Genetic Confirmation of Quinine-Resistant Plasmodium falciparum Malaria Followed by Postmalaria Neurological Syndrome in a Traveler from Mozambique

Abstract

A case of quinine-resistant Plasmodium falciparum malaria, followed by a postmalaria neurological syndrome and a recurrence episode, is described. Genetic characterization of the P. falciparum isolate obtained by analysis of msp1 and msp2 amplicons revealed the coexistence of two genotypes causing the first malaria episode and the presence of a unique isolate responsible for the recurrence. CASE REPORTFifteen days after returning from Bilene (Maputo Province, Mozambique), a previously healthy 42-year-old man was admitted to the National Institute for Infectious Diseases L. Spallanzani, Rome, Italy, with a 4-day history of headache and febrile illness. Plasmodium falciparum malaria was diagnosed on the basis of blood film examination; the initial level of parasitemia was Ͼ100,000 parasites/l. The patient had not taken antimalarial prophylaxis during a business trip to Mozambique. On examination, the patient was fully conscious and had a temperature of 38°C. Hepatosplenomegaly was detected. Acute complications included hemolysis and severe thrombocytopenia. The patient was treated with intravenous (i.v.) quinine (QN; 20 mg of the hydrochloride salt per kg initially and then 10 mg/kg three times a day) plus oral doxycycline (100 mg two times a day). The parasitemia was cleared by day 4, whereupon the patient was treated with oral QN (8 mg of base/kg three times daily) plus doxycycline until day 8. He was discharged from the hospital on day 9.Nine days later, however, the patient developed a low-grade fever with acute confusion (inappropriate speech and markedly disturbed behavior), postural tremor, and nominal aphasia. He was readmitted to our hospital on day 20. On examination, the patient had a temperature of 38.2°C with no clinically detectable focus of infection and without meningism. He was in an acute confusional state with nominal aphasia and showed a fine postural tremor of the arms that worsened when he tried to move his arms. The lowest Glasgow coma score was 12. No abnormalities were found in the cardiovascular and respiratory systems. No previous history of neurological or psychiatric illness was ascertained. No medication had been taken by the patient at home. Simultaneous thick and thin blood film tests on 3 different days were negative for malarial parasites. Computerized tomography and gadolinium-enhanced T 1 -and T 2 -weighted magnetic resonance imaging scans of the brain were also normal except for the presence of maxillary sinus exudate. On day 20, treatment with i.v. ceftriaxone (2,000 mg once a day) was begun. Analysis of a cerebrospinal fluid sample obtained by lumbar puncture revealed mild lymphocytic pleocytosis (45 lymphocytes/l), a normal glucose concentration, and an elevated protein concentration of 1.29 g/liter (normal range, 0.2 to 0.4 g/liter). Pending herpes simplex virus testing, i.v. acyclovir (10 mg/kg three times a day) was empirically added to the treatment regimen on day 24 and stopped on day 28. Subsequent tests of cerebrospinal fluid for viral, bacterial, and fungal infection...

Limited Ability of Plasmodium falciparum pfcrt , pfmdr1 , and pfnhe1 Polymorphisms To Predict Quinine In Vitro Sensitivity or Clinical Effectiveness in Uganda

“…The DNNND repeats are in block II, and the DDNNNDNHNDD repeats are in block V. Profiles ms4760-1 to ms4760-35 have been described previously (5,18,25,53); ms4760-36 to ms4760-59 are described in this study. Profiles 4,10,11,13,14,16,17,19,20,22,25,26,28,29,30,31,32,33, and 34 were not observed in the present study. Other differences among sequences are indicated in boldface.…”

“…First, the efficacy of quinine for the treatment of uncomplicated malaria is uncertain. A number of studies and case reports have demonstrated apparent failures after quinine therapy for falciparum malaria in Asia (9,41), South America (46,60), and Africa (22,31,38). Recent studies incorporating detailed assessments of treatment efficacy or effectiveness have shown 28-day failure rates of Ͼ10% after 7-day courses of quinine for uncomplicated malaria in Sudan (3), Thailand (40), and Uganda (1).…”

Plasmodium falciparum susceptibility to anti-malarial drugs in Dakar, Senegal, in 2010: an ex vivo and drug resistance molecular markers study

“…The IC 50 s for isolates collected in Senegal were 31 to 765 nM in 1984 (Thies and Kaolack) [81], 5 to 932 nM in 1996 (Dielmo) [49] and 6 to 1291 nM in 2009 (Dakar) [40]. The wide range in QN susceptibility and recent evidence for QN treatment failure seen across Africa [82,83] or in Senegal in a patient who spent two months in Dielmo in 2007 [84] suggest that the evolution of parasites with reduced susceptibility may contribute to QN decreased efficacy. QN used in combination with DOX in the treatment of severe malaria in Dakar.…”

Plasmodium falciparumNa+/H+Exchanger 1 Transporter Is Involved in Reduced Susceptibility to Quinine

“…The first cases of QN clinical failure were observed in Brazil and Asia in the 1960s (4,12). In the 1980s, clinical failures became more frequent in Southeast Asia, South America, and Africa (13,15,19,22,33). However, QNR…”