WO2014110149A2 - Method of testing or treating the presence of live viruses - Google Patents

Abstract

A process to determine the presence of live viruses within viral lesions, such as herpes lesions and warts, in the suspected site on persons or animals is provided. Also provided are methods of treating a viral infection at the site of a viral outbreak on a cutaneous surface of a subject. An aqueous detection reagent solution containing as one example, neutral red and water is applied to the test or treatment site and the test or treatment site to which the reagent has been applied is exposed to an light for a period of time sufficient to detect the presence or absence of the virus or to reduce the number of viral particles at the site.

Description

METHOD OF TESTING OR TREATING THE PRESENCE OF LIVE VIRUSES

CROSS REFERENCE TO RELATED .APPLICATIONS

[0001] This application depends from and claims priority to U.S. Provisional Patent Application No: 61/749,951 filed January 8, 2013 and U.S. Provisional Patent Application No: 61/908,921 filed November 26, 2013, the entire contents of each of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

[0002] The invention relates to the field of topical treatments and tests to determine the presence of live viruses, especially Herpes simplex virus infections and warts.

[0003] The human herpes viruses, including Herpes simplex virus (HSV), Varicella zoster virus (VZV), Cytomegalovirus (CMV), Epstein-Ban" vims (EBV), Human herpes virus 6 (HHV-6), Human herpes virus 7 (HHV-7), and Human herpes virus 8 (HHV-8) may produce a variety of clmically significant manifestations either as self-limited infections or non-resolving opportunistic infections.

[0004] Many herpes viruses commonly infect man, but clinically apparent or life- threatening illnesses are most often seen in persons who are immunocompromised, including persons with primary or secondary immunodeficiencies (including AIDS), persons undergoing cancer chemotherapy, transplant recipients, persons with lymphoreticular malignancies involving the hematologic and/or mononuclear phagocyte system, persons receiving chronic corticosteroid therapy or having increased endogenous corticosteroid production (Cushing's syndrome), and persons who are severely debilitated and/or malnourished.

[0005] The Herpes simplex virus (HSV) is a common cause of infections of the skin and mucous membranes, and may also cause more serious infections in other parts of the body. There are two distinct types of the HSV virus: HSV-1 that usually infects the oral cavity; and HSV-2 that is known as genital herpes and that is generally considered to be sexually transmitted.. Both types of the virus may be found at any area of the body.

[0006] HSV infections have become widespread. It is estimated that about 20% or more of the world's population would test positive blood for HSV-2.

[0007] Other types of the herpes viruses are responsible for different infections, with Herpes zoster causing chicken pox and Human herpes virus 8 thought to be responsible for Kaposi's sarcoma. [0008] When HSV enters the human body it penetrates vulnerable cells in the lower layers of the skin and attempts to replicate itself in the cell nuclei, thereby destroying the cells and causing the blisters and inflammation characteristic of the infection. The resulting skin lesions are often tiny blisters grouped together on an inflamed base. Viral particles are carried from the skin through branches of peripheral nerve cells to clusters of peripheral nerve cell bodies called ganglia. The HSV in the ganglia enters an inactive or latent state in which replication does not occur but in which the virus survives. Viral infection is not evident during the latent period, but the virus may begin to multiply again causing symptoms. With H8V-1 there is recurrence of infection in 20% to 40% of cases, while with HSV-2 there is a much higher rate of recurrence of up to 80%. Recurrences usually occur at the same site, and while the cause of this renewed infection is not completely known, factors such as sunlight, wind, fever, local injury, menstruation, suppression of the immune system and emotional stress are thought to be involved.

[0009] HSV infection triggers the body's immune system, and in healthy people infection tends to become less severe and less frequent. However, the immune system cannot completely eradicate the virus.

[0010] HSV is transmitted by skin-to-skin contact, often by sexual contact and kissing. While those with active sores are much more infectious than those without symptoms, a person does not need to have a visible lesion or ulcer to be infectious. One cannot predict when a person is "shedding" the vims. Viral shedding is when the herpes virus is "active" and "shedding" at the site of infection. The herpes virus is considered contagious during this "active" time and can therefore be spread through direct contact with the infected area.

[0011] It is possible for the virus to be actively shedding itself at the site of infection without showing any visible signs or symptoms. This is referred to as "Asymptomatic Viral Shedding".

[0012] While there is no cure for herpes infections, oral acyclovir has been found to be an effective treatment for patients with first or recurrent episodes of herpes, interfering with the ability of the virus to reproduce itself. While treatment of a primary infection with acyclovir will shorten the duration of lesions and decrease infectiousness, the virus remains in the body for life. Moreover, a small number of patients experience side effects from acyclovir, including headache, nausea, vomiting, rash and. impaired kidney function.

[0013] A number of topical treatments are known for active lesions, including topical antiviral medicines. Other topical treatments include those disclosed in U.S. Pat. Nos. 4,657,933 and 4,657,934, directed to ethyl ether-based compositions. [0014] A number of tests to detect the virus in the human body have also been developed. Various blood tests can detect antibodies for H8V-1 and HSV-2. Cultures made from cells taken from a suspected anatomical site can determine the presence of a virus at the suspected anatomical site, but may take days for results that are reliable. A test based on the polymerase chain reaction (PGR); a molecular biological method for amplifying (creating multiple copies of) DNA without using a living organism, such as E. coll or yeast, has also been attempted. PGR is commonly used in medical and biological research labs for a variety of tasks such as the detection of hereditary diseases, the identification of genetic fingerprints and genes, the diagnosis of infectious diseases, the cloning of genes, and paternity testing. PGR based assays are also time consuming and. expensive.

[0015] Warts are another type of topical viral infection. Warts are caused by viruses in the Human papilloma virus (HPV) family. The main types of warts are common warts, found on the elbows, arms and face, molluscum contagiosum, found on the face, back and. shoulders, plantar warts, found on the soles of the feet and genital warts, found in the genital area and anus.

[0016] Warts may be treated with salicylic acid preparations commonly sold over the counter, or with more sophisticated therapies such as cryotherapy, electrodessication, curettage and laser therapy.

[0017] While prior assays to detect the presence of a virus have been developed, each of these suffers significant drawbacks such as poor reliability, time consuming processes, or significant expense. As such, new methods for detecting the presence or absence of a viral infection in a subject are needed.

SUMMARY OF THE INVENTION

[0018] The following summary of the invention is provided to facilitate an understanding of some of the innovative feaiures unique to the present invention and. is not intended to be a full description. A full appreciation of the various aspects of the invention can be gained by taking the entire specification, claims, drawings, and. abstract as a whole.

[0019] As prior methods of diagnosing the presence of viral infection in a cutaneous lesion or systemically require expensive, and often time consuming processes, it is an object of the invention to provid e new materials and methods for the diagnosis of the presence or absence of a virus in a subject. In some embodiments, a process includes applying to a site of suspected viral infection an aqueous detection reagent solution comprising a detection reagent that is differentially detectable upon interacting with a virus; and exposing said site to light for a detection time sufficient to detect the presence or absence of said virus. A detection reagent optionally lias a pH greater than 7.0, optionally greater than 7.2. In other embodiments, a detection reagent has a pH less than or at 7.0. A detection reagent solution optionally further comprises one or more permeability enhancers. In some embodiments, a detection reagent solution optionally includes at least 0.01% by weight neutral red and at least 0.0001% by weight free chlorine. Optionally, a detection reagent solution includes at least 1 parts per million of a free electronegative element.

[0020] Optionally, a process includes exposing the site to light, optionally ultraviolet light, for a period of 20 minutes or less. Light used to expose the site is optionally ultraviolet light, optionally having a wavelength in excess of 320 nanometers. The wavelength of the light is optionally in a range from 340 to 370 nanometers. Optionally, the light is pulsed light. Pulsed light optionally has a pulse width of approximately 0.001 to 0.003 seconds. Optionally, the pulsed light is generated by a light source having a power in excess of 25 Watts. Optionally the pulsed light is generated by a light source having a power between 30 Watts and 100 Watts. Optionally, the pulsed light is generated by a light source having a power between 30 Watts and 100 Watts.

[0021] In some embodiments, a process of detecting the presence or absence of a topical virus in or on a cutaneous surface of a subject suspected of being infected with said virus further includes debriding the site. Optionally, debriding is chemical debriding with an aqueous acid solution.

[0022] A virus that is detected is optionally a human herpes vims. A site is optionally, a wart or other cutaneous lesion, optionally located on the lip, genitalia, mouth, anus, or vagina.

[0023] In other embodiments, a sample is removed from the site and tested for the presence or absence of a virus. As such, a process of detecting a presence or absence of a topical virus in or on a cutaneous surface of a subject suspected of being infected with a virus optionally includes debriding a site of suspected viral infection, removing a sample of skin or other cells from said site, applying an aqueous detection reagent solution, optionally comprising neutral red, to said sample, and exposing said sample to ultraviolet light for a detection time sufficient to detect the presence or absence of said vims in said sample. A detection reagent optionally has a pH greater than 7.0, optionally greater than 7.2. In other embodiments, a detection reagent has a pH less than or at 7.0. A detection reagent solution optionally further comprises one or more permeability enhancers. In some embodiments, a detection reagent solution optionally includes at least 0.01 % by weight neutral red and at least 0.0001% by weight free chlorine. Optionally, a detection reagent solution includes at least 1 parts per million of a free electronegative element. [0024] Optionally, a process includes exposing the sample for a period of 20 minutes or less. Light used to expose the site is optionally ultraviolet light, optionally having a wavelength in excess of 320 nanometers. The wavelength of the light is optionally in a range from 340 to 370 nanometers. Optionally, the light is pulsed light. Pulsed light optionally has a pulse width of approximately 0,001 to 0.003 seconds. Optionally, the pulsed light is generated by a light source having a power in excess of 25 Watts. Optionally the pulsed light is generated by a light source having a power between 30 Watts and 100 Watts. Optionally, the pulsed light is generated by a light source having a power between 30 Watts and 100 Watts.

[0025] In some embodiments, a process of detecting the presence or absence of a topical virus in or on a cutaneous surface of a subject suspected of being infected with said virus further includes debriding the site prior to sample collection. Optionally, debriding is chemical debriding with an aqueous acid solution.

[0026] A virus that is detected is optionally a human herpes vims. A site is optionally, a wart or other cutaneous lesion, optionally located on the lip, genitalia, mouth, anus, or vagina.

[0027] Another object of the invention is to treat a subject infected with a virus that optionally manifests infection in the skin or other cutaneous surface of the body. Such methods include applying to a site of suspected or diagnosed viral infection an aqueous detection reagent solution comprising a detection reagent, said detection reagent solution optionally comprising a free electronegative element; and exposing said site to light for a treatment time sufficient to reduce the number of said virus particles at said site. A free electronegative element is optionally chlorine. A detection reagent optionally has a pH greater than 7.0. In other embodiments, a detection reagent has a pH less than or at 7.0. A detection reagent solution optionally further comprises one or more permeability enhancers. In some embodiments, a detection reagent solution optionally includes at least 0.01% by weight neutral red. and at least 0.0001% by weight free chlorine. Optionally, a detection reagent solution includes at least 1 parts per million of a free electronegative element.

[0028] Optionally, a process includes exposing the site for a period of 30 minutes or less, optionally 20 minutes or less. Light used to expose the site is optionally ultraviolet light, optionally having a wavelength in excess of 320 nanometers. The wavelength of the light is optionally in a range from 340 to 370 nanometers. Optionally, the light is pulsed light. Pulsed light optionally has a pulse width of approximately 0.001 to 0.003 seconds. Optionally, the pulsed light is generated by a light source having a power in excess of 25 Watts. Optionally the pulsed light is generated by a light source having a power between 30 Watts and 100 Watts. Optionally, the pulsed light is generated by a light source having a power between 30 Watts and 100 Watts.

[0029] In some embodiments, a process of treating further includes debriding the site prior to the step of exposing, optionally prior to the step of applying. Optionally, debriding is chemical debriding with an aqueous acid solution.

[0030] A virus that is treated is optionally a human herpes vims or human immunodeficiency virus. A site is optionally, a wart or other cutaneous lesion, optionally located on the lip, genitalia, mouth, anus, or vagina. A site is optionally the blood or portion thereof.

[0031] Compositions for diagnosis and treatment of viral infections is also needed. As such, it is another object of the invention to provide compositions for use in diagnosis or treatment of viral infections, optionally cutaneous or systemic viral infections, or both. A composition is provided for the treatment or detection of a cutaneous or systemic virus in a subject including a detection reagent solution comprising a detection reagent consisting of an intravital or supravital stain, said detection reagent solution further comprising a free electronegative element, said free electronegative element is optionally not chlorine. The detection reagent solution is optionally aqueous. In some embodiments, the detection reagent solution has a pH greater than 7.0. In other embodiments, such as for treatment, a detection reagent solution has a pH of 7.0 or less, optionally less than 7.2. A free electronegative element, when present, is optionally selected from the group consisting of fluorine, hydroxy], nitrogen, bromine, In some embodiments, a detection reagent is selected from the group consisting of Toluidine Blue, Methylene Blue, Profiavin, Neutral Red, Acridine Orange, Hypericin, Zinc Phthalocyanine, Zinc Phihalocyaninetetrasulphonic acid, BPD-MA, Haematoporphyrin, SnET2, and MC540.

[0032] A detection reagent solution optionally further comprises one or more permeability enhancers. In some embodiments, a detection reagent solution optionally includes at least 0.01% by weight neutral red and at least 0.0001% by weight free chlorine. Optionally, a detection reagent solution includes at least 1 parts per million of a free electronegative element.

[0033] The compositions are for treatment or diagnosis of a viral infection by a process that optionally includes applying to a site of suspected viral in fection or of known viral infection said detection reagent solution; and exposing said site to light for a test time, or exposing for a treatment time sufficient to reduce the number of said virus particles at said site. Optionally, a process includes exposing the site for a period of 20 minutes or less. Light used to expose the site is optionally ultraviolet light, optionally having a wavelength in excess of 320 nanometers. The wavelength of the fight is optionally in a range from 340 to 370 nanometers. Optionally, the light is puised light. Pulsed light optionaliy has a pulse width of approximately 0.001 to 0.003 seconds. Optionally, the pulsed Hght is generated by a light source having a power in excess of 25 Watts. Optionally the pulsed light is generated by a light source having a power between 30 Watts and 100 Watts. Optionally, the pulsed light is generated by a light source having a power between 30 Watts and 100 Watts.

[0034] In some embodiments, the composition is used in a process of treating or detecting further including debriding the site, optionally before the step of applying, optionally before the step of exposing. Optionally, debriding is chemical debriding with an aqueous acid solution.

[0035] A virus that is detected is optionally a human herpes virus or human immunodeficiency vims. A site is optionaliy a wart or other cutaneous lesion, optionaliy located on the lip, genitalia, mouth, anus, or vagina. A site is optionally the blood or portion thereof.

[0036] In some embodiments, detection reagent solution is contacted extracorporeally with a sample that is blood. The blood is then returned to the subject in whole or in part. Optionally, a process further comprises removing at least a portion of said detection reagent from said blood following a treatment time.

BRIEF DESCRIPTION OF THE DRAWINGS

[0037] FIG. 1A illustrates a subject positively diagnosed with HSV infection in a lesion near the lips with the positive fluorescence indicated by the light shading on the lips with the photograph taken 1 minute following beginning of illumination;

[0038] FIG. I B illustrates a subject positively diagnosed with HSV infection in a lesion near the lips with the positive fluorescence indicated by the light shading on the lips;

[0039] FIG. 1C illustrates a subject positively diagnosed with HSV infection with the positive fluorescence indicated by the dark shading on the lesions of the forefoot and toe;

[0040] FIG. 2 illustrates two cotton swabs containing a sample and testing positive (dark shading) under illumination (right) as compared to a control swabs (left);

[0041] FIG. 3 illustrates the subject of FIG. 1A following a 30 minute treatment demonstrating a reduced viral content to the lesions.

[0042] FIG. 4A illustrates a lesion on the tongue of a second subject prior to treatment;

[0043] FIG. 4B illustrates the lesion on the tongue of the second subject 24 hours following a first treatment;

[0044] FIG. 4C illustrates the lesion on the tongue of the second subject following 5 consecutive days of with the image taken 10 days following presentation; [0045] FIG. 4D illustrates the lesion on the tongue of the second subject 2 weeks following presentation; and

[0046] FIG. 4E illustrates the lesion on the tongue of the second subject 3 weeks following presentation. DESCRIPTION OF EMBODIMENTS OF THE INVENTION

[0047] The following description of particular embodiments) is merely exemplary in nature and is in no way intended to limit the scope of the invention, its application, or uses, which may, of course, vary. The invention is described with relation to the non-limiting definitions and terminology included herein. These definitions and terminology are not designed to function as a limitation on the scope or practice of the invention but are presented for illustrative and descriptive purposes only. While the processes or compositions are described as an order of individual steps or using specific materials, it is appreciated that steps or materials may be interchangeable such that the description of the invention may include multiple parts or steps arranged in many ways as is readily appreciated by one of skill in the art.

[0048] It is an object of the invention to provide a safe and effective test for the presence or absence of live viruses at the suspected site of a human body, or in an animal, for correct diagnosis of herpes viruses, warts and other topical viral infections with minimal side effects.

[0049] To achieve this and other objects, some embodiments of the invention are directed to a method for testing suspected sites (or material/ viral particles/live viruses collected from suspected sites) of the human body or in animals the presence of live viruses to aid in the diagnosis of contagious viral infections. In some embodiments, a method of detection of the presence or absence of a virus includes preparing a detection reagent solution (optionally an aqueous solution), applying the detection reagent solution to a site of a human body or the material collected from the suspected site suspected of being infected by a virus, irradiating the suspected site/collected material with an energy source of a sufficient energy and wavelength for a detection time and determining whether a detection signal, optionally fluorescence, occurs during or after the detection period. Optionally, the detection reagent solution or the energy used to irradiate the light is not suitable for treatment of a viral infection either due to the unsuitability of the detection reagent, a lower or higher energy of light, a lower or higher wavelength of light, a pulsing or continuous exposure of the light, or other parameter that is not suitable for treatment is used.

[0050] The testing process of the invention falls into or is related to a treatment category known as "phototherapy" or "phototesting" in which a lesion/collected material is contacted with a particular compound, then exposed to light of a defined wavelength to treat a lesion. Porphyrins are known for use in phototherapy, as disclosed, for example, in U.S. Pat. Nos. 4,753,958, 4,925,736 and 5,399,583. U.S. Pat. No. 4,235,887 discloses chemically combining a drug with another moiety by a photo-cleavable bond, and irradiating a diseased area with ultraviolet radiation to cleave the bond and release the drug.

[0051] A process uses a detection reagent to either treat a viral infection or solely to detect the presence or absence of a virus. As such, the term "detection reagent" is used herein to describe a reagent that will interact with a virus, or portion thereof, to allow for detection, treatment (e.g. destruction), or both of the virus that is contacted by the detection reagent. A detection reagent is optionally an intravital or supravital stain. In some embodiments, a detection reagent is not an intravital stain. Illustrative examples of a detection reagent include, but are not limited to toluidine blue, profiavin, neutral red, acridine orange, hypericin, zinc phthalocyanine, zinc phthalocyanine tetra-sulphonic acid, BPD-MA, haematoporphyrin, SnET2, and MC540, or combinations thereof. Other reagents taught in Wainright, M, bit J Antimicrob Agents. 2003 Jun;21(6):510-20 may also be used. Optionally, a detection reagent has a structural formula of Formula I:

where Rl , R2, R3, and R4 are each independently an H, a branched or linear C₁ to C₅ alkyl, or R5; X and Y are each independently a carbon or nitrogen bonded to an H, a C₁ to C₅ alkyl, a

halogen, or combinations thereof; and R5 has the structure: where R6 and R7 are each independently an H or a branched or linear C1 to C5 alkyl.

[0052] A detection reagent is administered to the site of suspected or actual viral infection by contact with a cutaneous site or by contacting a sample collected from a site suspected of being infected by a virus. A detection reagent is optionally used at a concentration of 0.001% by weight to 1% by weight, or any value or range therebetween. Optionally, a detection reagent is used at a concentration from 1 μΜ to 1 mM, or any value or range therebetween. Optionally, a concentration of a detection reagent is from ί μΜ to 50 μΜ, Optionally, a detection reagent is used at approximately 0.5 μΜ to 50 μΜ.

[0053] In some embodiments, a detection reagent is neutral red used alone or in combination with acridine orange. Neutral red is a tricyclic planar aromatic phenazine compound, closely related chemically to other tricyclic dyes, including methylene blue, alizarin, acridine and proflavine (Fernando et al, 1967). Neutral red is mainly used as a histological stain and as a supravital stain to assess the viability of cells. There are a number of other vital dyes that may fluoresce in the presence of various forms of energy and certain pathogens such as viruses.

[0054] Neutral red, known chemically as N⁸ N⁸, 3-trimethyl, 2,8-phenazmediamme monohydrochloride. is a green powder soluble in water to yield a red color. The compound is known as a pH indicator and as a biological stain. Toluidine blue is a basic thiazine metachromatic dye with high affinity for acidic tissue components, thereby staining tissues rich in DNA and RNA. Proflavin (proflavine; acridine-3,6-diamine) may be used, for the detection or treatment of viral infection. Acridine orange (N,N,N'N'-Tetramethylacridine-3,6-diamine) is cell permeable interacts with DNA and. RNA by intercalation or electrostatic attractions respectively.

[0055] An exemplary testing composition of the invention is a water solution of neutral red. A neutral red concentration as low as about 0.01% by weight is thought to be effective, although about 0.05 to 0.1% is preferred. Higher concentrations, e.g. up to 1% by weight may be used but are not thought to provide any additional advantage.

[0056] A detection reagent is optionally in a detection reagent solution. A detection reagent solution is optionally an aqueous solution. It is hypothesized that the pH of the detection reagent solution selectively allows the detection reagent to interact with the viral envelope more effectively than with viral DNA or RNA. In some embodiments, a detection reagent solution has a pH in excess of 7.0 shows improved results by lowering possible side effects such as carcinogenesis of some detection reagents. As such, a detection reagent solution is optionally has a basic pH, A pH is optionally from 7.1 to 12. Optionally, a pH is from 7.1 to 8, optionally from 7.2 to 7.5. In processes of detection or diagnosis, a process optionally includes using a detection reagent solution that has a pH of 7.0 or less.

[0057] A detection reagent solution optionally includes a buffer or other component that promotes or maintains a basic pH to the solution. Optionally, a detection reagent solution includes a buffer such as a phosphate buffer, Tris buffer, HEPES (4-(2-hydroxyethyl)- 1- piperazineethanesulfonic acid) buffer, carbonate buffer, CHES (N-Cyclohexyl-2- aminoethanesulfonic acid) buffer, borate buffer, ammonia, or other known buffering agent capable of maintaining an alkaline pH. Optionally, the buffering agent used has a pKa at or within one pH unit of the target pH of the detection reagent solution.

[0058] Optionally, a detection reagent solution is or includes one or more electronegative materials. Optionally, one or more free electronegative elements are present in a detection reagent solution. Illustrative examples of electronegative materials include, but are not limited to, fluorine, oxygen (optionally in the form of a hydroxyl), nitrogen, bromine, and chlorine.

[0059] In some embodiments, a buffering agent solution includes chlorine. Chlorine in very small amounts, illustratively Ippm by weight, is thought to be effective, and thus chlorine in the amount found in tap water will provide some effectiveness in a treatment composition according to the invention. Amounts of 10 to 500 ppm are preferred.. While higher concentrations of free chlorine, e.g. up to 10,000 ppm (1%) may be used, they are not thought to provide any additional advantage. Chlorine is optionally provided in the form of sodium hypochlorite.

[0060] A detection reagent optionally includes one or more permeability enhancers. A permeability enhancer optionally is used to improve the ability of the detection regent to reach the site of the virus by penetrating layer(s) of skin or other biological material. A permeability- enhancer may be a chemical, a physical treatment or a biological. Illustrative physical treatments that may be used in addition to or in place of scrubbing and/or debriding the area include iontophoresis, sonophoersis, magnetophoresis, electroporation, the use of microneedles, needle- free injection methods, photomechanical waves, or laser assisted permeation. Such methods are known in the art.

[0061] One exemplary physical method of enhancing permeability is electroporation. Optionally, a test or treatment site is placed between two electrodes in close proximity to the lesion (e.g. less than 3 mm away from the lesion), applying an electrical impulse between the two electrodes during which or followed by applying a detection reagent solution to the lesion site. The site is then exposed to light to diagnose or treat a vims present within or under the lesion.

[0062] Optionally a chemical permeability enhancer is added to a detection reagent solution. A chemical permeability enhancer is optionally: polyvinylpyrrolidone (PVP); surfactants such as sodium lauryl sulfate, sodium laurate, Tween 80, polysorbates, among others; bile salts and derivatives such as Na Glycholate, Na deoxycholate, among others; fatty acids such as oleic acid, caprylic acid., among others; chelating agents such as EDTA, citric acid, among others; sulfoxides such as dimethyl sulfoxide (DMSO), DMA, DMF. DCMS, among others; polyols such as propylene glycol (PG), polyethylene glycol (PEG), glycerol, among others; monohydric alcohols such as methanol, ethanol, 2-propanol, 1-butanof, 1 -octanol, among others where such monohydric alcohols are used preferable at a concentration of 1-10%; essential oils, terpenes and terpenoids such as eucalyptus oil, peppermint oil, limonine, neroidol, among others; amides such as pyrrolodones and azone; cyclodextrms such as b-cyeiodextrin CME-b-CD, among others; urea; and phospholipids, [0063] In some embodiments, a detection reagent solution is prepared in a dispensing vial containing, detection reagent, e.g. neutral red (5 nig). To the vial is added 10 ml of bacteriostatic water suitable for injection, USP (containing 0.9% benzyl alcohol) although everyday common tap water is optionally used. The detection reagent solution contains by weight, approximately 0.05% detection reagent. Optionally, a detection reagent solution is contains by weight at or approximately 0.05% neutral red and 0.02% sodium hypochlorite, the solution thereby containing about 0.005% free chlorine.

[0064] In some embodiments, a suitable detection reagent solution is neutral red and water and a suitable energy source is ultraviolet light having a wavelength of 40-400 nm. Although test results with neutral red as the reagent show that 361 nm light (e.g. UVA light passed through a 5 or 10 nm bandpass filter) source seems to demonstrate the most reliable results, other reagents such as the various vital dyes (tricyclic dyes) may react more suitably with other wavelengths of light. Light applied to the site of suspected or known infection at or within 10-20 nm of the absoiption maximum for the particular detection reagent is preferred.

[0065] The detection reagent solution is optionally prepared just before use by adding the water to the neutral red or is optionally stored anaerobically in a pressurized sterile container. The detection reagent solution once mixed is thought to maintain effective results for up to six weeks if stored below 60 degrees Fahrenheit (e.g. kept in a refrigerator). A detection reagent solution is preferably stored in the dark to prevent unwanted exposure to light.

[0066] A subject to be tested should suspected of being infected by a virus or is already- known to be infected by a virus to be detected or treated by the processes of the invention. A "subject" as used herein is a human or non-human animal, preferably a mammal including a human, non-primates such as cows, pigs, horses, goats, sheep, cats, dogs, rodents and avian species; and non-human primates such as monkeys and apes.

[0067] Optionally, a site of suspected infection or manifesting signs of an infection such as by the presence of a lesion or wart is chosen as a treatment or test site. In some embodiments, a treatment or test site such as a lesion or wart is scrubbed, and if necessary, debrided, to remove surface material If vesicles containing an active viras are left unopened, and not fully exposed, the effectiveness of diagnosis or treatment may be diminished.

[0068] The specific preparation procedure of a test or treatment site depends upon the type of viras outbreak and the site of the lesion. If the lesion is on the face or other exposed cutaneous area, the area is optionally simply scrubbed to remove any scabs and the vesicles or sacs are broken or punctured, which may be accomplished using forceps or small tweezers. Topical anesthetic may be applied if necessary. If the lesion is on the gum line, a mild acid wash is optionally used to debride the affected area.

[0069] Exposed lesions on the genitalia or anus are optionally scrubbed or debrided. to the extent possible. For lesions within the vagina or rectum, an acidic douche or enema is optionally used to debride the affected tissue. Preparation of an area effected by genital warts also requires that the lesion area be debrided, and while the entire lesion does not need to be removed, the surface of each lesion must be opened.

[0070] In some embodiments, test or treatment site material may be collected from the subject for ex vivo testing. Collection of a sample is optionally preformed following scrubbing or debriding or the test material is the material removed during the scrubbing or debriding steps. Collection of the test site material is optionally performed using a tissue scraper, debriding instrument, sharp hollow instrument, or scalpel A sample is optionally collected from a scrubbed, or debrided site using a collection device, optionally a swab, paper, or other device suitable for collecting a sample from a test or treatment site.

[0071 [ A sample is optionally collected into a sample collection container. Any sterile container may be used to collect a sample into. A container may be a slide, such as a glass slide, a specimen container, a tissue or other paper sheet, an assay plate, a glass or other material tube, or other collection device. Optionally, a sample collection container is integrated with a scrubbing or debriding instrument or swabbing instrument.

[0072] As one exemplary embodiment of a process of diagnosing the presence or absence of a viral infection, a detection reagent solution is applied to the surface of the suspected infected area of the anatomy and light of a desired wavelength is used to irradiate the area for a minimum of 3 minutes or until fluorescence is noted. If the suspected area does indeed, fluoresce (optionally a yellow to orange or red visible light for neutral red) the area is diagnosed to contain live viruses. In test results, fluorescence is detected within 1 minute. If the fluorescence does not appear within 20 minutes it is considered a negative test and the suspected virus is not thought to be present. In. the presence of papilloma (HPV) the fluorescence may appear in the deep purple orange.

[0073] A detection reagent solution is applied to that suspected or treatment site by any suitable means. Optionally, the detection reagent solution is applied using a vial in which the detection reagent solution is contained where the vial optionally has an applicator top. Standard medicine vials have a rubber stopper at one end which can be penetrated by a needle for withdrawal of medication; for purposes of the invention, a vial could be used with a rubber stopper at one end and. a wick or applicator at the other end. For areas which are not. easily exposed, the solution may be applied by flushing the area with a plastic hypodermic syringe. Optionally, a detection reagent solution is merely wiped onto the site. Optionally, the detection reagent solution is sprayed onto the site or merely placed onto the site. Optionally the detection reagent solution is swabbed onto the site.

[0074] After the detection reagent solution is applied, the area is energized by exposure to light or a desired wavelength or wavelength range for a period, of time necessary for effective testing. In some embodiments, light is in the ultraviolet A (UVA) wavelength range. UVA light is defined as having a wavelength in the range of about 320 to 400 nm, or any value or range therebetween. In some embodiments, light has a wavelength in the middle UVA range, e.g. about 350 to 390. Optionally, light has a wavelength range from 355 to 370. Optionally, light has a wavelength of 355 to 365 or approximately similar thereto as is available using a commercially sourced bandpass filter,

[0075] Light is emitted and directed to a test or treatment site using a lamp, laser, light emitting diode (LED), or other known mono- or polychromatic light source. UVA lamps having a power of 1 to 36 Watts are commonly used. In some embodiments, such as when light is pulsed or when higher power light is desired, a lamp power may be as high as 100 Watts or more. A light optionally has a pow^rer from 1 to 100 Watts or any value or range therebetween, optionally from 20 to 100 Watts, optionally from 30 to 100 Watts. A light optionally has a power of greater than 5 Watts, optionally greater than 10 Watts, optionally greater than 30 Watts. In some embodiments, a light optionally has a power of 30 Watts or less, optionally 20 Watts or less, optionally 10 Watts or less, optionally 5 Watts or less, optionally less than 5 Watts.

[0076] In some embodiments, a light source is a laser. Illustrative examples of a laser include a potassium-titanyl-phosphate-(KTP-) crystal containing laser (KTP laser), a yttrium- aluminum-garnet fNdiYAG) laser, or other suitable laser system. A laser optionally has a power of 20 to 120 W atts, optionally 60 Watts, optionally 80 Watts.

[0077] A light source is optionally one or more light emitting diodes capable of emitting light of the desired irradiance, fluence, wavelength, etc. Optionally a plurality of light sources is used in close proximity to one another, LED lights commercially available are suitable for use in the present invention.

[0078] Light is illuminated onto a sample or onto the suspected, area of infection optionally with an irradiance of between 0.1 and 50 W/m². The irradiance is optionally from 0, 1 to 5 W/m², optionally 0.1 to 1 W/m², optionally from 0.3 to 0.8 W/m².

[0079] Light is optionally delivered in a pulsed or continuous emission format. In embodiments that employ a pulsed, fight source, the light optionally has a pulsing pattern with a pulse width of approximately 0.001 to 0.003 seconds although other pulse widths may be used. In some embodiments a predetermined pulsing pattern optionally includes pulse trains of between approximately 3 and 5 pulses with pulse train intervals of approximately 0.00155 seconds. It should be understood that other pulsing patterns could be used without departing from the scope of the present invention.

[0080] A light source may be held or positioned directly on the surface of the skin or may be held, a selected distance from the skin. A light source is optionally held close to the lesion, a distance of about 1-3 inches being preferable. A distance is optionally 0.1 to 5 inches or any value or range therebetween. Optionally, a distance is 3 inches. Optionally, a distance is 1 inch, Optionally, a distance is greater than 3 inches.

[0081] While the actual time of testing will vary depending on the wavelength of the light source, the intensity of the source and the distance from the lesion or suspected site of infection, the average exposure time (time light is irradiated, onto the site) of testing should require less than 5 minutes, optionally less than 3 minutes. Testing times up to 10 or 20 minutes may provide a more accurate diagnosis. It is appreciated that the process of exposing the site to light and optionally applying the detection reagent solution may be repeated, optionally 2-3 times at the same, adjacent, or distant sites to ensure adequate diagnosis of low level infections.

[0082] For therapeutic processes, a treatment may include more than one treatment time. A treatment time optionally includes an exposure time of 5-30 minutes or any value or range therebetween. Optionally, an exposure time is less than 10 minutes. Optionally, an exposure time is 10-20 minutes. Optionally, more than one exposure time is used. In some embodiments, 2-4 intervals of exposure time are applied, optionally with reapplication of detection reagent solution in between or during an exposure time.

[0083] When the testing/treatment site is not in an exposed area, such as the mouth, the vagina or the rectum, a UV light source which is narrow, e.g. less than one-half inch in diameter may be used; such sources are commonly used in dentistry to set polymers in the mouth. When used in the vagina or rectum, the light source should be coated with a lubricant such as a petroleum based jelly or cream.

[0084] The tested or treated area is optionally subsequently cleaned with soap and. water, The area may have a red. or pink colored stain which may persist for several days.

[0085] In some embodiments, systemic or blood borne viral infections are diagnosed or treated by processes of extracorporeal treatment. An inventive process optionally includes using the detection reagent solution as a diaiysate and embedding a UV light source within proximity to combined blood and. aqueous solution of neutral red such that the combined solution is exposed to the light after the combination process has happened (i.e. somewhere after the dialyzer). The process is similar to dialysis in that blood is taken from one site such as a vein, passes through a treatment area(s) and is returned to the body, optionally following additional filtering.

[0086] Traditional dialysis or pheresis equipment may be used with the addition of an exposure area. In such processes, blood is obtained from a subject and is passed to a treatment area that includes an administration area where one or more detection reagents are contacted with the blood. Such an exposure area optionally includes a membrane with a pore size suitable for the diffusion of one or more detection reagents from a detection reagent solution positioned on one side of the membrane and be transferred to the blood that passes on the opposite side of the membrane. At the administration site, or downstream therefrom, is an exposure area whereby the detection reagent containing blood is exposed to light for an exposure time. Longer exposure times are optionally achieved, by the blood passing by one or more fight sources multiple times or the blood is exposed, to the light source for an extended period of time such as by coiling the tubing housing the blood around the light source or in proximity to the light source. Optionally, the blood enters an exposure chamber such as a larger diameter or larger cross sectional area region of differing or similar material to adjacent tubing. Optionally, and exposure area is made from a material that has greater transparency to the wavelengths of light used to detect or treat the infection. Optionally, an exposure area is made from or contains one or more walls that are quartz or borosilicate glass,

[0087] Following exposure in an exposure area, the blood is returned to the subject. Optionally, the detection reagent containing blood is passed through a second filtration area that serves to remove as much free detection reagent from the blood as possible. Such a filtration area optionally includes a membrane that is permeable to the detection reagent whereby the detection reagent solution containing blood is passed on one side of the membrane and a diasylate or other aqueous fluid is located on the opposite side such that the detection reagent passes through the membrane by diffusion. It is appreciated that other known methods of selectively filtering blood are similarly operable for use in either a first or second filtration area.

[0088] The subject's blood is optionally contacted to an anticoagulant such as heparin, citrate, or other known anticoagulant. Often a subject experiences a tingling sensation during the process. In such a case, the subject is administered calcium solution until such a tingling effect is reduced or eliminated.

[0089] Using the above described, processes, a subject may be diagnosed or treated for a viral infection. A virus is optionally a topical virus. A topical virus is defined as a virus that produces symptoms of infection and may be located at a cutaneous site on a subject. A virus that is treatable or diagnosable by the invention includes HSV 1 or 2, HPV, herpes zoster (shingles), or any other virus within the HHV.

[0090] Various aspects of the present invention are illustrated by the following non-limiting examples. The examples are for illustrative purposes and are not a limitation on any practice of the present invention. It will be understood that variations and modifications can be made without departing from the spirit and scope of the invention.

EXAMPLES

[0091] Example 1 : Diagnosis of cutaneous viral infection.

[0092] 15 consenting human subjects presenting with lesions at or around the mouth, anus or genitalia are tested for the presence or absence of virus at the site of the lesion suspected of harboring HSV. A detection reagent solution is prepared in a dispensing vial. The detection reagent solution contains neutral red alone (5 mg) or a combination of neutral red and acridine orange (5 mg). To the vial is added 10 ml of bacteriostatic water suitable for injection, USP (containing 0.9% benzyl alcohol), or tap water. The detection reagent solution contains by weight, approximately 0.05% detection reagent.

[0093] The suspected site is scrubbed until generally open or oozing. Deep lesions are also debrided with a needle to further open the lesion. The detection reagent solution is then applied to the lesion with a cotton swab. Sufficient detection reagent solution is applied to the lesion to fully cover the lesion with the material. Some subjects indicated a mild tingling sensation.

[0094] A 3 watt UV lamp with a peak output of power at around 361 nm equipped with a 10 ran bandpass filter centered on 360 nm (+/- 2 nm) with available from ThorLabs, inc., Newton, New Jersey. The lamp is used to illuminate the suspected area with an irradiance of approximately 0.5 W/m² for a detection time of 5 minutes. The lesions testing positive for HSV fluoresces red indicating a positive diagnosis of HSV. Three subjects testing positive for HSV are illustrated in FIG. 1A-C. Subjects testing negative for HSV do not show fluorescence.

[0095] A subset of subjects is selected to be tested by obtaining a sample and testing the sample ex vivo. Following debriding the lesions are scraped with a plastic or metal scraping instrument to transfer material into a sample collection container. The sample material is placed on a glass slide. The detection reagent solution is then contacted with the sample to a level to wet the sample, but not totally cover it, and the sample illuminated as above. Subjects positive for HSV demonstrate red fluorescence.

[0096] A subset of subjects are tested ex vivo on a sample taken from a lesion. Following debriding the lesions swabbed with a cotton tip of a swab. The detection reagent solution is then contacted with the swab to a level to wet the sample, and the sample illuminated as above. Lesions that are positive for HSV demonstrate red fluorescence as illustrated in FIG. 2.

[0097] Example 2: Treatment of HSV in a subject diagnosed with HSV infection.

[0098] Subjects diagnosing positive for the presence of HSV have the diagnosis confirmed by independent methods. The subjects are treated for HSV as follows. A detection reagent solution is prepared in a dispensing vial. The detection reagent solution contains neutral red alone (5 mg) or a combination of neutral red and acridine orange (5 mg). To the vial is added 10 ml of bacteriostatic water suitable for injection, USP (containing 0.9% benzyl alcohol), or tap water. In some cases water was added that included 10 parts per million of free fluorine or 10 part per million of free chlorine, or both. The detection reagent solution contains by weight, approximately 0.05% detection reagent.

[0099] The lesions are scrubbed until generally open or oozing. Deep lesions are also debrided with a needle to further open the lesion. The detection reagent solution is then applied to the lesion with a cotton swab. Sufficient detection reagent solution is applied to the lesion to fully cover the lesion with the material. Some subjects indicated a mild tingling sensation.

[00100] An 8 watt UV lamp with a peak output of power at around 361 nm is equipped with a 10 nm bandpass filter centered on 360 nm (+/- 2 nm) available from ThorLabs, Inc., Newton, New Jersey. The lamp is used to illuminate the suspected area with an irradiance of approximately 0.5 W/m² for a treatment time of 30 minutes. The subjects demonstrate reduced fluorescence relative to 1 minute following treatment, FIG. 3 illustrates the lesion of the subject of FIG. 1A following treatment. FIGs. 4A-E illustrate a tongue lesion prior to treatment (FIG. 4A) after which the subject was treated for 5 consecutive days. FIG. 4B-E illustrate the progress of lesion healing following the first treatment (FIG, 4B) and following the four additional treatment regimens.

[00101] Example 3: Treatment of Herpes zoster.

[00102] Subjects affected by active Herpes zoster infection suffering skin lesions are treated as in Example 2. Subjects report increased rates of healing for treated lesions relative to non- treated lesions. A subset of subjects also report reduced pain at the lesions treated as per Example 2 relative to untreated lesions.

[00103] Example 4: Treatment of AIDS in a subject diagnosed with infection by HIV.

[00104] Three consenting human subjects who tested positive for AIDS within I year w^rere treated. Each subject's T-cell count was tested one day prior to the first treatment to compare to the results of the treatment. A detection reagent solution is prepared in a basin. The detection reagent used w^ras neutral red (5 mg). To the neutral red vial is added 10 ml of bacteriostatic water suitable for injection, USP (containing 0.9% benzyl alcohol), or tap water along with 5 parts per million of free chlorine and 5 parts per million of free fluorine. The detection reagent solution contains by weight, approximately 0.05% neutral red.

[00105] A 3 watt UV lamp with a peak output of power at 361 am equipped with a 10 nm bandpass filter centered on 360 nm (+/- 2 nm) available from ThorLabs, Inc., Newton, New Jersey is used. The lamp is used to treat the non-plasma portion of the blood when combined with the detection reagent solution as described below using an irradiance of between 2.6 mW/cm² and 6 mW/cm².

[00106] The plasma was separated from the cells using a machine dedicated to plasmapheresis and a UV emitting lamp w^ras inserted, in the tube in a location after the plasma was taken out of the patient's blood. The non-plasma portion of the blood was combined with the detection reagent solution such that the resulting non-plasma portion of the blood and detection reagent combination contained approximately 5% per volume of the detection reagent solution and 95% per volume of the non-plasma blood. The combined reagent and blood were passed over the light source within the tube. The non-plasma blood and blood plasma were then recombined and was put back into the patient. Each patient's blood was cycled twice per treatment. The treatment was repeated for 6 consecutive days.

[00107] One day after the completion of the treatment protocol, patient's T-celi counts were tested. All patients' T-cell counts were at least 90% higher than they tested prior to treatment.

[00108] Various modifications of the present invention, in addition to those shown and described herein, will be apparent to those skilled in the art of the above description. Such modifications are also intended to fall within the scope of the appended claims.

[00109] It is appreciated that all reagents and materials are obtainable by sources known in the art unless otherwise specified.

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[00110] Patents, publications, and applications mentioned in the specification are indicative of the levels of those skilled in the art to which the invention pertains. These patents, publications, and applications are incorporated herein by reference to the same extent as if each individual patent, publication, or application was specifically and individually incorporated herein by reference.

[00111] The foregoing description is illustrative of particular embodiments of the invention, but is not meant to be a limitation upon the practice thereof. The following claims, including all equivalents thereof, are intended to define the scope of the invention.

Claims

1. A process for detecting the presence or absence of a topical virus in or on a cutaneous surface of a subject suspected of being infected with said virus, comprising the steps of:

applying to a site of suspected viral infection an aqueous detection reagent solution comprising a detection reagent that is differentially detectable upon interacting with a virus; and exposing said site to light for a detection time sufficient to detect the presence or absence of said virus.

2. The process of claim 1 wherein said detection reagent solution has a pH greater than 7.0.

3. The process of claim 1. wherein said site is exposed for a period of less than 20 minutes.

4. The process of any one of claims 1-3, wherein said detection reagent solution further comprises one or more permeability enhancers.

5. The process of any one of claims 1-3, further comprising debriding said site.

6. The process of claim 5 wherein said debriding is chemical debriding with an aqueous acid solution.

7. The process of any one of claims 1-3, wherein said aqueous detection reagent solution contains at least 0.01% by weight neutral red and at least 0.0001 % by weight tree chlorine,

8. The process of any one of claims 1 -3, wherein said step of exposing is using pulsed light.

9. The process of any one of claims 1-3, wherein said detection reagent solution comprises at least 1 parts per million of a free electronegative element.

10. The process of any one of claims 1-3, wherein said virus is human herpes virus.

11. The process of any one of claims 1-3, wherein said site is a wart.

12. The process of any one of claims 1 -3, wherein said step of exposing is using an ultraviolet light source producing radiation having a wavelength in excess of 320 nanometers,

13. The process of claim 12 wherein said radiation has a wavelength of in a range from 340 to 370 nanometers.

14. A process for detecting a presence or absence of a topical virus in or on a cutaneous surface of a subject suspected of being infected with a virus, comprising the steps of: debriding a site of suspected viral infection;

removing a sample of skin cells from said, site;

applying an aqueous detection reagent solution comprising neutral red to said sample; and

exposing said sample to ultraviolet light for a detection time sufficient to detect the presence or absence of said virus in said sample.

15. The process of claim 14 wherein said sample is exposed for a period of Jess than

20 minutes.

16. The process of claim 14 wherein said aqueous detection reagent solution further comprises free chlorine.

17. The process of claim 14 wherein said step of exposing is exposing to an ultraviolet light source producing radiation having a wavelength in excess of 320 nanometers,

18. The process of claim 17 wherein said radiation has a wavelength of in a range from 340 to 370 nanometers,

19. The process of claim 14 wherein said virus is Herpes simplex virus.

20. The process of claim 14 wherein said light is pulsed ultraviolet light.

21. A process of treating a cutaneous surface of a subject infected with a topical vims comprising the steps of:

applying to a site of suspected viral infection an aqueous detection reagent solution comprising a detection reagent, said detection reagent solution comprising a free electronegative element; and

exposing said site to light for a treatment time sufficient to reduce the number of said virus particles at said site.

22. The process of claim 21 wherein said detection reagent solution has a pH greater than 7.0.

23. The process of claim 21 , wherein said site is exposed for a period of less than 20 minutes.

24. The process of any one of claims 21-23, wherein said detection reagent solution further comprises free chlorine.

25. The process of any one of claims 21 -23, further comprising debriding said site.

26. The process of claim 25 wherein said site is intravaginal. intraanal, or intraoral and said debriding is chemical debriding with an aqueous acid solution.

27. The process of any one of claims 21-23, wherein said aqueous detection reagent solution contains at least 0.01% by weight neutral red and at least 0.0001% by weight free chlorine.

28. The process of any one of claims 21-23, wherein said step of exposing is using pulsed light.

29. The process of any one of claims 21-23, wherein said detection reagent solution comprises at least 1 parts per million of a free electronegative element.

30. The process of any one of claims 21-23, wherein said virus is Herpes simplex virus.

31. The process of any one of claims 21-3, wherein said site is a wart.

32. The process of any one of claims 21-23, wherein said step of exposing is using an ultraviolet light source producing radiation having a wavelength in excess of 320 nanometers.

33. The process of claim 32 wherein said radiation has a wavelength of in a range from 340 to 370 nanometers.

34. A process of treating a cutaneous surface of a subject infected with a topical vims comprising the steps of:

applying to a site of suspected viral infection an aqueous detection reagent solution comprising a detection reagent; and

exposing said, site to pulsed light for a treatment time sufficient to reduce the number of said virus particles at said site.

35. The process of claim 34 wherein said pulsed light has a pulse width of approximately 0.001 to 0.003 seconds.

36. The process of claim 34, wherein said pulsed light is generated by a light source having a power in excess of 25 Watts.

37. The process of claim 34, wherein said pulsed light is generated by a fight source having a power between 30 Watts and 100 Watts.

38. The process of claim 34 wherein said detection reagent solution comprises a free el ectronega live element.

39. The process of any one of claims 34-38 wherein said detection reagent solution has a pH in excess of 7.0.

40. The process of any one of claims 34-38, wherein said detection reagent solution comprises at least i parts per million of a free electronegative element.

41. The process of any one of claims 34-38, wherein said vims is a human herpes virus or human immunodeficiency vims.

42. The process of any one of claims 34-38, wherein said site is a wart.

43. The process of any one of claims 34-38, wherein said step of exposing is using an ultraviolet light source producing radiation having a wavelength in excess of 320 nanometers.

44. The process of claim 43 wherein said radiation has a wavelength of in a range from 340 to 370 nanometers.

45. The process of any one of claims 34-38 wherein said aqueous detection reagent solution contains at least 0.01% by weight neutral red and at least 0.0001% by weight free chlorine.

46. A detection reagent solution for the treatment or detection of a cutaneous or systemic virus in a subject comprising:

a detection reagent solution comprising a detection reagent consisting of an intravital or supravital stain, said detection reagent solution further comprising a free electronegative element, said free electronegative element is optionally not chlorine.

47. The detection reagent solution of claim 46 that is aqueous.

48. The detection reagent solution of claims 46 or 47 that has a pH greater than 7.0.

49. The detection reagent solution of claims 46 o4 47 wherein said free electronegative element is selected from the group consisting of fluorine, hydroxyl, nitrogen, bromine.

50. The detection reagent solution of claims 46 of 47 wherein said detection reagent is selected from the group consisting of Toluidine Blue, Methylene Blue, Proflavin, Neutral Red. Acridine Orange, Hypericin, Zinc Phthalocyanine, Zink Phthaiocyaninetetrasulphonic acid, BPD-MA, Haematoporphyrin, SnET2, and MC540.

51. The detection reagent solution of claims 46 of 47 wherein said treatment or detection consists of applying to a site of suspected viral infection said detection reagent solution; and

exposing said site to light for a treatment time sufficient to reduce the number of said virus particles at said site.

52. The detection reagent solution of claim 51 , wherein said virus is a human Herpes virus, optionally Herpes simplex virus.

53. The detection reagent solution of claim 51 , wherein said site is a wart.

54. The detection reagent solution of claim 51, wherein said step of exposing is using an ultraviolet light source producing radiation having a wavelength in excess of 320 nanometers,

55. The detection reagent solution of claim 54 wherein said radiation has a wavelength of in a range from 340 to 370 nanometers.

56. A detection reagent solution for detection of the presence or absence of a cutaneous or systemic virus in a subject comprising:

a detection reagent solution comprising a detection reagent consisting of an intravital or supravital stain, said detection reagent solution optionally further comprising a free electronegative element, wherein said detection reagent solution is contacted extracorporeally with a sample that is blood.

57. The detection reagent solution of claim 56 that is aqueous.

58. The detection reagent solution of claims 56 or 57 that has a pH greater than 7.0.

59. The detection reagent solution of claims 56 or 57 wherein said detection reagent solution further comprises a free electronegative element optionally selected from the group consisting of fluorine, hydroxyl, nitrogen, bromine.

60. The detection reagent solution of claims 56 of 57 wherein said detection reagent is selected from the group consisting of toluidine blue, proflavin, neutral red, and acridine orange.

61. The detection reagent solution of claims 56 of 57 wherein said treatment or detection consists of applying to a site of suspected viral infection said detection reagent solution; and

exposing said site to pulsed light for a treatment time sufficient to reduce the number of said virus particles as detected by reduced fluorescence.

62. The detection reagent solution of claim 51, wherein said virus is a human herpes virus or a human immunodeficiency virus.

63. The detection reagent solution of claim 51, wherein said process further comprises removing at least a portion of said detection reagent from said blood following a treatment time.

64. The detection reagent solution of claim 61. wherein said step of exposing is using an ultraviolet light source producing radiation having a wavelength in excess of 320 nanometers,

65. The detection reagent solution of claim 64 wherein said, radiation has a wavelength of in a range from 340 to 370 nanometers.