1. Epidemiology and Global Health
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Infection-exposure in infancy is associated with reduced allergy-related disease in later childhood in a Ugandan cohort

  1. Lawrence Lubyayi  Is a corresponding author
  2. Harriet Mpairwe
  3. Gyaviira Nkurunungi
  4. Swaib A Lule
  5. Angela Nalwoga
  6. Emily L Webb
  7. Jonathan Levin
  8. Alison M Elliott
  1. Immuno-modulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Uganda
  2. Division of Epidemiology and Biostatistics, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa, South Africa
  3. Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, United Kingdom
  4. Department of Infection Biology, London School of Hygiene and Tropical Medicine, United Kingdom
  5. Institute for Global Health, University College London, United Kingdom
  6. MRC International Statistics and Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, United Kingdom
  7. Department of Clinical Research, London School of Hygiene and Tropical Medicine, United Kingdom
Research Article
Cite this article as: eLife 2021;10:e66022 doi: 10.7554/eLife.66022
6 figures, 4 tables and 3 additional files

Figures

Map of Entebbe and Katabi showing the study area and the three main geographical zones of maternal residence at enrolment.
Flowchart showing number of the Entebbe Mother and Baby Study participants with data on illnesses/infections during each year.

Numbers for each year (centre column of the flowchart) represent the children who presented at the study clinic at any point during that year. Numbers for malaria, diarrhoea, lower respiratory tract infection (LRTI) and upper respiratory tract infection (URTI) represent the children who were positively diagnosed (at least once during a given year) for each of those illnesses, on presentation at the study clinic. Numbers for any helminth, norovirus, cytomegalovirus (CMV), and herpes simplex virus (HSV) represent children samples assessed for any of those infections at the respective annual visit.

Proportion of children with illnesses/infections, over time, in the Entebbe Mother and Baby Study cohort.
Cumulative infection experience, over time, in the Entebbe Mother and Baby Study cohort.
Probability of having infections conditional on latent class membership during the first year.
Probability of having infections conditional on latent class membership considering cumulative prevalence of infections over all the 5 years.

Tables

Table 1
Number (and proportion) of children in each latent class at year 1 and at year 5 considering cumulative infection experience.
LC 1LC 2
Number (%)Number (%)
Year 1 (n = 2077)665 (32)1412 (68)
Year 5 (n = 1668)517 (31)1151 (69)
  1. LC is latent class. LC 1 represents the class with higher probabilities for various infections as compared to LC 2, however, the profile of infections changes at each time period.

Table 2
Odds ratio estimates for effects of covariates on membership in latent class 1 at year 1 and at year 5 considering cumulative infection experience.
Year 1 exposure5-Year cumulative exposure
CovariateOdds ratio(95% CI)Odds ratio(95% CI)
Mother’s social economic status
Higher vs. lower0.77(0.58, 1.02)0.51(0.31, 0.82)
Household’s social economic status
Higher vs. lower0.87(0.66, 1.14)0.58(0.25, 0.92)
Maternal history of asthma or eczema
History present vs. absent0.74(0.43, 1.27)0.50(0.24, 1.53)
Area of residence at birth
Kigungu vs. Entebbe0.33(0.18, 0.62)5.73(3.24, 8.12)
Manyago vs. Entebbe1.20(0.88, 1.63)1.08(0.88, 1.63)
Katabi vs. Entebbe2.43(1.62, 3.65)2.04(1.07, 3.54)
  1. CI is confidence interval. Bold values indicate statistically significant values at the 5% level.

Table 3
Probability of allergy-related disease (ARD) outcomes and atopy at 9 years by latent class membership at year 1.
95% CI*
ARD outcomes at 9 yearsLatent classEstimateLower CIUpper CIp-Value
WheezeLC 10.020.0070.0430.030
LC 20.050.0380.071
EczemaLC 10.030.0130.0560.043
LC 20.060.0470.084
RhinitisLC 10.020.0070.0440.015
LC 20.060.0450.081
SPT-anyLC 10.220.1780.2780.201
LC 20.270.2350.304
SPT-DermatophagoidesLC 10.140.1030.1880.051
LC 20.200.1710.232
SPT-cockroachLC 10.110.0740.1490.760
LC 20.110.0910.141
SPT-BlomiaLC 10.120.0890.1690.144
LC 20.160.1380.196
IgE-DermatophagoidesLC 10.260.2140.3220.261
LC 20.310.2710.343
IgE-cockroachLC 10.300.2490.3610.429
LC 20.330.2950.370
IgE-any§LC 10.420.3570.4780.395
LC 20.450.4110.490
  1. *

    CI is confidence interval.

  2. LC is latent class. LC 1 represents the class with higher probabilities for various infections as compared to LC 2.

  3. SPT-any is skin prick test reactivity to any of Dermatophagoides mix, Blomia tropicalis, German cockroach, cat, mould, grass pollen, Bermuda grass, or peanut.

  4. §

    IgE-any is allergen-specific plasma IgE (asIgE) to any of house dust mite (HDM, Dermatophagoides pteronyssinus) or German cockroach.

Table 4
Probability of allergy-related disease (ARD) outcomes and atopy at 9 years by latent class membership across the first 5 years.
95% CI*
ARD outcomes at 9 yearsLatent classEstimateLower CIUpper CIp-Value
WheezeLC 10.020.0090.0650.272
LC 20.050.0320.066
EczemaLC 10.020.0040.0620.056
LC 20.070.0500.090
RhinitisLC 10.020.0080.0670.139
LC 20.060.0420.080
SPT-anyLC 10.170.1210.2400.012
LC 20.290.2490.325
SPT-DermatophagoidesLC 10.110.0690.1690.010
LC 20.210.1800.248
SPT-cockroachLC 10.080.0480.1350.184
LC 20.120.0990.154
SPT-BlomiaLC 10.110.0700.1690.096
LC 20.170.1430.206
IgE-DermatophagoidesLC 10.320.2560.3980.416
LC 20.280.2470.325
IgE-cockroachLC 10.340.2710.4140.658
LC 20.320.2790.359
IgE-any§LC 10.480.4030.5550.316
LC 20.430.3860.471
  1. *

    CI is confidence interval.

  2. LC is latent class. LC 1 represents the class with higher probabilities for various infections as compared to LC 2.

  3. SPT-any is skin prick test reactivity to any of Dermatophagoides mix, Blomia tropicalis, German cockroach, cat, mould, grass pollen, Bermuda grass, or peanut.

  4. §

    IgE-any is allergen-specific plasma IgE (asIgE) to any of house dust mite (HDM, Dermatophagoides pteronyssinus) or German cockroach.

Additional files

Supplementary file 1

Additional results tables for model fit statistics and measurement invariance for year 1 and year 5 cumulative infection experience.

(a) Model fit statistics for latent class analysis at year 1 and at year 5 considering cumulative infection experience. (b) Results for measurement invariance by sex, at year 1 and at year 5.

https://cdn.elifesciences.org/articles/66022/elife-66022-supp1-v1.docx
Transparent reporting form
https://cdn.elifesciences.org/articles/66022/elife-66022-transrepform1-v1.pdf
Reporting standard 1

STROBE checklist.

https://cdn.elifesciences.org/articles/66022/elife-66022-repstand1-v1.pdf

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