Though rare, healthcare-associated malaria has been reported. Mechanisms of transmission have included exposure to contaminated blood through transfusion, glucometers, saline flushes, multidose vials, and contact with nonintact skin.Reference Alweis, DiRosario, Conidi, Kain, Olans and Tully 1 – Reference Gonzalez, Ochoa and Franco 5 We describe a case of Plasmodium falciparum infection in which person-to-person transmission in a hospital is supported by molecular genotyping of the parasites.
METHODS
On March 6, 2012, a woman in her early 40s (patient 1) was hospitalized with fever, abdominal and shoulder pain, and nausea. She had hemolytic anemia and thrombocytopenia, and a blood smear collected on March 7 revealed P. falciparum. She was treated successfully with doxycycline and quinidine. The patient denied domestic or international travel since emigrating from South America in 1996. She had a history of a psychiatric disorder and resided in a group home for more than 6 months before her hospitalization.
We requested patient 1’s travel history from the US Customs and Border Protection and interviewed the director of her group home. We reviewed medical records at hospital A, where the patient presented with malaria, and also at hospital B, where she had been hospitalized February 16–23, 2012, for a cholecystectomy. To determine whether local mosquito transmission had occurred, we deployed mosquito traps in the patient’s residence and hospital B.
At hospital B, we reviewed operating room records and obtained the patient census for a portion of patient 1’s hospitalization, searching for patients with malaria-like illnesses who were hospitalized at the same time and on the same floor as patient 1. We also reviewed the hospital’s hematology records to identify any suspected or confirmed malaria cases not reported to the New York City Department of Health and Mental Hygiene. The census was compared with P. falciparum surveillance reports reported to the Department of Health and Mental Hygiene since January 1, 2012.
We assessed the possibility of malaria transmission at hospital B through medical chart review, interviews, and onsite investigation. Potential exposures included injected medications and fluids, medical and surgical procedures, blood transfusions, and medical equipment. General infection control practices and environmental cleaning and disinfection were also reviewed.
P. falciparum was confirmed by light microscopy (blood smears) and real-time polymerase chain reaction (whole blood). P. falciparum specimens were compared by analysis of 12 polymerase chain reaction–amplified microsatellite repeat markers on a 3130x capillary sequencer (Applied Biosystems).Reference Anderson, Su, Bockarie, Lagog and Day 6 In addition, P. falciparum specimens were characterized by pyrosequencing, which evaluated and compared 10 single nucleotide polymorphic mutations associated with drug resistance in the chloroquine resistance transporter (crt), dihydrofolate reductase (dhfr), and dihydropteroate synthetase (dhps) genes of P. falciparum. Reference Zhou, Poe and Limor 7
RESULTS
The US Customs and Border Protection had no documented recent international travel for patient 1; her last known travel was to Trinidad in 2006. No evidence of local mosquito transmission or overwintering mosquito activity was detected within patient 1’s residence or in hospital B. She spent limited time outside the group home, her residence was not located near any airport, and she had no history of visitors who had traveled, eliminating the possibilities of “airport” and “baggage” malaria.Reference Isaacson 8 , Reference Castelli, Cabona, Brunori and Carosi 9 There was no history of intravenous drug use.
Patient 1 did not receive blood products during her time at either hospital. Her cholecystectomy followed a child’s circumcision as the second surgical procedure of the day at hospital B. Review of medical records for patients hospitalized at the same time and on the same floor at hospital B identified a 42-year-old woman (patient 2) who was admitted with fever and abdominal pain on the same day as patient 1. Patient 2 had returned from a 20-day trip to Nigeria and denied taking malaria chemoprophylaxis. Blood smears collected from patient 2 on February 16 and 18, 2012, were considered negative and positive, respectively, for the presence of malaria-like parasites. Though hospital laboratory protocol required the positive specimen be referred to a commercial laboratory for additional testing, the specimens were not sent. Consequently, the species of malaria was not identified during her hospitalization. The patient was treated with mefloquine for presumed P. falciparum infection. Because the malaria diagnosis was not confirmed, the case was not reported to the Department of Health and Mental Hygiene. Since January 1, 2012, hospital B had reported only 1 case of malaria, diagnosed 4 weeks before patient 1’s hospitalization.
Investigation at hospital B revealed patients 1 and 2 were simultaneously in the emergency department on February 16, 2012, but were cared for in different areas by different staff. The site investigation identified no infection control breaches in the emergency department, and all staff interviewed reported that the only common medication, sterile saline for injection, would have been obtained from different areas and administered by different staff. All staff reported intravenous fluid bags and tubing sets are never shared, and intravenous bags are not prepared (“pre-spiked”) in advance of their use.
Patients 1 and 2 were admitted to the same inpatient unit in hospital B and, for a week, resided in nearby rooms. While on the unit, patients 1 and 2 were cared for by common staff and underwent diagnostic phlebotomy; however, medical records indicated that different phlebotomists drew blood from each patient at different times. Individual saline syringes were used for flushing intravenous lines. Both patients may have received fingerstick blood glucose monitoring, but the medical record was inconsistent for patient 2. Staff reported that glucometers were not consistently cleaned and disinfected after each use.
P. falciparum was confirmed for patients 1 and 2. A blood smear collected from patient 2 on February 16, 2012, initially considered negative by light microscopy at the hospital laboratory, revealed P. falciparum on repeat light microscopy and by real-time polymerase chain reaction. P. falciparum specimens from both patients were identical at the 12 microsatellite loci tested, with the exception of 1 minor allele of a microsatellite marker that was detected in patient 2’s but not in patient 1’s specimen. They also had identical mutations identified by pyrosequencing at 10 positions in 3 genes associated with drug resistance; the pattern of mutations was consistent with P. falciparum of African or Asian, and not South American, origin.Reference Gbotosho, Folarin and Bustamante 10 The microsatellite analysis at 12 loci, along with the pyrosequencing results, indicated the parasites from the 2 patients were genetically identical.
DISCUSSION
Following a comprehensive investigation into potential sources of infection, we conclude that patient 1 acquired P. falciparum malaria through a breach in infection control precautions during her stay at hospital B. A lapse in glucometer cleaning and documentation was noted, but the precise mechanism by which this transmission occurred is unknown. However, the proximity and timing of patient 1’s exposure to patient 2 make such transmission likely, and molecular test results implicate malaria transmission from patient 2 to patient 1.
Several published reports describe cases of malaria for which healthcare-associated transmission is suspected but no mechanism is confirmed.Reference Moro, Romi and Severini 2 , Reference Jain, Persaud and Perl 3 , Reference Gonzalez, Ochoa and Franco 5 As in these other cases, molecular testing provided the evidence suggesting patient-to-patient transmission for the case reported here. Malaria should be considered in the differential diagnosis of patients with fever of unknown origin, even in the absence of an appropriate travel history. Though uncommon, the occurrence of healthcare-associated malaria transmission reveals a breach in standard precautions for bloodborne pathogens and should be considered when investigating cryptic cases of malaria.
ACKNOWLEDGMENTS
We are grateful for the contributions of the following individuals to this investigation: Mike Antwi, Paul Arguin, Prabhu Gounder, Scott Harper, Michael Henry, Curtis Huber, Marcelle Layton, Yin Ling Leung, Daniel Osuagwu, Jose Poy, Jennifer Rakeman, Kathrine Tan, and Sherif Zaki.
Financial support. None reported.
Potential conflicts of interest. All authors report no conflicts of interest relevant to this article.
