CT694 and pgp3 as Serological Tools for Monitoring Trachoma Programs

Goodhew, E. Brook; Priest, Jeffrey W.; Moss, Delynn M.; Zhong, Guangming; Muñoz, Beatriz; Mkocha, Harran; Martin, Diana L.; West, Sheila K.; Gaydos, Charlotte A.; Lammie, Patrick J.

doi:10.1371/journal.pntd.0001873

Cited by 108 publications

(179 citation statements)

References 24 publications

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“…Since chlamydiae can complete their biosynthesis inside the inclusion, any chlamydial proteins that are secreted outside the inclusion may be used by chlamydial organisms as virulence factors for interaction with the infected host. Second, Pgp3 is an immunodominant antigen in women who have acquired chlamydial infection via either the genital tract (42,43) or the ocular route (38,44). In general, chlamydia-secreted proteins are likely to be more immunogenic (43).…”

Section: Figmentioning

confidence: 99%

Plasmid-Encoded Pgp3 Is a Major Virulence Factor for Chlamydia muridarum To Induce Hydrosalpinx in Mice

et al. 2014

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dHydrosalpinx induction in mice by Chlamydia muridarum infection, a model that has been used to study C. trachomatis pathogenesis in women, is known to depend on the cryptic plasmid that encodes eight genes designated pgp1 to pgp8. To identify the plasmid-encoded pathogenic determinants, we evaluated C. muridarum transformants deficient in the plasmid-borne gene pgp3, -4, or -7 for induction of hydrosalpinx. C. muridarum transformants with an in-frame deletion of either pgp3 or -4 but not -7 failed to induce hydrosalpinx. The deletion mutant phenotype was reproduced by using transformants with premature termination codon insertions in the corresponding pgp genes (to minimize polar effects inherent in the deletion mutants). Pgp4 is known to regulate pgp3 expression, while lack of Pgp3 does not significantly affect Pgp4 function. Thus, we conclude that Pgp3 is an effector virulence factor and that lack of Pgp3 may be responsible for the attenuation in C. muridarum pathogenicity described above. This attenuated pathogenicity was further correlated with a rapid decrease in chlamydial survival in the lower genital tract and reduced ascension to the upper genital tract in mice infected with C. muridarum deficient in Pgp3 but not Pgp7. The Pgp3-deficient C. muridarum organisms were also less invasive when delivered directly to the oviduct on day 7 after inoculation. These observations demonstrate that plasmid-encoded Pgp3 is required for C. muridarum survival in the mouse genital tract and represents a major virulence factor in C. muridarum pathogenesis in mice.

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Section: Figmentioning

confidence: 99%

Plasmid-Encoded Pgp3 Is a Major Virulence Factor for Chlamydia muridarum To Induce Hydrosalpinx in Mice

et al. 2014

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“…Depending on the country, serum was prepared from whole blood by centrifugation, or serum was eluted from DBS as previously described. 13,14 TT (Massachusetts Biologic Laboratories, Boston, MA) was coupled to SeroMap microspheres (Luminex Corp., Austin, TX) at the Centers for Disease Control and Prevention (CDC) with 12.5 μg of toxoid per 12.5 × 10 6 beads in buffer containing 50 mM 2-(N-morpholino) ethanesulfonic acid and 0.85% NaCl at pH 5.0, as previously described. 13,15 Serum samples were diluted 1:400 and assayed in duplicate for IgG (along with control sera) against multiple bacterial, viral, and parasitic disease antigens at CDC in Atlanta, GA, or the Kenya Medical Research Institute (KEMRI) in Nairobi, Kenya, using the conditions previously described.…”

mentioning

confidence: 99%

Tetanus Immunity Gaps in Children 5–14 Years and Men ≥ 15 Years of Age Revealed by Integrated Disease Serosurveillance in Kenya, Tanzania, and Mozambique

Scobie

Patel

Martin

et al. 2017

The American Society of Tropical Medicine and Hygiene

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Abstract. Recent tetanus cases associated with male circumcision in Eastern and Southern Africa (ESA) prompted an examination of tetanus immunity by age and sex using multiplex serologic data from community surveys in three ESA countries during 2012-2013. Tetanus seroprotection was lower among children 5-14 years versus 1-4 years of age in Kenya (66% versus 90%) and Tanzania (66% versus 89%), but not in Mozambique (91% versus 88%), where children receive two booster doses in school. Among males ≥ 15 years of age, tetanus seroprotection was lower than females in Kenya (45% versus 96%), Tanzania (28% versus 94%), and Mozambique (64% versus 90%). Tetanus immunity from infant vaccination doses wanes over time, and only women of reproductive age routinely receive booster doses. To prevent immunity gaps in older children, adolescents, and adult men, a life-course vaccination strategy is needed to provide the three recommended tetanus booster doses.

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“…The first was an enzyme-linked immunosorbent assay (ELISA) assay that measured antibodies against the Ct antigen Pgp3 5, 6 . This tool has been used to assess transmission of both urogenital 7 and ocular 8 infections, including the study on Kiritimati Island, where we showed that there were strong associations between Ct infection, TF and anti-Pgp3 antibody levels. We also observed a rapid increase in Pgp3 seroprevalence throughout childhood years in that population 4 .…”

Section: Introductionmentioning

confidence: 94%

Clinical signs of trachoma are prevalent among Solomon Islanders who have no persistent markers of prior infection with Chlamydia trachomatis

Butcher¹,

Sokana²,

Jack³

et al. 2018

Wellcome Open Res

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Background: The low population-prevalence of trachomatous trichiasis and high prevalence of trachomatous inflammation–follicular (TF) provide contradictory estimates of the magnitude of the public health threat from trachoma in the Solomon Islands. Improved characterisation of the biology of trachoma in the region may support policy makers as they decide what interventions are required. Here, age-specific profiles of anti-Pgp3 antibodies and conjunctival scarring were examined to determine whether there is evidence of ongoing transmission and pathology from ocular Chlamydia trachomatis (Ct) infection. Methods: A total of 1511 individuals aged ≥1 year were enrolled from randomly selected households in 13 villages in which >10% of children aged 1–9 years had TF prior to a single round of azithromycin mass drug administration undertaken six months previously. Blood was collected to be screened for antibodies to the Ct antigen Pgp3. Tarsal conjunctival photographs were collected for analysis of scarring severity. Results: Anti-Pgp3 seropositivity was 18% in 1–9 year olds, sharply increasing around the age of sexual debut to reach 69% in those over 25 years. Anti-Pgp3 seropositivity did not increase significantly between the ages of 1–9 years and was not associated with TF (p=0.581) or scarring in children (p=0.472). Conjunctival scars were visible in 13.1% of photographs. Mild (p<0.0001) but not severe (p=0.149) scars increased in prevalence with age. Conclusions: Neither conjunctival scars nor lymphoid follicles were associated with antibodies to Ct, suggesting that they are unlikely to be a direct result of ocular Ct infection . Clinical signs of trachoma were prevalent in this population but were not indicative of the underlying rates of Ct infection. The current World Health Organization guidelines for trachoma elimination indicated that this population should receive intervention with mass distribution of antibiotics, but the data presented here suggest that this may not have been appropriate.

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CT694 and pgp3 as Serological Tools for Monitoring Trachoma Programs

Cited by 108 publications

References 24 publications

Plasmid-Encoded Pgp3 Is a Major Virulence Factor for Chlamydia muridarum To Induce Hydrosalpinx in Mice

Plasmid-Encoded Pgp3 Is a Major Virulence Factor for Chlamydia muridarum To Induce Hydrosalpinx in Mice

Tetanus Immunity Gaps in Children 5–14 Years and Men ≥ 15 Years of Age Revealed by Integrated Disease Serosurveillance in Kenya, Tanzania, and Mozambique

Clinical signs of trachoma are prevalent among Solomon Islanders who have no persistent markers of prior infection with Chlamydia trachomatis

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