Assessing critical gaps in COVID-19 testing capacity : the case of delayed results in Ecuador

Background: Testing is crucial for COVID-19 response and management, however, WHO's preparedness index omits estimations of actual testing capabilities, which influence the ability to contain, mitigate and clinically manage infectious diseases. With one of the highest excess death rates globally, Ecuador had a comparatively low number of confirmed COVID-19 cases, which may have been influenced by limited availability of data for decision-making due to low laboratory capacity. Methods: We examine de-identified data on 55,063 individuals with suspected COVID-19 between February 27 and April 30, 2020 included in the RT-PCR testing database collected by the Ministry of Health. Processing times and rates per province, and the number of pending tests, were tallied cumulatively. We assessed the relationship between sample shipping, laboratory capacity and case completion using a negative binomial generalized linear model. Results: The national average time for case completion was 3 days; 12.1% of samples took ≥10 days to complete; the national average daily backlog was 29.1 tests per 100,000 people. Only 8 out of 24 provinces had authorized COVID-19 processing laboratories but not all processed samples. There was an association between samples coming from outside the processing laboratory province, the number of other samples present at the laboratory during processing, and the amount of time needed to process a sample. Samples from another province took 1.29 times as long to process, on average. The percentage of pending results on April 30 was 67.1%. Conclusion: A centralized RT-PCR testing system contributes to critical delays in processing, which may mask a case burden higher than reported, impeding timely awareness, and adequate clinical care and vaccination strategies and subsequent monitoring. Although Ecuador adapted or authorized existing facilities to address limitations in laboratory capacity for COVID-19, this study highlights the need to estimate and augment laboratory capabilities for improved decision making and policies on diagnostic guidelines and availability. Support is needed to procure the necessary human and physical resources at all phases of diagnostic testing, including transportation of samples and supplies, and information management. Strengthening emergency preparedness enables a clear understanding of COVID-19 disparities within and across the country.Publisher PDFPeer reviewe

Genetic Diversity and Antimicrobial Susceptibility of Campylobacter jejuni Isolates Associated with Sheep Abortion in the United States and Great Britain

Campylobacter infection is a leading cause of ovine abortion worldwide. Historically, genetically diverse Campylobacter fetus and Campylobacter jejunistrains have been implicated in such infections, but since 2003 a highly pathogenic, tetracycline-resistant C. jejuni clone (named SA) has become the predominant cause of sheep abortions in the United States. Whether clone SA was present in earlier U.S. abortion isolates (before 2000) and is associated with sheep abortions outside the United States are unknown. Here, we analyzed 54 C. jejuniisolates collected from U.S. sheep abortions at different time periods and compared them with 42 C. jejuni isolates associated with sheep abortion during 2002 to 2008 in Great Britain, using multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and array-based comparative genomic hybridization (CGH). Although clone SA (ST-8) was present in the early U.S. isolates, it was not as tetracycline resistant (19% versus 100%) or predominant (66% versus 91%) as it was in the late U.S isolates. In contrast, C. jejuni isolates from Great Britain were genetically diverse, comprising 19 STs and lacking ST-8. PFGE and CGH analyses of representative strains further confirmed the population structure of the abortion isolates. Notably, the Great Britain isolates were essentially susceptible to most tested antibiotics, including tetracycline, while the late U.S. isolates were universally resistant to this antibiotic, which could be explained by the common use of tetracyclines for control of sheep abortions in the United States but not in Great Britain. These results suggest that the dominance of clone SA in sheep abortions is unique to the United States, and the use of tetracyclines may have facilitated selection of this highly pathogenic clone

Critical Role of LuxS in the Virulence of Campylobacter jejuni in a Guinea Pig Model of Abortion

Previous studies on Campylobacter jejuni have demonstrated the role of LuxS in motility, cytolethal distending toxin production, agglutination, and intestinal colonization; however, its direct involvement in virulence has not been reported. In this study, we demonstrate a direct role of luxS in the virulence of C. jejuni in two different animal hosts. The IA3902 strain, a highly virulent sheep abortion strain recently described by our laboratory, along with its isogenic luxS mutant and luxScomplement strains, was inoculated by the oral route into both a pregnant guinea pig virulence model and a chicken colonization model. In both cases, the IA3902luxS mutant demonstrated a complete loss of ability to colonize the intestinal tract. In the pregnant model, the mutant also failed to induce abortion, while the wild-type strain was highly abortifacient. Genetic complementation of the luxSgene fully restored the virulent phenotype in both models. Interestingly, when the organism was inoculated into guinea pigs by the intraperitoneal route, no difference in virulence (abortion induction) was observed between the luxS mutant and the wild-type strain, suggesting that the defect in virulence following oral inoculation is likely associated with a defect in colonization and/or translocation of the organism out of the intestine. These studies provide the first direct evidence that LuxS plays an important role in the virulence of C. jejuni using an in vivomodel of natural disease

The Relative Role of Climate Variation and Control Interventions on Malaria Elimination Efforts in El Oro, Ecuador: A Modeling Study

Malaria is a vector-borne disease of significant public health concern. Despite widespread success of many elimination initiatives, elimination efforts in some regions of the world have stalled. Barriers to malaria elimination include climate and land use changes, such as warming temperatures and urbanization, which can alter mosquito habitats. Socioeconomic factors, such as political instability and regional migration, also threaten elimination goals. This is particularly relevant in areas where local elimination has been achieved and consequently surveillance and control efforts are dwindling and are no longer a priority. Understanding how environmental change, impacts malaria elimination has important practical implications for vector control and disease surveillance strategies. It is important to consider climate change when monitoring the threat of malaria resurgence due to socioeconomic influences. However, there is limited assessment of how the combination of climate variation, interventions and socioeconomic pressures influence long-term trends in malaria transmission and elimination efforts. In this study, we used Bayesian hierarchical mixed models and malaria case data for a 29-year period to disentangle the impacts of climate variation and malaria control efforts on malaria risk in the Ecuadorian province of El Oro, which achieved local elimination in 2011. We found shifting patterns of malaria between rural and urban areas, with a relative increase of Plasmodium vivax in urbanized areas. Minimum temperature was an important driver of malaria seasonality and the association between warmer minimum temperatures and malaria incidence was greater for Plasmodium falciparum compared to P. vivax malaria. There was considerable heterogeneity in the impact of three chemical vector control measures on both P. falciparum and P. vivax malaria. We found statistically significant associations between two of the three measures [indoor residual spraying (IRS) and space spraying] and a reduction in malaria incidence, which varied between malaria type. We also found environmental suitability for malaria transmission is increasing in El Oro, which could limit future elimination efforts if malaria is allowed to re-establish. Our findings have important implications for understanding environmental obstacles to malaria elimination and highlights the importance of designing and sustaining elimination efforts in areas that remain vulnerable to resurgence

The origins of dengue and chikungunya viruses in Ecuador following increased migration from Venezuela and Colombia

This work was funded by the Armed Forces Health Surveillance Branch (AFHSB) and its Global Emerging Infections Surveillance (GEIS) Section, FY2018 ProMIS ID P0108_18_WR.Background: In recent years, Ecuador and other South American countries have experienced an increase in arboviral diseases. A rise in dengue infections was followed by introductions of chikungunya and Zika, two viruses never before seen in many of these areas. Furthermore, the latest socioeconomic and political instability in Venezuela and the mass migration of its population into the neighboring countries has given rise to concerns of infectious disease spillover and escalation of arboviral spread in the region. Results: We performed phylogeographic analyses of dengue (DENV) and chikungunya (CHIKV) virus genomes sampled from a surveillance site in Ecuador in 2014-2015, along with genomes from the surrounding countries. Our results revealed at least two introductions of DENV, in 2011 and late 2013, that initially originated from Venezuela and/or Colombia. The introductions were subsequent to increases in the influx of Venezuelan and Colombian citizens into Ecuador, which in 2013 were 343% and 214% higher than in 2009, respectively. However, we show that Venezuela has historically been an important source of DENV dispersal in this region, even before the massive exodus of its population, suggesting already established paths of viral distribution. Like DENV, CHIKV was introduced into Ecuador at multiple time points in 2013-2014, but unlike DENV, these introductions were associated with the Caribbean. Our findings indicated no direct CHIKV connection between Ecuador, Colombia, and Venezuela as of 2015, suggesting that CHIKV was, at this point, not following the paths of DENV spread. Conclusion: Our results reveal that Ecuador is vulnerable to arbovirus import from many geographic locations, emphasizing the need of continued surveillance and more diversified prevention strategies. Importantly, increase in human movement along established paths of viral dissemination, combined with regional outbreaks and epidemics, may facilitate viral spread and lead to novel virus introductions. Thus, strengthening infectious disease surveillance and control along migration routes and improving access to healthcare for the vulnerable populations is of utmost importance.Publisher PDFPeer reviewe

Household and climate factors influence Aedes aegypti presence in the arid city of Huaquillas, Ecuador

Funding: This study was funded by NSF EEID DEB 1518681 to SJR, EAM, AMS. EAM was also supported by NIH R35GM133439, NSF DEB-2011147, the Terman Award, the Helman Faculty Fellowship, and the Stanford Center for Innovation in Global Health.Arboviruses transmitted by Aedes aegypti (e.g., dengue, chikungunya, Zika) are of major public health concern on the arid coastal border of Ecuador and Peru. This high transit border is a critical disease surveillance site due to human movement-associated risk of transmission. Local level studies are thus integral to capturing the dynamics and distribution of vector populations and social-ecological drivers of risk, to inform targeted public health interventions. Our study examines factors associated with household-level Ae. aegypti presence in Huaquillas, Ecuador, while accounting for spatial and temporal effects. From January to May of 2017, adult mosquitoes were collected from a cohort of households (n = 63) in clusters (n = 10), across the city of Huaquillas, using aspirator backpacks. Household surveys describing housing conditions, demographics, economics, travel, disease prevention, and city services were conducted by local enumerators. This study was conducted during the normal arbovirus transmission season (January-May), but during an exceptionally dry year. Household level Ae. aegypti presence peaked in February, and counts were highest in weeks with high temperatures and a week after increased rainfall. Univariate analyses with proportional odds logistic regression were used to explore household social-ecological variables and female Ae. aegypti presence. We found that homes were more likely to have Ae. aegypti when households had interruptions in piped water service. Ae. aegypti presence was less likely in households with septic systems. Based on our findings, infrastructure access and seasonal climate are important considerations for vector control in this city, and even in dry years, the arid environment of Huaquillas supports Ae. aegypti breeding habitat.Publisher PDFPeer reviewe

Chronic kidney disease in Ecuador : an epidemiological and health system analysis of an emerging public health crisis

Funding: IT, AMSI, ML, SN, KB and RS were supported by a grant from Dialysis Clinic, Inc (DCI), award number 84232.The absence of a chronic kidney disease (CKD) registry in Ecuador makes it difficult to assess the burden of disease, but there is an anticipated increase in the incidence of CKD along with increasing diabetes, hypertension and population age. From 2012, augmented funding for renal replacement therapy expanded dialysis clinics and patient coverage. We conducted 73 in-depth sociological interviews with healthcare providers in eight provinces and collected quantitative epidemiological data on patients with CKD diagnoses from six national-level databases between 2015 and 2018. Datasets show a total of 17,484 dialysis patients in 2018, or 567 patients per million population (pmp), with an annual cost exceeding 11% of Ecuador’s public health budget. Each year, there were 139–162 pmp new dialysis patients, while doctors reported waiting lists. The number of patients on peritoneal dialysis was static; those on hemodialysis increased over time. Only 13 of 24 provinces were found to have dialysis services, and nephrologists were clustered in major cities, which limits access, delays medical attention, and adds a travel burden on patients. Prevention and screening programs are scarce, while hospitalization is an important reality for CKD patients. CKD is an emerging public health crisis that has increased dramatically over the last decade in Ecuador and is expected to continue, making coverage for all patients impossible and the current structure, unsustainable. A patient registry would help health policymakers and administrators estimate the demand and progression of patients with consideration for comorbidities, disease stage, requirements and costs, mortality and follow-up. This should be used to help identify where to focus prevention and improved treatment efforts. Organized monitoring of CKD patients would benefit from improvements in patient referral. Community-based education and prevention programs, the strengthening of primary healthcare capacity (including basic routine tests) and improved nephrology services are also urgently needed.Publisher PDFPeer reviewe

A decade of arbovirus emergence in the temperate southern cone of South America: dengue, Aedes aegypti and climate dynamics in Córdoba, Argentina

Background: Argentina is located at the southern temperate range of arboviral transmission by the mosquito Aedes aegypti and has experienced a rapid increase in disease transmission in recent years. Here we present findings from an entomological surveillance study that began in Córdoba, Argentina, following the emergence of dengue in 2009. Methods: From 2009 to 2017, larval surveys were conducted monthly, from November to May, in 600 randomly selected households distributed across the city. From 2009 to 2013, ovitraps (n = 177) were sampled weekly to monitor the oviposition activity of Ae. aegypti. We explored seasonal and interannual dynamics of entomological variables and dengue transmission. Cross correlation analysis was used to identify significant lag periods. Results: Aedes aegypti were detected over the entire study period, and abundance peaked during the summer months (January to March). We identified a considerable increase in the proportion of homes with juvenile Ae. aegypti over the study period (from 5.7% of homes in 2009–10 to 15.4% of homes in 2016–17). Aedes aegypti eggs per ovitrap and larval abundance were positively associated with temperature in the same month. Autochthonous dengue transmission peaked in April, following a peak in imported dengue cases in March; autochthonous dengue was not positively associated with vector or climate variables. Conclusions: This longitudinal study provides insights into the complex dynamics of arbovirus transmission and vector populations in a temperate region of arbovirus emergence. Our findings suggest that Córdoba is well suited for arbovirus disease transmission, given the stable and abundant vector populations. Further studies are needed to better understand the role of regional human movement.Fil: Estallo, Elizabet Lilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Sippy, Rachel. University of Florida; Estados Unidos. State University of New York; Estados UnidosFil: Stewart-Ibarra, Anna M.. State University of New York; Estados Unidos. InterAmerican Institute for Global Change Research ; UruguayFil: Grech, Marta Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Benitez, Elisabet Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Ludueña Almeida, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Investigaciones Entomológicas de Córdoba; ArgentinaFil: Ainete, Mariela. Provincia de Córdoba. Ministerio de Salud; ArgentinaFil: Frias Cespedes, María. Provincia de Córdoba. Ministerio de Salud; ArgentinaFil: Robert, Michael. University Of The Sciences In Philadelphia. Department Of Mathematics Physics And Statistics.; Estados UnidosFil: Romero, Moory M.. State University of New York; Estados UnidosFil: Almiron, Walter Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Investigaciones Entomológicas de Córdoba; Argentin

A decade of arbovirus emergence in the temperate southern cone of South America : dengue, Aedes aegypti and climate dynamics in Córdoba, Argentina

Background: Argentina is located at the southern temperate range of arboviral transmission by the mosquito Aedes aegypti and has experienced a rapid increase in disease transmission in recent years. Here we present findings from an entomological surveillance study that began in Córdoba, Argentina, following the emergence of dengue in 2009. Methods: From 2009 to 2017, larval surveys were conducted monthly, from November to May, in 600 randomly selected households distributed across the city. From 2009 to 2013, ovitraps (n = 177) were sampled weekly to monitor the oviposition activity of Ae. aegypti. We explored seasonal and interannual dynamics of entomological variables and dengue transmission. Cross correlation analysis was used to identify significant lag periods. Results: Aedes aegypti were detected over the entire study period, and abundance peaked during the summer months (January to March). We identified a considerable increase in the proportion of homes with juvenile Ae. aegypti over the study period (from 5.7% of homes in 2009-10 to 15.4% of homes in 2016-17). Aedes aegypti eggs per ovitrap and larval abundance were positively associated with temperature in the same month. Autochthonous dengue transmission peaked in April, following a peak in imported dengue cases in March; autochthonous dengue was not positively associated with vector or climate variables. Conclusions: This longitudinal study provides insights into the complex dynamics of arbovirus transmission and vector populations in a temperate region of arbovirus emergence. Our findings suggest that Córdoba is well suited for arbovirus disease transmission, given the stable and abundant vector populations. Further studies are needed to better understand the role of regional human movement.Publisher PDFPeer reviewe