Background
Acute undifferentiated febrile illness (AUFI) is one of the most frequent reasons for seeking healthcare in Africa [
1]. AUFI usually begins with nonspecific symptoms such as the sudden onset of fever, which rarely progresses to prolonged duration, headaches, chills, and myalgia, which may later involve specific organs. It can range from a mild and self-limiting illness to an advancing, deadly disease [
2]. Malaria and dengue fever are leading causes of AUFI [
3].
Africa carries the highest global malaria burden, with 2000 million cases (92%) in 2017 alone [
4]. Human malaria is mainly caused by four
Plasmodium species, namely,
Plasmodium falciparum,
Plasmodium vivax,
Plasmodium malariae, and
Plasmodium ovale, with a variable geographic distribution.
P. falciparum accounts for nearly all malaria deaths in sub-Saharan Africa, which bears over 90% of the global malaria burden [
5]. Likewise, the prevalence of dengue in the region has dramatically increased over the past few decades, although this specific infection is neither systematically investigated nor generally considered by clinicians [
6]. In 2013, approximately 16 million apparent and over 48 million inapparent cases of dengue were estimated to have occurred, and most countries on the continent reported recurrent outbreaks [
7]. Dengue fever is caused by four genetically distinct dengue viruses (serotypes 1–4) [
8].
Although malaria or dengue virus monoinfections can be severe, concomitant infections could be even more fatal [
9,
10]. The two mosquito-borne diseases have an overlapping epidemic pattern in Africa [
11]. Similar main symptoms, such as fever, headache, myalgia, arthralgia, rash, nausea, diarrhoea, vomiting, and abdominal pain, are present in both of these illnesses [
12]. Due to their similar clinical presentations, possible concurrent malaria-dengue fever is often neglected [
13] and generally misdiagnosed as malaria only [
6,
14]. Misdiagnosis is more probable during coinfection than mono-infection, and this may result in slow identification of dengue fever outbreaks with potentially high morbidity and mortality [
6,
15].
A concurrent second infection may obscure the symptoms of either infection, and the treatment regimens for these co-infection are not the same as those for mono-infections [
16], hence delaying the implementation of the appropriate treatment regimen or leading to serious complications [
12,
16].
The highly mobile lifestyle of the population today, the increased activities made available by reliable global transportation networks, and climate change are anticipated to enhance the prevalence of co-infection with dengue and malaria [
17]. This review aimed to gather evidence to answer how common could
Plasmodium and dengue virus coinfection in Africa be? The specific review objective was to determine the prevalence of malaria and acute dengue coinfection in Africa (by region and study time period).
Methods
The protocol of the review was registered in the International Prospective Register of Systematic Reviews, PROSPERO (CRD42022311301), and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist [
18]. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Studies Reporting Prevalence Data [
19] was used to assess the methodological quality of the included studies.
Inclusion and exclusion criteria
Cross-sectional studies that reported
Plasmodium and dengue virus coinfection among uncomplicated febrile cases attending health facilities in African regions were included. According to the United Nations, Africa is divided into five regions: Northern Africa, Central or Middle Africa, Southern Africa, East Africa, and Western Africa [
20]. Similarly, the World Bank lists a total of 48 countries in the sub-Saharan African region [
21].
Malaria might be diagnosed by malaria rapid diagnostic tests, microscopy and/or polymerase chain reaction, while dengue fever might be identified through an antigen or antibody test and/or reverse transcriptase-polymerase chain reaction. Acute dengue or dengue fever was defined as positive for dengue IgM or NS1 antigen testing or RT‒PCR.
Reviews, grey literature, books, posters, conference proceedings, unpublished articles, articles whose full texts could not be obtained or were not available in English or that reported asymptomatic infections, studies of malaria without coinfection, reports of dengue without coinfection, case–control studies, experimental studies, reports of coinfection in malaria patients, reports of coinfection in dengue patients, and studies outside Africa were excluded. The primary outcome measure was the prevalence of malaria and dengue coinfections in Africa.
Databases and search strategy
The CoCoPop mnemonic (condition, context, and population) [
22] was used to formulate the review question and systematically search all relevant studies from PubMed, Cochrane Library, and Google Scholar databases until 19 May 2023. The search strategy used was as follows:
PUBMED
((("Malaria, Falciparum"[Mesh] OR "Malaria"[Mesh] OR "Plasmodium"[Mesh] OR "Plasmodium falciparum"[Mesh] OR malaria [tiab] OR falciparum [tiab] OR marsh fever [tiab] OR plasmodium [tiab] OR plasmodium falciparum [tiab]) AND ("Dengue"[Mesh] OR "Dengue Virus"[Mesh] OR dengue [tiab] OR dengue fever [tiab] OR breakbone fever [tiab] OR break bone fever [tiab] OR dengue virus*[tiab])) OR ((malaria [tiab] OR falciparum [tiab] OR plasmodium [tiab] OR marsh fever [tiab] OR plasmodium falciparum [tiab]) AND (dengue [tiab] OR dengue fever [tiab] OR breakbone fever [tiab] OR break bone fever[tiab] OR dengue virus*[tiab]) NOT MEDLINE[sb])) NOT systematic [sb].
Discussion
Malaria has a complicated pathophysiology, causing pathologic alterations in all bodily systems. Direct red blood cell destruction and nonspecific inflammatory and immune responses are the major mechanisms involved [
46]. Similarly, dengue virus infection involves a multi-organ system and is attributed to a complex interplay between the virus, host genes, and host immune response [
47]. The dengue clinical spectrum includes asymptomatic infection, mild febrile sickness (dengue fever), and more severe presentations, including dengue shock syndrome and dengue haemorrhagic fever [
48]. Clinical presentations of malaria and dengue are similar, with minor differences. For instance, malaria can be chronic, while dengue cannot. In addition, atypical lymphocytosis, haemoconcentration, and thrombocytopenia are strong predictors of dengue, whereas anaemia is a major symptom seen in malaria infections, which is a consequence of the merozoites (blood stages) causing intense intravascular haemolysis [
13,
16].
Plasmodium and dengue virus coinfection occur when both of these mosquito-borne diseases occur simultaneously in an individual, which may increase the severity and duration of one or both [
16]. The first report of malaria and dengue virus coinfection in Africa was documented in 2005 [
15]. About 22,803 acute undifferentiated febrile patients were included from 22 studies conducted in 8 African countries (Senegal, Nigeria, Sierra Leone, Kenya, Tanzania, Ethiopia, Cameroon, and the DRC) for approximately 13 years.
Based on the meta-analysis, the pooled prevalence of malaria and dengue fever coinfection was 4.2%, and the highest rate was recorded in Central Africa (4.7%), followed by East Africa (2.7%) and West Africa (1.6%). This result is lower than the finding of a study [
49] on a meta-analysis of severe malaria and dengue coinfections, which estimated a prevalence of 32%. The variation could be due to the differences in the study population, model estimator employed, and/or geography of the primary studies included, where the analysis was focused on studies from Africa while the other study included studies from all over the globe. In addition, uncomplicated febrile cases were included in the analysis, unlike the study above, which estimated severe malaria prevalence among the coinfections.
Across the African continent, the prevalence of co-infection with
P. falciparum and dengue virus grew significantly from 0.9% between 2008 and 2013 to 3.8% between 2014 and 2017 and 5.5% between 2018 and 2021. This could be due to increased global transportation network dynamics, population movement, and climate change [
17].
In the study, children were more affected by coinfection than adults. Children are more susceptible to mosquito-borne illnesses because they are exposed to mosquito bites for longer periods during dangerous hours [
50]. Moreover, malaria [
51] and dengue [
52] mainly affect children due to their underdeveloped specific immunity to infection [
51].
Furthermore,
Plasmodium falciparum was the only malaria parasite specified in the coinfection among the included studies, as nearly all malaria cases in Africa are caused by
P. falciparum [
5].
The study showed a high and increasing trend of malaria and dengue coinfection prevalence in many parts of Africa. Nevertheless, healthcare workers misdiagnose dengue or malaria-dengue as malaria alone due to the institutionalisation of malaria as the primary febrile illness in the region by international development organizations and national malaria control programs [
53], limited access to medical care and laboratory diagnostic facilities, a lack of awareness of healthcare workers towards non-malarial febrile illnesses [
54], and the overlap of signs and symptoms of dengue with malaria [
55]. Clinical misdiagnosis often leads to overuse or misuse of antimicrobials, which often accelerates the emergence and spread of antimicrobial drug resistance [
56,
57]. On top of that, it causes mismanagement of the patient and dengue outbreaks [
55]. Hence, the study calls for devising a standardised protocol for the diagnosis and treatment of patients with AUFIs, including dengue. In addition, healthcare professionals should always keep malaria and dengue infections in mind when dealing with such clinical presentations.
The study had some strengths and limitations. A large sample size, good-quality included studies, no evidence of publication bias among the included studies, and subgroup analysis were some of the strengths of the study; however, restriction to those published in English only, including single-centred facility-based studies, a small sample size in six studies [
27,
29,
30,
34,
35,
39], and evidence of significant heterogeneity among the studies were some of the drawbacks of the study.
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