Effect of Primaquine on Gametocyte Carriage in the Case-Management of Uncomplicated Falciparum Malaria with Acts: Nigerian Perspective

Background: Drugs that kill or inhibit sexual stages of Plasmodium such as Primaqiune (PQ) could potentially amplify or synergize the impact of first line antimalarials by blocking transmission to mosquitoes. This study examined the effect of Primaquine on gametocyte carriage in the case management of uncomplicated falciparum malaria with artemisinin-based combination therapy (ACT) with the overall purpose of possibly recommending it as an adjunct drug for malaria control. Methods: A total of 181 patients with uncomplicated falciparum malaria, normal glucose-6-phosphate dehydrogenase (G6PD) enzyme levels, and haemoglobin levels ≥ 8 g/dL completed this two-arm randomized blinded clinical trial to test the efficacy of a single dose PQ (0.75 mg/kg) on falciparum gametocytaemia. 88 subjects were assigned to a standard 3-day course of Dihydroartemisinin-Piperaquine (DHP) alone (n = 88) while 93 others had DHP combined with a single dose of PQ on day 3 (n = 93). A 28-day follow-up schedule carried out in the outpatient clinic of a Primary health facility in Vom, Plateau State Nigeria where study participants were seen on days 1, 3, 7 and then weekly to assess the presence of asexual parasites and gametocytes by microscopy. A Kaplan-Meier analysis was employed to determine the survival function of gametocytes on day 3. The data was analyzed using Epi info version 7.1.5. Results: With a gametocyte prevalence of 27.1%, gametocyte carriage rate was lower in the PQ group due to higher probability of clearing gametocytes (Breslow test χ2 = 8.306, df = 1, p = 0.004) and significantly less likely to harbor gametocytes by day 7 when compared to the DHP-alone group (χ2 = 6.218, df = 1, p = 0.013). Conclusion: Addition of single-dose 0.75 mg/kg PQ was associated with reduced gametocyte carriage as a result of faster gametocyte clearance and lower incidence of gametocyte development in DHP-treated patients. PQ as gametocytocidal drug may be useful in combination with artemisinin-based combination therapy (ACT) regimen to clear gametocytes and thereby interrupt malaria transmission to mosquito vector more effectively than ACT alone.

The Technology for Preparation of Generic (Monoenantiomeric) Antimalarial Drug Primaquine by Using Supercritical Fluid Chromatography. Separation of Primaquine from Quinocide: Simultaneous Resolution of the Enantiomers of Primaquine and Their Separation from Quinocide in One Run

Malaria is one of the most harmful diseases on the globe. According to the World Health Organization (WHO), several million people die every year from malaria, and most of them are children. Hundreds of millions of fresh cases of ma- laria are registered by the WHO every year, and more than one-third of the earth’s population lives in malaria-endemic areas. Primaquine is an important antimalarial drug because it has gametocytocidal properties and prevents relapse in most cases. However, primaquine is a highly toxic substance, especially to the Negroid race (in Africa, Australia and North, Latin and South America) and some others. Negroid male children are most vulnerable to the toxic effects of primaquine. The toxicity of primaquine can be enhanced in mixtures with other antimalarial drugs. In the present study, unprocessed primaquine and primaquine tablets highly contaminated with quinocide (I. Brondz, Historical Overview of Chromatography and Related Techniques in Analysis of Antimalarial Drug Primaquine (Editor I. Brondz), Nova Sci- ence Publishers, Inc. (2011) ISSN 978-1-61761-944-1) are discussed versus monoenantiomeric primaquine as a drug. The contamination of primaquine with quinocide enhances the toxicity of primaquine by additive or synergistic action. The use of contaminated primaquine can be harmful. Development of a useful antimalarial vaccine can take a decade or longer. This paper describes the possibility of preparing antimalarial generic monoenantiomeric primaquine, free of both quinocide contamination and the ineffective enantiomer of primaquine, using fractionation by supercritical fluid chromatography equipped with a new experimental High Resolution Isomer Column (HRIC). By this approach, it is pos- sible to produce a significant amount of pharmacologically active enantiomer of primaquine at relatively low cost for a broad range of patients sensitive to contaminated primaquine. Leading pharmacopoeias should no longer deny the pre- sence of the toxic contaminant quinocide in relatively high concentrations in unprocessed primaquine and in prima- quine tablets. New standards for antimalarial primaquine diphosphate tablets must be adopted in pharmacopoeias and by the pharmaceutical industry.

Analytical Methods in Quality Control of Scientific Publications Part IV: Fraud Ordered by the Pharmaceutical Industry

In a series of papers under the common title: “Analytical Methods in Quality Control of Scientific Publications,” cases of undisputable breaches of publication ethics and breaches of acceptable rules in the publication of scientific information have been presented. Clear cases of fraud, falsification by some authors, and unqualified review of papers by reviewers and editors were presented in: Analytical Methods in Quality Control of Scientific Publications, (2012) American Journal of Analytical Chemistry, Vol. 3, No. 6, pp. 443-447 DOI:10.4236/ajac.2012.36058. The place of authors, reviewers, editors, and publisher was discussed in: Editorial: Analytical Methods in Quality Control of Scientific Publications Part II: The Authors’, Reviewers’, Editors’ Responsibility, and the Publishers’ Authority, (2013) International Journal of Analytical Mass Spectrometry and Chromatography, Vol. 1, No. 2, pp. 81-89 http://dx.doi.org/10.4236/ijamsc.2013.12010, Analytical Methods in Quality Control of Scientific Publications Part III: Publishers’ Ethics and Editors’ Com- plicity, (2014) International Journal of Analytical Mass Spectrometry and Chromatography, Vol. 2, No. 3, pp. 77-102. DOI: 10.4236/ijamsc.2014.23008 and in the book Historical Overview of Chromatography and Related Techniques in Analysis of Antimalarial Drug Primaquine (Editor, Ilia Brondz) Nova Science Publishers, Inc., (2011) ISSN 978-1-61761-944-1. Here, the corrupting influence of the pharmaceutical industry as a customer and employer of pseudoresearchers and corrupt editors and even to corrupt journal publishers for publication of fraudulent information and pseudoscientific data will be discussed by identifying the authors of pseudoscientific publications, the editors who gave the green light for the fraudulent publication, and the pharmaceutical companies involved. Documentation will be given to support the accusations of fabricated fraudulent “scientific” data, and the publication of such data without sufficient revision and sufficient background for publication of papers will be illustrated by discussing the content of papers: “Determination of Quinocide as Impurityin Primaquine Tablets by Capillary Zone Electrophoresis,” Abdalla A. Elbashir et al., (2009) Biomedical Chromatography, Vol. 23, pp. 464-471, published in Wiley Interscience, “Development of a Capillary Electrophoresis Method for the Enantioselective Estimation of Primaquine in Pharmaceutical Formulations,” Abdalla A. Elbashir et al., (2008) Journal of AOAC International, Vol. 91, No. 3, pp. 536-541, “Enantioselective Analysis of Primaquine and Its Impurity Quinocide by Capillary Electrophoresis,” Abdalla A. Elbashir et al., (2009) Biomedical Chromatography, Vol. 23, pp. 295-301, published in Wiley Interscience and other pseudoscientific publications by these teams of pseudoscientists.

Analytical Methods in the Quality Control of Scientific Publications Part V: The Fraud of Pseudoscientists Based on False Measurements and Method Development

Despite the obvious frauds published in [1] [2] and the involvement of Editors and Editors in Chief of the journals in the publication of these fraudulent papers, the Editors in Chief of publishers have not taken any action to retract the fraudulent papers or to dismiss the corrupt editors. By this passivity, these Editors in Chief are supporting plagiarism, dissemination of fraudulent data, lies and making published information unreliable. In the present paper, we evaluate examples of bold, fraudulent publications and give the names of some Editors directly participating in concealing fraudulent publications, together with the names of Editors in Chief who also concealed and covered the facts of fraud and were reluctant to remove the fraudulent papers from circulation or to remove cheaters from editorial positions. The truth is universal and international;in contrast, the lie is individual and partisan, social, political, confessional, cultural and dirty. Knowledge is a truth that is part of the Universe. Lies are a tool of manipulation and can exist only in distinct environments that produce and support them. In this paper, we will show how artificial prefabricated analytical procedures were used to disseminate false data with the aim of substituting the truth with fraud.

Analytical Methods in the Quality Control of Scientific Publications Part II: The Authors’, Reviewers’, Editors’ Responsibility, and the Publishers’ Authority

Publication of scientific documents as research reports and original papers has an important place in displaying the authors’ knowledge, integrity, responsibility, and honesty. The same is true for the reviewers and editors. The authority of a publisher strongly depends on the qualifications of the experts who review the manuscripts, and the recommendations they provide to the authors and editors. The honesty of the authors, reviewers, and editors is of the utmost importance. The author of the paper titled “Analytical Methods in Quality Control of Scientific Publications”, which was published in theAmerican Journal of Analytical Chemistry, 2012, 3, 443-447 (DOI: 10.4236/ajac.2012.36058) had criticized the paper published by Dongreet al., “Application of GC-EI-MS for the Identification and Investigation of Positional Isomer in Primaquine, an Antimalarial Drug, ”Journal of Pharmaceutical and Biomedical Analysis, 2005, 39, 111-116 (DOI: 10.1016/j.jpba.2005.03.019), for presenting falsifications in this publication. Neither the reviewer northe Edi-tor-in-Chief Bezhan Chankvetadze of the Journal of Pharmaceutical and Biomedical Analysishas reacted to accusations of falsification. If a reviewer and editor are poorly qualified, unprincipled, or even corrupt, as was suggested by Bob Grant inThe Scientistmagazine (http://www.the-scientist.com/display/55679/#ixzz0mmsPoMIS), it is not good enough to consider simply that the publisher / journal has a high ranking and is indexed in PubMed or the Institute for Scientific Information (ISI). In this editorial, we report a profound misunderstanding oralack of knowledge by the authors Shixue G., Zhuoyu L., and Wei W., in their paper published in ZhongguoYaoye China Pharmaceuticals, Vol. 14, No. 4, 2005, pp. 36-37 and a similar lack of professionalism by reviewers and editors. The influence and the role of internationally used pharmacopeias, such as The British Pharmacopoeia, European Pharmacopoeia, The United States Pharmacopeial Convention, and United States Pharmacopeia are shown as the main initiators and drivers of these misunderstandings.

Review: Can Toxic Substances Initiate Psychotic Behavior? Part I. Antimalarial Drugs

During and after every military conflict or war, there appears to be rapports about military crimes which were done by military and civil personal of conflicting sides. The basis of these offences is different;however the common to these is psychological and psychical background. The psychological background is an indoctrination of troopers that all what they are doing is right, well for country, nation or defends religion, or ideology. The life and property of enemy (opponent) are less worth than their oven. But most important in this indoctrination is the direct or indirect insurances about the absence of responsibility and promises about free for punishment for these actions. These aspects are well known and well-studied. The psychical background is less studied and more diverse;however in all cases the components of stress are present. The stress can be physical, psychical or toxic. The physical and psychical stress of engaged in military conflict personal is well studied, its action both during the war and as postwar syndrome have sufficient explanations. The action of intoxication especially by contaminants in medical forms, or toxins to induce the criminal behavior of military personal is nearly unstudied. The exceptions are alcohol, psychogenic substances as narcotics, LSD and special doping agents. This paper presented the evidences of additional toxic stress by contaminates in medical forms and intoxication by toxins of military personal engaged in different conflicts during last decades. The hypothesis about the influences of the additional toxic stress by medication with low quality pharmaceutical forms and some toxins on inducing the crimes generally and war crimes by military personal is launched in the paper. In this part the investigation will be concentrated on antimalarial drugs, especially on contaminated primaquine. Primaquine has a special position in preventing malaria infection in areas of conflict on the territories of endemic malaria. The possibility of induction of psychotic cases which lead to uncontrolled by person its-self actions and which are of criminal nature will be discussed, together with juridical responsibilities for these actions.

Analytical Methods in Quality Control of Scientific Publications

Plagiarism, fake or even falsified presentation has become a major plague for scientific publications. This paper is a response to personal appeal by David JW Lane the Editor-in-Chief of Research and Reports in Biodiversity Studies to support and promote the international author standards as developed by COPE for authors and editors-in-chief posted to me April 3rd 2012 (International standards for editors and authors http://www.dovepress.com/rrbscope.t9699812). As corresponding author for more than 100 scientific papers, dozens of scientific reviews, several chapters in scientific books, and author and editor of a book Historical Overview of Chromatography and Related Techniques in Analysis of Antimalarial Drug Primaquine, and as a reviewer of Journal of Chromatography, Journal of Chromatography A, Journal of Chromatography B: Biomedical Sciences and Applications, Lipids, Journal of General Microbiology, Journal of Clinical Microbiology, Journal of Microbiological Methods, Oral Microbiology and Immunology, Analytica Chimica Acta, Mycological Research and Journal of Pharmaceutical and Biomedical Analysis, and member of editorial board of Electronic Components and Systems, American Journal of Analytical Chemistry, ISRN Chromatography and Open Journal of Clinical Diagnostics I was adhered to a new ethical and moral standards in scientific publications. The presented paper is an example of use the analytical methods in visualizing of plagiarism and falsification in the published scientific literature. It is obvious that some of scientific publications need careful quality control. Some papers should have been rejected but were not. These papers clearly pollute the field of scientific information. It is not always easy to demonstrate inappropriate presentation even when many supporting facts are available. The facts should be obvious;there should be no hesitation about the quality or value of a paper presented for consideration to be published. Plagiarism is most common and harmful phenomenon in scientific publications. The plagiarism is based on an original discovery or reproduction of the results from the other authors. The analytical methods used in the quality control of the data can disclose plagiarism. An example is the publication under scrutiny “Applications of GC-EI-MS for the Identification of Positional Isomer in Primaquine, an Antimalarial Drug” by Dongre et al. (2005) Journal of Pharmaceutical and Biomedical Analysis 39, No. 1-2, 111-116.

Assessment of CareStart G6PD rapid diagnostic test and CareStart G6PD biosensor in Mauritania

Background::The elimination of Plasmodium vivax malaria requires 8-aminoquinolines,which are contraindicated in patients with glucose-6-phosphate dehydrogenase(G6PD)deficiency due to the risk of acute haemolytic anaemia.Several point-of-care devices have been developed to detect G6PD deficiency.The objective of the present study was to evaluate the performance of two of these devices against G6PD genotypes in Mauritania.Methods::Outpatients were screened for G6PD deficiency using CareStart?rapid diagnostic test(RDT)and CareStart?G6PD biosensor in Nouakchott,Mauritania,in 2019-2020.African-type and Mediterranean-type G6PD genotypes commonly observed in Africa were determined by polymerase chain reaction-restriction fragment length polymorphism and sequencing.Qualitative variables were compared using Fisher’s exact test.Results::Of 323 patients(74 males and 249 females),5 males and 2 homozygous females had the African-type A-genotype:A-(202)in 3 males and 2 females and G6PD A-(968)in 2 males.Among heterozygous females,13 carried G6PD A-(202),12 G6PD A-(968),and 3 G6PD A-(542)variants.None had the Mediterranean-type G6PD genotype.Eight had a positive G6PD RDT result,including all 7 hemizygous males and homozygous females with A-or A-A-(0.12 to 2.34 IU/g haemoglobin,according to G6PD biosensor),but RDT performed poorly(sensitivity,11.1%at the cutoff level of<30%)and yielded many false negative tests.Thirty-seven(50.0%)males and 141(56.6%)females were anaemic.The adjusted median values of G6PD activity were 5.72 and 5.34 IU/g haemoglobin in non-anaemic males(n=35)and non-anaemic males and females(n=130)with normal G6PD genotypes using G6PD biosensor,respectively.Based on the adjusted median of 5.34 IU/g haemoglobin,the performance of G6PD biosensor against genotyping was as follows:at 30%cut-off,the sensitivity and specificity were 85.7%and 91.7%,respectively,and at 80%cut-off,the sensitivity was 100%while the specificity was 64.9%.Conclusions::Although this pilot study supports the utility of biosensor to screen for G6PD deficiency in patients,further investigation in parallel with spectrophotometry is required to promote and validate a more extensive use of this point-of-care device in areas where P.vivax is highly prevalent in Mauritania.