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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

Amoebiasis: intestinal colitis, dysentery and liver abscess Amoebiasis is infection with the pathogenic protozoan Entamoeba histolytica. It may be asymptomatic, produce colitis and dysentery, or spread through the portal circulation to the liver and occasionally the pleura, lung, peritoneum, brain or skin. E. dispar and E. moshkovskii are morphologically similar but usually non-invasive; therefore the phrase “amoeba cysts seen” is not enough to prove invasive disease. Core treatment rule: invasive disease needs a tissue-active drug followed by a luminal cyst-eradicating agent. Learning outcomes Describe cyst and trophozoite morphology and the faecal–oral life cycle. Explain adherence, flask-shaped ulcers, portal spread and liver abscess formation. Differentiate asymptomatic carriage, amoebic colitis, fulminant colitis and extraintestinal disease. Interpret stool microscopy, antigen/PCR, serology and liver imaging. Manage dysentery, liver abscess, complications and treatment failure safely. Prevent transmission through sanitation, water safety and sexual-health counselling. Organism and life cycle Form Features Role in disease Mature cyst Resistant wall, multiple nuclei; survives outside the host Infectious form swallowed in contaminated food/water or transferred by hands. Trophozoite Motile, rapidly degenerates outside the colon Replicates in lumen, may adhere to and destroy epithelium, and can invade blood vessels. After cyst ingestion, excystation occurs in the small bowel. Trophozoites migrate to the caecum and colon, multiply and either remain luminal or invade. Encystation occurs during distal transit and cysts are passed in formed stool. Transmission and risk factors Faecally contaminated water, food, hands and household surfaces. Inadequate sanitation, crowded institutions and unsafe sewage disposal. Oral–anal sexual exposure and household contact. Travel/residence in endemic tropical settings. Malnutrition, pregnancy, immunosuppression and corticosteroid exposure, which can worsen invasive disease. Cysts are the major environmental and transmission form. Trophozoites in fresh diarrhoeal stool die quickly but may transmit directly during sexual contact. Pathogenesis E. histolytica uses lectin-mediated adherence to colonic mucin and epithelial cells, then releases proteases and cytotoxic molecules that damage cells and extracellular matrix. Initial mucosal lesions enlarge into characteristic flask-shaped ulcers with a narrow mucosal neck and broad submucosal base. Trophozoites can enter venules and travel through the portal system to the liver. The liver lesion contains necrotic material and inflammatory cells; it may be sterile initially but can become secondarily infected with bacteria. Clinical spectrum Asymptomatic intestinal infection Many infected people pass cysts without symptoms. Confirmed E. histolytica carriage matters because transmission and future invasion are possible. A luminal eradication regimen is generally required, but a non-specific microscopy report should be clarified before labelling every Entamoeba as pathogenic. Amoebic colitis Gradual abdominal pain, tenesmus and frequent loose stools. Mucus and blood ranging from mild dysentery to severe colitis. Weight loss, anorexia, fatigue and low-grade fever. Right iliac fossa tenderness or an amoeboma-like inflammatory mass. Fulminant necrotising colitis Extensive ulceration may cause severe pain, high fever, ileus, peritonism, toxic megacolon, perforation, massive haemorrhage, shock and death. Corticosteroids given for presumed inflammatory bowel disease can accelerate fulminant amoebiasis. Amoebic liver abscess Fever, right-upper-quadrant pain and tender hepatomegaly. Referred right shoulder pain, pleuritic pain or cough from diaphragmatic irritation. Often solitary and right-lobe dominant, but multiple lesions occur. Jaundice, respiratory distress, pleural effusion or peritonism suggest obstruction or rupture. Rupture may occur into the pleura, lung, pericardium, peritoneum or skin. Brain abscess is rare and rapidly life-threatening. History and examination Ask about water and sanitation, travel, household diarrhoea, oral–anal exposure, previous dysentery, recent antibiotics, steroid use, HIV/immunosuppression, weight loss and duration. For suspected liver abscess ask about RUQ/shoulder pain, cough, alcohol, biliary disease and prior treatment. Assess hydration, pulse, blood pressure, fever, pallor, abdominal tenderness, guarding, distension, bowel sounds, hepatomegaly, jaundice, pleural signs, skin lesions and mental status. Toxic appearance, peritonism, shock, severe anaemia or altered consciousness requires admission and urgent specialist review. Diagnosis and interpretation Intestinal disease Specific stool antigen or PCR: preferred where available because it distinguishes E. histolytica from look-alikes. Fresh microscopy: may show trophozoites or cysts; rapid examination is important. Multiple specimens increase yield. Haematophagous trophozoites: a classic clue, but erythrophagocytosis is not perfectly specific and should not replace antigen/PCR. Endoscopy/biopsy: reserved for uncertainty, severe colitis or suspected inflammatory bowel disease/amoeboma; biopsy risks must be considered. Extraintestinal disease Ultrasound: accessible first-line imaging for liver abscess. CT/MRI: defines size, number, rupture, pleural/peritoneal extension and alternative pathology. Serology: often positive in liver abscess but may remain positive after previous infection; interpret with imaging. Aspirate: may contain thick brown “anchovy-sauce” material; send for bacterial culture and amebic antigen/PCR where possible. Investigation What it adds Important limitation FBC Leukocytosis, anaemia, thrombocytosis Non-specific and may be normal early. LFTs Alkaline phosphatase/transaminase changes, bilirubin Cannot distinguish amoebic from pyogenic abscess alone. Stool culture/PCR for bacteria Detects co-infection Negative culture does not exclude amoebiasis. Blood cultures Important in toxic abscess/colitis May be negative in uncomplicated disease. Do not overinterpret microscopy: “Entamoeba cysts” without species confirmation may represent non-pathogenic species. Conversely, a negative stool test does not exclude liver abscess. Differential diagnosis For dysentery consider shigellosis, campylobacteriosis, salmonellosis, Yersinia, inflammatory bowel disease, intestinal tuberculosis, schistosomiasis, colorectal cancer and ischemic colitis. For liver lesions consider pyogenic abscess, hydatid disease, malignancy, tuberculosis, fungal abscess and infected biliary cysts. Amoebic and bacterial abscess may coexist. Management of intestinal infection Invasive colitis Use a tissue-active nitroimidazole such as metronidazole or tinidazole according to current UCG age/weight regimen. Rehydrate, maintain nutrition and monitor for perforation, toxic megacolon, haemorrhage and sepsis. Mandatory luminal course After the tissue-active course give paromomycin, diloxanide furoate, iodoquinol or another UCG-approved luminal agent. This clears residual cysts and reduces relapse and transmission. Asymptomatic confirmed E. histolytica Use a luminal agent even without symptoms. Clarify species when possible before treating a non-pathogenic Entamoeba report. Use oral or IV fluids according to dehydration and ability to drink. Avoid loperamide and other antimotility drugs in severe bloody diarrhoea or suspected invasive colitis. Do not give corticosteroids for presumed IBD until amoebic colitis is excluded; if steroids were started, involve specialists urgently. Review pregnancy, breastfeeding, liver disease, drug interactions and alcohol use before nitroimidazole therapy. Amoebic liver abscess Obtain ultrasound and baseline FBC/LFTs; take blood cultures if febrile/toxic. Start a tissue-active

Malaria: a complete clinical chapter for student doctors Malaria is an infection caused by protozoa of the genus Plasmodium and transmitted predominantly by the bite of an infected female Anopheles mosquito. It is one of the most important causes of fever, anaemia, hospital admission and preventable death in Uganda. The clinician’s task is not simply to recognise a positive test: it is to identify the species and parasite burden, recognise severe disease early, treat correctly, and continue searching for another diagnosis when the course does not fit malaria. Clinical anchor: every febrile patient may have malaria, but every positive malaria test does not explain every clinical problem. Learning outcomes Describe the vector, human and mosquito phases of the parasite life cycle. Explain why P. falciparum causes sequestration, cerebral malaria, acidosis, anaemia, hypoglycaemia and renal injury. Differentiate uncomplicated malaria, severe malaria, treatment failure and non-malarial fever. Interpret thick and thin films, rapid diagnostic tests, parasite density and repeat tests. Manage malaria safely in children, pregnancy, HIV, malnutrition, sickle-cell disease and renal dysfunction. Explain prevention, surveillance, counselling and follow-up. Definition and species Malaria is confirmed when a compatible clinical illness is accompanied by asexual Plasmodium parasites in blood or a validated parasite antigen test. Five species infect humans: Species Biology Clinical importance Microscopy clues P. falciparum Multiple parasites per red cell; mature forms sequester Most severe disease; cerebral malaria, acidosis, renal failure, severe anaemia, shock and death Delicate multiple rings, appliqué forms, crescent gametocytes; mature trophozoites often absent from peripheral film P. vivax Invades reticulocytes; dormant hypnozoites Relapse, splenic complications and occasional severe disease Enlarged red cells, Schüffner dots, amoeboid trophozoites P. ovale Hypnozoites; usually low parasitaemia Relapsing illness; can be misidentified as vivax Oval/fimbriated erythrocytes, Schüffner-type dots P. malariae Low-level long persistence Quartan pattern and chronic immune-complex nephropathy Band forms and rosette schizonts P. knowlesi Twenty-four-hour asexual cycle; macaque reservoir Rapidly progressive severe disease in Southeast Asia May resemble falciparum early and malariae later; travel history is essential Uganda epidemiology and determinants of risk Transmission intensity varies between regions and seasons. Rainfall and temperature affect breeding sites; altitude changes vector survival; housing, drainage, bed-net access and indoor residual spraying affect exposure. Repeated childhood infection can create partial immunity, but no endemic adult is completely protected. Severe disease is more likely in young children, pregnant women, non-immune visitors, people with HIV or malnutrition, and patients with sickle-cell disease or delayed access to treatment. Ask about residence, recent travel, season, occupation near water or forest, bed-net use, indoor spraying, previous malaria, recent antimalarial use and whether medicine was purchased from an informal source. An epidemiological risk does not replace parasitological testing; a low-risk patient can still have imported or transfusion-associated malaria. Transmission and life cycle Inoculation: the mosquito injects sporozoites with saliva. Hepatic invasion: sporozoites rapidly enter hepatocytes. Asexual multiplication forms liver schizonts, which rupture and release merozoites. This phase is clinically silent. Hypnozoites: P. vivax and P. ovale may remain dormant in hepatocytes and reactivate, producing relapses without a new mosquito bite. Erythrocytic cycle: merozoites invade red cells, develop through ring, trophozoite and schizont stages, and rupture the cell. The cycle is approximately 48 hours for falciparum/vivax/ovale and 72 hours for malariae. Gametocytogenesis: a proportion differentiates into male and female gametocytes, which are the forms infectious to mosquitoes. Mosquito development: gametocytes fuse in the gut, form an ookinete and oocyst, and generate sporozoites that migrate to the salivary glands. Radical cure is different from blood-stage cure: an ACT clears circulating parasites but does not reliably eradicate vivax/ovale hypnozoites. Follow current UCG guidance and assess G6PD risk before a relapse-prevention drug. Pathophysiology in detail Fever Rupture of schizont-infected erythrocytes releases parasite products such as glycosylphosphatidylinositol and haemozoin. Innate immune cells produce IL-1, IL-6, TNF and other mediators, causing rigors, fever, sweating and malaise. Antipyretics improve comfort but do not treat the parasite. Sequestration and microvascular disease Falciparum-infected erythrocytes express PfEMP1 and related adhesins. They bind endothelial receptors, form rosettes with uninfected cells and avoid splenic clearance. In the brain, placenta, kidneys and lungs this reduces perfusion and oxygen delivery. Sequestration explains why peripheral parasite density may underestimate total biomass. Anaemia Both infected and uninfected erythrocytes are removed by the spleen. Inflammation, dyserythropoiesis, bleeding, nutritional deficiency and repeated infection worsen anaemia. Severe anaemia reduces oxygen delivery and can itself cause heart failure, acidosis and death. Cerebral malaria Microvascular obstruction, endothelial activation, blood-brain barrier dysfunction, hypoxia and inflammatory injury produce impaired consciousness, seizures and coma. Cerebral malaria is a clinical diagnosis in a patient with falciparum parasitaemia after alternative causes of coma have been assessed; a positive malaria test must not stop evaluation for meningitis, hypoglycaemia, sepsis, intoxication or head injury. Acidosis and respiratory distress Lactate accumulates because of tissue hypoxia, anaerobic metabolism, severe anaemia, seizures, shock and impaired hepatic/renal clearance. Deep breathing is often compensatory Kussmaul breathing, not primary pneumonia. Pulmonary oedema may follow capillary leak or excessive fluid administration. Hypoglycaemia Glucose is consumed by parasites and sick patients often have poor intake. Hepatic dysfunction, quinine-related hyperinsulinaemia and pregnancy further increase risk. Neurological signs of hypoglycaemia can mimic cerebral malaria. Renal and hepatic injury Hypoperfusion, haemoglobinuria, inflammatory injury and parasite pigment can cause acute kidney injury. Jaundice may result from haemolysis, hepatocellular injury or cholestasis; marked jaundice with encephalopathy should trigger consideration of severe malaria plus hepatic failure or another diagnosis. Clinical presentation Uncomplicated malaria The typical patient has fever or a history of fever, chills, rigors, headache, weakness, myalgia, arthralgia, anorexia, nausea or vomiting. Abdominal pain and diarrhoea are common in children. The spleen may be palpable. Fever periodicity is often absent, especially early or after partial treatment. Severe malaria danger signs Impaired consciousness, coma, abnormal behaviour or repeated convulsions. Prostration: inability to sit, stand, drink or breastfeed. Respiratory distress, acidotic breathing, hypoxaemia or pulmonary oedema. Shock, cold extremities, weak pulse or delayed capillary refill. Severe pallor, haemoglobinuria, jaundice with organ dysfunction or abnormal bleeding. Hypoglycaemia, oliguria, acute kidney injury or severe electrolyte disturbance. Persistent vomiting, very high parasite density or rapid