Dengue, Chikunguña and Zika in Colombia 2015-2016

Dengue, Chikunguña y Zika en Colombia 2015-2016

Zika, Chikungunya and Dengue are three arboviruses transmitted by mosquitoes of the genus Aedes (A. Aegypti and A. Albopictus), able to simultaneously infect a patient (1). Although they have differences in their expression (2), these viral infections produce similar clinical manifestations, such as fever, rash, arthralgia, cephalea, and retroocular pain. However, in order to appropriately define each of the events, in Colombia the differences are determined as follows: a) in the case of Chikungunya, arthralgia is considered “severe” and there may be an onset of acute arthritis, b) for Dengue, the presence of Muscle ache and retroorbital pain are key: and c) for Zika, pruritus and non-purulent conjunctivitis are essential (3,4,5). This raises diagnostic challenges for physicians who should classify suspected cases of Dengue, Chikunguya and Zika.

Given the antibodies cross-reactivity phenomenon between Dengue, Chikunguya and Zika, the infection’s serological diagnosis, made by determining the IgM in relation to the virus, is not specific at all. Other more specific diagnostic techniques, such as the viral load determination using RT-PCR tests, cultures or neutralization methods are not routinely performed in the clinical laboratories of first or second level hospitals, but rather in reference or research centers, and in many cases this hinders a timely diagnosis, which makes it difficult to carry out a specific diagnosis, especially in areas exposed to three viruses.

These impact of these epidemics has been assessed from different perspectives, such as the epidemiological and economic impact on society and health systems (6,7,8). In addition, cases of microcephaly, that may be associated to this where studied during the Zika epidemic in Brazil. Until January 2016, 574 cases of microcephaly associated to the Zika infection during early stages of pregnancy were reported and the presence of the virus was confirmed in 22 of the 26 states in the five regions of the country (9). Rasmussen et al (10) suggest that, based on the different criteria required to prove the existence of teratogenesis in humans, there is sufficient scientific and epidemiological evidence to infer a causal relationship between Zika virus infection in women during prenatal period and congenital abnormalities in newborns and fetuses.

In Colombia, the main source of information about Dengue, Chikunguya and Zika cases is the Epidemiological Monitoring System (Sistema de Vigilancia Epidemiológica- SIVIGILA) of National Health Institute (Instituto Nacional de Salud). It discloses information through a Weekly Epidemiological Bulletin (Boletín Epidemiológico Semanal), which, in spite of the under-reporting, is an official source of information for the generation of morbidity reports due to these diseases (11). The objective of this study is to describe the behavior of this pathologies in Colombia during 2015 and 2016.

Study type. An observational, descriptive study was conducted, using the Epidemiological Reports (Boletines Epidemiológicos) of National Health Insitute (Instituto Nacional de Salud) of Colombia as a secondary source of information (11).

Geo-climatic conditions. Colombia has geographic conditions that affect temperature, which, on average, ranges from 30°C on the coasts and plains to temperatures below 0°C on the peaks of the Andes mountain chains and the Sierra Nevada.

Study Site Coordinates. Geo-astronomical location of Colombia: 12°26’46’’ north latitude to 4°12’30’’ south latitude, and 60°50’54’’ west longitude from Greenwich, to 79°02’33’’ west longitude.

Subjects. Information from epidemiological bulletins of the National Health Insitute (Instituto Nacional de Salud) (week 40 to 52 of 2015 and 1 to 52 of 2016), which describes 106.559 Zika cases (11.712 in 2015), 103.822 Dengue cases (454.463 in 2015) and 19,556 Chikunguya cases (359.728 in 2015) was analyzed.

Ethical aspects. As previously stated, the research group processed and analyzed the information from a secondary source. They did so, considering the Standards of Good Clinical Practice in Research (Normas de Buenas Prácticas Clínicas en Investigación) and Resolution 8430 of 1993 (Ministry of Health, 1993), according to which, this type work is classified as “without risk”, because it does not use confidential information related to the case, but consolidated data and the information is public and for academic and administrative purposes.

Results Analysis: Excel 2013 was used to digitize the data from the epidemiological bulletins into consolidated tables, to calculate percentages, ratios and trends, as well as measures of central tendency (mean and standard deviation) that do not show up in the bulletins. In addition, the T-test and P value were used to estimate differences in mean ages of Chikunguya cases, compared to Dengue and Zika cases.

The following cases were reported in the country during 2015: 11.712 Zika, 454.463 Dengue and 359.728 Chikunguya cases, and in 2016: 103.882 Dengue, 19.556 Chikunguya and 106.559 Zika cases. The incidence figures of the disease in Colombia for 52 epidemiological weeks of 2016 indicate that Dengue, Chikunguya and Zika affected people of all ages (epidemiological bulletins for 2015 cases were not distributed by age group). The 25 to 44 years old group had the highest case ratio, with 39.8% of Chikunguya and 42.5% Zika virus infection reported cases. In contrast, for Dengue and severe Dengue, about 50% of cases occurred in people under 25 years old (Figure 1). When calculating the mean age for pooled data, mean for Chikunguya (34.5; DE+/-: 38.1) was statistically higher (t:15.9; p: 0.000) than Dengue (29.8; DE+/-:35.0) and also (t:15.74; p:0.000) than Zika (29.9; DE+/-:33.8)

In the same way, in the year 2015, 34.1% of Zika virus infection cases were reported using laboratory diagnostics. By 2016, the highest percentage of laboratory-confirmed cases was recorded as of week 23 (8.6% on average), while suspicious cases began to noticeably decline from week 13 onwards, because before then, the percentage per week was 13% and from week 13 onwards the average was 4.3%. It is necessary to mention that by the week 30 from 2016 the Ministry of Health and Social Protection decreed the end of the Zika epidemic (Figure 2.)

The acute character of Zika infection in relation to Dengue and Chikunguya infections must be highlighted, because at the end of week 52 of 2016, 106,659 cases of the disease had been reported in the country. Regarding Dengue infection, the total number of reported cases for that week was 103,822, while those for Chikunguya were 19,556 (Table 1.) It is necessary to clarify that on week 40 of 2015 a Notice was issued for Zika, no cases of dengue were present on week 2, and Epidemiological Bulletin for week 10 was not available for consultation.

The case frequency ratio for the three infections is best visualized in 2016 (Figure 3). In the first epidemiological week of 2016, for each reported Dengue case there were 13 Zika and 19 Chikunguya cases, and as of the second week, except for week 43, there was a lower ratio of accumulated cases, indicating a decreasing behavior for Zika (The Ministry of Health and Social Protection decreed the end of the Zika epidemic on week 30, 2016). However, there is doubt as to whether Dengue was sub-diagnosed in 2016, since the number of cases reported in 2016 (103,822) was higher than the cases reported in 2015 (92,795 cases), but lower than those reported in 2014 (108,291 cases), and there is a wide difference when comparing with the Chikunguya Notice from 2014 to 2016, because it went from 106,763 in 2014, to 359,728 in 2015, to only 19,556 in 2016, as of week 52 on each of the three years.

On the other hand, the morbidity behavior associated to Zika and Chikunguya had an important impact on women of reproductive age. According to data from National Health Institute (12), the percentage of women reported was: 49.9% for Dengue, 63.3% for Chikunguya and 66.4% for Zika, which agrees with increase in reported cases of pregnant women between weeks one and fifty two of 2016, because among them, it went from 560 to 19.746 cases, with a lower frequency of laboratory-confirmed diagnosis (Figure 4.) Neurological syndromes and congenital defects were issued as a Notice on week 12 of 2016

This study shows the trends and relationships between case frequencies of three diseases transmitted by the same vector. In Colombia, Chikunguya and Zika have shown a greater presence among age groups of economically active population (20-39 years), as Nava-Frías et al (13) reported in Mexico in 2014, where 34.8% of patients were between 25 and 44 years old, similar to results of this study. Regarding Dengue, the results are similar to those of Romero et al (14), who evaluated the epidemiological situation of the disease in 11 Departments of Colombia during 2014, and found that 42% of the cases occurred in children under 14.

For gender, Duffy et al (15) found a greater ratio of women (61%) in the total confirmed and probable Zika cases during an outbreak studied in Yap, Micronesia. The attack rate obtained from this group of patients was 17.9 for each 1000 women vs 11.4 for each 1000 men. Nonetheless, the prevalence of antigens that counter Zika detected was higher in men. The authors suggest that these discrepancies could be the result of differences in the use of sanitary services and exposure frequency to the vector. In Puerto Rico (16), a sample of 30 patients with Zika infection confirmed through laboratory diagnosis, showed that disease was more frequent among women (60%) of a mean age of 40 years old.

In Colombia, the high number of women diagnosed with these diseases could be due to a generalized concern about their possible susceptibility to the adverse consequences associated with the diseases. For Zika, several studies have suggested a possible causal relationship between the arbovirus infection and a higher prevalence of neurological diseases in newborns and adults such as microcephaly and Guillain-Barré syndrome (17,18,19).

Thus, if the clinical and epidemiological criteria under which diagnoses were carried out in Colombia, are taken into account, the higher presence of reported cases of these diseases in female patients could be related to the degree of uncertainty that physicians and patients have about the possible adverse effects associated with Zika virus, and their susceptibility during pregnancy. Therefore, it is necessary to increase the number of laboratory tests to list confirmed cases, since a major share of these are reported as positive only through clinical criteria.

On the other hand, Cardoso et al (2) suggest that identifying Zika, Dengue and Chikunguya viruses as etiological agents represents a challenge to clinically differentiate infections during outbreaks. In this study, it is likely that, due to the similarities in the symptomatology of the three diseases, there has been a greater tendency to diagnose Zika when compared to the other two, as a result of the outbreak and proliferation of the virus and alert generated by health authorities at a national and international level (20); however, an analysis stratified by department is required.

Measures such as those carried out in Puerto Rico (16) should not be ruled out, where health authorities recommended treating all suspected cases of Zika or Chikunguya infection as potential Dengue cases, while a specific diagnosis is established through laboratory tests, due to the possible associated complications. This should be considered in countries like Colombia, where all three viruses circulate and Dengue cases are not decreasing.

Likewise, under-reporting represents one of the main problems associated with controlling this disease in low- and middle-income countries located in the tropical region. A study by Silva et al. (21) in Salvador, Brazil, found that for every twenty patients diagnosed with Dengue through laboratory tests, only one had been registered in the Information System for Diseases of Mandatory Registration (Sistema de Informação de Agravos de Notification-SINAN) as having Dengue. One in four patients, considered for the study, who presented symptoms of an acute febrile illness (AFI), was tested for Dengue in the laboratory. In addition, among the patients reported as patients with Dengue, 31.2% did not have the disease. The authors estimated that the mean annual incidence of the disease was 3,645 cases per 100,000 residents during the 2009-2011 period.

Vong et al. (22) found similar results in Cambodia, in a study for which a capture-recapture method to determine the effectiveness of the national dengue surveillance system was used. The estimated annual occurrence ranged from 13.4 to 57.8 per 1,000 people, compared to the rate reported by the national system of 1.1 to 5.7 per 1,000 people, with a difference of 3.9 and 29 points less.

Given the epidemiological behavior of the three infections, it is necessary to improve the diagnostic strategies that enable a better understanding of Dengue’s etiology and clinical behavior, because it remains a potentially lethal disease; of Chikunguya because of its after effects; and of Zika because of the alarming risk of neurological and maternal fetal damage.

Dengue, Zika and/or Chikunguya virus infections represent a challenge for health systems as their clinical presentation may be similar and therefore difficult to identify. If you consider that the diagnostic capacity is directly related to the knowledge of the natural history of the disease, the probability of problems such as underdiagnoses or over diagnosis appearing is high. These aspects influence the understanding of the clinical manifestations of the disease, its diagnosis, and possible prevention through vaccination. (23)

Finally, it must be considered that data provided by the National Health Institute through their Weekly Epidemiological Bulletin, isan important input when monitoring the behavior of health events that are considered important at a national level. However, it must be considered that, despite efforts, there are some territorial entities that do not issue timely Notices, which results in subsequent adjustments to consolidate information. Likewise, there is an important under-reporting which must be considered in decision making.