LP in cerebral malaria is safe

In 2015, the Blantyre Malaria Projects (BMP) research team published their findings which identified cerebral edema as the underlying cause of death in pediatric cerebral malaria.1 To some extent, this presented a conundrum to clinicians caring for children in the tropics. Determining whether a child in a malaria endemic region has malaria vs. meningitis isn’t a trivial undertaking and co-morbid disease with both conditions can occur.2-5 If cerebral edema, increased intracranial pressure (ICP) and eventual herniation is the underlying cause of death in pediatric cerebral malaria, should a lumbar puncture (LP) be avoided in children when cerebral malaria is in the differential diagnosis? The question is challenging to answer. An intervention study to evaluate the safety of LP in LMICs would raise many ethical issues, but observational studies of mortality outcomes after LP are fraught with bias. Clinicians in LMICs are often extremely reluctant to conduct the procedure on the most severely ill patients. This may be due to concerns that such patients are unlikely to tolerate the procedure.6 But clinicians are also acutely aware that if death occurs shortly following the LP, they may be personally blamed by the family for having caused the death.

The clinical conundrum presented by the 2015 finding that cerebral edema is the cause of death in cerebral malarial further complicated clinical decision-making in resource-limited tropical settings where there is a growing concern that the LP procedure is underutilized.6-10 Limited use of the LP may partly be due to clinicians overestimating the risks associated with it. The comment in a patient’s chart–“too sick for LP” is common in both Zambian and Malawian settings. In this week’s Neurology, more work out of Blantyre addresses this important question.

Moxon et al. used data from several years of BMP admissions including neuroimaging data available since 2007. Propensity scores were developed which adjusted for known risk factors for death as well as the probability of getting an LP. They then evaluated the mortality risk at 12 hours post admission and at any time during the admission for children admitted to the BMP. They found no increased risk of death in children who underwent LP including a sub-analysis of the risk in children with papilledema. Interestingly, a sub-analysis of children who had an MRI showed that those with severe cerebral edema actually had a lower mortality rate if they had an LP. So, LP in cerebral malaria is safe. Could it also potentially offer a therapeutic intervention to decrease ICP in this highly fatal condition? 2.

References

  1. Seydel KB, Kampondeni SD, Valim C, et al. Brain swelling and death in children with cerebral malaria. The New England journal of medicine 2015;372:1126-1137.
  2. Maltha J, Guiraud I, Kabore B, et al. Frequency of severe malaria and invasive bacterial infections among children admitted to a rural hospital in Burkina Faso. PloS one 2014;9:e89103
  3. Szabo I, Kulkova N, Sokolova J, et al. Neurologic complications and sequellae of infectious diseases in Uganda and Kenya: Analysis of 288 cases from two rural hospitals. Neuro Endocrinol Lett 2013;34:28-31.
  4. Laman M, Manning L, Greenhill AR, et al. Predictors of acute bacterial meningitis in children from a malaria-endemic area of Papua New Guinea. Am J Trop Med Hyg 2012;86:240-245.
  5. Berkley JA, Versteeg AC, Mwangi I, Lowe BS, Newton CR. Indicators of acute bacterial meningitis in children at a rural Kenyan district hospital. Pediatrics 2004;114:e713-719
  6. King MB, Rwegerera GM. An audit of consent practices and perceptions of lumbar puncture, Botswana inpatient setting experience. African Journal of Emergency Medicine 2015;5:66-69
  7. Thakur KT, Mateyo K, Hachaambwa L, et al. Lumbar puncture refusal in sub-Saharan Africa: A call for further understanding and intervention. Neurology 2015;84:1988-1990
  8. Sikazwe I, Elafros MA, Bositis CM, et al. HIV and new onset seizures: slipping through the cracks in HIV care and treatment. HIV medicine 2015
  9. Patel PB, Anderson HE, Keenly LD, Vinson DR. Informed consent documentation for lumbar puncture in the emergency department. The western journal of emergency medicine 2014;15:318-324
  10. Kirenga BJ, Levin J, Ayakaka I, et al. Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study. PloS one 2014;9:e90614.
Gretchen L. Birbeck, MD, MPH

Gretchen L. Birbeck, MD, MPH

Gretchen Birbeck is a neurologist who divides her time between the US and Africa. Her US academic home is the University of Rochester where she is the Rykenboer Professor of Neurology and Research Director for the Strong Epilepsy Center with adjunct appointments in the Center for Human Experimental Therapeutics and the Department of Public Health. Her additional skills in epidemiology, health services research, and tropical medicine are brought to bear during the 6-months annually she spends in Africa where she serves as Director for the Chikankata Epilepsy Care Team in rural Mazabuka, Zambia, an Honorary Lecturer at the University of Zambia and a consultant for the Paediatric Research Ward at Queen Elizabeth Central Hospital in Blantyre, Malawi. Gretchen’s research programs are aimed at identifying opportunities to prevent or ameliorate the medical and social morbidities of common neurologic conditions in low-income, tropical settings with the ultimate goal of developing successful interventions feasible for scale up and broad implementation. She has been recognized as an Ambassador for Epilepsy by the International League against Epilepsy, a Global Health Research Ambassador by the US Paul Rogers Society, a National Outreach Scholar by the WK Kellogg Foundation and a Leader in Medicine by the American Medical Students Association.

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