Talk:WikiJournal of Medicine/Plasmodium falciparum erythrocyte membrane protein 1

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<meta name='citation_doi' value='10.15347/wjm/2017.004'>

Article information

Author: Kholhring Lalchhandama Orcid icon.png 

Plagiarism check[edit]

YesY Done with SmallSEOtools today, with no plagiarism detected. Mikael Häggström (discusscontribs) 11:54, 24 November 2016 (UTC)

Editor's comments[edit]

Comments by Michaël R. Laurent, MD PhD
These comments refer to this previous version of the article

I would like to thank you for your excellent submission on PfEMP1, an important topic that appears not to have been previously covered by a Wikipedia article (i.e. a so-called missing article). Your contribution is very valuable and well referenced. The illustrations are very nice.

I have the following questions, comments or suggestions for improvement:

1. The abstract is probably too long. It is also not customary that the abstract has references. I suggest you shorten the abstract, keeping the first paragraph and then summarizing that this article describes the discovery, structure and molecular biology of PfEMP1.

2. Although the article makes a very good effort to explain technical jargon, it still appears too technical in certain places. Especially if this work is later transferred to Wikipedia, certain parts will be too technical.

3. You specify 438,000 death due to falciparum malaria based on the WHO 2016 record. In the original source document it is stated: "In 2015, it was estimated that 429 000 deaths from malaria occurred globally (UI: 235 000–639 000), ... Almost all deaths (99%) resulted from P. falciparum malaria. Plasmodium vivax is estimated to have been responsible for 3100 deaths in 2015 (range: 1800–4900),..." I therefore suggest that it would be better to indicate that the WHO estimates that in 2015 there were 429,000 deaths from malaria, >99% of which resulted from P. falciparum infection. I have also added that there are other Plasmodium species in the introduction (since this is discussed later in the article) and that 70% of death occur in children.

4. The figures are nice, but they could perhaps be better connected to the text. Would it be possible to label them Figure 1, Figure 2 etc. and refer to them in the text upon first appearance? The illustration of knobs is fascinating but it isn't so clear what the illustration actually shows, perhaps some additional arrows or explanation of panels A and B along with their actual magnification would be helpful. The illustration showing the knobs would be better suited in the paragraph on discovery I believe, since the paragraph in which it currently stands doesn't really discuss knobs.

(more comments on the synthesis/transport and function chapters and the illustrations themselves to follow later).

Response
Thank you very much for your comments and suggestions. I have addressed the points you raised.

  1. The abstract is now condensed, with references removed.
  2. I have tried to make technical jargons readable. But in this kind of technical topic, the technicality should not be reduced too much so as to deter technical readers, and make it worthless. As the policy says, "Wikipedia strives to be a serious reference resource, and highly technical subject matter still belongs in some Wikipedia articles."
  3. I thank you again for correcting, updating, and adding information on the statistics.
  4. Figures are now numbered, indicated in the text, and rearranged as suggested. Figure 1 (about knobs) is now explained in the legend. Chhandama (discusscontribs) 04:18, 18 December 2016 (UTC)


Comments by Michaël R. Laurent, MD PhD
These comments refer to this previous version of the article

I have made some further grammar style, grammar and spelling edits. You can review these in the above diff (click link previous version). Hope these are useful to you.

Structure[edit]

Comments by Thomas Shafee, PhD
These comments refer to this previous version of the article

Since the structure is solved, it may be good to include it as an additional figure, or part of the existing domain figure. It could be generated from scratch, or adapted from figure 5A of Vigan-Womas, Inès, et al. PLoS Pathog (2012). This is an optional recommendation, and not a requirement for publication.

External peer review 1[edit]

I copy to the box below the peer review sent to me today by Dr. Peter Bull, who has declared to have no conflict of interests (and has approved that I mention his name). Mikael Häggström (discusscontribs) 19:56, 22 December 2016 (UTC)

Review by Dr. Peter Bull  

The author has made a useful contribution by writing an article on PfEMP1. I have a number of suggestions to improve the article that I will list in the order in which they appear. There are also a few typos that need to be corrected.

1) I suggest changing “exerts its virulence” to “thought to play a key role in the high level of virulence associated with this species of malaria parasite”. The expression “exert its virulence” is also used later in the article. This is a confusing expression because it inaccurately conveys an idea that the parasite is somehow trying to cause damage to the host.
2) “a variety of PfEMP1”. This is understating the immense diversity in this molecule. It is important to emphasise the fact that every genome has around 60 genes but if you take two different parasites they are likely to have very different sets of 60 genes. These genes “encode” the PfEMP1 rather than control them. Different variants are not just “slightly different” but antigenically distinct.
3) It is important to clearly differentiate between different types of cytoadhesion. Binding to endothelial cells is one kind of adhesive property and binding to uninfected erythrocytes is another (called rosetting), so binding to endothelial cells does not facilitate rosetting.
4) “ultimately bringing about the fatal symptoms of malaria”. This is potentially misleading since around 300 million people are likely to be currently infected with sequestered parasites without having malaria.
5) Sequestration of parasites in tissues and away from the peripheral blood is brought about by cytoadhesion so “sequestration” and “stickiness” are linked but not the same thing.
6) It is the presence of parasite antigens on the surface of infected erythrocytes that induces antibody responses rather than the “sticking together” per se.
7) C2 domains are not now considered as separate from DBLbeta domains.
8) It would be useful to say more about var2CSA, the specific var PfEMP1 type associated with PAM
9) This discussion of domain cassettes should be clearly distinguished from older whole var gene classifications. Type3 PfEMP1 as a definition predates the domain cassette classification. Domain cassettes are classifications of segments of var genes.
10) The first paragraph of the section “synthesis and transport” restates some of the material in the previous section and seems out of place.
11) The section on Function contains a number of inaccuracies:
a. It would be better to say that some of the most important adhesive properties of PfEMP1 described to date are mediated by the head structure.
b. ICAM binding BDLbeta domains are not present within the head structure c. An important class of CIDRalpha do not bind to CD36. A subset bind to EPCR. It would be important to say more about the EPCR story as this has been proposed to be central in explaining the pathology of cerebral malaria.
d. The binding of DARC by DBL is referring to DBL domains in P. vivax Pkalpha-DBL that binds to DARC on erythrocytes during invasion. This interaction has not been described to my knowledge, by the DBL domains present in PfEMP1. This sentence and the following two sentences in the paragraph should be deleted.
e. The description of tissue specific expression is not accurate and little is known about differences in PfEMP1 expression by parasites that sequester in different tissues.

Many of the major endothelial molecules used by the parasites for adhesion are present in multiple tissues. The expression of PfEMP1 in different tissues will most likely be determined mainly by the availability of endothelial receptors rather than a direct activation. Switching between different PfEMP1 is as far as we know a stochastic process and this is followed by in host selection during which some parasites survive and others are cleared by the host, either by antibodies or by ineffective cytoadhesion leading to destruction in the spleen. It would be useful to include a section on placental malaria to illustrate this point as this provides the best example of how different tissues select for different PfEMP1.

Response
Thank you very much for the comments, and more so for pointing out serious flaws—some fatal, as cerebral malaria is. I have tried to improve the article according to the suggestions, including expansion on EPCR and PAM. Chhandama (discusscontribs) 12:42, 23 December 2016 (UTC)

Thank you Chhandama! I've notified the peer reviewer about your changes, in case there are remaining issues that should be amended. Mikael Häggström (discusscontribs) 16:09, 26 December 2016 (UTC)
Changes referred to by author can be seen here. 101.165.17.230 (discuss) 02:31, 2 January 2017 (UTC)
I haven't yet heard back from the peer reviewer, but in any case it has just recently been decided in the editorial board that 2 independent reviews are needed for new work. Therefore, we are now looking for an additional reviewer as well. Mikael Häggström (discusscontribs) 15:17, 4 January 2017 (UTC)
I did get a positive response for a second peer reviewer at first, but then I didn't hear back. I've now sent a reminder. Mikael Häggström (discusscontribs) 20:25, 19 February 2017 (UTC)

External peer review 2[edit]

The following peer review was emailed to me, and the reviewer prefers to be anonymous. Mikael Häggström (discusscontribs) 18:46, 1 March 2017 (UTC)

Review by anonymous peer reviewer  

Review for Wiki Journal of Medicine

This article provides a useful overview of Plasmodium falciparum erythrocyte membrane protein 1. The article is well-written and well structured.

1. The of 'Discovery of PfEMP1' section could be improved significantly. Several sentences are too long and difficult to read – please make sentences more concise or separate complex causes. . The section has several spelling mistakes (e.g. 'distinguih') and some sentences need to be made more concise (e.g. "the protein was difficult to isolate basically due to its low occurrence").

2. There could in general be a fuller section regarding clinical studies relating to PfEMP1. In particular this could correlate with a couple recent articles. Articles have been published recently which would be useful to cite to be fully up to date in the latest understanding of PfEMP1 function – the first correlating var transcript level with disease severity, and the second relating to telomeric control of var gene expression. Perhaps a final section regarding clinical aspects after function?

[1] S. I. Mkumbaye, C. W. Wang, E. Lyimo, J. S. Jespersen, A. Manjurano, J. Mosha, R. A. Kavishe, S. B. Mwakalinga, D. T. Minja, J. P. Lusingu, T. G. Theander, T. Lavstsen, Infect. Immun. 2017.

[2] M. F. Duffy, J. Tang, F. Sumardy, H. H. Nguyen, S. A. Selvarajah, G. A. Josling, K. P. Day, M. Petter, G. V. Brown, FEBS J. 2017, 284, 237-257.

Response
I believe I have addressed the reviewer's suggestions.

  1. The "Discovery" section is thoroughly revised. Sentences are restructured and typos are corrected.
  2. A new "Clinical importance" section is added with information as suggested. Chhandama (discusscontribs) 09:41, 3 March 2017 (UTC)