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Serology for trachoma surveillance after cessation of mass drug administration.

Martin DL, Bid R, Sandi F, Goodhew EB, Massae PA, Lasway A, Philippin H, Makupa W, Molina S, Holland MJ, Mabey DC, Drakeley C, Lammie PJ, Solomon AW - PLoS Negl Trop Dis (2015)

Bottom Line: Among 1-9 year olds, TF prevalence was 6.5%, whereas only 3.5% were seropositive.Force of infection modelling indicated a 10-fold decrease in seroconversion rate at a time corresponding to MDA commencement.Without baseline serological data, the inferences we can make about antibody status before MDA and the longevity of the antibody response are limited, though our use of catalytic modelling overcomes some of these limitations.

View Article: PubMed Central - PubMed

Affiliation: Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.

ABSTRACT

Background: Trachoma, caused by Chlamydia trachomatis (Ct), is the leading infectious cause of blindness worldwide. Yearly azithromycin mass drug administration (MDA) plays a central role in efforts to eliminate blinding trachoma as a public health problem. Programmatic decision-making is currently based on the prevalence of the clinical sign "trachomatous inflammation-follicular" (TF) in children. We sought to test alternative tools for trachoma surveillance based on serology in the 12-year cohort of Kahe Mpya, Rombo District, Tanzania, where ocular chlamydial infection was eliminated with azithromycin MDA by 2005.

Methodology and principal findings: The present study was a community-based cross-sectional survey in Kahe Mpya. Of 989 residents, 571 people aged 6 months to 87 years were enrolled: 58% of the total population and 73% of 1-9 year olds, the key WHO indicator age group. Participants were examined for TF, had conjunctival swabs collected for nucleic acid amplification test (NAAT)-based detection of Ct, and blood collected for analysis of antibodies to the Ct antigens pgp3 and CT694 by multiplex bead-based immunoassay. Seroconversion rate was used to estimate changes in the force of infection in a reversible catalytic model. No conjunctival swabs tested positive for Ct infection by NAAT. Among 1-9 year olds, TF prevalence was 6.5%, whereas only 3.5% were seropositive. Force of infection modelling indicated a 10-fold decrease in seroconversion rate at a time corresponding to MDA commencement. Without baseline serological data, the inferences we can make about antibody status before MDA and the longevity of the antibody response are limited, though our use of catalytic modelling overcomes some of these limitations.

Conclusions/significance: Serologic tests support NAAT findings of very low to zero prevalence of ocular Ct in this community and have potential to provide objective measures of transmission and useful surveillance tools for trachoma elimination programs.

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Related in: MedlinePlus

Antibody responses to Ct antigens 10 years after MDA cessation.A. Age-prevalence curves for antibody responses grouped by decade. Black squares represent individuals with any antibody-positive test (to pgp3 alone, CT694 alone, or both antigens), and red squares represent responses positive to both pgp3 and CT694. B. Plots show box-and-whiskers graph (min-max) of MFI-BG against age ranges grouped by decade for antibodies against pgp3 (left) and CT694 (right). C. Plots show age against MFI-BG for children aged 1–9. Each dot represents a single individual. Note the differences in the y-axis scales for pgp3 (left) and CT694 (right). Indeterminate range is shaded. Horizontal lines indicate cutoffs for antibody positivity. Ag = antigen.
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pntd.0003555.g001: Antibody responses to Ct antigens 10 years after MDA cessation.A. Age-prevalence curves for antibody responses grouped by decade. Black squares represent individuals with any antibody-positive test (to pgp3 alone, CT694 alone, or both antigens), and red squares represent responses positive to both pgp3 and CT694. B. Plots show box-and-whiskers graph (min-max) of MFI-BG against age ranges grouped by decade for antibodies against pgp3 (left) and CT694 (right). C. Plots show age against MFI-BG for children aged 1–9. Each dot represents a single individual. Note the differences in the y-axis scales for pgp3 (left) and CT694 (right). Indeterminate range is shaded. Horizontal lines indicate cutoffs for antibody positivity. Ag = antigen.

Mentions: Overall, 33.8% of participants were seropositive against at least one antigen (Fig. 1A). Seropositivity increased with age. By age 40, over 90% of participants tested positive to at least one antigen (pgp3 alone, CT694 alone, or both pgp3 and CT694, black squares, Fig. 1A), and over 60% tested positive to both antigens (Fig. 1A, red squares); this trend continued to the oldest age groups (Fig. 1A). The MFI also increased with age (Fig. 1B). Of 200 children aged 1–9, seven (3.5%) had antibody responses to one antigen, whereas only two (1%) had antibody responses to both antigens (Fig. 1C). Five of the seven samples with pgp3 reactivity fell into the indeterminate range, as did both of the CT694-reactive samples (Fig. 1C). Samples from six of the seven 1–9 year olds testing positive by serology were re-tested with separate pgp3 and CT694 bead sets and data replicated the original results (S1 Table).


Serology for trachoma surveillance after cessation of mass drug administration.

Martin DL, Bid R, Sandi F, Goodhew EB, Massae PA, Lasway A, Philippin H, Makupa W, Molina S, Holland MJ, Mabey DC, Drakeley C, Lammie PJ, Solomon AW - PLoS Negl Trop Dis (2015)

Antibody responses to Ct antigens 10 years after MDA cessation.A. Age-prevalence curves for antibody responses grouped by decade. Black squares represent individuals with any antibody-positive test (to pgp3 alone, CT694 alone, or both antigens), and red squares represent responses positive to both pgp3 and CT694. B. Plots show box-and-whiskers graph (min-max) of MFI-BG against age ranges grouped by decade for antibodies against pgp3 (left) and CT694 (right). C. Plots show age against MFI-BG for children aged 1–9. Each dot represents a single individual. Note the differences in the y-axis scales for pgp3 (left) and CT694 (right). Indeterminate range is shaded. Horizontal lines indicate cutoffs for antibody positivity. Ag = antigen.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4340913&req=5

pntd.0003555.g001: Antibody responses to Ct antigens 10 years after MDA cessation.A. Age-prevalence curves for antibody responses grouped by decade. Black squares represent individuals with any antibody-positive test (to pgp3 alone, CT694 alone, or both antigens), and red squares represent responses positive to both pgp3 and CT694. B. Plots show box-and-whiskers graph (min-max) of MFI-BG against age ranges grouped by decade for antibodies against pgp3 (left) and CT694 (right). C. Plots show age against MFI-BG for children aged 1–9. Each dot represents a single individual. Note the differences in the y-axis scales for pgp3 (left) and CT694 (right). Indeterminate range is shaded. Horizontal lines indicate cutoffs for antibody positivity. Ag = antigen.
Mentions: Overall, 33.8% of participants were seropositive against at least one antigen (Fig. 1A). Seropositivity increased with age. By age 40, over 90% of participants tested positive to at least one antigen (pgp3 alone, CT694 alone, or both pgp3 and CT694, black squares, Fig. 1A), and over 60% tested positive to both antigens (Fig. 1A, red squares); this trend continued to the oldest age groups (Fig. 1A). The MFI also increased with age (Fig. 1B). Of 200 children aged 1–9, seven (3.5%) had antibody responses to one antigen, whereas only two (1%) had antibody responses to both antigens (Fig. 1C). Five of the seven samples with pgp3 reactivity fell into the indeterminate range, as did both of the CT694-reactive samples (Fig. 1C). Samples from six of the seven 1–9 year olds testing positive by serology were re-tested with separate pgp3 and CT694 bead sets and data replicated the original results (S1 Table).

Bottom Line: Among 1-9 year olds, TF prevalence was 6.5%, whereas only 3.5% were seropositive.Force of infection modelling indicated a 10-fold decrease in seroconversion rate at a time corresponding to MDA commencement.Without baseline serological data, the inferences we can make about antibody status before MDA and the longevity of the antibody response are limited, though our use of catalytic modelling overcomes some of these limitations.

View Article: PubMed Central - PubMed

Affiliation: Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.

ABSTRACT

Background: Trachoma, caused by Chlamydia trachomatis (Ct), is the leading infectious cause of blindness worldwide. Yearly azithromycin mass drug administration (MDA) plays a central role in efforts to eliminate blinding trachoma as a public health problem. Programmatic decision-making is currently based on the prevalence of the clinical sign "trachomatous inflammation-follicular" (TF) in children. We sought to test alternative tools for trachoma surveillance based on serology in the 12-year cohort of Kahe Mpya, Rombo District, Tanzania, where ocular chlamydial infection was eliminated with azithromycin MDA by 2005.

Methodology and principal findings: The present study was a community-based cross-sectional survey in Kahe Mpya. Of 989 residents, 571 people aged 6 months to 87 years were enrolled: 58% of the total population and 73% of 1-9 year olds, the key WHO indicator age group. Participants were examined for TF, had conjunctival swabs collected for nucleic acid amplification test (NAAT)-based detection of Ct, and blood collected for analysis of antibodies to the Ct antigens pgp3 and CT694 by multiplex bead-based immunoassay. Seroconversion rate was used to estimate changes in the force of infection in a reversible catalytic model. No conjunctival swabs tested positive for Ct infection by NAAT. Among 1-9 year olds, TF prevalence was 6.5%, whereas only 3.5% were seropositive. Force of infection modelling indicated a 10-fold decrease in seroconversion rate at a time corresponding to MDA commencement. Without baseline serological data, the inferences we can make about antibody status before MDA and the longevity of the antibody response are limited, though our use of catalytic modelling overcomes some of these limitations.

Conclusions/significance: Serologic tests support NAAT findings of very low to zero prevalence of ocular Ct in this community and have potential to provide objective measures of transmission and useful surveillance tools for trachoma elimination programs.

Show MeSH
Related in: MedlinePlus