The Open Infectious Diseases Journal




ISSN: 1874-2793 ― Volume 10, 2018
SYSTEMATIC REVIEW

Varicella (Human Herpes Virus-3) Vaccine Potential Role Against Herpes (HSV-1/HSV-2) Viruses to Prevent HIV-1 Pandemic in Sub- Saharan Africa



Jacqueline Le Goaster1, *, Patrice Bourée1, Franck N. El Sissy1, Johanna Pokossy Epee1, Frédéric Tangy2, Anne-Lise Haenni3, Allan Goldstein4
1 Department of Tropical Diseases, Hôtel-Dieu, University Paris V, Paris, France
2 Viral Genomics, Vaccinations, CNRS, Pasteur Institute, Paris, France
3 Jacques Monod Institute, CNRS, University Paris VII, Paris, France
4 Department Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037, USA

Abstract

Background:

Synergy exists between DNA and RNA viruses. It was found that the Human Immunodeficiency Viruses (HIV-1) are RNA viruses at the origin of Acquired Immune Deficiency Syndrome (AIDS). The DNA recurrent herpes diseases are associated to AIDS virus at the origin of Sub-Saharan cancer AIDS pandemic.

Objective:

It is speculated that a varicella virus (HHV-3) immune defect could originate HSV- 1/HSV-2 recurrent herpes diseases that can be cured by varicella vaccine (2012).

Methods:

At a Symposium held in Kampala, Uganda (1962), impressive Sub-Saharan cancer epidemics: Hodgkin lymphomas and Kaposi sarcomas have been reported since the onset of the 20th century and remained unexplained. Over one thousand publications related to these cancer epidemics were presented. For millenniums, Bantu populations have been living in tropical forests close to chimpanzees infected by Simian Immune Deficiency viruses (SIV). SIV became Human Immune Deficiency viruses (HIV-1). AIDS is a zoonosis.

Results:

The DNA and RNA viruses, herpes with HIV-1 viruses, are correlated to Sub- Saharan AIDS infections. They induce an extensive immune deficiency with other herpes viruses such as HHV-4 and HHV-8, which are linked to lymphomas and Kaposi sarcomas. It is postulated that a primary HHV-3 immune weakness could be linked to herpes partnership with AIDS pandemic.

Conclusion:

The Oka, anti-HHV-3, varicella vaccine is able to cure HSV1/HSV2 recurrent herpes diseases. It induces a specific increase of the varicella antibodies. Thus varicella vaccination could prevent herpes recurrences in Sub-Saharan Africa. One- child dose varicella vaccine could be proposed as the first step to overcome HHV-3 herpes deficiency in order to prevent AIDS pandemic.

Keywords: Varicella (HHV-3) vaccine, HSV-1/HSV-2/Herpes viruses/HIV-1, AIDS prevention, Sub-Tropical Africa, Hodgkin lymphomas, Kaposi sarcomas.


Article Information


Identifiers and Pagination:

Year: 2018
Volume: 10
First Page: 116
Last Page: 123
Publisher Id: TOIDJ-10-116
DOI: 10.2174/1874279301810010116

Article History:

Received Date: 31/5/2018
Revision Received Date: 27/7/2018
Acceptance Date: 6/8/2018
Electronic publication date: 31/08/2018
Collection year: 2018

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© 2018 Le Goaster et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the Department of Tropical Diseases, Patrice Bouree Hotel Dieu, University Paris V, Paris, France; Tel: 00 33 1 45 03 11 35; E-mail: j.lego@free.fr




1. INTRODUCTION

For more than a century, unexplained cancers such as Hodgkin lymphomas and Kaposi sarcoma have occurred in Subtropical Africa (Fig. 1).

Fig. (1)
Correlation between Kaposi’s sarcoma and Bantu ethnies in subtropical Africa.
Location of Bantu populations. Sites of medical centers, in tropical Africa (1914-1960). Chimpanzee observatories (1914-1960).


In 1981 in San Francisco, this same type of tumors was related to unidentified viral infections; in 1983, HIV-1 was identified as being at the origin of AIDS cancer pandemic. Later in 2000, it was discovered that herpes viruses have a pathogenic power at the origin of tumors such as Hodgkin lymphomas, Kaposi sarcomas, etc.

It was established that these herpes viruses play a key role related to HIV-1 infections [1Herpes simplex virus type 2 (HSV-2) suppression to prevent HIV transmission, ClinicalTrialsgov Identifier: NCT00194519, 2011 A service of the US 2011.].

The human herpes simplex viruses HSV-1/HSV-2 and the varicella zoster virus HHV-3 are members of the subfamily Alphaherpesvirinae following the morphological order of herpes viruses distinct from all other viruses [2Davison AJ, Eberle R, Ehlers B, et al. The order Herpesvirales. Arch Virol 2009; 154(1): 171-7.[http://dx.doi.org/10.1007/s00705-008-0278-4] [PMID: 19066710] ]. (Fig. 2).

Fig. (2)
Phylogenetic tree of the members of the Herpesviridae family [2Davison AJ, Eberle R, Ehlers B, et al. The order Herpesvirales. Arch Virol 2009; 154(1): 171-7.[http://dx.doi.org/10.1007/s00705-008-0278-4] [PMID: 19066710] ].


The members of the Herpesviridae phylogenic tree refer to herpes virus pathogeny for humans: α herpesvirinae, β herpesvirinae and γ herpesvirinae according to McGeoch [3McGeoch DJ, Dolan A, Ralph AC. Toward a comprehensive phylogeny for mammalian and avian herpesviruses. J Virol 2000; 74(22): 10401-6.[http://dx.doi.org/10.1128/JVI.74.22.10401-10406.2000] [PMID: 11044084] ] (Fig. 3).

Fig.(3)
Phylogenetic tree of the Herpesviridae family includes numerous living animals [2Davison AJ, Eberle R, Ehlers B, et al. The order Herpesvirales. Arch Virol 2009; 154(1): 171-7.[http://dx.doi.org/10.1007/s00705-008-0278-4] [PMID: 19066710] ].


Infections caused by HSV-1 or HSV-2 result of cell-to-cell transmission, involve cell-mediated immunity [4Favoreel HW. Immune evasion of alphaherpesviruses. Verh K Acad Geneeskd Belg 2008; 70(1): 47-65.[PMID: 18512358] ]. The HHV-3/HSV-1/HSV-2 viruses must have a close relationship, that has however been sparsely explored by researchers in fundamental virology [5Schmidt NJ, Lennette EH, Magoffin RL. Immunological relationship between herpes simplex and varicella-zoster viruses demonstrated by complement-fixation, neutralization and fluorescent antibody tests. J Gen Virol 1969; 4(3): 321-8.[http://dx.doi.org/10.1099/0022-1317-4-3-321] [PMID: 4306713] , 6Giehl KA, Müller-Sander E, Rottenkolber M, Degitz K, Volkenandt M, Berking C. Identification and characterization of 20 immunocompetent patients with simultaneous varicella zoster and herpes simplex virus infection. J Eur Acad Dermatol Venereol 2008; 22(6): 722-8.[http://dx.doi.org/10.1111/j.1468-3083.2008.02587.x] [PMID: 18312326] ].

“Varicella is a common and very infectious disease in children” caused by VZV, known as varicella zoster virus (HHV-3) [7Takahashi M, Otsuka T, Okuno Y, Asano Y, Yazaki T, Isomura S. Live vaccine used to prevent the spread of varicella in children in hospital. Lancet 1974; 2(7892): 1288-90.[http://dx.doi.org/10.1016/S0140-6736(74)90144-5] [PMID: 4139526] ]. “The causative agent of varicella is one of the eight herpes viruses that include humans as natural hosts. “The Varicella Zoster Virus exhibits a low genomic diversity relatively to other studied herpesviruses” [8McGeoch DJ. Lineages of varicella-zoster virus. J Gen Virol 2009; 90(Pt 4): 963-9.[http://dx.doi.org/10.1099/vir.0.007658-0] [PMID: 19264671] ].

The varicella zoster virus (VZV/HHV-3) can be considered as a primordial event with a specific immunogenic Human Leucocyte Antigen (HLA) as a final result.

It is speculated that a varicella virus (HHV-3) immune defect could originate HSV- 1/HSV-2 recurrent herpes diseases which can be cured by varicella vaccine. Since 2005, based on this hypothesis, the varicella vaccine is used against herpes viruses, it has been efficient. It is possible to acquire positive long-term clinical results as it has been observed [9Le Goaster J, Gonzalo S, Bouree P, Tangy F, Haenni AL. Efficacy of the anti-VZV (anti-HSV3) vaccine in HSV1 and HSV2 recurrent herpes simplex disease: A prospective study. Open Access J Clin Trials 2012; 4: 51-8.[http://dx.doi.org/10.2147/OAJCT.S33292] ]. There have been no relapses concerning more than 70 patients (10 to 80 years old) so far.

The HSV-1/HSV-2 recurrent herpes diseases play a key role related to HIV-1 infections. The varicella vaccine will be used to cure herpes diseases and it could play a role, first against HSV-1/HSV-2 recurrent herpes diseases, further HIV-1 infections [9Le Goaster J, Gonzalo S, Bouree P, Tangy F, Haenni AL. Efficacy of the anti-VZV (anti-HSV3) vaccine in HSV1 and HSV2 recurrent herpes simplex disease: A prospective study. Open Access J Clin Trials 2012; 4: 51-8.[http://dx.doi.org/10.2147/OAJCT.S33292] ].

The first HHV-3 vaccine was the “Oka strain” vaccine, created by Takahashi et al. (1974) [7Takahashi M, Otsuka T, Okuno Y, Asano Y, Yazaki T, Isomura S. Live vaccine used to prevent the spread of varicella in children in hospital. Lancet 1974; 2(7892): 1288-90.[http://dx.doi.org/10.1016/S0140-6736(74)90144-5] [PMID: 4139526] ]. The original virus strain was used initially to prevent varicella in high-risk leukemic children who remained free from varicella with safety.

The varicella vaccine is a live attenuated herpes virus vaccine (1,350 UFP), available for children and adults. In the USA, in 1995, varicella vaccination program was decided using: an universal one dose childhood. It became an obligation for all children in 3 states: California, Massachusetts, Pennsylvania. The incidence of Varicella has fallen by 80%.

Studies of geographical variations of the varicella virus (VZV/HHV-3) have been performed. Isolates from Caucasian populations are represented by just one genome sequence. The strain related to the OKA vaccine is constituted by Japanese origin and an incomplete VZV Sub-Saharan African genome sequence [2Davison AJ, Eberle R, Ehlers B, et al. The order Herpesvirales. Arch Virol 2009; 154(1): 171-7.[http://dx.doi.org/10.1007/s00705-008-0278-4] [PMID: 19066710] ].

Therefore the OKA varicella vaccine is originated partly from Japan and partly from Sub-Sahara. This underlines the ancient human origin from sub-tropical Africa. This varicella vaccine is used to prevent shingles and zoster in immunodepressed individuals. The varicella vaccine has potential pharmacodynamic properties but these have not been deeply investigated [8McGeoch DJ. Lineages of varicella-zoster virus. J Gen Virol 2009; 90(Pt 4): 963-9.[http://dx.doi.org/10.1099/vir.0.007658-0] [PMID: 19264671] ]. However, recently the efficiency of such anti-VZV vaccine against recurrent HSV-1/HSV-2 infections has been already reported [9Le Goaster J, Gonzalo S, Bouree P, Tangy F, Haenni AL. Efficacy of the anti-VZV (anti-HSV3) vaccine in HSV1 and HSV2 recurrent herpes simplex disease: A prospective study. Open Access J Clin Trials 2012; 4: 51-8.[http://dx.doi.org/10.2147/OAJCT.S33292] ].

It appeared essential to increase the efficient HHV-3 (VZV) power to raise the immungenetic ability against recurrent HSV-1/HSV-2 herpes diseases. Then, as it is reported it is possible to prevent recurrent herpes diseases linked to HIV-1 infections [1Herpes simplex virus type 2 (HSV-2) suppression to prevent HIV transmission, ClinicalTrialsgov Identifier: NCT00194519, 2011 A service of the US 2011., 9Le Goaster J, Gonzalo S, Bouree P, Tangy F, Haenni AL. Efficacy of the anti-VZV (anti-HSV3) vaccine in HSV1 and HSV2 recurrent herpes simplex disease: A prospective study. Open Access J Clin Trials 2012; 4: 51-8.[http://dx.doi.org/10.2147/OAJCT.S33292] , 10Fauci AS. An HIV vaccine is essential for ending the HIV/AIDS pandemic. JAMA 2017; 318(16): 1535-6.[http://dx.doi.org/10.1001/jama.2017.13505] [PMID: 29052689] ].

The effect of the varicella vaccine on recurrent herpes diseases must be attributed to a cell-mediated immune response as it has been reported [9Le Goaster J, Gonzalo S, Bouree P, Tangy F, Haenni AL. Efficacy of the anti-VZV (anti-HSV3) vaccine in HSV1 and HSV2 recurrent herpes simplex disease: A prospective study. Open Access J Clin Trials 2012; 4: 51-8.[http://dx.doi.org/10.2147/OAJCT.S33292] , 11Ferenczy MW. Prophylactic vaccine strategies and the potential of therapeutic vaccines against herpes simplex virus. Curr Pharm Des 2007; 13(19): 1975-88.[http://dx.doi.org/10.2174/138161207781039779] [PMID: 17627531] ]. It suggests immunological induction of cell-mediated reactivity between HSV-1/HSV-2 and HHV-3 revealed by a specific raise of anti-HHV-3 Ab. induced by Varicella Vaccine.

Lymphocyte stimulation triggers the observed clinical anti-HSV-1/anti-HSV-2 efficiency using the varicella vaccine to prevent recurrent herpes diseases. It is clearly in favor of this hypothesis, a cell-mediated reactivity might be involved between HSV- 1/HSV-2 and HHV-3. As a matter of fact, a specific serological increase of anti-HHV-3 Ab levels correlated with the recurrent herpes diseases cure can be observed.

In 2000, a link was established between the sexually recurrent herpes disease HSV-1/HSV-2 with HIV-1 AIDS diseases which were prevalent in Subtropical Africa [12Abu-Raddad LJ, Magaret AS, Celum C, et al. Genital herpes has played a more important role than any other sexually transmitted infection in driving HIV prevalence in Africa. PLoS One 2008; 3(5): e2230.[http://dx.doi.org/10.1371/journal.pone.0002230] [PMID: 18493617] ].

It is important to underline the role played by the other members of the Betaherpesvirinae as HHV-5, the other members of the Gammaherpesvirinae include HHV-4 known as Epstein-Barr viruses are involved in lymphomas including Hodgkin lymphomas. Finally the HHV-8 viruses are linked to Kaposi sarcomas (Table 1).

Table 1
Features of the human pathogenic herpes viruses.


2. METHODS – DATA ANALYSIS

Subtropical African Cancer Epidemics in Bantu populations were reported in the early 20th century as an epicentre of Kaposi sarcomas and lymphoma epidemics.

Many clinicians in Central Africa proposed an infectious viral origin for outdoor Bantu tribes workers (1914). They failed to prove it. A resurgence of interest was stimulated by the high incidence of these cancers observed in South African histological samples tested in Johannesburg [13Gelfand M. Malignancy in the African. S Afr Med J 1949; 23(50): 1010-6.[PMID: 15398379] , 14Rothman S. Remarks on sex, age, and racial distribution of Kaposi’s sarcoma and on possible pathogenetic factors In: Ackerman LV, Murray JF, Eds. Symposium on Kaposi’s Sarcoma 1963; 13-6.]. Clinicians observed that outdoor Bantu hunters were the selected targets of these cancer epidemics [15Hallenberger O. Multiple Angiosarkome der Haut bei einem Kamerunneger. Arch Schiffs Trop Hyg 1914; 18: 647-51.]. They were exposed to the blood of chimpanzees which could be infected by Simian Immunodeficiency Virus (SIV). AIDS IS A ZOONOSIS [16Hahn BH, Shaw GM, De Cock KM, Sharp PM. AIDS as a zoonosis: Scientific and public health implications. Science 2000; 287(5453): 607-14.[http://dx.doi.org/10.1126/science.287.5453.607] [PMID: 10649986] ]. Primates are reservoirs for SIV and if they carry SIV they can contaminate the Bantu hunters, SIV thus became HIV-1 in human-beings. SIV and HIV-1 are both RNA viruses [16Hahn BH, Shaw GM, De Cock KM, Sharp PM. AIDS as a zoonosis: Scientific and public health implications. Science 2000; 287(5453): 607-14.[http://dx.doi.org/10.1126/science.287.5453.607] [PMID: 10649986] ]. Central Africa remains the global HIV-1 epicentre (Fig. 1).

HIV-1 viruses escape from immune and drug pressures. It appears to be a co-activator of micro-organisms such as Pneumocystis jiroveci and viruses such as herpes viruses: lymphomas and Kaposi sarcomas as it was observed in the San Francisco epidemic (1981) [17Barré-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983; 220(4599): 868-71.[http://dx.doi.org/10.1126/science.6189183] [PMID: 6189183] ]. In 2008 close similarities were observed between the African Kaposi sarcomas epidemics and the same epidemics in San Francisco. Mostly young adults were affected by these similar fatal diseases called Acquired Immune Deficiency Syndrome, AIDS disease, which then emerged worldwide.

The production of deficient anti-HHV-3 antibodies is postulated in front of recurrent herpes viruses HSV- 1/HSV-2, this could enhance the herpes immune deficiency facing HIV-1.

All human beings suffer from shingles caused by varicella virus (HHV-3/VZV) during childhood but an immunogenetic HHV- 3 failure can be a first prerequisite to favour HSV-1/HSV-2 recurrent herpes diseases followed by the fatal outcome HIV-1 cell anchorage as stated by Lawrence Corey [18Corey L. Herpes simplex virus type 2 and HIV-1: The dialogue between the 2 organisms continues. J Infect Dis 2007; 195(9): 1242-4.[http://dx.doi.org/10.1086/513570] [PMID: 17396990] ].

3. RESULTS

The evaluation of cancer epidemic data showed, Specific Environmental Factors that were proposed to play a key role in cancer epidemics in Subtropical Africa [19Oettle AG. Geographical and racial differences in the frequency of Kaposi’s sarcoma as evidence of environmental or genetic causes In: Ackerman LV, Murray JF, Eds. Symposium on Kaposi’s Sarcoma 1963; 17-50.]. These cancers are most frequent in South Africa as well as East Africa where the main part of the Bantu population is composed of outdoor forest farmers and where bare footedness is the rule. This suggested an etiological role of chronic injury among Bantu hunter inhabitants of tropical forests. Surprisingly, no case was reported among booted Bantu clerks living in cities in South Africa [19Oettle AG. Geographical and racial differences in the frequency of Kaposi’s sarcoma as evidence of environmental or genetic causes In: Ackerman LV, Murray JF, Eds. Symposium on Kaposi’s Sarcoma 1963; 17-50.] (Figs. 4 and 5).

Fig. (4)
Kaposi sarcomas and lymphoma epidemics (1914-1960) in [16Hahn BH, Shaw GM, De Cock KM, Sharp PM. AIDS as a zoonosis: Scientific and public health implications. Science 2000; 287(5453): 607-14.[http://dx.doi.org/10.1126/science.287.5453.607] [PMID: 10649986] ] Among black African populations report by Findlay [28Findlay GM, Leech RB. Kaposi’s multiple idiopathic haemorrhagic sarcoma. Trans R Soc Trop Med Hyg 1946; 40(3): 351-3.[http://dx.doi.org/10.1016/0035-9203(46)90075-2] [PMID: 20286133] ].


Fig. (5)
Kaposi’s sarcoma and lymphoma epidemics among all cancers from 1988 to 1997 in Gambia. Compared to the USA these cancers were related to AIDS diseases in Bah et al. [27Bah E, Parkin DM, Hall AJ, Jack AD, Whittle H. Cancer in the Gambia: 1988-97. Br J Cancer 2001; 84(9): 1207-14.[http://dx.doi.org/10.1054/bjoc.2001.1730] [PMID: 11336472] ].


In Tropical Africa, Whites and Indians remained relatively unaffected by Kaposi sarcomas and lymphomas. We can wonder why they were able to save their lives compared to the native tropical forest Bantu populations?

In industrialized countries such as in Europe and in the USA, Kaposi sarcomas are known as a disease of the elderly compared to the large infected young Bantu populations (Fig. 6).

Fig. (6)
Symposium in Kampala, Uganda, on Kaposi sarcomas, lymphomas and all cancers in Africa (1914-1960), series in black populations, Findlay [28Findlay GM, Leech RB. Kaposi’s multiple idiopathic haemorrhagic sarcoma. Trans R Soc Trop Med Hyg 1946; 40(3): 351-3.[http://dx.doi.org/10.1016/0035-9203(46)90075-2] [PMID: 20286133] ].


These Kaposi sarcomas and lymphomas were already proposed to be contagious [20Smith EC, Elmes BG. Malignant disease in natives of Nigeria: An analysis of five hundred tumours. Ann Trop Med Parasitol 1934; 28: 461-76.[http://dx.doi.org/10.1080/00034983.1934.11684817] , 21Clark M. A report of 50 consecutive cases of malignant growths seen amongst the Wa-Kikuyu. East Afr Med J 1948; 25(3): 123-5.[PMID: 18914589] ] with an incubation period of 1 to 10 years respectively in Mozambique [22Prates MD. Malignant neoplasms in Mozambique; A frequency ratio survey from 1944-December 31, 1957 and a comparison with other parts of Africa. Br J Cancer 1958; 12(2): 177-94.[http://dx.doi.org/10.1038/bjc.1958.21] [PMID: 13546516] ] linked to occupations, occurring among farmers who constitute 95% of the Bantu population in Cameroon, Gabon, Congo [13Gelfand M. Malignancy in the African. S Afr Med J 1949; 23(50): 1010-6.[PMID: 15398379] ].

Kaposi sarcomas identified at the histological level appeared at that time as clinically unique compared to American or European Kaposi sarcomas in terms of symptoms and fatal evolution [23Choisser RM, Ramsey EM. Aetiology of Kaposi’s disease, Preliminary report of investigations. Sci Med J 1940; 33: 392-5.].

4. DISCUSSION

Subtropical African human populations living in tropical forests were contaminated by zoonotic or cross-species transmission. Monkeys represent the natural reservoir of simian viruses, their infected females by SIV breast-fed for 4 years, so their simian babies were infected by SIV and these orphan animal were kept as pets which are able to contaminate all the hunter families [24Leakey R. The making of mankind. The Rainbird Publishing Group Ltd, ed 36 Park street 1981; 105., 25Picq P. Les Origines de l’Homme. Tallandier 2005; 111.].

For over several centuries, there have been frequent opportunities for human beings to become infected by SIV-infected chimpanzees but it is important to note that genetic mechanisms have been operating to enhance the immunogenic power of human beings to escape and survive attacks by endemic HIV-1 strains in Subtropical Africa.

It is necessary to help people in their immunological power against HIV-1. It is the medical priority of all physicians, as Lawrence Corey wrote it: the “two unrelated pathogens,HSV- 1/HSV-2 and HIV-1, occupy the same ecological space in Central Africa” [18Corey L. Herpes simplex virus type 2 and HIV-1: The dialogue between the 2 organisms continues. J Infect Dis 2007; 195(9): 1242-4.[http://dx.doi.org/10.1086/513570] [PMID: 17396990] ]. The observations reported here underline the basic role played by members of the Herpesviridae family at the onset of the HIV-1 pandemic worldwide [26Davison AJ. Human herpes virus evolution. Ann N Y Acad Sci 2012; 1230: 37-49.[http://dx.doi.org/10.1111/j.1749-6632.2011.06358.x] ].

Bantu simian hunters could have presented an immungenetic weakness against VZV with an another reason: consanguinity. They became the deficient victims of the HSV-1/HSV-2 recurrent herpes diseases. Then exposed to be infected by SIV, the chimpanzee hunters and their families became eligible for SIV/HIV-1 contaminations and AIDS disease.

CONCLUSION

Following the recent discovery of the links between HSV-1/HSV-2 recurrent herpes diseases with a first varicella (HHV-3) immune deficiency, it appears that there is a preliminary biological herpes viral defect able to precede and to favor HIV- 1 infection.

It is logical to postulate a preventive anti-herpes therapy using varicella vaccine. The use of a universal child dose of varicella vaccine could be the primary objective to cure the recurrent herpes infections and then to prevent AIDS pandemic.

This will represent the first step to push back herpes diseases related to HIV-1/AIDS pandemic.

Moreover, a first HHV-3 failure can precede or induce a large immune deficiency against all the other pathogenic herpes viruses such as HHV-4, HHV-5, HHV-6 and HHV-8.

Therefore, the use of varicella vaccine could represent the hope to prevent HSV1-/HSV-2 infections related to AIDS pandemic.

FUNDINGS

The authors thanked Physiologie et Tumeur, an independant non-profit Research Institution in Paris, France, for its support.

PATIENT AND PUBLIC INVOLVEMENT STATEMENT

Starting at the early 20th century, the authors have analyzed African population’s historical data. No recent patients were involved or concerned in this study.

CONSENT FOR PUBLICATION

Not applicable.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

The authors thank Professor Allan Goldstein for his constructive comments and valuable suggestions regarding the manuscript and Professor Michiaki Takahashi †, who originally created the Oka strain anti-varicella vaccine, for his enthusiasm, constant support, and encouragement to publish our research.

REFERENCES

[1] Herpes simplex virus type 2 (HSV-2) suppression to prevent HIV transmission, ClinicalTrialsgov Identifier: NCT00194519, 2011 A service of the US 2011.
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[3] McGeoch DJ, Dolan A, Ralph AC. Toward a comprehensive phylogeny for mammalian and avian herpesviruses. J Virol 2000; 74(22): 10401-6.[http://dx.doi.org/10.1128/JVI.74.22.10401-10406.2000] [PMID: 11044084]
[4] Favoreel HW. Immune evasion of alphaherpesviruses. Verh K Acad Geneeskd Belg 2008; 70(1): 47-65.[PMID: 18512358]
[5] Schmidt NJ, Lennette EH, Magoffin RL. Immunological relationship between herpes simplex and varicella-zoster viruses demonstrated by complement-fixation, neutralization and fluorescent antibody tests. J Gen Virol 1969; 4(3): 321-8.[http://dx.doi.org/10.1099/0022-1317-4-3-321] [PMID: 4306713]
[6] Giehl KA, Müller-Sander E, Rottenkolber M, Degitz K, Volkenandt M, Berking C. Identification and characterization of 20 immunocompetent patients with simultaneous varicella zoster and herpes simplex virus infection. J Eur Acad Dermatol Venereol 2008; 22(6): 722-8.[http://dx.doi.org/10.1111/j.1468-3083.2008.02587.x] [PMID: 18312326]
[7] Takahashi M, Otsuka T, Okuno Y, Asano Y, Yazaki T, Isomura S. Live vaccine used to prevent the spread of varicella in children in hospital. Lancet 1974; 2(7892): 1288-90.[http://dx.doi.org/10.1016/S0140-6736(74)90144-5] [PMID: 4139526]
[8] McGeoch DJ. Lineages of varicella-zoster virus. J Gen Virol 2009; 90(Pt 4): 963-9.[http://dx.doi.org/10.1099/vir.0.007658-0] [PMID: 19264671]
[9] Le Goaster J, Gonzalo S, Bouree P, Tangy F, Haenni AL. Efficacy of the anti-VZV (anti-HSV3) vaccine in HSV1 and HSV2 recurrent herpes simplex disease: A prospective study. Open Access J Clin Trials 2012; 4: 51-8.[http://dx.doi.org/10.2147/OAJCT.S33292]
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[11] Ferenczy MW. Prophylactic vaccine strategies and the potential of therapeutic vaccines against herpes simplex virus. Curr Pharm Des 2007; 13(19): 1975-88.[http://dx.doi.org/10.2174/138161207781039779] [PMID: 17627531]
[12] Abu-Raddad LJ, Magaret AS, Celum C, et al. Genital herpes has played a more important role than any other sexually transmitted infection in driving HIV prevalence in Africa. PLoS One 2008; 3(5): e2230.[http://dx.doi.org/10.1371/journal.pone.0002230] [PMID: 18493617]
[13] Gelfand M. Malignancy in the African. S Afr Med J 1949; 23(50): 1010-6.[PMID: 15398379]
[14] Rothman S. Remarks on sex, age, and racial distribution of Kaposi’s sarcoma and on possible pathogenetic factors In: Ackerman LV, Murray JF, Eds. Symposium on Kaposi’s Sarcoma 1963; 13-6.
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Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


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