Malaria Journal - Latest Comments

Authors Note

Penelope Lynch — 2013-03-19T19:01:53Z

A number of problems introduced during the copy-editing process for this paper remain unresolved in the currently published versions. We still hope to see these resolved by Biomed Central, but meanwhile note the following in an attempt to minimise confusion regarding the symbols representing model variables and parameters.

The symbol used to represent lifetime egg production should be lower case phi, as shown in on-line HTML text and tables, not the symbol shown in the pdf, which should be used only to represent the period of time spent finding an oviposition site and laying. In addition, although a number of different typefaces have been used, please assume that a given case of a given Arabic letter represents the same item in all tables and equations.

Figure 5 Legend

John Renschler — 2013-03-19T18:48:28Z

I think the colors described in the Figure 5 legend are backwards.

As written the red line represents halved drug pressure and the blue line is the baseline waiting time. If that were true then the panels show that Time to Emergence is shorter for the halved drug pressure than for baseline.

A pointer to previous work on this topic.

Ian Hastings — 2012-11-26T15:02:16Z

Readers should be aware that we published a very similar PK/PD methodology and analysis of antimalarial drugs last year in AAC that is not cited or discussed in this manuscript i.e.

Winter, K. and I. M. Hastings (2011). "Development, evaluation and application of an in silico model for antimalarial drug treatment and failure." Antimicrobial Agents and Chemotherapy 55: 3380-3392.

In summary, we reported that our models were very robust and generated model outputs that were highly consistent with clinical data. We have been further refining and applying these models (unpublished data) and continue to find excellent matches with field and clinical data.

[One notable difference is that we implemented our methodology in half- and one-day timesteps rather than the one-hour timesteps used by Zaloumis et al. This was to avoid having to incorporate, and further calibrate, the stage-specific killing of drugs: our reasoning was that artemisinins have a short half-life but broad stage-specific killing ranges while the partner drugs have narrower stage specificity but long half-lives so will be present at high concentrations throughout the malaria cell cycles subsequent to drug administration. This choice reflected a trade off between biological realism and the desire to avoid over-elaborating our PK/PD model.]

Ian Hastings and Katherine Winter

Pyrosequencing primers

Dylan Pillai — 2012-11-26T15:01:38Z

We thank Woodrow et al for their important commentary [1]. Analysis of the pyrosequencing primers used for the detection of the two mutations in question (pfatp6 A623E and S769N), in this and a previous publication [2], confirmed the following. The Genbank ID (EF564342), which has also been reported by others [3], was used in the design of the pyrosequencing primers. However, this sequence is missing 14 amino acids at the N-terminus. As such, though the primers were designed to target the correct amino acid positions, they were based on the incomplete coding sequence and therefore did not identify the mutations in question. Hence, further Sanger-based sequencing will be required to confirm the presence or absence of mutations in PfATP6 sequences of these clinical isolates in relation to 50% inhibitory concentration (IC50) data. This work is to be undertaken. We note that a recent publication from Iran [4] identifies S769N mutations appearing after the introduction of artesunate, suggesting these mutations are still being identified in disparate geographic areas.

1. Woodrow CJ, Gardner KB and Bustamante LY. Questions over high frequency of mutant PfATP6 haplotypes in traveller isolates. Malaria Journal 2012, 11:186.
2. Shahinas D, Lau R, Khairnar K, Hancock D, Pillai DR. Artesunate misuse and Plasmodium falciparum malaria in traveler returning from Africa. Emerg Infect Dis. 2010 Oct;16(10):1608-10.
3. Kwansa-Bentum B,Ayi I, Suzuki T et al. Plasmodium falciparum isolates from southern Ghana exhibit polymorphisms in the SERCA-type PfATPase6 though sensitive to artesunate in vitro. Malaria Journal 2011, 10:187.
4. Zakeri S, Hemati S, Pirahmadi S, Afsharpad M, Raeisi A, Djadid ND. Molecular assessment of atpase6 mutations associated with artemisinin resistance among unexposed and exposed Plasmodium falciparum clinical isolates to artemisinin-based combination therapy. Malar J. 2012 Nov 9;11(1):373

Dr. Krishna Khairnar
Environmental Health Division,
National Environmental Engineering Research Institute (NEERI),
Nehru Marg, Nagpur- 440020, Maharashtra
India
kskhairnar@gmail.com

Dr. Dylan Pillai
Department of Pathology and Laboratory Medicine
University of Calgary
Canada

Confusing nomenclature

Konrad Koehler — 2012-07-16T10:11:31Z

I applaud the authors for exploring this very interesting and worthwhile approach to developing new medicines.

One minor issue that may be a source of confusion is the use of the term "reverse pharmacology" to describe this method. I realize that this term was coined in India in the mid 2000s. However this same term has been widely used in the drug discovery literature with a very different and almost opposite meaning dating at least as far back as 1990:

Reverse pharmacology applied to the cannabinoid receptor.

Classical vs reverse pharmacology in drug discovery.

In this older usage, reverse pharmacology is defined as a drug discovery method based on screening of compounds against purified protein targets and then testing for efficacy in animals. In contrast, classical or forward pharmacology is based on screening compounds in biological systems looking for a desirable therapeutic effect and then determine the target afterwards. Hence the method described in this paper has far more in common with classical/forward pharmacology than reverse pharmacology.

I think a new phrase is needed to describe this approach in order to avoid confusion with the older drug discovery literature.

The address of the interim report of this study

Ahmad Raeisi — 2012-06-14T14:07:29Z

The authors wish to point out that an interim report of this study, including the data from the Hormozgan site, had been published a few weeks before this paper in the Iranian Journal of Parasitology:

Absence of asymptomatic malaria infection in endemic area of Bashagard district, Hormozgan Province in Iran; Turki H, Zoghi S, Mehrizi AA, Zakeri S, 7(1), 32-35

Re: Ishag Adam

Agnieszka Kempinska-Podhorodecka — 2012-06-14T12:24:03Z

Thank you for your interest in our paper. We would like to explain that our research was carried out during a scientific expedition organized by the Museum of Archaeology in Gda¿sk (MAG) (Poland). Since 1996, MAG has had a long-term concession for surface and excavation works in the region of the 4th Cataract on the right bank of the Nile, granted by the National Corporation for Antiquities and Museums (NCAM) in Khartoum. The expedition was led by the director of MAG, Henryk Paner. Our research is a part of a large-scale archaeological inventorisation of the middle Nile region, initiated by NCAM because of the intended dam erection in the area of Umm Duwemi village and Merowe Island. The aim of the campaign was to rescue cultural heritage and protect monuments in the areas to be flooded after the dam erection.
We received invaluable help in our efforts from dr Mahmoud el Tayeb, a Sudanese archaeologist living in Poland. Our gratitude towards him was expressed in the article in the Acknowledgements section.
Due to a high rate of illiteracy in the analyzed cohort, only oral consent for the participation in the study was obtained, in the presence of the local authorities representative.
The above information was included in our other articles from this series.

An alternative cellulose powder to CF11

Bruce Russell — 2012-06-14T12:23:35Z

Malaria groups at A*STAR and NUS (Singapore), Eijkman Institute for Molecular Biology(Indonesia) and SMRU (Thailand) have effectively substituted the use of CF11 with Sigma medium fiber Powder (cat # c6288) since September 2011. Preparation of the filter columns using the Sigma cellulose powder are as per Sriprawat et al 2009 (http://www.malariajournal.com/content/8/1/115) .

GMP artesunate

Arjen M Dondorp — 2012-05-11T16:17:23Z

I enjoyed reading this interesting study. I just wanted to comment on the statement made by the authors regarding the Guilin artesunate product that WHO prequalification "is not the same as GMP certification". It is a prerequisite that all WHO prequalified products are manufactured to GMP and verified as such by inspectors from WHO or a stringent authority.

Re Analysis for genotyping Duffy blood group in inhabitants of Sudan, the Fourth Cataract of the Nile

Ishag Adam — 2012-05-11T16:16:19Z

I read this article with great interest and I have to congratulate the authors.
However, It is not obvious is the methods how they approached the patients and how the patients were consented. It is var difficult to convey such study in Sudan with Polish scientists without one of the local researchers. Importantly in the ethics section authors mentioned that they received ethical clearance from Poland, we do respect this but is it valid to have an ethical clearance from Poland and fostered the study in Sudan?
I hope authors would to be able to clarify these points
Best Regards