Volume 26, Number 8—August 2020
Synopsis
Association of Dengue Virus and Leptospira Co-Infections with Malaria Severity
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Rajendra Mandage1, Charandeep Kaur1, Atreyi Pramanik1, Vinod Kumar2, Parul Kodan, Adarsh Singh, Sounak Saha, Shivam Pandey, Naveet Wig, Ravindra Mohan Pandey, Manish Soneja, and Pragyan Acharya
Abstract
Plasmodium infections are co-endemic with infections caused by other agents of acute febrile illnesses, such as dengue virus (DENV), chikungunya virus, Leptospira spp., and Orientia tsutsugamushi. However, co-infections may influence disease severity, treatment outcomes, and development of drug resistance. When we analyzed cases of acute febrile illness at the All India Institute of Medical Sciences, New Delhi, India, from July 2017 through September 2018, we found that most patients with malaria harbored co-infections (Plasmodium mixed species and other pathogens). DENV was the most common malaria co-infection (44% of total infections). DENV serotype 4 was associated with mild malaria, and Leptospira was associated with severe malaria. We also found the presence of P. knowlesi in our study population. Therefore, in areas with a large number of severe malaria cases, diagnostic screening for all 4 DENV serotypes, Leptospira, and all Plasmodium species should be performed.
In tropical countries, including India, acute febrile illnesses (AFIs) constitute a group of infections with similar manifestations, such as fever, malaise, body aches, chills, hepatic and renal dysfunction, and central nervous system effects. The causative agents of AFI can be bacterial (e.g., Orientia tsutsugamushi, Leptospira, and Salmonella enterica serovar Typhi), parasitic (protozoans of the apicomplexa family), or viral (e.g., dengue virus [DENV], chikungunya virus [CHIKV], influenza A[H1N1] virus) (1–4). Distinguishing between the causative agents of AFIs can be difficult. In tropical climates, several AFI pathogens, such as malaria parasites, DENV, and CHIKV, occur in the same areas and during the same seasons (5), making it possible that >1 pathogen can infect the same person. Indeed, recent retrospective analyses based on persons hospitalized with an AFI have uncovered malaria co-infections with dengue, chikungunya, and leptospirosis in different populations across the world (6–14).
Despite the increasing realization that co-infections may contribute to the course and outcome of malaria, only a few studies have investigated the prevalence and nature of co-infections (14–20), which limits our ability to manage and understand AFIs, as follows. First, we do not know the spectrum of infections that a person with an AFI may harbor, leading to inadequate drug therapy. Treatment strategies based on diagnosis of a single pathogen may lead to inadvertent exposure of the undetected pathogen to antimicrobial agents, thereby contributing to generation of antimicrobial-resistant species. Second, lack of adequate data on co-infections in clinical and field settings can misdirect the field of drug and vaccine development. Pathogens such as malaria parasites, DENV, and Orientia spp. have host immune-modulatory effects (21). Therefore, co-infections can aid or antagonize each other in terms of evading host immune responses. These interactions may have major effects on immune responses to vaccine candidates and need to be known during design of effective vaccination strategies (22). Third, we do not know how interactions of co-infecting pathogens lead to diverse disease outcomes affecting organ function and ultimately mortality. In India, the prevalence of malaria parasites, DENV, and CHIKV resembles the global prevalence and co-endemicity of these pathogens (5). Malaria infections in India are reportedly caused by Plasmodium falciparum, P. vivax, P. ovale, and P. malariae (23). Several studies have also reported the occurrence of P. vivax severe malaria in India as well as in Southeast Asia and South America (23–25). Our objective with this study was to define the spectrum of co-infections in patients with an AFI associated with malaria admitted to the All India Institute of Medical Sciences, New Delhi, India, a tertiary care research hospital.
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