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Volume 22, Number 2—February 2016
Letter

Vectorborne Infections, Mali

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To the Editor: As in many West Africa nations, vectorborne diseases represent a substantial health burden in Mali; however, beyond malaria, the incidence and etiology of many of these diseases is poorly understood. Of the estimated 14.1 million persons living in sub-Saharan Mali, ≈70% live in remote rural settings with an ecologic landscape that puts inhabitants at an increased risk for contact with rodent and arthropodborne diseases. We retrospectively analyzed serum samples for evidence of recent (IgM+) and previous (IgG+) infection with chikungunya (CHIKV), dengue (DENV), West Nile (WNV), Lassa (LASV), Crimean-Congo hemorrhagic fever (CCHFV), and Ebola (EBOV) virus, as well as Old World hantaviruses (OW-HANV) and Leptospira spp., which is regularly misdiagnosed as an acute viral infection.

We tested 376 deidentified serum samples collected from acutely ill patients who had a history of fever and hemorrhagic, diarrheal, or icteric syndromes (Technical Appendix Figure). Research on samples from humans was conducted in accordance with the policies and regulations of the National Institutes of Health and adhered to the principles of the Belmont Report (1979) (http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html). This research was conducted under an institutional review board–approved document.

Samples had previously tested negative for acute Plasmodium falciparum malaria and yellow fever virus infections. Commercially available IgM capture and conventional IgG ELISAs were used for serologic testing for CHIKV (GenWay Biotech, San Diego, CA, USA); DENV (all four serotypes) and WNV (both from Focus Diagnostics, Cypress, CA, USA); OW-HANVs (Euroimmun, Luebeck, Germany); and Leptospira spp. (Abnova, Taipei City, Taiwan). Conventional IgM/IgG ELISAs were used for LASV (Corgenix, Broomfield, CO, USA) and CCHFV (Vector-Best, Novosibirsk, Russia), and reagents for the EBOV IgM/IgG ELISA (infected/uninfected cell lysates) were prepared at the Rocky Mountain Laboratories (Hamilton, MT, USA) and validated with serum from experimentally infected monkeys. With the exception of the CHIKV, Leptospira spp., and in-house EBOV assays, the tests conducted in this study are under preclinical development for human diagnostic assays.

Samples were tested at a 1:100 dilution according to manufacturer specifications (CHIKV, CCHFV, WNV, DENV, OW-HANVs, LASV, and Leptospira spp.) or in-house quality-control assessments (EBOV), in a blinded fashion. Serologic reactivity was assessed according to manufacturer recommendations. For the EBOV ELISA, samples were deemed positive if optical density at 405 nm was >3 SD above that of the average of known negative samples.

Serologic evidence suggestive of acute infection (IgM+) with 1 of the pathogens tested for was observed for 39.9% of samples (Table). At 14.4%, Leptospira spp. was the most prevalent probable etiologic agent of acute disease identified. Of mosquitoborne viruses tested, DENV had the highest prevalence at 7.7%, followed by CHIKV (5.3%) and WNV (0.27%). Of rodentborne pathogens, OW-HANVs had a seroprevalence of 7.2%, whereas LASV was considerably lower (0.27%). CCHFV IgM was documented in 4.8% of samples. Overall, little annual variation in the IgM seroprevalence was noted, except for Leptospira spp., for which 2 obvious peaks in seroprevalence were observed (Table).

Most IgM+ samples demonstrated serologic reactivity in only 1 assay. The exception was 2 samples that were IgM+ for hantaviruses and Leptospira spp., an acute dual infection that might be underrecognized (1). With the exception of DENV, few samples were both IgM+ and IgG+, suggesting the results were not attributable to IgM persistence. The DENV IgM+/IgG+ results might represent IgM persistence. However, because the ELISA detected all 4 serotypes, it is plausible that some results represent recent infection with DENV in the presence of IgG reactive with a different serotype.

The relatively high IgG seroprevalence for most of the pathogens tested supports the findings of the IgM assays and further suggest the circulation of and potential for human exposure to these agents in Mali (Table). Geographically, serologic evidence of infections with Leptospira spp., DENV, WNV, OW-HANVs, and CHIKV was observed throughout Mali (online Technical Appendix). No samples were reactive with EBOV, and the low incidence of LASV infection is not surprising because the samples analyzed here were collected outside of the 1 documented LASV-endemic region in Mali (2).

We used commercially available diagnostic platforms, primarily IgM capture and conventional IgG ELISAs, many of which are validated for human diagnostics. Ideally, diagnostics for zoonotic diseases would not rely on IgM/IgG serologic analysis because of caveats including IgM persistence and cross-reactivity between closely related pathogens (3,4). In the industrialized world, as well as in several countries throughout Africa, molecular approaches are often used to genetically identify pathogens, or follow-up convalescent-phase serum samples are collected to determine seroconversion or increased antibody titers or to conduct plaque reduction neutralization assays. Unfortunately, because of the nature of the samples available, including time of collection, storage history, and remaining volume, many of these tests were not feasible for our study.

Despite these limitations, these serologic findings indicate that flaviviruses, bunyaviruses, and togaviruses, as well as Leptospira spp., are contributing to human illness in Mali. These results add to those recently documented in studies conducted in Sierra Leone, implying that several of these zoonotic pathogens are widely distributed yet underreported throughout West Africa (5,6).

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Acknowledgments

We thank Joseph Shott, Richard Sakai, and Salif Camara for logistical support, and Randal Schoepp for helpful comments and suggestions.

Tragically, a coauthor, Darin Oottamasathien, who assisted in the development of the LASV diagnostics, lost her life all too soon. We wish to honor her memory.

This work was funded by the International Centers for Excellence in Research program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

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David Safronetz1, Moussa Sacko, Nafomon Sogoba, Kyle Rosenke, Cynthia Martellaro, Sékou F. Traoré, Issa Cissé, Ousmane Maiga, Matt Boisen, Diana Nelson, Darin Oottamasathien, Molly Millett, Robert F. Garry, Luis M. Branco, Seydou Doumbia, Heinz FeldmannComments to Author , and Mamadou S. Traoré

Author affiliations: National Institutes of Health, Hamilton, Montana, USA (D. Safronetz, K. Rosenke, C. Martellaro, H. Feldmann); Institut National de Recherche en Sante Publique, Bamako, Mali (M. Sacko, S. Traoré, I. Cissé, M.S. Traoré); University of Sciences, Techniques and Technologies of Bamako, Bamako (N. Sogoba, O. Maiga, S. Doumbia); Corgenix Medical Corporation, Inc., Broomfield, Colorado, USA (M. Boisen, D. Nelson, D. Oottamasathien, M. Millett); Tulane School of Medicine, New Orleans, Louisiana, USA (R.F. Garry); Zalgen Labs, LLC, Germantown, Maryland, USA (L.M. Branco)

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References

  1. Sunil-Chandra  NP, Clement  J, Maes  P, De Silva  HJ, Van Esbroeck  M, Van Ranst  M. Concomitant leptospirosis-hantavirus co-infection in acute patients hospitalized in Sri Lanka: implications for a potentially worldwide underestimated problem. Epidemiol Infect. 2015;143:208193 . DOIPubMed
  2. Safronetz  D, Sogoba  N, Lopez  JE, Maiga  O, Dahlstrom  E, Zivcec  M, Geographic distribution and genetic characterization of Lassa virus in sub-Saharan Mali. PLoS Negl Trop Dis. 2013;7:e2582.PubMed
  3. Murray  KO, Garcia  MN, Yan  C, Gorchakov  R. Persistence of detectable immunoglobulin M antibodies up to 8 years after infection with West Nile virus. Am J Trop Med Hyg. 2013;89:9961000. DOIPubMed
  4. Prince  HE, Matud  JL. Estimation of dengue virus IgM persistence using regression analysis. Clin Vaccine Immunol. 2011;18:21835. DOIPubMed
  5. Schoepp  RJ, Rossi  CA, Khan  SH, Goba  A, Fair  JN. Undiagnosed acute viral febrile illnesses, Sierra Leone. Emerg Infect Dis. 2014;20:117682. DOIPubMed
  6. Boisen  ML, Schieffelin  JS, Goba  A, Oottamasathien  D, Jones  AB, Shaffer  JG, ; Viral Hemorrhagic Fever Consortium. Multiple circulating infections can mimic the early stages of viral hemorrhagic fevers and possible human exposure to filoviruses in Sierra Leone prior to the 2014 outbreak. Viral Immunol. 2015;28:1931. DOIPubMed

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Table

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Cite This Article

DOI: 10.3201/eid2202.150688

1Current affiliation: Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.

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Table of Contents – Volume 22, Number 2—February 2016

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Heinz Feldmann, Rocky Mountain Laboratories, National Institutes of Health, 903 S 4th St, Hamilton, MT 59840, USA

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Page created: January 19, 2016
Page updated: January 19, 2016
Page reviewed: January 19, 2016
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
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