Establishing Cutoffs for Streptococcal Antibody Titers in Uganda: Implications for Rheumatic Fever Diagnosis

• DOI: 10.2139/ssrn.3457410
• Publication Date: 2020-03-24T11:42:05Z
• Authors: Emmy Okello; Meghna Murali; Joselyn Rwebembera; Gloria Kaudha; Jenifer Atala; Nada Harik; Samalie Kitooleko; Chris T Longenecker; Emma Ndagire; Isaac Otim Omara; Linda Mary Oyella; Tom Parks; Jafes Pulle; Craig Sable; Rachel Sarnacki; Elizabeth Stein; Meghan Zimmerman; Nicholas de Klerk; Jonathan Carapetis; Andrea Beaton
• Keywords: Antibody titer; STREPTOCOCCAL INFECTIONS

Background: Central to rheumatic fever (RF) diagnosis is evidence of streptococcal exposure, specifically antistreptolysin O (ASO) and antideoxyribonuclease B (ADB) antibodies. It unknown if these antibody titers should be adjusted the background exposure rates GAS or published standards used. Here, we establish normal values ASO ADB in Uganda examine RF case detection using vs. population-specific thresholds. Methods: Participants (age 0-50 years) were recruited. was measured in-country by nephelometric technique. samples sent Australia (PathWest) for determination enzyme inhibition assay, 80% upper limit age established. The standard (200IU/ml) (375IU/ml) compared Ugandan (ULN) children 5-15 years. Findings: Of 428 participants, 16 excluded (9 sore throat, 1 skin sores, 5 fever, 4 echocardiograms showing occult RHD), 183 remaining median titer this group 220 IU/ml, with 80th percentile value 389 IU/ml. 375 568 Application new cutoffs 528 enrolled our prospective study, reduced number definite cases 120/528 (22·7%), as 173/528 (32·8%) values. Interpretation: ULN are higher than other countries. Applying results diagnostic specificity, but some loss sensitivity. Implications over-diagnosis missed will explored through a longitudinal follow-up study research program. Funding Statement: This work supported American Heart Association (#17SFRN33670607), DELTAS Africa Initiative (DEL-15-011 THRiVE-2), General Electric.Declaration Interests: There no conflicts interest conducting study.Ethics Approval Institutional review board (IRB) approval obtained from Research Ethics Committee at Makerere University School Medicine, Children’s National Medical Center IRB, Council Science Technology IRB. We approached all participants their consent, explained detail nurse participants’ primary language. All provided written informed consent before information collected only parent guardian assent aged 8 years older.