When fever is not malaria in Latin America: a systematic review

Abstract

Background: In malaria-endemic countries, febrile episodes caused by diseases other than malaria are a growing concern. However, limited knowledge of the prevalent etiologic agents and their geographic distributions restrict the ability of health services to address non-malarial morbidity and mortality through effective case management. Here, we review the etiology of fever in Latin America (LA) between 1980 and 2015 and map significant pathogens commonly implicated in febrile infectious diseases.

Methods: A literature search was conducted, without language restrictions, in three distinct databases in order to identify fever etiology studies that report laboratory-confirmed fever-causing pathogens that were isolated from usually sterile body sites. Data analyses and mapping was conducted with Tableau Desktop (version 2018.2.3).

Results: Inclusion criteria were met by 625 publications corresponding to data relative to 34 countries. Studies using serology (n = 339) predominated for viral infections, culture (n = 131) for bacteria, and microscopy (n = 62) for fungi and parasites. The pathogen groups most frequently reported were viral infections (n = 277), bacterial infections (n = 265), parasitic infections (n = 59), fungal infections (n = 47), and more than one pathogen group (n = 24). The most frequently reported virus was dengue virus (n = 171), followed by other arboviruses (n = 55), and hantavirus (n = 18). For bacteria, Staphylococcus spp. (n = 82), Rickettsia spp. (n = 70), and Leptospira spp. (n = 55) were frequently reported. Areas with biggest gaps on etiology of fever were apparent.

Conclusions: This review provides a landscape of pathogens causing febrile illness other than malaria in LA for over 30 years. Our findings highlight the need to standardize protocols and report guidelines for fever etiology studies for better comparability of results and improved interpretation. Lastly, we should improve existing national laboratory surveillance systems, especially from low- to middle-income countries, to inform global fever policy priorities and timely identify emerging infections threats.

Study registration: PROSPERO systematic review registration number: CRD42016049281.

Keywords: Fever; Latin America; Malaria; Non-malaria febrile illness; Public health.

Fig. 1

Geographical distribution and number of selected studies published between 1980 and 2015 in the different Latin America countries. Geographical distribution and number of studies included in the review by country between 1980 and 2015

Fig. 2

Laboratory methods according to pathogen over time, 1980–2015. Laboratory methods described in the included articles by organism category and time frame

Fig. 3

Etiology of non-malaria febrile illness according to age groups, 1980–2015. Etiology of non-malaria febrile illness in Latin America according to age group. Note that in some reports, age was not mentioned, and we referred to these studies as “unspecified age group”

Fig. 4

Dengue in Latin America, 1980–2015. Geographical distribution of study sites where dengue has been reported in Latin America. DENV denotes dengue virus

Fig. 5

Rickettsiosis in Latin America, 1980–2015. Geographical distribution of study sites where Rickettsia spp. has been reported in Latin America