Identification of Malaria Retinopathy Improves the Specificity of the Clinical Diagnosis of Cerebral Malaria: Findings from a Prospective Cohort Study

Gretchen L. Birbeck International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom; Kilimanjaro Centre for Community Ophthalmology, Tumaini University/KCMC, Moshi, Tanzania; Anatomy Department, University of Malawi College of Medicine, Blantyre, Malawi; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Malawi and The Liverpool School of Tropical Medicine and Hygiene, University of Liverpool, United Kingdom; Department of Neurology, Johns Hopkins Health Systems, Baltimore, Maryland; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi

Search for other papers by Gretchen L. Birbeck in
Current site
Google Scholar
PubMed
Close
,
Nicholas Beare International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom; Kilimanjaro Centre for Community Ophthalmology, Tumaini University/KCMC, Moshi, Tanzania; Anatomy Department, University of Malawi College of Medicine, Blantyre, Malawi; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Malawi and The Liverpool School of Tropical Medicine and Hygiene, University of Liverpool, United Kingdom; Department of Neurology, Johns Hopkins Health Systems, Baltimore, Maryland; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi

Search for other papers by Nicholas Beare in
Current site
Google Scholar
PubMed
Close
,
Susan Lewallen International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom; Kilimanjaro Centre for Community Ophthalmology, Tumaini University/KCMC, Moshi, Tanzania; Anatomy Department, University of Malawi College of Medicine, Blantyre, Malawi; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Malawi and The Liverpool School of Tropical Medicine and Hygiene, University of Liverpool, United Kingdom; Department of Neurology, Johns Hopkins Health Systems, Baltimore, Maryland; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi

Search for other papers by Susan Lewallen in
Current site
Google Scholar
PubMed
Close
,
Simon J. Glover International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom; Kilimanjaro Centre for Community Ophthalmology, Tumaini University/KCMC, Moshi, Tanzania; Anatomy Department, University of Malawi College of Medicine, Blantyre, Malawi; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Malawi and The Liverpool School of Tropical Medicine and Hygiene, University of Liverpool, United Kingdom; Department of Neurology, Johns Hopkins Health Systems, Baltimore, Maryland; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi

Search for other papers by Simon J. Glover in
Current site
Google Scholar
PubMed
Close
,
Malcolm E. Molyneux International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom; Kilimanjaro Centre for Community Ophthalmology, Tumaini University/KCMC, Moshi, Tanzania; Anatomy Department, University of Malawi College of Medicine, Blantyre, Malawi; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Malawi and The Liverpool School of Tropical Medicine and Hygiene, University of Liverpool, United Kingdom; Department of Neurology, Johns Hopkins Health Systems, Baltimore, Maryland; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi

Search for other papers by Malcolm E. Molyneux in
Current site
Google Scholar
PubMed
Close
,
Peter W. Kaplan International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom; Kilimanjaro Centre for Community Ophthalmology, Tumaini University/KCMC, Moshi, Tanzania; Anatomy Department, University of Malawi College of Medicine, Blantyre, Malawi; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Malawi and The Liverpool School of Tropical Medicine and Hygiene, University of Liverpool, United Kingdom; Department of Neurology, Johns Hopkins Health Systems, Baltimore, Maryland; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi

Search for other papers by Peter W. Kaplan in
Current site
Google Scholar
PubMed
Close
, and
Terrie E. Taylor International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom; Kilimanjaro Centre for Community Ophthalmology, Tumaini University/KCMC, Moshi, Tanzania; Anatomy Department, University of Malawi College of Medicine, Blantyre, Malawi; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Malawi and The Liverpool School of Tropical Medicine and Hygiene, University of Liverpool, United Kingdom; Department of Neurology, Johns Hopkins Health Systems, Baltimore, Maryland; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi

Search for other papers by Terrie E. Taylor in
Current site
Google Scholar
PubMed
Close
Restricted access

The diagnosis of cerebral malaria (CM) is difficult to confirm in endemic regions with limited neurodiagnostics. Accurate diagnoses are critical for trials and outcomes studies. Findings from an autopsy-based study suggest that identifying malaria retinopathy in children satisfying the standard clinical case definition of CM improves our ability to accurately diagnose CM in vivo. In a post hoc analysis of a prospective exposure-control study to evaluate CM as a risk factor for epilepsy, we stratified children meeting the standard case definition by their retinopathy status (presence versus absence) and compared these groups for pre-existing risk factors for epilepsy. We also compared them to the concurrently enrolled, non-comatose controls. Children meeting the standard case definition of CM who lacked malaria retinopathy had a higher prevalence of pre-existing developmental problems and family history of epilepsy. This subset of patients may represent children with a pre-existing propensity to adverse neurologic symptoms and outcomes.

Author Notes

*Address correspondence to Gretchen L. Birbeck, #324 West Fee Hall, East Lansing, MI 48824. E-mail: Gretchen.Birbeck@ht.msu.edu

Financial support: Funding for this work was provided by National Institutes of Health Grant NIH/NINDS K23 NS046086-01, National Institutes of Health Grant NIH/NIAID R01 AI034969-10AI, and The Wellcome Trust.

Authors’ addresses: Gretchen L. Birbeck, Michigan State University, International Neurologic and Psychiatric Epidemiology Program, East Lansing, MI, E-mail: Gretchen.Birbeck@ht.msu.edu. Nicholas Beare, St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, E-mail: nbeare@btinternet.com. Susan Lewallen, Kilimanjaro Centre for Community Ophthalmology, Tumaini University/KCMC, Moshi, Tanzania, E-mail: slewallen@kcco.net. Simon J. Glover, University of Malawi, Anatomy Department, Blantyre, Malawi, E-mail: simontheeyeman@hotmail.com. Malcolm E. Molyneux, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi, E-mail: mmolyneux999@gmail.com. Peter W. Kaplan, Johns Hopkins Health System, Department of Neurology, Baltimore, MD, E-mail: pkaplan@jhmi.edu. Terrie E. Taylor, Michigan State University, College of Osteopathic Medicine and University of Malawi College of Medicine, Blantyre Malaria Project, East Lansing, MI, E-mail: taylort@msu.edu.

  • 1.

    Brewster DR, Kwiatkowski D, White NJ, 1990. Neurological sequelae of cerebral malaria in children. Lancet 336: 10391043.

  • 2.

    Molyneux ME, Taylor TE, Wirima JJ, Borgstein A, 1989. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Quarterly Journal of Medicine 71: 441459.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    WHO, 1999. SEAR malaria incidence. WHO. Available at: http://www.rollbackmalaria.org/docs/burden.htm.

  • 4.

    Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, Fosiko NG, Lewallen S, Liomba NG, Molyneux ME, 2004. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med 10: 143145.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Bronzan RN, McMorrow ML, Kachur SP, 2008. Diagnosis of malaria: challenges for clinicians in endemic and non-endemic regions. Journal of Molecular Diagnostics 12: 299306.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Dal-Bianco MP, Koster KB, Kombila UD, Kun JF, Grobusch MP, Ngoma GM, Matsiegui PB, Supan C, Salazar CL, Missinou MA, Issifou S, Lell B, Kremsner P, 2007. High prevalence of asymptomatic Plasmodium falciparum infection in Gabonese adults. Am J Trop Med Hyg 77: 939942.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Smith T, Schellenberg JA, Hayes R, 1994. Attributable fraction estimates and case definitions for malaria in endemic areas. Stat Med 13: 23452358.

  • 8.

    Carter JA, Neville BG, White S, Ross AJ, Otieno G, Mturi N, Musumba C, Newton CR, 2004. Increased prevalence of epilepsy associated with severe falciparum malaria in children. Epilepsia 45: 978981.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Newton CR, Warrell DA, 1998. Neurological manifestations of falciparum malaria. Ann Neurol 43: 695702.

  • 10.

    Lewallen S, Harding SP, Ajewole J, Schulenburg WE, Molyneux ME, Marsh K, Usen S, White NJ, Taylor TE, 1999. A review of the spectrum of clinical ocular fundus findings in P. falciparum malaria in African children with a proposed classification and grading system. Trans R Soc Trop Med Hyg 93: 619622.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Lewallen S, White VA, Whitten RO, Gardiner J, Hoar B, Lindley J, Lochhead J, McCormick A, Wade K, Tembo M, Mwenechanyana J, Molyneux ME, Taylor TE, 2000. Clinical-histopathological correlation of the abnormal retinal vessels in cerebral malaria. Arch Ophthalmol 118: 924928.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Lewallen S, Bronzan RN, Beare NA, Harding SP, Molyneux ME, Taylor TE, 2008. Using malarial retinopathy to improve the classification of children with cerebral malaria. Trans R Soc Trop Med Hyg 102: 10891094.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Beare NA, Harding SP, Taylor TE, Lewallen S, Molyneux ME, 2009. Perfusion abnormalities in children with cerebral malaria and malarial retinopathy. J Infect Dis 199: 263271.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Beare NA, Taylor TE, Harding SP, Lewallen S, Molyneux ME, 2006. Malarial retinopathy: a newly established diagnostic sign in severe malaria. Am J Trop Med Hyg 75: 790797.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Placencia M, Sander JW, Shorvon SD, Ellison RH, Cascante SM, 1992. Validation of a screening questionnaire for the detection of epileptic seizures in epidemiological studies. Brain 115: 783794.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Durkin MS, Hasan ZM, Hasan KZ, 1995. The ten questions screen for childhood disabilities: its uses and limitations in Pakistan. J Epidemiol Community Health 49: 431436.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Durkin MS, Wang W, Shrout PE, Zaman SS, Hasan ZM, Desai P, Davidson LL, 1995. Evaluating a ten questions screen for childhood disability: reliability and internal structure in different cultures. J Clin Epidemiol 48: 657666.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Berg AT, 1992. Febrile seizures and epilepsy: the contributions of epidemiology. Paediatr Perinat Epidemiol 6: 145152.

  • 19.

    Berg AT, Shinnar S, 1991. The risk of seizure recurrence following a first unprovoked seizure: a quantitative review. Neurology 41: 965972.

  • 20.

    Berg AT, Shinnar S, 1996. Unprovoked seizures in children with febrile seizures: short-term outcome. Neurology 47: 562568.

Past two years Past Year Past 30 Days
Abstract Views 220 216 14
Full Text Views 429 15 0
PDF Downloads 133 11 0
 
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save