# **Viral, Bacterial,** # **Fungal Infections** # **of the Oral Cavity** **Dr Lalima Tiwari** BDSc (UWA), DCClinDent (OralMed) (UWA), MRACDS (OralMed), FOMAA **Oral Medicine Specialist | Adjunct Senior Lecturer** **Dr Lalima Tiwari** BDSc (UWA), DCClinDent (OralMed) (UWA), MRACDS (OralMed), FOMAA **Oral Medicine Specialist | Adjunct Senior Lecturer** # Learning Outcomes * Knowledge of **viral**, **bacterial** and **fungal** infections of the oral soft tissues including: * Herpes simplex infection * Varicella zoster infection * Hand foot and mouth disease * Syphilis * Gonorrhoea * Tuberculosis * Oral candidiasis 1. Discuss the clinical features, histopathology, investigation and management of common and important infections that: * Are primary or reactivated infections of oral soft tissues; * Have oral soft tissue manifestations but also involve other parts of the body. 2. Describe the clinical features of infections in immunocompromised patients. 3. Describe appropriate measures to reduce risks of infection spread. #### Core Knowledge Requirements Comprehensive knowledge of viral, bacterial, and fungal infections of the oral soft tissues, specifically focusing on: - **Viral Infections** - Herpes simplex infection - Varicella zoster infection - Hand foot and mouth disease - **Bacterial Infections** - Syphilis - Gonorrhoea - Tuberculosis - **Fungal Infections** - Oral candidiasis #### Clinical Competencies 1. Discuss the clinical features, histopathology, investigation, and management of common and important infections that: - Are primary or reactivated infections of oral soft tissues. - Have oral soft tissue manifestations but also involve other parts of the body. 2. Describe the clinical features of infections in immunocompromised patients. 3. Describe appropriate measures to reduce risks of infection spread. # **Viral Infections** * **Oral mucosa is a common site for primary viral infections** * **Types of viruses:** - Oral mucosa is a common site for primary viral infections - Various types of viruses can affect this region # **Herpes Simplex Virus** * **Background** * Part of HHV family * DNA virus * $\alpha$- herpevirinae virus * Short reproductive cycle * **Irreversible destruction of infected cells, then maintain latent infection in the sensorial neural ganglion** * $\mathrm{HSV}-1, \mathrm{HSV}-2, \mathrm{VZV}$  #### Viral Characteristics - Part of the Human Herpesvirus (HHV) family - DNA virus - $\alpha$-herpevirinae virus - Short reproductive cycle - Causes irreversible destruction of infected cells, then maintains latent infection in the sensorial neural ganglion - Includes HSV-1, HSV-2, and VZV A detailed diagram illustrating the structure of Herpes simplex virus 1 (HSV-1), showing its components such as the lipid envelope, envelope proteins, tegument, nucleocapsid, and DNA. The diagram also includes a linear representation of the HSV-1 genome, highlighting regions for regulation, capsid assembly, envelope proteins, and DNA replication. # Herpes Simplex Infection * **HSV-1** * Transmitted via close contact with infected fluids (usually saliva) or lesions * **Disease of mouth and surrounding skin** #### HSV-1 Transmission and Scope - Transmitted via close contact with infected fluids (usually saliva) or lesions - Primarily a disease of the mouth and surrounding skin     Close-up photo of an open mouth showing the upper palate with red spots and lesions, likely indicating a medical condition affecting the oral mucosa. Photo of a child's mouth with visible red sores and lesions on the lips and surrounding skin, suggesting a viral or inflammatory condition. Photo showing an open mouth with white vesicles or ulcers on the tongue and inner cheeks, indicative of a common oral infection. Close-up photo of the lower teeth and gums with redness and inflammation, possibly indicating gingivitis or another periodontal issue. Herpes Simplex Infection * **Primary HSV-1 Infection** * **Clinical Features** * Affects **any oral mucosal surface** * Arises 1 – 2 weeks of acquisition of the virus #### Clinical Features - Affects any oral mucosal surface - Arises within 1–2 weeks of acquisition of the virus Herpes Simplex Infection * Primary HSV-2 Infections * **Clinical Features** * Similar clinical picture to HSV – 1 * Illness may be less severe * Not as prolonged as that caused by HSV - 1 <img src="image.png" alt="Image showing oral lesions, likely herpes simplex vesicles/ulcers on the palate.">  #### Clinical Features - Similar clinical picture to HSV-1 - Illness may be less severe - Duration is typically not as prolonged as that caused by HSV-1 A close-up photo showing oral lesions, likely herpes simplex vesicles or ulcers on the palate, illustrating the clinical features of primary HSV-2 infections as described in the text. # Herpes Simplex Infection * **Secondary HSV- 1 infections** * **Clinical Features** * Reactivated HSV – 1 infection * Affects about 30% of patients with history of primary infection * Typically affects vermillion of lips = **herpes labialis** (cold sores) * Can also affect perioral or perinasal skin * Sole involvement of is rare manifestation * Clinical pattern: **paraesthesia** $\rightarrow$ **erythema** $\rightarrow$ **vesiculation** $\rightarrow$ **pustule** **formation** $\rightarrow$ **superficial ulceration** $\rightarrow$ **eventual spontaneous healing** * Lasts about 5–7 days #### Clinical Features and Progression - Reactivated HSV-1 infection - Affects approximately 30% of patients with a history of primary infection - Typically affects the vermillion of the lips (herpes labialis/cold sores) - Can also affect perioral or perinasal skin; sole intra-oral involvement is a rare manifestation - **Clinical pattern:** Paraesthesia $\rightarrow$ erythema $\rightarrow$ vesiculation $\rightarrow$ pustule formation $\rightarrow$ superficial ulceration $\rightarrow$ eventual spontaneous healing - Duration: Approximately 5–7 days # **Herpes Simplex Infection** **Clinical Features** * **Precipitating factors: concomitant illness, exposure to sunlight or UV, phases of menstrual cycle, pregnancy** * **Immunosuppression can also lead to onset of herpes labialis – severe, prolonged, involve intra-oral sites** * **Recur at exact same site each time** * **Location of residency of herpes simplex virus within the trigeminal ganglion** * **Precipitant of erythema multiforme minor** * **Herpetic Whitlow – complication of primary oral or genital herpes by inoculation of the virus through a break in the skin barrier**   #### Precipitating Factors and Complications - **Triggers:** Concomitant illness, exposure to sunlight or UV, phases of the menstrual cycle, and pregnancy - **Immunosuppression:** Can lead to more severe, prolonged onset of herpes labialis involving intra-oral sites - **Recurrence:** Typically recurs at the exact same site due to the location of residency of the virus within the trigeminal ganglion - **Associated Conditions:** - Precipitant of erythema multiforme minor - Herpetic Whitlow: A complication of primary oral or genital herpes caused by inoculation of the virus through a break in the skin barrier Close-up photo of a patient's tongue showing multiple small, red, and white lesions consistent with herpes simplex infection, illustrating the intra-oral involvement mentioned in the text. Close-up photo of a finger with a cluster of red, fluid-filled blisters, characteristic of herpetic whitlow, a complication of herpes simplex virus infection.  Close-up photograph of a person's lower lip showing a red, inflamed lesion on the vermilion border, with surrounding skin exhibiting fine hair and slight swelling. # Herpes Simplex Infection * **In Immunocompromised Patients** * Present as more severe disease and complications * Severe pharyngitis, oral exudative and ulcerative lesions, fever, malaise, myalgia, cervical lymphadenopathy * Chronic mucocutaneous herpes simplex infection extending into deeper cutaneous layers $\rightarrow$ tissue necrosis * Frequent recurrences * Risk factors for increased severity: * History of HIV infection – can occur anywhere: skin, oral, perianal ulcers * HSV can affect viral replication of HIV * Frequent mucosal reactivation of HSV is associated with higher levels of plasma HIV RNA * Malignancy * Organ Transplantation – reactivation rates of $60-80\%$ in patients previously infected with HSV -1 * Malnutrition * Pregnancy * Advanced age <img src="image1.jpg">  #### Disease Severity and Risk Factors - Presents as more severe disease with complications: - Severe pharyngitis, oral exudative and ulcerative lesions, fever, malaise, myalgia, and cervical lymphadenopathy - Chronic mucocutaneous herpes simplex infection extending into deeper cutaneous layers leading to tissue necrosis - Frequent recurrences #### Risk Factors for Increased Severity - **HIV Infection:** Can occur anywhere (skin, oral, perianal ulcers). HSV can affect HIV replication; frequent mucosal reactivation is associated with higher levels of plasma HIV RNA - **Malignancy** - **Organ Transplantation:** Reactivation rates of 60–80% in previously infected patients - **Malnutrition** - **Pregnancy** - **Advanced age** Two clinical photos showing severe herpes simplex infection in immunocompromised patients. Photo (a) depicts extensive ulcerative lesions on the lips and surrounding skin, while photo (b) shows similar lesions inside the mouth, illustrating the severe mucocutaneous involvement described in the text. Herpes Simplex Infection * **Histopathology** * Ballooning degeneration of infected epithelial cells * Inclusion bodies * Form Multinucleated giant epithelial cells * Acantholysis * Formation of Tzank Cells     #### Microscopic Findings - Ballooning degeneration of infected epithelial cells - Inclusion bodies - Formation of multinucleated giant epithelial cells - Acantholysis - Formation of Tzanck cells Microscopic image showing histopathological features of herpes simplex infection, including ballooning degeneration of epithelial cells and inclusion bodies, with a dense accumulation of inflammatory cells in the dermis. High-magnification view of infected epithelial tissue, displaying multinucleated giant cells and inclusion bodies, characteristic of herpes simplex infection, with prominent nuclear changes and cytoplasmic clearing. Histological section illustrating the formation of Tzanck cells, with large, pale cytoplasm and pyknotic nuclei, indicative of acantholysis and cellular degeneration in herpes simplex infection. Microscopic image showing multinucleated giant epithelial cells and inclusion bodies in the epidermis, with scattered inflammatory cells, highlighting the histopathological hallmark of herpes simplex infection. # **Herpes Simplex Infection** * **Investigations** * Molecular: PCR testing * Viral Culture: vesicular fluid removed with sterile cotton swab and placed in viral medium. Determine presence of HSV- 1, HSV – 2 or other Herpes viruses * Serology: > Four – fold rise in HSV – 1 specific IgG antibodies between acute (ulcerative) and convalescent phase of illness provides a retrospective diagnosis of primary HSV – 1 * Full blood count should be obtained for adults with primary HSV to rule out cause of immunosuppression * Immunofluorescence staining: examined for herpes antigens via immunofluorescence microscopy * Herpes labialis is a clinical diagnosis * Identification of HSV DNA via PCR can be helpful #### Diagnostic Methods - **Molecular:** PCR testing (helpful for identifying HSV DNA) - **Viral Culture:** Vesicular fluid removed with a sterile cotton swab and placed in viral medium to determine presence of HSV-1, HSV-2, or other herpes viruses - **Serology:** A greater than four-fold rise in HSV-1 specific IgG antibodies between acute (ulcerative) and convalescent phases provides a retrospective diagnosis of primary HSV-1 - **Full Blood Count (FBC):** Should be obtained for adults with primary HSV to rule out underlying causes of immunosuppression - **Immunofluorescence Staining:** Examination for herpes antigens via immunofluorescence microscopy - **Clinical Diagnosis:** Herpes labialis is typically diagnosed clinically # Herpes Simplex Infection * **Management** * Symptomatic relief * Topical anti-inflammatory: benzydamine hydrochloride spray or mouthwash * Topical anaesthetic: lidocaine (lignocaine) gel * Systemic analgesia and antipyretics: Ibuprofen, Paracetamol <img src="image_placeholder"> </img>  #### Symptomatic Relief - **Topical Anti-inflammatory:** Benzydamine hydrochloride spray or mouthwash - **Topical Anaesthetic:** Lidocaine (lignocaine) gel - **Systemic Analgesia and Antipyretics:** Ibuprofen, Paracetamol A product photo showing a bottle and box of Diffiam Oral Rinse, a 300 ml solution containing benzoydamine hydrochloride for relief of pain and inflammation in the throat and mouth. The product is displayed against a white background. # Herpes Simplex Infection * **Management** * Symptomatic relief * Topical anti-inflammatory: benzydamine hydrochloride spray or mouthwash * Topical anaesthetic: lidocaine (lignocaine) gel * Systemic analgesia and antipyretics: Ibuprofen, Paracetamol * Hydration * Acyclovir can be prescribed where symptoms/signs severe and early * 200 mg tablet or suspension, 5/day for 7 days * Acyclovir should always be considered for patients with immunosuppression, and reviewed by their specialist * Herpes Labialis does not always require treatment * Perioral 5% acyclovir cream applied 6 hourly or 1% penciclovir cream 2 hourly can hasten resolution * To be applied to affected area as soon as possible – vesicular stage * All patients with primary or secondary HSV should avoid direct contact with other individuals to lessen risk of transmission of causative virus  #### Pharmacological and General Care - **Symptomatic Relief:** - Topical anti-inflammatory: Benzydamine hydrochloride spray or mouthwash - Topical anaesthetic: Lidocaine (lignocaine) gel - Systemic analgesia and antipyretics: Ibuprofen, Paracetamol - **Hydration:** Essential for recovery - **Antiviral Therapy:** - Acyclovir (200 mg tablet or suspension, 5 times/day for 7 days) for severe or early symptoms - Acyclovir should always be considered for immunocompromised patients under specialist review - Herpes Labialis: 5% acyclovir cream (6 hourly) or 1% penciclovir cream (2 hourly) can hasten resolution if applied during the vesicular stage - **Transmission Prevention:** Patients should avoid direct contact with others to reduce the risk of spreading the virus A photo showing a bottle and box of Diffiam Oral Rinse, a 300 ml solution containing benzylamine hydrochloride for relief of pain and inflammation in the throat and mouth. The product is presented as a green liquid in a clear bottle with a white cap, alongside its packaging. # **Varicella Zoster Infection** - **Clinical Features** - VZV, HHV – 3 - Primary infection: Chicken Pox - Secondary infection: Shingles, Herpes Zoster - Transmitted via droplets or close contact with lesions #### Background and Transmission - Caused by VZV (HHV-3) - **Primary infection:** Chickenpox (Varicella) - **Secondary infection:** Shingles (Herpes Zoster) - **Transmission:** Via droplets or close contact with lesions # **Herpes Zoster** * **Clinical Features** * Shingles * Caused by reactivation of VZV in ganglia of cranial nerves or dorsal roots * Occurs when cellular immunity to VZV impaired * **Immunosuppression, HIV disease, malignancy** * Occurs later in life * Affect thoracic dermatomes via reactivation within spinal ganglia * Painful eruptions of vesicles, ulceration and prolonged erythema of skin supplied by one or more dermatome of one side of the thorax or upper abdomen <img src="image.png" width="400"/>  #### Pathogenesis and Presentation - Also known as Shingles - Caused by reactivation of VZV in the ganglia of cranial nerves or dorsal roots - Occurs when cellular immunity to VZV is impaired (e.g., immunosuppression, HIV, malignancy, or advanced age) - Affects thoracic dermatomes via reactivation within spinal ganglia - Characterized by painful eruptions of vesicles, ulceration, and prolonged erythema of skin supplied by one or more dermatomes on one side of the thorax or upper abdomen A photo showing a patient's torso with a painful eruption of vesicles and erythema on the right side of the chest, consistent with herpes zoster (shingles). The rash is localized to a dermatome, illustrating the clinical presentation described in the text.   Close-up photograph of a person's face showing red, inflamed skin lesions and pimples, particularly around the nose and cheeks, indicative of a dermatological condition. Close-up photograph of a skin lesion with a red, inflamed base and white pustules, likely representing a bacterial or viral infection on the skin. # **Herpes Zoster** * **Intense, sharp pain** * **Can affect trigeminal nerve – can affect any branch; ophthalmic > maxillary > mandibular division of one side** * **Bilateral involvement rare** * **Oral lesions can appear similar to HSV – 1 infections $\rightarrow$ superficial ulcers that coalesce to give large irregular outlined ulcers** * **Site affected depends on affected branch** * **Unilateral distribution** * **Minor crossover in the midline** * **Lasts 5 – 10 days without therapy in immunocompetent host, longer in immunocompromised** * **Mimics toothache when oral ulcer commences**  #### Trigeminal Nerve Involvement - Characterized by intense, sharp pain - Can affect any branch of the trigeminal nerve (Ophthalmic > Maxillary > Mandibular) - **Distribution:** Unilateral distribution with minor crossover in the midline; bilateral involvement is rare - **Oral Manifestations:** - Superficial ulcers that coalesce into large, irregular ulcers - Site depends on the affected nerve branch - Often mimics a toothache when oral ulceration commences - **Duration:** 5–10 days in immunocompetent hosts; longer in immunocompromised patients Three labeled photographs (a, b, c) showing clinical manifestations of herpes zoster. Photo a shows a patient's eye with vesicular lesions on the eyelid, photo b shows facial skin with red papules and vesicles, and photo c shows oral lesions with large irregular ulcers on the mucosa. These images illustrate the unilateral distribution and varied presentation of herpes zoster in different anatomical sites. # **Herpes Zoster** * **Clinical Features** * Complications of orofacial shingles: * Post-herpetic neuralgia – pain persisting for 3 or more months after healing of the shingles * Meningoencephalitis <table> <tr> <td colspan="2" rowspan="2">Prodrome onset</td> <td colspan="2">Rash onset</td> <td rowspan="3">Rash healed</td> <td rowspan="3">Pain cessation</td> </tr> <tr> <td><1 week</td> <td>2–4 weeks</td> </tr> <tr> <td>Acute herpetic neuralgia</td> <td colspan="2">Subacute herpetic neuralgia</td> <td>Can be years</td> </tr> <tr> <td colspan="2"></td> <td>30 days</td> <td colspan="2">4 months</td> <td>Post-herpetic neuralgia (PHN) →</td> </tr> </table>  #### Neurological and Systemic Complications - **Post-herpetic neuralgia (PHN):** Pain persisting for 3 or more months after the shingles rash has healed - **Meningoencephalitis** #### Neuralgia Timeline 1. **Acute herpetic neuralgia:** From prodrome onset to <1 week after rash onset 2. **Subacute herpetic neuralgia:** From rash onset through healing (approx. 2–4 weeks) 3. **Post-herpetic neuralgia (PHN):** Pain persisting beyond 4 months; can last for years A timeline diagram illustrating the progression of herpes zoster, showing the sequence from prodrome onset to rash onset, rash healed, and pain cessation. It highlights acute herpetic neuralgia (<1 week), subacute herpetic neuralgia (2-4 weeks), and post-herpetic neuralgia (PHN) lasting up to 4 months or longer, with pain potentially persisting for years. Ramsay Hunt Syndrome * **Clinical Features** * Rare manifestation of shingles * VZV reactivation within the geniculate ganglion * Otitis externa * Unilateral lower motor neuron palsy of facial nerve * Ulceration of anterior 2/3 of tongue and soft palate – all on same side as the palsy  #### Clinical Presentation - A rare manifestation of shingles involving VZV reactivation within the geniculate ganglion - **Symptoms:** - Otitis externa - Unilateral lower motor neuron palsy of the facial nerve - Ulceration of the anterior 2/3 of the tongue and soft palate (ipsilateral to the palsy) Three labeled photos showing clinical manifestations of Ramsay Hunt Syndrome: (A) a patient with facial asymmetry, (B) ulceration on the anterior two-thirds of the tongue, and (C) a swollen ear with vesicular rash, all illustrating the syndrome's features. # Varicella Zoster Virus * **Histopathology** * Identical to Herpes Simplex Virus * Clinical correlation, immunohistochemistry and/or viral culture or PCR required to differentiate viral infections * **Investigations** * Diagnosis of chicken pox based on clinical history and picture * Viral or serological investigations rarely warranted * Identification of VZV DNA via PCR * Retrospective serological confirmation (4 fold or more rise in specific antibodies between acute and convalescent phases) * Prudent to assess FBC for evidence of unknown neutropenia, leukemia, white blood cell dyscrasias #### Histopathology - Microscopic features are identical to Herpes Simplex Virus - Requires clinical correlation, immunohistochemistry, viral culture, or PCR to differentiate between the two #### Diagnostic Investigations - **Chickenpox:** Diagnosis is usually based on clinical history and presentation; investigations are rarely warranted - **Molecular:** Identification of VZV DNA via PCR - **Serology:** Retrospective confirmation via a 4-fold or greater rise in specific antibodies between acute and convalescent phases - **Systemic Screening:** Prudent to assess FBC for evidence of unknown neutropenia, leukemia, or white blood cell dyscrasias # **Varicella Zoster Infection** **Management** **Chicken Pox** - Treatment directed towards lessening symptoms - Local use of calamine to reduce pruritis - Warm baths with sodium bicarbonate or potassium permanganate - Antivirals not routinely indicated #### Chickenpox Management - Treatment is directed toward symptom relief - **Pruritus:** Local use of calamine lotion - **Soothing Baths:** Warm baths with sodium bicarbonate or potassium permanganate - **Antivirals:** Not routinely indicated for standard chickenpox # **Varicella Vaccines** Australian Government Department of Health National Immunisation Program Given on its own or as MMRV **Chickenpox immunization is recommended for:** * children at age 18 months, for free under the **National Immunisation Program (NIP)** * children under 14 years old who have had one dose of chickenpox vaccine but want to get a second dose to further reduce their risk of disease * children, teenagers and adults who have not had either the chickenpox disease or the chickenpox vaccine * women who are planning to get pregnant and have not had either the disease or the vaccine * children and adults who have not had either the disease or the vaccine and have been in contact with a person who has chickenpox in the past 5 days * those who have contact with people who have weakened immune systems * healthcare workers who have not had either chickenpox disease or 2 doses of the vaccine * people working in early childhood education and care who have not had either the disease or 2 doses of the vaccine * people working in long-term care who have not had either the disease or 2 doses of the vaccine. * People under 20 years old, refugees and other humanitarian entrants of any age, can get chickenpox vaccines for free under the **NIP**. This is if they did not receive the vaccines in childhood. This is called a catch-up vaccination. If they have already had chickenpox disease, they do not need a chickenpox vaccine. #### Varicella Vaccination Guidelines - Administered as a standalone vaccine or as MMRV - **Recommended for:** - Children at 18 months (free under the National Immunisation Program - NIP) - Children <14 years seeking a second dose for further risk reduction - Non-immune children, teenagers, and adults - Women planning pregnancy (non-immune) - Post-exposure prophylaxis (within 5 days of contact) - Contacts of immunocompromised individuals - Healthcare, early childhood, and long-term care workers - **Catch-up Program:** Free under the NIP for people under 20, refugees, and humanitarian entrants if not received in childhood # **Herpes Zoster Vaccines** * **Given as a single vaccine** * **Shingles immunization is recommended for:** * adults aged 60 years and over who have not previously received zoster vaccine * adults aged 70 years to 79 years, for free under the **<u>National Immunisation Program (NIP)</u>** * adults aged 50 or over who live in the same household as someone who has a weakened immune system. #### Shingles Vaccination Guidelines - Administered as a single vaccine - **Recommended for:** - Adults aged 60 years and over - Adults aged 70 to 79 years (free under the National Immunisation Program - NIP) - Adults aged 50 or over living with an immunocompromised individual # **Hand Foot and Mouth Disease** * **Coxsackie Virus (A16)** * **Typically affects infants and children ages 3 – 10** * **Most frequent in summer** * **Can spread throughout schools, affecting parents, carers, teachers** * **Transmission: faecal – oral contact or via inhalation of respiratory droplets, direct interaction with cutaneous lesions** * **Incubation period: 3 – 7 days** * **Most contagious in week 1 of illness** * **Present for 6 – 8 weeks in faeces, 1 week in respiratory system** #### Etiology and Transmission - **Causative Agent:** Coxsackie Virus (A16) - **Demographics:** Typically affects infants and children aged 3–10; common in summer - **Transmission:** Faecal-oral contact, inhalation of respiratory droplets, or direct interaction with cutaneous lesions - **Incubation and Contagion:** - Incubation period: 3–7 days - Most contagious during the first week of illness - Virus persists for 1 week in the respiratory system and 6–8 weeks in faeces Hand Foot and Mouth Disease * **Clinical Features** * Fever * Reduced appetite * Sore throat * Malaise * Numerous vesicles and oral ulcers (day 1 – 2); 2 – 7 mm in diameter * Sites affected: buccal mucosa, labial mucosa, tongue * Disappear after 1 week * Palms of hand and soles of feet affected after oral lesions * Vesicles or small blisters on distal flexor aspect of fingers or toes  #### Systemic and Local Signs - **Systemic:** Fever, reduced appetite, sore throat, and malaise - **Oral Lesions:** Numerous vesicles and ulcers (2–7 mm) appearing on day 1–2 - **Sites:** Buccal mucosa, labial mucosa, and tongue - **Duration:** Disappear after approximately 1 week - **Cutaneous Lesions:** Vesicles or small blisters on the palms of hands, soles of feet, and distal flexor aspects of fingers or toes; typically appear after oral lesions Three labeled photographs showing clinical manifestations of Hand Foot and Mouth Disease: (a) oral lesions with vesicles on the tongue and buccal mucosa, (b) vesicles on the palm of the hand, and (c) vesicles on the sole of the foot. **Hand Foot and Mouth** * **Histopathology** * Rarely biopsied * Lymphocytic infiltrates the epithelium * Keratinocyte apoptosis * Intraepithelial/ intraepidermal vesiculation as a consequence of epidermal oedema  #### Microscopic Findings - Biopsy is rarely performed - Lymphocytic infiltration of the epithelium - Keratinocyte apoptosis - Intraepithelial/intraepidermal vesiculation resulting from epidermal oedema Three histopathological images showing lymphocytic infiltrates in the epithelium, keratinocyte apoptosis, and intraepithelial/intraepidermal vesiculation due to epidermal edema, consistent with hand, foot, and mouth disease. # **Hand Foot and Mouth Disease** **Investigations** * **Viral culture** * **Immunoassay from cutaneous lesions, mucosal lesions or stool samples** * **Oral specimens have highest isolation rate** * **Diagnosis typically based on clinical picture** * **Biopsy of atypical lesions** * **Raised white cell count** * **Atypical lymphocytes** * **Raised serum C-reactive protein (CRP)** #### Diagnostic Procedures - **Clinical Diagnosis:** Typically based on the clinical presentation - **Laboratory Tests:** - Viral culture or immunoassay from cutaneous/mucosal lesions or stool samples - Oral specimens provide the highest isolation rate - Raised white cell count and atypical lymphocytes - Raised serum C-reactive protein (CRP) - **Biopsy:** Reserved for atypical lesions # Hand Foot and Mouth Disease * **Management** * Supportive * Hydration * Topical analgesics (lignocaine gel) * Systemic analgesics and antipyretics (paracetamol or ibuprofen) * No notable long-lasting consequences #### Clinical Care - **Supportive Care:** Hydration is key - **Pain Management:** - Topical analgesics (e.g., lidocaine/lignocaine gel) - Systemic analgesics and antipyretics (e.g., paracetamol or ibuprofen) - **Prognosis:** No notable long-lasting consequences Recap on viral infections Summary review of viral infection characteristics and management protocols. # Syphilis * Caused by ***Treponema pallidum*** * Anaerobic filamentous ***spirochete*** capable of **invading** any organ of the human body * Sexually transmitted infection * Acquired (sexual) or congenital (vertical) transmission * Easily transmissible by kissing or close contact with infectious lesion * Major global health resurgence * Rate of Syphilis doubled in WA between 2016 – 2020  - Caused by *Treponema pallidum* - Anaerobic filamentous **spirochete** capable of **invading** any organ of the human body - Sexually transmitted infection - Acquired (sexual) or congenital (vertical) transmission - Easily transmissible by kissing or close contact with infectious lesion - Major global health resurgence - Rate of Syphilis doubled in WA between 2016 – 2020 A microscopic image of Treponema pallidum, the spirochete bacterium that causes syphilis, shown as a coiled, filamentous structure in teal against a pinkish background. This visual representation illustrates the anaerobic spirochete capable of invading human organs, as described in the adjacent text. **Syphilis** * **Communities at Risk (in WA)** * Historically: Aboriginal communities in remote areas, Men who have sex with men * People experiencing homelessness * People who use methamphetamine and/or inject drugs * Culturally and linguistically diverse (CALD) people * People who are 16 – 35 years old * Aboriginal people 16 – 39 years old (Goldfields, Kimberley, Pilbara) * Women of child bearing age #### High-Risk Groups in Western Australia - Historically: Aboriginal communities in remote areas, Men who have sex with men - People experiencing homelessness - People who use methamphetamine and/or inject drugs - Culturally and linguistically diverse (CALD) people - People who are 16 – 35 years old - Aboriginal people 16 – 39 years old (Goldfields, Kimberley, Pilbara) - Women of child bearing age # Syphilis * **Clinical Features** * Acquired Syphilis * Primary * Secondary * Latent * Tertiary * Non-specific presentation and remarkable ability to mimic other diseases #### Acquired Syphilis Stages 1. Primary 2. Secondary 3. Latent 4. Tertiary #### Diagnostic Challenges - Non-specific presentation and remarkable ability to mimic other diseases. # Primary Syphilis **Clinical Features** * Characteristic Chancre * Highly infectious lesion occurring at site of inoculation * Incubation period: 3 – 90 days * Large, painless ulcer with indurated margin * Painless lymphadenopathy (80%) of cases occur after chancre develops * Sites: intrarectal, perianal, oral (4-12%) * Oral sites: tongue, gingiva, palate, lips * Chancres can heal in absence of treatment, within 8 weeks without scarring * Systemic dissemination can occur * **Low rate of diagnosis due to it going unnoticed in primary stage**  #### Characteristic Chancre - Highly infectious lesion occurring at site of inoculation. - Incubation period: 3 – 90 days. - Large, painless ulcer with indurated margin. - Painless lymphadenopathy (80% of cases) occurs after chancre develops. #### Clinical Presentation - **Sites:** Intrarectal, perianal, oral (4-12%). - **Oral sites:** Tongue, gingiva, palate, lips. - **Progression:** Chancres can heal in absence of treatment within 8 weeks without scarring. - **Systemic dissemination:** Can occur. - **Diagnosis:** Low rate of diagnosis due to it going unnoticed in the primary stage. A close-up photo of a chancre lesion in the oral cavity, showing a large, painless ulcer with an indurated margin on the inner cheek, consistent with primary syphilis. The lesion is located near the teeth and appears to be part of the clinical features described in the surrounding text. # **Secondary Syphilis** <br> **Clinical Features** * Occurs $2-12$ weeks after contact with T. pallidum * Localised or generalised skin rash (**maculopapular lesions on palms and soles**), can mimic eczema, psoriasis, drug eruption, lichen planus * Alopecia * Malaise * Sore throat * Headache * Weight loss * Low grade fever * Generalised lymphadenopathy * Muscle aches * Renal, ophthalmologic, hepatic, bone and joint diseases, CNS involvement can be seen * Oral lesions seen in $30\%$ of individuals * Mucous patches highly infectious * Slightly elevated plaques that may be ulcerated * Multiple lesions that coalesce to give rise to serpiginous lesions * Lasts for weeks or months with relapses occurring <br>  #### Systemic Manifestations - Occurs 2–12 weeks after contact with *T. pallidum*. - Localised or generalised skin rash (**maculopapular lesions on palms and soles**); can mimic eczema, psoriasis, drug eruption, or lichen planus. - Alopecia. - Malaise, sore throat, headache, weight loss, and low-grade fever. - Generalised lymphadenopathy and muscle aches. - Potential involvement: Renal, ophthalmologic, hepatic, bone and joint diseases, and CNS. #### Oral Lesions - Seen in 30% of individuals. - **Mucous patches:** Highly infectious. - Slightly elevated plaques that may be ulcerated. - Multiple lesions that coalesce to give rise to serpiginous lesions. #### Duration - Lasts for weeks or months with relapses occurring. Three photographs showing clinical manifestations of secondary syphilis: (a) a close-up of maculopapular lesions on the forearm, (b) similar lesions on the palms of the hands, and (c) oral mucous patches and lesions on the soles of the feet, illustrating the diverse skin and mucosal involvement. # Latent Syphilis * **Clinical Features** * After untreated secondary stage * No signs of primary or secondary disease * Only detected by serologic testing * Sexual transmission unlikely * Can develop Tertiary Syphilis with neurological, cardiovascular complications - Occurs after an untreated secondary stage. - No signs of primary or secondary disease. - Only detected by serologic testing. - Sexual transmission is unlikely. - Can progress to Tertiary Syphilis with neurological and cardiovascular complications. # **Tertiary Syphilis** * **Clinical Features** * Can manifest 1 year after initial infection or decades later * **Nodular, ulcerative lesion = gumma** * Involve skin, mucous membranes, CNS, liver, spleen, bones and other organs * Cardiovascular complications: aortitis, aneurysm, aortic regurgitation * CNS manifestations: general paralysis, aortic regurgitation * Oral cavity: palate, tongue, tonsils, lips, bone involvement * Pain, swelling, oronasal fistula, osteonecrosis, atrophic glossitis, syphilitic leukoplakia, parotid gland involvement  #### Progression and Systemic Involvement - Can manifest 1 year after initial infection or decades later. - **Nodular, ulcerative lesion = gumma**. - Involves skin, mucous membranes, CNS, liver, spleen, bones, and other organs. - **Cardiovascular complications:** Aortitis, aneurysm, aortic regurgitation. - **CNS manifestations:** General paralysis. #### Oral Cavity Involvement - **Sites:** Palate, tongue, tonsils, lips, and bone involvement. - **Symptoms/Signs:** Pain, swelling, oronasal fistula, osteonecrosis, atrophic glossitis, syphilitic leukoplakia, and parotid gland involvement. A clinical photograph showing a nodular, ulcerative lesion in the oral cavity, consistent with a gumma, which is a characteristic feature of tertiary syphilis. The lesion appears as a large, reddish, necrotic mass on the tongue, illustrating the severe tissue involvement described in the accompanying text. # Congenital Syphilis * **Clinical Features** * Transmitted in utero or during delivery * Newborn comes in contact with contagious genital lesion * 25 – 50% result in miscarriage * Risk of vertical transmission: 70 – 100% * Infected infants can have symptoms at birth * Majority of untreated children who survive first 6 – 12 months will progress to latent and tertiary syphilis * Generalized lymphadenopathy, maculopapular rash. Hepatosplenomegaly, glomerulonephritis, gummas, bone alterations * Saddle nose, high arched palate, Frontal bossing of skull, mental retardation * Oral manifestations: peg-shaped incisors, defective molars, atrophic glossitis, skin fissures  #### Transmission and Risk - Transmitted in utero or during delivery via contact with contagious genital lesions. - 25–50% result in miscarriage. - Risk of vertical transmission: 70–100%. #### Clinical Presentation in Infants - Infected infants can have symptoms at birth. - Majority of untreated children who survive the first 6–12 months will progress to latent and tertiary syphilis. - Generalized lymphadenopathy, maculopapular rash, hepatosplenomegaly, glomerulonephritis, gummas, and bone alterations. - Saddle nose, high arched palate, frontal bossing of skull, and mental retardation. #### Oral Manifestations - Peg-shaped incisors (Hutchinson's incisors). - Defective molars (Mulberry molars). - Atrophic glossitis. - Skin fissures. A collage of four photographs showing clinical manifestations of congenital syphilis in an infant, including skin lesions on the face, ear, and extremities. # **Syphilis** <br> * **<font color="blue">Histopathology</font>** * Plasma cell infiltration * Proliferative endarteritis * Plasma cell, lymphocytes, macrophages found in a perivascular distribution or band like infiltrate in lamina propria * Oral tertiary syphilis shows absence of epithelial lamina with peripheral psuedoepitheliomatous hyperplasia * Lamina propria contains foci of granulomatous inflammation with large centra zone of acellular necrosis * Well-circumscribed collections of histiocytes and multinucleated giant cells * Can be demonstrated in some lesions by silver stain   #### General Microscopic Features - Plasma cell infiltration. - Proliferative endarteritis. - Plasma cells, lymphocytes, and macrophages found in a perivascular distribution or band-like infiltrate in the lamina propria. #### Tertiary Syphilis Specifics - Oral tertiary syphilis shows absence of epithelial lamina with peripheral pseudoepitheliomatous hyperplasia. - Lamina propria contains foci of granulomatous inflammation with a large central zone of acellular necrosis. - Well-circumscribed collections of histiocytes and multinucleated giant cells. - Spirochetes can be demonstrated in some lesions by silver stain. Microscopic image showing plasma cell infiltration in tissue, with a dense accumulation of cells in a perivascular distribution, consistent with histopathological findings of syphilis. Microscopic image highlighting proliferative endarteritis and a band-like infiltrate of plasma cells, lymphocytes, and macrophages in the lamina propria, with an arrow pointing to a specific area of interest. # **Syphilis** * **Investigations** * **Clinical and Serological findings** * Biopsy can be undertaken to rule out other pathosis * Nontreponemal tests – screening * Become positive 1 - 4 weeks after appearance of primary lesion * 6 weeks after exposure * Venereal Disease Research Laboratory (VDRL) test * Rapid Plasma Reagin test (RPR) * Detect IgM and IgG antibodies to lipoidal material released from damaged cells * Can be negative in some latent and tertiary cases * Treponemal tests – diagnostic confirmation * Fluorescent treponemal antibody absorption (FTA-ABS) and agglutination (TP-PA) * Once a patient tests positive to any of these tests, they remain positive for life, even after treatment * Syphilis PCR test {| class="wikitable" |+ Syphilis Serological Tests ! Non-Treponemal Tests (non-specific test) !! Confirmatory Treponemal Tests |- | Veneral Disease Research Laboratory test (VDRL) || Treponemal pallidum particle agglutination test (TP-PA) |- | Rapid plasma reagin test (RPR) || Fluorescent treponemal antibody absorbed test (FTA-ABS) |- || T. pallidum enzyme immunoassay antibody test (TP-EIA) |- || Chemiluminescence immunoassay (CIA) |} Note: The non-treponemal tests (titers) detect antibodies that are not specific for *Treponema pallidum*. Note: As a group, these tests are based upon the detection of antibodies directed against specific treponemal antigens. Treponemal tests are qualitative only and are reported as "reactive" or "non-reactive". **The use of only one type of serologic test is insufficient for diagnosis.**  #### Diagnostic Approach - Based on clinical and serological findings. - Biopsy may be undertaken to rule out other pathosis. - **Syphilis PCR test** is also available. #### Nontreponemal Tests (Screening) - Detect IgM and IgG antibodies to lipoidal material released from damaged cells. - Become positive 1–4 weeks after appearance of primary lesion (approx. 6 weeks after exposure). - **Tests:** Venereal Disease Research Laboratory (VDRL) and Rapid Plasma Reagin (RPR). - Note: Can be negative in some latent and tertiary cases. #### Treponemal Tests (Diagnostic Confirmation) - Qualitative tests reported as "reactive" or "non-reactive". - Once positive, patients usually remain positive for life. - **Tests:** - Fluorescent treponemal antibody absorption (FTA-ABS). - *T. pallidum* particle agglutination (TP-PA). - *T. pallidum* enzyme immunoassay (TP-EIA). - Chemiluminescence immunoassay (CIA). #### Serological Test Summary | Non-Treponemal Tests (Non-specific) | Confirmatory Treponemal Tests | | :--- | :--- | | Venereal Disease Research Laboratory (VDRL) | *T. pallidum* particle agglutination (TP-PA) | | Rapid plasma reagin (RPR) | Fluorescent treponemal antibody absorbed (FTA-ABS) | | | *T. pallidum* enzyme immunoassay (TP-EIA) | | | Chemiluminescence immunoassay (CIA) | **The use of only one type of serologic test is insufficient for diagnosis.** A table comparing non-treponemal tests (such as VDRL and RPR) with confirmatory treponemal tests (such as TP-PA, FTA-ABS, TP-EIA, and CIA), detailing their use in syphilis diagnosis. The table includes notes on the nature of these tests, highlighting that non-treponemal tests detect non-specific antibodies while treponemal tests are qualitative and remain positive for life after infection. # **Syphilis** * **Management** * **High sensitivity to penicillin** * **Treatment Regime (Primary, Secondary, Early Latent):** * Benzathine penicillin G 2.4 million units IM in single dose * Or 50,000 units/kg IM up to 2.4 million units in single dose in children #### General Sensitivity - High sensitivity to penicillin. #### Treatment Regime (Primary, Secondary, Early Latent) - **Adults:** Benzathine penicillin G 2.4 million units IM in a single dose. - **Children:** 50,000 units/kg IM up to 2.4 million units in a single dose. # **Syphilis** * **Management** * High sensitivity to penicillin * Treatment Regime (Primary, Secondary, Early Latent): * Benzathine penicillin G 2.4 million units IM in single dose * Or 50,000 units/kg IM up to 2.4 million units in single dose in children * Clinical and serologic evaluation performed at 6 and 12 months after treatment * Late latent or Latent Syphilis: * Benzathine penicillin G 7.2 million units total (3 doses of 2.4 million units IM) each at 1 week intervals * 50,000 units/kg IM up to 2.4 million units at three doses, 1 week intervals in children * Non-treponemal serologic tests repeated at 6, 12, 24 months * Tertiary syphilis * Normal CSF examination: Benzathine penicillin G 7.2 million units total (3 doses of 2.4 million units IM) each at 1 week intervals * Neurosyphilis: crystalline penicillin G 18–24 million units per day, as 3–4 million units IV every 4 h or continuous infusion, for 10–14 days #### Late Latent or Latent Syphilis of Unknown Duration - **Adults:** Benzathine penicillin G 7.2 million units total (3 doses of 2.4 million units IM at 1-week intervals). - **Children:** 50,000 units/kg IM up to 2.4 million units for three doses at 1-week intervals. - **Follow-up:** Non-treponemal serologic tests repeated at 6, 12, and 24 months. #### Tertiary Syphilis - **Normal CSF examination:** Benzathine penicillin G 7.2 million units total (3 doses of 2.4 million units IM at 1-week intervals). - **Neurosyphilis:** Crystalline penicillin G 18–24 million units per day (administered as 3–4 million units IV every 4 hours or continuous infusion) for 10–14 days. #### Clinical Evaluation - Clinical and serologic evaluation performed at 6 and 12 months after treatment for early stages. # **Syphilis** * **Management** * Tested for HIV infection * Management of sex partners * Unless oral lesions present, necessary dental care can be provided and normal treatment can recommence once oral lesions successfully treated * Disease prevention centred around education, reduction of sexual partners, consistent use of barrier protection #### Patient Care and Prevention - Patients should be tested for HIV infection. - Management of sex partners is required. - **Dental Care:** Unless oral lesions are present, necessary dental care can be provided. Normal treatment can recommence once oral lesions are successfully treated. - **Prevention:** Centred around education, reduction of sexual partners, and consistent use of barrier protection. # **Gonorrhoea** * Sexually transmitted infection * *Neisseria gonorrhoeae* * Most common STIs * Can develop and retain antimicrobial resistance * **Oral mucosa usually resistant to gonococcal infection as organism cannot invade intact epithelium, but infection can occur when integrity of barrier compromised** * Transmitted primarily by sexual activity * Needs moist environment to remain viable - Caused by *Neisseria gonorrhoeae*. - One of the most common STIs. - Can develop and retain antimicrobial resistance. - Transmitted primarily by sexual activity; requires a moist environment to remain viable. - **Oral Resistance:** Oral mucosa is usually resistant as the organism cannot invade intact epithelium; however, infection can occur when the barrier integrity is compromised. # **Gonorrhoea** * **Clinical Features** * Urethritis in men * Cervicitis in women * Urogenital symptoms – dysuria, clear to **mucopurulent discharge** * Pain when urinating, **purulent** vaginal discharge, vaginal bleeding * Can be asymptomatic, especially children * Infertility * **Purulent** conjunctivitis $\rightarrow$ corneal ulceration * Newborns: ophthalmia neonatorum $\rightarrow$ blindness * Gonococcemia $\rightarrow$ febrile, endocarditis, cutaneous rash, meningitis, polyarthritis, ulceration of soft palate and oropharynx * TMJ can be involved in gonococcal arthritis #### Urogenital and Systemic Symptoms - **Men:** Urethritis, dysuria, clear to mucopurulent discharge. - **Women:** Cervicitis, purulent vaginal discharge, vaginal bleeding, dysuria. - **General:** Can be asymptomatic (especially in children); may lead to infertility. - **Ocular:** Purulent conjunctivitis which can lead to corneal ulceration and blindness (ophthalmia neonatorum in newborns). - **Gonococcemia:** Febrile state, endocarditis, cutaneous rash, meningitis, polyarthritis, and ulceration of the soft palate and oropharynx. - **Musculoskeletal:** TMJ can be involved in cases of gonococcal arthritis. # **Gonorrhoea** **Oropharyngeal Involvement:** * **20 – 25%** * Diffuse oropharyngeal erythema * Small pustules noted * Submandibular or cervical lymphoidadenopathy * Gonococcal Tonsillitis * Fever infrequent <img src="image.png" alt="Image of oropharyngeal gonorrhea showing inflammation and small red pustules on the uvula and tonsils.">  - Occurs in 20–25% of cases. - Diffuse oropharyngeal erythema. - Small pustules may be noted. - Submandibular or cervical lymphadenopathy. - Gonococcal Tonsillitis. - Fever is infrequent. A close-up photo showing oropharyngeal gonorrhea with diffuse erythema and small pustules on the uvula and tonsils, illustrating the clinical presentation of the condition. # Gonorrhoea **Histopathology** * **Gram-stained samples** * **Sensitivity and specificity varies** * **Tests for characteristic Gram-negative diplococci within PMNL's** * **Gram-stain not suitable for diagnosis of N. gonorrhoeae from pharyngeal specimens** * **Methylene blue staining alternative method to gram stain**  #### Staining Techniques - **Gram-stained samples:** Tests for characteristic Gram-negative diplococci within polymorphonuclear leukocytes (PMNLs). - **Limitations:** Sensitivity and specificity vary; Gram-stain is not suitable for diagnosis of *N. gonorrhoeae* from pharyngeal specimens. - **Alternative:** Methylene blue staining is an alternative method to Gram stain. A photomicrograph showing Gram-stained samples of Neisseria gonorrhoeae, with purple-stained Gram-negative diplococci visible within polymorphonuclear leukocytes (PMNLs). The image highlights the characteristic appearance of the bacteria, which are labeled as 'N. gonorrhoeae'. # **Gonorrhoea** ## **Investigations** <table><thead> <tr> <td colspan="2"><strong>Parameter</strong></td> <td><strong>Microscopy</strong></td> <td><strong>Culture</strong></td> <td><strong>NAAT</strong></td> </tr> </thead><tbody> <tr> <td colspan="2"><em><strong>Specimen types<sup>a</sup></strong></em></td> <td></td> <td></td> <td></td> </tr> <tr> <td colspan="2">Urine</td> <td>Female</td> <td>No</td> <td>No</td> <td>Yes<sup>b</sup></td> </tr> <tr> <td colspan="2"></td> <td>Male</td> <td>No</td> <td>No</td> <td>Yes</td> </tr> <tr> <td colspan="2">Urethral swab</td> <td></td> <td>Yes</td> <td>Yes</td> <td>Yes</td> </tr> <tr> <td colspan="2">Rectal swab</td> <td></td> <td>No</td> <td>Yes</td> <td>Yes/no<sup>c</sup></td> </tr> <tr> <td colspan="2">Pharyngeal swab</td> <td></td> <td>No</td> <td>Yes</td> <td>Yes/no<sup>c</sup></td> </tr> <tr> <td colspan="2">Conjunctival swab</td> <td></td> <td>Yes</td> <td>Yes</td> <td>Yes/no<sup>c</sup></td> </tr> <tr> <td colspan="2"><em><strong>Performance</strong></em></td> <td></td> <td></td> <td></td> </tr> <tr> <td colspan="2">Sensitivity<sup>d</sup></td> <td></td> <td>Low–high</td> <td>Moderate–high</td> <td>Very high</td> </tr> <tr> <td colspan="2">Specificity<sup>d</sup></td> <td></td> <td>Moderate–high</td> <td>Very high</td> <td>Moderate–very high</td> </tr> <tr> <td colspan="2">Cost</td> <td></td> <td>Low</td> <td>Moderate</td> <td>Moderate–very high</td> </tr> <tr> <td colspan="2">Instrumentation</td> <td></td> <td>Microscope</td> <td>Routine microbiology</td> <td>Moderate–large footprint</td> </tr> <tr> <td colspan="2">Technical complexity</td> <td></td> <td>Low–moderate</td> <td>Moderate</td> <td>Low–high</td> </tr> <tr> <td colspan="2">Level of laboratory infrastructure</td> <td></td> <td>Low</td> <td>Low–intermediate</td> <td>Intermediate–high</td> </tr> <tr> <td colspan="2">Potential as a POCT</td> <td></td> <td>Yes</td> <td>No</td> <td>Yes</td> </tr> </tbody></table> NAAT, nucleic acid amplification test; POCT, point-of-care test. $^a$Yes or no indicates appropriateness of specimen type. $^b$The sensitivity is substantially lower than in other approved specimen types and a negative result does not exclude gonococcal infection. $^c$Yes/no indicates that not all platforms have received FDA approval for that specific specimen. $^d$Can highly depend on specimen type. Adapted from Unemo,  #### Diagnostic Modalities by Specimen Type | Specimen Type | Microscopy | Culture | NAAT | | :--- | :--- | :--- | :--- | | **Urine (Female)** | No | No | Yes (Lower sensitivity) | | **Urine (Male)** | No | No | Yes | | **Urethral swab** | Yes | Yes | Yes | | **Rectal swab** | No | Yes | Yes/No | | **Pharyngeal swab** | No | Yes | Yes/No | | **Conjunctival swab** | Yes | Yes | Yes/No | #### Performance and Logistics - **Sensitivity:** NAAT (Very high) > Culture (Moderate-high) > Microscopy (Low-high). - **Specificity:** Culture/NAAT (Very high) > Microscopy (Moderate-high). - **Cost:** Microscopy (Low), Culture/NAAT (Moderate to Very high). - **POCT Potential:** Microscopy and NAAT have potential as point-of-care tests. *Note: NAAT = Nucleic Acid Amplification Test. Sensitivity in female urine is substantially lower than other types; a negative result does not exclude infection.* A comparative table titled 'Investigations' for gonorrhoea, detailing specimen types and performance parameters for microscopy, culture, and NAAT (nucleic acid amplification test). The table compares sensitivity, specificity, cost, instrumentation, technical complexity, laboratory infrastructure requirements, and potential as a point-of-care test across the three diagnostic methods. # **Gonorrhoea** * **Management** * Dual antimicrobial therapy * Uncomplicated gonococcal infections of cervix, urethra, rectum, pharynx: * ceftriaxone 250 mg IM as single dose * azithromycin 1 g orally as single dose * Infected individuals should be counselled about importance of referring any-one with whom they have had sexual contact in the preceding 60 days for screening * Check for co-infections #### Antimicrobial Therapy - Dual antimicrobial therapy is recommended. - **Uncomplicated infections (Cervix, Urethra, Rectum, Pharynx):** - Ceftriaxone 250 mg IM as a single dose. - Azithromycin 1 g orally as a single dose. #### Partner Management and Screening - Counsel infected individuals to refer sexual contacts from the preceding 60 days for screening. - Check for co-infections. # **Tuberculosis** * Mycobacterium tuberculosis * Aerobic, acid-fast, non-motile, non-encapsulated and non-spore forming bacillus * Transmitted through respiratory droplets through coughing, sneezing, talking * Mortality > 50% if untreated * Immunocompromised people at greatest risk * HIV positive individuals 20 – 40 times more likely to develop active disease $\rightarrow$ leading cause of death in these patients * Accelerates progression of HIV * Impacts efficacy of HIV treatment <img src="image_description.png"> </img>  - Caused by *Mycobacterium tuberculosis*. - Aerobic, acid-fast, non-motile, non-encapsulated, and non-spore forming bacillus. - **Transmission:** Respiratory droplets (coughing, sneezing, talking). - **Mortality:** > 50% if untreated. - **High-Risk Groups:** Immunocompromised individuals. - HIV-positive individuals are 20–40 times more likely to develop active disease. - TB is a leading cause of death in HIV patients and accelerates HIV progression. A microscopic image of Mycobacterium tuberculosis, depicted as red, rod-shaped bacteria against a blue and purple gradient background, illustrating the pathogen responsible for tuberculosis. # Tuberculosis **Clinical Features** * Pulmonary TB accounts for 85% of all clinical presentations * 15 – 25% can manifest as extra-pulmonary sites * Lymph nodes – painful, firm, not mobile * Pleura * Bones * Meninges * Genitourinary tract * Night sweats, fever, weight, cough, haemoptysis, pleuritic pain * Tuberculous meningitis follows CNS involvement  #### Pulmonary vs. Extra-pulmonary TB - **Pulmonary TB:** Accounts for 85% of clinical presentations. - **Extra-pulmonary TB (15–25%):** - Lymph nodes (painful, firm, not mobile). - Pleura, bones, meninges, and genitourinary tract. #### Constitutional Symptoms - Night sweats, fever, weight loss. - Cough, haemoptysis, and pleuritic pain. - Tuberculous meningitis follows CNS involvement. A composite medical image showing two CT scans of the lungs, labeled 'a' and 'b', illustrating pulmonary tuberculosis. Scan 'a' displays a cross-sectional view with a lesion in the lower lobe, while scan 'b' shows a coronal view with multiple nodular opacities in the upper lobe, indicated by arrows and circles. # Tuberculosis <br> * **Clinical Features** * Oral Manifestations: * Uncommon ($0.1-0.5\%$) * **More common in men than women** * **Can present as primary or secondary to systemic disease** * Primary oral TB more common in younger individuals * Common on tongue – but can include any oral site * Non-specific * Oral ulceration most common – indurated, ill-defined margins, hard necrotic base, or covered with grayish-yellow slough * Can range from patches, papillomatous lesions, indurated soft tissue lesions * Single or multiple * Tuberculosis osteomyelitis involve maxilla, mandible with sequestration of bone, pain * Rare involvement of parotid gland <img src = "image.png" width = "300">  #### Prevalence and Presentation - Uncommon (0.1–0.5% of cases). - More common in men than women. - Can be primary or secondary to systemic disease. - Primary oral TB is more common in younger individuals. #### Clinical Appearance - **Common site:** Tongue (though any oral site can be involved). - **Oral Ulceration:** Most common; features indurated, ill-defined margins, and a hard necrotic base (often covered with grayish-yellow slough). - **Other forms:** Patches, papillomatous lesions, or indurated soft tissue lesions. - **Bone involvement:** Tuberculosis osteomyelitis involving the maxilla or mandible with bone sequestration and pain. - **Salivary glands:** Rare involvement of the parotid gland. A close-up clinical photo showing an oral lesion consistent with tuberculosis, featuring an indurated ulcer with ill-defined margins and a necrotic base on the tongue, adjacent to a tooth with a dental restoration. # **Tuberculosis** * **Histopathology** * Central area of caseous necrosis * Epithelioid macrophages * Langerhans giant cells * Lymphocytes * Outer zone of lymphocytes, plasma cells, immature macrophages * Peripheral fibrosis * Special stains: Ziehl – Neelsen stain positive for the bacilli  #### Granulomatous Inflammation - Central area of caseous necrosis. - Epithelioid macrophages. - Langerhans giant cells. - Outer zone of lymphocytes, plasma cells, and immature macrophages. - Peripheral fibrosis. #### Special Stains - **Ziehl–Neelsen stain:** Positive for acid-fast bacilli. Two microscopic images labeled 'a' and 'b' showing histopathological features of tuberculosis. Image 'a' displays a central area of caseous necrosis surrounded by epithelioid macrophages and Langerhans giant cells. Image 'b' shows a dense infiltration of lymphocytes and plasma cells in the outer zone, with peripheral fibrosis, consistent with the described histopathology. # **Tuberculosis** * **Investigations** * TST: Tuberculin Skin Test * IGRA: Interferon-$\gamma$- release assay * Fine needle aspiration cytology * Histopathology * Ultrasound * MRI * CT can be additionally used in diagnosis of TB of major salivary glands <table> <tr> <td>Consider TB</td> <td rowspan="2"></td> <td rowspan="2"></td> <td rowspan="2"></td> </tr> <tr> <td>Symptoms</td> </tr> <tr> <td>No</td> <td>Latent</td> <td></td> <td></td> </tr> <tr> <td></td> <td>TST</td> <td></td> <td></td> </tr> <tr> <td></td> <td>More difficult to interpret if previous BCG vaccine</td> <td>IGRA</td> <td></td> </tr> <tr> <td></td> <td></td> <td>Not if <2 years of age</td> <td>Active</td> </tr> <tr> <td></td> <td>If TST or IGRA positive exclude active TB AND follow up</td> <td></td> <td>Chest X-ray and 3 x sputum samples</td> </tr> <tr> <td></td> <td></td> <td></td> <td>Microscopy</td> </tr> <tr> <td></td> <td></td> <td></td> <td> <table> <tr> <td>Culture</td> <td>And consider</td> <td>Molecular assay</td> </tr> </table> </td> </tr> <tr> <td></td> <td></td> <td></td> <td>Drug susceptibility testing</td> </tr> <tr> <td colspan="4">Liaise with experts about appropriate treatment</td> </tr> </table>   #### Diagnostic Tools - **TST:** Tuberculin Skin Test. - **IGRA:** Interferon-γ release assay. - **Imaging:** Ultrasound, MRI, CT (useful for major salivary gland TB), and Chest X-ray. - **Laboratory:** Fine needle aspiration cytology, histopathology, microscopy, culture, and molecular assays. #### Diagnostic Pathway 1. **Screening for Latent TB:** - TST (difficult to interpret if previous BCG vaccine). - IGRA (not for children <2 years). - If positive, exclude active TB and follow up. 2. **Suspected Active TB:** - Chest X-ray and 3x sputum samples. - Microscopy and Culture. - Molecular assay and drug susceptibility testing. - Liaise with experts for treatment. A flowchart detailing the diagnostic pathway for tuberculosis, starting with 'Consider TB' and branching based on the presence of symptoms. It outlines testing for latent TB (TST, IGRA) and active TB (Chest X-ray, sputum samples, microscopy, culture, molecular assay, drug susceptibility testing), with a final step to liaise with experts for treatment. A table listing investigations for tuberculosis, including TST, IGRA, fine needle aspiration cytology, histopathology, ultrasound, MRI, and CT, with a note that CT can be used for diagnosing TB of major salivary glands. # Tuberculosis * **Management** * Appropriate antimicrobials * High antibiotic resistance * Adults with TB: * 2 month-long course of combination of isoniazid, rifampin, pyrazinamide, etheambutol * Further 4 month course of combination of isoniazid and rifampicin * Antibiotic susceptibility: isoniazid, rifampin, pyrazinamide * Sputum specimen for acid fast bacilli and culture obtained at monthly intervals #### Antibiotic Therapy - Treatment involves appropriate antimicrobials; high antibiotic resistance is a concern. - **Standard Adult Course:** - **Initial phase (2 months):** Combination of isoniazid, rifampin, pyrazinamide, and ethambutol. - **Continuation phase (4 months):** Combination of isoniazid and rifampicin. #### Monitoring - Sputum specimens for acid-fast bacilli and culture should be obtained at monthly intervals to monitor response. # Tuberculosis **Prevention** * Occupational risk for healthcare workers * Universal Infection control policies * Use of appropriate ventilation, filtration, control of aerosols * Good quality face masks * Notifiable disease * BCG (bacille Calmette-Guérin) vaccine is recommended for: (highest risk for TB) in Australia * Aboriginal and Torres Strait Islander neonates * some healthcare workers * some travelers * some Australian-born children of migrants * young children born to parents with leprosy, or household contacts with leprosy  #### Clinical and Occupational Safety - TB is a notifiable disease. - Occupational risk for healthcare workers requires universal infection control policies. - Use of appropriate ventilation, filtration, aerosol control, and good quality face masks. #### Vaccination (BCG) - The Bacille Calmette-Guérin (BCG) vaccine is recommended for high-risk groups in Australia: - Aboriginal and Torres Strait Islander neonates. - Certain healthcare workers and travelers. - Australian-born children of migrants. - Young children born to parents with leprosy or household contacts of leprosy. A photo showing a vial labeled 'BCG Vaccine Injection only' with a blue cap, surrounded by other similar vials and a stethoscope in the background. This image is associated with the BCG vaccine recommendation for tuberculosis prevention. Recap on Bacterial Infections * 1) What are the stages of acquired syphilis? * 2) What are some manifestations of oral/oropharyngeal gonorrhoea? * 3) What tests are required if you suspect active TB? 1. What are the stages of acquired syphilis? 2. What are some manifestations of oral/oropharyngeal gonorrhoea? 3. What tests are required if you suspect active TB? # **Oral Candidiasis** * **Thrush** * **Candida albicans; opportunistic** * **Colonize mucocutaneous surfaces which can be portals of entry into deeper tissues when host defences are compromised** * **Dimorphic fungus** * **Exists in yeast and hyphal phase** * **Host factors play an important role than organism virulence attributes in pathogenesis of oral candidiasis** * **Imbalance between fungal virulence factors and host defence that gives rise to infection** <img src="image.png" alt="Diagram illustrating the morphology of Candida albicans with labels for Blastospores, Chlamydospore, and Pseudohyphae.">  #### Characteristics of Oral Candidiasis - **Thrush**: Common clinical name. - **Organism**: *Candida albicans*; an opportunistic pathogen. - **Nature**: Dimorphic fungus existing in both yeast and hyphal phases. - **Pathogenesis**: - Colonizes mucocutaneous surfaces; these can serve as portals of entry into deeper tissues when host defenses are compromised. - Infection arises from an imbalance between fungal virulence factors and host defense. - Host factors play a more significant role in pathogenesis than the specific virulence attributes of the organism. A diagram illustrating the morphology of Candida albicans, showing its various forms including blastospores, chlamydospores, and pseudohyphae. The diagram is positioned next to a bulleted list describing oral candidiasis, emphasizing the fungus's dimorphic nature and its role in infection. # **Candidiasis** ## Predisposing factors to oral candidiasis <table> <tr> <td><b>Local predisposing factors</b></td> <td><b>Systemic predisposing factors</b></td> </tr> <tr> <td>Prostheses (changes in environmental conditions, trauma, denture usage, oral hygiene)</td> <td>Physiological (e.g., elderly, pregnancy, infancy)</td> </tr> <tr> <td>Endogenous epithelial changes (atrophy, hyperplasia, dysplasia)</td> <td>Endocrine disorders (e.g., diabetes mellitus)</td> </tr> <tr> <td>Qualitative (pH, glucose concentrations) and quantitative (xerostomia, Sjögren's syndrome, radiotherapy, drug-therapy) salivary changes</td> <td>Nutritional deficiency (e.g., iron, folate, vitamin B12)</td> </tr> <tr> <td>Commensal flora</td> <td>Malignancies (e.g., leukemia, agranulocytosis, others)</td> </tr> <tr> <td>High-carbohydrate diet</td> <td>Primary immunodeficiency (e.g., DiGeorge's syndrome)</td> </tr> <tr> <td>Smoking (?)</td> <td>Secondary immunodeficiency (e.g., HIV disease, corticosteroids, anticancer therapy)</td> </tr> </table>  #### Local Predisposing Factors - **Prostheses**: Changes in environmental conditions, trauma, denture usage, and oral hygiene. - **Epithelial Changes**: Endogenous changes such as atrophy, hyperplasia, and dysplasia. - **Salivary Changes**: - Qualitative: Changes in pH and glucose concentrations. - Quantitative: Xerostomia, Sjögren's syndrome, radiotherapy, and drug therapy. - **Commensal Flora**: Alterations in the balance of oral microorganisms. - **Diet**: High-carbohydrate intake. - **Smoking**: Potential contributing factor. #### Systemic Predisposing Factors - **Physiological**: Factors related to age (elderly, infancy) or pregnancy. - **Endocrine Disorders**: Such as Diabetes Mellitus. - **Nutritional Deficiencies**: Lack of iron, folate, or vitamin B12. - **Malignancies**: Leukemia, agranulocytosis, and other neoplastic diseases. - **Primary Immunodeficiency**: Genetic conditions such as DiGeorge's syndrome. - **Secondary Immunodeficiency**: HIV disease, use of corticosteroids, or anticancer therapy. A table titled "Predisposing factors to oral candidiasis" that lists local and systemic factors contributing to the condition. The table is divided into two columns: "Local predisposing factors" and "Systemic predisposing factors," with examples such as prostheses, endogenous epithelial changes, salivary changes, and commensal flora on the left, and physiological conditions, endocrine disorders, nutritional deficiencies, malignancies, and immunodeficiency on the right. **Table 2 Classification of oral candidosis** <table> <thead> <tr> <td>Primary oral candidosis (Group I)</td> <td>Clinical features</td> <td>Site involved</td> </tr> </thead> <tbody> <tr> <td>Pseudomembranous candidosis (acute and chronic)</td> <td>Semi-adherent, whitish, soft and creamy, drop-like, or confluent patches. They can be removed leading to a red and slightly bleeding surface. The lesions may recur in patients using corticosteroids topically or by aerosol, in HIV-infected patients or in immunocompromised patients</td> <td>Acute form: palate, dorsum of the tongue, buccal mucosa<br>Chronic form: palate, oral pharynx, dorsum of the tongue</td> </tr> <tr> <td>Erythematous candidosis (acute and chronic)</td> <td>Small or large erythematous areas following topical or systemic corticosteroid use, broad-spectrum antibiotic therapy, or HIV disease</td> <td>Dorsum of the tongue, opposing palate surface, rarely buccal mucosa</td> </tr> <tr> <td>Chronic hyperplastic candidosis</td> <td>Small or large erythematous areas following topical or systemic corticosteroid use, broad-spectrum antibiotic therapy, or HIV disease</td> <td>Commissures of the mouth, less commonly on the buccal mucosa, palate, tongue</td> </tr> </tbody> </table>  #### Primary Oral Candidosis (Group I) | Type | Clinical Features | Site Involved | | :--- | :--- | :--- | | **Pseudomembranous candidosis** (acute and chronic) | Semi-adherent, whitish, soft and creamy, drop-like, or confluent patches. Can be removed to reveal a red, slightly bleeding surface. May recur in patients using topical/aerosol corticosteroids, or those with HIV/immunocompromise. | **Acute**: Palate, dorsum of tongue, buccal mucosa. <br>**Chronic**: Palate, oral pharynx, dorsum of tongue. | | **Erythematous candidosis** (acute and chronic) | Small or large erythematous areas following topical or systemic corticosteroid use, broad-spectrum antibiotic therapy, or HIV disease. | Dorsum of the tongue, opposing palate surface, rarely buccal mucosa. | | **Chronic hyperplastic candidosis** | Small or large erythematous areas following topical or systemic corticosteroid use, broad-spectrum antibiotic therapy, or HIV disease. | Commissures of the mouth, less commonly on the buccal mucosa, palate, tongue. | Table 2 classifying primary oral candidosis (Group I) into three types: pseudomembranous candidosis, erythematous candidosis, and chronic hyperplastic candidosis. It details their clinical features and the sites involved in the mouth, such as the palate, tongue, and buccal mucosa. **Pseudomembranous candidiasis** Fig. 1 Pseudomembranous candidosis presenting on the soft palate (a) and tongue (b) in same patient  Pseudomembranous candidosis typically presents as white patches on the oral mucosa. Common clinical presentations include involvement of the soft palate and the tongue within the same patient. The image displays two photographic views of pseudomembranous candidiasis. Panel (a) shows the condition on the soft palate, characterized by white, patchy lesions on a red, inflamed mucosal surface. Panel (b) shows similar white, adherent plaques on the tongue, illustrating the same patient's presentation. Pseudomembranous Candidiasis * **Histopathology** * Hyphae penetrate epithelium up to spinous cell layer * Presence of oedema * Micro-abscesses containing polymorphonuclear leukocytes within outer layers of epithelium * Deeper parts of epithelium show acanthosis and inflammatory infiltrate  #### Microscopic Features of Pseudomembranous Candidiasis - **Fungal Invasion**: Hyphae penetrate the epithelium up to the spinous cell layer. - **Tissue Response**: - Presence of oedema. - Micro-abscesses containing polymorphonuclear leukocytes within the outer layers of the epithelium. - **Deep Epithelial Changes**: Deeper parts of the epithelium show acanthosis and inflammatory infiltrate. Two microscopic images showing histopathological features of pseudomembranous candidiasis. Image (a) displays tissue with hyphae penetrating the epithelium and micro-abscesses containing polymorphonuclear leukocytes. Image (b) highlights the presence of fungal hyphae within the epithelial layers, consistent with the described histopathology. **Erythematous candidiasis** <br> <br> <br> Fig. 3 Erythematous candidiasis of the dorsum of the tongue Fig. 4 Erythematous candidiasis of the palate occurring simultaneously with tongue lesions (kissing lesions)   Erythematous candidiasis often affects the dorsum of the tongue. It may occur simultaneously with lesions on the palate, a presentation sometimes referred to as "kissing lesions." A close-up photo showing erythematous candidiasis on the dorsum of the tongue, characterized by a red, inflamed surface with a slightly raised texture. The image is labeled as Fig. 3. A close-up photo depicting erythematous candidiasis of the palate with a red, inflamed lesion, occurring simultaneously with tongue lesions, referred to as 'kissing lesions.' This image is labeled as Fig. 4. Erythematous Candidiasis * **Histopathology** * Similar to Pseudomembranous Candidiasis * Pseudo hyphae penetrating and extending to superficial layers of epithelium * Inflammatory reaction seen in epithelium and connective tissue #### Microscopic Features of Erythematous Candidiasis - **General Appearance**: Histopathology is similar to Pseudomembranous Candidiasis. - **Fungal Presence**: Pseudo-hyphae penetrate and extend to the superficial layers of the epithelium. - **Inflammation**: Inflammatory reactions are observed in both the epithelium and the underlying connective tissue. # **Chronic hyperplastic candidiasis** **Fig. 5** Chronic hyperplastic candidiasis in the postmodiolus area of the right (a) and left (b) buccal mucosa (same patient)  Chronic hyperplastic candidiasis frequently presents in the postmodiolus area of the buccal mucosa, often appearing bilaterally. A photo showing chronic hyperplastic candidiasis in the postmodiolus area of the right (a) and left (b) buccal mucosa, with white patches and erythematous lesions visible on the mucosal surfaces. Chronic hyperplastic candidiasis **Histopathology** * Parakeratosis * Hyperplastic epithelium * Inflammatory infiltrate * Candida hyphae invasion of upper layers o  #### Microscopic Features of Chronic Hyperplastic Candidiasis - **Epithelial Changes**: Parakeratosis and hyperplastic epithelium. - **Fungal Invasion**: Candida hyphae invade the upper layers of the epithelium. - **Inflammation**: Presence of inflammatory infiltrate. Microscopic image showing histopathological features of chronic hyperplastic candidiasis, including parakeratosis, hyperplastic epithelium, inflammatory infiltrate, and Candida hyphae invasion of the upper layers of the tissue. | **Candida-associated lesions** | Clinical features | Site involved | |---|---|---| | Angular cheilitis | Edema, soreness, burning, and fissuring with a tendency to local bleeding. **Candida spp.** and **Staphylococcus aureus** involved | Angles of the mouth | | Median rhomboid glossitis | Area of papillary atrophy (occasionally hyperplastic, exophytic) elliptical or rhomboid in shape | Midline of the tongue, centrally, anterior to the circumvallate papillae | | Denture-associated erythematous stomatitis | Chronic erythema and edema of the oral mucosa in contact with a denture | Palatal mucosa, the mucosa below the mandibular denture is rarely affected | | Linear gingival erythema | Non-plaque-induced linear erythematous gingival band of 2–3 mm. First described in HIV-infected patients | Localized or diffuse marginal gingivae and attached gingiva | | **Secondary oral candidosis** | Clinical features | Site involved | | Chronic mucocutaneous candidosis | Persistent or recurrent candidal infections of the oral cavity and other sites of the body. Associated with several immunodeficiency disorders | Infections of the oral cavity (90%), possibly the larynx and pharynx. Cutaneous and vulvovaginal involvement is frequent |  #### Clinical Classification of Associated and Secondary Lesions | Condition | Clinical Features | Site Involved | | :--- | :--- | :--- | | **Angular cheilitis** | Edema, soreness, burning, and fissuring with a tendency to local bleeding. Involves *Candida spp.* and *Staphylococcus aureus*. | Angles of the mouth | | **Median rhomboid glossitis** | Area of papillary atrophy (occasionally hyperplastic/exophytic) elliptical or rhomboid in shape. | Midline of the tongue, anterior to the circumvallate papillae | | **Denture-associated erythematous stomatitis** | Chronic erythema and edema of the oral mucosa in contact with a denture. | Palatal mucosa (mandibular mucosa is rarely affected) | | **Linear gingival erythema** | Non-plaque-induced linear erythematous gingival band (2–3 mm). Associated with HIV. | Marginal and attached gingiva | | **Secondary Oral Candidosis (Chronic mucocutaneous candidosis)** | Persistent or recurrent infections of the oral cavity and other body sites. Associated with immunodeficiency. | Oral cavity (90%), larynx, pharynx, skin, and vulvovaginal areas | A table detailing Candida-associated lesions, listing their clinical features and the sites involved. The table includes conditions such as angular cheilitis, median rhomboid glossitis, denture-associated erythematous stomatitis, linear gingival erythema, and chronic mucocutaneous candidosis, with descriptions of symptoms and affected areas. **Angular Cheilitis**  Angular cheilitis is characterized by inflammation and cracking at the corners of the mouth, often involving a co-infection of fungal and bacterial agents. A close-up clinical photograph showing a patient's mouth with angular cheilitis, characterized by red, inflamed, and cracked skin at the corners of the lips. The image is labeled 'Angular Cheilitis' above the photo. # **Median Rhomboid Glossitis**  Median rhomboid glossitis presents as a distinct, often asymptomatic, rhomboid-shaped lesion on the central dorsum of the tongue. A close-up clinical photograph showing median rhomboid glossitis, characterized by a reddish, smooth, and slightly raised lesion on the dorsal surface of the tongue, located near the midline. The surrounding tongue tissue appears textured with normal papillae, highlighting the contrast between the affected and unaffected areas. Denture-Associated Erythematous Stomatitis <br> <br>   Denture-associated erythematous stomatitis is a chronic inflammatory condition restricted to the mucosa covered by a dental prosthesis, most commonly the palate. Close-up photo showing red, inflamed mucosa of the oral cavity with scattered erythematous patches, labeled as 'a', indicative of denture-associated erythematous stomatitis. Close-up photo showing a red, inflamed area on the oral mucosa with a denture base visible, labeled as 'b', demonstrating the condition of denture-associated erythematous stomatitis. Linear Gingival Erythema  Linear gingival erythema is a distinctive gingival manifestation often seen in immunocompromised patients, appearing as a bright red band along the gum line. A close-up clinical photograph showing a case of Linear Gingival Erythema, characterized by a band of bright red, inflamed gingival tissue along the gumline, with adjacent teeth appearing discolored and slightly worn. The image is labeled 'Linear Gingival Erythema' above it. **Oral Candidiasis** * **Investigations** * Several clinical and laboratory techniques used to confirm provisional diagnosis * Presence of candida hyphae confirmed with Periodic Acid-Shiff Staining of cytology smear of pseudomembrane * Cultures of swabs taken from mucosal tissues and under surface of denture useful in erythematous candidosis * Quantitative determination of fungal burden also marker of infection * Infected individual counts range from 4,000 to 20,000 CFU/ml * Haematologic investigations to check for underlying immunosuppression, or nutritional deficiencies #### Clinical and Laboratory Investigations - **Cytology**: Periodic Acid-Schiff (PAS) staining of a smear from the pseudomembrane to confirm the presence of Candida hyphae. - **Cultures**: Swabs from mucosal tissues or the fitting surface of dentures are particularly useful for diagnosing erythematous candidosis. - **Quantitative Analysis**: Determination of fungal burden (CFU/ml). - Infected individuals typically show counts ranging from 4,000 to 20,000 CFU/ml. - **Systemic Screening**: Haematologic investigations to identify underlying immunosuppression or nutritional deficiencies (e.g., anemia). **DIAGNOSIS OF ORAL CANDIDIASIS** $\downarrow$ **1. CLINICAL diagnosis** $\longrightarrow$ **Hyperplastic candidiasis** $\downarrow$ **2. MICROBIOLOGICAL diagnosis: ORAL SAMPLE** $\longrightarrow$ **BIOPSY** $\begin{cases} \text{Microscopic examination} \\ \begin{cases} \text{- Fresh sample (10% KOH)} \\ \text{- Smear or imprint (with} \\ \text{conventional or rapid stains)} \end{cases} & \begin{cases} \text{Fungal culture (macroscopic)} \\ \begin{cases} \text{Sabouraud dextrose agar} \\ \text{+} \\ \text{(chloramphenicol / gentamycin)} \end{cases} \end{cases} \end{cases}$ $\swarrow$ $\quad$ $\searrow$ **Isolation of the genus *Candida*** $\longrightarrow$ **Species identification** $\downarrow$ **Early filamentation or germ tube test** $\downarrow$ **Production of germ tubes** **and chlamydoconidia** $\downarrow$ **Yes (+)** $\quad$ $\swarrow$ $\quad$ **No (-)** $\begin{cases} \text{Candida albicans} \\ \text{Candida dubliniensis} \\ \downarrow \\ \text{Differentiation:} \\ \text{- Immunological methods} \\ \text{- Genetic methods} \end{cases}$ $\quad$ $\begin{cases} \textbf{Identification of other species of Candida:} \\ \textbf{Biochemical methods:} \\ \text{- Nutrient assimilation tests} \\ \text{- Enzymatic tests} \\ \underline{\text{Immunological methods}} \\ \underline{\text{Genetic methods}} \end{cases}$  #### Diagnostic Pathway 1. **Clinical Diagnosis**: Direct identification (e.g., Hyperplastic candidiasis). 2. **Microbiological Diagnosis (Oral Sample)**: - **Microscopic Examination**: - Fresh samples using 10% KOH. - Smears or imprints using conventional or rapid stains. - **Fungal Culture**: - Use of Sabouraud dextrose agar supplemented with chloramphenicol or gentamycin. 3. **Species Identification**: - **Isolation of Genus *Candida***. - **Germ Tube Test**: Early filamentation test. - **Positive (+)**: *Candida albicans* or *Candida dubliniensis* (differentiated via immunological or genetic methods). - **Negative (-)**: Identification of other *Candida* species using biochemical methods (nutrient assimilation, enzymatic tests), immunological methods, or genetic methods. 4. **Biopsy**: Indicated for specific cases like hyperplastic candidiasis. A flowchart titled 'DIAGNOSIS OF ORAL CANDIDIASIS' that outlines the diagnostic process, starting with clinical diagnosis and progressing to microbiological diagnosis using oral samples. The diagram details steps including microscopic examination, fungal culture, isolation of Candida, species identification, and differentiation methods such as germ tube tests, biochemical tests, immunological methods, and genetic methods. # **Oral Candidiasis** * **Management** * Identify and correct underlying predisposing factors – e.g. underlying anaemia * Pharmacologic treatment should be started * Determined by immunological status of patient * Polylenes: nystatin, amphotericin B) * Azoles: miconazole, clotrimazole, ketoconazole, itraconazole, fluconazole) * Echnocandins: caspofungin, micafungin, anidulafungin * Adjunctive chlorhexidine #### Treatment Strategies - **Address Underlying Causes**: Identify and correct predisposing factors, such as underlying anaemia. - **Pharmacologic Treatment**: Selection is determined by the patient's immunological status. - **Polyenes**: Nystatin, Amphotericin B. - **Azoles**: Miconazole, Clotrimazole, Ketoconazole, Itraconazole, Fluconazole. - **Echinocandins**: Caspofungin, Micafungin, Anidulafungin. - **Adjunctive Therapy**: Use of chlorhexidine mouthwashes. # **Oral Candidiasis** | Antifungalagent | Form | Dosage | |---|---|---| | Amphotericin B | Lozenge, 10 mg | Slowly dissolved in the mouth 3–4 times a day after meals for 2 weeks | | | Oral suspension, 100 mg/ml | Placed in the mouth after meal and retained near lesions 4 times daily for 2 weeks | | Nystatin | Pastille, 100,000 units | Dissolve 1 pastille slowly after meals 4 times daily, usually for 7 days | | | Oral suspension, 100,000 units | Apply after meals 4–5 times daily, usually for 15 days, and continue use for several days after post-clinical healing | | Clotrimazole | Cream | Apply to affected area 2–3 times daily for 3–4 weeks | | | Solution | 5 ml 3–4 times daily for at least 2 weeks | | Miconazole | Oral gel | Apply to affected area 3–4 times daily for 3–4 weeks | | | Cream | Apply twice per day and continue for 10–14 days after post-clinical healing | | | Muco-adhesive buccal tablets, 50 mg | Apply on the upper gum once a day for 7–14 days | | Ketoconazole | Tablets | 200–400 mg tablets taken once or twice daily with food for 2 weeks | | Fluconazole | Capsules | 50–200 mg capsules once daily for 2–3 weeks | | | Oral suspension | 200 mg once on the first day, then 100 mg for at least 2 weeks | | Itraconazole | Capsules | 100 mg capsule once daily taken after meals for 2 weeks | **CHECK FOR DRUG INTERACTIONS**  #### Antifungal Dosage and Administration | Agent | Form | Dosage | | :--- | :--- | :--- | | **Amphotericin B** | Lozenge (10 mg) | Dissolve in mouth 3–4 times daily after meals for 2 weeks. | | | Oral suspension (100 mg/ml) | Retain near lesions 4 times daily after meals for 2 weeks. | | **Nystatin** | Pastille (100,000 units) | Dissolve 1 pastille 4 times daily after meals for 7 days. | | | Oral suspension (100,000 units) | Apply 4–5 times daily after meals for 15 days; continue for several days after healing. | | **Clotrimazole** | Cream | Apply to affected area 2–3 times daily for 3–4 weeks. | | | Solution | 5 ml 3–4 times daily for at least 2 weeks. | | **Miconazole** | Oral gel | Apply to affected area 3–4 times daily for 3–4 weeks. | | | Cream | Apply twice daily; continue 10–14 days after clinical healing. | | | Muco-adhesive tablet (50 mg) | Apply to upper gum once daily for 7–14 days. | | **Ketoconazole** | Tablets (200–400 mg) | Once or twice daily with food for 2 weeks. | | **Fluconazole** | Capsules (50–200 mg) | Once daily for 2–3 weeks. | | | Oral suspension | 200 mg on day one, then 100 mg for at least 2 weeks. | | **Itraconazole** | Capsules (100 mg) | Once daily after meals for 2 weeks. | **Note**: Always check for drug interactions before prescribing. A table detailing antifungal agents for oral candidiasis, listing the antifungal agent, form, and dosage. The table includes agents such as Amphotericin B, Nystatin, Clotrimazole, Miconazole, Ketoconazole, Fluconazole, and Itraconazole, with specific forms like lozenges, suspensions, creams, and capsules, along with their respective dosages and treatment durations. The table is structured with three columns: Antifungal agent, Form, and Dosage. Oral Candidiasis - **Management** - Avoid nocturnal use of denture - Clean them, keep them in **DRY** environment - Mechanical cleaning with soft toothbrush and soap 2/day effective to remove biofilm from denture material - Twice weekly soaking in white vinegar (diluted 1:20) or 0.1% hypochlorite (diluted 1: 10) or chlorhexidine - If appropriate, miconazole gel application to denture bearing surface – 4/day for 4 weeks #### Denture Hygiene and Maintenance - **Usage**: Avoid wearing dentures overnight (nocturnal use). - **Storage**: Keep dentures in a **DRY** environment when not in use. - **Mechanical Cleaning**: Use a soft toothbrush and soap twice daily to remove biofilm. - **Disinfection**: Soak twice weekly in one of the following: - White vinegar (diluted 1:20). - 0.1% Hypochlorite (diluted 1:10). - Chlorhexidine solution. - **Topical Treatment**: If appropriate, apply miconazole gel to the denture-bearing surface 4 times daily for 4 weeks. # **Recap on Oral Candidiasis** * **1) Name some predisposing factors that increase chances of candidiasis?** * **2) Are there any special considerations needed for a patient who presents with pseudomembranous candidiasis?** * **3) What investigations would you request for persistent angular cheilitis?** #### Review Questions 1. Name some predisposing factors that increase the chances of candidiasis. 2. Are there any special considerations needed for a patient who presents with pseudomembranous candidiasis? 3. What investigations would you request for persistent angular cheilitis? Questions Further Reading: Contemporary Oral Medicine Textbook **lalima.tiwari@uwa.edu.au** #### Review and Study Resources - **Questions**: Review the core concepts regarding viral, bacterial, and fungal infections of the oral cavity to test your understanding of clinical presentations and diagnostic features. - **Further Reading**: For in-depth study and comprehensive details, refer to the *Contemporary Oral Medicine* textbook. #### Contact Information For further inquiries or academic support, please contact: - **Lalima Tiwari**: lalima.tiwari@uwa.edu.au [^1]: Original PDF page 1: [[L5 Bacterial, Fungal and Viral Infections_slides.pdf#page=1|L5 Bacterial, Fungal and Viral Infections slides, p.1]] [^2]: Original PDF page 2: [[L5 Bacterial, Fungal and Viral Infections_slides.pdf#page=2|L5 Bacterial, Fungal and Viral Infections slides, p.2]] [^3]: Original PDF page 3: [[L5 Bacterial, Fungal and Viral Infections_slides.pdf#page=3|L5 Bacterial, Fungal and Viral Infections slides, p.3]] 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