Medicine-Infectious Diseases

Syphilis: comprehensive clinical diagnosis and management Syphilis is a chronic, systemic infection caused by the motile spirochaete Treponema pallidum. It spreads mainly through sexual contact with an infectious lesion and crosses the placenta. The disease evolves through primary, secondary, latent and tertiary stages, but stages can overlap and neurosyphilis or ocular disease may occur at any time. A painless ulcer that has healed does not exclude infection. Every patient with syphilis needs HIV testing, a sexual-exposure history, neurological/ocular review, pregnancy assessment where relevant, and a plan for partner notification. Learning objectives Recognise the stages and infectiousness of syphilis. Interpret treponemal and non-treponemal tests, including titre changes after treatment. Diagnose and manage neurosyphilis, ocular/otosyphilis and congenital syphilis. Choose stage-appropriate penicillin treatment and manage allergy, pregnancy and follow-up. Prevent reinfection through partner management, safer sex and antenatal screening. Organism, transmission and pathogenesis T. pallidum enters through microscopic breaks in skin or mucosa. It multiplies locally, spreads through lymphatics and blood, and can persist in tissues for decades. Infectiousness is highest during primary and secondary disease and early latent infection. Transmission occurs through vaginal, anal or oral sex, direct contact with mucous patches or condylomata lata, and vertically across the placenta. Fomites are not an important route because the organism is fragile outside the body. Stage Key findings Infectiousness Primary Solitary or multiple chancre with regional nodes High at lesion Secondary Generalised rash, mucous patches, condylomata lata, systemic symptoms Very high Early latent No symptoms, infection acquired recently Meaningful sexual/vertical risk Late latent Asymptomatic infection of longer duration Low sexual risk, ongoing fetal risk Tertiary Gummas, cardiovascular disease, neurosyphilis Usually not sexually infectious Clinical stages Primary syphilis After an incubation of roughly 10–90 days, a chancre appears at the inoculation site: classically painless, indurated and clean-based, with non-tender regional lymphadenopathy. Rectal, cervical, oral or vaginal chancres may be hidden or mistaken for trauma, herpes or malignancy. It heals spontaneously in two to six weeks without eradication of infection. Secondary syphilis Haematogenous dissemination produces fever, malaise, headache, generalised lymphadenopathy and a diffuse rash that characteristically involves palms and soles but may be subtle in dark skin. Mucous patches, broad moist condylomata lata, patchy alopecia, hepatitis, nephritis, uveitis and meningitis can occur. Symptoms may relapse if untreated. Latent syphilis There are no clinical signs, but serology remains positive. Classify as early or late using documented symptoms, previous negative testing or a credible recent exposure; if timing is uncertain, manage as late latent/unknown duration. Tertiary and late complications Gummatous disease causes destructive granulomas in skin, bone or viscera. Cardiovascular disease includes aortitis, aneurysm and aortic-valve insufficiency. Neurosyphilis can cause meningitis, meningovascular stroke, tabes dorsalis, general paresis, sensory ataxia and psychiatric/cognitive change. Neurosyphilis, ocular and otic disease Suspect neurosyphilis with cranial-nerve palsy, meningitis, stroke in a young adult, altered cognition, sensory ataxia, lightning pains or unexplained psychiatric change. Ocular syphilis causes uveitis, retinitis, optic neuritis or vision loss; otosyphilis causes tinnitus, vertigo or sensorineural hearing loss. These are treated as neurosyphilis, with urgent ophthalmology or ENT input. Do not delay treatment while awaiting cerebrospinal-fluid results when sight or hearing is threatened. History and examination Ask about ulcers, rash, mucous lesions, hair loss, visual/hearing symptoms, headache, neuropathy and previous treatment. Record all sexual sites and partners, condom use, gender of partners, recent STI, HIV/PrEP status and exposure timing. Examine skin including palms/soles, mouth, genital/perianal area, lymph nodes, eyes, cranial nerves, gait, reflexes and cognition. Determine pregnancy status and assess newborn risk if pregnant. Diagnosis Use both a non-treponemal test (RPR or VDRL) and a treponemal test (TPPA/TPHA or EIA/CLIA). One test alone is insufficient for staging and treatment decisions. RPR/VDRL titres reflect activity and are used for follow-up; treponemal tests usually remain positive for life. Dark-field microscopy or lesion PCR, where available, can confirm early disease but a negative result does not exclude it. Perform lumbar puncture when neurological signs, ocular/otic disease, tertiary disease or treatment failure raises concern; interpret CSF cell count, protein and CSF-VDRL with serum results. Test for HIV and other STIs, check pregnancy, and evaluate hepatitis or renal disease when clinically indicated. Do not use a falling or negative RPR as proof of cure without clinical context: a fourfold titre decline is meaningful, but some patients remain serofast and others are reinfected. Differential diagnosis Genital herpes, chancroid, lymphogranuloma venereum, donovanosis, traumatic ulcer, aphthosis, drug eruption, pityriasis rosea, psoriasis, viral exanthem, HIV-associated disease, autoimmune vasculitis and malignancy. Management Primary, secondary or early latent Benzathine penicillin G intramuscularly as the recommended single-dose regimen in current national guidance. Use the appropriate local formulation and needle technique. Late latent or unknown duration Benzathine penicillin G intramuscularly in three weekly doses. If a dose is substantially delayed, restart according to guideline; document every dose. Neurosyphilis/ocular/otic disease Use an aqueous crystalline penicillin G intravenous regimen for the recommended duration, followed by specialist-directed follow-up. Ocular disease requires urgent ophthalmology; do not substitute routine benzathine penicillin alone. Penicillin allergy In non-pregnant patients with confirmed early disease, a guideline-approved alternative may be used only when neurosyphilis is excluded. Penicillin desensitisation is required in pregnancy and for neurosyphilis. Pregnancy and congenital syphilis Penicillin is the only proven treatment that prevents congenital syphilis. Screen at the first antenatal visit and repeat later in pregnancy or at delivery according to national policy and risk. Treat promptly; do not wait for a partner. Ultrasound may show fetal anaemia, hepatomegaly, placentomegaly or hydrops, but a normal scan does not exclude fetal infection. Evaluate exposed infants with paediatrics, including examination, quantitative serology and treatment based on maternal stage, treatment timing and infant findings. Jarisch–Herxheimer reaction Within 24 hours of therapy, fever, chills, myalgia, headache or transient rash may occur due to cytokine release. It is not penicillin allergy. Provide fluids, antipyretics and observation. In pregnancy it may precipitate contractions or fetal distress; treat syphilis promptly and monitor obstetrically rather than withholding therapy. Follow-up and partner management Repeat quantitative RPR/VDRL at guideline-defined intervals; compare using the same test and laboratory where possible. Assess for a fourfold titre decline, persistent

Gonorrhoea: comprehensive diagnosis, treatment and prevention Gonorrhoea is caused by Neisseria gonorrhoeae, a gram-negative diplococcus that infects columnar epithelium of the urethra, cervix, rectum, pharynx and conjunctiva. It may be asymptomatic—especially in women, pharyngeal infection and rectal infection—yet still transmit and cause pelvic inflammatory disease, infertility, ectopic pregnancy, neonatal blindness and disseminated infection. Take specimens from every exposed site before antibiotics when possible, treat promptly, test for chlamydia/HIV/syphilis, and plan partner treatment and test-of-cure. Learning objectives Recognise the site-specific clinical syndromes and complications of gonorrhoea. Choose NAAT, microscopy and culture appropriately, including for antimicrobial-resistance surveillance. Apply current ceftriaxone-based treatment while adapting to local Uganda guidelines and susceptibility data. Manage pregnancy, disseminated infection, pelvic inflammatory disease, epididymo-orchitis and neonatal disease. Prevent reinfection through partner services, abstinence during treatment and retesting. Organism, transmission and resistance Transmission occurs through vaginal, anal or oral sex and from an infected mother to the newborn. The organism attaches to mucosa using pili and opacity proteins, invades epithelial cells and provokes neutrophilic inflammation. It rapidly acquires resistance through mutation and horizontal gene transfer; treatment must follow current national recommendations and local resistance surveillance. A previous infection does not confer reliable immunity. Site Common features Important complications Urethra Dysuria, purulent discharge, meatal erythema Epididymo-orchitis, urethral stricture Cervix Often silent; discharge, postcoital/intermenstrual bleeding, pelvic pain PID, infertility, ectopic pregnancy Rectum Discharge, pain, tenesmus or asymptomatic Proctitis and transmission Pharynx Usually asymptomatic; sore throat occasionally Persistent infection, treatment failure Eye/blood Severe conjunctivitis or fever, rash, arthritis Corneal ulceration, blindness, septic arthritis Clinical presentation Urogenital infection Men commonly present with urethral discharge and dysuria after a short incubation. Women may have increased vaginal discharge, dysuria, lower abdominal pain, postcoital bleeding or no symptoms at all. Cervicitis is suggested by mucopurulent endocervical discharge or easy bleeding on swabbing. Rectal and pharyngeal disease Rectal infection may cause anorectal pain, pruritus, tenesmus, bleeding or discharge. Pharyngeal infection is often silent; sore throat and cervical nodes are non-specific. Ask about oral and anal exposure rather than relying on symptoms. Pelvic inflammatory disease Lower abdominal pain with cervical-motion, uterine or adnexal tenderness is PID until proven otherwise. Fever, tubo-ovarian abscess or peritonism requires urgent escalation. Gonorrhoea may coexist with chlamydia and anaerobic infection. Disseminated gonococcal infection Fever, migratory polyarthralgia, tenosynovitis, pustular lesions and asymmetric septic arthritis suggest dissemination. Endocarditis and meningitis are rare but life-threatening. Neonatal infection Severe purulent conjunctivitis in the first weeks of life can rapidly ulcerate the cornea. Neonates may also develop sepsis, arthritis or meningitis. History and examination Clarify symptoms, onset, all exposed sites, last sexual contact, condom use and partner symptoms. Ask about previous STI, antibiotics, allergies, pregnancy, HIV/PrEP, immunosuppression and violence or safeguarding concerns. Examine urethra, cervix, vagina, anus, pharynx, eyes, joints, skin and epididymis as indicated. In a patient with pelvic pain, assess for PID, pregnancy and surgical abdomen; in a febrile patient inspect joints and skin for dissemination. Diagnosis NAAT on first-void urine or genital swab is highly sensitive; collect rectal and pharyngeal swabs when exposed. Culture with antimicrobial susceptibility testing is essential for treatment failure, pharyngeal infection where feasible, disseminated disease, medico-legal cases and resistance surveillance. Gram-stained urethral discharge showing intracellular gram-negative diplococci supports diagnosis in symptomatic men but is less sensitive in cervix, pharynx and rectum. Test for chlamydia, syphilis and HIV; pregnancy-test patients who could be pregnant. Blood cultures and synovial-fluid culture/PCR are required when disseminated infection or septic arthritis is suspected. A negative urine test does not exclude extragenital disease: specimen selection must match sexual exposure. Pharyngeal infection is a frequent reservoir for reinfection and resistance. Differential diagnosis Chlamydia, Mycoplasma genitalium, trichomoniasis, candidiasis, bacterial vaginosis, genital herpes, chemical urethritis, urinary tract infection, PID from other organisms, reactive arthritis and septic arthritis. Management Uncomplicated infection Give the current recommended ceftriaxone regimen according to Uganda guidance, weight and site. If chlamydia has not been excluded, add the recommended chlamydia treatment. Check allergy, pregnancy and renal/hepatic considerations. Pharyngeal infection Use the guideline-preferred ceftriaxone dose and arrange test-of-cure because eradication is less reliable. Culture and susceptibility testing are particularly valuable when symptoms persist. PID or epididymo-orchitis Use a combination regimen covering gonorrhoea, chlamydia and anaerobes according to syndrome-specific national guidance. Treat promptly; admit for severe illness, pregnancy, tubo-ovarian abscess or inability to tolerate oral therapy. Disseminated disease Hospitalise for parenteral ceftriaxone, blood/joint cultures, joint drainage where needed and evaluation for endocarditis or meningitis. Continue treatment for the recommended duration after clinical improvement. Partner management and public health Notify and evaluate sexual partners within the guideline-defined exposure window; presumptive treatment is often appropriate. Advise no sex until at least seven days after treatment is completed and partners have been treated, following current national guidance. Retest around three months because reinfection is common; repeat sooner if symptoms persist. Use condoms, reduce overlapping partners and offer HIV prevention (testing, PrEP/PEP assessment) where appropriate. Do not share antibiotics or use leftover medication: incomplete exposure drives resistance. Pregnancy and neonatal prevention Screen and treat during pregnancy using the recommended ceftriaxone regimen; avoid contraindicated alternatives. Ensure partner treatment and document cure when indicated. At delivery, examine infants carefully and provide national prophylaxis for neonatal ophthalmia. A newborn with purulent conjunctivitis needs urgent ocular swabs, systemic treatment and specialist care—topical drops alone are inadequate. Treatment failure and antimicrobial resistance Consider failure when symptoms persist beyond expected recovery, NAAT remains positive at the test-of-cure interval, or reinfection is unlikely. Reassess adherence, new exposure and specimen site; obtain culture and susceptibility testing before retreatment if feasible. Consult STI/microbiology specialists and notify public-health surveillance of suspected resistant strains. Exam pearls Many women and most pharyngeal infections are asymptomatic. Take specimens from all exposed anatomic sites. Purulent neonatal conjunctivitis is an emergency because corneal destruction can be rapid. Disseminated infection classically combines tenosynovitis, migratory arthralgia and pustular skin lesions. Always test for chlamydia, HIV and syphilis, and actively manage partners. References SlideShare: Gonorrhea. Uganda Clinical Guidelines: Gonorrhoea. WHO and current antimicrobial-resistance guidance. Safety note: Verify the current Uganda ceftriaxone dose, test-of-cure timing and resistance recommendations before prescribing.

Candidiasis: vulvovaginal, balanitis and sexually associated disease Candidiasis is caused by overgrowth of Candida yeasts, most often C. albicans. Vulvovaginal candidiasis (VVC) is usually endogenous rather than a classic sexually transmitted infection, but sexual activity can contribute to irritation and occasional transmission. Recurrent or complicated disease requires confirmation because bacterial vaginosis, trichomoniasis, dermatitis, herpes and diabetes can look similar. Invasive candidiasis is a separate, life-threatening illness seen mainly in hospitalised or immunocompromised patients. Do not diagnose VVC from itch alone: examine, test the discharge when possible, identify non-albicans species and look for diabetes, antibiotics, pregnancy or immunosuppression. Learning objectives Distinguish uncomplicated, severe, recurrent, complicated and non-albicans VVC. Recognise male balanitis, oral disease and invasive candidiasis. Use pH, microscopy, culture/NAAT and clinical findings to establish diagnosis. Select safe treatment in pregnancy, diabetes, HIV and recurrent disease. Counsel patients about partner care, hygiene, recurrence prevention and when to refer. Organism and predisposition Candida is part of normal mucosal flora in many people. Disease follows altered vaginal ecology, increased oestrogen, antibiotic exposure, diabetes, pregnancy, HIV or immunosuppression. Most VVC is C. albicans; C. glabrata and other non-albicans species are less susceptible to standard azoles and are common in recurrent disease. VVC is not proof of partner infidelity or poor hygiene. Pattern Definition/setting Clinical implication Uncomplicated VVC Infrequent, mild–moderate, likely C. albicans, immunocompetent Short topical or oral azole regimen Severe VVC Marked erythema, oedema, fissures or excoriations Longer topical course or repeat oral therapy Recurrent VVC At least three symptomatic episodes in a year Culture/speciation and induction plus maintenance plan Complicated/non-albicans Pregnancy, diabetes, HIV, immunosuppression or resistant species Confirm diagnosis and specialist-directed treatment Clinical features Vulvovaginal candidiasis Intense vulval itch, soreness, burning, dyspareunia, dysuria from external inflammation and thick white, usually non-offensive discharge are typical. Examination may show erythema, oedema, excoriations and fissures. The discharge is not always clumpy, and absence of odour does not prove candidiasis. Male candidal balanitis Itching, burning, erythematous glans, small papules, moist patches and fissuring may occur, particularly with diabetes, antibiotics or a partner with symptoms. Recurrent balanitis warrants diabetes testing and assessment for phimosis or dermatoses. Oral and oesophageal disease Creamy plaques that scrape away leaving an erythematous base, angular cheilitis, sore mouth or odynophagia suggest mucosal candidiasis. Oesophageal symptoms require systemic therapy and assessment for HIV or other immunosuppression. Invasive candidiasis Persistent fever or sepsis, central-line exposure, abdominal surgery, neutropenia or prolonged antibiotics raise concern for candidemia. This is not managed with topical vaginal medication. History and examination Ask about onset, recurrence count, pregnancy, menstrual relation, antibiotics, diabetes, HIV, steroids, contraception and prior treatments. Clarify odour, colour, pelvic pain, fever, bleeding, urinary symptoms, dyspareunia and STI exposure. Inspect vulva, vagina, cervix, penis and oral mucosa; assess for ulcers, vesicles, cervical motion tenderness or dermatoses. Check glucose/HbA1c, HIV status and medication interactions when disease is recurrent or complicated. Diagnosis Vaginal pH is usually normal (<4.5) in VVC; a higher pH suggests bacterial vaginosis or trichomoniasis, though mixed infection can occur. Wet mount with saline and KOH may show budding yeast or pseudohyphae; a negative microscopy does not exclude disease. Culture or validated NAAT is recommended for recurrent, severe, persistent or non-albicans disease and before prolonged suppression. Do not treat asymptomatic colonisation except in specific specialist situations; a positive culture must match symptoms and examination. Consider gonorrhoea, chlamydia, trichomoniasis, bacterial vaginosis, genital herpes, contact dermatitis, lichen sclerosus and desquamative inflammatory vaginitis. Repeated empiric over-the-counter azoles can delay the correct diagnosis: persistent symptoms need examination and laboratory confirmation, not endless self-treatment. Management Uncomplicated VVC Use a recommended topical azole course or single-dose oral fluconazole where appropriate and not contraindicated. Explain correct intravaginal application and that creams may weaken latex condoms/diaphragms temporarily. Pregnancy Use only topical azoles for the recommended longer course. Avoid oral fluconazole in pregnancy unless a specialist specifically directs otherwise. Examine persistent symptoms rather than repeatedly treating empirically. Severe VVC Use a longer topical azole regimen or repeat dosing under current guideline. Assess for fissures, oedema, diabetes and mixed infection; review if symptoms do not improve. Recurrent VVC Obtain culture/speciation, address diabetes or antibiotic exposure, then use guideline-based induction followed by suppressive therapy for the recommended duration. Recurrence after stopping suppression is common and requires reassessment. Non-albicans Candida Exclude other causes and use a longer non-fluconazole azole regimen or specialist-directed alternative. Avoid repeated fluconazole when susceptibility is unlikely; refractory disease merits specialist input. Partner care and sexual health Routine treatment of an asymptomatic male partner is not recommended for uncomplicated VVC. Symptomatic balanitis should be examined and treated with appropriate topical therapy, while recurrent couple-associated symptoms may justify assessment of both partners. Advise abstinence or condoms until pain and inflammation settle. Screen for other STIs when history or examination indicates risk; candidiasis alone does not establish an STI. Prevention and self-care Avoid unnecessary antibiotics and scented vaginal products, douching and harsh soaps. Keep the area dry, use breathable underwear and change out of wet clothing. Optimise glycaemic control and HIV treatment; do not rely on probiotics as a substitute for therapy. Explain medication adherence and avoid stopping treatment as soon as itch improves in recurrent disease. Seek review for fever, pelvic pain, ulcers, pregnancy, recurrent episodes or failure after treatment. When candidiasis is not the answer Fishy odour, thin grey discharge and clue cells suggest bacterial vaginosis. Frothy yellow-green discharge and strawberry cervix suggest trichomoniasis. Vesicles or painful ulcers suggest herpes. Cervical motion tenderness, fever or lower abdominal pain raises PID. Vulval fissures, white plaques or architectural change may indicate dermatosis and require specialist assessment. Invasive candidiasis red flags Hospitalised patients with fever or shock, central venous catheters, recent abdominal surgery, neutropenia, renal replacement therapy or persistent candidemia require blood cultures, source control, systemic antifungal treatment and evaluation for metastatic infection. Obtain ophthalmic and cardiac assessments according to current local protocol. Vaginal treatment is never adequate for candidemia. Exam pearls VVC usually has normal vaginal pH; BV and trichomoniasis usually raise it. Recurrent VVC requires culture/speciation and evaluation for diabetes or immunosuppression. Topical azoles are preferred in

Intestinal nematodes: an integrated clinical approach Intestinal nematodes are roundworms that live in or pass through the gastrointestinal tract. They include Ascaris lumbricoides, hookworms (Necator americanus and Ancylostoma duodenale), Trichuris trichiura, Strongyloides stercoralis, and Enterobius vermicularis. Disease ranges from asymptomatic infection to anaemia, malnutrition, intestinal obstruction, rectal prolapse and fatal hyperinfection in immunosuppressed patients. Always ask about soil exposure, sanitation, footwear, household clustering, eosinophilia, anaemia and corticosteroid or transplant treatment. Learning objectives Identify the major intestinal nematodes by transmission route, morphology and life cycle. Link worm burden and tissue migration to the patient’s symptoms and complications. Select and interpret stool microscopy, concentration, culture, tape tests, serology and blood counts. Choose appropriate anthelmintic treatment, repeat dosing, contact management and follow-up. Recognise obstruction, severe anaemia and Strongyloides hyperinfection as emergencies. Classification and transmission Parasite Main acquisition Typical disease Ascaris Ingestion of embryonated eggs from contaminated soil, food or hands Abdominal symptoms, malnutrition, biliary/pancreatic migration, obstruction Hookworm Larvae penetrate bare skin, migrate through lungs and mature in small bowel Iron-deficiency anaemia, protein loss, abdominal pain Trichuris Ingestion of embryonated eggs Colitis, diarrhoea, growth failure, rectal prolapse Strongyloides Skin penetration; autoinfection permits lifelong persistence Larva currens, abdominal disease, hyperinfection Enterobius Ingestion/inhalation of eggs; hand-to-mouth autoinfection Nocturnal perianal pruritus, vulvovaginitis Life cycles and pathophysiology Ascaris Eggs embryonate in warm moist soil. After ingestion, larvae hatch in the intestine, cross the mucosa, travel via portal circulation to the liver and then lungs, ascend the trachea, are swallowed and mature in the jejunum. Adult worms consume little host nutrition but compete for micronutrients, form boluses and migrate into the biliary tree or pancreatic duct. Hookworms Filariform larvae penetrate skin, enter blood, pass through lungs and are swallowed. Adults attach to duodenal and jejunal mucosa and feed on blood. Ongoing mucosal bleeding causes iron deficiency; A. duodenale may also cause substantial blood loss during tissue dormancy. Trichuris Eggs mature in soil and hatch after ingestion. Adults embed their thin anterior ends in colonic mucosa. Heavy infection produces epithelial inflammation, blood loss, protein-losing enteropathy and impaired growth. Strongyloides Parthenogenetic adult females in the mucosa produce larvae. Some pass in stool; others penetrate colonic mucosa or perianal skin and restart infection. Corticosteroids, HTLV-1, transplantation and severe immunosuppression accelerate autoinfection, causing thousands of migrating larvae and Gram-negative sepsis. Risk factors and epidemiology Open defecation, contaminated soil or vegetables and unsafe water. Walking barefoot or occupational soil contact. Crowded households and inadequate hand hygiene, particularly for pinworm. Children, pregnancy, malnutrition and chronic blood loss increase consequences. Before steroids, chemotherapy or transplantation, screen for possible Strongyloides exposure even if stool tests are negative. Clinical presentation General symptoms Many infections are asymptomatic. Possible features include abdominal pain, nausea, altered bowel habit, anorexia, bloating, fatigue, urticaria, cough during larval migration and eosinophilia. Ascaris syndromes Heavy infection can cause colicky pain, vomiting, abdominal distension and intestinal obstruction. Migrating worms produce biliary colic, cholangitis, pancreatitis or obstructive jaundice. Pulmonary migration may cause transient fever, wheeze and eosinophilic pneumonitis (Löffler syndrome). Hookworm disease Early itchy dermatitis occurs at the entry site. Later, patients develop fatigue, exertional dyspnoea, pallor, dizziness, pica, oedema from hypoalbuminaemia or cognitive and growth effects in children. Severe anaemia may precipitate heart failure. Trichuriasis Light infection is often silent. Heavy disease causes chronic mucoid or bloody diarrhoea, tenesmus, abdominal pain, anaemia, growth retardation and rectal prolapse. Strongyloidiasis Intermittent abdominal pain, diarrhoea, constipation, urticaria and rapidly moving linear rash (larva currens) may occur. Hyperinfection presents with fever, cough, dyspnoea, wheeze, abdominal pain, ileus, meningitis or sepsis; eosinophilia may disappear in severe disease. Enterobiasis Intense nocturnal perianal itching disturbs sleep. Excoriations, secondary infection, vulvovaginitis or rarely appendiceal/urinary symptoms may occur. History and examination Ask about onset, stool appearance, pruritus, weight change, fever, respiratory symptoms, jaundice and obstructive pain. Document diet, pica, menstrual and pregnancy history, drug exposure, prior deworming and household symptoms. Map residence, travel, sanitation, footwear, farming and contact with contaminated soil. Examine hydration, nutrition, pallor, oedema, abdomen, perianal skin, lungs, jaundice and signs of heart failure. In suspected hyperinfection, assess sepsis, oxygenation, meningism and ileus urgently. Investigations Full blood count: eosinophilia supports tissue migration but may be absent in severe Strongyloides; assess haemoglobin and indices for iron deficiency. Stool ova and parasite microscopy on properly collected samples; concentration improves yield. Multiple samples are useful for intermittent shedding. Perianal adhesive tape test on three early mornings for Enterobius; routine stool examination is insensitive. Strongyloides stool culture or PCR where available; serology helps chronic infection but may be unreliable in immunosuppression. Chest radiograph during pulmonary migration; ultrasound/MRCP/ERCP for biliary obstruction; abdominal radiograph or CT for obstruction, perforation or abscess. Iron studies, albumin, renal/electrolyte profile and stool occult blood when anaemia or protein loss is suspected. Do not exclude Strongyloides because of one negative stool test: intermittent larval output and low burden are common. Exposure history and planned immunosuppression justify sensitive testing or specialist-directed empiric therapy. Differential diagnosis Giardiasis, amoebiasis, inflammatory bowel disease, coeliac disease, bacterial dysentery, tuberculosis, appendicitis, biliary stones, peptic disease, malignancy, iron deficiency from other causes and eosinophilic gastrointestinal disease. Management Ascaris, hookworm and Trichuris Use a nationally recommended benzimidazole regimen such as albendazole or mebendazole; Trichuris and hookworm often require a multi-day course or repeat treatment. Treat iron deficiency, malnutrition and dehydration. Confirm local dosing for children and pregnancy. Strongyloidiasis Ivermectin is preferred for uncomplicated disease. Treat before corticosteroids, transplant or other immunosuppression whenever possible. Hyperinfection requires daily ivermectin, sometimes via an alternative route, prolonged until clinical improvement and repeatedly negative specimens; manage sepsis and involve specialists. Enterobiasis Give a recommended single-dose antihelminthic and repeat after about two weeks to target newly emerged worms. Treat household contacts simultaneously, wash bedding and clothing, trim nails and reinforce morning bathing and hand hygiene. Emergency complications Obstruction: nil by mouth, IV fluids, electrolyte correction, imaging, surgical review and nasogastric decompression when indicated. Do not give laxatives in suspected complete obstruction. Biliary or pancreatic migration: manage cholangitis/sepsis and arrange endoscopic or surgical extraction where required. Severe hookworm anaemia: assess haemodynamic compromise and heart failure; transfuse only when

Trematodes (flukes): clinical diagnosis and management Trematodes are leaf-shaped flatworms whose complex life cycles usually involve freshwater snails and, for some species, fish, crustaceans or aquatic plants. Human disease is determined by the adult habitat: intestinal flukes cause enteritis and malabsorption; liver flukes cause biliary inflammation and obstruction; and blood flukes (Schistosoma) cause intestinal, hepatosplenic, urinary or genital disease. Chronic inflammation and fibrosis can produce portal hypertension, renal disease, infertility and cancer. Ask specifically about freshwater contact, swimming, fishing, raw/undercooked fish or crab, water plants, sanitation and residence in endemic districts. Learning objectives Classify trematodes by habitat and route of human infection. Explain snail and intermediate-host stages and relate them to prevention. Recognise acute schistosomiasis, hepatobiliary disease, portal hypertension, urinary disease and ectopic complications. Interpret stool/urine microscopy, concentration, serology, antigen tests and imaging. Use praziquantel safely, manage complications and prevent reinfection. Classification Group Examples Acquisition and main disease Blood flukes S. mansoni, S. haematobium, S. japonicum Cercariae penetrate skin in freshwater; intestinal/hepatosplenic or urinary disease Liver flukes Clonorchis, Opisthorchis, Fasciola Raw fish for clonorchiasis/opisthorchiasis; water plants for fascioliasis; biliary disease Intestinal flukes Fasciolopsis, Heterophyes Raw aquatic plants or fish; enteritis and protein loss Lung flukes Paragonimus Raw/undercooked crab or crayfish; chronic haemoptysis and ectopic CNS disease Life cycle and pathogenesis Eggs leave the definitive host in stool or urine. In water they hatch, infect a snail, multiply asexually and emerge as cercariae. Schistosome cercariae directly penetrate human skin; other trematodes encyst as metacercariae on plants or in fish/crustaceans and are swallowed. Adult worms mature in target organs. Most tissue injury comes from host granulomatous and fibrotic responses to eggs rather than adult worms themselves. Schistosomiasis Adult pairs live in mesenteric or vesical venous plexuses. Eggs traverse bowel or bladder walls and cause granulomas, polyps, bleeding and fibrosis. Eggs that embolise to liver, lungs, spinal cord or brain cause ectopic disease. S. mansoni and S. japonicum mainly cause intestinal/hepatosplenic disease; S. haematobium causes urinary and genital disease. Fascioliasis Metacercariae on watercress or other aquatic plants excyst in the duodenum, cross the intestinal wall and migrate through liver parenchyma before entering bile ducts. The hepatic migratory phase causes fever, right-upper-quadrant pain and eosinophilia; the chronic phase causes cholangitis and obstruction. Clonorchis/Opisthorchis Metacercariae in raw fish mature in intrahepatic ducts. Repeated inflammation, epithelial hyperplasia and pigment stones increase cholangitis and cholangiocarcinoma risk. Clinical features Acute schistosomiasis (Katayama syndrome) Weeks after a new exposure: fever, urticaria, cough, malaise, headache, abdominal pain, diarrhoea, hepatosplenomegaly and marked eosinophilia. Stool or urine egg shedding may still be negative early. Chronic intestinal/hepatosplenic disease Abdominal pain, bloody diarrhoea, fatigue and hepatosplenomegaly progress to periportal fibrosis, portal hypertension, varices, hypersplenism and preserved liver function until late. Ascites or gastrointestinal bleeding requires urgent care. Urinary and genital schistosomiasis Terminal haematuria, dysuria, frequency, recurrent urinary infection, bladder wall calcification, hydronephrosis, renal impairment, genital lesions, infertility and increased bladder cancer risk may occur. Fascioliasis Fever, painful hepatomegaly, right-upper-quadrant pain, urticaria and high eosinophilia occur during migration. Chronic disease causes biliary colic, obstructive jaundice, cholangitis and gallbladder involvement. Paragonimiasis and intestinal flukes Paragonimus causes chronic cough, pleuritic pain, rusty or blood-stained sputum and pleural effusion; cerebral disease causes seizures or focal deficits. Intestinal flukes cause diarrhoea, abdominal pain, malabsorption and protein loss. History and examination Map all freshwater exposure, including bathing, fishing, irrigation and childhood swimming. Ask about raw fish, crab, crayfish, watercress and other uncooked aquatic foods. Document haematuria, dysuria, genital symptoms, diarrhoea, blood in stool, cough, haemoptysis, jaundice and weight loss. Examine pallor, fever, urticaria, hepatosplenomegaly, ascites, oedema, abdominal tenderness, neurological signs and respiratory findings. Look for chronic liver disease and portal-hypertension complications, while remembering that schistosomal portal hypertension may occur with relatively preserved hepatocyte function. Investigations Full blood count with eosinophils, liver profile, renal function, urinalysis and urine microscopy. Stool microscopy with concentration and Kato-Katz where available; collect multiple samples because egg output varies. Urine filtration or sediment microscopy for S. haematobium, ideally midday urine after activity; inspect for haematuria. Serology or circulating antigen tests assist when egg shedding is low, especially early or light infection, but may not distinguish past infection. Ultrasound assesses periportal fibrosis, splenomegaly, portal vein, bladder lesions and hydronephrosis; CT/MRI evaluates ectopic disease. Endoscopy for varices; ERCP or MRCP for biliary obstruction; chest imaging and sputum microscopy for paragonimiasis. Biopsy is occasionally required when eggs are suspected in tissue and non-invasive tests are inconclusive. Do not dismiss haematuria in an endemic area: urinary schistosomiasis can cause obstruction, renal damage and bladder cancer. Investigate and treat even when pain is minimal. Differential diagnosis Malaria, typhoid, viral hepatitis, bacterial cholangitis, gallstones, liver abscess, inflammatory bowel disease, tuberculosis, urinary stones, glomerulonephritis, urological malignancy, eosinophilic disease and other helminths. Management Schistosomiasis Praziquantel is the standard treatment; dose and number of administrations depend on species and national guideline. In heavy infection or early treatment, repeat dosing after maturation of immature worms may be required. Treat anaemia and complications, and reassess egg clearance. Fascioliasis Triclabendazole is preferred because Fasciola is not reliably cured by praziquantel. Treat biliary infection and obstruction, and involve specialists for cholangitis or persistent duct disease. Clonorchis/Opisthorchis and intestinal flukes Use praziquantel or another locally recommended regimen, treat cholangitis, and counsel about avoiding raw fish or aquatic plants. Evaluate persistent biliary symptoms and malignancy risk. Paragonimus Use praziquantel or an alternative guideline-recommended agent; drain significant pleural collections and assess the brain urgently when seizures or focal signs occur. Complications and emergencies Variceal haemorrhage, severe anaemia, portal-hypertension ascites and hypersplenism. Obstructive uropathy, recurrent pyelonephritis and renal failure from urinary schistosomiasis. Acute cholangitis, obstructive jaundice, pancreatitis or liver abscess-like lesions. Neurological schistosomiasis or paragonimiasis with seizures, myelopathy or raised intracranial pressure. Secondary bacterial infection of damaged urinary or biliary tracts. Cholangiocarcinoma and bladder squamous-cell carcinoma risk in chronic endemic infection. Prevention and public health Safe water, sanitation and elimination of open defecation reduce egg contamination. Avoid swimming or wading in potentially infested freshwater; provide safe bathing and occupational alternatives. Cook freshwater fish, crab, crayfish and aquatic plants thoroughly; do not rely

Opportunistic fungal infections Opportunistic mycoses occur when fungi that are normally controlled by intact cellular immunity, neutrophils, mucosal barriers or normal flora cause invasive disease. They are major causes of illness in advanced HIV, transplant recipients, cancer chemotherapy, prolonged corticosteroid use, neutropenia, diabetes, severe malnutrition and intensive-care patients. The same organism can produce superficial colonisation in one patient and rapidly fatal disseminated disease in another. Fever plus a compatible risk state is not enough: define the syndrome, obtain specimens early, start appropriate antifungal therapy promptly when invasive disease is likely, and reverse the immune defect. Learning objectives Recognise Candida, Cryptococcus, Aspergillus, Mucorales, Pneumocystis and other opportunistic fungi. Relate each organism to immune defects, route of entry and characteristic organ disease. Interpret cultures, microscopy, antigen tests, fungal biomarkers and CT findings. Manage life-threatening pulmonary, CNS, bloodstream and disseminated disease. Integrate antifungal therapy with ART, neutrophil recovery, surgery, source control and prophylaxis. Who is at risk? Host problem Fungal syndromes to consider Advanced HIV, low CD4 count Cryptococcal meningitis, oesophageal candidiasis, disseminated histoplasmosis, recurrent mucosal Candida, Pneumocystis. Neutropenia/chemotherapy Invasive Candida, Aspergillus, Mucorales and disseminated mould infection. Transplant or prolonged steroids Aspergillosis, Candida, cryptococcosis, Pneumocystis and endemic mycoses. Diabetes/ketoacidosis Mucormycosis, invasive Candida and severe dermatophyte infection. ICU, central lines, broad antibiotics Candidemia, intra-abdominal Candida and catheter-associated infection. Major pathogens and pathogenesis Candida Candida colonises the mouth, gut and genital tract. Barrier disruption, antibiotics, central lines and neutropenia permit invasion, candidemia and organ seeding. Candida can cause thrush, oesophagitis, vulvovaginitis, candidemia, endocarditis, hepatosplenic disease and endophthalmitis. Cryptococcus Cryptococcus neoformans and C. gattii are inhaled and may disseminate to the brain, particularly in advanced HIV. Encapsulated yeast, high organism burden and raised intracranial pressure drive meningitis. Aspergillus Inhaled conidia germinate when neutrophil function is impaired. Disease ranges from allergic bronchopulmonary aspergillosis to invasive pulmonary nodules, infarction, haemoptysis, sinus/orbital invasion and CNS dissemination. Mucorales Angioinvasive moulds invade vessels, causing thrombosis and tissue necrosis. Diabetic ketoacidosis, iron overload, neutropenia and steroids are key risks. Rh inocerebral, pulmonary, cutaneous and gastrointestinal forms are emergencies. Pneumocystis jirovecii This organism causes diffuse interstitial pneumonia in advanced HIV and other T-cell immunodeficiency. It produces profound exertional hypoxaemia and dry cough despite initially modest chest signs. Clinical syndromes Mucosal and oesophageal candidiasis White plaques that scrape off leaving an erythematous base, angular cheilitis, sore mouth, odynophagia or retrosternal pain. Oesophageal disease can occur without visible oral thrush. Candidemia and invasive candidiasis Persistent fever or sepsis despite antibacterial therapy, central-line infection, abdominal surgery, pancreatitis, neutropenia, renal replacement therapy or multiple antibiotics. Metastatic endophthalmitis, endocarditis, osteomyelitis and hepatosplenic lesions may follow. Cryptococcal meningitis Subacute headache, fever, malaise, visual symptoms, nausea, confusion, cranial-nerve palsy, papilloedema or reduced consciousness. Fever may be mild in advanced HIV. Raised intracranial pressure is a major cause of death. Invasive pulmonary aspergillosis Persistent fever, pleuritic chest pain, cough, dyspnoea, haemoptysis and nodular or cavitating CT lesions in neutropenia or transplant. Sinus pain, orbital swelling, focal neurological deficit or skin necrosis suggests dissemination. Mucormycosis Rapidly progressive facial pain, orbital swelling, black necrotic nasal/palatal tissue, cranial neuropathy, pulmonary fever/haemoptysis or necrotic skin lesions. Do not wait for culture before surgical consultation. Pneumocystis pneumonia Subacute dry cough, fever, progressive exertional dyspnoea, tachypnoea and hypoxaemia. Oxygen saturation may fall dramatically with exertion; auscultation can be deceptively normal. Assessment and investigations Stabilise first: oxygen saturation, respiratory effort, shock, mental status and glucose. Define the host: HIV test/CD4/viral load where appropriate, neutrophil count, transplant/chemotherapy dates, steroids, diabetes and ART adherence. Obtain specimens: two sets of blood cultures, catheter samples, sputum/BAL, CSF, tissue, urine or lesion swabs before therapy when this does not delay emergency treatment. Use targeted tests: cryptococcal antigen in blood/CSF, Histoplasma antigen where available, galactomannan and beta-D-glucan in appropriate settings, Pneumocystis PCR or induced sputum/BAL, fungal culture and histopathology. Image early: chest X-ray/CT, sinus/orbit CT/MRI, brain imaging before lumbar puncture when raised pressure or focal neurology is suspected, and echocardiography for candidemia with persistent fungemia. Colonisation is not invasion: Candida from sputum or a non-sterile swab may represent colonisation. Blood culture, sterile-site isolation, compatible syndrome and imaging determine invasive disease. Differential diagnosis Bacterial sepsis, TB, viral pneumonia, Pneumocystis, nocardiosis, mycobacteria, malignancy, pulmonary embolism, drug toxicity, bacterial meningitis and non-infectious inflammatory disease. Mixed infections are common in advanced HIV. Management principles Candidemia Start an echinocandin or another guideline-recommended initial agent in unstable, azole-exposed or resistant-risk patients; step down to fluconazole when susceptible and clinically stable. Remove/replace a likely infected central line, repeat blood cultures and assess eyes/heart according to protocol. Cryptococcal meningitis Use an amphotericin-based induction regimen with flucytosine where available, followed by fluconazole consolidation and maintenance. Manage raised intracranial pressure with therapeutic lumbar punctures; do not rely on mannitol or steroids routinely. Invasive aspergillosis Use voriconazole, isavuconazole or liposomal amphotericin B according to species, interactions and local guideline. Reduce immunosuppression where safe, assess for surgery and monitor drug levels/interactions. Mucormycosis Immediate liposomal amphotericin B, aggressive surgical debridement and correction of ketoacidosis/neutropenia. Posaconazole or isavuconazole may be used for step-down or salvage under specialist care. Pneumocystis High-dose trimethoprim–sulfamethoxazole for the recommended duration, oxygen and corticosteroids when hypoxaemia meets guideline criteria. Start or optimise ART at the appropriate time and provide secondary prophylaxis. Cryptococcal raised intracranial pressure Measure opening pressure at lumbar puncture when safe. Headache, vomiting, visual change, papilloedema, sixth-nerve palsy or confusion require urgent pressure management. Therapeutic lumbar puncture is repeated based on symptoms and pressure; antifungals alone may not prevent early death. Avoid routine corticosteroids unless another specific indication exists. Antifungal stewardship and monitoring Check renal function, potassium and magnesium with amphotericin. Check liver tests and interactions with azoles; consider therapeutic drug monitoring for voriconazole/itraconazole/posaconazole. Review QT prolongation, CYP interactions, anticoagulants, anticonvulsants and antiretrovirals. Repeat cultures and imaging to document response; treatment often lasts weeks to months. Do not stop therapy solely because fever improves if sterilisation or immune recovery is incomplete. HIV, ART and immune recovery Test for HIV where appropriate and link patients to ART. Timing of ART must be coordinated with the infection: cryptococcal meningitis requires a delayed, carefully

Systemic fungal infections (endemic mycoses) Systemic mycoses are infections in which fungi enter through the lungs or skin and disseminate to organs such as brain, bone, skin, lymph nodes and adrenal glands. Many are caused by thermally dimorphic fungi that grow as moulds in the environment and convert to yeast or another tissue form in the host. Severity depends on inoculum, immunity, lung structure, pregnancy, HIV, corticosteroids and delayed diagnosis. A chronic “TB-like” illness that fails TB treatment, especially after soil, bird/bat or agricultural exposure, should trigger fungal investigation. Learning objectives Explain dimorphism, environmental acquisition and pulmonary-to-disseminated spread. Recognise histoplasmosis, blastomycosis, coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and other deep mycoses. Interpret microscopy, culture, antigen, serology, imaging and biopsy. Plan induction, consolidation, maintenance and surgical management with specialist input. Identify severe respiratory, CNS, adrenal, mucocutaneous and bone disease. Important systemic fungi Infection Exposure/organism Clinical pattern Histoplasmosis Histoplasma capsulatum; soil enriched with bird/bat droppings Pneumonia, mediastinal disease, chronic cavitation and disseminated reticuloendothelial infection. Blastomycosis Blastomyces; soil/decaying wood in endemic areas Pulmonary disease with verrucous skin, bone and genitourinary dissemination. Coccidioidomycosis Coccidioides; desert dust Pneumonia, erythema nodosum, meningitis, bone and disseminated skin disease. Paracoccidioidomycosis Paracoccidioides; rural soil in Latin America Chronic pulmonary and mucosal disease, lymphadenopathy and adrenal involvement. Sporotrichosis Sporothrix; thorn/plant inoculation or zoonotic cat exposure Lymphocutaneous nodules; pulmonary, osteoarticular or disseminated disease in immune compromise. Acquisition and pathogenesis Inhaled conidia reach alveoli, where macrophages and neutrophils attempt containment. Dimorphic conversion at body temperature enables tissue survival. Granulomas may contain organisms for years; reactivation occurs when cellular immunity falls. Dissemination follows lymphatic or haematogenous spread. The lungs, reticuloendothelial system, skin, bone, CNS and adrenal glands are common targets. Large inoculum, smoking, chronic lung disease, diabetes, HIV, TNF-inhibitor or corticosteroid therapy, transplant, malignancy, malnutrition and pregnancy can shift a mild pulmonary syndrome toward progressive or disseminated disease. Clinical presentation Acute pulmonary disease Fever, dry cough, dyspnoea, chest pain, myalgia, headache and fatigue may follow a shared soil or dust exposure. Chest imaging can show diffuse infiltrates, nodules, hilar/mediastinal adenopathy or focal consolidation. Chronic pulmonary disease Weeks to months of cough, weight loss, night sweats, fever, haemoptysis and progressive dyspnoea can mimic tuberculosis, malignancy or bacterial bronchiectasis. Cavities may develop. Disseminated disease Persistent fever, weight loss, hepatosplenomegaly and lymphadenopathy. Mucocutaneous ulcers, papules, plaques or verrucous lesions. Adrenal insufficiency with postural hypotension, hyperpigmentation, hyponatraemia and hyperkalaemia. Osteomyelitis, arthritis, genitourinary disease or CNS infection. Sepsis, respiratory failure and multiorgan dysfunction in severe cases. History and examination Ask about soil, caves, poultry houses, bat/bird droppings, construction, farming, mining, desert travel, decaying wood, cat scratches/bites, chronic lung disease, HIV, steroids, transplant and anti-TNF therapy. Examine temperature, weight, respiratory effort, oxygen saturation, lymph nodes, liver/spleen, skin/mucosa, bones/joints, neurological status and signs of adrenal insufficiency. Diagnosis Method Use Interpretive caution Direct microscopy/histopathology Yeast, spherules, broad-based budding or characteristic tissue forms Organism burden varies; morphology requires expertise. Fungal culture Species confirmation and susceptibility May take weeks; laboratory biosafety is essential. Antigen tests Histoplasma urine/serum antigen and other assays Cross-reactivity occurs; test availability varies. Serology Exposure/support for coccidioides, histoplasma and paracoccidioides May be negative early or in immunosuppression; antibodies can persist. Imaging Chest X-ray/CT, ultrasound, MRI brain/bone/adrenal Findings overlap TB, malignancy and bacterial infection. Send sputum, bronchoalveolar lavage, blood, marrow, skin lesion, lymph node, CSF or tissue according to the syndrome. Always alert the laboratory when a dimorphic fungus is suspected because mould cultures may pose an aerosol risk. Differential diagnoses Tuberculosis, bacterial pneumonia, nocardiosis, lung cancer, sarcoidosis, vasculitis, leishmaniasis, lymphoma, HIV-related opportunistic infection and chronic melioidosis. Disseminated fungal disease and TB can coexist; a negative TB test does not prove fungus, and a positive fungal antigen may require confirmation. Management principles Mild-to-moderate pulmonary disease Use an oral azole such as itraconazole or another guideline-recommended agent after species and severity assessment. Ensure absorption, adherence, drug-interaction review and liver monitoring. Severe or disseminated disease Hospitalise and use liposomal amphotericin B or another recommended induction regimen, then step down to prolonged oral azole consolidation. Monitor renal function, potassium, magnesium, FBC and infusion reactions. CNS, bone or adrenal disease Obtain specialist infectious-disease input; treatment is longer and may require CNS-penetrating azole, amphotericin induction, surgery or endocrine replacement. Assess oxygenation, sepsis, renal function and drug interactions before therapy. Itraconazole absorption depends on formulation and gastric conditions; verify administration and levels where available. Azoles inhibit CYP enzymes and interact with rifampicin, some antiretrovirals, anticoagulants and anticonvulsants. Therapy often lasts months; premature cessation causes relapse. Organ-specific emergencies Respiratory failure: oxygen, ventilatory support, sepsis management and urgent antifungal induction. Meningitis: lumbar puncture when safe, brain imaging, CNS-active therapy and intracranial-pressure management. Adrenal crisis: immediate hydrocortisone and isotonic saline, then endocrine evaluation. Spinal/bone disease: MRI, prolonged therapy and surgical stabilisation/drainage when required. Massive haemoptysis: airway protection, imaging, bronchoscopy/interventional support and treatment of the cavity. Follow-up and prevention Review symptoms, weight, oxygenation, imaging, inflammatory markers and organ function. Monitor azole levels or interactions where available and check liver tests. Follow disseminated disease for relapse after completing therapy. Reduce exposure to bird/bat droppings, disturbed desert soil and decaying vegetation; use masks and wet-cleaning during high-risk work. Optimise HIV treatment, nutrition and immunosuppression decisions. Exam pearls Dimorphic fungi are moulds in the environment and tissue forms at body temperature. Chronic cavitary disease can mimic TB; tissue, culture and antigen testing may be decisive. Disseminated histoplasmosis commonly involves reticuloendothelial organs and is strongly associated with advanced HIV. Amphotericin B is potent but nephrotoxic; azoles require interaction and liver monitoring. References SlideShare: Systemic mycoses. WHO and national guidance for endemic mycoses and HIV-associated fungal disease. Current Uganda Clinical Guidelines and specialist infectious-disease protocols. Safety note: Systemic antifungals are specialist medicines. Confirm species, severity, pregnancy status, organ function and interactions before prescribing.

Superficial fungal infections Superficial mycoses are infections of keratinised tissues—skin, hair and nails—or the moist mucosal folds. They range from cosmetically disturbing but mild colour changes to inflammatory dermatophyte infection, scalp disease with permanent alopecia, and extensive disease in diabetes or immunosuppression. The key clinical skill is to identify the anatomic site, distinguish dermatophytes from yeast and non-fungal mimics, and choose topical or systemic therapy based on depth and extent. Do not treat every itchy rash as “ringworm”: confirm the morphology, site and likely organism. Learning objectives Classify dermatophyte, yeast and other superficial infections. Explain transmission, keratin digestion and inflammatory patterns. Recognise tinea of the body, groin, foot, scalp and nail, pityriasis versicolor, piedra, tinea nigra and cutaneous candidiasis. Perform and interpret KOH microscopy, culture, Wood-lamp examination and dermoscopy where available. Select topical versus oral treatment and prevent recurrence, reinfection and steroid-modified tinea. Classification Group Examples Typical tissue Dermatophytes Trichophyton, Microsporum, Epidermophyton Stratum corneum, hair and nails; named tinea/ringworm. Yeasts Candida, Malassezia Moist folds, mucosa, skin surface and sebaceous areas. Other superficial fungi Hortaea werneckii, Piedraia, Trichosporon Palms/soles or hair shafts, usually limited disease. Transmission and risk factors Dermatophytes spread by direct contact, infected humans or animals, contaminated floors, combs, clothing and towels. Warm humid climates, occlusive footwear, communal bathing, contact sports, obesity, diabetes, peripheral vascular disease, HIV, corticosteroids and immunosuppressive medicines increase risk. Auto-inoculation from the feet to groin, nails or hands is common. Chronic steroid-containing combination creams suppress inflammation while allowing fungal growth, producing tinea incognito. Pathophysiology Dermatophytes digest keratin using proteases and remain mainly in the stratum corneum. The advancing edge of active infection contains more fungus and inflammation, producing an annular plaque with central clearing. Host cell-mediated immunity determines inflammation: strong response causes vesicles and pustules, while impaired immunity allows extensive or atypical lesions. Malassezia alters melanocyte function and produces azelaic-acid-like metabolites, leading to hypo- or hyperpigmented macules. Candida overgrowth follows moisture, maceration and altered local immunity. Clinical syndromes Tinea corporis Annular scaly plaques with a raised active border, central clearing and peripheral vesicles. Lesions may be multiple or confluent. Examine feet, nails and household contacts as reservoirs. Tinea cruris Itchy erythematous plaques begin in the groin and spread onto the upper thigh, usually sparing the scrotum. Bilateral scrotal involvement or satellite pustules suggests candidiasis instead. Tinea pedis Interdigital maceration and fissuring (“athlete’s foot”). Moccasin-type diffuse scale on soles and lateral feet. Inflammatory vesiculobullous type after an immune response. Complications: bacterial cellulitis through fissures and onychomycosis. Tinea capitis Common in children: scaling, broken hairs, black dots, alopecia, kerion (boggy inflammatory plaque) or favus. Kerion can scar and cause permanent hair loss; treat systemically and assess contacts. Tinea unguium/onychomycosis Thickened, discoloured, brittle or separated nails. Distal-lateral, white superficial and proximal patterns occur. Psoriasis, trauma and lichen planus mimic fungal nails; confirm before prolonged oral therapy. Pityriasis versicolor Fine-scaling hypo- or hyperpigmented macules on trunk, neck and upper arms. More obvious after sun exposure. KOH shows short curved hyphae and round yeast (“spaghetti and meatballs”). Pigment normalisation may take months after cure. Candidal intertrigo Beefy-red macerated plaques in folds with satellite papules/pustules. Risk factors include obesity, diabetes, antibiotics, pregnancy and immunosuppression. Piedra and tinea nigra White/soft or black/hard nodules attached to hair shafts occur in piedra. Tinea nigra produces a slowly enlarging brown-black palm/sole macule without inflammation and can mimic melanoma. History and examination Ask duration, itch/pain, spread, contacts, animal exposure, footwear, shared showers, prior steroid creams, diabetes, HIV, medicines and previous treatment. Examine the entire skin, scalp, nails, interdigital spaces, groin, mouth and mucosal sites; a local lesion may coexist with an untreated reservoir elsewhere. Look for bacterial infection, lymphadenopathy, fever, kerion and scarring. Diagnosis Test Use Limitations KOH preparation Skin scale, nail scrapings or hair; demonstrates branching septate hyphae or yeast Operator-dependent; negative test does not exclude disease if sampling is poor. Fungal culture Species identification, scalp/nail/refractory infection Slow; prior antifungal use can cause false negatives. Wood lamp Some Microsporum hair infections and erythrasma comparison Many dermatophytes do not fluoresce; not a rule-out test. Nail clipping/PAS Confirms onychomycosis before oral therapy Requires laboratory processing; nail dystrophy has many mimics. Sample the active scaly edge after cleaning off creams. For scalp, pluck broken hairs and scrape scale. In steroid-modified lesions stop unnecessary steroid and sample multiple sites. Differential diagnosis Atopic or contact dermatitis, psoriasis, seborrhoeic dermatitis, pityriasis rosea, erythrasma, intertrigo, bacterial impetigo, scabies, lichen planus, vitiligo, post-inflammatory pigment change and cutaneous lymphoma. A changing pigmented acral lesion requires melanoma assessment, not empirical antifungal therapy alone. Management General measures Keep folds and feet dry; change socks and underwear daily. Do not share towels, combs, hats, shoes or nail instruments. Treat infected pets or close contacts when indicated. Control diabetes, reduce occlusion and stop non-prescribed steroid combinations. Topical therapy For limited tinea corporis/cruris/pedis use a topical allylamine or azole for the recommended duration, extending slightly beyond clinical clearing. For pityriasis versicolor use topical selenium sulfide, ketoconazole or another UCG-approved agent. Oral therapy Use oral terbinafine, itraconazole, griseofulvin or another guideline-recommended agent for tinea capitis, extensive disease, nail infection, recurrent disease or treatment failure. Check liver disease, pregnancy, interactions and local formulary before prescribing. Inflammatory disease Kerion, severe vesicular tinea or bacterial superinfection needs prompt systemic antifungal treatment and sometimes antibacterial therapy. Avoid steroid monotherapy; specialist-directed short anti-inflammatory treatment may be considered after antifungal coverage. Special syndromes Tinea capitis: topical therapy alone is inadequate. Examine household members and avoid sharing combs; oral treatment and shampoo to reduce spores are usually required. Onychomycosis: confirm fungus before months of systemic therapy; assess liver function and interactions. Diabetes/HIV: search for extensive disease, bacterial cellulitis and recurrent infection. Pregnancy/children: choose agents with UCG/obstetric guidance; avoid unnecessary systemic exposure. Complications and referral Permanent scarring alopecia after untreated kerion/favus. Bacterial cellulitis or lymphangitis through fissured feet. Disseminated or atypical disease in immunosuppression. Drug hepatotoxicity and interactions from prolonged oral treatment. Refer uncertain pigmented lesions, severe scalp inflammation, nail disease requiring systemic therapy, recurrent disease and immunocompromised patients. Exam pearls Sample the active edge, not the

Giardiasis: intestinal protozoal infection and malabsorption Giardiasis is caused by Giardia duodenalis (synonyms G. lamblia and G. intestinalis). It is acquired by swallowing cysts from contaminated water, food, hands, objects or sexual contact. The organism attaches to the small-bowel surface rather than invading tissue, so the central clinical problem is brush-border injury, altered digestion and malabsorption. Illness ranges from asymptomatic carriage to prolonged diarrhoea, steatorrhoea, weight loss and post-infectious bowel dysfunction. Think giardiasis when diarrhoea is greasy, foul-smelling, bloating is prominent and fever or blood is absent. Learning outcomes Describe the cyst and trophozoite forms and the excystation–encystation cycle. Explain how mucosal attachment produces lactase deficiency, steatorrhoea and weight loss. Recognise acute, persistent, asymptomatic and immunodeficiency-associated disease. Choose stool antigen, PCR and serial microscopy appropriately. Manage hydration, nutrition, antiprotozoal treatment, reinfection and persistent symptoms. Give practical water, food, household and sexual-transmission prevention advice. Organism and morphology Form Features Clinical meaning Cyst Oval, environmentally hardy, multiple nuclei when mature Infectious form; survives in water and on surfaces; passed in formed stool. Trophozoite Pear-shaped, two nuclei, flagella and ventral adhesive disc Replicating intestinal form; survives poorly outside the body; passed in watery stool. After cyst ingestion, gastric acid triggers excystation in the duodenum. Trophozoites multiply by binary fission, attach to the duodenal/jejunal brush border and encyst during distal transit. Cysts are immediately infectious when excreted. Transmission and risk factors Untreated surface water, shallow wells, streams, lakes, ice and contaminated recreational water. Food washed or prepared with contaminated water. Person-to-person spread in households, childcare centres, schools and institutions. Fecal–oral sexual exposure, including oral–anal contact. Travel, crowded housing, poor sanitation and unsafe faeces disposal. Hypochlorhydria, malnutrition, hypogammaglobulinaemia, HIV and other immune deficits. Giardia is found worldwide. The most important route is swallowing human faecal contamination; cats and dogs are not the usual source of human infection, although animal-associated transmission can occur. Pathophysiology Trophozoites form a dense surface layer over enterocytes. Their adhesive disc and secreted products disrupt microvilli, tight junctions, brush-border enzymes and bile-salt handling. Villous shortening and epithelial inflammation impair digestion and absorption of fat, carbohydrates, folate, vitamin B12 and other nutrients. Lactase deficiency commonly causes temporary secondary lactose intolerance. Because tissue invasion and systemic bacteraemia are not typical, high fever, frank blood, peritonism or marked inflammatory toxicity should prompt another diagnosis or co-infection. Clinical spectrum Incubation and acute disease Symptoms usually begin about one to two weeks after exposure. The patient may develop watery diarrhoea, cramps, bloating, nausea, fatigue, anorexia and excessive flatus. Stool is often pale, greasy, foul-smelling and difficult to flush. Mild fever can occur but high fever is unusual. Persistent and chronic disease Symptoms fluctuate over weeks. Steatorrhoea, weight loss, weakness, abdominal distension, lactose intolerance and micronutrient deficiency may develop. Children can have poor growth and reduced school performance. Post-infectious irritable bowel symptoms may persist after eradication. Asymptomatic carriage Some infected people have no symptoms yet shed cysts. A positive test should be interpreted with exposure, symptoms, outbreak context and alternative diagnoses. Public-health or household treatment decisions should follow current guidance rather than indiscriminate treatment. Severe or unusual disease Infants, malnourished patients, people with hypogammaglobulinaemia and patients with HIV may have prolonged diarrhoea, dehydration and wasting. Extraintestinal giardiasis is not the expected syndrome. History and examination Ask duration, stool character, blood/mucus, fever, vomiting, weight change, travel, camping, water source, swimming, childcare exposure, household diarrhoea, oral–anal sex, recent antibiotics and previous therapy. Ask about lactose-containing foods and immune deficiency. Assess hydration, pulse, blood pressure, mucous membranes, postural symptoms, skin turgor, abdominal distension/tenderness, weight and growth. Look for fever, blood, peritonism, severe pain or toxicity that suggest invasive bacterial disease, amoebiasis, inflammatory bowel disease or surgical pathology. Diagnosis Stool testing Antigen detection: enzyme immunoassays and direct fluorescent antibody methods are useful where available. Nucleic-acid amplification/PCR: highly sensitive and can identify mixed infections, but a positive result may reflect carriage. Microscopy: look for cysts and trophozoites on concentration and wet preparations. Because shedding is intermittent, submit two or three specimens collected on separate days when suspicion persists. Tests rarely required Duodenal aspirate, biopsy or an enterotest is reserved for persistent unexplained disease after stool testing. There is no routine blood test that confirms intestinal giardiasis. Interpret in context: a positive Giardia result does not explain high fever, bloody diarrhoea, severe inflammatory markers or peritonism. Investigate co-infection and non-infectious causes. Differential diagnosis Cholera, shigellosis, campylobacteriosis, salmonellosis, cryptosporidiosis, amoebiasis, helminths, viral gastroenteritis, HIV enteropathy, coeliac disease, pancreatic insufficiency, lactose intolerance, inflammatory bowel disease and irritable bowel syndrome. Management Rehydration and nutrition Use oral rehydration solution for ongoing losses; give IV isotonic fluid for shock, severe dehydration or inability to drink. Continue breastfeeding and age-appropriate feeding. Avoid prolonged fasting. Temporarily reduce lactose if it clearly worsens symptoms, then reintroduce gradually. Assess weight, electrolytes and nutrition in prolonged disease. Antiprotozoal choices Use a current UCG regimen such as metronidazole, tinidazole or nitazoxanide. Select dose and duration by age, weight, pregnancy, breastfeeding, liver disease and local formulary. Tinidazole may allow a short course; metronidazole requires adherence to multiple doses. Medication counselling Avoid alcohol during metronidazole/tinidazole therapy and for the recommended period afterward. Review warfarin, anticonvulsants, lithium, antiretrovirals and other interactions. Discuss nausea and metallic taste so the patient can complete therapy. Persistent symptoms Confirm ongoing Giardia before repeating treatment. Check adherence, reinfection, immune deficiency, mixed infection and secondary lactose intolerance. Specialist-guided alternative or combination therapy may be required. Persistent or refractory giardiasis: a structured approach Confirm that the original test was specific and that symptoms fit giardiasis. Repeat stool testing using serial specimens, antigen or PCR after treatment if symptoms persist. Review the dose, timing, vomiting, interactions and completion of therapy. Ask about untreated symptomatic contacts, unsafe water, childcare or sexual re-exposure. Test for HIV, hypogammaglobulinaemia, coeliac disease, inflammatory bowel disease or pancreatic disease when clinically indicated. Look for post-infectious lactose intolerance or IBS when tests are negative. Routine “test of cure” in an asymptomatic patient is not generally required. Retesting is most useful when symptoms continue, reinfection is suspected or a public-health outbreak is being

Human African trypanosomiasis (sleeping sickness) Human African trypanosomiasis (HAT) is a vector-borne protozoal disease caused by extracellular Trypanosoma brucei subspecies and transmitted by tsetse flies of the genus Glossina. It is fatal without treatment but curable when detected early. The two epidemiological forms behave differently: T. b. gambiense is usually chronic and lymphatic, whereas T. b. rhodesiense is acute, has higher parasitaemia and is highly relevant to eastern and southeastern Africa, including Uganda. Do not wait for the patient to “look sleepy”: fever plus tsetse exposure, a chancre, lymphadenopathy or neurological change warrants urgent HAT evaluation. Learning outcomes Differentiate gambiense and rhodesiense HAT by geography, reservoir, tempo, parasitaemia and clinical pattern. Explain tsetse transmission, antigenic variation and CNS invasion. Recognise haemolymphatic and meningoencephalitic stages. Plan specimen collection, microscopy, concentration tests, molecular tests and CSF staging. Understand why treatment is species- and stage-specific and why specialist supervision is essential. Provide follow-up, contact investigation and vector-control counselling. Species, geography and reservoirs Feature Gambiense HAT Rhodesiense HAT Parasite T. b. gambiense T. b. rhodesiense Typical area West/Central African riverine and forest regions East/Southeast African savannah and wildlife–livestock interfaces Reservoir Humans are the main reservoir Wild and domestic animals maintain zoonotic cycles Course Months to years Weeks to months Parasitaemia Often low and intermittent Often high and easier to detect in blood Classic clue Posterior cervical nodes, chronic fever and sleep–wake reversal Chancre, high fever, myocarditis and rapid deterioration American trypanosomiasis (Chagas disease, T. cruzi) is a different infection transmitted mainly by triatomine bugs in the Americas; it should not be confused with HAT. Vector and life cycle An infected tsetse takes a blood meal and inoculates metacyclic trypomastigotes into skin. Parasites multiply extracellularly in lymph and blood. They periodically change variant surface glycoproteins, escaping antibody responses and creating waves of fever. Parasites disseminate into lymphatics and tissues; later they cross the blood–brain barrier and multiply in CSF and CNS tissue. A second tsetse ingests bloodstream forms. In the fly gut they transform, multiply and migrate to salivary glands, where infective metacyclic forms develop. Rare transmission routes include congenital infection, contaminated blood, laboratory exposure and sexual transmission. A history of travel to a tsetse region is more useful than a patient’s ethnic label or passport. Pathophysiology Antigenic variation: recurring surface-antigen changes produce waves of parasitaemia and fever. Immune activation: cytokines, immune complexes and polyclonal B-cell activation contribute to lymphadenopathy, anaemia, thrombocytopenia, pruritus and hypergammaglobulinaemia. Vascular/cardiac disease: rhodesiense infection can cause myocarditis, arrhythmias, pericarditis, hypotension and sudden deterioration. Neuroinvasion: inflammation and parasite growth in CNS tissue cause sleep–wake reversal, endocrine changes, movement disorders, psychiatric change, seizures and coma. Systemic wasting: prolonged infection causes weight loss, fever, malnutrition and susceptibility to secondary infection. Clinical stages and features Inoculation chancre A painful, erythematous nodule at the bite site may enlarge, ulcerate and heal over one to three weeks. It is more often recognised in rhodesiense disease. Absence of a chancre does not exclude HAT because the bite may be unnoticed or the lesion may have healed before presentation. Haemolymphatic disease Intermittent fever, rigors, headache and profound malaise. Pruritus, rash, facial oedema and weight loss. Posterior cervical lymphadenopathy (Winterbottom sign), especially in gambiense disease. Hepatosplenomegaly, anaemia, thrombocytopenia, oedema and arthralgia. Rhodesiense disease: abrupt high fever, high parasitaemia, chancre, myocarditis, shock and rapid organ dysfunction. Meningoencephalitic disease Daytime somnolence and inability to remain awake, followed by nocturnal insomnia. Personality change, irritability, apathy, confusion, hallucinations or psychosis. Ataxia, tremor, dysarthria, hyperreflexia, abnormal movements, rigidity or weakness. Endocrine/autonomic features, headache, cranial-nerve abnormalities and incontinence. Seizures, coma and death if untreated. Focused history and examination Ask about residence/travel in endemic districts, farming, fishing, hunting, game-park work, riverine exposure, livestock, tsetse bites, chancre, recurrent fever, lymph-node swelling and new sleep or behaviour changes. Ask relatives whether the patient sleeps during conversations, stays awake at night, has become apathetic or has lost work skills. Examine skin and bite sites, nodes, fever, pallor, jaundice, oedema, hepatosplenomegaly, cardiac rhythm, murmurs, heart failure, hydration, mental state, gait, coordination, cranial nerves, tone, reflexes, sensation and meningeal signs. A normal neurological examination does not exclude early CNS invasion. Diagnosis: practical algorithm Raise suspicion: compatible exposure plus fever, node, chancre or neurological symptoms. Collect specimens before treatment if safe: chancre fluid, lymph-node aspirate and blood for thick/thin films and concentration methods. Confirm the parasite: examine immediately or send to a reference laboratory. Molecular testing/PCR can help when available. Use screening correctly: CATT and related tests are primarily gambiense screening tools; they do not replace parasite confirmation and are not reliable stand-alone tests for rhodesiense. Stage: perform lumbar puncture after confirmation unless contraindicated. CSF white-cell count, protein and direct examination for trypanosomes determine CNS involvement under the applicable protocol. Assess safety: FBC, renal/liver tests, glucose, ECG, pregnancy test and HIV testing according to consent and local policy. One negative film is not enough: gambiense parasitaemia can be very low. Repeat, concentrate or refer specimens rather than dismissing a compatible illness. Differential diagnosis Malaria, relapsing fever, visceral leishmaniasis, tuberculosis, HIV, bacterial endocarditis, lymphoma, viral encephalitis, meningitis, autoimmune disease, drug intoxication, psychiatric illness and other causes of movement/sleep disorders. HAT and malaria may coexist. Treatment principles HAT treatment is potentially toxic and is selected by subspecies, stage, age, weight, pregnancy, renal function and the current WHO/UCG programme protocol. Recent WHO guidance expanded fexinidazole for selected rhodesiense disease, but eligibility must be checked at a referral centre. Gambiense, early stage Pentamidine is used in many national programmes. Fexinidazole is an option for eligible patients aged at least 6 years and weighing at least 20 kg under current guidance; take with food and supervise adherence. Rhodesiense, early stage Suramin remains important, especially for young/low-weight children or patients who do not meet fexinidazole criteria. Fexinidazole is an all-oral option for eligible patients ≥6 years and ≥20 kg according to the current protocol. Gambiense CNS stage Eflornithine plus nifurtimox (NECT) is used for eligible CNS disease. It requires intensive dosing, IV support and laboratory monitoring. Rhodesiense CNS stage Fexinidazole may be used in eligible adults and