Dynamics of anti-Strongyloides IgG antibody responses and implications for strongyloidiasis surveillance in rural Amazonians: A population-based panel data analysis

Abstract

Background: Human strongyloidiasis was recently incorporated into the World Health Organization roadmap for neglected tropical diseases targeted for control in 2021-2030. However, the prevalence, incidence, and clinical burden of Strongyloides stercoralis infection remain understudied in remote communities across the Amazon due to its chronic nature, usually with absent or unspecific clinical manifestations, and the lack of practical and sensitive diagnostics for large-scale use. Here, we apply repeated antibody testing to estimate the prevalence of anti-Strongyloides IgG responses and identify incident infections in five farming settlements in the Amazonas State of Brazil.

Methodology/principal findings: We used an in-house enzyme immunoassay, with a S. venezuelensis larval extract as the solid-phase antigen, to detect specific IgG antibodies in 898 plasma samples collected during consecutive cross-sectional surveys over 4 years from 426 study participants aged >3 months, with an average of 35.9 years. Overall, 465 (51.8%) samples tested positive. However, only two infections that had been detected by fecal microscopy at survey 1 (March-May 2010) were treated with ivermectin. Antibody prevalence rose from 45.9% in 2010 to 61.1% in 2013, consistent with an increased (re)exposure to infective larvae over time. On average, there were 24.5 seroconversion events (a proxy of recent exposure to infection) per 100 person-years of follow-up, with 18.1 seroreversion events per 100 person-years. Nearly all participants with high antibody levels (i.e., above the median absorbance of seropositive tests) remained seropositive over the next years, with a single instance of high-to-nil antibody transition. Long-lasting high-level IgG responses were most likely due to frequent re-exposure to infective S. stercoralis larvae, chronic carriage of adult worms in the absence of treatment, or both. Conversely, over one-third of participants with low anti-Strongyloides antibody levels had transient IgG responses and seroreversed within 12 months.

Conclusions/significance: The results support the use of repeated antibody testing for monitoring temporal changes in S. stercoralis transmission in remote populations.

Fig 1. Distribution of participants in consecutive surveys carried out in farming settlements in Amazonas State, Brazil, according to anti-Strongyloides IgG antibody status.

Panel A, blood draws approximately 12 months apart (data from 2010 vs. 2011, 2011 vs. 2012, 2012 vs 2013, and 2013 vs. 2014; n = 408 comparisons); Panel B, blood draws approximately 24 months apart (data from 2010 vs. 2012, 2011 vs. 2013, and 2012 vs. 2014; n = 262 comparisons); Panel C, blood draws approximately 36 months apart (data from 2010 vs. 2013 and 2011 vs. 2014; n = 130 comparisons); Panel D, blood draws approximately 48 months apart (2010 vs. 2014; n = 45 comparisons). Anti-Strongyloides IgG responses were stratified as negative (absorbance ≤ 0.286; light gray), low (absorbance between 0.287 and 0.561; light purple) and high (absorbance > 0.561; purple), with the absorbance value of 0.561 corresponding to the median absorbance value among positive samples during the study. Numbers of individuals within each antibody status category are shown. Data from Panel A (see also the italicized numbers in S2 Table) were used to estimate the 12-month seroconversion rate: of 213 initially seronegative participants, 47 (22.1%) had low antibody titers detected 12 months later (nil-to-low conversions) and 6 (2.8%) had high antibody titers detected 12 months later (nil-to-high conversions).

Fig 2. Individual anti-Strongyloides IgG antibody trajectories among 51 participants who presented one or more seroconversions event during consecutive surveys in farming settlements in Amazonas State, Brazil, 2010-2014.

Data are displayed in four panels from left to right and each row within a panel represents an individual (n = 12 in the leftmost panel and n = 13 in the other panels). Seroconversion events were defined as an IgG-positive test (absorbance > 0.286) preceded by a negative test 12 months earlier. Samples are ordered in relation to the time of seroconversion and empty spaces indicate missing samples at specific time points. Color codes indicate antibody test results: white means negative (absorbance ≤ 0.286) and coral orange tones indicate quartiles of absorbance in positive samples, 0.287 to 0.366 for the first quartile (lightest tone), 0.367 to 0.561 for the second quartile (coral), 0.562 to 1.121 for the third quartile (darker tone), and above 1.121 for the fourth quartile (brown). By definition, all samples collected 12 months before seroconversion (time point “-12”) were negative. Arrows indicate two participants with two seroconversion events each (months 0 and 24).