Concurrent malaria and arbovirus infections in Kedougou, southeastern Senegal
- Abdourahmane Sow†1, 5, 7,
- Cheikh Loucoubar†1,
- Diawo Diallo2,
- Oumar Faye1,
- Youssoupha Ndiaye3,
- Cheikh Saadibou Senghor4,
- Anta Tal Dia5,
- Ousmane Faye1,
- Scott C. Weaver6,
- Mawlouth Diallo2,
- Denis Malvy7 and
- Amadou Alpha Sall1Email author
© Sow et al. 2016
Received: 15 September 2015
Accepted: 12 January 2016
Published: 28 January 2016
Malaria is one of the leading causes of acute febrile illness (AFI) in Africa. With the advent of malaria rapid diagnostic tests, misdiagnosis and co-morbidity with other diseases has been highlighted by an increasing number of studies. Although arboviral infections and malaria are both vector-borne diseases and often have an overlapping geographic distribution in sub-Saharan Africa, information about their incidence rates and concurrent infections is scarce.
From July 2009 to March 2013 patients from seven healthcare facilities of the Kedougou region presenting with AFI were enrolled and tested for malaria and arboviral infections, i.e., yellow fever (YFV), West Nile (WNV), dengue (DENV), chikungunya (CHIKV), Crimean Congo haemorrhagic fever (CCHFV), Zika (ZIKV), and Rift Valley fever viruses (RVFV). Malaria parasite infections were investigated using thick blood smear (TBS) and rapid diagnostics tests (RDT) while arbovirus infections were tested by IgM antibody detection (ELISA) and RT-PCR assays. Data analysis of single or concurrent malaria and arbovirus was performed using R software.
A total of 13,845 patients, including 7387 with malaria and 41 with acute arbovirus infections (12 YFV, nine ZIKV, 16 CHIKV, three DENV, and one RVFV) were enrolled. Among the arbovirus-infected patients, 48.7 % (20/41) were co-infected with malaria parasites at the following frequencies: CHIKV 18.7 % (3/16), YFV 58.3 % (7/12), ZIKV 88.9 % (8/9), DENV 33.3 % (1/3), and RVF 100 % (1/1). Fever ≥40 °C was the only sign or symptom significantly associated with dual malaria parasite/arbovirus infection.
Concurrent malaria parasite and arbovirus infections were detected in the Kedougou region from 2009 to 2013 and need to be further documented, including among asymptomatic individuals, to assess its epidemiological and clinical impact.
KeywordsArbovirus Malaria Co-infection Kedougou
Arboviral infections and malaria are acute vector-borne diseases and concurrent infections are observed [1, 2], especially for dengue in American and Asian tropical regions where their endemic areas overlap extensively [3–10]. However, in African tropical regions, arboviral and malaria parasite co-infections are scarce in the scientific literature and likely under-reported due to the limited number of laboratories capable of diagnosing arboviral infections. Arboviruses are not systematically investigated and are generally only considered by clinicians, at best, when samples test negative for malaria. In addition, arboviral infections are often misdiagnosed as malaria due to their similar clinical presentation . Consequently, this may result in the slow identification of an arboviral disease outbreak and potentially high morbidity and mortality [12–14]. Arboviral and malaria parasite co-infections have previously been reported in Nigeria , Senegal  and in European travellers in Senegal, Guinea and Sierra Leone .
In Senegal, the introduction of malaria rapid diagnostics tests (RDT) in 2007 showed that the prevalence of malaria among acute febrile illnesses (AFI) was largely overestimated while other infections, such as bacteria and arbovirus illnesses were under-reported [17, 18]. In 2009, more robust surveillance of AFI was implemented in Kedougou to detect arboviral infection outbreaks and malaria in order to accurately measure disease morbidity and mortality in this geographical location. In this paper, malaria prevalence and diagnostics as well as co-infections with dengue (DENV), chikungunya (CHIKV), zika (ZIKV), yellow fever (YFV), and Rift Valley fever viruses (RVFV) are reported from 2009 to 2013 in Kedougou region, Senegal, an area known to be endemic for many arboviruses.
Population and study design
Patients presenting with AFI were recruited from seven healthcare facilities of the Kedougou region, including Ninefesha rural hospital, Kedougou and Saraya health centres, Bandafassi and Khossanto health posts, the Kedougou military health post, and the Catholic Mission mobile team, which targets populations in remote areas (Fig. 1). AFI was defined as any patient older than 1 year of age with a fever (axillar temperature >38 °C) lasting for less than 2 weeks and exhibiting two or more of the following signs or symptoms: headache, myalgia, eye pain, arthralgia, cough, nausea/vomiting, diarrhoea, jaundice, bleeding, and neurological signs. Clinical manifestations and sociodemographic data were recorded on a standardized interview form. From each consented and eligible patient, health workers sampled 5 ml of venous blood in healthcare centres. The same day, samples were centrifuged and serum aliquoted and transported to the field where they were tested and stored at −20 °C until further use.
Human sera were systematically tested for malaria parasite and arbovirus infections. The malaria diagnosis procedure was performed using thick blood smear (TBS) and an RDT (Malaria Antigen P.f, Standard diagnostics, Ingbert, Germany) as previously described [21, 22], while IgM ELISA, real-time RT-PCR and other viral infection detection methods [23–26] were used for detection of DENV, CHIKV, ZIKV, Crimean-Congo haemorrhagic fever (CCHFV) or West Nile virus (WNV), YFV, and RVFV infections. Negative and positive controls were used for serology and molecular methods and any samples with Ct value 35 was considered as positive for RT-PCR. Consequently, a case of confirmed arboviral infection was defined as any AFI that tested positive by any method used for detection of IgM and/or the genome of ZIKV, DENV, CHIKV, RVFV, YFV, CCHFV, or WNV, while a confirmed malaria case was defined as any AFI testing positive for TBS. Only TBS was used for the definition of confirmed malaria case as it is the gold standard for malaria diagnostics. Concurrent infection was defined as any AFI confirmed for both arboviral and malaria infections.
Statistical analysis of data
Data were analysed using STATA  and R software . For small numbers of samples, exact methods, such as exact logistic regression and Fisher’s exact test or other non-parametric methods such as Kruskal–Wallis test, were used for qualitative and quantitative variables to investigate differences in measures between sub-groups. Significance was assigned at p < 0.05 and when pair-wise comparisons were performed among more than two groups, p values corrected for multiple testing by the Bonferroni method were considered.
Ethics, consent and permissions
The study objectives, benefits and risks were explained in the French language or local dialects to all participants before inclusion. Written informed consent was obtained from all adult participants and from parents or legal guardians of children. The study was examined and approved by the Senegalese National Health Research Committee.
Arboviruses detected in Kedougou region and test used
Co-infection with malaria parasites and arboviruses
Risk of co-infection according to temperature and age
95 % CI
2.6 × 10−3
Age <15 years
This study revealed that concurrent infections of malaria parasites and arboviruses were detected among 48.7 % patients infected with arboviruses in southeastern Senegal. ZIKV was the most prevalent arbovirus in the co-infections with malaria (88.9 %). Further, high-grade fever (≥40 °C) was significantly associated with patients exhibiting dual infection of malaria parasites and arbovirus compared to patients with single malaria attack. Although Plasmodium falciparum, P. ovale, P. malariae, and P. vivax  were reported in Senegal, only P. falciparum was detected in this study.
Arboviral infections and malaria are known to be endemic in the Kedougou region [13, 14], allowing the occurrence of concurrent infections in patients as previously reported in endemic areas . The overall arboviral and malaria co-infection rates were similar to those reported in previous studies in Nigeria and French Guiana [1, 3, 11]. Evidence of co-infection in ZIKV and malaria parasites is reported. The latter high co-infection rate, rising up to 89 %, may be explained by the almost permanent circulation of ZIKV repeatedly isolated from mosquitoes in the Kedougou region since 1968 . Conversely, the other arboviruses investigated are known to emerge periodically after a few years of silent circulation or absence .
An individual can become co-infected when bitten by a mosquito harbouring both the malaria parasite and an arbovirus. In fact, malaria vectors have previously been found infected with arboviruses, emphasizing the plausibility of the dual infection of malaria parasites and an arbovirus within the same mosquito. For example, wild caught Anopheles funestus, a major malaria vector in southeastern Senegal and elsewhere in Africa , have been found infected with CHIKV and YFV in the Kedougou region (, Diallo et al. unpublished data). Moreover, A. coustani, which were found infected with CHIKV, YFV and ZIKV in Kedougou region ([30, 33], Diallo et al. unpublished data), may be competent in malaria transmission in this region considering it is abundant, highly anthropophilic and has already been incriminated as a secondary malaria vector in Kenya . Therefore, arbovirus and Plasmodium spp co-infection of A. funestus and A. coustani is possible in nature and needs to be further investigated.
Another mechanism by which a patient may become infected by both Plasmodium spp and arboviruses is consecutive bites from two different infected mosquitoes or species (e.g., anopheline vectors for malaria and Aedes spp. for arboviruses). When considering the high number of asymptomatic malaria and arboviral infections in endemic regions where both vectors co-exist [1, 35, 36], as Kedougou region, concurrent infections are very plausible through consecutive bites of humans by two infected mosquitoes. The latter condition could even lead to more severe presentations as shown in a previous study concerning DENV and malaria co-infection .
Main clinical characteristics of co-infected patients and patients infected with only malaria parasites
Arbovirus-infected patients n (%)
Co-infected patients n (%)
One the limitation of the present study is that all the enrolled individuals were febrile patients. However, given that malaria parasites as well as arboviruses can be detected using molecular tools  in asymptomatic individuals, studies enrolling asymptomatic individuals are needed to evaluate the real burden of co-infections of malaria and arboviruses in Kedougou area and should be performed in the future.
This study showed that co-infections between Plasmodium spp. and arboviruses are frequent in Kedougou where competent vectors of both diseases are abundant. Vector competence and co-infection of certain malaria vectors, also regularly found infected by arboviruses, deserves further investigation. The frequent detection of arboviral disease outbreaks in the Kedougou region highlights the need to strengthen surveillance of AFI for a better estimation of human impact of arboviruses, as well as morbidity and mortality associated with concurrent malaria and arboviral infections. Finally, the high-grade fever ≥40 °C suggests the possibility of malaria and arboviral infection and should help to establish prompt and better care of individuals.
yellow fever virus
thick blood smear
rapid diagnostic test
acute febrile illnesses
enzyme-linked immunosorbent assay
reverse transcription polymerase chain reaction
histidine rich protein
west nile virus
rift valley fever viruses
AS, CL, MD, SCW, and AAS designed the study. AS, CL, DD, YN, CSS, MD, OusF, and OumF performed the experiments, collect and analysed the data. AS, CL, DD, SW, MD, and AAS wrote the manuscript. All authors read and approved the final manuscript.
The authors thank the population, healthcare workers and medical authorities in Kedougou region for their support and cooperation in conducting this study, and Linsey Yeager for editorial assistance. The research was supported by the National Institutes of Health (NIH)Grant Number AI1069145.
The authors declare they have no competing interests.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Mohapatra MK, Patra P, Agrawala R. Manifestation and outcome of concurrent malaria and dengue infection. J Vector Borne Dis. 2012;49:262–5.PubMedGoogle Scholar
- Mushtaq MB, Qadri MI, Rashid A. Concurrent infection with dengue and malaria: an unusual presentation. Case Rep Med. 2013;2013:520181.PubMedPubMed CentralGoogle Scholar
- Carme B, Matheus S, Donutil G, Raulin O, Nacher M, Morvan J. Concurrent dengue and malaria in Cayenne Hospital, French Guiana. Emerg Infect Dis. 2009;15:668–71.PubMedPubMed CentralView ArticleGoogle Scholar
- Arya CS, Mehta KL, Agarwal N, Agarwal BK, Mathai G, Moondhara A. Episodes of concurrent dengue and malaria. Dengue Bull. 2005;29:208–9.Google Scholar
- Deresinski S. Concurrent Plasmodium vivax malaria and dengue. Emerg Infect Dis. 1802;2006:12.Google Scholar
- Abbasi A, Butt N, Sheikh QH, Bhutto AR, Munir SM, Ahmed SM. Clinical features, diagnostic techniques and management of dual dengue and malaria infection. J Coll Physicians Surg Pak. 2009;19:25–9.PubMedGoogle Scholar
- Ali N, Nadeem A, Anwar M, Tariq WU, Chotani RA. Dengue fever in malaria endemic areas. J Coll Physicians Surg Pak. 2006;16:340–2.PubMedGoogle Scholar
- Ward DI. A case of fatal Plasmodium falciparum malaria complicated by acute dengue fever in East Timor. Am J Trop Med Hyg. 2006;75:182–5.PubMedGoogle Scholar
- Thangaratham PS, Jeevan MK, Rajendran R, Samuel PP, Tyagi BK. Dual infection by dengue virus and Plasmodium vivax in Alappuzha District, Kerala, India. Jpn J Infect Dis. 2006;59:211–2.PubMedGoogle Scholar
- Vdos Santana S, Lavezzo LC, Mondini A, Terzian AC, Bronzoni RV, Rossit AR, et al. Concurrent dengue and malaria in the Amazon region. Rev Soc Bras Med Trop. 2010;43:508–11.View ArticleGoogle Scholar
- Senn N, Suarkia DL, Manong D, Siba PM, McBride WJH. Contribution of dengue fever to the burden of acute febrile illnesses in Papua New Guinea: an age-specific prospective study. Am J Trop Med Hyg. 2011;85:132–7.PubMedPubMed CentralView ArticleGoogle Scholar
- Baba M, Logue CH, Oderinde B, Abdulmaleek H, Williams J, Lewis J, et al. Evidence of arbovirus co-infection in suspected febrile malaria and typhoid patients in Nigeria. J Infect Dev Ctries. 2013;7:51–9.PubMedView ArticleGoogle Scholar
- Monlun E, Zeller H, Le Guenno B, Traoré-Lamizana M, Hervy JP, Adam F, Ferrara L, Fontenille D, Sylla R, Mondo M, Digoutte JP. [Surveillance of the circulation of arbovirus of medical interest in the region of eastern Senegal (1988-1991)](in French). Bull Soc Pathol Exot. 1993;86:21–8.PubMedGoogle Scholar
- WHO: Word malaria report 2010. Geneva: Word Health Organization.
- Robin Y, Cornet M, Heme G, Le Gonidec G. Isolement du virus de la dengue au Sénégal. Ann Virol (Inst. Pasteur). 1980;131E:149–54.View ArticleGoogle Scholar
- Charrel RN, Brouqui P, Foucault C, De Lamballerie X. Concurrent dengue and malaria. Emerg Infect Dis. 2005;11:1153–4.PubMedPubMed CentralView ArticleGoogle Scholar
- Thiam S, Thior M, Faye B, Ndiop M, Diouf ML, Diouf MB, et al. Major reduction in antimalarial drug consumption in Senegal after nationwide introduction of malaria rapid diagnostic tests. PLoS One. 2011;6:e18419.PubMedPubMed CentralView ArticleGoogle Scholar
- Programme national de lutte contre le paludisme au Sénégal. Rapport annuel. Dakar; 2009.
- Agence nationale de la démographie et de la Statistique (Service régional de Kédougou). Rapport annuel. Kedougou; 2012.
- Food and Agriculture Organization. Animal Production and Health paper 41, Integrating crops and livestock in West Africa. 1983. http://www.fao.org/docrep/004/x6543e/x6543e01.htm. Accessed 25 Mar 2014.
- Organisation mondiale de la Santé: L’utilisation des tests diagnostiques rapides du paludisme. Genève: WHO publications; 2004. p. 19.
- WHO Guidelines for the treatment of malaria. Geneva: World Health Organization; 2010, p. 210.
- Nabeth P, Cheikh DO, Lo B, Faye O, Vall IO, Niang M, et al. Crimean-Congo hemorrhagic fever, Mauritania. Emerg Infect Dis. 2004;10:2143–9.PubMedPubMed CentralView ArticleGoogle Scholar
- Saluzzo JF, Anderson GW Jr, Hodgson LA, Digoutte JP, Smith JF. Antigenic and biological properties of Rift Valley fever virus isolated during the 1987 Mauritanian epidemic. Res Virol. 1989;140:155–64.PubMedView ArticleGoogle Scholar
- Weidmann M, Faye O, Faye O, Kranaster R, Marx A, Nunes MRT, et al. Improved LNA probe based assay for the detection of African and South-American Yellow Fever virus strains. J Clin Virol. 2010;48:187–92.PubMedView ArticleGoogle Scholar
- Wu SJ, Pal S, Ekanayake S, Greenwald D, Lara S, Raviprakash K, et al. A dry-format field-deployable quantitative reverse transcriptase-polymerase chain reaction assay for diagnosis of dengue infections. Am J Trop Med Hyg. 2008;79:505–10.PubMedGoogle Scholar
- StataCorp. 2007. Stata Statistical Software: Release 10. College Station, TX: StataCorp LP.
- R Development Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna: Austria 2008, ISBN 3-900051-07-0, URL. http://www.R-project.org.
- Niang M, Thian LG, Sow A, Loucoubar C, Bob NS, Diop F, et al. A molecular Survey of acute febrile illnesses reveals Plasmodium vivax infections in Kedougou, southeastern Senegal. Malar J. 2015;14:281.PubMedPubMed CentralView ArticleGoogle Scholar
- http://www.pasteur.fr/recherche/banques/CRORA/virus. Accessed 27 Jul 2013.
- Traoré LM, Fontenille D, Zeller HG, Mondo M, Diallo M, Adam F, et al. Surveillance for yellow fever virus in eastern Senegal during 1993. J Med Entomol. 1996;33:760–5.View ArticleGoogle Scholar
- Dia I, Diop T, Rakotoarivony I, Kengne P, Fontenille D. Bionomics of Anopheles gambiae Giles, An. arabiensis Patton, An. funestus Giles and An. nili (Theobald) (Diptera: Culicidae) and transmission of Plasmodium falciparum in a Sudano-Guinean zone (Ngari, Senegal). J Med Entomol. 2003;40:279–83.PubMedView ArticleGoogle Scholar
- Diallo D, Sall AA, Buenemann M, Chen R, Faye O, Diagne CT, et al. Landscape ecology of sylvatic chikungunya virus and mosquito vectors in southeastern Senegal. PLoS Negl Trop Dis. 2012;6:e1649.PubMedPubMed CentralView ArticleGoogle Scholar
- Mwangugangi JM, Muturi EJ, Muriu SM, Nzovu J, Midega JT, Mbogo C. The role of Anopheles arabiensis and Anopheles coustani in indoor and outdoor malaria transmission in Taveta District, Kenya. Parasit Vectors. 2013;6:114.View ArticleGoogle Scholar
- Le Port A, Cot M, Etard JF, Gaye O, Migot-Nabias F, Garcia A. Relation between Plasmodium falciparum asymptomatic infection and malaria attacks in a cohort of Senegalese children. Malar J. 2008;7:193.PubMedPubMed CentralView ArticleGoogle Scholar
- Epelboin L, Hanf M, Dussart P, Ouar-Epelboin S, Djossou F, Nacher M, et al. Is dengue and malaria co-infection more severe than single infections? A retrospective matched-pair study in French Guiana. Malar J. 2012;11:142.PubMedPubMed CentralView ArticleGoogle Scholar
- Mourembou G, Fenollar F, Socolovschi C, Lemamy GJ, Nzoughe H, Kouna LC, et al. Molecular detection of fastidious and common bacteria as well as Plasmodium spp. in febrile and afebrile children in Franceville, Gabon. Am J Trop Med Hyg. 2015;92:926–32. doi:10.4269/ajtmh.14-0699.PubMedView ArticleGoogle Scholar