Deferral for travel to malaria-endemic areas excludes many blood donors in the United States. Most transfusion-transmitted malaria is associated with lengthy residence in malaria-endemic areas rather than routine travel. This study compares the impact of existing deferral requirements to the risk that a presenting donor with malaria travel history harbors malaria parasites under current and hypothetical alternate regulations.
STUDY DESIGN AND METHODS
Deferred donors from six blood centers were sampled to estimate a national cohort of donors deferred annually for malaria travel to different geographic regions. Risk for malaria infection following travel to each region, and distribution of incubation periods for each malaria species were estimated for U.S. travelers. Region-specific travel risks were used to estimate the risk that a presenting blood donor with malaria travel might asymptomatically harbor malaria parasites at different intervals following return to the United States.
Travel to Africa presents risk for malaria infection >1000 times that of travel to malaria-endemic parts of Mexico, yet Mexico accounts for >10 times as many deferred donors. Shortening the deferral period from 12 to 3 months for travelers to Mexico increases the risk of collecting a contaminated unit by only 1 unit per 57 years (sensitivity analysis, 1 every 29 - 114 years), at annual gain of >56,000 donations.
This study provides the first systematic appraisal of the U.S. requirements for donor qualification regarding travel to malarial areas. Consideration should be given to relaxing the guidelines for travel to very low-risk areas such as Mexico.
Plasmodium; malaria; blood donor; deferral; malaria travel; transfusion transmitted disease
Policies concerning the prevention of transfusion transmitted malaria (TTM) are the responsibility of blood transfusion services and malaria control programmes. To prevent spreading drug resistance due to over-use of malaria drugs, recent malaria treatment guidelines recommend prompt parasitological confirmation before treatment is started. In contrast, blood safety policies from the World Health Organisation (WHO) recommend presumptive malaria treatment for recipients of blood in endemic countries but evidence supporting this approach is lacking. Our study documented how these conflicting policies relating to malaria transmission through blood transfusion impact on clinical practice in a teaching hospital in West Africa.
We randomly selected and reviewed case notes of 151 patients within 24 hours of their receiving a blood transfusion. Transfusion practices including the confirmation of diagnosis and anti-malarial treatment given were compared across three departments; Obstetrics and Gynaecology (O&G), Paediatrics and Medicine. Overall, 66 (44%) of patients received malaria treatment within 24 hrs of their blood transfusion; of which only 2 (3%) received anti-malarials based on a laboratory confirmation of malaria. Paediatric patients (87%) received the most anti-malarials and only 7% and 24% of recipients in medicine and O&G respectively received anti malarials. In 51 patients (78%), the anti-malarials were prescribed at the same time as the blood transfusion and anti-malarials prescriptions exceeded the number of patients with a presumptive diagnosis of malaria.
It is common practice in paediatrics to prescribe anti-malarials routinely with blood transfusions. This contravenes the malaria treatment guidelines of laboratory confirmation before treatment but is in accordance with the less-well evidenced blood safety guidelines. There is an urgent need for more evidence about the clinical impact of transfusion transmitted malaria to enable malaria and blood transfusion programmes to harmonize their policies and give clear guidance to clinicians who prescribe blood transfusions in malaria-endemic areas
Transfusion Transmitted Infection (TTI) continue to be a problem in many parts of world and multi-transfused patients of beta thalassaemia major are at a particularly increased risk of TTI. This study is aimed to estimate the prevalence of blood TTI in multiple blood transfused patients of beta thalassaemia major. Cross-sectional study of 200 multi-transfused patients of beta thalassaemia major, who were interviewed using a structured questionnaire and history was taken regarding sero-status of HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus) infection from their case papers. This study was conducted at the department of Pathology, M.P. Shah medical college, Jamnagar and Thalassemia ward, G.G. Hospital, Jamnagar (Gujarat, India) from March to May 2010. Out of 200 multiple blood transfused patients 7% patients were infected with TTI. Total 9 male patients and 5 female patients were infected with TTI. The seroreactivity for HIV was 3% (06/200); 1% (02/200) were males and 2% (04/200) were females. The seroreactivity for HBV was 2% (04/200) all were males. The seroreactivity for HCV was 2% (04/200); 1.5% (03/200) were males and 0.5% (01/200) was female. HIV, HBV, HCV infections are most prevalent TTI among multiple blood transfused patients of beta thalassemia major, and remains a major health problem for these patients.
Transfusion transmitted infection; Multiple blood transfused patients of beta thalassemia major; Human immunodeficiency virus; Hepatitis B virus; Hepatitis C virus
Current European regulations require a deferral period of 6 months or 3 years, depending on the risk of exposure, for prospective blood donors at risk of malaria. This period may be reduced to 4 months if an immunological or molecular genomic test is negative at each donation, but Italian regulations have not adopted this provision. As cases of transfusion-transmitted malaria have been recorded in medical literature in blood donors deferred for 3 years and not tested, the Immunohaematology and Transfusion Centre of the Ca’ Grande Polyclinic Hospital in Milan decided to introduce immunological testing for all donors at risk of malaria.
Materials and methods.
Four hundred and twelve blood donors at risk of malaria, who had lived in a malarial area during the first 5 years of life or for more than 6 consecutive months, were tested for malarial antibodies using an enzyme immunoassay kit. The kit (Malaria EIA, Newmarket, UK) uses four recombinant antigens specific for P. falciparum and P. vivax and with cross-reactivity for P. ovale and P. malariae. The kit detects total immunoglobulin antibodies against P. falciparum and P. vivax and shows 80% cross-reactivity with P. ovale and 67% with P. malariae. Antibody-positive samples were further checked by an immunochromatographic test for P. falciparum, P. vivax, P. ovale and P. malariae antigens and by haemoscopy (thin film and thick smear).
Italian citizens accounted for 16.8% (69/412) of the whole group of donors examined. We found that 8.7% of the donors who were classified as being at risk of malaria were positive for total immunoglobulin antibodies. Only one Italian citizen resulted positive for the test. The positive candidates were deferred from blood donation. None of the antibody-positive donors was confirmed positive by the immunochromatographic test and by haemoscopy.
The introduction of a malarial screening test in the assessment of blood donor eligibility may increase the safety of blood donations, but could further reduce blood availability. If immunological testing were to be accepted nationally as a valid method of assessing the risk of malaria, more than 90% of the donors who are currently deferred for 3 years could be accepted 4 months after their last visit to an endemic area, thus increasing the availability of blood
transfusion-transmitted malaria; enzyme immunoassay; donor’s risk
About 90% of all malaria deaths in sub-Saharan Africa occur in children under five years. Fast and reliable diagnosis of malaria requires confirmation of the presence of malaria parasites in the blood of patients with fever or history suggestive of malaria; hence a prompt and accurate diagnosis of malaria is the key to effective disease management. Confirmation of malaria infection requires the availability of a rapid, sensitive, and specific testing at an affordable cost. We compared two recent methods (the novel Partec Rapid Malaria Test® (PT) and the Binax Now® Malaria Rapid Diagnostic Test (BN RDT) with the conventional Giemsa stain microscopy (GM) for the diagnosis of malaria among children in a clinical laboratory of a hospital in a rural endemic area of Ghana.
Blood samples were collected from 263 children admitted with fever or a history of fever to the pediatric clinic of the Agogo Presbyterian Hospital. The three different test methods PT, BN RDT and GM were performed independently by well trained and competent laboratory staff to assess the presence of malaria parasites. Results were analyzed and compared using GM as the reference standard.
In 107 (40.7%) of 263 study participants, Plasmodium sp. was detected by GM. PT and BN RDT showed positive results in 111 (42.2%) and 114 (43.4%), respectively. Compared to GM reference standard, the sensitivities of the PT and BN RDT were 100% (95% CI: 96.6-100) and 97.2% (95% CI: 92.0-99.4), respectively, specificities were 97.4% (95% CI: 93.6-99.3) and 93.6% (95% CI: 88.5-96.9), respectively. There was a strong agreement (kappa) between the applied test methods (GM vs PT: 0.97; p < 0.001 and GM vs BN RDT: 0.90; p < 0.001). The average turnaround time per tests was 17 minutes.
In this study two rapid malaria tests, PT and BN RDT, demonstrated a good quality of their performance compared to conventional GM. Both methods require little training, have short turnaround times, are applicable as well as affordable and can therefore be considered as alternative diagnostic tools in malaria endemic areas. The species of Plasmodium cannot be identified.
Transfusion-associated hepatitis B viral infection continues to be a major problem in India even after adoption of mandatory screening for HBsAg by ELISA method. The high incidence of TAHBV is reported in patients receiving multiple transfusions.
To study the seroprevalence of hepatitis B core antibody among healthy voluntary blood donors
Subjects and Methods
The study was conducted in the department of Transfusion Medicine of a tertiary care referral hospital. A total of 12,232 volunteers after passing through the stringent criteria were selected for blood donation. Donor samples were tested for all mandatory transfusion transmissible infections and anti HBc IgM (Monolisa HBc IgM PLUS:BIO-RAD, France). Reactive results were confirmed by repeat testing in duplicate. Donor data was analyzed using SPSS software and Chi-square test was used to calculate the significance of difference between the groups.
A total of 12,232 healthy voluntary blood donors were recruited. Majority (93.4%) were males. Median age of donor population was 26 years (range: 18–60 years). Eighty six (0.7%) were positive for HBsAg, which comes under “low prevalence (<2%) zone” as per WHO. On screening for HBcAg Ig M, 15 (0.1%) were found to be positive and none were HBsAg reactive. There was no significance of difference in the mean age between reactive and non-reactive donors.
Evaluating the usefulness of anti-HBc screening is critical. Anti HBcAg IgM screening may be included in routine screening of donors as it is an indicator of occult HBV during window period. The cost and the unnecessary wastage of the blood units when they are positive for anti HBsAg along with the core antibody need to be studied.
Background and Objective:
Hepatitis B and hepatitis C are significant health problems that might involve the late sequel of liver cirrhosis and hepatocellular carcinoma. A high prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in blood donors poses an increased risk of window period transmission through blood transfusion. The present study aimed to know the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) among blood donors in regional blood transfusion services of Nepal.
Materials and Methods:
This was a retrospective study conducted among blood donors in Banke (5,211), Morang (5,351), and Kaski (5,995) blood transfusion services. Serum samples were tested for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies using rapid enzyme immunoassays. The donors information was collected via the donor record register through their respective blood transfusion services. The software “Winpepi ver 3.8” was used for statistical analysis.
The seroprevalence rate of HBV was highest in the Banke (1.2%) followed by Biratnagar (0.87%) and Kaski (0.35%) (P < 0.0001). The seroprevalence of HCV was highest in the Morang (0.26%) followed by Kaski (0.16%) and Banke (0.11%) (P > 0.05). The seroprevalence of HBV was significantly higher than HCV in all three blood transfusion services. The burden of HBV as well as HCV seems to be higher in male donors (P > 0.05).
The study revealed that the seroprevalence of HBV was alarmingly higher in two of the three blood transfusion services. Implementation of community-based preventive measures and improved strategies for safe blood supply might prove useful to decrease the seroprevalence.
Blood donors; hepatitis B virus; hepatitis C virus; Nepal; seroprevalence
The World Health Organization recommends parasitological confirmation of all malaria cases. Tanzania is implementing a phased rollout of malaria rapid diagnostic tests (RDTs) for routine use in all levels of care as one strategy to increase parasitological confirmation of malaria diagnosis. This study was carried out to evaluated artemisinin combination therapy (ACT) prescribing patterns in febrile patients with and without uncomplicated malaria in one pre-RDT implementation and one post-RDT implementation area.
A cross-sectional health facility surveys was conducted during high and low malaria transmission seasons in 2010 in both areas. Clinical information and a reference blood film on all patients presenting for an initial illness consultation were collected. Malaria was defined as a history of fever in the past 48 h and microscopically confirmed parasitaemia. Routine diagnostic testing was defined as RDT or microscopy ordered by the health worker and performed at the health facility as part of the health worker-patient consultation. Correct diagnostic testing was defined as febrile patient tested with RDT or microscopy. Over-testing was defined as a non-febrile patient tested with RDT or microscopy. Correct treatment was defined as patient with malaria prescribed ACT. Over-treatment was defined as patient without malaria prescribed ACT.
A total of 1,247 febrile patients (627 from pre-implementation area and 620 from post-implementation area) were included in the analysis. In the post-RDT implementation area, 80.9% (95% CI, 68.2-89.3) of patients with malaria received recommended treatment with ACT compared to 70.3% (95% CI, 54.7-82.2) of patients in the pre-RDT implementation area. Correct treatment was significantly higher in the post-implementation area during high transmission season (85.9% (95%CI, 72.0-93.6) compared to 58.3% (95%CI, 39.4-75.1) in pre-implementation area (p = 0.01). Over-treatment with ACT of patients without malaria was less common in the post-RDT implementation area (20.9%; 95% CI, 14.7-28.8) compared to the pre-RDT implementation area (45.8%; 95% CI, 37.2-54.6) (p < 0.01) in high transmission. The odds of overtreatment was significantly lower in post- RDT area (adjusted Odds Ratio (OR: 95%CI) 0.57(0.36-0.89); and much higher with clinical diagnosis adjusted OR (95%CI) 2.24(1.37-3.67)
Implementation of RDTs increased use of RDTs for parasitological confirmation and reduced over-treatment with ACT during high malaria transmission season in one area in Tanzania. Continued monitoring of the national RDT rollout will be needed to assess whether these changes in case management practices will be replicated in other areas and sustained over time. Additional measures (such as refresher trainings, closer supervisions, etc.) may be needed to improve ACT targeting during low transmission seasons.
Malaria rapid diagnostic tests; ACT; HDSS; INDEPTH network; Tanzania
Cytomegalovirus (CMV) is one of the most significant pathogens infecting immunosuppressed individuals. CMV is transmissible through transfusion of blood components.
The goal of this study was to determine the seroprevalence of antibodies to CMV among blood donors seen at the 37 Military Hospital Blood Transfusion Unit, (MHBTU) Accra, Ghana.
The seroprevalence of antibodies specific for CMV was tested using CMV IgG/IgM particle agglutination test kit and ELISA.
Of the 264 blood donors, 18 were negative and 246 were positive for CMV IgG antibodies, giving an overall CMV prevalence rate of 93.2%. None of the 264 blood donors was positive for CMV IgM antibodies. About 96% of the donors aged between 30 to 39 years were seropositive for CMV, as against 91.9% in those aged 20–29 years, 88.6% in 40 to 49 years, 75.0% (3 out of 4) in 50 to 59 years, and 100% (1 out 1) in 60–69 years. There was no statistically significant difference (P>0.05) in the CMV IgG status in different age groups. The blood donors comprised largely of male donors (236 out of 264), making sex comparisons statistically undesirable. However, all the female (n=28) donors were positive for CMV IgG.
Since about 93% of blood donors at the MHBTU are seropositive for CMV, it would be very useful to screen blood donors in Ghana for CMV to identify the very few CMV-seronegative blood donors, and maintain an inventory of them for use as donors.
Cytomegalovirus; blood donors; seroprevalence
In this position paper, the European Society for Clinical Microbiology and Infectious Diseases, Study Group on Clinical Parasitology, summarizes main issues regarding the management of imported malaria cases. Malaria is a rare diagnosis in Europe, but it is a medical emergency. A travel history is the key to suspecting malaria and is mandatory in patients with fever. There are no specific clinical signs or symptoms of malaria although fever is seen in almost all non-immune patients. Migrants from malaria endemic areas may have few symptoms.
Malaria diagnostics should be performed immediately on suspicion of malaria and the gold- standard is microscopy of Giemsa-stained thick and thin blood films. A Rapid Diagnostic Test (RDT) may be used as an initial screening tool, but does not replace urgent microscopy which should be done in parallel. Delays in microscopy, however, should not lead to delayed initiation of appropriate treatment. Patients diagnosed with malaria should usually be hospitalized. If outpatient management is preferred, as is the practice in some European centres, patients must usually be followed closely (at least daily) until clinical and parasitological cure. Treatment of uncomplicated Plasmodium falciparum malaria is either with oral artemisinin combination therapy (ACT) or with the combination atovaquone/proguanil. Two forms of ACT are available in Europe: artemether/lumefantrine and dihydroartemisinin/piperaquine. ACT is also effective against Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi, but these species can be treated with chloroquine. Treatment of persistent liver forms in P. vivax and P. ovale with primaquine is indicated after excluding glucose 6 phosphate dehydrogenase deficiency. There are modified schedules and drug options for the treatment of malaria in special patient groups, such as children and pregnant women. The potential for drug interactions and the role of food in the absorption of anti-malarials are important considerations in the choice of treatment.
Complicated malaria is treated with intravenous artesunate resulting in a much more rapid decrease in parasite density compared to quinine. Patients treated with intravenous artesunate should be closely monitored for haemolysis for four weeks after treatment. There is a concern in some countries about the lack of artesunate produced according to Good Manufacturing Practice (GMP).
To evaluate the rate of seropositivity to hepatitis B and C and Human Immunodeficiency Virus (HIV) infections among children with β-thalassemia major receiving multiple transfusions in Ahmedabad, India, compared with healthy controls.
Materials and Methods:
The study was performed during January 2007 to January 2009 on multi-transfused children suffering with β-thalassemia major registered in the Prathama Blood Centre, Ahmedabad; Jeevandeep hospital, Ahmedabad; and Red Cross Blood Centre, Ahmedabad, and investigated for the prevalence and development of transfusion-transmitted infections. Hepatitis B surface Antigen (HBsAg), anti-Hepatitis C Virus (HCV) Antibodies (Ab), and HIV Ab were checked using a fourth-generation Enzyme-Linked Immunosorbent Assay (ELISA). Positive tests were confirmed by western blots. Healthy blood donors were used for the control group.
Hepatitis B surface antigen, anti-HCV Ab, and HIV Ab were positive in one of 96 (1.04%; 95% Confidence Interval (CI) = 0.17–1.3), 24 of 96 (25%; 95% CI = 11.4–14.2), and one of 96 (1.04%; 95% CI = 0.12–1.3), respectively. The rate of anti-HCV Ab was significantly higher in multi-transfused children suffering with β-thalassemia major. In thalassemia patients, the rate of positive anti-HCV Ab was significantly higher than that for positive HBsAg (P<0.001) and HIV Ab (P<0.001).
It is concluded that HCV is the current major problem in multi-transfused children with thalassemia major and more careful pretransfusion screening of blood for anti-HCV must be introduced in blood centers.
Hepatitis B; hepatitis C; Human immunodeficiency virus; β-thalassemia major; seroprevalence
Human parvovirus B19 (B19) virus is a newly recognized agent for transfusion transmitted diseases. Beta-thalassemia major patients receive a hypertransfusion regimen, hence, are prone to acquire B19 infection; moreover, B19 escapes viral inactivation methods and donor units are not tested for B19, but there are just a couple of studies globally and none from the Asian continent. Hence, a study was designed to find the frequency of B19 infection and its transmission in multitransfused thalassemia patients.
Materials and Methods:
Ninety multitransfused beta-thalassemia major (thalassemia) patients, 32 controls (age, sex matched) without any history of transfusion were enrolled. Besides the donor units were tested in B19 un-infected patients. B19 specific IgG and IgM antibodies in the sera were analyzed by ELISA (in-house), using B19 VPI and VP2 recombinant and purified antigens; additionally HBsAg and anti-HIV and anti-HCV antibodies were tested for coexisting infections.
Seventy-three (81%) thalassemia patients tested positive for anti-B19 IgG antibodies as compared to seven (21%) in the controls group (P < 0.01), while anti-B19 IgM antibodies were detected in 37 (41.1%) compared to two (6.2%) in the controls (P < 0.01). Mean age of the thalassemia patient was eight years (range 2 – 18 years) and B19 infection was highest in the six-to-ten year range. Seropositivity increased with the number of transfusions. Two of the four HBsAg positive and five of the seven anti-HCV IgM antibody-positive patients also had anti-B19 IgM. After a six-month follow-up, four (25%) of the 16 seronegative patients seroconverted and anti-B19 IgM antibodies were detected in their donor units.
Most of multitransfused thalassemics were B19 seropositive or had anti-B19 IgM; in the remaining uninfected group, B19 got transmitted through infected / IgM-positive donor units.
B19; blood transfusion; parvovirus; seroconversion; thalassemia
Antibodies to human leukocyte antigens (HLA) in donated blood have been implicated as a cause of transfusion related acute lung injury (TRALI). A potential measure to reduce the risk of TRALI includes screening platelet apheresis donors for HLA antibodies. The prevalence of HLA antibodies and their relationship to previous transfusion or pregnancy in blood donors was determined.
Study design and methods
8171 volunteer blood donors were prospectively recruited by 6 U.S. blood centers from December 2006 to May 2007. Donors provided a detailed history of pregnancy and transfusion, and a sample for HLA class I and II antibody testing by multi-antigen bead flow analysis.
8171 donors were enrolled, 7920 (96.9%) had valid HLA antibody test results and 7841(99%) of those had complete pregnancy and transfusion information. The prevalence of any HLA antibody was similar in non-transfused (n=1138) and transfused (n=895) men, 1.0 vs. 1.7% (p=0.16). HLA antibodies were detected in 17.3% of all female donors (n=5834) and in 24.4 % of those with a history of previous pregnancy (n=3992). The prevalence of HLA antibodies increased in women with greater numbers of pregnancy: 1.7%(zero), 11.2%(one), 22.5%(two), 27.5%(three) and 32.2%(four or more pregnancies), p<0.0001.
HLA class I and class II antibodies are detectable at low prevalence in male donors regardless of transfusion and in female donors without known immunizing events. The prevalence of HLA antibodies increases significantly with more pregnancies. These data will allow blood centers to estimate the impact of HLA antibody testing as a potential TRALI risk-reduction measure.
HLA antibody; pregnancy; transfusion; transfusion related acute lung injury
Induced malaria by blood transfusion is a potential health hazard but is often neglected in many malaria endemic areas. Standard parasitological technique was used to determine the prevalence of malaria among blood donors in the South-eastern Nigeria. Of the total 325 blood donors (310 males and 15 females) screened, 133 (40.9%, CI 95%: 35.6–46.2%) were infected with malaria parasite, 78 (58.6%) had 1–10 parasites per 100 thick film fields (‘+’ or 4–40 parasites per mm3) while 55 (41.4%) had 11–100 parasites per 100 thick film fields (‘++’ or 41–400 parasites per mm3). P. falciparum was identified in all the infected cases, however 3 (2.3%) persons had mixed infection with P. malariae. Males were more infected (41.3%, CI 95%: 35.8–46.8%) than females (33.3%, CI 95%: 9.4–57.2%). The infection decreased with age with highest prevalence of 48.5% among those aged 20–25 years. The infection significantly varied with age but not with sex (P<0.05). Individuals with blood group B were slightly more infected (42.1%, 95%CI., 19.6–64.6%) than those of groups O (41.0%,CI 95%: 35.3–46.7%) and A (40.0%, CI 95%: 20.8–59.2%) but there was no significant difference (P < 0.05). Highest prevalence of infection was recorded in the month of April corresponding to the onset of the wet season. An overhaul of existing blood donation policies in many health facilities in the sub-Saharan Africa to incorporate malaria screening is advocated. Curative antimalarial drugs followed by prophylactic drugs should be given to all recipients of Parasitized blood.
Blood donor; malaria; Plasmodium falciparum; infection; prevalence; blood group
When selecting blood donors in transfusion centres, one important problem is to identify, during screening, individuals with infectious diseases that can be transmitted by blood, such as malaria, especially when the parasite densities are very low. This problem is particularly severe in endemic areas, such as the Brazilian Amazon. In the present study, molecular diagnostic (real-time PCR) of Plasmodium vivax was used to identify blood donors infected with malaria parasites.
Samples from 595 blood donors were collected in seven haemotherapy centres in northern Brazil located in areas at risk for malaria transmission, and the analyses were performed by real-time PCR with TaqMan probes on 7500 Real-Time PCR Systems, to genotype the mitochondrial DNA region specific to P. vivax. The experiment was designed for hybridization of the cytochrome c oxidase genes of the mitochondrial genome (GenBank GI63022502). The serological data were obtained using enzyme-linked immunosorbent assay - ELISA (Anti-HIV, Anti-HTLV I-II; Anti-HVC, HBsAg, Anti-HBc, Chagas disease) and VDRL (Syphilis) from the Blood Bank System of the Haematology and Haemotherapy Centre of Pará.
The assay identified eight individuals in the sample (1.34%) infected with P. vivax at the time of blood donation. This percentage was higher than the altered serological results (reactive or inconclusive) of the prevalence of anti-HIV (0.67%), anti-hepatitis C virus (0.34%), anti-hepatitis B surface antigen (0.67%), anti-human T-lymphotropic virus I/II (1.18%), anti-Chagas disease (0.17%) and syphilis (VDRL) (0.50%), but not higher than anti-hepatitis B core antigen antibodies (4.37%). This result indicates the need to use more sensitive methods of diagnosing malaria in blood banks.
The real-time PCR with TaqMan probes enabled the identification of P. vivax in a high proportion of clinically healthy donors, highlighting the potential risk for transfusion-transmitted malaria. Additionally, this molecular diagnostic tool can be adopted as a new laboratory screening method in haemotherapy centres, especially in malaria-endemic areas.
Malaria; Molecular diagnostic; Plasmodium vivax; Blood donors
Despite low endemicity, malaria remains a major health problem in urban areas where a high proportion of fevers are presumptively treated using anti-malarial drugs. Low acquired malaria immunity, behaviour of city-dwellers, access to health care and preventive interventions, and heterogenic suitability of urban ecosystems for malaria transmission contribute to the complexity of the malaria epidemiology in urban areas.
The study was designed to identify the determinants of malaria transmission estimated by the prevalence of anti-circumsporozoite (CSP) antibodies, the prevalence and density of Plasmodium falciparum infection, and the prevalence of malarial disease in areas of Ouagadougou, Burkina-Faso. Thick blood smears, dried blood spots and clinical status have been collected from 3,354 randomly chosen children aged 6 months to 12 years using two cross-sectional surveys (during the dry and rainy seasons) in eight areas from four ecological strata defined according to building density and land tenure (regular versus irregular). Demographic characteristics, socio-economic information, and sanitary and environmental data concerning the children or their households were simultaneously collected. Dependent variables were analysed using mixed multivariable models with random effects, taking into account the clustering of participants within compounds and areas.
Overall prevalences of CSP-antibodies and P. falciparum infections were 7.7% and 16.6% during the dry season, and 12.4% and 26.1% during the rainy season, respectively, with significant differences according to ecological strata. Malaria risk was significantly higher among children who i) lived in households with lower economic or education levels, iii) near the hydrographic network, iv) in sparsely built-up areas, v) in irregularly built areas, vi) who did not use a bed net, vii) were sampled during the rainy season or ii) had traveled outside of Ouagadougou.
Malaria control should be focused in areas which are irregularly or sparsely built-up or near the hydrographic network. Furthermore, urban children would benefit from preventive interventions (e.g. anti-vectorial devices or chemoprophylaxis) aimed at reducing malaria risk during and after travel in rural areas.
The transmission of parasitic organisms through transfusion is relatively rare. Of the major transfusion-transmitted diseases, malaria is a major cause of TTIP in tropical countries whereas babesiosis and Chagas’ disease pose the greatest threat to donors in the USA In both cases, this is due to the increased number of potentially infected donors. There are no reliable serologic tests available to screen donors for any of these organisms and the focus for prevention remains on adherence to donor screening guidelines that address travel history and previous infection with the etiologic agent. One goal is the development of tests that are able to screen for and identify donors potentially infectious for parasitic infections without causing the deferral of a large number of non-infectious donors or significantly increasing costs. Ideally, methods to inactivate the infectious organism will provide an element of added safety to the blood supply.
Parasites; transfusion; transmitted
Approximately 3.2 billion people live in areas where malaria is endemic, and WHO estimates that 350 to 500 million malaria cases occur each year worldwide. This high prevalence, and the high frequency of international travel, creates significant risk for the exportation of malaria to countries where malaria is not endemic and for the introduction of malaria organisms into the blood supply. Since all four human infectious Plasmodium species have been transmitted by blood transfusion, we sought to develop an enzyme-linked immunosorbent assay (ELISA) capable of detecting antibodies elicited by infection with any of these species. The merozoite surface protein 1 (MSP1), a P. falciparum and P. vivax vaccine candidate with a well-characterized immune response, was selected for use in the assay. The MSP1 genes from P. ovale and P. malariae were cloned and sequenced (L. Birkenmeyer, A. S. Muerhoff, G. Dawson, and S. M. Desai, Am. J. Trop. Med. Hyg. 82:996-1003, 2010), and the carboxyl-terminal p19 regions of all four species were expressed in Escherichia coli. Performance results from individual p19 ELISAs were compared to those of a commercial test (Lab 21 Healthcare Malaria enzyme immunoassay [EIA]). The commercial ELISA detected all malaria patients with P. falciparum or P. vivax infections, as did the corresponding species-specific p19 ELISAs. However, the commercial ELISA detected antibodies in 0/2 and 5/8 individuals with P. malariae and P. ovale infections, respectively, while the p19 assays detected 100% of individuals with confirmed P. malariae or P. ovale infections. In experimentally infected nonhuman primates, the use of MSP1-p19 antigens from all four species resulted in the detection of antibodies within 2 to 10 weeks postinfection. Use of MSP1-p19 antigens from all four Plasmodium species in a single immunoassay would provide significantly improved efficacy compared to existing tests.
HLA antibody testing of previously transfused or pregnant donors may help reduce the risk of transfusion-related acute lung injury (TRALI). However, the prevalence of HLA antibodies in transfused donors has not been well characterized.
Transfusion and pregnancy history was obtained from consenting donors. HLA Class I & II antibody testing was performed by multi-antigen bead Luminex platform. Cut off values for class I & II antibodies used normalized background ratio of 10.8 and 6.9 respectively. Linear probability models were used to evaluate potential associations between HLA alloimmunization and donor characteristics.
7,920 donors (2,086 males and 5,834 females) were tested. HLA antibody prevalence did not significantly differ between 895 transfused (1.7%) and 1138 non-transfused males (1.0%), [odds ratio (OR) 1.75; 95% CI 0.80, 3.82]. Prevalence in 45 transfused nulliparous females (4.4%, 95% CI 0.1%, 11.8%) was not statistically different from the 1.6% prevalence in 1732 non-transfused nulliparous females (odds ratio 2.94, 95% CI 0.68, 12.74). Transfused parous females had higher prevalence than non-transfused counterparts (p=0.004), odds ratio 1.39 (95% CI 1.07, 1.80). In a linear probability model, the estimated additive risk of transfusion-induced alloimmunization was only 0.8% (95% CI -0.2%, 1.8%), (p=0.10). Donor transfusion history showed that 58% of transfusions occurred >10 years previously.
Transfused volunteer blood donors do not appear to have a significantly higher prevalence of HLA antibodies than their non-transfused counterparts. Thus, in an effort to reduce TRALI risk, ascertaining past history of transfusion and testing these donors for HLA antibodies is not necessary.
The National Blood Policy in India relies heavily on voluntary blood donors, as they are usually assumed to be associated with low levels of transfusion‐transmitted infections (TTIs). In India, it is mandatory to test every unit of blood collected for hepatitis B, hepatitis C, HIV/AIDS, syphilis and malaria. Donors come to the blood bank with altruistic intentions. If donors test positive to any of the five infections, their blood is discarded. Although the blood policy advocates disclosure of TTI status, donors are not, in practice, informed about their results. The onus is on the donor to contact the blood bank. Out of approximately 16 000 donations in the past 2 years, 438 tested positive for TTI, including 107 for HIV. Only 20% of the donors contacted the blood bank; none of them were HIV positive. Disclosure by blood banks of TTI status by telephone or mail has resulted in serious consequences for some donors. Health providers face an ethical dilemma, in the absence of proper mechanisms in place for disclosure of test results, regarding notification to donors who may test positive but remain ignorant of their TTI status. Given the high cost of neglecting to notify infected donors, the authors strongly recommend the use of rapid tests before collecting blood, instead of the current practice, which takes 3 h to obtain results, and disclosure of results directly to the donor by a counsellor, to avoid dropouts and to ensure confidentiality.
Prompt, accurate diagnosis and treatment with artemisinin combination therapy remains vital to current malaria control. Blood film microscopy the current standard test for diagnosis of malaria has several limitations that necessitate field evaluation of alternative diagnostic methods especially in low income countries of sub-Saharan Africa where malaria is endemic.
The accuracy of axillary temperature, health centre (HC) microscopy, expert microscopy and a HRP2-based rapid diagnostic test (Paracheck) was compared in predicting malaria infection using polymerase chain reaction (PCR) as the gold standard. Three hundred patients with a clinical suspicion of malaria based on fever and or history of fever from a low and high transmission setting in Uganda were consecutively enrolled and provided blood samples for all tests. Accuracy of each test was calculated overall with 95% confidence interval and then adjusted for age-groups and level of transmission intensity using a stratified analysis. The endpoints were: sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). This study is registered with Clinicaltrials.gov, NCT00565071.
Of the 300 patients, 88(29.3%) had fever, 56(18.7%) were positive by HC microscopy, 47(15.7%) by expert microscopy, 110(36.7%) by Paracheck and 89(29.7%) by PCR. The overall sensitivity >90% was only shown by Paracheck 91.0% [95%CI: 83.1-96.0]. The sensitivity of expert microscopy was 46%, similar to HC microscopy. The superior sensitivity of Paracheck compared to microscopy was maintained when data was stratified for transmission intensity and age. The overall specificity rates were: Paracheck 86.3% [95%CI: 80.9-90.6], HC microscopy 93.4% [95%CI: 89.1-96.3] and expert microscopy 97.2% [95%CI: 93.9-98.9]. The NPV >90% was shown by Paracheck 95.8% [95%CI: 91.9-98.2]. The overall PPV was <88% for all methods.
The HRP2-based RDT has shown superior sensitivity compared to microscopy in diagnosis of malaria and may be more suitable for screening of malaria infection.
Malaria management policies currently recommend that the treatment should only be administered after laboratory confirmation. Where microscopy is not available, rapid diagnostic tests (RDTs) are the usual alternative. Conclusive evidence is still lacking on the safety of a test-based strategy for children. Moreover, no formal attempt has been made to estimate RDTs accuracy on malaria-attributable fever. This study aims at estimating the accuracy of a RDT for the diagnosis of both malaria infection and malaria - attributable fever, in a region of Burkina Faso with a typically seasonal malaria transmission pattern.
Cross-sectional study. Subjects: all patients aged > 6 months consulting during the study periods. Gold standard for the diagnosis of malaria infection was microscopy. Gold standard for malaria-attributable fever was the number of fevers attributable to malaria, estimated by comparing parasite densities of febrile versus non-febrile subjects. Exclusion criteria: severe clinical condition needing urgent care.
In the dry season, 186/852 patients with fever (22%) and 213/1,382 patients without fever (15%) had a Plasmodium falciparum infection. In the rainy season, this proportion was 841/1,317 (64%) and 623/1,669 (37%), respectively. The attributable fraction of fever to malaria was 11% and 69%, respectively. The RDT was positive in 113/400 (28.3%) fever cases in the dry season, and in 443/650 (68.2%) in the rainy season. In the dry season, the RDT sensitivity and specificity for malaria infection were 86% and 90% respectively. In the rainy season they were 94% and 78% respectively. In the dry season, the RDT sensitivity and specificity for malaria-attributable fever were 94% and 75%, the positive predictive value (PPV) was 9% and the negative predictive value (NPV) was 99.8%. In the rainy season the test sensitivity for malaria-attributable fever was 97% and specificity was 55%. The PPV ranged from 38% for adults to 82% for infants, while the NPV ranged from 84% for infants to over 99% for adults.
In the dry season the RDT has a low positive predictive value, but a very high negative predictive value for malaria-attributable fever. In the rainy season the negative test safely excludes malaria in adults but not in children.
Endemic malaria has been eradicated from France, but some falciparum malaria cases have been described in patients who have never travelled outside the country. Ms. V. 21 year-old and Mr. M. 23 year-old living together in Paris were on holiday in Saint Raphaël (French Riviera). They presented with fever, vertigo and nausea. A blood smear made to control thrombocytopaenia revealed intra-erythrocytic forms of Plasmodium falciparum. The parasitaemia level was 0.15% for Ms. V and 3.2% for Mr. M. This couple had no history of blood transfusion or intravenous drug use. They had never travelled outside metropolitan France, but had recently travelled around France: to Saint Mard (close to Paris Charles de Gaulle (CdG) airport), to Barneville plage (in Normandy) and finally to Saint Raphaël. The most probable hypothesis is an infection transmitted in Saint Mard by an imported anopheline mosquito at CdG airport. The DNA analysis of parasites from Ms. V.'s and Mr. M.'s blood revealed identical genotypes. Because it is unlikely that two different anopheline mosquitoes would be infected by exactly the same clones, the two infections must have been caused by the infective bites of the same infected mosquito.
To guide malaria elimination efforts in Swaziland and other countries, accurate assessments of transmission are critical. Pooled-PCR has potential to efficiently improve sensitivity to detect infections; serology may clarify temporal and spatial trends in exposure.
Using a stratified two-stage cluster, cross-sectional design, subjects were recruited from the malaria endemic region of Swaziland. Blood was collected for rapid diagnostic testing (RDT), pooled PCR, and ELISA detecting antibodies to Plasmodium falciparum surface antigens. Of 4330 participants tested, three were RDT-positive yet false positives by PCR. Pooled PCR led to the identification of one P. falciparum and one P. malariae infection among RDT-negative participants. The P. falciparum-infected participant reported recent travel to Mozambique. Compared to performing individual testing on thousands of samples, PCR pooling reduced labor and consumable costs by 95.5%. Seropositivity was associated with age ≥20 years (11·7% vs 1·9%, P<0.001), recent travel to Mozambique (OR 4.4 [95% CI 1.0–19.0]) and residence in southeast Swaziland (RR 3.78, P<0.001).
The prevalence of malaria infection and recent exposure in Swaziland are extremely low, suggesting elimination is feasible. Future efforts should address imported malaria and target remaining foci of transmission. Pooled PCR and ELISA are valuable surveillance tools for guiding elimination efforts.
As a resource, allogenic blood has never been more in demand than it is today. Escalating elective surgery, shortages arising from a fall in supply, a lack of national blood transfusion services, policies, appropriate infrastructure, trained personnel, and financial resources to support the running of a voluntary nonremunerated donor transfusion service, and old and emerging threats of transfusion-transmitted infection, have all conspired to ensure that allogenic blood remains very much a vital but limited asset to healthcare delivery particularly in Sub-Saharan Africa. This is further aggravated by the predominance of family replacement and commercially remunerated blood donors, rather than regular benevolent, nonremunerated donors who give blood out of altruism. The demand for blood transfusion is high in Sub-Saharan Africa because of the high prevalence of anemia especially due to malaria and pregnancy-related complications. All stakeholders in blood transfusion have a significant challenge to apply the best available evidenced-based medical practices to the world-class management of this precious product in a bid to using blood more appropriately. Physicians in Sub-Saharan Africa must always keep in mind that the first and foremost strategy to avoid transfusion of allogenic blood is their thorough understanding of the pathophysiologic mechanisms involved in anemia and coagulopathy, and their thoughtful adherence to the evidenced-based good practices used in the developed world in a bid to potentially reduce the likelihood of allogenic blood transfusion in many patient groups. There is an urgent need to develop innovative ways to recruit and retain voluntary low-risk blood donors. Concerns about adverse effects of allogenic blood transfusion should prompt a review of transfusion practices and justify the need to search for transfusion alternatives to decrease or avoid the use of allogenic blood. These strategies should include the correction of anemia using pharmacological measures (use of antifibrinolytics to prevent bleeding and the use of erythropoietin and oral and intravenous iron to treat anemia) use of nonpharmacologic measures (preoperative autologous blood transfusion, perioperative red blood cell salvage and normothermia to reduce blood loss in surgical patients). All these strategies will help optimize the use of the limited blood stocks.
challenges; blood transfusion; Sub-Saharan Africa; alternatives