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      COVID-19 and dengue, co-epidemics in Ecuador and other countries in Latin America: Pushing strained health care systems over the edge

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          Abstract

          Dear Editor, Currently, the spread of Coronavirus-19 disease (COVID-19) from the emerging SARS-CoV-2 virus in Wuhan, China, has reached other Asian countries, Europe, North America as a pandemic situation, and has already entered Latin America with multiple implications [1]. One of these is the continuous dengue epidemic in Ecuador and other countries in 2019–2020. This period comprises a further increase in cases and one of the largest dengue outbreaks in the region with nearly 3 million cases, 8416 of them in Ecuador [2,3]. COVID-19 cases in Ecuador reached 1595 confirmed cases with 36 deaths nationwide (March 27, 2020) [4], while dengue, reached 3549 cases. Ecuador has four geographic regions with marked climatic, social, and travellers entry differences (Coast, Andeans-Sierra, Amazon, and the Galapagos Islands) that influence dengue eco-epidemiological dynamics as well as the COVID-19 epidemic. The coast and the city of Guayaquil present, simultaneously, 82.57% of the confirmed cases of COVID-19 and the highest number of dengue cases (84%). La Sierra (Quito, Capital and the principal city) presents 3.7% of dengue and 15.36% of the COVID-19 cases. Amazonia presents 11.3% of dengue and 1.82% of COVID-19, and Galapagos zero and four (0.25%) cases respectively. Thus, the most significant public health problem occurs on the coast, with Guayaquil (officially Santiago de Guayaquil), capital of Guayas province, as the primary source of transmission and contagion. This city has not adopted new COVID-19 containment measures, nor is it conducting an optimal mitigation campaign. Its climatic characteristics and deficiencies in public services have led to the high endemic-epidemic transmission of dengue. The Sierra (Quito) has adopted drastic mitigation measures even with a low number of cases, while the average altitude (above 1,700 m, with the absence of Aedes aegypti) and its low temperatures provide areas free of dengue transmission. Galapagos island has a higher containment capacity and has adopted recently substantial restrictions on tourist income. For their part, the Amazonian provinces have air and land access, however, their population density is very low. Only moderately large cities usually present cases of dengue, not the westernized indigenous communities [5], and the few cases of COVID-19 have been tourists who entered with infection or local non-community transmission. Ecuador, with 17 million inhabitants (58% coast, 38% sierra, 12% amazon, 3% Galapagos), has an availability of 389 intensive care units (ICU) (2 units/100,000 inhabitants) and 1183 ICU beds (7 beds/100,000 inhabitants) (Fig. 1 ). Galapagos has neither ICU rooms nor beds, and Amazonia only 10 and 19, respectively. The Coast, has the fewest number of ICU units and beds (139 rooms and 534 beds), the Sierra with 240 and 1219 respectively. Additionally, we will have a high probability of co-infections of both viruses, with mixing symptoms, which can worsen the epidemiological situation of diagnostic, control and treatment in Latin America, unlike in Europe and the USA and not reported in Asia due to the winter period. These data suggest that the health system on the coast could be simultaneously affected by both epidemics, and the number of seriously ill patients will exceed the availability of units and beds if mitigation measures are not carried out rigorously, and immediately. Fig. 1 ICUs and beds in Ecuador national health system. Fig. 1 According to the estimates of the percentage of seriously ill patients who may require ICU bed intake (5% of the total cases), if a doubling of cases is initiated every seven days, and with each patient requiring about 21 days on average to recover, the region could be outnumbered in the number of beds in a few weeks at the start of the infection exponential stage. ICU care for patients with severe dengue will have less pressure on the system (severe dengue <1%). However, most of the febrile dengue cases will overlap in health centres along with cases of COVID-19, sharing clinical features. If we add the possibility of some false positives by rapid dengue tests, the failure to consider COVID-19 due to this result will have serious implications not only for the patient but also for the public health. Hence, the importance of developing rapid and reliable tests for SARS-CoV-2/Dengue in the immediate future. Likewise, the differentiated supply of drugs such as ibuprofen, with different severity-COVID19 in Italy [6], and aspirin (contraindicated for dengue) will increase the complexity of medical care in the simultaneous epidemics. On April 5, 2020, time of proofs correction, there were 3,646 cases of COVID-19 in Ecuador. Author credit JCN, Conceptualization; Writing - original draft; Writing - review & editing. JAH, Writing - review & editing. JS, Writing - review & editing. AJRM, Writing - review & editing. Funding UISEK-P0116171_2 (JCN). Declaration of competing interest None of the authors reports a conflict of interests.

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          Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?

          The most distinctive comorbidities of 32 non-survivors from a group of 52 intensive care unit patients with novel coronavirus disease 2019 (COVID-19) in the study by Xiaobo Yang and colleagues 1 were cerebrovascular diseases (22%) and diabetes (22%). Another study 2 included 1099 patients with confirmed COVID-19, of whom 173 had severe disease with comorbidities of hypertension (23·7%), diabetes mellitus (16·2%), coronary heart diseases (5·8%), and cerebrovascular disease (2·3%). In a third study, 3 of 140 patients who were admitted to hospital with COVID-19, 30% had hypertension and 12% had diabetes. Notably, the most frequent comorbidities reported in these three studies of patients with COVID-19 are often treated with angiotensin-converting enzyme (ACE) inhibitors; however, treatment was not assessed in either study. Human pathogenic coronaviruses (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARS-CoV-2) bind to their target cells through angiotensin-converting enzyme 2 (ACE2), which is expressed by epithelial cells of the lung, intestine, kidney, and blood vessels. 4 The expression of ACE2 is substantially increased in patients with type 1 or type 2 diabetes, who are treated with ACE inhibitors and angiotensin II type-I receptor blockers (ARBs). 4 Hypertension is also treated with ACE inhibitors and ARBs, which results in an upregulation of ACE2. 5 ACE2 can also be increased by thiazolidinediones and ibuprofen. These data suggest that ACE2 expression is increased in diabetes and treatment with ACE inhibitors and ARBs increases ACE2 expression. Consequently, the increased expression of ACE2 would facilitate infection with COVID-19. We therefore hypothesise that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19. If this hypothesis were to be confirmed, it could lead to a conflict regarding treatment because ACE2 reduces inflammation and has been suggested as a potential new therapy for inflammatory lung diseases, cancer, diabetes, and hypertension. A further aspect that should be investigated is the genetic predisposition for an increased risk of SARS-CoV-2 infection, which might be due to ACE2 polymorphisms that have been linked to diabetes mellitus, cerebral stroke, and hypertension, specifically in Asian populations. Summarising this information, the sensitivity of an individual might result from a combination of both therapy and ACE2 polymorphism. We suggest that patients with cardiac diseases, hypertension, or diabetes, who are treated with ACE2-increasing drugs, are at higher risk for severe COVID-19 infection and, therefore, should be monitored for ACE2-modulating medications, such as ACE inhibitors or ARBs. Based on a PubMed search on Feb 28, 2020, we did not find any evidence to suggest that antihypertensive calcium channel blockers increased ACE2 expression or activity, therefore these could be a suitable alternative treatment in these patients. © 2020 Juan Gaertner/Science Photo Library 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
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            COVID-19 in Latin America: The implications of the first confirmed case in Brazil

            Over the past weeks the spread of the Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [1], has been steady in Asia and other regions in the world. Latin America was an exception until February 25, 2020, when the Brazilian Ministry of Health, confirmed the first case. This first case was a Brazilian man, 61 years-old, who traveled from February 9 to 20, 2020, to Lombardy, northern Italy, where a significant outbreak is ongoing. He arrived home on February 21, 2020, and was attended at the Hospital Albert Einstein in São Paulo, Brazil. At this institution, an initial real-time RT-PCR was positive for SARS-CoV-2 and then confirmed by the National Reference Laboratory at the Instituto Adolfo Lutz using the real-time RT-PCR protocol developed by the Institute of Virology at Charité in Berlin, Germany [2]. The established protocol also included now, as part of the Sao Paulo State Health Secretary, metagenomics and immunohistochemistry with PCR, as part of the response plan to COVID-19 outbreak in the city [3]. The patient presented with fever, dry cough, sore throat, and coryza. So far, as of February 27, the patient is well, with mild signs. He received standard precautionary care, and in the meantime, he is isolated at home [4]. Local health authorities are carrying out the identification and tracing of contacts at home, at the hospital, and on the flight. For now, other cases are under investigation in São Paulo, and other cities in Latin America. In addition to the São Paulo State Health Secretary, the Brazilian Society for Infectious Diseases have developed technical recommendations [4]. This is the first case of COVID-19 in the South American region with a population of over 640 million people [5] who have also experienced significant outbreaks of infections which were declared Public Health Emergencies of International Concern (PHIC), by the World Health Organization (WHO). So it was with Zika in 2016. The Zika outbreak also began in Brazil [6]. In the current scenario, the spread of COVID-19 to other neighboring countries is expected and is probably inevitable in the light of the arrival of suspected cases from Italy, China, and other significantly affected countries. São Paulo is the most populated city in South America, with more than 23 million people and high flight connectivity in the region (Fig. 1 ). Its main airport, the São Paulo-Guarulhos International Airport, is the largest in Brazil, with non-stop passenger flights scheduled to 103 destinations in 30 countries, and 52 domestic flights, connecting not only with major cities in Latin America but also with direct flights to North America, Europe, Africa and the Middle East (Dubai). There are also buses that offer a service to and from the metropolitan centers of Paraguay, Argentina, Uruguay and Bolivia. Brazil also connects with the countries of Chile, Argentina and Bolivia through some rail connections. The main seaport of Brazil is in Rio de Janeiro, where many international cruises also arrive. Thus, over the course of the next few days, a significant expansion in the region would be possible. Fig. 1 Flight connections from São Paulo's main international airport, Brazil. Source: flightconnections.com. Fig. 1 The healthcare systems in this region are already fragile [7]. Moreover, fragmentation and segmentation are ongoing challenges for most of these vulnerable systems. Multiple social and economic issues are ongoing and will impact the situation, including the massive exodus from Venezuela to many countries in the region. This human migration is associated with other infectious diseases, such as malaria or measles [8]. The burden that will be imposed on the region, if and when COVID-19 spreads, would be an additional challenge for the healthcare systems and economies in the region, as we faced with Zika and even the Chikungunya outbreaks [9]. For example, there is concern about the availability of intensive care units, that are necessary for at least 20–25% of patients hospitalized with COVID-19—also, the availability of specific diagnostic tests, particularly the real-time RT-PCR is a crucial challenge for early detection of COVID-19 importation and prevention of onward transmission. Even maybe in some countries, cases have been not diagnosed due to lack of availability of specific tests. Are Latin American healthcare systems sufficiently prepared? Probably not, but in general, this is the same in other regions of the world, such as in many parts of Asia and Africa [10]. Although most countries in Latin America are trying to step up their preparedness to detect and cope with COVID-19 outbreaks, it will be essential to intensify inter-continental and intra-continental, communication and health workforce training. In the Latin American region, there is a large heterogeneity of political and social development, economic growth, and political capacities. For example, in the Caribbean subregion, countries such as Haiti have a low Human Development Index. In such areas, and Venezuela where a humanitarian crisis had occurred since 2019 spreading measles, diphtheria, and vector-borne diseases, such as malaria, over the region [[11], [12], [13]], the impact of a COVID-19 outbreak will be more devastating than in the more developed economies, such as Brazil or Mexico. Most of the countries in the region are remembering the lessons learned during SARS (2003) and pandemic influenza (2009). Protocols already developed during those crises, including laboratory and patient management, may prove useful in this new situation. Good communication strategies for preventive measures in the population, and in neighboring countries in addition to Brazil, will be essential and this response should be aligned with the recommendations of the WHO. In Latin America, the Pan-American Health Organization (PAHO/WHO) recent epidemiological alert for measles shows that from January 1, 2019 to January 24, 2020, 20,430 confirmed cases of measles were reported, including 19 deaths, in 14 countries: Argentina, Bahamas, Brazil, Chile, Colombia, Costa Rica, Cuba, Curaçao, Mexico, Peru, Uruguay and Venezuela. Brazil contributed 88% of the total confirmed cases in the Americas [14]. In the first 4 weeks of 2020, a staggering 125,514 cases of measles were notified. The dengue incidence rate is 12.86 cases/100,000 inhabitants in the region for the ongoing year, including 27 deaths, 12,891 cases confirmed by laboratory and 498 cases classified as severe dengue (0.4%). Countries like Bolivia, Honduras, Mexico and Paraguay have reported an increase of double or triple the number of cases of dengue compared to the same period from the previous year [15]. In this complex epidemiological scenario, we are about to witness a syndemic [16] of measles, dengue, and COVID-19, among others, unfold. The World Health Organization (WHO) has published guidelines encouraging the provision of information to health professionals and the general public. Resources, intensified surveillance, and capacity building should be urgently prioritized in countries with a moderate risk that might be ill-prepared to detect imported cases and to limit onward transmission, as has already occurred in Brazil. [For the moment of proofs correction of this Editorial –Mar. 1, 2020–, 2 cases have been confirmed in Brazil, but also new 5 confirmed cases were also reported in Mexico (2° country that reported cases), 6 in Ecuador (3°) and 1 in Dominican Republic (4°), summarizing 14 cases in Latin America]. Credit author statement AJRM conceived the idea of the Editorial and wrote the first draft. The rest of the authors reviewed and improved the second draft. All authors approved the final version. Author contributions Conceptualization: AJRM. Writing—original draft preparation: AJRM. Writing—review, and editing: All the authors. Funding source None. Ethical approval Approval was not required. Declaration of competing interest None of the authors has any conflict of interest to declare.All authors report no potential conflicts. All authors have submitted the Form for Disclosure of Potential.
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              Dengue in Honduras and the Americas: The epidemics are back!

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                Author and article information

                Contributors
                Journal
                Travel Med Infect Dis
                Travel Med Infect Dis
                Travel Medicine and Infectious Disease
                Elsevier Ltd.
                1477-8939
                1873-0442
                5 April 2020
                5 April 2020
                : 101656
                Affiliations
                [1]Universidad Internacional SEK, Center for Biodiversity, Emerging Diseases and Environmental Health, Master School of Biomedicine, Natural Sciences and Environment Faculty, Quito, Ecuador
                [3]Colombian Collaborative Network on Zika and Other Arboviruses (RECOLZIKA), Pereira, Risaralda, Colombia
                [4]Latin American Network of Coronavirus Disease 2019-COVID-19 Research (LANCOVID-19), Pereira, Risaralda, Colombia
                [5]Universidad Central del Ecuador, Environmental and Territory Area, THC-FACSO, Quito, Ecuador
                [6]Universidad Internacional SEK, Center for Biodiversity, Emerging Diseases and Environmental Health, Master School of Biomedicine, Natural Sciences and Environment Faculty, Quito, Ecuador
                [7]Colombian Collaborative Network on Zika and Other Arboviruses (RECOLZIKA), Pereira, Risaralda, Colombia
                [8]Latin American Network of Coronavirus Disease 2019-COVID-19 Research (LANCOVID-19), Pereira, Risaralda, Colombia
                [9]Grupo de Investigación Biomedicina, Faculty of Medicine, Fundación Universitaria Autónoma de las Américas, Pereira, Risaralda, Colombia
                [10]Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnológica de Pereira, Pereira, Risaralda, Colombia
                Author notes
                [∗∗ ]Corresponding author. Universidad Internacional SEK, Center for Biodiversity, Emerging Diseases and Environmental Health, Master School of Biomedicine, Natural Sciences and Environment Faculty, Quito, Ecuador. juancarlos.navarro@ 123456uisek.edu.ec
                []Corresponding author. Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnológica de Pereira, Pereira, Risaralda, Colombia. arodriguezm@ 123456utp.edu.co
                Article
                S1477-8939(20)30124-1 101656
                10.1016/j.tmaid.2020.101656
                7130119
                32268196
                c3a16083-221f-4c43-bf65-c2c2dbcb82c4
                © 2020 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 24 March 2020
                : 29 March 2020
                : 30 March 2020
                Categories
                Article

                Infectious disease & Microbiology
                pandemic,sars-cov-19,coivid19,dengue,travellers,latin america
                Infectious disease & Microbiology
                pandemic, sars-cov-19, coivid19, dengue, travellers, latin america

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