Neurocysticercosis in Low- and Middle-Income Countries, a Diagnostic Challenge from Oyam District, Uganda
, Elda De Vita 2,†, James Amone 3, Daniel Ongaro 3, Ritah Nassali 3, Bonny Oceng 3, Samuel Okori 3, Giovanni Putoto 4, Peter Lochoro 5, Jerry Ictho 5, Massimo Fantoni 1, Annalisa Saracino 2 and Francesco Di Gennaro 2,4,*
Round 1
Reviewer 1 Report
This manuscript reports a clinical case of neurocysticercosis caused by the larval stages of Taenia solium in a Ugandan woman showing fever and neurological symptoms, highlighting the usefulness of computed tomography (CT) for the diagnosis of this important human parasitic disease. The authors correctly report that the incidence of human neurocysticercosis is particularly high in low- and middle-income countries, where it is responsible for a high number of associated epilepsy, disability, and deaths, and that the disease is listed by the World Health Organization among the neglected tropical diseases. For all these reasons, the topic of this manuscript is extremely important.
Nevertheless, the manuscript shows serious inaccuracies and gaps on parasitological and other aspects, and it is essential that the authors correct and fill them before this manuscript can deserve to be published.
First, the authors do not explain clearly how humans can acquire neurocysticercosis. In fact, the authors say that in the life cycle of T. solium humans play the role of definitive hosts, harboring the adult parasite stages in the intestine, while pigs represent the intermediate host, harboring T. solium larval stages mainly within their muscles. Therefore, based on that, neurocysticercosis should be only a pig disease, since it is caused by the larval stages of T. solium. In my opinion, how humans can acquire neurocysticercosis should be very clear for those who will read this article, and for the authors themselves, since they give the impression of not knowing this parasite in depth. Furthermore, since the larval stages of T. solium have a precise name, it would be appropriate for the authors to refer to them by using the proper terms and not simply refer to them as “cysticerci”, also considering that T. solium larval stage is the focus of this case report.
Furthermore, it is extremely important that the authors highlight in detail in the manuscript the reasons for the higher incidence of neurocysticercosis in tropical countries, particularly in low- and middle-income countries, compared to higher-income countries. In fact, although the correct etiological diagnosis of a disease is undoubtedly extremely important to implement an appropriate therapy and reduce the suffering and even the death of diseased human subjects, it is necessary and fundamental that researchers are first of all able to suggest these countries the tools to reduce the incidence of this serious disease, also considering their scarce economic possibilities. For the latter reason, moreover, in addition to highlighting the advantages of the use of CT over magnetic resonance imaging (MRI), it would be very useful for these countries if the authors also include in their discussion other diagnostic tools that could have much lower cost and instrumentation need than CT (see Corda et al. 2022. A recombinant monoclonal-based Taenia antigen assay that reflects disease activity in extra-parenchymal neurocysticercosis. PLoS neglected tropical diseases, 16(5), e0010442. https://doi.org/10.1371/journal.pntd.0010442).
Other necessary minor revisions are listed below.
-MRI, CT…: the first time they are mentioned in the abstract and in the text, they should be written in full and with the abbreviation in round brackets
-LMIC: write in full, and add computed tomography scan in key words
- Taenia solium’s larval cysts: replace with Taenia solium larval cysts
- At line 43, the meaning of “Disability Adjusted Life Years (DALYs)” should be explained in detail
-At line 82, T. solium should be in italics
-In the reference n. 12 “Taenia Solium” should be written in italics
Author Response
We have appreciated the positive feedback to our manuscript “Neurocysticercosis in low- and middle income- countries, a diagnostic challenge from Oyam District, Uganda”. We have considered all the useful suggestions made by the referees and we have implemented the text. We have also satisfied the technical requirements according to the journal guidelines. Modifications have been highlighted using the "track changes" feature. Also, a native English speaker has been engaged to improve the fluency and the readability of the manuscript.
We believe that the revision proposed by the referees, and further implemented in the text, contributed to improve the manuscript.
Best regards,
Dr. Francesco Di Gennaro
REVIEWER 1
This manuscript reports a clinical case of neurocysticercosis caused by the larval stages of Taenia solium in a Ugandan woman showing fever and neurological symptoms, highlighting the usefulness of computed tomography (CT) for the diagnosis of this important human parasitic disease. The authors correctly report that the incidence of human neurocysticercosis is particularly high in low- and middle-income countries, where it is responsible for a high number of associated epilepsy, disability, and deaths, and that the disease is listed by the World Health Organization among the neglected tropical diseases. For all these reasons, the topic of this manuscript is extremely important.Nevertheless, the manuscript shows serious inaccuracies and gaps on parasitological and other aspects, and it is essential that the authors correct and fill them before this manuscript can deserve to be published.
Response: We thank you very much for the encouraging feedback on our manuscript. We followed your suggestions and believe that now the paper is more usable for the scientific community. Thanks to your suggestions the paper, in our opinion, is notably improved.
Question:
First, the authors do not explain clearly how humans can acquire neurocysticercosis. In fact, the authors say that in the life cycle of T. solium humans play the role of definitive hosts, harboring the adult parasite stages in the intestine, while pigs represent the intermediate host, harboring T. solium larval stages mainly within their muscles. Therefore, based on that, neurocysticercosis should be only a pig disease, since it is caused by the larval stages of T. solium. In my opinion, how humans can acquire neurocysticercosis should be very clear for those who will read this article, and for the authors themselves, since they give the impression of not knowing this parasite in depth. Furthermore, since the larval stages of T. solium have a precise name, it would be appropriate for the authors to refer to them by using the proper terms and not simply refer to them as “cysticerci”, also considering that T. solium larval stage is the focus of this case report.
Response: Thank you so much for your suggestion. We appreciate a lot your comments that give us the possibility to improve the paper. We modify as following: “Cysticercosis is a parasitic zoonosis of both humans and pigs caused by the larval stages of the cestode, a pig tapeworm, Taenia solium. [1] When some cysticerci will migrate to the central nervous system, causing neurocysticercosis (NCC) with devasting consequences. NCC is listed by the World Health Organization (WHO) among the neglected tropical diseases, a group of pathologies that affect more than 1 billion of people living in tropical areas[1]. Swine are T. solium's typical intermediate host, however after ingesting infected eggs, humans, who are typically the final host, can also act as unintended intermediate hosts. Cysticercosis is acquired by human after the ingestion of eggs from the fecal-oral route (e.g. caused by poor hand hygiene, not by eating undercooked pork that contains cysticerci, which is linked to intestinal taeniasis.). Infact, oncospheres hatch in the colon, infiltrate the intestinal wall, enter the blood circulation, and move to different tissues and organs where they mature into cysticerci within 3 months (typically 60–70 days) after people eat infected food, drink, or excrement carrying these eggs or proglottids. The lungs, liver, skin, subcutaneous tissues, heart muscle and other tissues, including the oral mucosa, can be invaded by cysticerci. Some cysticerci will migrate to the brain, causing NCC with potential fatal consequences [2]”
Question:
Furthermore, it is extremely important that the authors highlight in detail in the manuscript the reasons for the higher incidence of neurocysticercosis in tropical countries, particularly in low- and middle-income countries, compared to higher-income countries. In fact, although the correct etiological diagnosis of a disease is undoubtedly extremely important to implement an appropriate therapy and reduce the suffering and even the death of diseased human subjects, it is necessary and fundamental that researchers are first of all able to suggest these countries the tools to reduce the incidence of this serious disease, also considering their scarce economic possibilities. For the latter reason, moreover, in addition to highlighting the advantages of the use of CT over magnetic resonance imaging (MRI), it would be very useful for these countries if the authors also include in their discussion other diagnostic tools that could have much lower cost and instrumentation need than CT (see Corda et al. 2022. A recombinant monoclonal-based Taenia antigen assay that reflects disease activity in extra-parenchymal neurocysticercosis. PLoS neglected tropical diseases, 16(5), e0010442. https://doi.org/10.1371/journal.pntd.0010442).
Response: Thank you so much for your suggestion. We appreciate a lot and add in our discussion section the result of Corda and collegues that we think really relevant in NCC diagnosis in low resource setting.
We add: “ New perspectives on diagnosis came from an very recent paper that define the role of recombinant monoclonal-based Taenia antigen. From this study, the effectiveness of therapy may be monitored in the CSF, serum/plasma, and urine using a recently created recombinant monoclonal antibody-based Ts Ag detection ELISA, with high sensitive in the detection of extra-parenchymal NCC. This method could be crucial in NCC control and diagnosis especially in low resources setting where are rare the possibility of CT scane or MRI. (references 16. Corda M, Sciurba J, Blaha J, Mahanty S, Paredes A, Garcia HH, Nash TE, Nutman TB, O'Connell EM. A recombinant monoclonal-based Taenia antigen assay that reflects disease activity in extra-parenchymal neurocysticercosis. PLoS Negl Trop Dis. 2022 May 26;16(5):e0010442. doi: 10.1371/journal.pntd.0010442)
Question:
Other necessary minor revisions are listed below.
-MRI, CT…: the first time they are mentioned in the abstract and in the text, they should be written in full and with the abbreviation in round brackets
-LMIC: write in full, and add computed tomography scan in key words
- Taenia solium’s larval cysts: replace with Taenia solium larval cysts
- At line 43, the meaning of “Disability Adjusted Life Years (DALYs)” should be explained in detail
-At line 82, T. solium should be in italics
-In the reference n. 12 “Taenia Solium” should be written in italics
Response: thanks a lot for your suggestions. We modify the paper following your comments.
Reviewer 2 Report
I have a few notes only.
Line 17. The summary mentions the Latin name of the parasite for the first time. Summary is a separate part of the article, so it is advisable to include the name in full.
Line 41. It is advisable to add a link, since a specific figure (30%) is given.
Line 82. The Latin name of the helminth should be italicized.
Line 87. I propose to replace the word "infections" with the word "invasions".
I would like to suggest adding a sentence saying that a serological test was not performed (and explain why). Question: was there eosinophilia in the general blood test?
Author Response
We have appreciated the positive feedback to our manuscript “Neurocysticercosis in low- and middle income- countries, a diagnostic challenge from Oyam District, Uganda”. We have considered all the useful suggestions made by the referees and we have implemented the text. We have also satisfied the technical requirements according to the journal guidelines. Modifications have been highlighted using the "track changes" feature. Also, a native English speaker has been engaged to improve the fluency and the readability of the manuscript.
We believe that the revision proposed by the referees, and further implemented in the text, contributed to improve the manuscript.
Best regards,
Dr. Francesco Di Gennaro
Reviewer 2
I have a few notes only.
Line 17. The summary mentions the Latin name of the parasite for the first time. Summary is a separate part of the article, so it is advisable to include the name in full.
Line 41. It is advisable to add a link, since a specific figure (30%) is given.
Line 82. The Latin name of the helminth should be italicized.
Line 87. I propose to replace the word "infections" with the word "invasions".
Response: We thank you very much for the encouraging feedback on our manuscript. We followed your suggestions and believe that now the paper is more usable for the scientific community. Thanks to your suggestions the paper, in our opinion, is notably improved.
Question:
I would like to suggest adding a sentence saying that a serological test was not performed (and explain why). Question: was there eosinophilia in the general blood test?
Response: many thanks for your suggestions.
We add in the text “The serological test was not performed because not was available in hospital” and for your second question, eosinophilia was in haemochrome range
Reviewer 3 Report
Page 3 line 82: T. solium - > T. solium
Author Response
We have appreciated the positive feedback to our manuscript “Neurocysticercosis in low- and middle income- countries, a diagnostic challenge from Oyam District, Uganda”. We have considered all the useful suggestions made by the referees and we have implemented the text. We have also satisfied the technical requirements according to the journal guidelines. Modifications have been highlighted using the "track changes" feature. Also, a native English speaker has been engaged to improve the fluency and the readability of the manuscript.
We believe that the revision proposed by the referees, and further implemented in the text, contributed to improve the manuscript. Thus, we kindly ask you to re-consider the manuscript for publication.
Best regards,
Dr. Francesco Di Gennaro
Reviewer 3
Page 3 line 82: T. solium - > T. solium
Response: We thank you very much for the encouraging feedback on our manuscript. We followed your suggestions and believe that now the paper is more usable for the scientific community.
Round 2
Reviewer 1 Report
The manuscript has greatly improved after the revisions; however, some changes are still needed before it can be published.
Abstract
Line 17 Please, correct “Tenia” with “Taenia” (in italics) and delete the full stop after Taenia
Introduction
Line 31- "Taenia" should be written in italics
Lines 35-37- Replace this sentence with the following:
In the life cycle of T. solium, humans are the definitive host, while swine are the intermediate host (please add a reference). However, after ingesting infected eggs, humans can also act as intermediate hosts. More specifically, cysticercosis is acquired by humans after the ingestion of eggs by the fecal-oral route, e.g., caused by poor hand hygiene, not by eating undercooked pork that contains cysticerci, which is linked to intestinal taeniasis. Autoinfection may occur in humans if proglottids pass from the intestine to the stomach via reverse peristalsis (please add a reference). In these cases, oncospheres hatch in the colon, infiltrate the intestinal wall, enter the blood circulation, and move to different tissues and organs where they mature into cysticerci within 3 months (typically 60–70 days) after the infection [1-2].
Line 57- replace “for the parasite of Taenia solium” with “for T. solium”
Case presentation
Line 76- replace “Tenia solium” with “T. solium”
Line 77- replace Albendazole with albendazole
Discussion
Line 90 Put “T.” in italics
Lines 96-97 replace with “Neuroimaging with either computed tomography scan (CT) or magnetic resonance imaging (MRI)”
Line 106 delete “Ironically,”
Lines 109-111 replace with “In a survey conducted by Yadav et al. [14], the most available diagnostic tools were point-of care testing for HIV, malaria, viral hepatitis and syphilis, whereas radiologic imaging was among the least available.”
Line 119- write “Taenia” in italics and delete the extra spacing
Line 120- replace “CSF”with cerebrospinal fluid (CSF)
References
In references 4, 12, and 16, put “Taenia” in italics; moreover, in reference 12 replace “Solium” with “solium”
Author Response
To Infectious Disease Reports Editor,
We have appreciated the positive feedback to our manuscript “Neurocysticercosis in low- and middle income- countries, a diagnostic challenge from Oyam District, Uganda”. We have considered all the useful suggestions made by the referees and we have implemented the text. We have also satisfied the technical requirements according to the journal guidelines. Modifications have been highlighted using the "track changes" feature. Also, a native English speaker has been engaged to improve the fluency and the readability of the manuscript.
We believe that the revision proposed by the referees, and further implemented in the text, contributed to improve the manuscript. Thus, we kindly ask you to re-consider the manuscript for publication.
Please find a point-by-point response to the referees’ comments below.
Best regards,
Dr. Francesco Di Gennaro
REVIEWER 1
The manuscript has greatly improved after the revisions; however, some changes are still needed before it can be published.
Response: We thank you very much for the encouraging feedback on our manuscript. We followed your suggestions and believe that now the paper is more usable for the scientific community. Thanks to your suggestions the paper, in our opinion, is notably improved.
Abstract
Line 17 Please, correct “Tenia” with “Taenia” (in italics) and delete the full stop after Taenia
Response: thanks. We modify it.
Introduction
Line 31- "Taenia" should be written in italics
Response: thanks. We modify it.
Lines 35-37- Replace this sentence with the following:
In the life cycle of T. solium, humans are the definitive host, while swine are the intermediate host (please add a reference). However, after ingesting infected eggs, humans can also act as intermediate hosts. More specifically, cysticercosis is acquired by humans after the ingestion of eggs by the fecal-oral route, e.g., caused by poor hand hygiene, not by eating undercooked pork that contains cysticerci, which is linked to intestinal taeniasis. Autoinfection may occur in humans if proglottids pass from the intestine to the stomach via reverse peristalsis (please add a reference). In these cases, oncospheres hatch in the colon, infiltrate the intestinal wall, enter the blood circulation, and move to different tissues and organs where they mature into cysticerci within 3 months (typically 60–70 days) after the infection [1-2].
Response: thanks. We modify it and add a references World Health Organization (WHO) Taeniasis/cysticercosis. Key facts. 11 January 2022 available at https://www.who.int/news-room/fact-sheets/detail/taeniasis-cysticercosis (last access 26 June 2022)
Line 57- replace “for the parasite of Taenia solium” with “for T. solium”
Response: thanks. We modify it.
Case presentation
Line 76- replace “Tenia solium” with “T. solium”
Response: thanks. We modify it.
Line 77- replace Albendazole with albendazole
Response: thanks. We modify it.
Discussion
Line 90 Put “T.” in italics
Response: thanks. We modify it.
Lines 96-97 replace with “Neuroimaging with either computed tomography scan (CT) or magnetic resonance imaging (MRI)”
Response: Many thanks for your suggestion. We modify following it.
Line 106 delete “Ironically,”
Response: Many thanks. We delete it.
Lines 109-111 replace with “In a survey conducted by Yadav et al. [14], the most available diagnostic tools were point-of care testing for HIV, malaria, viral hepatitis and syphilis, whereas radiologic imaging was among the least available.”
Response: Many thanks for your suggestion. We modify following it.
Line 119- write “Taenia” in italics and delete the extra spacing
Response: thanks. We modify it.
Line 120- replace “CSF”with cerebrospinal fluid (CSF)
Response: thanks. We modify it.
References
In references 4, 12, and 16, put “Taenia” in italics; moreover, in reference 12 replace “Solium” with “solium”
Response: thanks. We modify it.
