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Acne vulgaris is a common skin condition that affects a large proportion of teenagers and young adults. Despite the availability of various treatment options, many patients experience inadequate relief or intolerable side effects. Photodynamic therapy (PDT) is a growing interest in the treatment of acne vulgaris, with 5-Aminolaevulinic acid (ALA) being one of the most commonly used photosensitizers. Adalimumab is a biologic medication used to treat inflammatory skin conditions such as Psoriasis and Hidradenitis suppurativa (HS), which targets TNF-α. Combining different therapies, such as ALA-PDT and adalimumab, can often provide more effective and longer-lasting results. This report presents the case of a patient with severe and refractory acne vulgaris who was treated with a combination of ALA-PDT and adalimumab, resulting in significant improvement in the condition. The literature review highlights the significant comorbidity associated with acne, emphasizing the need for potential of TNF-α inhibitors for its effective treatments that address physical symptoms and ALA-PDT is known to treat scar hyperplasia, and to prevent or minimize the formation of post-acne hypertrophic scars. The combination of TNF inhibitors and ALA-PDT or adalimumab has shown promising results in treating inflammatory skin conditions, including severe and refractory acne vulgaris, as per recent studies.

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Cholera, a diarrheal disease caused by Vibrio cholerae (V. cholerae) O139 and O1 strains, remains a public health problem. The existing World Health Organization (WHO)-licenced, killed, multiple-dose oral cholera vaccines demand 'cold-chain supply' at 2 °C-8 °C. Therefore, a live, single-dose, cold-chain-free vaccine would relieve significant bottlenecks and costs of cholera vaccination campaigns. Our cholera vaccine development journey started in 2000 at Universiti Sains Malaysia with isolation of the hemA gene from V. cholerae, followed by development of a gene mutant vaccine candidate VCUSM2 against V. cholerae O139 in 2006. In 2010, VCUSM2 reactogenicity was reduced by replacing its two wild-type ctxA gene copies with mutated ctxA to produce strain VCUSM14. Introducing the hemA gene into VCUSM14 created VCUSM14P, a strain with the 5-aminolaevulinic acid (ALA) prototrophic trait and excellent colonisation and immunological properties (100% protection to wild-type challenged rabbits). It was further refined in Asian Institute of Medicine, Science and Technology (AIMST University), with completion of single- and repeated-dose toxicity evaluations in 2019 in Sprague Dawley (SD) rats, followed by development of a novel cold-chain-free VCUSM14P formulation in 2020. VCUSM14P is unique for its intact cholera toxin B, a known mucosal adjuvant. The built-in adjuvant makes VCUSM14P an ideal vaccine delivery platform for emerging diseases (e.g. severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] and tuberculosis). Our vaccine formulation mimics natural infection, remains non-reactogenic and immunogenic in vivo, and protects against infection and disease. It will also cost less and be less cumbersome to distribute due to its stability at room temperature. These features could revolutionise the outreach of this and other vaccines to meet global immunisation programmes, particularly in low-resourced areas. The next stage of our journey will be meeting the requisite regulatory requirements to produce the vaccine for rollout to countries where it is most needed.

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BACKGROUND: There are insufficient studies comparing the efficacy of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) against CO2 laser therapy in the treatment of cervical low-grade squamous intraepithelial lesion (LSIL) with high-risk human papillomavirus (HR-HPV), especially for long-term efficacy. METHODS: Patients with cervical LSIL and HR-HPV infection were divided into two treatment groups based on their own choice. All patients had a follow-up test including HPV testing, cytology and colposcopy at 4-6 months and 12 months after the treatment. RESULTS: (1) Among 277 patients, 176 patients received 5-ALA PDT and 101 patients received CO2 laser therapy. (2) 4-6 months after treatment, there was no significant difference between two groups in the complete remission (CR) rates of cervical LSIL and the clearance rate of HR-HPV infection. (3) 12 months after treatment, compared with the CO2 laser group, the CR rates of cervical LSIL in the 5-ALA PDT group was significantly higher than the CO2 laser group. There was no statistical difference in the clearance rate of HR-HPV infection between the two groups. (4) 12 months after treatment, the recurrence rate of cervical lesions and the reinfection rate of HR-HPV infection in 5-ALA PDT group were significantly lower than those in CO2 laser group. CONCLUSION: The effect of 5-ALA PDT is similar to CO2 laser at 4-6 months. The long-term efficacy of 5-ALA PDT appears better than CO2 laser. As a non-invasive treatment, 5-ALA PDT is a highly effective therapeutic procedure for cervical LSIL with HR-HPV infection.

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In an in vitro study, the effect of light polarization on the efficiency of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) of basal cell carcinoma (BCC) was investigated. Three states of light polarization (non-polarized, linearly polarized, and circularly polarized) were considered. Cells were exposed to green (532 pm 20 nm) irradiation from light emitting diodes. Cell survival was measured by the colorimetric assay (WST-1) and Trypan blue staining. The colorimetric assay showed a pronounced decrease in the cell viability (up to 30%) using polarized light compared to the non-polarized one in the wavelength region used. Similar results were obtained by the cell counting method (20-30% increase in cell death). The observed effect was dependent on the concentration of photosensitizer. The effect is more expressed in the case of linearly polarized light compared to the circularly polarized one. Results show that the use of polarized light increases the efficiency of in vitro ALA-PDT of BCC. Utilizing polarized light, it is possible to obtain the same effect from PDT by lower concentrations of photosensitizer. Additionally, the concentration dependency of PDT response and photo-bleaching is also reduced.

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BACKGROUND: Anal Intraepithelial Neoplasia (AIN), a pre-cursor of anal squamous carcinoma, is increasingly detected in individuals with impaired immune function. However, choices for effective, low morbidity treatment are limited. Photodynamic Therapy (PDT) is promising as it is known to ablate more proximal gastrointestinal mucosa with safe healing, without damage to underlying muscle. It can also ablate skin with safe healing and minimal scarring. METHODS: Pharmacokinetics: Normal rats were sensitised with 200mg/kg 5-aminolaevulinic acid (ALA) and killed 1-8h later. Anal tissues were examined by fluorescence microscopy to quantify the concentration of PPIX (protoporphyrin IX, the active derivative of ALA) in anal mucosa and in the underlying sphincter. PDT: Normal rats were sensitised similarly 3h later, laser light (635 nm) was delivered. Anal canal: 50-150 J/cm using 1cm diffuser fibre; for peri-anal skin, 50-200 J/cm(2), using microlens fibre. In each group, 2 rats were killed 3, 7, 14 and 28 days later and the anal region removed for histological examination. RESULTS: Pharmacokinetics: Peak concentration of PPIX in mucosa was at 3h, peak ratio mucosa: muscle, 6, seen at same time. PDT. Anal canal 50 J/cm: complete mucosal ablation by 3 days, complete regeneration by 28 days. Higher energies caused muscle damage with scarring. Peri-anal skin: 200 J/cm(2); complete ablation of skin, including appendages, complete healing by 28 days. Minimal effect with lower energy. CONCLUSION: ALA-PDT can ablate anal mucosa and peri-anal skin with safe healing and no underlying damage. However, over treatment can damage the sphincters. This technique is ready to undergo clinical trials.

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BACKGROUND: Photodynamic therapy(PDT) is a treatment modality using a photosensitizer, light and oxygen to cause photochemically induced selective cell death. Topical PDT is an effective therapy for nonmalignant skin disease as well as various skin conditions. OBJECTIVE: The purpose of this study is to evaluate the effectiveness of PDT in the treatment of precancerous disease, and to evaluate the serial histopathologic findings after PDT. METHOD: PDT using 5-aminolaevulinic acid(ALA) was performed in 6 patients who had been diagnosed with extramammary Paget's disease, actinic cheilitis, actinic keratosis, Bowen's disease and arsenic keratosis. Histopathologic changes after PDT were evaluated by serial biopsy at pre-PDT and 2, 24, 48 hours, 7days post-PDT. TUNEL staining for detecting apoptotic cells was also performed. Light was administered at a wavelength of 600~800nm. The light intensity was 120mW/cm2 and the light dose ranged from 144J/cm2 to 216J/cm2. RESULT: Five patients showed a complete response at 1 month after the PDT and continued to show a complete response over six months. One patient showed a partial response and surgical intervention including laser ablation or conventional surgical excision has been needed. Early histopathologic changes after PDT were epidermal necrosis, band like dermal infiltration of inflammatory cells and thrombi formation in venules. At seven days after PDT, there was significant disappearance of abnormal cells in epidermis. Apoptotic cells were detected at 2, 24 hours post-PDT specimen and decreased from 48 hours post-PDT. CONCLUSION: PDT using 5-ALA is an effective and useful treatment modality for various precancerous skin tumors.

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