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Malaria infection progress report

In this document we keep track of the exercise of going through the datasets.

  • [X] Running R
  • [X] Install Rstudio
  • [X] Install packages described in README.md

Francis Ndungu & Pjotr Prins

Terminology

  • SampleID – Volunteer enrolment number
  • Age – Age at time of trial (years)
  • Gender – Participant’s gender (1 = male, 0 = female)
  • Location – Location of normal residence
  • ELISA – Titre or anti-schizont antibody at screening (relative ELISA
  • units)
  • ELISA maps to Schizont column (log10 transformed)
  • anti-schizont antibody is measured before infection
  • Lumefantrine log10 too. Lumefantrine is an antimalarial drug. It is
  • only used in combination with artemether. The term "co-artemether" is sometimes used to describe this combination. Lumefantrine has a much longer half-life compared to artemether, and is therefore thought to clear any residual parasites that remain after combination treatment.
  • Treg_freq – The frequency of Tregs as a proportion of CD4+ T cells
  • Treg_Ki67_FC – The fold change in the number of Tregs expressing
  • Ki-67 (a proliferation marker) between C-1 and C+14
  • Treg_CD45RA – The proportion of Tregs expressing CD45RA (naïve T
  • cell marker)
  • Teff_Ki67_FC – The fold change in the number of Teffs expressing
  • Ki-67 (a proliferation marker) between C-1 and C+14
  • Teff_CD45RA – The proportion of Tregs expressing CD45RA (naïve T
  • cell marker)
  • Cytokine_status_cm1 – Detectable level of pro-inflammatory cytokines
  • at C-1 (1 = yes, 0 = no)
  • Measured cytokines IFNa, IFNg, IL1.b, IL.2, LI.4, IL.17, TNFa,
  • TGFb, IL10.
  • Screening PCR – Whether the volunteer had detectable parasitaemia at
  • screening by qPCR (1 = yes, 0 = no)
  • Symptoms_DoD – (Treated group only) whether the volunteer was
  • symptomatic (indicated by raise in temperature) at the day of diagnosis (1 = yes, 0 = no)
  • IL10_cm1 – Whether the volunteer had detectable IL-10 at C-1 (1 </li> yes, 0 no)
  • IL10_DoD – Whether the volunteer had detectable IL-10 at the day of
  • Diagnosis (1 = yes, 0 = no)

Notes

Cytokines

Cytokines are a broad and loose category of small proteins (~5–20 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. A given cytokine may be produced by more than one type of cell. They act through cell surface receptors and are especially important in the immune system; cytokines modulate the balance between humoral and cell-based immune responses.

For malaria the relative balance between Th1 and Th2 cytokines appears crucial. Th1 cytokines, interleukin-12 (IL-12) and gamma interferon (IFN-γ), and anti-inflammatory Th2 cytokines, IL-4 and IL-10 play a role.

Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. In humans, interleukin 10 is encoded by the IL10 gene. IL-10 downregulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. IL-10 can block NF-κB activity, and is involved in the regulation of the JAK-STAT signaling pathway. IL-10 counteracts the hyperactive immune response in the human body.

T helper cells (CD4+)

The T helper cells (Th cells), also known as CD4+ cells, are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system. They help the activity of other immune cells by releasing T cell cytokines. These cells help suppress or regulate immune responses.

Regulatory T cells (Tregs)

The regulatory T cells (Tregs ˈtiːrɛɡ or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Tregs are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells.