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Malaria Clinical Cases Presentation Gail Stennies, M.D., M.P.H. Medical Officer Malaria Epidemiology Branch DPD/ NCID/ CDC May, 2002 Information requested when evaluating a potential case of malaria • Age • Sex and pregnancy status • Travel history, travel outside major or urban areas • Visitors from endemic areas • Exposure to mosquitoes • Malaria prophylaxis used • Receipt of blood transfusions or transplant • Past history of malaria • Drug allergies • Clinical status of the patient, esp. neurological • Lab results Congenital malaria • Previously healthy 10-week old female developed an fever and dark urine on September 7, 2000 • Temp 103.7o F, WBC 24,600/µl, and Hb 8.7 g/dL • She was admitted for possible sepsis • Blood, urine, and cerebral spinal fluid cultures were done • Treated with IV ampicillin and cefotaxime Congenital malaria • Past medical history • Uncomplicated pregnancy and delivery • Seen in ER on July 17 for abnormal breathing • Normal exam and chest Xray, no diagnosis made or treatment given • Parents from DR Congo- dad came in 1995, mom in 1996 • Mom completed course of chloroquine prior to immigration for malaria (?self-diagnosis) Congenital malaria • Smears taken on September 8 showed P.m. • Treatment with chloroquine was started • She received 2 units of packed RBCs after Hgb dropped to 5.6 g/dL • Responded well to treatment with negative smears 1 week post therapy Congenital malaria • Parents denied • • • • any episodes of malaria febrile illness foreign travel or blood transfusion since in US • Lived in screened apartment, some mosquitoes seen indoors in August • Friend from Kinshasha visited in August, he was well during visit Congenital malaria • Pretreatment labs on mother • Blood smears were negative • Positive IgG titers • P.f. and P.m. 1:16,384 • P.v. and P.o. 1:102 • PCR - negative • Mother was treated empirically with chloroquine Transfusion-transmitted malaria • 72 yo female with history of multiple medical problems admitted September 15, 1995 with neutropenic fever post chemotherapy • Intracellular parasites found on peripheral smear – diagnosed with Babesia • Improved after quinine and clindamycin were started on September 25 Transfusion-transmitted malaria • Smears read as P.f. by CDC, same for smears from September 4 • Risk factors • No travel to endemic areas • No IVDA, tattoos, acupuncture • Yes recent recipient of blood • • • • • April August 9 September 3 September 9 September 24 quantity unknown 4 units 2 units 2 units 2 units Transfusion-transmitted malaria • Which units are most suspect? • American Red Cross centers were notified • Identify donors – defer for future donation during investigation • Put any unused blood products on hold • Contact donors – reinterview about risk factors • Obtain blood from donors – segments from units or new collection for smears and serology Transfusion-transmitted malaria • 1/6 donors was Nigerian national with remote history of malaria • Thick & thin smears – too few parasites to identify species at CDC • Species Index case Donor N P.v. < 16 64 P.f. 1:1024 > 1:4096 P.m. < 16 > 1:4096 P.o. < 16 1:256 IFA results on other 5 donors were negative for all species Donor N advised to seek treatment for P.f. and not donate Unusual but possible case # 1 • 27 yo health care assistant with 3-day history of fever, sweats, rigors & frontal headache • Past medical history was unremarkable • Never had clinical malaria • No recent foreign travel • Left Sri Lanka 7.5 yrs earlier • Visited France 3 yrs earlier Unusual but possible case # 1 • Exam – 38.5o, no other abnormal findings, no focal neurological signs • Smears – P.f. , 0.001% parasitemia • Started on oral quinine 600 mg 3x/day • Initial increase in density to 0.005% but after 5 days of treatment parasites cleared • 3 tabs of Fansidar were given prior to discharge Unusual but possible case # 1 • ? Exposure Unusual but possible case # 1 • 10 days prior to admission, he had sustained a needlestick injury with a nonsterile needle while resuscitating a patient • Patient was 16 yo Ghanaian boy with P.f., 1.7% parasitemia and febrile convulsion • Haworth FLM, Cook CG. Needlestick malaria. Lancet 1995;346:1361. Unusual but possible case # 2 • 28 yo English woman admitted to hospital on April 20 1997, had been unwell for 3 weeks with intermittent fever and diarrhea • P. f. with 30% parasitemia was diagnosed • Treated with IV quinine, blood transfusion, and prostacyclin and recovered fully • Traveled to Sub-Saharan Africa previous month • Used chloroquine + proguanil for prophylaxis Unusual but possible case # 2 • Flew to Italy on March 25, seen in Sicilian hospital on April 16 • Given IV fluids and antibiotic, no specific diagnosis made, was not admitted • Was still ill when returned to England on April 19 Unusual but possible case # 2 • Patient’s story is not unusual HOWEVER • Italian physician who treated her died 21 days later on May 6 • Diagnosis of P.f was made on necropsy • He had no travel history • ?Risk Unusual but possible case # 2 • He had sustained a needlestick injury with the needle he used to start the woman’s IV drip • Anonymous. Needlestick malaria with tragic consequences. Communicable Disease Report Weekly. 7(28)11 July 1997. Unusual but possible case # 3 • 69 yo developed fever and chills on December 15, 1998 while at work • Thick and thin smears showed rare intracellular rings consistent with P.v. or P.o. • The diagnosis was confirmed at a reputable reference lab with PCR showing P.v. • Patient did well with chloroquine and primaquine Unusual but possible case # 3 • Patient denied recent blood transfusion or international travel • Last visit to a malarious area had been 10 yrs earlier • Why is malaria on the differential diagnosis list, esp. during cold and flu season? Unusual but possible case # 3 • Occupational history? Unusual but possible case # 3 • Occupational history? • Parasitologist • Denies recent needlestick exposure • Hmm? Unusual but possible case # 3 • During the 14 days prior to his illness, he had worked in the insectory with infective Anopheles mosquitoes carrying a Southeast Asian strain of P.v. and a West African strain of P.o. • On December 8, a colleague had noticed a mosquito flying free in the work area but was unable to catch it Things that keep risk management staff busy - Case 1 • 31 yo female returned home to South Florida on January 18, 1996 following a 16-day trip to Bolivia • No antimalarial chemoprophylaxis taken; had significant rural exposure on trip • Upon returning home she developed fever, chills, headache and malaise and was admitted that same day to Hospital A and evaluated for sepsis Things that keep risk management staff busy - Case 1 • Treated with IV antibiotics administered through a heparin lock • Blood films obtained on January 23, 1996 were positive for P.v., later confirmed at CDC • The patient was treated with oral chloroquine and primaquine, improved promptly, and was discharged on January 24, 1996 Things that keep risk management staff busy - Case 2 • 83 yo male with multiple medical problems including congestive heart failure and bradycardia • Presented to another hospital in the same county as Hospital A on February 11, 1996 with a history of fever and chills • P.v. parasites were identified on blood films obtained for a complete blood count at the time of admission. • Diagnosis confirmed by CDC Things that keep risk management staff busy - Case 2 • Risk factors • No history of travel outside the United States except for visiting the Bahamas more than 10 years previously • No IVDA or malariotherapy • No recent blood transfusions • From January 22-24, 1996 he had been admitted to Hospital A for bradycardia • Was in a room adjacent to that of Case 1 Things that keep risk management staff busy - Case 2 • During that hospitalization he received intravenous medications through a heparin lock. • The patient improved after treatment with chloroquine and was discharged. Things that keep risk management staff busy - Déjà vu? • 60 yo female patient with chronic obstructive pulmonary disease presented to the hospital A on February 12, 1996 with a similar history of fever and chills • P.v. parasites were identified on her admission blood film, diagnosis confirmed at CDC • Risk factors • No travel outside the United States • No IDVA or malariotherapy • No recent transfusions of blood or blood products Things that keep risk management staff busy– Case 3 • However, she had also been hospitalized from January 20-26, 1996 in a room adjacent to Case 1 • During that hospitalization, she had received IV medications through a heparin lock • The patient improved after treatment with chloroquine and was discharged home. Things that keep risk management staff busy – Discussion • Investigation by the County Health Department and the hospital administration revealed • All three patients had heparin locks at the same time • All were cared for by the same health worker • Deficient infection control practices • In particular, nursing staff used 10 cc vials of sterile water to flush heparin locks • Occasionally used the same vial for two or more patients Things that keep risk management staff busy - Discussion • Although this practice could not be retrospectively linked to the three cases, it seems the most plausible explanation for these three cases • Following the investigation, the hospital routinely began to use single-dose vials for flushing intravenous devices Management of induced or congenital cases • No sporozoites are injected into the human by mosquito • Therefore no exo-erythrocytic (hepatic) cycle • No need for primaquine Malaria Life Cycle Oocyst Sporozoites Mosquito Salivary Gland Zygote Exoerythrocytic (hepatic) cycle Gametocytes Erythrocytic Cycle Hypnozoites The following will become knee-jerk questions • Age • Sex and pregnancy status • Travel history, travel outside major or urban areas • Visitors from endemic areas • Exposure to mosquitoes • Malaria prophylaxis used • Receipt of blood transfusions or transplant • Past history of malaria • Drug allergies • Clinical status of the patient, esp. neurological • Labs Don’t forget to ask • Occupational history • Healthcare workers • Exposure to mosquitoes • Needle exposure • • • • IV drug abuse Needlestick injuries Tattoos Acupuncture • Other meds used with potential antimalarial effect • • • • Sulfa – Bactrim ® Tetra – or doxycycline Quinine Hydroxychloroquine – Plaquenil® • Atovaquone • Clindamycin • Meds received abroad • Artesunates • Halofantrine All “malaria” is not malaria • • • • • • • Incubation periods unlikely Parasite density very high for nonfalciparum Species not likely given travel history Drug resistance? Misdiagnosis – species or parasite or negative Miscalculation of density Previously undetected mixed infection