title={Modelling primaquine-induced haemolysis in G6PD deficiency},
journal={{eLife}}
}
@article{Simpson02,
title={Population dynamics of untreated Plasmodium falciparum malaria within the adult human host during the expansion phase of the infection},
volume={124},
ISSN={1469-8161},
DOI={10.1017/s0031182001001202},
number={3},
journal={Parasitology},
publisher={Cambridge University Press (CUP)},
author={Simpson, J. A. and Aarons, L. and Collincs, W. E. and Jeffery, G. M. and White, N. J.},
year={2002},
month=mar,
pages={247–263}
}
@article{Koepke86,
title={Reticulocytes},
volume={8},
ISSN={0141-9854},
DOI={10.1111/j.1365-2257.1986.tb00093.x},
number={3},
journal={Clinical & Laboratory Haematology},
publisher={Wiley},
author={Koepke, J. F. and Koepke, J. A.},
year={1986},
month=sep,
pages={169–179}
}
@article{Urban05,
title={Fatal {P}lasmodium falciparum Malaria Causes Specific Patterns of Splenic Architectural Disorganization},
volume={73},
ISSN={1098-5522},
DOI={10.1128/iai.73.4.1986-1994.2005},
number={4},
journal={Infection and Immunity},
publisher={American Society for Microbiology},
author={Urban, Britta C. and Hien, Tran T. and Day, Nicholas P. and Phu, Nguyen H. and Roberts, Rachel and Pongponratn, Emsri and Jones, Margret and Mai, Nguyen T. H. and Bethell, Delia and Turner, Gareth D. H. and Ferguson, David and White, Nicholas J. and Roberts, David J.},
year={2005},
month=apr,
pages={1986–1994}
}
@article{Harris62,
title={The total cellularity of the bone marrow in man},
Parameter == "MaxFold" ~ "[Maximum fold increase in RBC production]"
Parameter == "MaxFold" ~ "[Maximum fold increase in RBC production]",
Parameter == "PMF" ~ "[Parasite multiplication]",
.default = ""
))
knitr::kable(
...
...
@@ -112,6 +113,14 @@ knitr::kable(
)
```
## Macrophage population in the spleen
Steven Kho:
> I cannot find a reference showing this exact figure.
> Our own estimates of total macrophages in the spleen based on counts by histology is \(8.7 \times 10^9\) cells, though our spleens are infected and enlarged, therefore may not represent baseline steady-state.
> I have done similar calculations from published histological counts in control spleens [@Urban05], and the number comes to \(1.2 \times 10^9\) cells.
## Maximum fold increase in RBC production
As per @Watson17:
...
...
@@ -120,4 +129,35 @@ As per @Watson17:
Figure 3 of Appendix 1 shows the haematocrit response and reticulocyte count response for max-fold values of \(1..10\).
## Normoblast population in the bone marrow
Steven Kho:
> I have done a literature search and couldn't find a reference that states the exact number above or in that range.
> The reference we have previously used for bone marrow cellularity and content is [@Harris62] which states a mean of \(11.1 \times 10^9\) nucleated cells/kg body weight, of which 28.4% are normoblasts.
> Therefore, in an average 60kg Papuan male, this data suggests the bone marrow contains \(6.7 \times 10^{11}\) normoblasts, which is about 2 log-folds higher than the current value in the model.
> If I look at other studies cited in this paper (Table 5), values do fall in this range when you adjust to total bodyweight.
> Could it be possible that the current model value is still corrected per kg bodyweight?
> Were there any clues in the script to where this value was obtained
## Parasite multiplication
From @Simpson02:
> The mean population estimate of "PMR" was approximately 8, and was highly dependent on the P. falciparum "strain".
> PMR also varied significantly between patients with a 90% prediction interval varying from 5.5 to 12.3-fold.
## Reticulocyte release from bone marrow
As per the caption of Figure 2 in @Koepke86:
> With increasing anaemia (and erythropoietin production) the maturation time of the erythroid marrow normoblasts and reticulocytes progressively shortens from a normal 3.5 days to 1.5 days or less.
> Conversely the reticulocytes in the peripheral blood persist for a longer time when the patient is anaemic.
The manuscript text also states:
> The maturation time of the reticulocyte in the peripheral blood is taken as 1 day when the PCV is 0.45±0.5, 1.5 days when the PCV is 0.35±0.05, 2 days when the PCV is 0.25±0.05, and 3 days when the PCV is 0.15±0.05 (Hillman & Finch 1967).
Accordingly, the residence time in the bone marrow decreases from 3.5 days when the PCV is 0.45±0.5, down to 1 day when the PCV is 0.15±0.05.
