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An Experimental Model to Study Tuberculosis-Malaria Coinfection upon Natural Transmission of Mycobacterium tuberculosis and Plasmodium berghei
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Lethal malaria: Marchiafava and Bignami were right.

Nicholas J White1, Gareth D H Turner, Nicholas P J Day

  • 1Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. nickw@tropmedres.ac

The Journal of Infectious Diseases
|April 16, 2013
PubMed
Summary

Microvascular obstruction is the key pathological process in lethal falciparum malaria, as initially proposed 120 years ago. Recent evidence supports this original hypothesis, refuting alternative theories and ineffective treatments.

Keywords:
P. falciparumcerebral malariamalariapathology

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Area of Science:

  • Tropical medicine
  • Pathology
  • Vascular biology

Background:

  • The fundamental pathology of lethal falciparum malaria has been debated for over a century.
  • Marchiafava and Bignami first proposed microvascular obstruction as the primary cause.
  • Subsequent alternative hypotheses led to adjunctive treatments with poor outcomes.

Purpose of the Study:

  • To re-evaluate the original hypothesis of Marchiafava and Bignami regarding falciparum malaria pathology.
  • To assess the validity of alternative hypotheses and their impact on treatment strategies.
  • To synthesize recent evidence supporting microvascular obstruction in lethal malaria.

Main Methods:

  • Review of historical pathological findings in falciparum malaria.
  • Analysis of evidence from recent clinical and experimental studies.
  • Comparative assessment of proposed pathological mechanisms.

Main Results:

  • Strong evidence supports microvascular obstruction as the core pathology in lethal falciparum malaria.
  • Alternative hypotheses have not been substantiated by recent findings.
  • Ineffective or harmful adjunctive interventions were based on flawed premises.

Conclusions:

  • The original hypothesis by Marchiafava and Bignami regarding microvascular obstruction is strongly supported by current evidence.
  • Revisiting this foundational concept is crucial for understanding malaria pathogenesis.
  • Future research and therapeutic strategies should focus on addressing microvascular dysfunction in falciparum malaria.