Spatiotemporal dynamics and recurrence of chikungunya virus in Brazil: an epidemiological study.

BACKGROUND: Chikungunya virus (CHIKV) is an Aedes mosquito-borne virus that has caused large epidemics linked to acute, chronic, and severe clinical outcomes. Currently, Brazil has the highest number of chikungunya cases in the Americas. We aimed to investigate the spatiotemporal dynamics and recurrence pattern of chikungunya in Brazil since its introduction in 2013. METHODS: In this epidemiological study, we used CHIKV genomic sequencing data, CHIKV vector information, and aggregate clinical data on chikungunya cases from Brazil. The genomic data comprised 241 Brazilian CHIKV genome sequences from GenBank (n=180) and the 2022 CHIKV outbreak in Ceará state (n=61). The vector data (Breteau index and House index) were obtained from the Brazilian Ministry of Health for all 184 municipalities in Ceará state and 116 municipalities in Tocantins state in 2022. Epidemiological data on laboratory-confirmed cases of chikungunya between 2013 and 2022 were obtained from the Brazilian Ministry of Health and Laboratory of Public Health of Ceará. We assessed the spatiotemporal dynamics of chikungunya in Brazil via time series, mapping, age-sex distribution, cumulative case-fatality, linear correlation, logistic regression, and phylogenetic analyses. FINDINGS: Between March 3, 2013, and June 4, 2022, 253 545 laboratory-confirmed chikungunya cases were reported in 3316 (59·5%) of 5570 municipalities, mainly distributed in seven epidemic waves from 2016 to 2022. To date, Ceará in the northeast has been the most affected state, with 77 418 cases during the two largest epidemic waves in 2016 and 2017 and the third wave in 2022. From 2016 to 2022 in Ceará, the odds of being CHIKV-positive were higher in females than in males (odds ratio 0·87, 95% CI 0·85-0·89, p<0·0001), and the cumulative case-fatality ratio was 1·3 deaths per 1000 cases. Chikungunya recurrences in the states of Ceará, Tocantins (recurrence in 2022), and Pernambuco (recurrence in 2021) were limited to municipalities with few or no previously reported cases in the previous epidemic waves. The recurrence of chikungunya in Ceará in 2022 was associated with a new East-Central-South-African lineage. Population density metrics of the main CHIKV vector in Brazil, Aedes aegypti, were not correlated spatially with locations of chikungunya recurrence in Ceará and Tocantins. INTERPRETATION: Spatial heterogeneity of CHIKV spread and population immunity might explain the recurrence pattern of chikungunya in Brazil. These results can be used to inform public health interventions to prevent future chikungunya epidemic waves in urban settings. FUNDING: Global Virus Network, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, São Paulo Research Foundation, Brazil Ministry of Education, UK Medical Research Council, Brazilian National Council for Scientific and Technological Development, and UK Royal Society. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Tracking the emergence of disparities in the subnational spread of COVID-19 in Brazil using an online application for real-time data visualisation: A longitudinal analysis.

BACKGROUND: Brazil is one of the countries worst affected by the COVID-19 pandemic with over 20 million cases and 557,000 deaths reported by August 2021. Comparison of real-time local COVID-19 data between areas is essential for understanding transmission, measuring the effects of interventions, and predicting the course of the epidemic, but are often challenging due to different population sizes and structures. METHODS: We describe the development of a new app for the real-time visualisation of COVID-19 data in Brazil at the municipality level. In the CLIC-Brazil app, daily updates of case and death data are downloaded, age standardised and used to estimate the effective reproduction number (Rt ). We show how such platforms can perform real-time regression analyses to identify factors associated with the rate of initial spread and early reproduction number. We also use survival methods to predict the likelihood of occurrence of a new peak of COVID-19 incidence. FINDINGS: After an initial introduction in São Paulo and Rio de Janeiro states in early March 2020, the epidemic spread to northern states and then to highly populated coastal regions and the Central-West. Municipalities with higher metrics of social development experienced earlier arrival of COVID-19 (decrease of 11·1 days [95% CI:8.9,13.2] in the time to arrival for each 10% increase in the social development index). Differences in the initial epidemic intensity (mean Rt ) were largely driven by geographic location and the date of local onset. INTERPRETATION: This study demonstrates that platforms that monitor, standardise and analyse the epidemiological data at a local level can give useful real-time insights into outbreak dynamics that can be used to better adapt responses to the current and future pandemics. FUNDING: This project was supported by a Medical Research Council UK (MRC-UK) -São Paulo Research Foundation (FAPESP) CADDE partnership award (MR/S0195/1 and FAPESP 18/14389-0).

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Report 46: Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals.

The SARS-CoV-2 Gamma variant spread rapidly across Brazil, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 to document the extensive shocks in hospital fatality rates that followed Gamma's spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time periods. We show that extensive fluctuations in COVID-19 in-hospital fatality rates also existed prior to Gamma's detection, and were largely transient after Gamma's detection, subsiding with hospital demand. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates are primarily associated with geographic inequities and shortages in healthcare capacity. We project that approximately half of Brazil's COVID-19 deaths in hospitals could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries. NOTE: The following manuscript has appeared as 'Report 46 - Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals' at https://spiral.imperial.ac.uk:8443/handle/10044/1/91875 . ONE SENTENCE SUMMARY: COVID-19 in-hospital fatality rates fluctuate dramatically in Brazil, and these fluctuations are primarily associated with geographic inequities and shortages in healthcare capacity.

Global disparities in SARS-CoV-2 genomic surveillance.

Genomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes >21 days after sample collection, and 77% of low and middle income countries sequenced <0.5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT <21 days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness.

Higher risk of death from COVID-19 in low-income and non-White populations of São Paulo, Brazil.

INTRODUCTION: Little evidence exists on the differential health effects of COVID-19 on disadvantaged population groups. Here we characterise the differential risk of hospitalisation and death in São Paulo state, Brazil, and show how vulnerability to COVID-19 is shaped by socioeconomic inequalities. METHODS: We conducted a cross-sectional study using hospitalised severe acute respiratory infections notified from March to August 2020 in the Sistema de Monitoramento Inteligente de São Paulo database. We examined the risk of hospitalisation and death by race and socioeconomic status using multiple data sets for individual-level and spatiotemporal analyses. We explained these inequalities according to differences in daily mobility from mobile phone data, teleworking behaviour and comorbidities. RESULTS: Throughout the study period, patients living in the 40% poorest areas were more likely to die when compared with patients living in the 5% wealthiest areas (OR: 1.60, 95% CI 1.48 to 1.74) and were more likely to be hospitalised between April and July 2020 (OR: 1.08, 95% CI 1.04 to 1.12). Black and Pardo individuals were more likely to be hospitalised when compared with White individuals (OR: 1.41, 95% CI 1.37 to 1.46; OR: 1.26, 95% CI 1.23 to 1.28, respectively), and were more likely to die (OR: 1.13, 95% CI 1.07 to 1.19; 1.07, 95% CI 1.04 to 1.10, respectively) between April and July 2020. Once hospitalised, patients treated in public hospitals were more likely to die than patients in private hospitals (OR: 1.40%, 95% CI 1.34% to 1.46%). Black individuals and those with low education attainment were more likely to have one or more comorbidities, respectively (OR: 1.29, 95% CI 1.19 to 1.39; 1.36, 95% CI 1.27 to 1.45). CONCLUSIONS: Low-income and Black and Pardo communities are more likely to die with COVID-19. This is associated with differential access to quality healthcare, ability to self-isolate and the higher prevalence of comorbidities.

Emergence of the Asian lineage of Zika virus in Angola: an outbreak investigation.

BACKGROUND: Zika virus infections and suspected microcephaly cases have been reported in Angola since late 2016, but no data are available about the origins, epidemiology, and diversity of the virus. We aimed to investigate the emergence and circulation of Zika virus in Angola. METHODS: Diagnostic samples collected by the Angolan Ministry of Health as part of routine arboviral surveillance were tested by real-time reverse transcription PCR by the Instituto Nacional de Investigação em Saúde (Ministry of Health, Luanda, Angola). To identify further samples positive for Zika virus and appropriate for genomic sequencing, we also tested samples from a 2017 study of people with HIV in Luanda. Portable sequencing was used to generate Angolan Zika virus genome sequences from three people positive for Zika virus infection by real-time reverse transcription PCR, including one neonate with microcephaly. Genetic and mobility data were analysed to investigate the date of introduction and geographical origin of Zika virus in Angola. Brain CT and MRI, and serological assays were done on a child with microcephaly to confirm microcephaly and assess previous Zika virus infection. FINDINGS: Serum samples from 54 people with suspected acute Zika virus infection, 76 infants with suspected microcephaly, 24 mothers of infants with suspected microcephaly, 336 patients with suspected dengue virus or chikungunya virus infection, and 349 samples from the HIV study were tested by real-time reverse transcription PCR. Four cases identified between December, 2016, and June, 2017, tested positive for Zika virus. Analyses of viral genomic and human mobility data suggest that Zika virus was probably introduced to Angola from Brazil between July, 2015, and June, 2016. This introduction probably initiated local circulation of Zika virus in Angola that continued until at least June, 2017. The infant with microcephaly in whom CT and MRI were done had brain abnormalities consistent with congenital Zika syndrome and serological evidence for Zika virus infection. INTERPRETATION: Our analyses show that autochthonous transmission of the Asian lineage of Zika virus has taken place in Africa. Zika virus surveillance and surveillance of associated cases of microcephaly throughout the continent is crucial. FUNDING: Royal Society, Wellcome Trust, Global Challenges Research Fund (UK Research and Innovation), Africa Oxford, John Fell Fund, Oxford Martin School, European Research Council, Departamento de Ciência e Tecnologia/Ministério da Saúde/National Council for Scientific and Technological Development, and Ministério da Educação/Coordenação de Aperfeicoamento de Pessoal de Nível Superior.

Addressing gaps in international blood availability and transfusion safety in low- and middle-income countries: a NHLBI workshop.

In April 2017, a workshop sponsored by the National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources, and the Center for Translation Research and Implementation Science was held to discuss blood availability and transfusion safety in low- and middle-income countries (LMICs). The purpose of the workshop was to identify research opportunities for implementation science (IS) to improve the availability of safe blood and blood components and transfusion practices in LMICs. IS describes the late stages of the translational research spectrum and studies optimal and sustainable strategies to deliver proven-effective interventions. Regional working groups were formed to focus on opportunities and challenges in East Africa, Central/West Africa, Middle East and North Africa, Latin America and the Caribbean, Southeast Asia, Western Pacific Asia, Eastern Europe, and Central Asia. The need for an "adequate supply of safe blood" emerged as the major overriding theme. Among the regional working groups, common cross-cutting themes were evident. The majority of research questions, priorities, and strategies fell into the categories of blood availability, blood transfusion safety, appropriate use of blood, quality systems, health economics and budgeting, and training and education in IS. The workshop also brought into focus inadequate country-level data that can be used as the basis for IS initiatives. A mixed approach of needs assessment and targeted interventions with sufficient evidence base to move toward sustainment is an appropriate next step for blood availability and transfusion safety research in LMICs.

The impact of simple donor education on donor behavioral deferral and infectious disease rates in São Paulo, Brazil.

BACKGROUND: Studies have shown that human immunodeficiency virus (HIV) residual risk is higher in Brazilian than in US and European blood donors, probably due to failure to defer at-risk individuals in Brazil. This study assessed the impact of an educational brochure in enhancing blood donors' knowledge about screening test window phase and reducing at-risk individuals from donating. STUDY DESIGN AND METHODS: This trial compared an educational intervention with a blood center's usual practice. The brochure was distributed in alternating months to all donors. After donating, sampled participants completed two questions about their HIV window period knowledge. The impact on HIV risk deferral, leaving without donation, confidential unit exclusion (CUE) use, and test positivity was also analyzed. RESULTS: From August to November 2007 we evaluated 33,940 donations in the main collection center of Fundação Pró-Sangue/Hemocentro de São Paulo in São Paulo, Brazil. A significant (p < 0.001) pamphlet effect was found on correct responses to both questions assessing HIV window phase knowledge (68.1% vs. 52.9%) and transfusion risk (91.1% vs. 87.2%). After adjusting for sex and age, the pamphlet effect was strongest for people with more than 8 years of education. There was no significant pamphlet effect on HIV risk deferral rate, leaving without donation, use of CUE, or infectious disease rates. CONCLUSION: While the educational pamphlet increased window period knowledge, contrary to expectations this information alone was not enough to make donors self-defer or acknowledge their behavioral risk.

[External serology quality control programs developed in Latin America with the support of PAHO from 1997 through 2000]. / Programas de control externo de calidad en serología desarrollados en América Latina con el apoyo de la OPS entre 1997 y 2000.

OBJECTIVE: To evaluate the quality of serological screening of blood donors in five groups of blood banks in Latin America that participated over the 1997-2000 period in an external serology control project developed with support from the Pan American Health Organization (PAHO). METHODS: With assistance from PAHO, the Serology Authority of the Pro-Blood Foundation/Blood Center of São Paulo (Fundação Pró-Sangue/Hemocentro de São Paulo), of São Paulo, Brazil, carried out the external quality control project and served as its "organizing center" (OC). The OC developed five external serology quality control "programs" (ESQCPs), or external evaluation activities, for the respective groups of participating blood banks. There was one ESQCP each in 1997, 1999, and 2000, and there were two in 1998. In these five programs, the number of participating blood banks ranged from 13 to 21, and the number of countries ranged from 11 to 16. In each program, the OC used a set of 24 blinded sera samples with different reactivities for the various infectious agents for which screening is obligatory in Brazil. Each participating institution in each program received a sera set, to be processed using that institution's standard screening procedures. After returning its results to the OC, each participant received an answer key for the sera set, to be used in evaluating its own performance. All the individual results were kept strictly confidential. At the end of each program, the OC prepared and sent to all the participants a final report that contained information on the overall results from that program. RESULTS: An analysis of the five programs showed that there was a lack of homogeneity among the countries with respect to the strategies and the parameters used in screening blood donors. Few laboratories screened for human T-cell-lymphotropic virus (beginning with the 1997 program, the respective rates were 17%, 27%, 35%, 39%, and 45%). Rates of screening were also low for antibodies to the hepatitis B core antigen (again, beginning with the 1997 program, the rates were 42%, 27%, 39%, 50%, and 60%). There were also important differences with respect to which tests and which combinations of tests were used, making it hard to compare the types of screening done. In the five programs, with the various tests used, the overall rate of false positive results fluctuated around 2%. The highest false positive rate for any of the tests, 4.6%, was for antibodies against the hepatitis C virus. The lowest false positive rate, 0.4%, was for antibodies against Trypanosoma cruzi. CONCLUSIONS: These results show the need for PAHO to continue using these external quality control programs as well as other activities in order to strengthen the procedures for serological screening blood banks in Latin America, until there is more uniformity in the procedures that the countries use.

Programas de control externo de la calidad en serología desarrollados en América Latina con el apoyo de la OPS entre 1997 y 2000 / External serology quality control programs developed in Latin America with the support of PAHO from 1997 through 2000

OBJETIVOS: Con el apoyo de la Organización Panamericana de la Salud (OPS), desarrollamos entre 1997 y 2000 cinco programas de control externo de la calidad en serología (PCECS) en los que participaron entre 13 y 21 bancos de sangre de 11 a 16 países de América Latina. El objetivo fue evaluar el desempeño de los bancos de sangre con respecto al tamizaje serológico realizado en donantes de sangre. MÉTODOS: Como herramienta de trabajo utilizamos conjuntos de 24 muestras de sueros anónimos con reactividades variables para los parámetros de uso obligatorio en el tamizaje serológico de donantes de sangre en Brasil. En cada PCECS enviamos un multipanel a cada institución participante para que lo procesara en las mismas condiciones de su rutina de tamizaje. Cada participante recibió la clave del multipanel para autoevaluación, después de haber devuelto los resultados obtenidos en su laboratorio. Se mantuvo siempre la más estricta confidencialidad sobre los resultados obtenidos individualmente. Al terminar de cada programa, el Centro Organizador (Superintendencia de Serología de la Fundaçäo Pró-Sangue/Hemocentro de Säo Paulo) elaboró un informe final que contenía toda la información obtenida en el programa y que fue enviado a los participantes. RESULTADOS: En el análisis de los cinco PCECS se observó falta de homogeneidad entre los países con respecto a las estrategias y a los parámetros utilizados en el tamizaje de donantes de sangre. Pocos laboratorios practicaron el tamizaje de los virus linfotrópico de células T humanas (HTLV) (17 por ciento, 27 por ciento, 35 por ciento, 39 por ciento y 45 por ciento, respectivamente y en orden creciente para los cinco PCECS) y de anticuerpos contra el antígeno nuclear del virus de la hepatitis B (anti-HBc) (42 por ciento, 27 por ciento, 39 por ciento, 50 por ciento y 60 por ciento). También se observaron diferencias importantes en cuanto a las pruebas o combinaciones de pruebas utilizadas, lo cual puede dificultar el estudio comparativo de los tipos de tamizaje. El número total de resultados positivos falsos osciló alrededor del 2 por ciento, correspondiendo el mayor valor al tamizaje de anticuerpos contra el virus de la hepatatis C (anti-VHC) (4,6 por ciento) y el menor a anti-Trypanosoma cruzi (0,4 por ciento). CONCLUSIONES: Los resultados obtenidos en este trabajo demuestran la necesidad de continuar las acciones de la OPS en América Latina para reforzar los procedimientos de...