Talk:WikiJournal of Medicine/Orientia tsutsugamushi, the agent of scrub typhus

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WikiJournal of Medicine
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WikiJournal of Medicine is an open-access, free-to-publish, Wikipedia-integrated academic journal for Medical and Biomedical topics. <seo title=" WJM, WikiJMed, Wiki.J.Med., WikiJMed, Wikiversity Journal of Medicine, WikiJournal Medicine, Wikipedia Medicine, Wikipedia medical journal, WikiMed, Wikimedicine, Wikimedical, Medicine, Biomedicine, Free to publish, Open access, Open-access, Non-profit, online journal, Public peer review "/>

<meta name='citation_doi' value='10.15347/wjm/2019.004'>

Article information

Author: Kholhring Lalchhandama ORCID iD.svg , et al.

Lalchhandama, K; et al.. 


Plagiarism check

Artículo bueno.svg Pass. According to Earwig's Copyvio Detector, this article contains minor segments of similar wording to other works of the same author [1], which is acceptable. Those works are:

Mikael Häggström (discusscontribs) 20:03, 16 September 2018 (UTC)

External peer review 1

Review by Dr. (Prof.) Tapabrata Chatterjee , MD (Ped), FRCP (UK), FRCPCH (UK). Professor of Paediatrics, Vivekananda Institute of Medical Sciences and Ramakrishna Mission Seva Pratisthan
This review was submitted on , and refers to this previous version of the article

The article is comprehensive, well-written in a lucid language, pleasure to read, and fit for publication in any indexed journal. It needs no modification.

Conflict of Interest: None declared.

External peer review 2

WikiJournal Preprints Orientia tsutsugamushi line numbered.pdf


Reviewer-annotated pdf file.

Review by Dr. (Prof.) Charles S. Apperson and Dr. (Prof.) Logu Ponnusamy , PhD (Entomology), Entomological Society of America Fellow (2009), William Neal Reynolds Distinguished Professor Emeritus, North Carolina State University, USA; PhD (Microbiology, Botany) Principal Research Scholar, North Carolina State University, USA
This review was submitted on , and refers to this previous version of the article

The article, labeled “WikiJournal Preprints/Orientia tsutsugamushi, the agent of scrub typhus,” is a brief review of the biology of the pathogen causing scrub typhus and the epidemiology of the disease. There is no question that this review in its final form will be informative.  Extensive copy editing is required, however, to improve the writing and specifically to eliminate ambiguous language.

To help orient the authors to the specific areas that my comments refer to, I converted the pdf document into a MS Word document and added line numbers.  This Word document is attached and specific line numbers are given for each of my comments.

1. Abstract, line 11.  “…transmitted by mite larvae (chiggers) to humans and rodents through accidental bite.”  Rodents are the natural hosts of these mites, so only humans received “accidental” bites.

2. It is worth mentioning in the abstract that novel species of Orientia (O. chuto) have recently been described.

3. Line 15.  “…which renders the bacterium to exist…”  This awkward statement should be revised.

4. Line 31.  “…requires laborious techniques…”  The meaning of this statement is not clear.

5. Lines 35-36.  “Eschar, if present on the skin, is a good indicator.” An eschar is an indicator of what condition?  By “good” do the authors mean “diagnostic”?

6. Lines 36-42.  It is important to mention that the geographic distribution of scrub typhus extends beyond the Tsutsugamushi Triangle, as cases have recently been reported from South America.

7. Line 44.  “…working vaccine.”  Please delete “working” from this sentence.

8. Biology, line 50.  “…originally categorized in the genus Rickettsia…”  This statement conflicts with that given in the abstract about the description of O. tsutsugamushi as a species in the genus Theileria.

9. Line 52.  “…larger and broader, but shorter…”  These adjectives are ambiguous.  The authors should make this description quantitative.

10. Line 55.  “One complete budding takes…”  “Budding cycle”?

11. Line 59-60.  “The bacterium is enclosed by a cell wall on the outside and cell membrane on the inside (Figure 2).”  Which panel in Fig. 2 are the authors referencing? There are 4 panels in the figure, but only one panel is identified in the figure caption.  Also, it is not clear what is shown in the figure.

12. Line 64.  “The cell wall is soft and tender…”  Please clarify what is meant by this statement.

13. Line 72.  " very small quantity that can hardly be detected and plays minor or no role in the cell wall."  Here again, the authors use ambiguous descriptions.

14. Line 73.  “There are unique genes such as PBP1, alr, dapF, and murl…”  Wouldn’t it be informative to state what proteins these unique genes encode?

15. Lines 79-82.  The authors should clearly state that Orientia and other members of the Rickettsiaceae will only grow inside of cells.

16. Figure 3 because of its low resolution is not informative.

17. Life cycle and transmission.  Lines 108-109.  “In fact, in rodents and humans the transmission is stopped, and the bacterium meets a dead end.”  This last sentence needs to be rewritten.  Rodents and humans are "dead-end" hosts as mites, for unknown reasons, can not be infected if they feed on an infected rodent host. Mites can be infected by co-feeding; i.e., an uninfected mite can be infected when it feeds adjacent to an infected mite.

18. Line 110.  “…is the most universal vector…”  Please change “universal” to “common”.

19. Line 113.  “The third-stage larvae…”  To my knowledge, there are no 1st, 2nd, or 3rd stage larvae. Eggs transform into an inactive prelarval stage before hatching into an active larval stage, called a chigger. Authors please reference this description.

20. Lines 114-115.  “…they are the only stage in the life of mites that cause infection.” The pathogen causes infection, the chiggers transmit the pathogen when the mites bite.

21. Lines 117-118.  “They possess a special feeding apparatus called stylostome on their heads.” The feeding tube or stylosome forms in response to the saliva that the mites secrete into the skin after attachment. A description of stylosome formation is given in Shatrov, A. B.  2009. Stylostome formation in trombiculid mites (Acariformes: Trombiculidae).  Exp. Appl. Acarol. 49:261-280.

22. Cellular invasion. Lines 128.  “…the process of swallowing the bacterium…”  Please change “swallowing” to “ingesting”.

23. Lines 131-132.  “…it makes an exit from the vesicle (now known as an endosome) before it is destroyed (in the process of cell-eating called autophagy)…”  It is not clear what is destroyed--the endosome or Orientia?

24. Strains.  Line 143.  “He observed…”  Ida Bengtson is female not male.

25. Line 144. “…and that the blood sera having different strains could cross react.”  Antibodies in the blood sera of patients cross react to different strains of O. tsutsugamushi. 

26. Line 146.  “Akira Shishido discovered Kato strain…” “Described the Kato strain” would be more appropriate.

27. Lines 148-149.  “So far, more than 30 different strains have been established in humans.” What biological trait distinguishes one strain from another?

28. Line 152.  “Genetic methods have revealed even greater complexity…”  This sentence suggests that non-genetic methods were used in references 30 & 31 to characterize the various strains of O. tsutsugamushi.  Would it be informative to state what methods were used?

29. Antigenic variation. Line 159. “…detected by sophisticated diagnostic tests.”  What is meant by “sophisticated”?

30. Lines 158-160.  “…TSA56, making it the main target in diagnosis.”  By use of what diagnostic method?

31. Lines 162-163.  “…antigenically different protein but of the same kind.”  The meaning of “the same kind” is not clear.

32. Lines 163-1643.  Please italicize GroES and GroEL as they designate genes.

33. Disease. Line 170.  “…and dangerous infection…”  Please change “dangerous infection” to “potentially life-threatening disease”.

34. Lines 171-172.  “The bacteria are deposited at the site of feeding (inoculation) where they multiply. They cause progressive tissue damage (necrosis).”  The authors should mention that the necrosis results in the formation of an eschar.

35. Line 176-177.  “Moreover, death rate can be as high as 13% where medical treatment is not properly handled.”  In a previous sentence, the authors state that mortality can be as high as 30-70% if patients receive improper treatment or are misdiagnosed.

36. Lines 180-181.  “Harmful symptoms involving multiple organ failure and neurological impairment…”  Multiple organ failure and neurological impairment are outcomes of the disease not symptoms of the disease.

37. Lines 184-185.  This sentence does not make sense.  Which is the main cause of acute encephalitis syndrome in India, scrub typhus or JEE?

38. Epidemiology.  Lines 199-200.  “In the absence of proper medical care, the case fatality rate can go beyond 30% to as high as 70% in some areas.”  This information has been given previously.

39. What segment of populations within the Tsutsugamushi Triangle are most at risk of infection? What gender and age groups are most vulnerable?

40. Diagnosis.  This section should be presented before the section describing treatment procedures.

41. Lines 212-215. “…the symptom is not unique and is similar to a group of acute undifferentiated fever, which includes those of malaria, leptospirosis, typhoid, murine typhus,

chikungunya, and dengue fever.”  Here it would be sufficient to state that the early symptoms of scrub typhus are similar to some other vector-borne tropical diseases.

42. Blood test.  Most rickettsial infections are presumptively diagnosed and treated based on the occurrence of concordant symptoms (headache, fever, etc.), occurrence of the illness during the time of year when vectors would be active, self-reported contact with a vector, and the patient’s exposure to high risk landscape. A blood test is used to confirm the presumptive diagnosis.

43. When in the course of illness would these tests be expected to be diagnostic for scrub typhus?  In other words, how soon after the onset of illness would a PCR assay be expected to detect Orientia?  The same question applies to the other assays mentioned in this section.

44. Vaccine.  Line 241.  Please define ScaA.

45. Immunity.  Line 244. “There is no complete immunity to O. tsutsugamushi infection.”  Do the authors mean that there is no “lasting immunity O. tsutsugamushi infection”?

46. Lines 244-245.  “Enormous antigenic variation among O. tsutsugamushi strains makes the immune system unable to fully recognise them.”  Antigenic variation prevents the development of cross immunity to the various strains of O. tsutsugamushi.

47. History.  Line 266.  “The aetiology of the disease was never apparent.”  Please rephrase to state that the aetiology of the disease was unknown until the early 20th century.

Conflict of Interest: None declared.


I have revised the article. I hope reviewer's comments are adequately addressed:

1. Line 11. Changed to “...from rodents, the natural hosts of mites, to humans through accidental bites.”
2. Info on O. chuto added as “It is most closely related to Candidatus Orientia chuto, a species described in 2010.”
3. Line 15. Sentence revised as “...which gives rise to many strains (sub-types) of the bacterium.”
4. Line 31. Sentence revised as “Diagnosis is difficult and requires laborious detection methods such as Weil–Felix test.”
5. Lines 35-36. Sentence revised as “...a good diagnostic indicator.”
6. Lines 36-42. Africa, Europe and South America are mentioned.
7. Line 44. Deleted “working”.
8. Line 50. Rephrased as “ was previously classified in the genus.”
9. Line 52. Proper description with cell size mentioned.
10. Line 55. Changed to “One complete budding cycle takes…”
11. Line 59-60. Statement revised to link Figure 2. Figure 2 is also revised with descriptive legends. All the plates are defined.
12. Line 64. Changed to “The cell wall is less rigid...”.
13. Line 72. Changed to “...the bacterium cannot synthesise typical peptidoglycan cell wall but make peptidoglycan-like structure on its surface.”
14. Line 73. Genes and their products are explained.
15. Lines 79-82. Clarification and “rickettsiales can be cultured only in living cells” is added.
16. Figure 3 is linked to the original and high-resolution image (directly from the original publication at Wikimedia Commons. WJM shows only the thumbnail version by default. It is the discretion of the editors to display as it is, delete or show a bigger version.
17. Lines 108-109. Transmission from infected rodents is clarified.
18. Line 110. Changed “universal” to “common”.
19. Line 113. Removed “...third-stage ...”.
20. Lines 114-115. Changed to “…that transmit the infection.”
21. Lines 117-118. This statement does not contradict the stylosome formation (as in Shatrov, A. B. 2009. Exp. Appl. Acarol. 49:261-280. For clarity, I add “...which is a tube formed by solidified saliva” for clarity.
22. Lines 128. Changed “swallowing” to “ingesting”.
23. Lines 131-132. Changed to “...before the endosome is destroyed...”
24. Line 143. Changed “He observed…” to “She observed…”
25. Line 144. Changed to “...antibodies in the blood sera of patients cross react to different strains”.
26. Line 146. Changed “... discovered…” to “...described...”
27. Lines 148-149. Changed to “So far, more than 30 different strains have been established in humans based on antigenic variation.” The strain differentiation and antigenic variation are covered in the next section.
28. Line 152. Non-genetic methods are mentioned as in point 27 “...using serological tests such as complement fixation and immunofluorescence assay.”
29. Sentence changed as “are not strain specific so that TSA56 is the main target in sophisticated diagnostic tests such as immunoblotting, ELISA and DNA analysis” to clarify “sophisticated”.
30. Lines 158-160. Diagnostic methods are defined in point 29.
31. Lines 162-163. Changed to “Its gene contains four hypervariable regions, indicating that it synthesises many antigenically different proteins.”
32. Lines 163-164. No need to italicise GroES and GroEL as they designate proteins, and not genes, in this context. The genes in the later sentence are properly italicised.
33. Line 170. Changed “dangerous infection” to “potentially life-threatening disease”.
34. Lines 171-172. Sentence extended as “...which leads to formation of an eschar on the skin.”
35. Line 176-177. Changed to “...14% with neurological problems and 24% with multi-organ dysfunction among treated patients.”
36. Lines 180-181. Changed to “Harmful effects...”
37. Lines 184-185. Sentence rephrased as “In India, scrub typhus has become the major cause of acute encephalitis syndrome, which was earlier caused mainly by a viral infection...”
38. Epidemiology. Repetitive sentence deleted.
39. Population, risk group, and gender are now mentioned.
40. Sub-section “Diagnosis” moved before “Treatment”.
41. Lines 212-215. Changed to “...the symptom is similar to other vector-borne tropical diseases.”
42. Blood test. Preliminary diagnosis should be clear from the “Symptoms” and addition of “Suspected infections are confirmed with serological tests.”
43. The above point clarifies the application of the tests.
44. Line 241. ScaA is already defined in the section “Cellular invasion”.
45. Line 244. Changed “...complete immunity” to “...lasting immunity”.
46. Lines 244-245. Changed to “Antigenic variation prevents the development of cross immunity to the various strains of O. tsutsugamushi.”
47. Line 266. Changed to “The aetiology of the disease was unknown until the early 20th century.”
Chhandama (discusscontribs) 12:44, 2 June 2019 (UTC)

Review by Drs. Apperson and Ponnusamy ,
This review was submitted on , and refers to this previous version of the article

The revised manuscript should be accepted for publication.