Transcript- FDA- Blood Products
Quotes Below on Babesia
FOOD AND DRUG ADMINISTRATION
CENTER FOR BIOLOGICS EVALUATION AND RESEARCH
BLOOD PRODUCTS ADVISORY COMMITTEE
July 26, 2010
The Hilton Washington DC North/Gaithersburg
620 Perry Parkway
Gaithersburg, Maryland
Quotes
Page 142- S_o_ _w_h_a_t_ _i_s_ _t_h_e_ _n_a_t_u_r_e_ _o_f_ _t_h_e_ _c_h_a_l_l_e_n_g_e_ _f_o_r_ _d_o_n_o_r_ _t_e_s_t_i_n_g_ _f_o_r_ _b_a_b_e_s_i_o_s_i_s_?_ _A_s_y_m_p_t_o_m_a_t_i_c_ _c_a_r_r_i_e_r_s_ _a_r_e_ _t_h_e_ _p_r_i_m_a_r_y_ _s_o_u_r_c_e_._ _I_n_f_e_c_t_i_o_n_ _c_a_n_ _p_e_r_s_i_s_t_,_ _l_o_w_-_g_r_a_d_e_ _p_a_r_a_s_i_t_e_m_i_a_,_ _f_o_r_ _m_o_n_t_h_s_ _o_r_ _p_o_s_s_i_b_l_y_ _t_w_o_ _y_e_a_r_s_ _o_r_ _m_o_r_e_._ _W_e_ _d_o_n_’t_ _k_n_o_w_ _w_h_a_t_ _i_s_ _t_h_e_ _m_i_n_i_m_a_l_ _i_n_f_e_c_t_i_o_u_s_ _d_o_s_e_ _t_h_a_t_ _c_a_n_ _c_a_u_s_e_ _t_r_a_n_s_f_u_s_i_o_n_-_t_r_a_n_s_m_i_t_t_e_d_ _b_a_b_e_s_i_o_s_i_s_._ _
Neither do we know the level of parasitemia that is present. What is the minimum parasitemia that is needed to maintain infection? That is not known. Together, these two problems make it difficult to where to set the sensitivity limit even for direct detection.
There is no recommendation to treat persons with asymptomatic Babesia infections. These are silent infections, asymptomatic infections. People could be infected and, in a sense, could be serving as a live human reservoir of infections, actually.
Both clinical cases and TTB cases are underreported. That underreporting is a cause of many problems.
Page 143 B_o_t_h_ _a_ _n_u_c_l_e_i_c_ _a_c_i_d_-_b_a_s_e_d_ _t_e_s_t_,_ _N_A_C_,_ _a_n_d_ _a_n_t_i_b_o_d_i_e_s_ _h_a_v_e_ _b_e_e_n_ _u_s_e_d_,_ _b_a_s_e_d_ _o_n_ _l_a_b_o_r_a_t_o_r_y_ _t_e_s_t_s_._ _B_u_t_ _t_h_e_y_ _b_o_t_h_ _h_a_v_e_ _l_i_m_i_t_a_t_i_o_n_s_ _i_n_ _t_h_e_ _w_a_y_ _t_h_e_y_ _a_r_e_ _c_u_r_r_e_n_t_l_y_ _u_s_e_d_ _i_n_ _d_o_n_o_r_ _s_c_r_e_e_n_i_n_g_._ _T_h_e_r_e_ _i_s_ _l_a_c_k_ _o_f_ _s_u_f_f_i_c_i_e_n_t_ _g_e_n_o_m_i_c_/_p_r_o_t_e_o_m_i_c_ _c_r_o_s_s_-_r_e_a_c_t_i_v_i_t_y_._ _
T_h_e_r_e_ _i_s_ _e_v_i_d_e_n_c_e_ _t_h_a_t_ _t_h_e_ _t_e_s_t_s_ _d_e_v_e_l_o_p_e_d_ _f_o_r_ _Babesia microti,_ _b_o_t_h_ _I_F_A_-_b_a_s_e_d_ _a_n_d_ _a_n_t_i_b_o_d_y_-_b_a_s_e_d_,_ _a_n_d_ _p_o_s_s_i_b_l_y_ _P_C_R_ _t_e_s_t_s_,_ _a_r_e_ _n_o_t_ _s_e_n_s_i_t_i_v_e_ _e_n_o_u_g_h_ _t_o_ _d_e_t_e_c_t_ _n_o_n_-_Babesia microti s_p_e_c_i_e_s_._ _I_ _t_h_i_n_k_ _t_h_a_t_’s_ _a_ _v_e_r_y_ _i_m_p_o_r_t_a_n_t_ _t_h_i_n_g_ _t_o_ _k_e_e_p_ _i_n_ _m_i_n_d_._ _I_ _d_o_n_’t_ _t_h_i_n_k_ _w_e_ _h_a_v_e_ _s_u_f_f_i_c_i_e_n_t_ _g_e_n_o_m_i_c_ _a_n_d_ _p_r_o_t_e_o_m_i_c_ _i_n_f_o_r_m_a_t_i_o_n_ _r_i_g_h_t_ _n_o_w_._ _
Page 144- I_ _w_a_s_ _r_e_a_l_l_y_ _p_u_z_z_l_e_d_._ _I_ _l_o_o_k_e_d_ _i_n_ _t_h_e_ _e_n_t_i_r_e_ _l_i_t_e_r_a_t_u_r_e_,_ _t_a_l_k_e_d_ _t_o_ _p_e_o_p_l_e_._ _N_o_b_o_d_y_ _h_a_s_ _e_v_e_n_ _t_r_u_l_y_ _d_e_m_o_n_s_t_r_a_t_e_d_ _t_h_e_ _a_n_a_l_y_t_i_c_a_l_ _s_e_n_s_i_t_i_v_i_t_y_ _o_f_ _t_h_e_ _N_A_T_ _t_h_a_t_ _h_a_s_ _b_e_e_n_ _u_s_e_d_,_ _a_c_t_u_a_l_l_y_,_ _i_n_ _Babesia._ _
T_h_e_ _p_a_r_a_s_i_t_e_m_i_a_ _m_a_y_ _b_e_ _v_e_r_y_ _l_o_w_ _d_u_r_i_n_g_ _t_h_e_ _e_a_r_l_y_ _p_h_a_s_e_ _o_f_ _a_c_u_t_e_ _i_n_f_e_c_t_i_o_n_._ _T_h_a_t_’s_ _t_h_e_ _w_i_n_d_o_w_ _p_e_r_i_o_d_._ _T_h_e_ _p_a_r_a_s_i_t_e_m_i_a_ _m_a_y_ _b_e_ _a_g_a_i_n_ _v_e_r_y_ _l_o_w_ _d_u_r_i_n_g_ _t_h_e_ _a_s_y_m_p_t_o_m_a_t_i_c_ _i_n_f_e_c_t_i_o_n_s_._ _B_u_t_,_ _t_r_u_l_y_,_ _w_e_ _d_o_ _n_o_t_ _k_n_o_w_ _w_h_a_t_ _i_s_ _t_h_e_ _p_a_r_a_s_i_t_e_ _b_u_r_d_e_n_ _i_n_ _a_s_y_m_p_t_o_m_a_t_i_c_ _c_a_r_r_i_e_r_s_._ _
Page 145
B_e_c_a_u_s_e_ _o_f_ _t_h_a_t_,_ _i_n_ _t_h_e_ _a_b_s_e_n_c_e_ _o_f_ _c_l_i_n_i_c_a_l_ _s_t_u_d_i_e_s_,_ _i_t_’s_ _r_e_a_l_l_y_ _d_i_f_f_i_c_u_l_t_ _t_o_ _t_r_u_l_y_ _s_a_y_ _t_h_a_t_ _w_h_a_t_ _w_i_l_l_ _b_e_ _t_h_e_ _v_a_l_u_e_ _o_f_ _a_ _h_i_g_h_l_y_ _s_e_n_s_i_t_i_v_e_ _n_u_c_l_e_i_c_ _a_c_i_d_-_b_a_s_e_d_ _t_e_s_t_ _i_n_ _i_n_t_e_r_d_i_c_t_i_n_g_ _t_h_e_s_e_ _i_n_f_e_c_t_e_d_ _b_l_o_o_d_ _d_o_n_o_r_s_._ _
A_s_ _a_ _r_e_s_u_l_t_,_ _a_ _f_e_w_ _i_n_f_e_c_t_e_d_ _r_e_d_ _c_e_l_l_s_ _m_a_y_ _b_e_ _p_o_t_e_n_t_i_a_l_l_y_ _p_r_e_s_e_n_t_ _i_n_ _a_ _u_n_i_t_ _o_f_ _b_l_o_o_d_._ _T_o_ _b_e_ _e_f_f_e_c_t_,_ _a_ _N_A_T_ _t_e_s_t_ _m_u_s_t_ _b_e_ _h_i_g_h_l_y_ _s_e_n_s_i_t_i_v_e_ _t_o_ _b_e_g_i_n_ _w_i_t_h_,_ _a_n_d_ _t_h_e_ _l_i_m_i_t_ _o_f_ _d_e_t_e_c_t_i_o_n_ _o_f_ _N_A_T_ _f_o_r_ _Plasmodium falciparum -_-_ _s_o_ _w_h_e_r_e_ _s_h_o_u_l_d_ _b_e_ _t_h_e_ _l_i_m_i_t_?_ _T_h_e_ _l_i_m_i_t_ _s_h_o_u_l_d_ _b_e_ _w_h_a_t_ _i_s_ _b_i_o_l_o_g_i_c_a_l_l_y_ _f_e_a_s_i_b_l_e_ _a_n_d_ _w_h_a_t_ _h_a_s_ _b_e_e_n_ _g_o_n_e_._ _I_f_ _w_e_ _l_o_o_k_ _a_t_ _-_-_ _a_n_o_t_h_e_r_ _p_a_r_a_s_i_t_e_,_ _Plasmodium falciparum -_-_ _p_e_o_p_l_e_ _a_r_e_ _l_o_o_k_i_n_g_ _a_t_ _i_t_ _b_y_ _u_s_i_n_g_ _t_h_e_ _r_i_b_o_s_o_m_a_l_ _R_N_A_ _g_e_n_e_,_ _w_h_i_c_h_ _h_a_s_ _f_i_v_e_ _t_o_ _s_e_v_e_n_ _c_o_p_i_e_s_ _f_o_r_ _Plasmodium
k_n_o_w_ _h_o_w_ _m_a_n_y_ _c_o_p_i_e_s_ _o_f_ _r_i_b_o_s_o_m_a_l_ _R_N_A_ _g_e_n_e_ _a_r_e_ _t_h_e_r_e_ _i_n_ _Babesia microti._ _B_u_t_ _u_s_i_n_g_ _t_h_a_t_ _t_e_s_t_,_ _i_t_ _c_a_n_ _d_e_t_e_c_t_ _2_0_ _p_a_r_a_s_i_t_e_s_ _p_e_r_ _m_l_ _o_f_ _b_l_o_o_d_._ _S_o_ _t_h_a_t_ _j_u_s_t_ _g_i_v_e_s_ _u_s_ _s_o_m_e_ _s_o_r_t_ _o_f_ _c_l_u_e_ _o_f_ _w_h_a_t_ _s_h_o_u_l_d_ _b_e_ _s_c_i_e_n_t_i_f_i_c_a_l_l_y_ _f_e_a_s_i_b_l_e_._ _
P_o_s_s_i_b_l_y_ _t_h_e_r_e_ _c_o_u_l_d_ _b_e_ _o_t_h_e_r_ _m_o_l_e_c_u_l_e_s_ _w_h_i_c_h_ _a_r_e_ _h_i_g_h_e_r_ _c_o_p_y_ _n_u_m_b_e_r_,_ _a_n_d_ _t_h_e_y_ _m_a_y_ _b_e_ _a_ _g_o_o_d_ _t_a_r_g_e_t_,_ _a_c_t_u_a_l_l_y_._ _
O_t_h_e_r_ _t_h_i_n_g_s_ _c_o_u_l_d_ _b_e_ _d_o_n_e_ _i_n_ _t_e_r_m_s_ _o_f_ _s_a_m_p_l_e_ _c_o_n_c_e_n_t_r_a_t_i_o_n_s_,_ _s_i_n_c_e_ _t_h_i_s_ _i_s_ _a_n_ _i_n_t_r_a_e_r_y_t_h_r_o_c_y_t_i_c_ _p_a_r_a_s_i_t_e_._ _L_a_r_g_e_r_ _b_l_o_o_d_ _v_o_l_u_m_e_s_ _c_o_u_l_d_ _b_e_ _u_s_e_d_ _t_o_ _i_m_p_r_o_v_e_ _s_e_n_s_i_t_i_v_i_t_y_._ _C_o_n_c_e_n_t_r_a_t_i_o_n_ _o_f_ _i_n_f_e_c_t_e_d_ _r_e_d_ _c_e_l_l_s_,_ _i_f_ _t_h_a_t_’s_ _p_o_s_s_i_b_l_e_,_ _b_e_f_o_r_e_ _t_e_s_t_i_n_g_ _m_i_g_h_t_ _i_m_p_r_o_v_e_ _s_e_n_s_i_t_i_v_i_t_y_._ _T_h_e_n_ _a_g_a_i_n_,_ _a_s_ _I_ _s_a_i_d_,_ _i_t_ _m_a_y_ _b_e_ _a_ _g_o_o_d_ _i_d_e_a_ _t_o_ _b_e_c_o_m_e_ _m_o_r_e_ _c_r_e_a_t_i_v_e_ _a_n_d_ _l_o_o_k_ _f_o_r_ _s_o_m_e_ _o_t_h_e_r_ _n_o_v_e_l_ _m_u_l_t_i_-_c_o_p_y_ _g_e_n_e_ _t_a_r_g_e_t_s_ _a_s_ _N_A_T_._ _
Page 145- Antibody testing: IFA, ELISA, and Western blot have been used for diagnosis and epidemiology. IFA is sensitive for acute babesiosis cases. But the biggest problem is -- not need to be even said -- that it’s not adapted for high-throughput donor screening. Similarly, Western blot is not adapted for high-throughput screening.
If we look at the literature, the sensitivity -- the antibody positivity goes in the range of .3 percent -- in Connecticut, up to 17 percent. That shows these assays have low specificity. There are a lot of asymptomatic i_n_f_e_c_t_i_o_n_s_ _t_h_a_t_ _w_e_ _d_o_n_’t_ _k_n_o_w_ _a_b_o_u_t_._ _
Page 146- I_g_G_ _t_i_t_e_r_s_ _m_a_y_ _p_e_r_s_i_s_t_ _f_o_r_ _m_o_n_t_h_s_ _o_r_ _y_e_a_r_s_,_ _p_o_s_s_i_b_l_y_,_ _a_n_d_ _t_h_e_r_e_f_o_r_e_ _t_h_e_y_ _c_a_n_n_o_t_ _b_e_ _u_s_e_d_ _f_o_r_ _d_i_s_t_i_n_g_u_i_s_h_i_n_g_ _c_u_r_r_e_n_t_ _f_r_o_m_ _p_a_s_t_ _i_n_f_e_c_t_i_o_n_s_._
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DR. BOWER: You mentioned that there were four implicated donors from non-endemic areas. Do you know if t_h_e_y_ _h_a_d_ _t_r_a_v_e_l_e_d_ _t_o_ _e_n_d_e_m_i_c_ _a_r_e_a_s_?_ _
D_R_._ _K_U_M_A_R_:_ _T_h_e_y_ _d_i_d_ _t_r_a_v_e_l_ _t_o_ _e_n_d_e_m_i_c_ _a_r_e_a_s_,_ _y_e_s_._ _I_ _d_i_d_n_’t_ _s_a_y_ _t_h_a_t_._ _T_h_e_y_ _r_e_p_o_r_t_e_d_ _t_r_a_v_e_l_s_ _t_o_ _e_n_d_e_m_i_c_ _a_r_e_a_s_,_ _y_e_s_._ _
Page 155- When we think of B. microti in U.S. foci, we have the parasite -- and, by the way, it’s probably not homogeneous. There may be strain differences. There may be a species complex, particularly when we consider babesiosis in other areas of the world, where there are B. microti-like organisms. We have a tick vector and various reservoir hosts, particularly deer mice.
Page 156- A_s_ _S_a_m_ _T_e_l_f_o_r_d_,_ _a_n_ _e_n_t_o_m_o_l_o_g_i_s_t_,_ _h_a_s_ _p_o_i_n_t_e_d_ _o_u_t_ _b_e_f_o_r_e_ _-_-_ _a_n_d_ _h_e_ _w_a_s_n_’t_ _r_e_s_t_r_i_c_t_i_n_g_ _t_h_i_s_ _r_e_m_a_r_k_ _t_o_ _t_e_m_p_e_r_a_t_u_r_e_ _-_-_ _s_o_m_e_ _y_e_a_r_s_ _a_r_e_ _h_o_t_ _a_n_d_ _s_o_m_e_ _y_e_a_r_s_ _a_r_e_ _c_o_o_l_,_ _a_n_d_ _p_r_e_d_i_c_t_i_n_g_ _t_h_e_ _r_i_s_k_ _f_o_r_ _h_u_m_a_n_s_ _o_n_ _t_h_e_ _b_a_s_i_s_ _o_f_ _e_c_o_l_o_g_i_c_ _d_a_t_a_ _w_o_u_l_d_ _b_e_ _v_e_r_y_,_ _v_e_r_y_ _d_i_f_f_i_c_u_l_t_._ _
Page 156- Also, just as a point to stick in, as you know, don’t expect to see ticks. I don’t know how many of you know how small the nymphal stage of the Ixodes scapularis tick is. This, of course, is before it’s engorged. Tiny, tiny, tiny. And, of course, don’t expect to see tetrads. You are not going to expect to see them on a donor’s blood smear, but even on a patient blood smear they can be few and far between.
Page 157- S_i_n_c_e_ _t_h_e_ _1_9_9_0_s_,_ _s_p_o_r_a_d_i_c_ _U_._S_._ _c_a_s_e_s_ _c_a_u_s_e_d_ _b_y_ _o_t_h_e_r_ _-_-_ _m_e_a_n_i_n_g_ _n_o_n_-_B. microti -_-_ _a_g_e_n_t_s_ _h_a_v_e_ _b_e_e_n_ _d_e_s_c_r_i_b_e_d_,_ _s_u_c_h_ _a_s_ _-_-_ _a_n_d_ _t_h_i_s_ _i_s_ _n_o_t_ _a_n_ _a_l_l_-_i_n_c_l_u_s_i_v_e_ _l_i_s_t_ _-_-_ _B. duncani,_ _t_h_e_ _W_A_1_-_t_y_p_e_ _p_a_r_a_s_i_t_e_,_ _a_n_d_ _r_e_l_a_t_e_d_ _o_r_g_a_n_i_s_m_s_ _i_n_ _s_e_v_e_r_a_l_ _w_e_s_t_e_r_n_ _s_t_a_t_e_s_,_ _B. divergens-_l_i_k_e_ _a_g_e_n_t_s_,_ _s_u_c_h_ _a_s_ _M_O_1_,_ _i_n_ _v_a_r_i_o_u_s_ _r_e_g_i_o_n_s_._ _T_h_e_s_e_ _a_g_e_n_t_s_ _-_-_ _b_y_ _t_h_e_ _w_a_y_,_ _I_’m_ _c_a_l_l_i_n_g_ _t_h_e_m_ _a_g_e_n_t_s_ _b_e_c_a_u_s_e_ _n_o_t_ _a_l_l_ _o_f_ _t_h_e_m_ _h_a_v_e_ _r_e_a_c_h_e_d_ _t_h_e_ _s_p_e_c_i_e_s_ _s_t_a_t_u_s_ _y_e_t_._ _T_h_e_y_ _m_a_y_ _i_n_ _t_h_e_ _f_u_t_u_r_e_._ _T_h_e_i_r_ _g_e_o_g_r_a_p_h_i_c_ _r_a_n_g_e_s_,_ _t_i_c_k_ _v_e_c_t_o_r_s_,_ _a_n_d_ _r_e_s_e_r_v_o_i_r_ _h_o_s_t_s_ _l_a_r_g_e_l_y_ _r_e_m_a_i_n_ _u_n_k_n_o_w_n_._ _O_f_ _c_o_u_r_s_e_,_ _i_t_ _v_a_r_i_e_s_ _s_o_m_e_w_h_a_t_ _f_r_o_m_ _o_r_g_a_n_i_s_m_ _t_o_ _o_r_g_a_n_i_s_m_._ _
Page 157- A key point is that infection with these parasites is not detected by the currently available molecular or serologic tests for B. microti.
Page 166- These points are self-evident to people in the room. Even persons who have asymptomatic infection or whose symptoms resolve may have low-level infection -- of course, how low do you go? -- for weeks to months, sometimes longer than a year. Of course, we wish we knew what factors influence chronicity.
Page 166- A_g_a_i_n_,_ _i_f_ _I_ _r_e_c_a_l_l_ _c_o_r_r_e_c_t_l_y_,_ _h_e_ _t_e_s_t_e_d_ _t_h_e_m_ _b_y_ _P_C_R_ _t_w_i_c_e_,_ _t_h_r_e_e_ _m_o_n_t_h_s_ _a_p_a_r_t_,_ _a_n_d_ _i_f_ _t_h_e_y_ _h_a_d_ _n_e_g_a_t_i_v_e_s_ _t_w_i_c_e_,_ _t_h_e_n_ _h_e_ _n_o_ _l_o_n_g_e_r_ _m_o_n_i_t_o_r_e_d_ _t_h_e_m_._ _S_o_ _t_h_a_t_ _d_o_e_s_n_’t_ _e_x_c_l_u_d_e_ _t_h_e_ _p_o_s_s_i_b_i_l_i_t_y_ _1_6_7_ _
t_h_a_t_ _t_h_e_y_ _w_e_r_e_ _p_a_r_a_s_i_t_e_m_i_c_ _l_o_n_g_e_r_._ _B_u_t_ _h_e_r_e_ _y_o_u_ _h_a_v_e_ _s_o_m_e_o_n_e_ _w_h_o_ _w_a_s_ _n_o_t_ _t_r_e_a_t_e_d_,_ _w_i_t_h_ _d_e_m_o_n_s_t_r_a_b_l_e_ _p_a_r_a_s_i_t_e_m_i_a_ _u_p_ _t_o_ _2_7_ _m_o_n_t_h_s_._ _T_h_a_t_ _p_a_r_t_i_c_u_l_a_r_ _p_e_r_s_o_n_ _h_a_d_ _a_n_ _u_n_f_o_r_t_u_n_a_t_e_ _s_t_o_r_y_,_ _w_h_e_r_e_ _h_e_ _w_a_s_ _b_e_i_n_g_ _m_o_n_i_t_o_r_e_d_ _e_v_e_r_y_ _t_h_r_e_e_ _m_o_n_t_h_s_ _u_p_ _t_o_ _1_8_ _m_o_n_t_h_s_ _a_n_d_ _t_h_e_n_ _s_a_i_d_,_ _“E_n_o_u_g_h_._ _N_o_ _m_o_r_e_ _m_o_n_i_t_o_r_i_n_g_._” _N_i_n_e_ _m_o_n_t_h_s_ _l_a_t_e_r_,_ _a_t_ _2_7_ _m_o_n_t_h_s_,_ _h_e_ _b_e_c_a_m_e_ _v_e_r_y_ _i_l_l_,_ _w_a_s_ _h_o_s_p_i_t_a_l_i_z_e_d_,_ _f_o_r_t_u_n_a_t_e_l_y_ _d_i_d_ _w_e_l_l_ _w_i_t_h_ _t_r_e_a_t_m_e_n_t_,_ _b_u_t_ _a_ _r_e_n_a_l_ _t_u_m_o_r_ _w_a_s_ _d_i_s_c_o_v_e_r_e_d_._ _
Page 168- More cautionary notes, again just generically. As most of you know, some commercial labs for diagnostic testing offer serologic and molecular testing, but there are no FDA-cleared test kits for in vitro diagnostic use, even for B. microti. Testing is done with -- I purposely have this in quotation marks -- reagents that are assembled and evaluated by the individual laboratory. Not surprisingly, there can be inter- and intra-laboratory variability with respect to sensitivity and specificity and in terms of the patient data results, the reliability and validity.
Page 169- B_u_t_ _I_ _d_o_n_’t_,_ _f_r_a_n_k_l_y_,_ _t_h_i_n_k_ _t_h_a_t_’s_ _o_u_r_ _b_i_g_g_e_s_t_ _c_o_n_c_e_r_n_ _a_t_ _t_h_e_ _m_o_m_e_n_t_._ _B_u_t_ _i_t_ _d_o_e_s_ _n_o_t_ _r_e_l_i_a_b_l_y_ _d_i_s_t_i_n_g_u_i_s_h_ _a_c_t_i_v_e_ _f_r_o_m_ _p_a_s_t_ _i_n_f_e_c_t_i_o_n_._ _
Page 169- B_u_t_ _t_h_e_ _b_o_t_t_o_m_ _l_i_n_e_ _i_s_ _t_h_a_t_ _t_h_e_ _r_e_s_u_l_t_s_ _a_r_e_ _h_e_l_p_f_u_l_ _i_f_ _p_o_s_i_t_i_v_e_,_ _a_n_d_ _n_e_g_a_t_i_v_e_ _r_e_s_u_l_t_s_ _d_o_n_’t_ _e_x_c_l_u_d_e_ _l_o_w_-_l_e_v_e_l_ _p_a_r_a_s_i_t_e_m_i_a_,_ _
Page 170- I_n_ _o_u_r_ _e_x_p_e_r_i_e_n_c_e_ _-_-_ _n_o_ _s_u_r_p_r_i_s_e_ _-_-_ _t_h_e_ _l_i_k_e_l_i_h_o_o_d_ _o_f_ _P_C_R_ _p_o_s_i_t_i_v_i_t_y_ _i_s_ _h_i_g_h_e_r_ _f_o_r_ _s_e_g_m_e_n_t_s_ _t_h_a_n_ _f_o_r_ _f_o_l_l_o_w_-_u_p_ _p_o_s_t_-_d_o_n_a_t_i_o_n_ _s_p_e_c_i_m_e_n_s_,_ _b_u_t_ _d_o_e_s_ _n_o_t_ _a_p_p_r_o_a_c_h_ _1_0_0_ _p_e_r_c_e_n_t_._ _A_g_a_i_n_,_ _i_t_’s_ _a_ _g_e_n_e_r_i_c_ _s_t_a_t_e_m_e_n_t_._ _I_t_ _w_o_u_l_d_n_’t_ _m_a_t_t_e_r_ _i_f_ _-_-_ _t_y_p_e_ _o_f_ _P_C_R_,_ _w_h_a_t_e_v_e_r_._ _B_u_t_ _I_ _t_h_i_n_k_ _e_v_e_r_y_o_n_e_ _w_o_u_l_d_ _a_g_r_e_e_ _t_h_a_t_ _i_t_’s_ _n_o_t_ _1_0_0_ _p_e_r_c_e_n_t_._ _W_h_e_t_h_e_r_ _i_t_’s_ _7_0_ _p_e_r_c_e_n_t_ _o_r_ _8_0_ _o_r_ _9_0_,_ _d_e_p_e_n_d_i_n_g_ _o_n_ _t_h_e_ _t_e_c_h_n_i_q_u_e_ _a_n_d_ _t_h_e_ _l_e_v_e_l_ _o_f_ _p_a_r_a_s_i_t_e_m_i_a_ _-_-_ _b_u_t_ _i_t_’s_ _n_o_t_ _1_0_0_ _p_e_r_c_e_n_t_._ _
Page 171- E_v_e_n_ _t_h_o_u_g_h_ _b_a_b_e_s_i_o_s_i_s_ _h_a_s_n_’t_ _b_e_e_n_ _o_f_f_i_c_i_a_l_l_y_ _n_o_t_i_f_i_a_b_l_e_ _-_-_ _a_n_d_ _i_t_ _w_i_l_l_ _b_e_ _-_-_ _w_e_ _h_a_v_e_ _a_l_r_e_a_d_y_ _h_a_d_ _c_a_s_e_s_ _f_o_r_ _y_e_a_r_s_ _v_o_l_u_n_t_a_r_i_l_y_ _r_e_p_o_r_t_e_d_ _t_o_ _u_s_,_ _a_n_d_ _w_e_ _a_r_e_ _i_n_ _t_h_e_ _t_h_o_u_s_a_n_d_s_._ _B_u_t_ _t_h_i_s_ _i_s_ _w_i_t_h_o_u_t_ _a_ _s_t_a_n_d_a_r_d_ _c_a_s_e_ _d_e_f_i_n_i_t_i_o_n_._ _
Page 182- CT study- This is a summary of data from 1999 to 2007. You can see the number of tested donors per year. It ranges anywhere from about 2,000 to as high as 5,200 donors. This is all by IFA testing.
Page 183- Also from the beginning of that time, we were deferring donors. So all the extremely chronic carriers are being weeded out of the population in Connecticut over time. As I will show you later in the last slide, it has had some impact upon our look-back investigations in Connecticut as well.
Page 184- But I think the take-home message is, while that may be highly endemic in that area, you can find other areas of endemicity throughout the state. So as you move distally from that highly endemic area, you can also find other hotspots. There is probably no area in the state of Connecticut that is free of babesiosis.
Page 187- Our attempt here is, every 30 to 60 days, to test the enrolled donors by serology to antibodies to B. microti. We looked at blood smears. We did PCR, and with the cooperation of the CDC, for the first three years, we looked at hamster inoculations as well.
Page 188- Half of the donors we looked at remained seropositive. But if you look at their patterns, you can see that a full 38 percent of those are also resolving infection. Actually, most donors who become infected resolve infection, clear antibody titers.
Page 188- T_h_i_r_t_y_-_o_n_e_ _p_e_r_c_e_n_t_ _o_f_ _t_h_e_ _s_u_b_s_e_t_ _a_p_p_e_a_r_ _t_o_ _h_a_v_e_ _c_h_r_o_n_i_c_ _i_n_f_e_c_t_i_o_n_s_,_ _w_h_i_c_h_ _I_’l_l_ _t_a_l_k_ _a_b_o_u_t_ _b_r_i_e_f_l_y_._ _A_ _s_m_a_l_l_e_r_ _s_u_b_s_e_t_,_ _1_2_ _p_e_r_c_e_n_t_,_ _h_a_d_ _r_e_i_n_f_e_c_t_i_o_n_s_._ _
Page 190- A_s_ _y_o_u_ _c_a_n_ _s_e_e_,_ _t_h_e_i_r_ _a_n_t_i_b_o_d_y_ _t_i_t_e_r_s_ _o_v_e_r_ _t_i_m_e_,_ _a_ _l_i_t_t_l_e_ _b_i_t_ _o_v_e_r_ _a_ _y_e_a_r_,_ _d_i_s_a_p_p_e_a_r_ _a_n_d_ _b_e_c_o_m_e_ _n_e_g_a_t_i_v_e_ _a_s_ _w_e_l_l_._ _S_o_ _i_n_ _t_h_i_s_ _d_o_n_o_r_,_ _w_h_i_l_e_ _t_h_e_y_ _w_e_r_e_ _I_F_A_-_p_o_s_i_t_i_v_e_,_ _w_e_ _c_o_u_l_d_ _n_e_v_e_r_ _d_e_m_o_n_s_t_r_a_t_e_ _p_a_r_a_s_i_t_e_m_i_a_._ _I_t_ _d_o_e_s_n_’t_ _m_e_a_n_ _t_h_e_y_ _w_e_r_e_n_’t_ _p_a_r_a_s_i_t_e_m_i_c_;_ _i_t_ _j_u_s_t_ _m_e_a_n_s_ _t_h_a_t_ _w_e_ _d_i_d_n_’t_ _d_e_t_e_c_t_ _p_a_r_a_s_i_t_e_m_i_a_._ _ … What we do see in probably about 15 to 20 percent overall of the donors enrolled in the natural history study are people who appear to be perhaps chronic carriers.
Page 190- They were treated for the babesiosis, which sometimes is successful -- not always; sometimes patients require retreatment. Shortly after treatment, they were no longer parasitemic, but for a full three years, every time we tested them, with the exception of this one test, they had a titer of 1 to 512. So they remained with an elevated antibody titer, which I think, to Dr. Herwaldt and me and others, suggests they have an underlying infection that is stimulating their immune response.
Page 191- If you look at the Western blot analysis, very little IgM, which disappears, but the IgG response stays strong the entire time -- very high antibody titers.
B_u_t_ _w_h_a_t_’s_ _i_n_t_e_r_e_s_t_i_n_g_ _i_n_ _t_h_i_s_ _d_o_n_o_r_ _i_s_,_ _w_i_t_h_ _t_h_e_ _e_x_c_e_p_t_i_o_n_ _o_f_ _s_o_m_e_ _e_a_r_l_y_ _i_n_f_e_c_t_i_o_n_s_ _i_n_ _P_C_R_ _a_n_d_ _h_a_m_s_t_e_r_,_ _w_e_ _w_e_r_e_ _n_o_t_ _a_b_l_e_ _t_o_ _d_e_m_o_n_s_t_r_a_t_e_ _t_h_e_i_r_ _b_e_i_n_g_ _p_a_r_a_s_i_t_e_m_i_c_,_ _e_v_e_n_ _t_h_o_u_g_h_ _t_h_e_y_ _h_a_v_e_ _e_v_e_r_y_ _s_u_g_g_e_s_t_i_o_n_ _o_f_ _b_e_i_n_g_ _r_e_-_e_x_p_o_s_e_d_ _a_n_d_ _r_e_i_n_f_e_c_t_e_d_._ _
Page 192- Of note, of all the donors, the 227, that have been in our natural history study, this was the only donor that we ever identified positive by blood smear. You need significant numbers of parasites to pick up by blood smear, and this guy had them. H_e_ _w_a_s_ _t_r_e_a_t_e_d_,_ _1_0_ _d_a_y_s_ _o_f_ _t_r_e_a_t_m_e_n_t_,_ _c_a_m_e_ _b_a_c_k_._ _H_e_ _s_t_i_l_l_ _h_a_d_ _a_ _h_i_g_h_ _t_i_t_e_r_._ _I_t_ _d_i_p_p_e_d_ _s_h_o_r_t_l_y_,_ _b_u_t_ _f_r_o_m_ _t_h_e_n_ _o_n_,_ _h_e_ _r_e_m_a_i_n_e_d_ _r_e_l_a_t_i_v_e_l_y_ _h_i_g_h_ _f_o_r_ _t_h_r_e_e_ _y_e_a_r_s_ _t_h_e_r_e_a_f_t_e_r_._ _B_y_ _P_C_R_,_ _w_e_ _o_n_l_y_ _i_d_e_n_t_i_f_i_e_d_ _h_i_m_ _a_s_ _b_e_i_n_g_ _p_o_s_i_t_i_v_e_ _o_n_c_e_,_ _b_u_t_ _o_n_c_e_ _w_e_ _d_e_v_e_l_o_p_e_d_ _a_ _m_o_r_e_ _s_e_n_s_i_t_i_v_e_ _r_e_a_l_-_t_i_m_e_ _P_C_R_,_ _w_e_ _c_o_u_l_d_ _p_i_c_k_ _h_i_m_ _u_p_ _s_e_v_e_r_a_l_ _t_i_m_e_s_._ _
H_o_w_e_v_e_r_,_ _t_h_a_t_’s_ _n_o_t_ _o_f_t_e_n_ _t_h_e_ _c_a_s_e_._ _M_a_n_y_ _t_i_m_e_s_ _w_e_ _t_e_s_t_e_d_ _d_o_n_o_r_s_ _a_n_d_ _w_e_ _n_e_v_e_r_ _d_e_t_e_c_t_e_d_ _t_h_e_m_ _a_s_ _b_e_i_n_g_ _p_a_r_a_s_i_t_e_m_i_c_._ _A_s_ _I_ _t_h_i_n_k_ _D_r_._ _H_e_r_w_a_l_d_t_ _s_t_a_t_e_d_,_ _a_ _n_e_g_a_t_i_v_e_ _P_C_R_ _d_o_e_s_ _n_o_t_ _r_e_a_l_l_y_ _c_l_e_a_r_ _t_h_e_m_ _o_f_ _b_e_i_n_g_ _p_a_r_a_s_i_t_e_m_i_c_._ _I_t_ _j_u_s_t_ _m_e_a_n_s_ _t_h_a_t_ _w_e_ _c_o_u_l_d_n_’t_ _d_e_t_e_c_t_ _i_n_f_e_c_t_i_o_n_._ _
Page 192- I_ _l_i_k_e_ _t_o_ _u_s_e_ _t_h_i_s_ _e_x_a_m_p_l_e_._ _I_’m_ _s_u_r_e_ _t_h_e_ _N_I_H_ _f_o_l_k_s_ _i_n_ _h_e_r_e_ _r_e_m_e_m_b_e_r_ _t_h_i_s_ _c_a_s_e_ _v_e_r_y_ _w_e_l_l_ _o_f_ _a_ _c_h_r_o_n_i_c_ _c_a_r_r_i_e_r_ _w_h_o_ _i_n_f_e_c_t_e_d_ _s_e_v_e_r_a_l_ _p_e_o_p_l_e_._ _T_h_i_s_ _w_a_s_ _a_ _d_o_n_o_r_ _i_n_ _t_h_e_ _N_I_H_ _b_l_o_o_d_ _p_r_o_g_r_a_m_._ _W_e_ _g_o_t_ _i_n_v_o_l_v_e_d_ _b_e_c_a_u_s_e_ _h_e_ _w_a_s_ _i_m_p_l_i_c_a_t_e_d_ _i_n_ _a_ _t_r_a_n_s_f_u_s_i_o_n_ _c_a_s_e_._ _T_h_i_s_ _g_u_y_ _w_a_s_ _a_n_ _a_s_y_m_p_t_o_m_a_t_i_c_ _c_h_r_o_n_i_c_ _c_a_r_r_i_e_r_._ _H_e_ _w_a_s_ _a_c_t_u_a_l_l_y_ _a_ _h_e_r_e_d_i_t_a_r_y_ _h_e_m_a_t_o_c_h_r_o_m_a_t_o_s_i_s_ _p_a_t_i_e_n_t_ _w_h_o_ _c_a_m_e_ _i_n_t_o_ _N_I_H_ _r_o_u_t_i_n_e_l_y_ _t_o_ _b_e_ _b_l_e_d_._ _
Page 193- In follow-up studies, he was actually implicated in an additional transfusion case. The NIH, because he was a long-term hereditary hematochromatosis patient, had samples in the freezers, I think, over five to six years. We tested every one of those samples. He was 1 to 1024 every single time. But by any test that was ever done, he was never shown to be PCR-positive. Yet he transmitted infection twice.
Page 194- O_u_r_ _o_n_l_y_ _e_x_p_l_a_n_a_t_i_o_n_ _-_-_ _a_n_d_ _w_e_ _d_o_n_’t_ _h_a_v_e_ _a_ _w_h_o_l_e_ _l_o_t_ _o_f_ _d_a_t_a_ _s_u_p_p_o_r_t_i_n_g_ _i_t_ _-_-_ _i_s_ _t_h_a_t_,_ _b_e_c_a_u_s_e_ _w_e_ _a_r_e_ _d_e_f_e_r_r_i_n_g_ _d_o_n_o_r_s_,_ _t_h_e_ _c_h_r_o_n_i_c_a_l_l_y_ _i_n_f_e_c_t_e_d_ _o_n_e_s_,_ _a_s_ _w_e_l_l_ _a_s_ _o_t_h_e_r_ _d_o_n_o_r_s_,_ _t_h_e_y_ _a_r_e_ _n_o_t_ _t_h_e_r_e_ _t_o_ _t_r_a_n_s_m_i_t_ _i_n_f_e_c_t_i_o_n_s_ _a_n_y_m_o_r_e_,_ _l_i_k_e_ _t_h_a_t_ _l_a_s_t_ _N_I_H_ _d_o_n_o_r_ _y_o_u_ _s_a_w_._ _
Page 196- D_R_._ _G_L_Y_N_N_:_ _I_ _j_u_s_t_ _w_a_n_t_e_d_ _t_o_ _k_n_o_w_,_ _h_o_w_ _l_o_n_g_ _d_i_d_ _i_t_ _t_a_k_e_,_ _o_n_ _a_v_e_r_a_g_e_,_ _t_o_ _r_e_s_o_l_v_e_ _t_h_e_ _i_n_f_e_c_t_i_o_n_ _i_n_ _t_h_e_ _7_0_ _p_e_r_c_e_n_t_ _o_f_ _d_o_n_o_r_s_?_ _
D_R_._ _L_E_I_B_Y_:_ _I_ _w_o_u_l_d_ _s_a_y_ _g_e_n_e_r_a_l_l_y_ _a_n_y_w_h_e_r_e_ _b_e_t_w_e_e_n_ _s_i_x_ _a_n_d_ _n_i_n_e_ _m_o_n_t_h_s_.__P_a_r_t_ _o_f_ _t_h_e_ _d_i_f_f_i_c_u_l_t_y_ _i_s_ _t_h_a_t_ _w_e_ _d_o_n_’t_ _k_n_o_w_ _-_-_ _w_e_ _a_r_e_ _p_i_c_k_i_n_g_ _t_h_e_m_ _u_p_ _a_s_ _b_e_i_n_g_ _a_n_t_i_b_o_d_y_-_p_o_s_i_t_i_v_e_ _-_-_ _w_e_ _d_o_n_’t_ _k_n_o_w_ _i_n_ _t_h_e_ _i_n_f_e_c_t_i_o_u_s_ _c_u_r_v_e_,_ _o_f_t_e_n_,_ _w_h_e_n_ _w_e_ _a_r_e_ _p_i_c_k_i_n_g_ _u_p_ _t_h_e_ _d_o_n_o_r_._ _T_h_a_t_’s_ _a_n_ _a_v_e_r_a_g_e_._ _I_t_ _c_o_u_l_d_ _b_e_ _l_o_n_g_e_r_;_ _i_t_ _c_o_u_l_d_ _e_v_e_n_ _b_e_ _s_h_o_r_t_e_r_._ _
D_R_._ _G_L_Y_N_N_:_ _S_o_ _i_f_ _y_o_u_ _w_e_r_e_ _t_h_i_n_k_i_n_g_ _a_b_o_u_t_ _a_ _r_e_e_n_t_r_y_ _a_l_g_o_r_i_t_h_m_,_ _w_o_u_l_d_ _y_o_u_ _w_a_i_t_ _n_i_n_e_ _m_o_n_t_h_s_,_ _1_2_ _m_o_n_t_h_s_?_ _
D_R_._ _L_E_I_B_Y_:_ _I_’m_ _n_o_t_ _a_b_o_u_t_ _t_o_ _f_o_r_m_u_l_a_t_e_ _p_o_l_i_c_y_,_ _I_ _d_o_n_’t_ _t_h_i_n_k_._ _B_u_t_ _I_ _t_h_i_n_k_ _t_h_e_ _w_a_y_ _t_o_ _d_o_ _i_t_ _-_-_ _m_y_ _o_p_i_n_i_o_n_ _o_n_l_y_ _-_-_ _w_o_u_l_d_ _b_e_ _t_o_ _w_a_i_t_ _s_o_m_e_ _p_e_r_i_o_d_ _o_f_ _t_i_m_e_,_ _s_i_x_ _t_o_ _n_i_n_e_ _m_o_n_t_h_s_,_ _a_s_ _y_o_u_ _s_u_g_g_e_s_t_e_d_,_ _o_r_ _e_v_e_n_ _a_ _y_e_a_r_ _a_n_d_ _r_e_t_e_s_t_ _t_o_ _s_e_e_ _i_f_ _t_h_e_y_ _a_r_e_ _n_e_g_a_t_i_v_e_._ _I_ _t_h_i_n_k_ _t_i_m_e_ _i_s_ _l_e_s_s_ _a_n_ _i_s_s_u_e_ _a_s_ _o_p_p_o_s_e_d_ _t_o_ _t_h_e_ _r_e_s_u_l_t_ _o_f_ _b_e_i_n_g_ _s_e_r_o_n_e_g_a_t_i_v_e_ _a_n_d_ _a_t_ _t_h_e_ _s_a_m_e_ _t_i_m_e_,_ _b_e_i_n_g_ _N_A_T_-_ _o_r_ _P_C_R_-_n_e_g_a_t_i_v_e_ _a_s_ _w_e_l_l_._ _
Page 196- DR. BOWER: Is there anything in the literature or through your work that might suggest how long someone is parasitemic before they develop a detectable antibody response?DR. LEIBY: I think that would generally be within weeks to months. There is evidence in some cases that that really varies. I think one of the things Dr. Herwaldt was trying to point out is that, depending on the patient, sometimes that varies widely. K_e_e_p_ _i_n_ _m_i_n_d_ _t_h_a_t_ _w_e_ _a_r_e_ _l_o_o_k_i_n_g_ _a_t_,_ _a_t_ _l_e_a_s_t_ _i_n_ _r_e_c_i_p_i_e_n_t_s_,_ _i_n_ _t_h_e_s_e_ _c_a_s_e_s_ _-_-_ _m_a_n_y_ _o_f_ _t_h_e_ _c_a_s_e_s_ _a_r_e_ _i_n_ _a_s_p_l_e_n_i_c_s_,_ _c_o_m_p_r_o_m_i_s_e_d_,_ _o_r_ _e_l_d_e_r_l_y_._ _Q_u_i_t_e_ _f_r_a_n_k_l_y_,_ _t_h_a_t_’s_ _w_h_e_r_e_ _a_ _l_o_t_ _o_f_ _t_h_e_m_ _a_r_e_._ _S_o_ _t_h_e_r_e_ _i_s_ _a_ _r_e_a_l_l_y_ _w_i_d_e_ _r_a_n_g_e_,_ _l_o_o_k_i_n_g_ _a_t_ _t_h_e_ _i_n_c_u_b_a_t_i_o_n_ _p_e_r_i_o_d_ _a_n_d_ _w_h_e_n_ _i_t_ _a_r_i_s_e_s_._ _I_t_ _i_s_ _d_i_f_f_e_r_e_n_t_ _i_n_ _e_a_c_h_ _c_a_s_e_._ _
D_R_._ _K_A_Z_M_I_E_R_C_Z_A_K_:_ _Y_o_u_ _g_a_v_e_ _t_h_e_ _e_x_a_m_p_l_e_ _o_f_ _y_o_u_r_ _N_I_H_ _p_e_r_s_o_n_ _w_h_o_ _w_a_s_ _P_C_R_-_n_e_g_a_t_i_v_e_,_ _s_e_r_o_p_o_s_i_t_i_v_e_,_ _a_n_d_ _y_e_t_ _t_r_a_n_s_m_i_t_t_e_d_ _t_o_ _a_ _r_e_c_i_p_i_e_n_t_._ _A_r_e_ _t_h_e_r_e_ _a_n_y_ _o_t_h_e_r_ _e_x_a_m_p_l_e_s_ _o_r_ _i_s_ _t_h_i_s_ _t_h_e_ _o_n_l_y_ _o_n_e_ _t_h_a_t_ _y_o_u_ _k_n_o_w_ _o_f_?_ _
D_R_._ _L_E_I_B_Y_:_ _N_o_,_ _t_h_a_t_’s_ _n_o_t_ _t_h_e_ _o_n_l_y_ _e_x_a_m_p_l_e_._ _T_h_e_r_e_ _a_r_e_ _o_t_h_e_r_ _e_x_a_m_p_l_e_s_ _o_f_ _p_e_o_p_l_e_ _b_e_i_n_g_ _P_C_R_-_n_e_g_a_t_i_v_e_._ _
T_h_e_r_e_ _a_r_e_ _a_ _c_o_u_p_l_e_ _o_f_ _i_s_s_u_e_s_ _t_h_e_r_e_._ _F_i_r_s_t_ _o_f_ _a_l_l_ _-_-_ _a_n_d_ _g_o_i_n_g_ _b_a_c_k_ _t_o_ _w_h_a_t_ _D_r_._ _H_e_r_w_a_l_d_t_ _s_a_i_d_ _-_-_ _t_h_e_ _b_e_s_t_ _o_p_p_o_r_t_u_n_i_t_y_ _t_o_ _d_e_t_e_c_t_ _a_ _d_o_n_o_r_ _a_s_ _b_e_i_n_g_ _P_C_R_-_p_o_s_i_t_i_v_e_ _i_s_ _t_h_a_t_ _y_o_u_ _h_a_v_e_ _s_e_g_m_e_n_t_s_,_ _b_e_c_a_u_s_e_ _t_h_e_ _s_e_g_m_e_n_t_s_ _a_r_e_ _c_l_o_s_e_s_t_ _t_o_ _t_h_e_ _o_r_i_g_i_n_a_l_ _d_o_n_a_t_i_o_n_ _t_h_a_t_ _t_r_a_n_s_f_u_s_e_d_ _t_h_e_ _i_n_f_e_c_t_i_o_n_._ _M_a_n_y_ _t_i_m_e_s_ _w_e_ _g_e_t_ _r_e_p_o_r_t_s_ _f_r_o_m_ _a_ _r_e_c_i_p_i_e_n_t_ _w_h_o_ _h_a_s_ _b_e_c_o_m_e_ _i_n_f_e_c_t_e_d_,_ _a_n_d_ _i_t_ _h_a_s_ _b_e_e_n_,_ _l_e_t_’s_ _s_a_y_,_ _a_ _c_o_u_p_l_e_ _o_f_ _m_o_n_t_h_s_ _s_i_n_c_e_ _t_h_e_i_r_ _d_o_n_a_t_i_o_n_._ _T_h_e_n_ _a_n_ _i_n_v_e_s_t_i_g_a_t_i_o_n_ _o_f_ _t_h_e_ _t_r_a_n_s_f_u_s_i_o_n_ _c_a_s_e_ _w_i_l_l_ _b_e_ _i_n_i_t_i_a_t_e_d_._ _B_y_ _t_h_e_ _t_i_m_e_ _w_e_ _g_e_t_ _
d_o_n_o_r_s_ _w_h_o_ _h_a_s_ _c_l_e_a_r_e_d_ _i_n_f_e_c_t_i_o_n_._ _S_o_ _t_h_e_ _r_e_s_u_l_t_ _i_s_,_ _y_o_u_ _t_e_s_t_ _a_l_l_ _t_h_e_ _d_o_n_o_r_s_ _a_n_d_ _t_h_e_y_ _a_r_e_ _a_l_l_ _n_e_g_a_t_i_v_e_._ _A_n_d_ _w_h_i_l_e_ _y_o_u_ _a_s_s_u_m_e_ _i_t_’s_ _a_ _t_r_a_n_s_f_u_s_i_o_n_ _c_a_s_e_,_ _y_o_u_ _d_o_n_’t_ _k_n_o_w_,_ _b_e_c_a_u_s_e_ _t_h_e_ _d_o_n_o_r_s_ _a_r_e_ _n_e_g_a_t_i_v_e_._ _I_f_ _y_o_u_ _d_o_ _f_i_n_d_ _a_ _d_o_n_o_r_,_ _i_n_ _a_l_m_o_s_t_ _e_v_e_r_y_ _c_a_s_e_ _t_h_e_y_ _a_r_e_ _I_F_A_-_p_o_s_i_t_i_v_e_,_ _b_u_t_ _P_C_R_-_n_e_g_a_t_i_v_e_._ _
Page 281- W_e_ _a_l_w_a_y_s_ _n_e_e_d_ _m_o_r_e_ _d_a_t_a_._ _B_u_t_ _b_a_s_e_d_ _o_n_ _w_h_a_t_ _I_ _h_e_a_r_d_ _t_o_d_a_y_,_ _i_f_ _D_a_v_i_d_ _L_e_i_b_y_ _i_s_ _c_o_r_r_e_c_t_ _t_h_a_t_ _t_h_e_ _p_r_e_s_e_n_c_e_ _o_f_ _a_n_t_i_b_o_d_y_ _i_n_d_i_c_a_t_e_s_ _p_e_r_s_i_s_t_e_n_t_ _p_a_r_a_s_i_t_e_m_i_a_ _-_-_ _a_l_t_h_o_u_g_h_ _i_t_’s_ _p_r_e_s_u_m_a_b_l_y_ _d_w_i_n_d_l_i_n_g_ _o_v_e_r_ _t_i_m_e_ _-_-_ _t_h_e_n_ _a_n_t_i_b_o_d_y_ _t_a_k_e_s_ _o_n_ _a_ _d_i_f_f_e_r_e_n_t_ _m_e_a_n_i_n_g_._ _
Page 282- There were questions before about how you distinguish between asymptomatic donors with active infection and those with resolved infection. We did have a fair amount of information on that in terms of the fact that we do have PCR, and real-time PCR seems to be more sensitive. This can help distinguish an active infection from a resolved infection. Perhaps even high concentrations of antibody in some patients may provide that information.
W_e_ _s_t_i_l_l_ _d_o_n_’t_ _k_n_o_w_ _t_h_e_ _f_r_e_q_u_e_n_c_y_ _o_f_ _a_c_u_t_e_ _v_e_r_s_u_s_ _c_h_r_o_n_i_c_ _d_i_s_e_a_s_e_ _t_h_a_t_ _o_c_c_u_r_s_ _i_n_ _p_o_p_u_l_a_t_i_o_n_s_ _o_r_ _t_h_e_ _i_n_c_i_d_e_n_c_e_ _o_f_ _d_i_s_e_a_s_e_ _t_h_a_t_’s_ _o_c_c_u_r_r_i_n_g_ _i_n_ _e_n_d_e_m_i_c_ _a_r_e_a_s_._ _
W_e_ _d_o_n_’t_ _k_n_o_w_ _t_h_e_ _d_u_r_a_t_i_o_n_ _o_f_ _I_g_M_ _a_n_t_i_b_o_d_y_,_ _h_o_w_ _l_o_n_g_ _i_t_’s_ _p_r_e_s_e_n_t_,_ _a_n_d_ _w_h_e_t_h_e_r_ _t_h_a_t_ _w_o_u_l_d_ _b_e_ _u_s_e_f_u_l_ _i_n_ _d_e_t_e_r_m_i_n_i_n_g_ _a_c_u_t_e_ _i_n_f_e_c_t_i_o_n_s_._ _
W_e_ _d_o_n_’t_ _k_n_o_w_ _t_h_e_ _p_e_r_c_e_n_t_ _o_f_ _c_u_r_r_e_n_t_ _i_n_f_e_c_t_i_o_n_s_ _t_h_a_t_ _a_r_e_ _n_o_n_-_B. microti._ _
T_h_e_ _f_i_n_a_l_ _o_n_e_ _i_s_,_ _w_e_ _d_i_d_ _h_a_v_e_ _d_a_t_a_ _t_h_a_t_ _p_e_r_h_a_p_s_ _t_h_e_ _n_e_w_ _I_F_A_ _t_h_a_t_ _i_s_ _a_v_a_i_l_a_b_l_e_,_ _o_r_ _t_h_e_ _n_e_w_ _t_e_c_h_n_o_l_o_g_y_ _t_h_a_t_ _i_s_ _a_v_a_i_l_a_b_l_e_,_ _w_o_u_l_d_ _b_e_ _a_d_a_p_t_a_b_l_e_ _t_o_ _m_a_s_s_ _d_o_n_o_r_ _s_c_r_e_e_n_i_n_g_._ _
S_o_ _w_h_i_l_e_ _t_h_e_r_e_ _h_a_s_ _b_e_e_n_ _s_o_m_e_ _m_o_v_e_m_e_n_t_ _a_f_o_o_t_,_ _t_h_e_r_e_ _a_r_e_ _m_a_n_y_ _q_u_e_s_t_i_o_n_s_ _w_e_ _d_o_n_’t_ _k_n_o_w_._ _I_ _t_h_i_n_k_ _t_h_a_t_’s_ _t_h_e_ _p_r_o_b_l_e_m_ _t_h_a_t_ _t_h_e_ _c_o_m_m_i_t_t_e_e_ _i_s_ _f_a_c_i_n_g_._ _M_a_n_y_ _o_f_ _y_o_u_ _h_e_r_e_ _h_a_v_e_ _e_x_p_r_e_s_s_e_d_ _i_s_s_u_e_s_ _a_b_o_u_t_ _t_e_s_t_i_n_g_,_ _a_b_o_u_t_ _t_h_e_ _s_p_e_c_i_f_i_c_i_t_y_ _a_n_d_ _s_e_n_s_i_t_i_v_i_t_y_ _o_f_ _t_h_e_ _t_e_s_t_i_n_g_,_ _a_n_d_ _s_o_ _o_n_._ _W_h_i_l_e_ _I_ _t_h_i_n_k_ _w_e_ _h_a_v_e_ _g_i_v_e_n_ _t_h_e_ _F_D_A_ _s_o_m_e_ _i_n_f_o_r_m_a_t_i_o_n_ _a_b_o_u_t_ _-_-_ _i_f_ _t_h_e_r_e_ _i_s_ _a_ _t_e_s_t_ _a_n_d_ _i_f_ _i_t_’s_ _g_o_i_n_g_ _t_o_ _b_e_ _t_e_s_t_e_d_,_ _p_e_r_h_a_p_s_ _s_o_m_e_ _s_o_r_t_ _o_f_ _r_e_g_i_o_n_a_l_ _t_e_s_t_i_n_g_ _w_o_u_l_d_ _b_e_ _u_s_e_f_u_l_ _h_e_r_e_._ _I_ _t_h_i_n_k_ _t_h_e_ _W_e_ _s_t_i_l_l_ _d_o_n_’t_ _k_n_o_w_ _t_h_e_ _f_r_e_q_u_e_n_c_y_ _o_f_ _a_c_u_t_e_ _v_e_r_s_u_s_ _c_h_r_o_n_i_c_ _d_i_s_e_a_s_e_ _t_h_a_t_ _o_c_c_u_r_s_ _i_n_ _p_o_p_u_l_a_t_i_o_n_s_ _o_r_ _t_h_e_ _i_n_c_i_d_e_n_c_e_ _o_f_ _d_i_s_e_a_s_e_ _t_h_a_t_’s_ _o_c_c_u_r_r_i_n_g_ _i_n_ _e_n_d_e_m_i_c_ _a_r_e_a_s_._ _
W_e_ _d_o_n_’t_ _k_n_o_w_ _t_h_e_ _d_u_r_a_t_i_o_n_ _o_f_ _I_g_M_ _a_n_t_i_b_o_d_y_,_ _h_o_w_ _l_o_n_g_ _i_t_’s_ _p_r_e_s_e_n_t_,_ _a_n_d_ _w_h_e_t_h_e_r_ _t_h_a_t_ _w_o_u_l_d_ _b_e_ _u_s_e_f_u_l_ _i_n_ _d_e_t_e_r_m_i_n_i_n_g_ _a_c_u_t_e_ _i_n_f_e_c_t_i_o_n_s_._ _
W_e_ _d_o_n_’t_ _k_n_o_w_ _t_h_e_ _p_e_r_c_e_n_t_ _o_f_ _c_u_r_r_e_n_t_ _i_n_f_e_c_t_i_o_n_s_ _t_h_a_t_ _a_r_e_ _n_o_n_-_B. microti._ _
T_h_e_ _f_i_n_a_l_ _o_n_e_ _i_s_,_ _w_e_ _d_i_d_ _h_a_v_e_ _d_a_t_a_ _t_h_a_t_ _p_e_r_h_a_p_s_ _t_h_e_ _n_e_w_ _I_F_A_ _t_h_a_t_ _i_s_ _a_v_a_i_l_a_b_l_e_,_ _o_r_ _t_h_e_ _n_e_w_ _t_e_c_h_n_o_l_o_g_y_ _t_h_a_t_ _i_s_ _a_v_a_i_l_a_b_l_e_,_ _w_o_u_l_d_ _b_e_ _a_d_a_p_t_a_b_l_e_ _t_o_ _m_a_s_s_ _d_o_n_o_r_ _s_c_r_e_e_n_i_n_g_._ _
S_o_ _w_h_i_l_e_ _t_h_e_r_e_ _h_a_s_ _b_e_e_n_ _s_o_m_e_ _m_o_v_e_m_e_n_t_ _a_f_o_o_t_,_ _t_h_e_r_e_ _a_r_e_ _m_a_n_y_ _q_u_e_s_t_i_o_n_s_ _w_e_ _d_o_n_’t_ _k_n_o_w_._ _I_ _t_h_i_n_k_ _t_h_a_t_’s_ _t_h_e_ _p_r_o_b_l_e_m_ _t_h_a_t_ _t_h_e_ _c_o_m_m_i_t_t_e_e_ _i_s_ _f_a_c_i_n_g_._ _M_a_n_y_ _o_f_ _y_o_u_ _h_e_r_e_ _h_a_v_e_ _e_x_p_r_e_s_s_e_d_ _i_s_s_u_e_s_ _a_b_o_u_t_ _t_e_s_t_i_n_g_,_ _a_b_o_u_t_ _t_h_e_ _s_p_e_c_i_f_i_c_i_t_y_ _a_n_d_ _s_e_n_s_i_t_i_v_i_t_y_ _o_f_ _t_h_e_ _t_e_s_t_i_n_g_,_ _a_n_d_ _s_o_ _o_n_._ _W_h_i_l_e_ _I_ _t_h_i_n_k_ _w_e_ _h_a_v_e_ _g_i_v_e_n_ _t_h_e_ _F_D_A_ _s_o_m_e_ _i_n_f_o_r_m_a_t_i_o_n_ _a_b_o_u_t_ _-_-_ _i_f_ _t_h_e_r_e_ _i_s_ _a_ _t_e_s_t_ _a_n_d_ _i_f_ _i_t_’s_ _g_o_i_n_g_ _t_o_ _b_e_ _t_e_s_t_e_d_,_ _p_e_r_h_a_p_s_ _s_o_m_e_ _s_o_r_t_ _o_f_ _r_e_g_i_o_n_a_l_ _t_e_s_t_i_n_g_ _w_o_u_l_d_ _b_e_ _u_s_e_f_u_l_ _h_e_r_e_._ _I_ _t_h_i_n_k_ _t_h_e_ _
D_R_._ _A_L_T_E_R_:_ _I_ _d_e_f_i_n_i_t_e_l_y_ _a_g_r_e_e_ _w_i_t_h_ _w_h_a_t_ _D_r_._ _B_e_n_j_a_m_i_n_ _j_u_s_t_ _s_a_i_d_._ _W_e_ _a_l_w_a_y_s_ _n_e_e_d_ _m_o_r_e_ _d_a_t_a_._ _B_u_t_ _b_a_s_e_d_ _o_n_ _w_h_a_t_ _I_ _h_e_a_r_d_ _t_o_d_a_y_,_ _i_f_ _D_a_v_i_d_ _L_e_i_b_y_ _i_s_ _c_o_r_r_e_c_t_ _t_h_a_t_ _t_h_e_ _p_r_e_s_e_n_c_e_ _o_f_ _a_n_t_i_b_o_d_y_ _i_n_d_i_c_a_t_e_s_ _p_e_r_s_i_s_t_e_n_t_ _p_a_r_a_s_i_t_e_m_i_a_ _-_-_ _a_l_t_h_o_u_g_h_ _i_t_’s_ _p_r_e_s_u_m_a_b_l_y_ _d_w_i_n_d_l_i_n_g_ _o_v_e_r_ _t_i_m_e_ _-_-_ _t_h_e_n_ _a_n_t_i_b_o_d_y_ _t_a_k_e_s_ _o_n_ _a_ _d_i_f_f_e_r_e_n_t_ _m_e_a_n_i_n_g_._ _I_’m_ _e_n_c_o_u_r_a_g_e_d_ _b_y_ _t_h_e_ _f_a_c_t_ _t_h_a_t_ _t_h_e_ _a_n_t_i_b_o_d_y_ _d_i_s_a_p_p_e_a_r_s_ _e_v_e_n_t_u_a_l_l_y_._ _Y_o_u_ _w_i_l_l_ _b_e_ _a_b_l_e_ _t_o_ _r_e_e_n_t_e_r_ _t_h_e_s_e_ _d_o_n_o_r_s_ _l_a_t_e_r_ _o_n_._ _S_o_ _i_f_ _I_ _h_a_d_ _t_o_ _p_i_c_k_ _o_n_e_ _t_e_s_t_,_ _I_F_A_ _m_a_k_e_s_ _m_o_r_e_ _s_e_n_s_e_ _t_o_ _m_e_,_ _g_i_v_e_n_ _t_h_e_ _p_i_t_f_a_l_l_s_ _o_f_ _t_h_a_t_ _p_a_r_t_i_c_u_l_a_r_ _P_C_R_._ _Y_o_u_ _w_o_u_l_d_ _m_i_s_s_ _a_n_ _o_c_c_a_s_i_o_n_a_l_ _w_i_n_d_o_w_-_p_e_r_i_o_d_,_ _b_u_t_ _w_e_ _k_n_o_w_ _w_e_’r_e_ _g_o_i_n_g_ _t_o_ _m_i_s_s_ _t_h_i_n_g_s_._ _B_u_t_ _y_o_u_ _w_o_u_l_d_ _c_a_p_t_u_r_e_ _t_h_e_ _p_e_o_p_l_e_ _w_h_o_ _a_r_e_ _i_n_f_e_c_t_e_d_ _f_o_r_ _a_ _l_o_n_g_e_r_ _t_i_m_e_._ _Y_o_u_ _b_e_c_o_m_e_ _p_o_s_i_t_i_v_e_ _r_e_l_a_t_i_v_e_l_y_ _e_a_r_l_y_ _i_n_ _t_h_e_ _i_n_f_e_c_t_i_o_n_._ _I_ _t_h_i_n_k_ _i_t_’s_ _m_o_r_e_ _d_o_a_b_l_e_ _o_n_ _a_ _b_l_o_o_d_-_b_a_n_k_ _
Page 284- T_h_e_ _F_D_A_’s_ _p_o_s_i_t_i_o_n_ _i_s_,_ _b_e_t_t_e_r_ _t_o_ _b_e_ _d_o_i_n_g_ _s_o_m_e_t_h_i_n_g_ _t_h_a_t_,_ _a_t_ _l_e_a_s_t_ _o_n_ _a_ _b_a_s_i_c_ _s_c_i_e_n_t_i_f_i_c_ _c_o_n_s_i_d_e_r_a_t_i_o_n_,_ _i_s_ _l_i_k_e_l_y_ _t_o_ _h_a_v_e_ _b_e_n_e_f_i_t_ _t_h_a_n_ _t_o_ _b_e_ _d_o_i_n_g_ _n_o_t_h_i_n_g_._ _
Page 136- Clinical presentation: The signs and symptoms of transfusion-transmitted babesiosis are no different from natural infection, more or less the same. As I said earlier, it may remain asymptomatic or present as a flu-like infection or fulminant febrile illness, usually within one to nine weeks post-transfusion and maybe up to three months. I have seen one report goes up to six months also. The fatality rates may be a high as 20 percent, and possibly more. There are the underlying causes, such as -- or immunocompromised.
Page 136- The areas of Babesia transmission are expanding, as I said earlier. One point I did not put here is the reclaiming of the agricultural lands now, so more reforestation. Also the crux of the issue is here, increased recognition and diagnosis of babesiosis. That may seem like the transmission is expanding now. So areas which were not known to be Babesia-endemic areas -- infections are showing up here.Probably one reason could be better recognition and could be more infected ticks also expanding.
Page 139- But then again, antibody positivity and parasitemia have been seen year round. So the seasonal testing scenario may not be very effective.
Page 140- There is on FDA-approved laboratory test available to screen blood donors for Babesia infections, and this compounds the problem.
T_h_e_ _b_o_t_t_o_m_ _l_i_n_e_ _h_e_r_e_ _i_s_ _t_h_a_t_ _t_h_e_s_e_ _m_a_p_s_ _n_e_e_d_ _t_o_ _b_e_ _c_u_r_r_e_n_t_,_ _a_c_t_u_a_l_l_y_._ _I_t_’s_ _a_ _m_o_v_i_n_g_ _t_a_r_g_e_t_,_ _a_n_d_ _c_o_n_s_t_a_n_t_ _w_o_r_k_ _w_i_l_l_ _b_e_ _n_e_e_d_e_d_ _t_o_ _k_e_e_p_ _a_b_r_e_a_s_t_ _o_f_ _t_h_e_ _c_u_r_r_e_n_t_ _
Page 141- T_h_e_r_e_ _w_a_s_ _g_e_n_e_r_a_l_ _a_g_r_e_e_m_e_n_t_ _t_h_a_t_ _f_u_r_t_h_e_r_ _s_t_u_d_i_e_s_ _a_r_e_ _n_e_e_d_e_d_ _t_o_ _d_e_t_e_r_m_i_n_e_ _t_h_e_ _u_t_i_l_i_t_y_ _o_f_ _a_v_a_i_l_a_b_l_e_ _l_a_b_o_r_a_t_o_r_y_ _t_e_s_t_i_n_g_,_ _i_d_e_n_t_i_f_y_i_n_g_ _a_s_y_m_p_t_o_m_a_t_i_c_ _d_o_n_o_r_s_._ _T_h_e_n_ _a_l_s_o_ _n_o_v_e_l_ _m_e_t_h_o_d_s_ _a_r_e_ _n_e_e_d_e_d_ _t_h_a_t_ _c_a_n_ _d_i_s_t_i_n_g_u_i_s_h_ _b_e_t_w_e_e_n_ _c_u_r_r_e_n_t_l_y_ _i_n_f_e_c_t_e_d_ _v_e_r_s_u_s_ _t_h_o_s_e_ _w_i_t_h_ _p_a_s_t_ _i_n_f_e_c_t_i_o_n_s_._ _I_ _t_h_i_n_k_ _t_h_a_t_’s_ _s_o_m_e_t_h_i_n_g_ _t_h_a_t_ _i_s_ _m_o_s_t_ _n_e_e_d_e_d_ _a_t_ _t_h_i_s_ _t_i_m_e_._ _