Wilmer E. Villamil-Gómez

Fatal Sickle Cell Disease and Zika Virus Infection in Girl from Colombia.

To the Editor: Zika virus, a mosquito-borne flavivirus, causes, a usually self-limiting febrile and exanthematic arthralgia syndrome that resembles dengue and chikungunya (1). This arboviral disease has emerged in tropical areas of Latin America, particularly in Brazil and Colombia (2), as a public health threat in 2015 and has spread into areas to which dengue virus (DENV) and chikungunya virus (CHIKV) are endemic (1–4).

Zika virus associated deaths in Colombia

Zika virus infection has emerged in Latin America as an important threat due to its association with GuillainBarré syndrome, which can lead to deaths, and microcephaly in newborn babies. Cases of fatal Zika virus infection are rare and misunderstood. The spectrum of clinical disease remains uncertain and considering the rapidly evolving epidemics of this new arbovirus in Latin America, it deserves further detailed assessment. Here, we describe four well documented fatal cases of Zika virus infection in Tolima, Colombia. Between Oct 2 and Oct 22, 2015, four febrile patients attended Tolima’s Hospitals in the central region of Colombia. Patients were a 2-year-old girl, a 30-year-old woman, a 61-yearold man, and a 72-year-old woman, with 2–6 previous days with fever. The infant girl also had dehydration, somnolence, hepatomegaly, mucosa haemorrhage, and thrombocytopenia, evolving to respiratory distress, disseminated intravascular coagulation, and shock. The 30-year-old woman had exanthema in upper and lower limbs, severe thrombocytopenia, and leukopenia, evolving in 10 days to intracerebral and subarachnoid haemorrhages, sepsis, acute respiratory failure, seizures, and shock. The older man had myalgias and arthralgias, with dehydration, mucosa haemorrhage, also evolving to respiratory distress, acute coronary syndrome, and shock. This patient’s history included high blood pressure under medication control. The older woman presented with abdominal pain, vomiting, dehydration, somnolence, and thrombocytopenia, evolving to acute respiratory failure and shock. This patient’s history included diabetes mellitus type 2 under control with insulin. In all four patients, giving the endemicity of the zone, dengue fever or chikungunya were suspected. All patients presented with anaemia (haemoglobin range 90–120 g/L), three of them with leukopenia. The 30-year-old woman had leukocytosis, and all but the older man had severe thrombocytopenia (<14 000 platelets per mL). Despite medical management at the intensive care unit, all of four patients died. The infant girl died 24 h after admission (5 days after symptoms began); the 30-year-old woman died after 10 days (12 days after symptoms began); the 61-year-old man at 24 h (7 days after symptoms begun), and the 72-year-old woman in less than 24 h (48 h after symptoms began). In all these cases, RT-PCR for dengue (including tissues), anti-dengue IgM, and NS1 ELISA and western-blot tests were negative. In the 61-year-old man, IgM for chikungunya was positive. IgM for Leptospira spp was negative in all cases. Finally, in all patients RT-PCR for Zika virus was positive, confi rmed at the Colombia national reference laboratory. In the infant girl and 30-yearold woman, necropsy revealed probable acute leukaemias (lymphoblastic and myeloid, respectively). In the 61 yearold man, necropsy showed ischaemic lesions in the brain with areas of necrosis in the liver and of systemic infl ammatory response in the spleen. In this patient, RT-PCR of tissues was positive for Zika virus. In the 72-year-old woman, necropsy showed oedema and ischemic lesions in brain. From Sept 22, 2015, to March 19, 2016, there were 58 838 cases of Zika virus infection in Colombia ( 2 3 6 1 l a b o r a t o r yc o n f i r m e d , 49 211 diagnosed by clinical criteria, and 7266 suspected); nevertheless before the current report, only one previous fatal case has been described, from our group in Colombia. Before the current outbreak in Latin America, Zika virus was not linked to deaths, but as of Nov 28, 2015, the Brazil Ministry of Health has also reported three deaths associated with Zika virus infection (two in adults and one in a newborn baby). These cases call attention to the need for evidence-based guidelines for clinical management of Zika, as well as the possible occurrence of atypical and severe cases (including possibly congenitally-related microcephaly). Based in our first case report, such guidelines have been considered and suggested by the European Centre for Disease Control in its recent Rapid Risk Assessment.

Zika, dengue, and chikungunya co-infection in a pregnant woman from Colombia

The clinical findings of a pregnant woman from Colombia with a triple co-infection caused by dengue, chikungunya, and Zika viruses are described. Weekly obstetric ultrasounds from 14.6 to 29 weeks of gestation were normal. She remains under follow-up and management according to the standard guidelines for the management of Zika virus-infected pregnant women.

Congenital Chikungunya Virus Infection in Sincelejo, Colombia: A Case Series

Congenital chikungunya virus (CHIK) infection has been infrequently reported, even more so during the current 2013-15 outbreak in Latin America. In this study, the consequences of CHIK on pregnancy outcomes and particularly consequences in infants born to infected women were assessed in a case series from a single private institution in the north of Colombia. During September 2014 to February 2015, seven pregnant women with serological and reverse transcription-polymerase chain reaction-positive test for CHIK delivered eight infants with CHIK. These newborns required admission to pediatric intensive care, and related support, owing to severe clinical manifestations, which included respiratory distress, sepsis, necrotizing enterocolitis, meningoencephalitis, myocarditis, edema, bullous dermatitis and pericarditis. There were three deaths (case fatality rate of 37.5%). Pregnant women and newborns with CHIK long term should be followed up, given the implications of chronic sequelae (e.g. chronic inflammatory rheumatism in women) as well as recently described neurocognitive impairment in infants.

Estimating the burden of disease and the economic cost attributable to chikungunya, Colombia, 2014

BACKGROUND Chikungunya (CHIK) virus disease is expected to be a considerable cause of disability and economic burden in Latin America given its chronic sequelae, particularly its chronic inflammatory rheumatism. There have been no previous studies assessing CHIK costs and disability in Latin America. METHODS We calculated incidence rates for CHIK during the 2014 outbreak in Colombia using epidemiological data provided by the Colombian National Institute of Health, using demographic data from the National Administrative Department of Statistics. The burden of disease was estimated through disability adjusted life years (DALYs) lost and the costs were estimated based on the national recommendations for CHIK acute and chronic phase attention. RESULTS There were a total of 106 592 cases, with incidence rates ranging from 0 to 1837.3 cases/100 000 population in different departments. An estimate was made of total DALYs lost of 40.44 to 45.14 lost/100 000 population. The 2014 outbreak estimated costs were at least US

ChikDenMaZika Syndrome: the challenge of diagnosing arboviral infections in the midst of concurrent epidemics

73.6 million. CONCLUSIONS Our estimates raise concerns about the effects of continued CHIK spread in Colombia and other Latin-American countries. The lack of transmission control for this disease and potential for spread means that there will be significant acute and chronic disability and related costs in the short and long term for Latin American health care systems.

Healthcare students and workers' knowledge about transmission, epidemiology and symptoms of Zika fever in four cities of Colombia.

Arthropod-borne viruses are becoming and increasing threat worldwide, especially in the New World, which has recently witnessed an unprecedented outburst of Arboviral outbreaks [1–4], such as the recent and ongoing chikungunya (CHIKV) [1] and Zika (ZIKV) [2] epidemics throughout the Pacific and the Americas. These emerging viral infections are largely due to a number of factors such as climate change [5–7], ever-increasing trends towards urbanization and growing travel and commercial exchange activities [8–12]; which have led to a spillover of these pathogens from their naturally occurring sylvatic niches and reservoirs into susceptible urban settings and newly unexposed geographic areas [13–16].

Post-chikungunya chronic arthralgia: a first retrospective follow-up study of 39 cases in Colombia

Please cite this article as: Sabogal-Roman JA, Murillo-García DR, Yepes-Echeverri MC, RestrepoMejia JD, Granados-Álvarez S, Paniz-Mondolfi AE, Villamil-Gómez WE, Zapata-Cerpa DC, BarretoRodriguez K, Rodríguez-Morales AJ, Healthcare students and workers’ knowledge about transmission, epidemiology and symptoms of Zika fever in four cities of Colombia, Travel Medicine and Infectious Disease (2016), doi: 10.1016/j.tmaid.2015.12.003.

Mapping Zika in municipalities of one coastal department of Colombia (Sucre) using geographic information systems during the 2015–2016 outbreak: implications for public health and travel advice

As has been previously described [1], chikungunya virus disease (CHIK) has emerged in Latin America as a significant acute infectious disease condition, but also with multiple implications during its chronic phase, including the postchikungunya chronic inflammatory rheumatism (pCHIKCIR). Until today, no observational studies in the region have described its prevalence, but recent estimations indicated that probably about 48 % of infected people in Latin America in a median of 20 months would develop it [2]. In this scenario, where over one million cases of CHIK were reported in the Americas during 2014, observational studies describing this rheumatologic consequence are urgently needed. Then, here, we detailed the prevalence of pCHIK chronic polyarthralgia (pCHIK-CPA) in patients that suffered from confirmed CHIK at least 6 weeks before current assessment with a maximum follow-up of 65 weeks (15 months) (median time of 35 weeks). From 39 patients that suffered CHIK (diagnosed by PCR during acute phase) between April 2014 and May 2015 who attended in Since, Sucre (one of the newly endemic departments), Colombia, 30 (76.9 %) corresponded to female patients, with a median age of 61 years old (range 17–88). Of them, 89.7 % developed persistent polyarthralgia (pCHIKCPA) that met the American College of Rheumatology/ European League Against Rheumatism 2010 criteria for (seronegative) RA-presented persistent polyarthralgia [3], during the last week when all of them were reassessed after CHIK infection (June 2015), 92.3 % during the last month. A cumulated prevalence of pCHIK-CPA curve was drawn using the Kaplan-Meier method to describe the pCHIK-CPA persistence time (Fig. 1). After the follow-up, only 10.3 % patients remain free of polyarthralgia. The median time for pCHIK-CPA in this cohort was 37 weeks (95 %CI 31.4– 42.6). Among the studies assessing pCHIK-CIR, its relative frequency is highly variable, ranging from 14.4 to 87.2 % (including variable number of patients and follow-up times) [2, 4, 5]. Unfortunately, only studies assessing acute polyarthralgia (96 %) and arthritis (47 %) have been published in Latin America during the current CHIK epidemics [6], even without laboratory serological or molecular confirmation, which is highly relevant [7]. The current cohort, the first in Latin America of pCHIK chronic polyarthralgia, shows a higher prevalence. These findings will require more detailed prospective studies, but despite its limitations, it * Alfonso J. Rodriguez-Morales arodriguezm@utp.edu.co

Ophthalmologic aspects of chikungunya infection.

Zika virus (ZIKV) infection emerged in 2015 as one of the most significant tropical infectious diseases in Latin America, following the geographical distribution of chikungunya virus (CHIKV). These viruses share high transmissibility due to the extended presence of the main vector mosquito Aedes aegypti in the region. Travelers to endemic areas in Latin American countries should be aware of the risk of exposure to infection through mosquito bites when visiting these areas. In order to provide useful advice for travelers, epidemiological information is of the utmost importance. Such advice includes the availability of detailed maps in order to assess the risk when visiting a specific destination. We have developed among the first published epidemiological maps for ZIKV in Colombia using geographical information systems (GIS) in the department of Sucre, which is located in one of the main tourist regions of the country (Caribbean coast region). We have previously provided GIS-based epidemiological maps for CHIKV for this region. Scientific reports in which GIS has been used for the development of epidemiological maps for ZIKV are not yet available for Colombia and Latin America, particularly the north Caribbean coastal areas of Colombia (including the department of Sucre), which have been affected significantly by the 2015–2016 Americas outbreak. Surveillance case data (2015–2016; officially reported by the National Institute of Health of Colombia) were used to estimate the cumulative incidence rates using reference population data (2016) of ZIKV infections (cases/100 000 population) and to develop the first maps for the municipalities of Sucre. The GIS used was Kosmo 3.1. Up to February 13, 2016 (epidemiological week 6), 1253 cases of ZIKV were reported in Sucre, for a cumulative rate of 145.71 cases/100 000 population (3.4%). Rates at the municipality level ranged from 0 to 405.9 cases/100 000 population. The rate in cases per 100 000 population was 405.9 in Buenavista municipality (3.11% of the department cases), 248.36 in Sincelejo (capital of the department; 55.3%), 240.01 in Morroa (2.8%), 230.29 in Tolú