Dhillon, Baljean

Dondorp, Arjen M

Maude, Richard James

Wellcome Trust

2017-07-06T13:00:00Z

2017-07-06T13:00:00Z

2016-07-02

Introduction Malaria retinopathy is a set of visible changes in the retina which are specific to falciparum malaria. Studies to date have been mostly limited to comatose African children. Retinal changes in adults with severe malaria and severely unwell patients without malaria have been less well studied and the specificity, pathogenesis, diagnostic and prognostic value of malarial retinopathy in adults are not known. Methods A series of observational studies of retinopathy in Bangladesh, India and Malaysia were done from 2008-2012. The aims were to describe the spectrum of retinal changes in falciparum and knowlesi malaria in adults, determine their specificity for severe falciparum malaria, quantify the impact of malaria retinopathy on visual function, understand its pathogenesis and assess the potential contribution of retinopathy to confirming diagnosis of malarial coma, predicting prognosis and understanding pathogenesis of cerebral malaria. Results 495 patients were enrolled and underwent retinal photography (305 with P. falciparum malaria (112 cerebral, 68 noncerebral severe, 125 uncomplicated), 44 P. knowlesi, 43 sepsis, 41 encephalopathy and 62 healthy). Retinal whitening and white-centred haemorrhages were common and specific to severe falciparum malaria. Retinopathy was most common and severe in cerebral (88%) and fatal (91%) falciparum malaria. Moderate-severe retinopathy was 95% specific for cerebral malaria in comatose patients, and its severity correlated with depth of coma. Vessel whitening was not seen and papilloedema was rare. In noncerebral severe falciparum malaria, retinopathy predicted increased likelihood of later development of coma and death. Retinal findings in Bangladeshi children were similar to those in adults. Optic nerve sheath diameter was mildly increased and brain swelling minimal on MRI. Severity of retinopathy correlated with plasma lactate, serum bicarbonate, sequestered parasite load and red cell stiffness suggesting a central role for microvascular obstruction in the pathogenesis. Severity of retinal whitening correlated with decreased visual acuity. Conclusions Retinal changes seen in severe P. falciparum malaria in Asian adults is similar, but not identical, to that seen in African children. They have potential to help with diagnosis and prognosis of Asian adults with severe falciparum malaria. Microvascular obstruction is prominent in the pathogenesis of retinopathy and coma in adults whereas raised intracranial pressure is not.

http://hdl.handle.net/1842/22807

en

The University of Edinburgh

Govindasamy G, Barber BE, Ghani SA, William T, Grigg MJ, Borooah S, Dhillon B, Dondorp AM, Yeo TW, Anstey NM, Maude RJ. Retinal Changes in Uncomplicated and Severe Plasmodium knowlesi Malaria. J Infect Dis. 2016;213:1476-82.

Maude RJ, Kingston H, Joshi S, Mishra S, Mohanty S, White NJ, Dondorp AM. Reversibility of retinal microvascular changes in severe malaria. Am J Trop Med Hyg. 2014;91:493-5.

Maude RJ, Barkhof F, Hassan MU, Ghose A, Hossain A, Faiz MA, Choudhury E, Rashid R, Abu Sayeed A, Charunwatthana P, Plewes K, Kingston H, Maude RR, Silamut K, Day NPJ, White NJ, Dondorp AM. Magnetic resonance imaging of the brain in adults with severe falciparum malaria. Malar J. 2014;13:177.

Maude RR, Hossain MA, Hassan MU, Osbourne S, Langan K, Sayeed MA, Karim MR, Samad R, Borooah S, Dhillon B, Day NPJ, Dondorp AM, Maude RJ. Transorbital sonographic evaluation of normal optic nerve sheath diameter in healthy volunteers in Bangladesh. PLOS One. 2013; 8:e81013.

Vink JP, Laubscher M, Vlutters R, Silamut K, Maude RJ, Hasan MU, de Haan G. An automatic vision-based malaria diagnosis system. J Microscopy. 2013;250:166-78.

Maude RJ, Plewes K, Dimock J, Dondorp AM. Low-cost portable fluorescein angiography. Br J Ophthal. 2011;95:1213-5.

Glover S, Maude RJ, Beare NAV, Taylor TE, Molyneux M. Malarial retinopathy and fluorescein angiography findings in a Malawian child with cerebral malaria. Lancet Infect Dis. 2010;10:440.

Maude RJ, Beare NAV, Abu Sayeed A, Chang CC, Charunwatthana P, Faiz MA, Hossain A, Bin Yunus E, Hoque MG, Hasan MU5, White NJ, Day NPJ, Dondorp AM. The spectrum of retinopathy in adults with P. falciparum malaria. Trans R Soc Trop Med Hyg. 2009;103:665-71.

Maude RJ, Hasan MU, Beare NAV. Severe retinal whitening in an adult with cerebral malaria. Am J Trop Med Hyg. 2009;80:881.

Maude RJ, Dondorp AM, Abu Sayeed A, Day NPJ, White NJ, Beare NAV. The eye in cerebral malaria: what can it teach us? Trans R Soc Trop Med Hyg. 2009;103:661-4.

Zaloumis S, Tarning J, Krishna S, Price R, White NJ, Davis T, McCaw J, Olliaro P, Maude RJ, Kremsner P, Dondorp AM, Gomes M, Barnes K, Simpson J. Population pharmacokinetics of intravenous artesunate: a pooled analysis of individual data from patients with severe malaria. CPT Pharmacometrics Syst Pharmacol. 2014;3:e145.

Maude RJ, Ahmed BUMW, Rahman AHMW, Rahman R, Majumder MI, Braganza Menezes D, Abu Sayeed A, Hughes L, MacGillivray TJ, Borooah S, Dhillon B, Dondorp AM, Faiz MA. Retinal Changes in Visceral Leishmaniasis by Retinal Photography. BMC Infect Dis. 2014;14:527.

Plewes K, Royakkers AA, Hanson J, Hasan MM, Alam S, Ghose A, Maude RJ, Stassen PM, Charunwatthana P, Lee SJ, Turner GD, Dondorp AM, Schultz MJ. Correlation of biomarkers for parasite burden and immune activation with acute kidney injury in severe falciparum malaria. Malar J. 2014;13:91.

Hanson J, Lee SJ, Mohanty S, Faiz MA, Anstey NM, Price RN, Charunwatthana P, Yunus EB, Mishra SK, Tjitra E, Rahman R, Nosten F, Htut Y, Maude RJ, Thi Hong Chau T, Phu NH, Hien TT, White NJ, Day NP, Dondorp AM. Rapid clinical assessment to facilitate the triage of adults with falciparum malaria, a retrospective analysis. PLoS One. 2014; 9:e87020.

Maude RJ, Silamut K, Plewes K, Charunwatthana P, Ho M, Faiz MA, Rahman R, Hossain MA, Hassan MU, Yunus EB, Hoque G, Islam F Ghose A, Hanson J, Schlatter J, Lacey R, Eastaugh A, Tarning J, Lee SJ, White NJ, Chotivanich K, Day NPJ, Dondorp AM. Randomised controlled trial of levamisole hydrochloride as adjunctive therapy in severe falciparum malaria with high parasitaemia. J Infect Dis. 2014; 209:20-9.

Kolyva C, Kingston H, Tachtsidis I, Mohanty S, Mishra S, Patnaik R, Maude RJ, Dondorp AM, Elwell CE. Oscillations in cerebral hemodynamics in patients with falciparum malaria. Adv Exp Med Biol. 2013;300:121.

Maude RR, Vaid N, Ghose A, Amin R, Samad R, Bin Yunus E, Rahman MR, Bengali AM, Hoque MG, Day NP, White NJ, White LJ, Dondorp AM, Faiz MA. Temporal trends in severe malaria in Chittagong, Bangladesh. Malar J. 2012;11:323.

Joshi VS, Maude RJ, Reinhardt JM, Tang L, Garvin MK, Sayeed AA, Ghose A, Hassan MU, Abràmoff MD. Automated detection of malarial retinopathy-associated retinal hemorrhages. Invest Ophthalmol Vis Sci. 2012;53:6582-8.

Hanson J, Lam S, Mahanta KC, Pattnaik R, Alam S, Mohanty S, Hasan MU, Hossain A, Charunwatthana P, Chotivanich K, Maude RJ, Kingston H, Day NPJ, Mishra S, White NJ, Dondorp AM. Relative contributions of macrovascular and microvascular dysfunction to disease severity in falciparum malaria. Malar J. 2012;206:571-9.

Maude RJ, Hoque MG, Hasan MU, Abu Sayeed M, Akter S, Samad R, Alam B, Bin Yunue E, Rahman MR, Rahman MW, Chowdhury R, Seal T, Charunwatthana P, Chang CC, White NJ, Faiz MA, Day NPJ, Dondorp AM, Hossain MA. Timing of enteral feeding in cerebral malaria in resource-poor settings: a randomized trial. PLOS One. 2011;6:e27273.

Hanson J, Hasan MM, Royakkers AA, Alam S, Charunwatthana P, Maude RJ, Douthwaite ST, Yunus EB, Mantha ML, Schultz MJ, Faiz MA, White NJ, Day NP, Dondorp AM. Laboratory prediction of the requirement for renal replacement in acute falciparum malaria. Malar J. 2011;10:217

Abu Sayeed A, Maude RJ, Uddin Hassan M, Mohammed N, Hoque M, Dondorp AM, Faiz MA. Malarial retinopathy in Bangladeshi adults. Am J Trop Med Hyg. 2011;84:141-7.

Löwenberg EC, Charunwatthana P, Cohen S, van den Born BJ, Meijers JC, Yunus EB, Hassan MU, Hoque G, Maude RJ, Nuchsongsin F, Levi M, Dondorp AM. Severe malaria is associated with a deficiency of von Willebrand factor cleaving protease, ADAMTS13. Thromb Haemost. 2010;103:181-7.

Maude RJ, Hasan MU, Douthwaite ST, Ghose A, Faiz MA, Dondorp AM. Studies on severe malaria are still possible and essential. Clin Infect Dis. 2010;50:281-2.

Maude RJ, Bin Yunus E, Hoque MG, Hassan MU, Hossain MA, Samad R, Rahman R, Ghose A, White NJ, Dondorp AM, Faiz MA. MORU and CMCH: a highly successful collaboration. JCMCTA. 2009:20:2-5.

Maude RJ, Beare NAV. Fluorescein angiography findings strengthen the theoretical basis for trialling neuroprotective agents in cerebral malaria. Trends Parasitol. 2009;25:350-1.

malaria

falciparum

knowlesi

retina

MRI

pathogenesis

prognosis

diagnosis

Retinopathy and central nervous system microcirculatory abnormalities in adult cerebral malaria and their prediction of outcome

Thesis or Dissertation

Doctoral

MD Doctor of Medicine