Risk of transfusion-transmitted Babesia microti in Canada.

BACKGROUND: Babesia microti has gained a foothold in Canada as tick vectors become established in broader geographic areas. B. microti infection is associated with mild or no symptoms in healthy individuals but is transfusion-transmissible and can be fatal in immunocompromised individuals. This is the first estimate of clinically significant transfusion-transmitted babesiosis (TTB) risk in Canada. STUDY DESIGN AND METHODS: The proportion of B. microti-antibody (AB)/nucleic acid amplification test (NAT)-positive whole blood donations was estimated at 5.5% of the proportion of the general population with reported Lyme Disease (also tick-borne) based on US data. Monte Carlo simulation estimated the number and proportion of infectious red cell units for three scenarios: base, localized incidence (risk in Manitoba only), and donor study informed (prevalence from donor data). The model simulated 1,029,800 donations repeated 100,000 times for each. RESULTS: In the base scenario 0.5 (0.01, 1.75), B. microti-NAT-positive donations would be expected per year, with 0.08 (0, 0.38) recipients suffering clinically significant TTB (1 every 12.5 years). In the localized incidence scenario, there were 0.21(0, 0.7) B. microti-NAT-positive donations, with 0.04 (0, 0.14) recipient infections (about 1 every 25 years). In the donor study informed scenario, there were 4.6 (0.3, 15.8) B. microti-NAT-positive donations expected, and 0.81 (0.05, 3.14) clinically significant TTB cases per year. DISCUSSION: The likelihood of clinically relevant TTB is low. Testing would have very little utility in Canada at this time. Ongoing pathogen surveillance in tick vectors is important as B. microti prevalence appears to be slowly increasing in Canada.

[Babesiosis could be more common in Sweden than previously thought]. / Babesia-infektion kan vara vanligare i Sverige än vi tidigare trott - Parasiten kan spridas via fästingar och blodtransfusion.

Babesia is a malaria-like, intraerythrocytic parasite with more than 100 different species. It is a zoonosis and some of the species are transmitted to humans by ticks and also as a possible transfusion-transmitted infection. In Sweden the disease has been well known in veterinary medicine for a long time, but only a few but severe cases have been published in humans during the last decades. Common symptoms from human Babesia infections (babesiosis) are fever, chills and myalgia and they vary from subclinical to potentially fatal among those with risk factors such as immunosuppression and splenectomy. In the U.S. more than 2,000 cases of babesiosis are found yearly and it is one of the most frequent fatal infections following blood transfusion. A study from southern Sweden has recently revealed a seroprevalence of 16% of Babesia antibodies among Borrelia-infected persons. These results indicate that there is a need to broaden awareness of Babesia in Sweden.

Characteristics of transfusion-transmitted Babesia microti, American Red Cross 2010-2017.

BACKGROUND: Babesia microti, a red blood cell (RBC) parasite transmitted naturally to vertebrate hosts by ixodid ticks, is endemic to the northeastern and upper midwestern United States, with the geographic range of infected ticks expanding. B. microti is a blood safety issue with >200 transfusion-transmissions reported. METHODS: The American Red Cross's Hemovigilance program investigated hospital-reported transfusion-transmitted babesiosis (TTB) cases. Follow-up samples from involved donors were tested for B. microti antibodies and parasite DNA, the latter by real-time polymerase chain reaction (PCR). Test-positive donors were permanently deferred from future donations. RESULTS: B. microti-positive donors were implicated in 77 of 143 suspect TTB cases investigated from 2010 through 2017. In four cases, two positive donors were identified for a total of 81 positive donors. In three cases, a RBC unit was split and components transfused multiple times to the same pediatric recipient. RBCs were the transmitting product in all cases. At follow-up, all involved donors were antibody positive; 25 donors were also PCR positive. Positive donations were collected throughout the year, peaking in the summer. Most donors (78) were resident of, or traveled to (2), an endemic state. One donor resided in a non-endemic state without relevant travel history. One fatality listed babesia as a contributing factor. No implicated donation was screened by an investigational protocol. CONCLUSIONS: Babesiosis remains a blood safety issue. Prior to FDA-licensed screening test availability and final FDA Guidance, blood collectors in endemic states investigationally tested none, a portion, or all collections. Future expanded testing will reduce the frequency of TTB cases.

[Enfermedad de Chagas en México].

Chagas disease, which is caused by Trypanosoma cruzi, is considered to be the most serious parasitic disease in America. It is transmitted mainly by triatominae ("kissing bugs"). Mazzoti reported the first two human cases in Mexico. The form of transmission is by parasites entering the organism in feces of the insect, by blood transfusion, from mother to child, by organ transplant and laboratory accidents. In Mexico, 1.1 million people are estimated to be infected; the incidence in 2012 was 0.70 per 1,00,000 population. In 2017, the highest incidence rates were registered in Yucatán, Oaxaca and Hidalgo. The infection causes cardiomyopathies and mega-organs of the digestive tract. Diagnosis in the acute phase is by parasitological approach and, in the chronic phase, by laboratory screening studies. In Mexico's blood banks, screening for Chagas disease is mandatory; from 2007 to 2016, seroprevalence has decreased from 0.40 to 0.32 due to the improvement of donor selection processes and the ad hoc questionnaire. The targets of the parasite are neurons and smooth and myocardial muscle cells. The association of neuronal and smooth muscle destruction defines the presentation of chagas mega-syndromes. Initial manifestations of the disease can go unnoticed; 5% show apparent signs and symptoms and 30% will progress to the chronic asymptomatic phase. Currently available treatments have effect in the acute phase. For the control of Chagas disease, the Specific Action Program for the Prevention and Control of Chagas Disease (PAE Chagas 2013-2018) is available to initiate activities aimed at eliminating transfusion and congenital transmission and controlling vector transmission. The success of medical care depends on oportune detection, early etiological treatment and coverage broadening. On the other hand, monitoring and screening of pregnant women living in risk areas and blood and organ donors universal screening will enable the elimination congenital and transfusion transmission.

La enfermedad de Chagas, causada por el Trypanosoma cruzi, está considerada como la parasitosis más grave en América. Se transmite principalmente por triatominos (chinches). El doctor Mazzoti reportó los dos primeros casos humanos en México. La forma de transmisión es por la entrada al organismo de los parásitos en heces del insecto, por transfusión sanguínea, de madre a hijo, por trasplante de órganos y por accidentes de laboratorio. En México se estima que 1.1 millones de personas están infectadas; la incidencia en 2012 fue de 0.70 por 100 000 habitantes. En 2017, las mayores tasas de incidencia se registraron en Yucatán, Oaxaca e Hidalgo. La infección ocasiona miocardiopatías y megaórganos del tracto digestivo. El diagnóstico en fase aguda es por abordaje parasitológico y en fase crónica, por estudios de tamizaje por laboratorio. En los bancos de sangre de México, el estudio de la enfermedad de Chagas es de observancia obligatoria; de 2007 a 2016, la seroprevalencia ha disminuido de 0.40 a 0.32 debido a la mejora de los procesos de selección al donante y al cuestionario ad hoc. Los blancos del parásito son las células neuronales y las de los músculos liso y miocárdico. La asociación de la destrucción neuronal y del músculo liso define la presentación de los síndromes megachagásicos. Las manifestaciones iniciales de la enfermedad pueden pasar desapercibidas; 5 % de los pacientes presenta signos y síntomas aparentes y 30 % evolucionará a la fase crónica asintomática. Los tratamientos actuales tienen efecto en la fase aguda. Para el control de la enfermedad de Chagas se dispone del Programa de Acción Específico para la Vigilancia Prevención y Control de la Enfermedad de Chagas (PAE Chagas 2013-2018), encaminado a eliminar la transmisión transfusional y congénita y a controlar la transmisión vectorial. De la detección oportuna, el tratamiento etiológico temprano y la ampliación de cobertura depende el éxito de la atención médica. Por su parte, la vigilancia y tamizaje de las mujeres embarazadas que viven en zonas de riesgo y el tamizaje universal de donadores de sangre y órganos harán posible la eliminación de la transmisión connatal y transfusional.

Investigation of a case of suspected transfusion-transmitted malaria.

BACKGROUND: Transfusion-transmitted malaria (TTM) is a rare occurrence with serious consequences for the recipient. A case study is presented as an example of best practices for conducting a TTM investigation. CASE REPORT: A 15-year-old male with a history of sickle cell disease developed fever after a blood transfusion. He was diagnosed with Plasmodium falciparum malaria and was successfully treated. The American Red Cross, New York State Department of Health, and the Centers for Disease Control and Prevention investigated the eight donors who provided components to the transfusion. The investigation to identify a malaria-positive donor included trace back of donors, serologic methods to identify donor(s) with a history of malaria exposure, polymerase chain reaction (PCR) testing, microsatellite analysis to identify the parasite in a donor and match its genotype to the parasite in the recipient, and reinterview of all donors to clarify malaria risk factors. RESULTS: One donor had evidence of infection with P. falciparum by PCR, elevated antibody titers, and previously undisclosed malaria risk factors. Reinterview revealed that the donor immigrated to the United States from Togo just short of 3 years before the blood donation. The donor was treated for asymptomatic low parasitemia infection. CONCLUSION: This investigation used standard procedures for investigating TTM but also demonstrated the importance of applying sensitive laboratory techniques to identify the infected donor, especially a donor with asymptomatic infection with low parasitemia. Repeat interview of all donors identified as having contributed to the transfused component provides complementary epidemiologic information to confirm the infected donor.

First report of Cytauxzoon sp. infection in domestic cats in Switzerland: natural and transfusion-transmitted infections.

BACKGROUND: Cytauxzoonosis is an emerging tick-borne disease of domestic and wild felids. Cytauxzoon felis induces severe and often fatal disease in domestic cats. In Europe, clinical and subclinical infections caused by Cytauxzoon sp. are described. We report the first cases of Cytauxzoon sp. infection in domestic cats in Switzerland. METHODS: Clinical and laboratory data and results of PCR analyses were collected from Cytauxzoon sp. PCR-positive cats and the cats followed for up to 851 days. RESULTS: The cases were three two-month old kittens from the same litter (Cases 1-3) and two adult domestic shorthair cats (Cases 4 and 5). The cats originated from the north-west and west of Switzerland. Cases 1-3 presented with moderate to severe regenerative anaemia and intraerythrocytic inclusions. Cytauxzoon sp. was confirmed by PCR and sequencing. The kittens made a clinical and haematological recovery after blood transfusion and/or treatment with azithromycin and atovaquone, but erythroparasitaemia persisted. Case 4 presented with severe non-regenerative anaemia. Case 5 was healthy and used as a blood donor for Case 4. Following blood transfusion, Case 4 showed intraerythrocytic inclusions, and Cytauxzoon sp. was confirmed in both Cases 4 and 5 using PCR and sequencing. Case 4 achieved clinical and haematological remission after treatment with azithromycin, atovaquone and immunosuppressive drugs. Eight months later, Case 4 was presented again with anaemia but tested Cytauxzoon sp. PCR-negative. Sequencing of 1637 bp of the 18S rRNA gene of Cytauxzoon sp. revealed 100% nucleotide sequence identity among isolates of Cases 1-3 and between isolates of Cases 4 and 5, and 99% sequence identity between isolates of all cases. Phylogenetic analysis revealed the closest relationship of the Swiss isolates to Cytauxzoon sp. isolates from domestic cats and wild felids from France, Spain and Romania and to Cytauxzoon manul from a Pallas's cat. CONCLUSIONS: This is the first report of Cytauxzoon sp. infection in domestic cats in Switzerland. It is also the first report of infection in very young kittens and transmission of Cytauxzoon sp. to an adult cat by transfusion of blood from an asymptomatic cat. The cats recovered but some developed chronic asymptomatic erythroparasitaemia for up to 28 months. Domestic cats may act as reservoirs for Cytauxzoon sp. in Europe and blood donor cats should be screened for this agent by PCR.

Superior real-time polymerase chain reaction detection of Babesia microti parasites in whole blood utilizing high-copy BMN antigens as amplification targets.

BACKGROUND: Babesiosis is a zoonotic disease transmitted to humans by the bite of infected ticks and caused by apicomplexan parasites, most commonly Babesia microti. Additionally, blood and blood products collected from asymptomatically infected blood donors may cause transfusion-transmitted infections in recipients. Highly sensitive molecular assays that detect parasite nucleic acid are needed for laboratory diagnosis and to identify and defer clinically silent but parasitemic blood donors. STUDY DESIGN AND METHODS: Here we report the development and analytical and clinical characterization of a real-time polymerase chain reaction (RT-PCR)-based assay for the detection of B. microti genomic DNA in whole blood. We evaluate the detection of Babesia parasites using two separate targets, the traditional18S ribosomal subunit gene (Bm18S) and members of the abundant BMN family of seroreactive antigens (BmBMN). RESULTS: Analytical sensitivity determination using a probit analysis demonstrated an analytical sensitivity of 30.9 parasites/mL for 18S amplification and 10.0 parasites/mL for BMN amplification The BMN primer set also demonstrates superior sensitivity for serial dilution panels prepared from clinically diagnosed Babesia-infected blood samples, generally detecting 10-fold more dilute nucleic acid. CONCLUSIONS: Cumulatively, our data demonstrate that RT-PCR detection of the BMN family of seroreactive antigens reflects a sensitive and superior assay for the detection of B. microti in whole blood samples.

Plasmodium falciparum infection transmitted by transfusion: A cause of hemophagocytic syndrome after bone marrow tranplantation in a non-endemic country.

A 27-year-old man with severe aplastic anemia underwent bone marrow transplantation from his HLA identical brother in July 2016. Conditioning included ATGAM 30 mg/kg for 3 days and Cyclophosphamide 50 mg/kg for 4 days. The patient received several platelet and red blood cell transfusions before and after the conditioning. The patient received broad spectrum antibiotics and caspofungin because persistant febrile neutropenia without bacteriological or mycological documentation. Hemophagocytic syndrome was diagnosed on day +12. Steroids at 1 mg/kg were started on day +12. Fever resolved the same day but resumed 3 days later associated to intravascular hemolysis with no schizocytes on blood smears and negative DAT. Thick blood film smears performed on day +26 revealed Plasmodium falciparum parasites (parasitemia = 20%). Except the level of parasitemia, there were no signs of gravity. Quinine was started on day 26 at a loading dose of 15 mg/kg followed by 8 mg/kg three times a day for 20 doses. Fever vanished after 2 days. Parasitemia cleared in 3 days and remained negative thereafter. Investigations revealed that the patient was transfused by a red cell unit harvested in a voluntary donor native of a malaria endemic country. PCR for P. falciparum performed in this donor in the frame of investigations was positive. The patient is alive with a normal blood count 1 year after BMT.

Transfusion-transmitted malaria masquerading as sickle cell crisis with multisystem organ failure.

BACKGROUND: Fever accompanying vaso-occlusive crisis is a common presentation in patients with sickle cell disease (SCD) and carries a broad differential diagnosis. Here, we report a case of transfusion-transmitted malaria in a patient with SCD presenting with acute vaso-occlusive crisis and rapidly decompensating to multisystem organ failure (MSOF). CASE REPORT: An 18-year-old African American male with SCD was admitted after multiple days of fever and severe generalized body pain. He received monthly blood transfusions as stroke prophylaxis. A source of infection was not readily identified, but treatment was initiated with continuous intravenous fluids and empiric antibiotics. The patient developed acute renal failure, acute hypoxic respiratory failure, and shock. He underwent red blood cell (RBC) exchange transfusion followed by therapeutic plasma exchange and continuous veno-venous hemodialysis. A manual peripheral blood smear revealed intraerythrocytic inclusions suggestive of Plasmodium, and molecular studies confirmed Plasmodium falciparum infection. Intravenous artesunate was given daily for 1 week. A look-back investigation involving two hospitals, multiple blood suppliers, and state and federal public health departments identified the source of malaria as a unit of RBCs transfused 2 weeks prior to admission. CONCLUSIONS: Clinical suspicion for transfusion-related adverse events, including hemolytic transfusion reactions and transfusion-transmitted infections, should be high in typically and atypically immunocompromised patient populations (like SCD), especially those on chronic transfusion protocols. Manual blood smear review aids in the evaluation of patients with SCD presenting with severe vaso-occlusive crisis and MSOF and can alert clinicians to the need for initiating aggressive therapy like RBC exchange and artesunate therapy.

A systematic review of transfusion-transmitted malaria in non-endemic areas.

BACKGROUND: Transfusion-transmitted malaria (TTM) is an accidental Plasmodium infection caused by whole blood or a blood component transfusion from a malaria infected donor to a recipient. Infected blood transfusions directly release malaria parasites in the recipient's bloodstream triggering the development of high risk complications, and potentially leading to a fatal outcome especially in individuals with no previous exposure to malaria or in immuno-compromised patients. A systematic review was conducted on TTM case reports in non-endemic areas to describe the epidemiological characteristics of blood donors and recipients. METHODS: Relevant articles were retrieved from Pubmed, EMBASE, Scopus, and LILACS. From each selected study the following data were extracted: study area, gender and age of blood donor and recipient, blood component associated with TTM, Plasmodium species, malaria diagnostic method employed, blood donor screening method, incubation period between the infected transfusion and the onset of clinical symptoms in the recipient, time elapsed between the clinical symptoms and the diagnosis of malaria, infection outcome, country of origin of the blood donor and time of the last potential malaria exposure. RESULTS: Plasmodium species were detected in 100 TTM case reports with a different frequency: 45% Plasmodium falciparum, 30% Plasmodium malariae, 16% Plasmodium vivax, 4% Plasmodium ovale, 2% Plasmodium knowlesi, 1% mixed infection P. falciparum/P. malariae. The majority of fatal outcomes (11/45) was caused by P. falciparum whilst the other fatalities occurred in individuals infected by P. malariae (2/30) and P. ovale (1/4). However, non P. falciparum fatalities were not attributed directly to malaria. The incubation time for all Plasmodium species TTM case reports was longer than what expected in natural infections. This difference was statistically significant for P. malariae (p = 0.006). A longer incubation time in the recipient together with a chronic infection at low parasite density of the donor makes P. malariae a subtle but not negligible risk for blood safety aside from P. falciparum. CONCLUSIONS: TTM risk needs to be taken into account in order to enhance the safety of the blood supply chain from donors to recipients by means of appropriate diagnostic tools.

Comparison of three blood transfusion guidelines applied to 31 feline donors to minimise the risk of transfusion-transmissible infections.

Objectives The increased demand for animal blood transfusions creates the need for an adequate number of donors. At the same time, a high level of blood safety must be guaranteed and different guidelines (GLs) deal with this topic. The aim of this study was to evaluate the appropriateness of different GLs in preventing transfusion-transmissible infections (TTI) in Italian feline blood donors. Methods Blood samples were collected from 31 cats enrolled as blood donors by the owners' voluntary choice over a period of approximately 1 year. Possible risk factors for TTI were recorded. Based on Italian, European and American GLs, specific TTI, including haemoplasmas, feline leukaemia virus (FeLV), feline immunodeficiency virus (FIV), Anaplasma phagocytophilum, Ehrlichia species, Bartonella species, Babesia species, Theileria species, Cytauxzoon species, Leishmania donovani sensu lato and feline coronavirus (FCoV), were screened. Rapid antigen and serological tests and biomolecular investigations (PCR) were used. Several PCR protocols for haemoplasma and FeLV DNA were compared. Results The presence of at least one recognised risk factor for TTI was reported in all cats. Results for FIV and FeLV infections were negative using rapid tests, whereas five (16.1%) cats were positive for FCoV antibodies. Four (12.9%) cats were PCR positive for haemoplasma DNA and one (3.2%) for FeLV provirus, the latter being positive only using the most sensitive PCR protocol applied. Other TTI were not detected using PCR. Conclusions and relevance Blood safety increases by combining the recommendations of different GLs. To reduce the risk of TTI, sensitive tests are needed and the choice of the best protocol is a critical step in improving blood safety. The cost and time of the screening procedures may be reduced if appropriate tests are selected. To this end, the GLs should include appropriate recruitment protocols and questionnaire-based risk profiles to identify suitable donors.

Silent killers: Transfusion Transmissible Infections-TTI, among asymptomatic population of Pakistan.

OBJECTIVE: To analyse transfusion transmissible infections in asymptomatic population. METHODS: This study was conducted at the Allama Iqbal Medical College and Jinnah Hospital, Lahore, Pakistan, from December 2014 to November 2015, and comprised healthy asymptomatic blood donors.Every sample was screened for the presence of antibodies/antigens of hepatitis C virus, human immunodeficiency virus, treponemapallidum, hepatitis B virus and malaria parasite through rapid immunochromatographic technique. RESULTS: Of the 18,274 blood donors, 17,276(94.53%) were found healthy and 998(5.46%) were infected. Besides, 71(0.38%) had multiple infections. The overall frequency of anti-hepatitis C virus, treponemapallidum (syphilis), hepatitis B surface antigen, malaria parasite and anti-human immunodeficiency virus was 480(2.62%), 284(1.55%), 210(1.10%), 20(0.10%) and 4(0.02%), respectively. CONCLUSIONS: Blood transfusion was found to be a significant but preventable mode of spread of transfusion transmissible infections.

[(INDUCED MALARIA)].

Induced malaria continues to be one of the most pressing public health problems in malaria-endemic countries. Ma- laria parasites remain viable in stored blood at a temperature of 2-6°C for 3 weeks. The paper presents current problems associated with transfusion-induced malaria. In the USSR and then in the Russian Federation, sporadic cases of induced malaria (Plasniodium vivax, P.malariae, rarely P.falciparum) were notified (230 cases in 1958 to 1990 and only 5 in 1991 to 2016). Current (immunological and molecular) methods for the laboratory diagnosis of malaria do not provide a 100% detection rMfteor its pathogens; therefore, it is necessary to search for highly efficient, rapid, and low-cost diagnostic methods to ensure the biological safety of donation.