1. Epidemiology and Global Health
  2. Microbiology and Infectious Disease
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Sex-based differences in clearance of chronic Plasmodium falciparum infection

  1. Jessica Briggs  Is a corresponding author
  2. Noam Teyssier
  3. Joaniter I Nankabirwa
  4. John Rek
  5. Prasanna Jagannathan
  6. Emmanuel Arinaitwe
  7. Teun Bousema
  8. Chris Drakeley
  9. Margaret Murray
  10. Emily Crawford
  11. Nicholas Hathaway
  12. Sarah G Staedke
  13. David Smith
  14. Phillip J Rosenthal
  15. Moses Kamya
  16. Grant Dorsey
  17. Isabel Rodriguez-Barraquer
  18. Bryan Greenhouse
  1. Department of Medicine, University of California San Francisco, United States
  2. Infectious Diseases Research Collaboration, Uganda
  3. Department of Medicine, Makerere University College of Health Sciences, Uganda
  4. Department of Medicine, Stanford University, United States
  5. Department of Clinical Research, London School of Hygiene and Tropical Medicine, United Kingdom
  6. Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Netherlands
  7. Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, United Kingdom
  8. Chan-Zuckerberg Biohub, United States
  9. Department of Medicine, University of Massachusetts, United States
  10. Institute for Health Metrics & Evaluation, University of Washington, United States
Research Article
Cite this article as: eLife 2020;9:e59872 doi: 10.7554/eLife.59872
2 figures, 3 tables and 2 additional files

Figures

Study design.
Estimates of duration of infection from sex- and age-adjusted model.

Estimated duration of infection in days, calculated by adjusting the point estimate of the baseline hazard by the coefficients of the sex- and age-adjusted model. Error bars represent standard errors of duration obtained from variance in the model coefficients. Point estimates of duration are labeled (*).

Tables

Table 1
Behavioral risk factors for malaria infection and measures of malaria burden in study population, stratified by age and sex.
MetricAge and gender categories
All<5 years old5–15 years old16 years and older
MaleFemaleMaleFemaleMaleFemaleMaleFemale
Number of participants, n2332447384101715989
Median days of follow-up per participant530.0530.0525.0524.5530.0531.0530.0530.0
Slept under LLIN the previous night53.6%56.3%54.1%56.3%47.9%47.8%63.7%64.3%
Person-years of follow-up324.2345.487.396.7152.6118.584.22130.1
Number of overnight trips4410721199101478
Incidence of overnight trips*, (95% CI)0.14
(0.09–0.20)
0.31
(0.20–0.49)
0.24
(0.14–0.42)
0.20
(0.09–0.42)
0.06
(0.03–0.13)
0.08
(0.03–0.24)
0.17
(0.09–0.31)
0.60
(0.30–1.18)
Episodes of malaria*1113525912
Incidence of malaria**, (95% CI)0.03
(0.02–0.06)
0.04
(0.02–0.09)
0.06
(0.02—0.16)
0.02
(0.00–0.11)
0.03
(0.01–0.08)
0.08
(0.03–0.23)
0.01
(0.00–0.08)
0.02
(0.00–0.17)
Number of routine visits, n43164583116412932034156811181722
Prevalence of microscopic parasitemia***2.9%1.4%1.8%1.1%4.4%2.7%1.3%0.5%
Prevalence of parasitemia by qPCR14.4%9.2%5.8%3.7%17.0%15.3%18.5%7.7%
Geometric mean parasite density****3.413.064.8613.066.314.201.091.02
Median complexity of infection, (IQR)3 (1–7)2 (1–2)1 (1–2.5)2 (1–2.3)4 (2–9)2 (1–2)1 (1–2)1 (1–2)
  1. *Malaria includes one episode (female,<5 years old), due to non-falciparum species (P. malariae).

    **per person-year.

  2. ***Parasitemia by light microscopy includes one episode (female, 5–15 years old) due to non-falciparum species (P. ovale).

    ****Geometric mean parasite density in parasites/µL of all qPCR-positive routine visits.

Table 2
Molecular force of infection (FOI) by clone and by infection event, stratified by age and sex.
Molecular force of infection (FOI)SexAge category
All<5 years5–15 years16 years or older
By clone, ppy* (95% CI)All0.18 (0.13–0.24)0.14 (0.07–0.28)0.19 (0.08–0.43)0.20 (0.08–0.46)
Male0.19 (0.12–0.30)0.16 (0.07–0.39)0.19 (0.10–0.37)0.22 (0.09–0.54)
Female0.17 (0.09–0.31)0.12 (0.03–0.49)0.19 (0.08–0.45)0.18 (0.06–0.54)
By event, ppy* (95% CI)All0.14 (0.11–0.18)0.09 (0.06–0.16)0.16 (0.09–0.30)0.16 (0.08–0.32)
Male0.16 (0.11–0.22)0.13 (0.07–0.27)0.18 (0.11–0.28)0.15 (0.07–0.29)
Female0.13 (0.08–0.21)0.06 (0.02–0.18)0.14 (0.07–0.27)0.17 (0.07–0.41)
  1. *per person-year.

Table 3
Hazard ratios for rates of clearance of infection, by clone and by infection event.
PredictorsCategoriesHazard ratio by clone (95% CI)Hazard ratio by infection event (95% CI)
UnadjustedAdjustedUnadjustedAdjusted
SexMalerefrefrefref
Female1.92 (1.19–3.11)1.82 (1.20–2.75)2.30 (1.20–4.42)2.07 (1.24–3.47)
Age16 years or greaterrefrefrefref
5–15 years0.66 (0.39–1.10)0.81 (0.49–1.36)0.82 (0.39–1.74)1.27 (0.72–2.25)
<5 years1.64 (0.79–3.41)1.55 (0.76–3.17)2.01 (0.80–5.00)1.75 (0.87–3.53)
Complexity of infection (COI)Polyclonal (COI > 1)ref--ref--
Monoclonal (COI = 1)1.63 (1.03–2.57)--0.95 (0.38–2.34)--
Infection statusPresent at baselinerefrefrefref
New infection1.94 (1.22–3.07)1.75 (1.05–2.94)4.66 (2.58–8.42)4.32 (2.59–7.20)
Parasite density *0.85 (0.69–1.06)0.81 (0.65–1.00)0.41 (0.32–0.51)0.44 (0.35–0.54)
  1. *Increasing parasite density (log10) in parasites/microliter, as measured by qPCR.

Additional files

Supplementary file 1

(a) AMA-1 hemi-nested PCR protocol for amplicon deep-sequencing. (b) Bioinformatics workflow. (c) Declining qPCR density over time in the cohort. (d) Detailed explanation of skip rule criteria. (e) Haplotype sequences and frequencies. (f) Sensitivity analysis of molecular force of infection: Table 2 replicated using 2 skips or 1 skip. (g) Sensitivity analysis of duration of infection: Table 3 replicated using 2 skips or 1 skip.

https://cdn.elifesciences.org/articles/59872/elife-59872-supp1-v1.docx
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