Research Article: A Re-Examination of the History of Etiologic Confusion between Dengue and Chikungunya

Date Published: November 12, 2015

Publisher: Public Library of Science

Author(s): Goro Kuno, Scott B Halstead.

Abstract: Contrary to the perception of many researchers that the recent invasion of chikungunya (CHIK) in the Western Hemisphere marked the first episode in history, a recent publication reminded them that CHIK had prevailed in the West Indies and southern regions of the United States from 1827–1828 under the guise of “dengue” (DEN), and that many old outbreaks of so-called “dengue” actually represented the CHIK cases erroneously identified as “dengue.” In hindsight, this confusion was unavoidable, given that the syndromes of the two diseases—transmitted by the same mosquito vector in urban areas—are very similar, and that specific laboratory-based diagnostic techniques for these diseases did not exist prior to 1940. While past reviewers reclassified problematic “dengue” outbreaks as CHIK, primarily based on manifestation of arthralgia as a marker of CHIK, they neither identified the root cause of the alleged misdiagnosis nor did they elaborate on the negative consequences derived from it. This article presents a reconstructed history of the genesis of the clinical definition of dengue by emphasizing problems with the definition, subsequent confusion with CHIK, and the ways in which physicians dealt with the variation in dengue-like (“dengue”) syndromes. Then, the article identifies in those records several factors complicating reclassification, based on current practice and standards. These factors include terms used for characterizing joint problems, style of documenting outbreak data, frequency of manifestation of arthralgia, possible involvement of more than one agent, and occurrence of the principal vector. The analysis of those factors reveals that while some of the old “dengue” outbreaks, including the 1827–1828 outbreaks in the Americas, are compatible with CHIK, similar reclassification of other “dengue” outbreaks to CHIK is difficult because of a combination of the absence of pathognomonic syndrome in these diseases and conflicting background information.

Partial Text: In recent decades, we have witnessed dramatic increases in the frequency and magnitude of chikungunya (CHIK) in dengue-endemic regions in Africa, Asia, and the Pacific; beginning in late 2013, CHIK suddenly emerged in the Western Hemisphere.

The major sources of early DEN and CHIK documents used for this review are comprehensive treatises of early “dengue” outbreaks compiled by August Hirsch and George Melvyn Howe [7,8] and a bibliographic database [9]. In the text, the word “dengue” in double quotation marks is used in reference to the etiology of dengue-like illness or outbreaks not definitively confirmed by the current standards. The same practice is applied to CHIK and O’nyong nyong fever (ONN) as well. This analysis of the factors complicating reclassification is based only on the “dengue” outbreaks selected in Carey’s review [3].

Establishing a clinical definition of dengue was known to be notoriously difficult in tropical environments because of the existence of multiple infectious diseases manifesting similar syndromes. Although this article is about misdiagnosis with CHIK, the confusion between “dengue” and other viral diseases ranges from a myth that it is a benign form of yellow fever to a belief that it is a tropical variety of influenza. The traditional definition also fostered a practice of lumping multiple diseases known under various names in different parts of the tropics into one category, such as “dengue.” The reconstructed history below reveals how the dengue definition originated, the problems that emerged, how physicians dealt with the variations of the syndrome, and how CHIK entered into the history of misdiagnosis.

Despite the troubled history of the clinical definition of dengue, retrospective serology on the survivors of “dengue” human experiments or outbreaks (such as those in the Philippines from 1924–1930, South Africa in 1927, and Greece from 1927–1928) confirmed the accuracy of the clinical diagnosis in the early part of the 20th century. In this period, the correct identification of dengue-infected patients in epidemiologic studies and of viremic patients (in order to secure the source of the infectious material for human experiments or virus isolation) was similarly based on the “traditional,” if troubled, clinical definition of “dengue.”

A combination of the lack of pathognomonic syndrome and the unavailability of specific diagnostic methods in the past frequently contributes to the difficulty of retrospective etiologic identification. Furthermore, the meaning of a medical term pertaining to a particular symptom (or syndrome) or concept of a disease can shift over time, as shown in the example of pleurisy [57]. The definition for characterizing “joint pain” is another example—sources of the term have been variable and changing. According to one of the medical dictionaries in the 19th century, joint pain is covered in three terms: “arthralgia” (meaning joint pain and used synonymously with arthrodynia), arthritis (joint pain in gout and acute rheumatism), and arthrosia (joint pain with inflammation) [58]. However, the term “arthralgia” was not used in “dengue” reports in the 19th century. In another dictionary in the early 20th century, arthralgia was defined as “articular pain without appreciable lesion of the joint” [59]. Thus, because of the variation of definition and change in usage by physicians, caution is necessary in evaluating the etiologies of old “dengue” that are heavily based on arthralgia. While some of them, including the 1827–1828 outbreaks in the Americas, are compatible with CHIK, similar reclassification of other “dengue” outbreaks to CHIK is difficult because of a combination of the variability in reporting and conflicting background information. The critical review of old outbreaks also suggests intriguing possibilities about the development of the earliest epidemics of severe dengue and their spread.