by the high presence of non targeted vaccine HR-HPVs, such as the HPV genotype groups 56/59/66, 35/39/68 and individually HPV-52 and HPV-45, some of which contribute to high-grade lesion.

Study on the persistence of Zika virus (ZIKV) in body fluids of patients with ZIKV infection in Brazil.

BACKGROUND: Zika virus (ZIKV) has been identified in several body fluids of infected individuals. In most cases, it remained detected in blood from few days to 1 week after the onset of symptoms, and can persist longer in urine and in semen. ZIKV infection can have dramatic consequences such as microcephaly and Guillain-Barré syndrome. ZIKV sexual transmission has been documented. A better understanding of ZIKV presence and persistence across biologic compartments is needed to devise rational measures to prevent its transmission. METHODS: This observational cohort study will recruit non-pregnant participants aged 18 years and above with confirmed ZIKV infection [positive reverse transcriptase-polymerase chain reaction (RT-PCR) test in blood and/or urine]: symptomatic men and women in ZIKV infection acute phase, and their symptomatic or asymptomatic household/sexual infected contacts. Specimens of blood, urine, semen, vaginal secretion/menstrual blood, rectal swab, oral fluids, tears, sweat, urine and breast milk (if applicable) will be collected at pre-established intervals and tested for ZIKV RNA presence by RT-PCR, other co-infection (dengue, Chikungunya, HIV, hepatitis B and C, syphilis), antibody response (including immunoglobulins M and G), plaque reduction neutralization test (if simultaneously positive for ZIKV and dengue), and ZIKV culture and RNA sequencing. Data on socio-demographic characteristics and comorbidities will be collected in parallel. Participants will be followed up for 12 months. DISCUSSION: This prolonged longitudinal follow-up of ZIKV infected persons with regular biologic testing and data collection will offer a unique opportunity to investigate the presence and persistence of ZIKV in various biologic compartments, their clinical and immunological correlates as well as the possibility of ZIKV reactivation/reinfection over time. This valuable information will substantially contribute to the body of knowledge on ZIKV infection and serve as a base for the development of more effective recommendation on the prevention of ZIKV transmission. TRIAL REGISTRATION: NCT03106714 . Registration Date: April, 7, 2017.

Drug resistance in antiretroviral-naive children newly diagnosed with HIV-1 in Manaus, Amazonas.

Objectives: To determine the prevalence of drug resistance mutations (DRM), the prevalence of drug susceptibility [transmitted drug resistance (TDR)] and the prevalence of HIV-1 variants among treatment-naive HIV-infected children in Manaus, Amazonas state, Brazil. Methods: Children born to HIV-infected mothers and diagnosed with HIV in an HIV reference service centre and with available pol sequence between 2010 and 2015 prior to antiretroviral initiation were included. TDR was identified using the Calibrated Population Resistance Tool. HIV-1 subtypes were defined by Rega and phylogenetic analyses. Results: One hundred and seventeen HIV-infected children with a median age of 3.7 years were included. Among them, 28.2% had been exposed to some form of prevention of mother-to-child transmission (PMTCT). HIV DRM were present in 21.4% of all children. Among PMTCT-exposed children, 3% had NRTI mutations, 15.2% had NNRTI mutations and 3% had PI mutations. Among PMTCT-unexposed children, 1.2% had NRTI mutations, 21.4% had non-NNRTI mutations and 1.2% had PI mutations. The most common DRM was E138A (8.5%). The prevalence of TDR was 16.2%; 21.1% among PMTCT-exposed children and 14.3% among PMTC-unexposed children. The analysis of HIV-1 subtypes revealed that 80.2% were subtype B, 6.0% were subtype C, 3.4% were subtype F1 and 10.3% were possible unique recombinant forms (BF1, 4.3%; DB, 4.3%; BC, 0.9%; KC, 0.9%). Conclusions: We report a high prevalence of DRM in this population, including in almost a quarter of children with no reported PMTCT. The high prevalence of TDR observed might compromise ART effectiveness. Results show extensive HIV-1 diversity and expansion of subtype C, which highlights the need for surveillance of HIV-1 subtypes in Amazonas state.

Evaluation of seven rapid tests for syphilis available in Brazil using defibrinated plasma panels.

OBJECTIVES: In 2012, the WHO estimated that 6 million new cases of syphilis per year would occur worldwide, including 937 000 in Brazil. Early diagnosis and treatment of syphilis are essential to reduce morbidity and prevent transmission. The availability of rapid tests (RTs) for this diagnosis means that testing can be performed more quickly, as a point-of-care test, even in non-laboratory environments and requires only simple technical training to antibodies detection. The objective of this study was to evaluate the performance and operational aspects of seven commercially available RTs for syphilis in Brazil. METHODS: Seven rapid treponemal tests were evaluated for sensitivity, specificity, accuracy and Kappa value, according to a panel composed of 493 members. The operational performance of the assay was also determined for these tests. RESULTS: The seven RTs showed sensitivity ranging from 94.5% to 100% when compared with the reference tests and specificity of between 91.5% and 100%. All the RTs evaluated presented good operational performance, and only one failed to present the minimum specificity as defined by Brazil's Ministry of Health. CONCLUSION: All the tests presented good operational performance, and the professionals who performed them considered them to be easy to use and interpret. This evaluation is important for making informed choices of tests to be used in the Brazilian Unified Health System.

Transitioning from antenatal surveillance surveys to routine HIV testing: a turning point in the mother-to-child transmission prevention programme for HIV surveillance in Brazil.

BACKGROUND: In Brazil, due to the rapid increase in programmes for the prevention of mother-to-child transmission (PMTCT), routine programme data are widely available. The objective of this study was to assess the utility of programmatic data to replace HIV surveillance based on the antenatal care (ANC) surveillance survey (SS). METHODS: We analysed ANC SS data from 219 maternity service clinics. PMTCT variables were extracted from the ANC SS data collection form, which allowed us to capture and compare the ANC SS data and PMTCT HIV test results for each pregnant woman who completed the ANC SS. Both the PMTCT programme and the ANC SS tested for HIV using sequential ELISA and western blot for confirmation. We assessed the completeness (% missing) of the PMTC data included in the ANC SS. RESULTS: Of the 36,713 pregnant women who had ANC SS HIV tests performed, 30,588 also underwent PMTCT HIV testing. The HIV prevalence rate from routine PMTCT testing was 0.36%, compared to 0.38% from the ANC SS testing (relative difference -0.05%; absolute difference -0.02%). The relative difference in prevalence rates between pregnant women in northern Brazil and pregnant women central-west Brazil was -0.98 and 0.66, respectively. Of the 29,856 women who had HIV test results from both the PMTCT and ANC SS, the positive percent agreement of the PMTCT versus the surveillance test was 84.1% (95% confidence interval [CI]: 74.8-91.0), and the negative percent agreement was 99.9% (95% CI: 99.9-100.0). The PMTCT HIV testing uptake was 86.4%. The ANC SS HIV prevalence was 0.33% among PMTCT non-refusers and 0.59% among refusers, with a percent bias of -10.80% and a differential prevalence ratio of 0.56. Syphilis and HIV testing results were complete in 98% and 97.6% of PMTCT reports, respectively. The reported HIV status for the women at clinic entry was missing. CONCLUSIONS: Although there were consistent HIV prevalence estimates from the PMTCT data and the ANC SS, the overall positive percent agreement of 84.1% falls below the World Health Organization benchmark of 94.7%. Therefore, Brazil must continue to reinforce data collection practices and ensure the quality of recently introduced rapid HIV testing before replacing the PMTCT data with surveillance techniques. However, some regions with better results could be prioritized to pilot the use of PMTCT data for surveillance.

HIV and syphilis in the context of community vulnerability among indigenous people in the Brazilian Amazon.

BACKGROUND: Contextual factors shape the risk of acquiring human immunodeficiency virus (HIV) and syphilis. We estimated the prevalence of both infections among indigenous people in nine indigenous health districts of the Brazilian Amazon and examined the context of community vulnerability to acquiring these infections. METHODS: We trained 509 health care workers to screen sexually active populations in the community for syphilis and HIV using rapid testing (RT). We then assessed the prevalence of HIV and syphilis using RT. A multivariable analysis was used to identify factors associated with syphilis infection (sociodemographic, condom use, intrusion, population mobility, and violence). RESULTS: Of the 45,967 indigenous people tested, the mean age was 22.5 years (standard deviation: 9.2), and 56.5% were female. Overall, for HIV, the prevalence was 0.13% (57/43,221), and for syphilis, the prevalence was 1.82% (745/40,934). The prevalence in men, women, and pregnant women for HIV was 0.16%, 0.11%, and 0.07%, respectively, and for syphilis, it was 2.23%, 1.51%, and 1.52%, respectively. The district Vale do Javari had the highest prevalence of both infections (HIV: 3.38%, syphilis: 1.39%). This district also had the highest population mobility and intrusion and the lowest availability of prenatal services. Syphilis infection was independently associated with age (odds ratio [OR] 1.04, 95% confidence interval [CI]: 1.03-1.05), male sex (OR 1.32, 95% CI: 1.14-1.52), and mobility (moderate: OR: 7.46, 95% CI: 2.69-20.67; high: OR 7.09, 95% CI: 3.79-13.26). CONCLUSIONS: The large-scale integration of RT in remote areas increased case detection among pregnant women, especially for syphilis, in districts with higher vulnerability. Mobility is an important risk factor, especially in districts with higher vulnerability. Contextually appropriate approaches that address this factor could contribute to the long-term success of HIV and syphilis control programs.

The Brazilian comprehensive response to hepatitis C: from strategic thinking to access to interferon-free therapy.

BACKGROUND: Hepatitis C affects over 185 million people around the world. This silent disease is responsible for up to 700,000 deaths per year. Despite the scientific revolution in diagnosis and treatment, hepatitis C control remains a huge challenge due to the cost of effective medications. In response to the global outcry of hepatitis epidemic and the need to improve the nation's public health response, the Ministry of Health of Brazil revolutionized hepatitis C treatment by incorporating highly effective drugs that can be accessed through sustainable and universal means. DISCUSSION: This paper describes the unique process of implementing evidence-informed policy to respond to hepatitis C epidemic through the update of hepatitis C treatment in Brazil based on the estimate of disease prevalence, current international guidelines, and the cost-effectiveness impact in the Brazilian Unified Health System. Through a debate of an experience report, the authors underlie the strategic plan implemented according to the situation analysis that emphasized the need to improve its current response over a relatively short-term period. The comprehensive response is detailed comprising three main objectives: improve treatment outcomes by evaluating and incorporating new and effective medications at a sustainable price; elaborate on clinical guidelines to treat hepatitis C patients; and develop awareness and diagnosis campaigns targeted at the population of interest. In this scenario, Brazil was able to obtain an unprecedented discount for a high-medium income country; provided treatment to more than 7000 individuals in the last 2 months of 2015; and expects to treat 38,000 new patients in 2016. The remarkable process applied in Brazil was developed according to epidemiological data and scientific evidence, and it was motivated by the engagement of the country in the Sustainable Development Goals, which may inspire other developing countries to identify ways to achieve these goals by 2030.