ORIGINAL ARTICLE
REVISTA DE LA FACULTAD DE MEDICINA HUMANA 2023 - Universidad Ricardo Palma
1 Instituto de Enfermedades Tropicales, Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas (UNTRM),
Amazonas, Peru.
2 Laboratorio Referencial de Salud Pública Amazonas, Dirección Regional de Salud Amazonas, Peru.
3 Faculty of Human Medicine, Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas, Amazonas, Peru.
4 Instituto de Investigaciones en Ciencias Biomédicas (INICIB), Universidad Ricardo Palma, Lima, Peru.
a Biologist. Bachelor's Degree in Biological Sciences.
b Biologist. Bachelor's Degree in Microbiology and Parasitology.
c Medical Surgeon. Doctorate in Physiological Sciences.
d Biologist. Doctorate in Microbiology.
ABSTRACT
Introduction: The increase in dengue cases in Amazonas represents a public health risk. In 2021, Balsas reported a dengue
outbreak for the first time.
Methodology: The population included patients who met the case definition between December 2021 and February 2022.
Serotype identification was determined using a multiplex qRT-PCR.
Results: A total of 72 patients were identified, of which 53 (74%) were confirmed by serology (NS1 Ag). The prevalent
serotype was DENV-2 (94%), and 6% were DENV-1. Patients aged 19 to 45 years had the highest percentage of cases (59%). The most
frequent symptoms were headache, myalgia, fever, and arthralgia; 23% had intense abdominal pain.
Conclusion: This was the first confirmed dengue outbreak in the Balsas district, with DENV-2 being the main cause of the
outbreak, highlighting the need to improve surveillance in areas without autochthonous transmission of the disease.
RESUMEN
Introducción: El aumento de casos de dengue en Amazonas es un riesgo para la salud pública. En el 2021, Balsas reportó por
primera vez un brote de dengue.
Metodología: La población incluyó a pacientes que cumplían con la definición de caso entre diciembre 2021 y febrero 2022.
La identificación de los serotipos se determinó mediante una qRT-PCR múltiplex.
Resultados: Se identificaron 72 pacientes de los cuales 53 (74%) se confirmaron por serología (Ag NS1). El serotipo
prevalente fue DENV-2 (94%), y el 6% fue DENV-1. Los pacientes de 19 a 45 años presentaron el mayor porcentaje de casos (59%).
Los síntomas más frecuentes fueron cefalea, mialgias, fiebre y artralgias; el 23 % presentó dolor abdominal intenso.
Conclusión: Este fue el primer brote de dengue confirmado en el distrito de Balsas, siendo DENV-2 el principal causante,
destacando la necesidad de mejorar la vigilancia en zonas sin transmisión autóctona de la enfermedad.
INTRODUCTION
Dengue is one of the most significant arboviruses globally, primarily transmitted by the Aedes aegypti vector, which spreads in
tropical and subtropical regions, causing socioeconomic and health impacts (1,2).
The dengue virus belongs to the flaviviridae
family and is divided into 4 serotypes (DENV-1, DENV-2, DENV-3, DENV-4), which are further subdivided into phylogenetically
distinct genotypes (3).
Dengue has been circulating in Peru since 1990 and presented an epidemic caused by the DENV-1 serotype in the city of Iquitos,
marking the first laboratory-confirmed case of autochthonous transmission in the country. Another smaller outbreak occurred in
Tarapoto, and data indicates that the same dengue serotype was involved in both outbreaks (4).
Subsequently, larger and smaller
outbreaks occurred in various areas of the country. Dengue incidence in recent years has been primarily restricted to the
northern part of the country and much of the Amazon (5). In 2019, the introduction of the
Cosmopolitan genotype of the DENV-2
serotype was first detected in the Madre de Dios region of Peru (2). Genomic surveillance of this
genotype is vital as its
genomic diversity, evolution, and transmission dynamics are still unknown (3). Recently, Peru has
experienced an increase in the
number of dengue cases, with 44,791 cases reported in 2021 and 63,168 in 2022, with Amazonas being one of the most affected
regions. In 2020, there were 845 reported cases, increasing to 2,304 in 2021, and further to 3,502 in 2022
(5).
The unusual increase in dengue cases in the Amazonas region poses a significant risk to public health due to the lack of a
proper vector prevention and control system. In December 2021, the district of Balsas in the Chachapoyas province reported its
first cases of dengue following a magnitude 7.5 earthquake in the department (6). This earthquake
may have been a factor
contributing to the emergence of reemerging diseases like dengue due to the absence of an adequate epidemiological surveillance
system. To date, Balsas is the first and only district in this province to report autochthonous dengue cases. The ability of
the Aedes aegypti vector to infest new locations and adapt to climate changes, even after natural disasters, has been
substantial in the transmission, establishment, and spread of the disease. The objective of this study was to describe the first
dengue outbreak in Balsas, its clinical-epidemiological characteristics, and the circulating serotypes.
METHODS
The district of Balsas has a population of 1,158 inhabitants and is located in the southwest of the Chachapoyas province
(Figure 1). It includes 20 populated centers. The presence of the vector was only evidenced in the populated center of Balsas,
which has 6 annexes and comprises 676 inhabitants (58% of the total population). It is situated at an altitude of 859 meters
above sea level, has a warm-humid climate, and temperatures ranging from 11°C to 35°C with an annual average of 20°C. The rainy
season occurs between October and May, with an annual precipitation of 780 mm (7), providing ideal
climatic conditions for vector development.
A descriptive study was conducted. The Amazonas Regional Health Directorate (DIRESA) conducted active and passive surveillance,
with some cases confirmed only through epidemiological linkage. The study population included all patients meeting the dengue
case definition (8) between December 2021 and February 2022 in the populated center of Balsas,
excluding patients without
samples for serological diagnosis. Demographic, clinical, epidemiological, and laboratory data were obtained from
clinical-epidemiological research forms collected by DIRESA-Amazonas. RNA extraction from serum samples of patients who tested
positive for the NS1 antigen serological diagnosis was performed manually using the silica column method, following the
instructions of the Viral Nucleic Acid extraction II kit (Geneaid®). The identified serotypes were determined using a qRT-PCR
multiplex based on the protocol established by the Instituto Nacional de Salud, using the TransScript II Multiplex Probe
One-Step qRT-PCR SuperMix UDG kit. The amplification process was carried out in the Quant Studio 5 thermocycler. Data were
imported into an Excel database, and data reliability was verified through duplication. Frequencies, percentages, and ranges
were used for statistical analysis with STATA v17 software.
This study is part of the METAVEC project with contract No. 050-2021-FONDECYT, which has approval from the Institutional
Research Ethics Committee of the Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas, with certificate No. 011. This
study is part of the surveillance activities carried out by DIRESA – Amazonas, and the necessary permissions were obtained.
RESULTS
Dengue was introduced into the district of Balsas in December 2021, with the first confirmed case reported on December 28th in a laboratory healthcare worker. In this outbreak, 72 patients who met the dengue case definition were identified, of which 53 (74%) were confirmed by serology (NS1 Ag). The percentage of females was slightly higher (53%), and the median age was 37 years [IQR 23 – 53.5 years], with the age range of 19 to 45 years having the highest percentage of cases (59%) (Table 1). Regarding clinical-epidemiological characteristics, the most frequent symptoms were headache and myalgia (90.6%), fever (89%), and arthralgia (75.5%); 23% presented intense abdominal pain (warning sign). 58.5% of cases were diagnosed within 2 days or less of symptoms, while 15% were diagnosed between 6 and 8 days of symptoms, with a median of 1 day [IQR 1 – 2 days]. 38% of cases had 5 or fewer days between the onset of symptoms and the confirmation of the dengue case, while 49% had between 6 and 9 days, with a median of 2 days [IQR 1 – 2 days] (Table 2). The circulating serotypes in this outbreak were DENV-2 (94%) and DENV-1 (6%).
Table 1. Sociodemographic characteristics of the population
Variable |
Positive (%) |
Negative (%) |
Total |
---|---|---|---|
Gender |
|||
Male |
25 (65.8) |
13 (34.2) |
38 |
Female |
28 (82.4) |
6 (17.6) |
34 |
Age |
|||
≤ 18 |
7 (63.6) |
4 (36.4) |
11 |
19 - 45 |
31 (83.8) |
6 (16.2) |
37 |
≥ 46 |
15 (62.5) |
9 (37.5) |
24 |
Education level |
|||
Primary |
4 (50.0) |
4 (50.0) |
8 |
Secondary |
28 (68.3) |
13 (31.7) |
41 |
Higher |
21 (91.3) |
2 (8.7) |
23 |
Occupation |
|||
At home |
28 (80.0) |
7 (20.0) |
35 |
Outside home |
25 (67.6) |
12 (32.4) |
37 |
Table 2. Clinical Characteristics of the Population
Variable |
Positive (%) |
Negative (%) |
Total |
---|---|---|---|
Days of symptoms |
|||
≤ 2 |
31 (73.8) |
11 (26.2) |
42 |
3 - 5 |
14 (66.7) |
7 (33.3) |
21 |
≥ 6 |
8 (88.9) |
1 (11.1) |
9 |
Days of result |
|||
≤ 5 |
20 (62.5) |
12 (37.5) |
32 |
6 - 9 |
26 (78.8) |
7 (21.2) |
33 |
≥ 10 |
7 (100) |
0 |
7 |
Fever |
|||
Yes |
47 (75.8) |
15 (24.2) |
62 |
No |
6 (60.0) |
4 (40.0) |
10 |
Arthralgia |
|||
Yes |
40 (83.3) |
8 (16.7) |
48 |
No |
13 (54.2) |
11 (45.8) |
24 |
Myalgia |
|||
Yes |
48 (77.4) |
14 (22.6) |
62 |
No |
5 (50.0) |
5 (50.0) |
10 |
Headache |
|||
Yes |
48 (72.7) |
18 (27.3) |
66 |
No |
5 (83.3) |
1 (16.7) |
6 |
Ocular pain |
|||
Yes |
38 (79.2) |
10 (20.8) |
48 |
No |
15 (62.5) |
9 (37.5) |
24 |
Lumbar pain |
|||
Yes |
35 (79.6) |
9 (20.4) |
44 |
No |
18 (64.3) |
10 (35.7) |
28 |
Rash |
|||
Yes |
11 (91.7) |
1 (8.3) |
12 |
No |
42 (70.0) |
18 (30.0) |
60 |
Non-Purulent Conjunctivitis |
|||
Yes |
12 (92.3) |
1 (7.7) |
13 |
No |
41 (69.5) |
18 (30.5) |
59 |
Nausea/Vomiting |
|||
Yes |
29 (76.3) |
9 (23.7) |
38 |
No |
24 (70.6) |
10 (29.4) |
34 |
Case classification |
|||
Without warning signs |
39 (68.4) |
18 (31.6) |
57 |
With warning signs |
14 (93.3) |
1 (6.7) |
15 |
DISCUSSION
Environmental-climatic phenomena are related to dengue outbreaks and play a role in the survival, behavior, and reproduction
of the Aedes aegypti vector (1). In November 2021, an earthquake occurred, causing
environmental-climatic disruptions in the
Amazonas region (6), leading to flooding due to heavy rains and the overflow of the Utcubamba
River, creating an environment
conducive to the emergence of diseases. This natural disaster disrupted the main road, causing increased human mobility, with
Balsas serving as the access route for transportation and trade. Increased population movement and vector dissemination are
factors contributing to disease establishment (9).
In this outbreak, 53 cases of dengue were confirmed, representing 7% of the population in the populated center of Balsas. Other
suspected dengue cases could not be confirmed due to residents' refusal to provide samples and a shortage of healthcare
workers to handle cases. Dengue infections can affect a significant portion of the population in a short period during an
epidemic, leading to adverse economic consequences and potential healthcare system overload.
The dengue virus affects all age groups in different proportions and with different clinical presentations. While younger than
15 years and older than 60 years are the most vulnerable age groups, studies have reported a higher frequency of dengue cases
in the 16 to 45-year age group (9,10). In this outbreak, the most affected age
group ranged from 19 to 45 years, possibly
because adults engage in more daytime activities and are thus more exposed to vector bites, resulting in a higher infection
rate.
Clinical manifestations of dengue vary, ranging from asymptomatic infections to mild and severe classic cases, and in some
instances, hemorrhagic cases, which can be fatal (11). While there are limited studies evaluating
differences in clinical
presentations based on serotypes, currently, DENV-2 is more strongly associated with cases exhibiting greater symptoms and
severity worldwide (12). In our study, no hospitalizations or severe cases were reported, likely
because all cases were
first-time dengue infections. The most common symptoms found were headache, myalgia, fever, and arthralgia
(10,13). It was also
noted that only 23% of cases presented intense abdominal pain related to one of the four warning signs (
14). The majority of
cases were diagnosed within two or fewer days of symptoms (58.5%), contributing to early symptom treatment and a better
prognosis for the disease (15).
The confirmed circulating serotypes in this study were DENV-1 and DENV-2, with the latter being the primary cause of most
infections. This serotype predominates in various regions of Asia and has gradually spread to other parts of the world
(16).
The co-circulation of two or more serotypes is important because it results in specific immunity for each serotype, making
individuals susceptible to a second infection by a different serotype, thus maintaining virus transmission (17). Recent reports
have indicated the presence of a new DENV-2 serotype genotype in the Americas, the Cosmopolitan genotype, which was first
reported in Madre de Dios, Peru, and two years later in Brazil. This serotype circulates globally and exhibits a wide range of
genotypic dispersion patterns, which may explain the rapid increase in the incidence and prevalence of the DENV-2 serotype
(2,3,16).
This study was limited by the small sample size, which prevented statistical analysis of associations with serotypes and
clinical variables, as well as the low severity of cases due to them being primary infections. Therefore, there is a need to
improve surveillance systems in healthcare facilities in areas without autochthonous transmission of the disease, and
integrated vector control strategies and timely case detection should be implemented. Due to the outbreaks of DENV-2, genomic
surveillance is important to assess the impact on the transmission and spread of predominant serotypes and genotypes. This is
crucial for disease control at the local and regional levels.
CONCLUSIONS
This was the first report of a confirmed dengue outbreak in the district of Balsas, with the DENV-2 serotype being the primary causative agent.
Author contributions:
Luis M. Rojas, Christian J. Campos, Stella M. Chenet, and Lizandro Gonzales contributed to the conception of the idea
and project design. Lourdes Ramírez-Orrego, Luis M. Rojas, Christian J. Campos, Carmen Gutierrez, and Lizandro Gonzales
participated in data analysis and interpretation and in writing the manuscript of this research work.
Funding:
This study was funded by the project with CONTRACT No. 050-2021-FONDECYT "Metagenomics in Vectors of the Amazon Region:
Identifying Potential Foci of Emerging and Re-emerging Diseases" - METAVEC.
Declaration of conflict of interest:
No conflicts of interest are declared.
Received:
July 1st, 2023.
Approved:
September 1st, 2023.
Correspondence author:
Lizandro Gonzales Cornejo
Address:
Jr. Hermosura 531 - Chachapoyas.
Phone:
+51 978010658
E-mail:
lgonzalesc@hotmail.com
Article published by the Journal of the faculty of Human Medicine of the Ricardo Palma University. It is an open access article, distributed under the terms of the Creatvie Commons license: Creative Commons Attribution 4.0 International, CC BY 4.0 (https://creativecommons.org/licenses/by/1.0/), that allows non-commercial use, distribution and reproduction in any medium, provided that the original work is duly cited. For commercial use, please contact revista.medicina@urp.edu.pe.