Chikungunya Fever in Clinically Diagnosed Patients: A Brief Report of Comparison Between Laboratory Confirmed and Discarded Cases
Archives of Clinical Infectious Diseases: October 2017,
12 (4); e12980
October 31, 2017
Article Type: Brief Report
July 4, 2016
May 10, 2017
September 19, 2017
S. et al. Chikungunya Fever in Clinically Diagnosed Patients: A Brief Report of Comparison Between Laboratory Confirmed and Discarded Cases,
Arch Clin Infect Dis.
In 2015, a total of 1607 chikungunya cases were confirmed in Yucatan, Mexico, where they all took place in the second half of the year, meaning a simultaneous occurrence of both chikungunya and dengue outbreaks. This coexistence of both outbreaks posed a challenge to differentiate clinical diagnosis. The current study aimed at identifying signs and symptoms to clinically discriminate chikungunya from dengue fever in ambulatory cases.
The results of a case series observational, descriptive, retrospective study of suspected ambulatory patients whose samples were referred to the laboratory for polymerase chain reaction (PCR)/serum analysis from August to December 2015 were provided.
The study included 181 cases of which 152 were positive, finding that pruritus was a suggestive symptom of an acute infection caused by chikungunya virus (CHIKV). Polyarthralgia and pruritus were significantly associated with chikungunya confirmed cases, compared with discarded cases.
Polyarthralgia and pruritus are suggestive symptoms of an acute infection caused by CHIKV.
Due to the abundance of vector Aedes aegypti and the constant circulation of the 1, 2, 4 serotypes, Yucatan, Mexico, is a dengue endemic region. In 2015, chikungunya virus (CHIKV) infection was common because the population was immunologically naive (
1). During the CHIKV outbreak in Yucatan, all samples from clinically suspected cases were confirmed and samples from ambulatory patients were randomly selected to be confirmed by laboratory tests.
The occurrence of clinical diagnostic mistakes is described both in endemic areas and during outbreak seasons, in which the agent associated with the outbreak is usually suspected to be the etiologic factor of every similar case. In Yucatan, an unpredicted increase in dengue cases also took place simultaneously with CHIKV outbreak. The characterization of the clinical manifestations of chikungunya and dengue are similar and might represent a diagnostic challenge to clinicians practicing in endemic regions during outbreak seasons. It is important to properly identify the etiologic nature of the disease, since chikungunya and dengue have different clinical spectrum and prognosis, while dengue is more prone to generate hemorrhagic manifestations in the short-term, chikungunya might develop a prolonged arthritis-like pain and disability. In Mexico, since the national standard epidemiologic procedures do not allow an acute sample to be tested for both dengue and chikungunya, clinicians must rely on their experience to define which of those agents should be confirmed or discarded by laboratory (if randomly selected). CHIKV generates a febrile illness in most people with an incubation period of 2 to 4 days after being bitten by Aedes mosquitoes. There is also affectation of the mayor joints such as the knee, shoulder, and vertebral spine. The current case series study compared the clinical manifestations in ambulatory patients whose samples were processed in the laboratory and according to their test results signs and symptoms that might aid during clinical differential diagnosis were identified (
CHIKV cases can be categorized as confirmed, discarded, and suspected. The confirmed cases are the ones with a positive result to CHIKV by any of the following laboratory tests: 1, Detection of viral ribonucleic acid (RNA) by reverse transcription polymerase chain reaction (RT-PCR) in serum samples taken in the first 5 days; 2, Detection of IgM antibodies in paired samples. An increase of at least 4 times in the antibody titer for chikungunya fever should be noted with a difference of at least 1 week between the first and second sample; 3, Detection of IgG antibodies in paired serum sample. An increase of at least 4 times in the antibody titers should be noted with a difference of at least 1 week between the first and the second. Discarded cases are the ones in which the presence of virus or specific antibodies (depending on the time elapsed since the onset of symptoms) is not demonstrated. Finally, the suspected cases consist of fever with arthritis and arthralgia reported in the areas where transmission of CHIKV is confirmed (
The results of a descriptive observational study on suspected ambulatory patients are presented here whose samples were referred from the ambulatory medical consultation for their confirmation by laboratory from August to December 2015. Every patient included in the current study met the inclusion criteria as a suspected CHIKV. All analyses followed the criteria included in the normative epidemiological reference laboratories, analyzed by RT-PCR detection routinely or IgM antibody, depending on the number of evolution days from the onset of symptoms.
The clinical data and the anonymized laboratory results were provided to the authors in a spreadsheet dataset for further analysis using STATA 12©, using a logistic regression for binary variables (
The study included 181 cases of which 152 were positive for chikungunya virus (by RT-PCR or IgM) and 29 were negative for chikungunya (1 Newcastle virus, 2 cases of Rickettsia, and the remaining cases were diagnosed as dengue virus).
In terms of general sociodemographic characteristics (
Table 1, it was found that most of the patients were from Merida city and the residents were the most at-risk population.
Table 1. Sociodemographic Characteristics of the Chikungunya Cases Among Ambulatory Patients in Merida, Yucatan Features
Characteristics Category Number (%) CHIK cases in the neighborhood Yes 128 70.7/20.3 Female Female 92 49/51 Urban community Yes 111 14.4/38.6 Place of acquisition Home/work/school 178/2/1 98.3/1.1/0.6 Previous medical evaluation Yes 32 17.6 Hospitalization Yes 36 19.8
Table 2. Clinical Manifestation in Laboratory Confirmed and Negative Chikungunya Cases
Chikungunya Positive Cases Number % Odds Ratio P Value 95%CI Myalgia 151 83 1.408 0.625 0.35 - 5.55 Arthralgia (local) 134 74 0.575 0.341 0.18 - 1.79 Polyarthralgia 132 73 2.098 0.041 0.38 - 0.99 Retro-ocular pain 86 47.5 1.104 0.815 0.48 - 2.53 Arthritis 75 41 0.523 0.129 0.22 - 1.20 Lumbalgia 27 15 0.955 0.933 0.32 - 2.83 Abdominal pain 22 12 0.492 0.204 0.16 - 1.47 Headache 121 67 0.761 0.670 0.21 - 2.84 Exanthema 76 42 1.759 0.203 0.73 - 4.96 Pruritus 87 48 2.864 0.035 1.07 - 7.66 Chills 59/122 32.5 0.590 0.264 0.23 - 1.48 Nausea 35/146 19 1.260 0.653 0.45 - 3.45 Vomiting 42/139 23 1.429 0.532 0.46 - 4.37 Photophobia 31/150 17 0.635 0.432 0.20 - 1.97 Diarrhea 12/169 7 0.278 0.050 0.7 - 1.00 Dysgeusia 10/171 5.5 2.119 0.442 0.313 - 14.337 Conjunctivitis 9/172 5 0.580 0.452 0.141 - 2.395 Pharyngitis 6/175 3 0.290 0.232 0.038 - 2.210 Dyspnea 3/178 2 7.716 0.799 0.054 - 9.408
The most frequent symptoms were: headache, rash, pruritus, and chills described in
Table 2. Polyarthralgia and pruritus were significantly more frequent in the CHIKV confirmed cases.
The coexistence of both outbreaks posed a challenge to differential clinical diagnosis between Chikv and dengue in Yucatan in 2015. Based on the results of the current case series study, it can be concluded that polyarthalgia and pruritus are the suggestive symptoms of an acute infection caused by CHIKV that could orient the differential diagnosis.
The results of the current study, due to its misbalanced sample of negative and positive cases and its retrospective nature as a case series, can only be considered as preliminary. Further prospective, comparative studies are needed to confirm the current preliminary findings.