Malaria screening of donors and donations - issues and outcomes lan Kitchen National Transfusion Microbiology NHS Blood & Transplant London IPF/PEI, Rome, May 2014 Blood and Transplant
Key elements Nature of the problem? Defining malaria risk Dealing with the risk Screening & outcomes Confirmation & outcomes
Nature of the problem? Malaria is a serious disease with significant morbidity and mortality currently five spp. known to infect humans Plasmodium falciparum, vivax, ovale, malariae, knowlesi Transmission via blood/products into a malaria naïve individual is likely to result in infection Transfusion transmitted malaria is serious and may be fatal 3/5 identified cases in England were fatal Malaria is a significant transfusion risk in many non-endemic countries, but it can be dealt with effectively
Nature of the problem Non-endemic countries face the risk of malaria transmission through donations from donors who have been exposed to malaria Limited options: defer or screen Whatever approach is taken, malaria risk has to be defined, including deferral periods
changing situation Changing donor populations require changing strategies Changing donation types require changing strategies Malarial b screening of donations from risk donors is effective in minimising risk
Defining malaria risk ny donor who has been exposed to malaria previous residents (those born in and/or lived in endemic areas for at least 6/12) travellers to endemic areas (for a defined period after last return) donors with a history of diagnosed malaria Of these, those with a residency risk are arguably the group with the highest risk, due to semi-immunity semi-immunity is presence of persistent low level parasitaemia with high titre b (expected in donors from endemic countries with high EIR)
Dealing with the risk Ignore - do nothing no donors with malaria risk; not an option within the EU Defer permanent/temporary If temporary, for how long? llow donation and screen for malarial b, releasing to inventory if malarial b negative: at least 4-6/12 after their last return from an endemic area at least 3 years after cessation of treatment/symptoms Travellers may donate without b screening after 12/12 since last return from a malarious area
The extent of the issue Significant number of NHSBT donors with malaria risk England has very broad range of nationalities Migrants bring in the diseases present in their home countries, a significant proportion come from malaria endemic countries Migrant populations both volunteer blood donation and are specifically targeted to match blood and tissue types to recipient populations UK born donors travel NHSBT malarial b screening figures Year No. screened 2009 56500 2010 52570 2011 45476 2012 36541 2013 25972 2014 (Q1) 5887
Screening options The sensitivity/appropriateness of the individual potential screening targets, in the context of donation screening, is the issue Parasite malarial DN malarial g insufficient sensitivity in this context (very low infectious dose ) Immune response malarial b with appropriate length deferral (to allow b to appear) is an appropriate strategy
Screening Within NHSBT all donations from malaria risk donors screened for malarial b at least 6/12 after their last return from an endemic area approximately 97% overall screen negative approximately 3% overall screen reactive NHSBT donor risk breakdown: 21% Residency 77% Travel 2% History of malaria
Screen reactive breakdown by region Screen reactive malaria risk donors by risk & region: frica, Indian sub-continent, Other (Gulf, sia, S. merica) Residency 32% frica, 65% India, 3% Other Travel 25% frica, 57% India, 18% Other Had malaria 67% frica, 29% India, 4% Other
Confirmation of screen reactivity REMEMBER - all donors screened have a defined malaria risk Performed to try to determine in which of the screen reactive donations the reactivity is specific assumed to have been infected at some time Previous transmissions in England have demonstrated that there are donors who are still parasitaemic identification of parasitaemic donors was deemed important as these individuals need clinical review identification of such individuals helps define and refine malaria risk and screening policy and strategy
Confirmation of screen reactivity 2 additional microplate immunoassays (Cellabs & DiaPro) Immunofluorescent b using cultured falciparum infected human red cells Donors with reactivity in any of the above assays look for malarial DN using a pair of assays that detect ssrrn gene sequence, but where falciparum has a small but stable sequence difference to vivax, ovale, malariae and knowlesi
Confirmatory outcomes Breakdown of malaria risk in donors Donations Referred for Risk screened confirmation Residency 21% 63% Travel 77% 17% Had malaria 2% 20% Overall breakdown of confirmatory outcomes: 36% positive (approx 0.95% of donations screened) 23% inconclusive 41% negative 16 malarial DN positives (0.6% of screen reactives)
Malaria DN positive donors Case Lab Conf. Diapro Cellabs IFT No. 21 DN Comments 1 Pos Pos Pos 1/640 Pf Male, dob 05/03/91, from Nigeria, came to UK in Sept 2009. 2 Pos Neg Pos 1/640 Pf Male, dob 26/09/76, from Ivory Coast, came to UK in 2005. 3 Pos Pos Pos Neg Pv Male, dob 18/02/89, from India, came to UK in 2009. 4 Pos Pos Neg 1/80 Po Male, dob 17/03/67, from Nigeria, came to UK in 2004 5 Pos Pos Pos Neg Pv Male, dob 19/12/88, student from India, came to UK in Oct 2010 6 Pos Neg Pos 1/160 Po Female, dob 09/10/90, from Nigeria, came to UK 2008, malaria aged 16 7 Pos Neg Pos 1/640 Pf/Pm Male, dob 01/6/82, from Ghana, came to UK in 2009. Revisit in 2010 8 Pos Pos Pos Neg Pv Male, dob 11/11/91, from Pakistan, came UK in Feb 2011 9 Pos Pos Pos 1/640 Pf Female, dob 11/10/81, from Nigeria, came to UK in 2009 10 Pos Neg Pos Neg Po Male, dob 03/06/86, from South frica, came to UK in 2009. Malaria when aged 6 11 Pos Neg Pos 1/640 Pm Male, dob 01/09/81, Born in Nigeria, came to UK in 2011 12 Pos Neg Pos 1/320 Pm Male, black frican, born in Nigeria 22/09/77. UK in 2004, last visit endemic area 2007 13 Pos Pos Pos Neg Pv Male, dob 23/9/87, born India, lived in frica, Dubai. Came to UK 2011. Subsequently declared diagnosed with malaria in June 2012 14 Pos Pos Pos Neg X Male, dob 28/10/1980, born India, last return Jan 2013. Donor admitted to malaria in India in 2011 but was treated at the time. 15 Pos Pos Pos Neg Pv Male, dob 24/09/91, born Pakistan, came to UK in May 2011 16 Pos Pos Pos 1/640 Pf Male, dob 10/01/77. Born Sierra Leone, came to UK 1983. Cerebral malaria 2008, treated Kingston Hospital. Visit to
Case No. Lab21 ratio Malarial DN positives serology results Diapro ratios Cellabs ratios Diamed ratios Novatec ratios Conf. DN IFT 1 7.46 6.76/6.9 16.54/17.05 5.21/4.2 2.57 1/640 Pf 2 7.51 0.69/0.62 19.1/18.79 11.39/13.2 2.45 1/640 Pf 9 26.61 1.49/1.83 13.94/14.4 ND 2.78 1/640 Pf 16 8.88 1.32/1.24 15.7/15.71 ND ND 1/640 Pf 7 86.12 0.44/0.48 25.97/25.83 7.79/8.27 1.54 1/640 Pf/Pm 3 94.15 4.73/4.61 23.56/23.56 7.52/6.28 2.99 Neg Pv 5 96.89 2.29/2.65 12.37/12.8 4/4.46 1.83 Neg Pv 8 76.44 5.64/5.77 6.453/8.03 4.70/4.69 1.06 Neg Pv 13 99.79 5.05/5.95 9.11/9.32 ND ND Neg Pv 15 76.8 100/100 5.42/4.98 ND ND Neg Pv 14 70.16 9.19/9.27 3.31/3.52 ND ND Neg X 4 1.82 2.39/2.48 0.83/0.92 4.07/3.55 0.51 1/80 Po 6 19.36 0.37/0.38 9.12/9.64 2.77/3.07 1.92 1/160 Po 10 4.65 0.39/0.43 1.88/2.04 ND 0.54 Neg Po 11 7.14 0.75/1.0 13.71/13.8 ND 2.51 1/640 Pm Blood 12 and Transplant 2.75 0.36/0.34 9.9/8.41 ND 0.77 IPF/PEI, 1/320 Rome, May 2014 Pm
Risk group Malaria - resident Malaria traveller Resident Traveller Final result Pos 13.8 1.3-93 Incon. 8 2-23.2 Neg 4.7 1.2-22 Early analysis of serology results v. risk Lab21/Trinity (screen) Cellabs (Ref) DiaPro (Ref) No. IFT % by region I O I O I O positive I O Pos 4.71 3.3-5.5 Incon. 5.72 1.2-10 Neg 4.63 1.05-17 Pos 12.3 1-95 Incon. 6.3 1-19.5 Neg 4.6 1-14.6 Pos 12 1.1-87 Incon. 6.51 1-16.7 Neg 2.4 1-8.3 44.8 3.1-100 45.5 6.3-96 7.8 1.3-22 58.1 11-98 14.36 1.2-95 15.7 10.5-21 53 1.6-100 26.2 1-101 5.58 0.3-25 49.7 5.3-100 19.4 1.1-95 5.25 1-20 51.9 11.5-92 Too few 3.3 2-5.3 9.37 1.1-100 1.65 0.3-4.2 0.55 0.2-0.96-6.36 3.2-11.7 Too few 8.22 2.1-14 54 7-99 21.5 1.2-85 3.6 1-12 13.6 1.4-24 7.14 1.2-11 1.95 1-5.4 1.72 1.4-2.7 0.47 0.19-0.9 8.5 0.7-100 1.93 0.64-5.3 0.56 0.07-0.9 6.87 2.5-14.2 3.76 1.1-14 0.48 0.2-1 3.01 0.3-16 1.2 0.2-3.5 0.5 0.15-0.9 4.04 0.4-9.8 1.33 0.5-1.8 0.54 0.3-0.8 3.05 0.2-57 0.96 0.17-4 0.53 0.1-1.1 3.41 0.2-12.5 1.49 0.5-2.7 0.5 0.1-0.9 1.64 0.77-3.1 1.13 0.1-11.5 Too few 0.5 0.12-1 0.5 0.3-0.71 0.34 0.04-0.9-0.24 0.16-0.3 Too few 0.29 0.1-0.5 0.44 0.3-0.5 3.4 0.7-6.8 1.27 0.5-1.2 0.5 0.17-0.8 2.16 0.7-3.1 2.02 0.9-4.1 0.47 0.1-0.9 0.41 0.16-0.9 3.975 0.17-8.4 1.2 0.7-1.8 0.46 0.16-0.9 17.1 0.1-100 0.45 0.1-1.6 0.32 0.2-0.45 2.7 1.3-3.9 38/63 () 2/32 (I) 64 32 4 Too few 2/25 () 74 24 2 0.39 0.18-0.7 0 67 30 3-0 30 70 0 Too few 0 60 30 10 0.44 0.2-0.6 0 84 8 8 1.1 0.1-55 0.4 0.1-1.5 0.29 0.09-0.7 0.58 0.06-3.6 0.44 0.16-0.8 0.23 0.1-0.5 5.5 0.2-100 1.4 0.12-4.9 0.38 0.1-0.95 3.59 0.4-8.8 0.84 0.1-1.7 0.32 0.05-1 2.4 0.6-4.3 0.72 0.1-1.7 0.3 0.14-0.5 1.37 0.1-2.5 0.32 0.1-0.5 0.17 0.05-0.4 61/102 () 6/187 (I) 35 64 1 0 26 70 4 0 31 64 5 5/12 () 1/24 (I) 2/7 () 1/3 (O) 29 59 12 32 55 13 0 21 56 23
Is screening effective? With the correct deferral guidelines Yes since updating guidelines no reported cases in England no reported cases in ustralia from 2002-2013 Occasional breakthrough cases, but the number of safe donations released should be the focus cases in France in 2002, 2006, 2012 In US, deferral but no screening, there have been 7 cases of TTM reported between 2002 2013 ll reported cases, including previous English cases, involved donors who had lived in frica
In conclusion Identifying malaria risk in donors of blood and other products is essential Malarial antibody screening of at risk donors/donations is effective the majority (>95%) of donations are screen negative Parasitaemic donors are being identified, even after some years since last in an endemic area donations from these donors will transmit malaria strategies need to take account of this More detailed analysis of serology data against donor risk may help: understand the specificity of the reactivity improve the specificity and predictiveness of confirmation influence/improve malaria screening strategies