Beware the Plasmodial Infection Indicators: Plasmodium Falciparum Prevalence and Parasitaemia During two Years in Symptomless below 5 years old Children of Two Villages with long-Lasting Insecticide Treated Nets and two Villages without Nets in Angol

Research Article

Beware the Plasmodial Infection Indicators: Plasmodium Falciparum Prevalence and Parasitaemia During two Years in Symptomless below 5 years old Children of Two Villages with long-Lasting Insecticide Treated Nets and two Villages without Nets in Angol

  • P. Carnevale 1*
  • JC Toto 2
  • V. Foumane 2
  • L. Eugenio 3
  • G. Carnevale 4
  • R. Ouarou 5
  • F. Gay 5

*Corresponding Author: P. Carnevale, Le Majoral Building 34420 Portiragnes Plage, France.

Citation: P. Carnevale, JC Toto, V. Foumane, L. Eugenio, G. Carnevale, R. Ouarou, F. Gay (2023), Beware the Plasmodial Infection Indicators: Plasmodium Falciparum Prevalence and Parasitaemia During two Years in Symptomless below 5 years old Children of Two Villages with long-Lasting Insecticide Treated Nets and two Villages without Nets in Angola, Clinical Medical Reviews and Reports, 5(5);10.31579/2690-8794/175

Copyright: © 2023, P. Carnevale. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 29 August 2023 | Accepted: 09 September 2023 | Published: 18 September 2023

Keywords: vector control; parasitological evaluation; long lasting insecticide treated nets; P. falciparum prevalence and parasitaemia; indicator of impact

Abstract

Forty parasitological cross-sectional surveys (CSS) were regularly done during two consecutive years in four villages around Balombo town (Benguela Province, Angola) to assess the influence of a full coverage with long lasting insecticide treated net (LLIN) PermaNet© 2.0 on plasmodial infection of under 5 years old symptomless children (“U5”).

Two villages received LLIN following a two steps process: 1rst year 1 LLIN per house; 2nd year: 1 LLIN per sleeping unit (= everything regularly used for sleeping) while two close villages remained as control for these two years.

Overall P. falciparum infections were microscopically observed in 1006 of the 2865 blood thick films made i.e., a plasmodial prevalence of 35.1%.

During these two years the plasmodial prevalence decreased significantly in the two LLIN furnished villages but also in the two control villages.

Therefore, the plasmodic index could not be considered as a relevant indicator to evaluate the parasitological efficacy of LLINs implemented in this study.

The gametocytic index did not significantly changed from year to year neither in LLIN villages nor in control villages and did not appear also as a relevant indicator in this study.

But on the other hand, the analysis of the evolution of the parasite load procured a crucial information with a significant decreased of the parasitaemia of U5 children in LLINs villages while it remained at the same level in control villages without any organized vector control operations.

Parasite load appeared as the relevant indicator showing the actual impact of LLIN in reducing the parasitaemia, and therefore the risk of malaria, in under five children in this area.

Introduction

In the WHO Global technical strategy for malaria 2016-2030 [1]. vector control “is an essential component of malaria control and elimination” and “National malaria control programmes need to ensure that all people living in areas where the risk of malaria is high are protected through the provision, use and timely replacement of long-lasting insecticidal nets or, where appropriate, the application of indoor residual spraying”.

According to the WHO Report of Malaria in the World [2]. «An estimated 663 million cases of malaria have been averted in sub-Saharan Africa since 2001 as a direct result of the scale-up of 3 key interventions: ITNs, ACTs and IRS. It is estimated that 69% of the 663 million fewer malaria cases attributable to interventions were due to the use of mosquito nets, 21% due to ACTs and 10% due to indoor spraying”. Therefore some 524 million cases were averted thanks to vector control and 457 million cases with large scale implementation of insecticide treated mosquito nets.

Some groups such as children below 5 years old and pregnant women are « particularly susceptible to malaria illness, infection and death” and are considered as “at risk groups which deserve a high priority of protection.

According to the WHO Malaria report (2022) “between 2019 and 2020 estimated malaria cases increased from 218 million cases to 232 million, and deaths from 544,000 to 599,000 in the WHO African Region. In 2021, while cases increased to 234 million, deaths decreased to 593,000. This region accounted for about 95% of cases and 96% of deaths, 78.9% of deaths in this region were among children aged under 5 years in 2021 compared to 91% in 2000.”

Universal ITN coverage is recommended, which is expected to provide community protection, and it was estimated that in 2017,” about half of the population at risk of malaria in Africa was protected by impregnated mosquito nets”; however, “protection by persistent spray did not exceed 3% in 2017” [3]. 

To assess the ITN coverage one indicator was at least one impregnated net per house[4]. In the double concept “one net/house” and “universal coverage” we developed a program of distribution of longlasting insecticide treated nets (“LLIN”) PermaNet 2.0 in two villages, Caala and Cahata, in a classical two steps process: first year, in February 2007, distribution of nets to obtain “at least one net/house” then in February and December 2008 second distribution to get one net/sleeping units. These operations were part of a general malaria vector project implemented in eight villages around Balombo town (Benguela Province, Angola) to compare the efficacy of four method of vector control: classical LLIN alone, Insecticide treated plastic sheeting (ITPS) alone or associated with LLIN or following two rounds of indoor residual spraying [5].

One of the problems for the epidemiological evaluation of vector control is the choice of indicators considering that the aim of the control is to reduce the “burden” of malaria that can be understood in terms of «malaria-parasite» and/or “malaria-disease”.

Several methods can be used for epidemiological surveys [6]. mainly “passive detection case” in Health Center or “active detection case” directly in communities [7].  One of the problems in Health Centre is often the well-known lack of reliability of data, from both clinical and parasitological examinations [8].  with some overdiagnosis of “malaria” reported as high as 85% [9].  and its consequences on drug pressure and the risk of increasing drug resistance. 

As early as 1949 it was considered that “when diagnoses are based on symptomatology alone it is likely of any errors will be commonly inclusive rather than exclusive and as a consequence malaria will appear to be of exaggerated importance in the community” [10]. 

As there is no health center, in the villages studied, the population must go to the Hospital of the nearby city, Balombo, with a Pediatrics department. Active detection case in communities procured reliable information in bed net assessment studies [11,12]. but requires resources that are not always available. “For an extended period the detection of the malaria parasite in blood smears was the only available laboratory aid to diagnosis” [13]. But in endemic malaria areas the classical crosssectional surveys reveal plasmodial prevalence of 50% and more in symptomless people, prevalence which was noticed in studied area [14-19].  And “the opinion is entertained that if in any ambulatory group in whom 50 per cent infection is found on a single examination, the group is actually nearly 100 per cent infected” [10]. 

An additional criterion was then proposed taking into account the level of parasitaemia [20,21]. as a “pyrogenic threshold” or “parasite threshold” or “pyrogenic level” or “pyrexia level” [10-23]. which is variable according to ages, epidemiological conditions and other factors. It has been the subject of several studies [24-26].  and even some controversies considering that “the determination of this level in falciparum infections is practically impossible” [10]. 

The objective of our study was not to determine this pyrogenic threshold in the targeted populations but to analyse, and compare, the evolution of both the parasite prevalence and parasite density of P. falciparum during two consecutive years in the “at risk” group (i.e. children ≤ 5 years) of two villages with insecticide treated nets and two close villages without nets (= “control”) but which will received vector control in the framework of the large village-scale vector control “Balombo project” [5]. 

II-Materials & methods

II-1. First census

A house census was done in each village by the local health worker. Each house received a number and was localized by GPS.

Implementation of deltamethrin treated LLIN PermaNet© 2.0 was done in Caala village (14°47’E ; 12°25’S ; 238 houses ; 792 inhabitants ; 469 sleeping units) and Cahata village (14°48’E ; 12°20’ S ; 138 houses ; 484 inhabitants ; 442 sleeping units). A sleeping unit is “anything” used by inhabitants to sleep: mattress, piece of cardboard, loincloth, grass skirt, etc.

Two villages of the same area served as “control” for the first two years: Candiero (14°45’E; 12°22’S; 190 houses; 654 inhabitants) few kilometers West of Caala and Chisséquélé (14°47’E; 12°22’S; 181 houses; 418 inhabitants) few kilometers South of Cahata.

These four villages, with four others, are involved in the long-term large scale Balombo vector control comprehensive program implemented to compare four methods of vector control: LLIN alone; LLIN+ deltamethrin Insecticide Treated Plastic Sheeting (ITPS) pinned on the wall; ITPS alone and lambdacyhalothrin Inside Residual Spraying (IRS), two rounds followed by ITPS implementation to increase the long-lasting efficacy 

II-2. LLIN distribution process

The distribution of LLINs in Caala and Cahata was done following a two steps process according to the objectives in coverage:

  • February 2007: the objective was 1 LLIN per house (distribution of 360 LLIN in Caala and 310 in Cahata);
  • February 2008: the objective was a full coverage with 1 LLIN per sleeping unit (distribution of 277 LLIN in Caala and 195 in Cahata);
  • December 2008: complementary distribution of 49 LLIN in Caala and 25 in Cahata

Therefore, 686 LLIN were given in Caala for 469 sleeping units and 530 LLIN for 442 sleeping units in Cahata allowing a complete coverage in LLIN in both villages.

II-3. Parasitological evaluation 

In November 2006, before any intervention in this area, a cluster-based sampling parasitological survey was done in urban Balombo and some surrounding villages. A plasmodial prevalence of 54.9% (± 4.9%) in children < 15 n=557)>

From these information cross-sectional parasitological surveys (css) were planned and regularly made every two months, two weeks after the entomological survey, following the protocol implemented in Côte d’Ivoire to assess the efficacy of lambdacyhalothrin-treated nets in area where the main vector, An. gambiae was resistant to pyrethroids with a high frequency of kdr gene [12]. 

Field made blood thick films were Giemsa colored in situ then microscopically examined in Lobito in the Medical Department of the Angolan Sonamet© Society which sponsored a «Malaria Control Program” (MCP) including this village-scale vector-control project in Balombo.

Parasite density was estimated in counting the number of parasite versus 200 white blood cells with a further evaluation of parasitaemia/ml of blood considering 8000 white blood cells/ml. 10% of these blood films were double-blind checked in Yaoundé (OCEAC Parasitology Department).

As the team was well-known and well accepted, people of the villages come spontaneously to have their blood analysed for malaria diagnosis; this was done for everyone and results given to the village health worker for action according to the guidelines of the National Malaria Control Program.

From the initial listing of symptomless patients having had a thick blood film in the field, we extracted data of under-five (≤) children considered as the “at risk” group to analyze the evolution of both prevalence and parasite load for P. falciparum according to the two steps implementation of LLIN coverage in Caala and Cahata and comparing to the situation observed in the two control villages.

II-4. Statistical analyses

Percentages were compared with the classical Chi2 test (CDC EpiInfo software) and parasitaemia were analyzed with the non-parametric Mann-Whitney test with GraphPad software.

III. Results

III-1 Evolution of plasmodial prevalence in U5 symptomless children

2865 thick blood films were done on symptomless under-five children during the 40 surveys carried in the four villages during the first two years. Plasmodium infections (mainly P. falciparum with few P. malariae, most of them in association with P. falciparum) were observed in 1006 i.e. an overall plasmodial prevalence rate of 35.1% ±1.7% (Table 1).

yearsindicatorsCaalaCahataCandieroChisséquélétotal
Year 2007Nb Pf+1612047779521
 n3904062232161235
 %41,3%50,2%34,5%36,6%42,2%
 G+111961854
 nb css553316
Year 2008Nb Pf+144137103101485
 n4473764074001630
 %32,2%36,4%25,3%25,3%29,8%
 G+172625977
 nb css666624
totalNb Pf+3053411801801006
 n8377826306162865
 %36,4%43,6%28,6%29,6%35,1%
 G+28453127131
 nb css11119940

Table 1: Results of parasitological surveys done in 2007 and 2008 in the four villages among the ≤ 5 years old children (nb Pf+= number of P. falciparum positives thick films; n= number of thick films made; % = % of Pf positive thick films; G+= number of blood films with gametocytes; Nb surveys= number of cross- sectional surveys made).

Overall, it appeared a significant reduction of plasmodic index in the four villages, from year to year (fig.1), but which was different according to villages.

Figure 1: Evolution of P. falciparum prevalence in symptomless children ≤ 5 years old during the two years in the four villages surveyed.

In Caala: Plasmodium were observed in 305 of the 837 thick blood films prepared during the 11 surveys done in 2007 and 2008 (i.e. plasmodial infection= 36.4%) and the plasmodic prevalence significantly dropped (by 22%) from 41.3% (n= 390) to 32.2% (n= 447) (χ2= 7.39; p-value=< 0 xss=removed>

In Cahata: Plasmodium were observed in 341 of the 782 thick blood films (i.e. plasmodial infection= 43.6%) with a significant reduction (by 27%) of plasmodial prevalence, from 50.2% (n= 406) to 36.4% (n=376) (χ2= 15.14; p value < 0 xss=removed>

In Candiero: Plasmodium were observed in 180 of the 630 thick blood films (i.e. plasmodial infections= 28.6%) with a significant reduction (by 27%) from 34.5% (n=223) to 25.3% (n= 407) (χ2= 6.00; p value= 0.014; OR= 0.64 [0.45-0.92]).

In Chisséquélé: Plasmodium were observed in 180 of the 616 thick blood films (i.e. plasmodial infections= 29.6%) with a significant reduction (by 31%) from 36.6% (n= 216) to 25.3% (n= 400) (χ2= 8.69; p value= 0.0032; OR= 0.58 [0.41-0.84]).

From the year 2007 to the year 2008 the plasmodial prevalence significantly dropped by 25.6% in villages with LLIN (from 45.8%; n= 796 to 34.1%, n= 823; χ2= 23.1; OR= 0.61 [0.50-0.75]) and by 28.7% in villages without nets (from 35.5%, n= 439 to 25.3%, n= 807; χ2= 14.6; OR= 0.61 [0.48-0.79]).

As a significant reduction of plasmodial prevalence was observed in LLIN furnished villages and in control villages the plasmodial prevalence itself could not be considered as a relevant indicator in the condition of this field trial.

II-2. Evolution of parasite load in U5 symptomless children

The parasite load significantly decreased from year to year in villages with LLIN (P value= 0.0031 in Caala; < 0 value=0.65>

Adding and comparing the parasitaemia of the two LLIN villages and the two control villages clearly showed the significant reduction of parasite load in villages with LLIN while it remained at the same level in control villages (fig 2b).

Considering the relation between parasite density and the risk of clinical malaria, the parasite load appeared as an interesting relevant indicator of the impact of LLINs installation on the malaria burden in the area studied.

Figure 2a: Evolution of parasite load in each villages, with LLIN (Caala, Cahata) and without (Chisséquélé, Candiero) in under five symptomless children.

Figure 2b: Comparison of the evolution of P. falciparum parasitaemia in symptomless children ≤ 5 years old in the 2 villages with LLIN and in the 2 control villages (C).

III-3. Gametocytic index in U5 symptomless children

From the Table 1 it is possible to calculate the gametocyte index, and its evolution in each village and each year (Table 2).

 GI CaalaGI CahataGI CandieroGI ChisséquéléGI Total
Year 20076,83%4,68%2,69%8,33%4,37%
Year 20083,80%6,91%6,14%2,25%4,72%
Total3,35%5,75%4,92%4,38%4,57%

Table 2: Evolution of the gametocyte index (GI) in symptomless U5 children in each village and for each year.

The evolution, from year to year, appeared different according to village (figure. 3) with a decrease in Caala and Chisséquélé and an increase in Cahata and Candiero. But the overall gametocyte index in 2007 and 2008 were remarkably similar, respectively 4.37% (=1,235) and 4.72% (n=1,006).

                                                                                
Figure 3: Evolution of gametocyte index in symptomless U5 children in each year for each village.

The gametocyte index in LLIN villages were similar in years 2007 (GI= 3.77%; n= 796) and 2008 (GI=5.22%; n=823) (χ2= 1.99; p=0.16; OR=0.71 [0.44-1.14]).

But they were also similar in control villages, GI= 5.47% (n= 439) in years 2007 and GI= 4.21% (n= 807) in 2008 (χ2= 0.042; p= 0.84; OR=0.94 [0.53-1.67]).

There fore the gametocyte index did not appear as a relevant indicator of the impact of LLIN in this trial.

IV. Discussion

Since the first observations of the entomological and epidemiological efficacy of impregnated mosquito nets [27-31].  numerous studies have demonstrated that large-scale use of impregnated mosquito nets (“ITNs”) drastically reduces transmission, malaria morbidity and overall infant and child mortality [11-34]. 

Vector control can still keep actual efficacy against malaria [35].  even when vectors are resistant to pyrethroid insecticides [12-41].  this issue represents an increasingly worrying problem [42-45].  and new mosquito nets are treated with the association of pyrethroid and other chemical such as PBO [46-48].  or PPF [49,50]. 

Another problem arises with the assessment of the actual epidemiological impact of impregnated mosquito nets on malaria morbidity given the several "co-factors" [51].  involved in this issue which requires specific protocols [7-52].  The two main problems, among several others, are the challenge of “malaria” diagnosis with the lack of pathognomonic symptoms and the high percentage of symptomless Plasmodium falciparum carriers in malaria endemic areas, inducing a lack of reliability of data, often reported [7-26].  with a great overdiagnosis of “malaria” [53,54]. 

As early as 1949, Boyd [10-13]. underlined "it must be stressed that the present-day diagnosis of malaria should imply the existence of a plasmodial infection, and that such a diagnosis is not adequate unless the species of the causative parasite is identified. This criterion necessitates a microscopic diagnosis…the presence of Plasmodium is a necessary but not sufficient condition”. According to the results of various malariological surveys, Boyd (loc.cit.) underlined "in view of the fluctuations of parasite density above and below the level of microscopic detectability, the opinion that if in any ambulatory group in whom 50 per cent infection is found on a single examination, the group is actually nearly 100 per cent infected”. A situation regularly observed during “routine” cross sectional malaria surveys in the field [14]. and which questioned the validity of the “plasmodial presence” only for the diagnosis of “malaria” in endemic area and hence for the epidemiological evaluation of a vector control program. 

In Balombo area, several cross sectional malaria parasite surveys showed a high frequency of plasmodial infections in symptomless carriers [15].  and it appeared that the plasmodic index significantly decreased in LLIN furnished villages as well as in control villages showing that the classical plasmodic index could not be a relevant indicator in this study.

Another parasitological indicator should therefore be taken into consideration. As Christophers (in Boyd, loc. cit.) underlined, "a parasite rate of say 50 per cent may largely be made up of scanty infections representing little or no morbidity or of a relatively heavy infections with all the signs of a community suffering severely from malaria "and further on "we can therefore only adequately describe the parasitaemia in a community by ascertaining the numerical value of the infections encountered. The number of parasites per cu.mm is the PARASITE COUNT. All these are means of expressing the PARASITE DENSITY for the individual or community as the case may be”.

A new interest was devoted to this notion of parasite load and the issue of its relationship with malaria morbidity [24-55].  inducing the notion of pyrogenic threshold [25-60]. In a study on malaria morbidity in children under 3 years old in Benin it is reported that "the comparison with a control group demonstrated that children with parasitaemia exceeding 1000 infected red blood cells per microliter of blood had fever significantly more often than children with lower levels of parasitaemia” [56]. For [61]. Plucinski et al “Malaria parasites must be present at sufficiently high densities in order to cause symptoms such as fever, especially among individuals living in high-transmission settings who have been exposed multiple times and developed antimalarial adaptive immunity. The P. falciparum parasite density necessary to provoke fever, i.e., the pyrogenic threshold, is dependent on factors that influence host responses and immunity and can vary substantially”. Numerous studies were done on this notion of pyrogenic threshold, and its estimation [57-62]. but this is not the aim of our study. 

On the other hand, this notion of the parasite load appeared relevant in our study to compare the evolution of malaria parasitaemia in the two villages provided with impregnated mosquito nets versus the two villages without any organized vector control operations.

Actually, the statistical analysis of the distributions of the parasite densities showed a significant reduction in parasitaemia with the overall implementation of impregnated mosquito nets while in the two control villages these parasitic loads remained similar during the first two years.

The findings in Balombo studies clearly showed that several parasite indicators are needed to better appreciate the natural, or induced, evolution of situation of malaria parasite and the impact of mosquito nets in reducing the potential of malaria burden in under 5 years children. 

V. Conclusion

The choice of indicators is essential to monitor, and evaluate, a malaria control program and take eventual action.

Gaining base line data is a crucial component of any control program, and for having forgotten this point, a recent house spraying operation in Angola was a failure, and loss of funds.

The initial two years studies at the beginning of the village scale long term malaria vector control program around Balombo town (Benguela Province, Angola) clearly showed how conclusions could be different according to the selected indicators. 

Plasmodium prevalence, and its evolution from year to year, were the same in symptomless children ≤ 5 years old (= “at risk” age group) of the two villages with treated nets and the two villages without, leading to a conclusion of the inefficiency of treated nets if based upon this indicator only.

But the parasitaemia of children of villages with treated nets was significantly lower than in children of villages without nets leading to the conclusion on the actual efficacy of nets to reduce potential malaria morbidity as there is a link between parasite load and clinical illness a point well in the line of some recent analysis [35]. 

This two years study shows how the conclusion could be completely different according to the indicator and the Balombo project underlined, once again, the key point of “Beware the plasmodial infection indicators”.

Contributions of authors.

This work was carried out in collaboration among all authors. PC elaborated the protocol, participated in field surveys, did analyzing of data and drafted the report. JCT, VF and LE participated in field surveys, VF participated in microscopical examination of blood slides and verification, GC participated in the interpretation data and English version. FG and RO participated in data statistical analysis.

All authors read and approved the final manuscript.

Ethical approved. 

Studies done at the request and with the National Malaria Control Program and the Public Health Provincial Department in the context of the ongoing “Malaria Control Program” of the Angolese Society Sonamet.

Competing interest. 

Authors have no competing interests.

Acknowledgements.

We would like to thank the managers of the Angolan company Sonamet© and its medical department; as well as the international company SubSea©7 for their permanent support for this work and their implication in malaria control in the region.

We thank Dr Titelman who procured the material for vector control: nets and plastic sheeting.

Our thanks also to the national and provincial authorities for their authorization and participation in these studies as well as to the population of the villages for their positive cooperation.

References

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I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

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Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

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Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

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Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

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Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

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Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

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Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

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S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

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Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

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George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

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Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

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Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

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Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

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Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

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Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

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Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

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Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

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Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

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Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

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Dr Susan Weiner

My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.

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Lin-Show Chin

My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.

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Sonila Qirko

My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.

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Luiz Sellmann