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Swine Flu (Influenza A H1N1): Clinical Features, Diagnosis, Treatment and Prevention Clinical Medicine Year 3 • pandemic H1N1, current seasonal H1N1pdm09 illness and severity-based clinical care Clinical safety note: “Swine flu” usually refers to the 2009 pandemic influenza A(H1N1) strain, now circulating as seasonal A(H1N1)pdm09. Follow current influenza guidance and local protocols. Do not delay antiviral treatment in severe disease, pregnancy or high-risk patients while waiting for laboratory confirmation. What “swine flu” means today Swine flu is the popular name used during the 2009 influenza A(H1N1) pandemic. That virus was a reassortant containing gene segments from human, avian and swine lineages. After the pandemic, A(H1N1)pdm09 became part of seasonal human influenza circulation. Separate swine-influenza viruses can infect people after direct occupational exposure to pigs and require public-health subtyping. H1N1 illness may be mild, but it can also cause viral pneumonia, ARDS, myocarditis, encephalitis, secondary bacterial pneumonia, sepsis and death. The key clinical questions are severity, host risk and whether the illness could represent a novel animal-origin influenza infection. Learning outcomes Explain influenza A structure, H1N1 nomenclature, antigenic drift and reassortment. Describe transmission, incubation, infectious period and high-risk groups. Recognise uncomplicated influenza, pneumonia, sepsis, ARDS and neurologic complications. Select molecular testing and understand the limits of rapid tests. Use oseltamivir, supportive care, isolation, vaccination and outbreak-control principles safely. Virology and epidemiology Influenza A is an enveloped, segmented, negative-sense RNA virus in the Orthomyxoviridae family. H1N1 identifies haemagglutinin 1 and neuraminidase 1. Haemagglutinin binds respiratory epithelial receptors and neuraminidase helps release progeny virions. Antigenic drift causes gradual seasonal change; reassortment can create a novel virus with limited population immunity. The 2009 pandemic spread globally because many people had little pre-existing immunity. H1N1pdm09 is now included in seasonal influenza surveillance and vaccine composition, but severe illness remains possible when care is delayed or the patient has reduced cardiopulmonary/immune reserve. Transmission, incubation and communicability Respiratory droplets and aerosols from coughing, sneezing, talking and clinical procedures. Contaminated hands and surfaces followed by touching the eyes, nose or mouth. Close household, school, workplace and healthcare contact. Rare occupational infection with swine influenza after direct pig exposure; unusual cases require notification and subtype testing. Incubation is commonly 1–4 days, often about 2 days. Infectiousness may begin about one day before symptoms and last 5–7 days after onset, longer in young children, immunocompromised people and severe illness. Fever may be absent in older or immunosuppressed patients. Pathophysiology Virus enters airway epithelial cells and replicates. Damage to ciliated epithelium impairs mucociliary clearance. Innate immune activation causes fever, malaise, myalgia and headache. Lower-airway infection can produce diffuse alveolar inflammation, hypoxaemia and ARDS. Damaged epithelium predisposes to pneumococcal or staphylococcal superinfection. Inflammation or direct viral invasion can affect the heart, brain, muscles and kidneys. Clinical features Uncomplicated influenza Fever, chills, malaise, headache and profound fatigue. Dry cough, sore throat, hoarseness and rhinorrhoea. Myalgia, arthralgia, backache, eye discomfort and photophobia. Nausea, vomiting or diarrhoea, particularly in children. Complicated influenza Primary viral pneumonia with breathlessness, hypoxaemia and diffuse infiltrates. Secondary bacterial pneumonia with recurrent fever, purulent sputum, focal consolidation or sepsis. ARDS, shock, acute kidney injury, rhabdomyolysis and myocarditis. Encephalitis, encephalopathy, seizures or Guillain–Barré syndrome. Exacerbation of asthma, COPD, heart failure, diabetes or other chronic disease. High-risk groups Group Reason for increased risk Pregnant/recently postpartum women Respiratory and immune physiologic changes Young children and older adults Immature or reduced immune and cardiopulmonary reserve Chronic lung/heart disease Reduced reserve and decompensation risk Diabetes, renal/liver/neurologic disease or obesity Higher risk of organ complications HIV, cancer, transplant or long-term steroids Impaired immune control and prolonged shedding Red flags requiring urgent admission Shortness of breath, tachypnoea, chest pain, cyanosis or low oxygen saturation. Haemoptysis, persistent high fever, hypotension or sepsis. Confusion, drowsiness, seizures or inability to wake. Inability to drink, persistent vomiting, dehydration or markedly reduced urine. Recurrent fever or worsening cough after initial improvement. High-risk patient with rapidly progressive symptoms. In children: poor feeding, grunting, chest indrawing, convulsions or lethargy. History and examination Domain What to assess Time course Day of illness, sudden onset, improvement followed by deterioration Exposure Household outbreak, school/workplace, healthcare, travel and pig contact Risk status Pregnancy, age, chronic disease, HIV, immunosuppression and obesity Respiratory status Respiratory rate, work of breathing, SpO2, chest signs and ability to feed/speak Systemic severity Pulse, BP, capillary refill, hydration, mental state, glucose and urine Complications Focal chest signs, cardiac symptoms, muscle weakness, seizures or neurologic change Investigations RT-PCR/molecular respiratory panel: preferred for severe, admitted, unusual or outbreak-associated cases and for subtype information. Rapid antigen tests are less sensitive; a negative result does not exclude influenza in severe illness. Chest radiograph or ultrasound for pneumonia, oedema, effusion or ARDS. Full blood count, electrolytes, renal/liver tests, glucose, CRP and lactate as indicated. Blood/sputum cultures when bacterial superinfection or sepsis is suspected. ECG/troponin for myocarditis, CK for rhabdomyolysis and blood gas for respiratory failure. Test for malaria and other local causes of fever where appropriate; coinfection is possible. Differential diagnosis Condition Key issue Seasonal influenza A/B Often clinically indistinguishable; molecular testing identifies the virus. COVID-19/other respiratory viruses Overlap in symptoms and pneumonia; use local testing. Bacterial pneumonia Focal consolidation, purulent sputum, recurrent fever or sepsis. Malaria Fever, headache, anaemia, thrombocytopenia or altered mental state. Typhoid, dengue and other tropical infections Consider exposure, rash, GI disease and laboratory patterns. Management Antiviral treatment Oseltamivir A common adult treatment dose with normal renal function is 75 mg orally twice daily for 5 days. Start promptly in severe disease, hospitalisation, pregnancy and high-risk patients; adjust for renal function, age and local guidance. Timing Benefit is greatest within 48 hours, but treatment can benefit severe, progressive, hospitalised or high-risk patients even when started later. Do not wait for PCR when treatment is clinically indicated. Novel exposure Unusual illness after pig exposure requires public-health notification, subtype testing and specialist advice about resistance and duration. Outpatient care Rest, oral fluids, nutrition and safe-dose paracetamol. Stay home, improve ventilation and wear a mask around others while infectious. Give clear return precautions for breathlessness, chest pain, confusion, dehydration,

Avian Influenza (Bird Flu, Including H5N1): Clinical Features, Diagnosis and Management Clinical Medicine Year 3 • zoonotic influenza at the human–animal interface and its pandemic potential Clinical safety note: Suspected human infection with avian influenza A—especially H5N1—requires immediate notification to public health authorities and expert laboratory coordination. Ask about sick/dead birds, poultry farms, live markets, dairy cattle, raw milk and contaminated environments. Begin infection-control precautions and discuss antiviral treatment promptly; do not wait for a routine influenza test to rule it out. Why bird flu matters Avian influenza is caused by influenza A viruses that normally circulate among birds. Most avian strains do not infect humans efficiently, but some—particularly highly pathogenic H5 viruses—can cause severe human disease after direct or environmental exposure. Human illness ranges from conjunctivitis or mild upper-respiratory symptoms to severe viral pneumonia, acute respiratory distress syndrome (ARDS), gastrointestinal disease, encephalitis, multiorgan failure and death. The immediate clinical task is to separate ordinary seasonal influenza from a possible novel zoonotic influenza infection. The difference is made by exposure history, specimen choice, public-health testing and rapid treatment—not by the appearance of fever alone. Learning outcomes Explain influenza A subtypes, haemagglutinin/neuraminidase nomenclature and avian influenza ecology. Recognise the exposure history and clinical spectrum of human H5N1/H7N9 infection. Plan testing, isolation, antiviral treatment and monitoring of contacts. Identify respiratory, ocular, gastrointestinal and neurologic complications. Explain how reassortment, mutation and poultry control influence pandemic risk. Influenza virology Influenza A viruses are enveloped, segmented, negative-sense RNA viruses in the family Orthomyxoviridae. Their surface proteins are haemagglutinin (H) and neuraminidase (N), which define subtypes such as H5N1, H7N9 and H1N1. The segmented genome allows reassortment when two influenza viruses infect the same cell. Gradual mutation is called antigenic drift; abrupt reassortment can produce a virus to which humans have little immunity. “Highly pathogenic” and “low pathogenic” refer primarily to disease severity in poultry, not automatically to severity in humans. A low-pathogenic avian virus in birds may still cause serious human illness. Animal reservoirs and human exposure Wild aquatic birds are important reservoirs. Poultry, wild birds and some mammals can become infected. Human infections are uncommon and usually follow close exposure to infected animals or contaminated environments rather than efficient human-to-human spread. Handling sick or dead poultry, wild birds, cats or other infected animals. Slaughtering, defeathering, butchering, cleaning cages or handling droppings and secretions. Working on farms, in live-bird markets, veterinary services or culling teams. Contact with infected dairy cattle or raw milk in settings where H5 viruses are circulating in mammals. Unprotected contact with contaminated surfaces, equipment or aerosols. Human infection is not acquired by eating properly cooked poultry or pasteurised milk. The primary concern is exposure during handling, slaughter, milking or preparation of infected animals and contaminated materials. Pathogenesis and pandemic risk Virus enters through the eye, nose, mouth or lower respiratory tract. Avian influenza viruses preferentially bind receptors in the respiratory tract, but some strains can infect conjunctival, gastrointestinal or neurologic tissues. Viral replication and an exaggerated inflammatory response can damage alveoli, causing diffuse pneumonitis and ARDS. Gastrointestinal and neurologic involvement may occur in severe or unusual presentations. Pandemic risk would rise if a novel avian virus acquired sustained, efficient human-to-human transmission through mutation or reassortment. That is a surveillance concern—not evidence that every human case spreads readily. Clinical presentations 1. Conjunctivitis Red, watery, painful or gritty eyes may be the first or only symptom after ocular exposure. Conjunctivitis in a person who handled infected birds, cattle or contaminated equipment should prompt avian-influenza testing and public-health notification. 2. Upper-respiratory and systemic illness Fever, chills, headache, myalgia, malaise and anorexia. Sore throat, cough, rhinorrhoea and shortness of breath. Diarrhoea, nausea, vomiting or abdominal pain—particularly described with H5N1. 3. Severe lower-respiratory disease Viral pneumonia can progress rapidly to hypoxaemic respiratory failure, ARDS, shock, secondary bacterial infection, acute kidney injury and multiorgan failure. Findings include tachypnoea, hypoxaemia, crackles, cyanosis, confusion, chest pain and increasing work of breathing. 4. Neurologic complications Encephalitis, encephalopathy, seizures, ataxia and altered consciousness have been reported. Consider neurologic disease particularly when respiratory findings do not fully explain the level of altered mental status. History and examination Ask/examine Examples Clinical importance Animal exposure Sick/dead birds, poultry, wild birds, dairy cattle, cats, live markets Determines whether a novel influenza pathway is needed Type of contact Slaughter, defeathering, milking, culling, cage cleaning, droppings Estimates intensity and route of exposure Eye symptoms Redness, tearing, pain, photophobia, blurred vision May be the dominant presentation Respiratory status Respiratory rate, SpO2, work of breathing, chest signs Detects pneumonia/ARDS early Neurologic/GI status Confusion, seizures, vomiting, diarrhoea Identifies severe or atypical disease Contacts Household and occupational contacts with symptoms Supports monitoring and outbreak investigation Investigations Specific virologic testing Collect respiratory specimens in consultation with the reference laboratory: nasopharyngeal/oropharyngeal swabs for upper-respiratory illness and lower-respiratory specimens when severe pneumonia is present. Collect conjunctival swabs when conjunctivitis is present. Use real-time RT-PCR with assays that detect influenza A and differentiate avian subtypes. Routine seasonal influenza rapid tests may be negative or cannot subtype the virus. Do not delay public-health notification while waiting for a result. Use appropriate PPE and specimen packaging; laboratory workers require trained procedures for potentially high-consequence pathogens. Severity assessment Pulse oximetry, arterial/venous blood gas, chest radiograph or CT when indicated. Full blood count, electrolytes, renal/liver tests, glucose, CRP and lactate. Blood cultures and tests for bacterial coinfection when pneumonia or sepsis is suspected. ECG/troponin and neurologic imaging/CSF only when clinically indicated and safe. Differential diagnosis Condition Clues Seasonal influenza A/B Community circulation without unusual animal exposure; confirm by routine testing. COVID-19 and other respiratory viruses Respiratory syndrome; test according to local protocol. Avian influenza Conjunctivitis, severe pneumonia or GI disease plus bird/mammal exposure. Bacterial pneumonia/sepsis Focal consolidation, purulent sputum, shock or positive cultures; coinfection can occur. Malaria and other tropical febrile diseases Fever after travel/exposure; test in parallel when appropriate. Management Start treatment and infection-control planning early. Current guidance supports prompt antiviral treatment for suspected novel avian-influenza infection, particularly severe disease, while confirmatory testing is arranged. Antiviral therapy

Marburg Virus Disease: Clinical Features, Diagnosis, Management and Prevention Clinical Medicine Year 3 • a severe filovirus infection linked to bats, caves, body fluids and high-consequence outbreaks Clinical safety note: Suspected Marburg virus disease (MVD) is a public-health emergency. Isolate immediately, notify the designated authorities, use trained staff and appropriate PPE, and coordinate all specimen collection, transfer, burial and laboratory work through the national viral-haemorrhagic-fever pathway. Do not assume that absence of bleeding makes the patient safe or that an ordinary fever ward can manage suspected MVD. Why Marburg matters Marburg virus disease is a rare but highly severe viral haemorrhagic fever caused by Marburgvirus or Ravn virus. It begins abruptly with fever, severe headache, malaise and muscle pain, then may progress to watery diarrhoea, vomiting, abdominal pain, rash, shock, organ failure, encephalopathy and bleeding. The presentation overlaps heavily with malaria, typhoid, Ebola, dengue and bacterial sepsis, so exposure history and immediate infection prevention are as important as laboratory confirmation. Marburg and Ebola are both filoviruses and share many clinical and control principles, but they are different viruses. There are currently no approved Marburg vaccine or antiviral treatment; early intensive supportive care is the intervention most likely to improve survival. Learning outcomes Describe Marburg virus classification, morphology, reservoir and routes of transmission. Explain the incubation period, phases of illness and mechanisms of shock and coagulopathy. Recognise early, gastrointestinal, haemorrhagic, neurologic, ocular and genital complications. Plan safe diagnostic testing and differential diagnosis. Describe supportive care, infection prevention, contact monitoring and survivor counselling. Definition and virology Marburg virus and Ravn virus are enveloped, filamentous, non-segmented, negative-sense RNA viruses in the family Filoviridae and genus Marburgvirus (often called Orthomarburgvirus in current taxonomy). The virion contains nucleoprotein and polymerase-associated proteins surrounded by a lipid envelope with glycoprotein spikes. The virus replicates in macrophages, dendritic cells, endothelial cells, hepatocytes and other tissues. Marburg disease was first recognised in 1967 after laboratory-associated outbreaks in Marburg and Frankfurt and Belgrade linked to imported African green monkeys from Uganda. Later outbreaks in Africa have been associated with cave or mine exposure and human-to-human transmission. Reservoir and transmission The Egyptian fruit bat, Rousettus aegyptiacus, is the principal natural reservoir identified for Marburg virus. People may become infected while entering caves/mines or handling bats, then transmit virus to others through body fluids after symptoms begin. Blood, vomit, stool, urine, saliva, sweat, breast milk, semen and other body fluids. Direct contact with a symptomatic patient’s mucous membranes or broken skin. Unsafe injections, contaminated instruments or blood products. Contact with a body during funeral preparation or burial. Sexual exposure to survivors because virus may persist in semen. Patients are not generally infectious before symptoms. Casual contact without body-fluid exposure is not the usual route, but every suspected patient should be assessed conservatively until testing and an exposure history are clear. Incubation and infectious period The incubation period is usually 2–21 days. Early illness may resemble malaria or influenza. Infectivity increases as viral load rises and as vomiting, diarrhoea, bleeding and other wet symptoms develop. In fatal cases, deterioration commonly occurs during the second week, but course and fatality vary by outbreak, viral strain, timing of care and access to intensive support. Pathophysiology Virus enters through mucosa, broken skin, injection or contaminated body-fluid exposure. It replicates in antigen-presenting cells and macrophages and spreads through lymphatics and blood. Immune dysregulation causes high cytokine activity while adaptive immune responses are delayed or ineffective. Endothelial injury and inflammatory mediators increase vascular permeability and promote capillary leak. Hepatocellular injury reduces clotting-factor synthesis; platelet and coagulation abnormalities amplify bleeding. Vomiting and diarrhoea cause severe volume and electrolyte loss, while shock leads to kidney, liver, brain and cardiac dysfunction. Important: A patient with Marburg may die from dehydration, shock, acidosis, kidney failure or multiorgan dysfunction without dramatic external bleeding. Early fluid, electrolyte, glucose and organ support are therefore essential. Clinical presentation 1. Early dry phase Abrupt high fever and severe frontal or temporal headache. Severe malaise, profound weakness, chills and myalgia/arthralgia. Photophobia, conjunctival injection, sore throat and anorexia. Nausea and early abdominal discomfort. 2. Gastrointestinal/wet phase From approximately day 3–5, many patients develop watery diarrhoea, repeated vomiting, abdominal pain, chest pain, cough, hiccups, dehydration and rapid weight loss. The combination of high stool/vomit volume and capillary leak can produce shock even before bleeding appears. 3. Rash and bleeding A non-itchy maculopapular rash may appear around days 5–7. Severe disease may cause petechiae, ecchymoses, bleeding from gums and nose, haematemesis, melaena, haematuria, vaginal bleeding or oozing from venepuncture sites. Bleeding is a late and serious sign, but is neither necessary nor sufficient to diagnose MVD. 4. Neurologic, ocular and genital complications Confusion, agitation, drowsiness, seizures, encephalitis or coma. Eye pain, photophobia, uveitis, visual loss or other post-acute ocular disease. Orchitis, testicular pain and possible viral persistence in semen. Pregnancy complications, fetal loss and infection of placental/reproductive tissues. History and examination Risk domain Questions Clinical significance Cave/mine exposure Entering caves, mines or bat habitats; bat contact Strongly supports a possible index exposure Outbreak contact Household, healthcare, funeral or caregiving contact Identifies high-risk contacts requiring monitoring Body-fluid exposure Blood, vomit, diarrhoea, sexual exposure, needlestick Determines urgent occupational/public-health follow-up Symptoms Fever, headache, diarrhoea, vomiting, abdominal pain, rash, bleeding Guides isolation and severity assessment Organ function Urine, glucose, mental state, breathing, visual and testicular symptoms Identifies complications needing specialist care Investigations Safety first Before collecting blood or swabs, notify the reference laboratory and infection-prevention team. Use trained personnel, appropriate PPE, leak-proof triple packaging and approved transport. Never send a suspected high-risk specimen through an ordinary uncoordinated route. Specific tests RT-PCR: detects viral RNA during acute disease and is the principal confirmatory method. Antigen detection: can support early diagnosis in approved reference or field systems. IgM/IgG serology: helps distinguish recent infection or later immune response but may be negative early. Virus isolation/electron microscopy: specialised high-containment methods; electron microscopy identifies filovirus morphology but does not reliably distinguish Marburg from Ebola. Severity assessment Full blood count, platelets, glucose, electrolytes, urea, creatinine and bicarbonate. AST/ALT, bilirubin, albumin,

Ebola Virus Disease: Clinical Features, Diagnosis, Treatment and Outbreak Control Clinical Medicine Year 3 • a high-consequence viral haemorrhagic fever requiring early isolation, testing and supportive care Clinical safety note: A patient with fever or unexplained illness plus a compatible travel, outbreak, funeral, healthcare or animal-exposure history must be managed through the national viral-haemorrhagic-fever pathway. Call infection-prevention and public-health teams before collecting specimens or moving the patient. Do not perform unsafe injections, venepuncture or invasive procedures without appropriate PPE, trained staff and a plan for contaminated waste. Why Ebola matters Ebola virus disease (EVD) is a severe zoonotic infection caused by viruses in the genus Orthoebolavirus. It can begin as a nonspecific febrile illness and progress to profuse vomiting and diarrhoea, dehydration, shock, organ failure, coagulopathy, encephalopathy and death. The most important clinical intervention is not waiting for bleeding: early recognition, safe isolation, rapid testing, aggressive supportive care and contact tracing save lives. Ebola is not spread by casual contact before symptoms. Once symptoms begin, however, blood, vomit, stool, urine, breast milk, semen, vaginal fluids, saliva and other body fluids can transmit virus. Patients, caregivers, healthcare workers and people involved in funerals are at greatest risk when body fluids are handled without protection. Learning outcomes Describe Ebola virus structure, species, reservoirs and transmission. Explain the incubation period and the pathophysiology of endothelial, immune and hepatic injury. Recognise early, gastrointestinal, haemorrhagic and neurologic stages. Construct a safe diagnostic approach and distinguish EVD from malaria, typhoid, dengue, yellow fever and other VHF. Plan isolation, supportive care, approved species-specific therapeutics, survivor care and outbreak control. Definition and virology Ebola viruses are enveloped, filamentous, non-segmented, negative-sense single-stranded RNA viruses in the family Filoviridae. Important species include Zaire ebolavirus, Sudan ebolavirus, Bundibugyo ebolavirus, Taï Forest ebolavirus and Reston ebolavirus. Zaire ebolavirus is the species associated with many of the largest human outbreaks; Sudan and Bundibugyo viruses require separate clinical and vaccine considerations. The virion contains nucleoprotein, polymerase-associated proteins, matrix proteins and a surface glycoprotein. The glycoprotein enables attachment and entry into host cells and contributes to endothelial dysfunction and immune evasion. Mononuclear phagocytes, dendritic cells, endothelial cells, hepatocytes and adrenal cells become infected, leading to viraemia and multiorgan injury. Reservoir and transmission The exact natural reservoir is not fully established, but fruit bats are an important suspected reservoir. Human index cases may arise after exposure to infected wildlife or carcasses, followed by human-to-human transmission. Direct contact with blood or body fluids of a symptomatic patient. Contact with a deceased patient during preparation or burial. Unsafe injections, blood transfusion or contaminated instruments. Sexual exposure to survivors because Ebola virus can persist in semen for months. Breast milk and other secretions in selected clinical contexts. Animal exposure, including hunting, butchering or handling sick/dead wildlife. Incubation and communicability The incubation period is approximately 2–21 days, most often about one week. People are generally not infectious before symptoms begin. Infectivity rises with illness severity and is highest when the patient has vomiting, diarrhoea, bleeding or large amounts of virus-containing body fluid. Survivors require structured follow-up because viral persistence in semen, breast milk, ocular fluid or other immune-privileged sites can affect counselling and transmission prevention. Pathophysiology Virus enters through mucosa, broken skin, injection or inhalation of contaminated droplets/aerosols during high-risk procedures. It replicates in macrophages and dendritic cells and spreads through lymphatic tissue and blood. Innate immune signalling is disrupted; infected cells release inflammatory mediators while antigen presentation is impaired. Endothelial injury, cytokines and loss of vascular integrity cause capillary leak, hypotension and tissue oedema. Liver injury reduces clotting-factor synthesis; platelet and coagulation abnormalities produce coagulopathy. Vomiting, diarrhoea, fever and capillary leak cause profound dehydration, electrolyte disturbance, acidosis, kidney injury and shock. Clinical reasoning: Haemorrhage is dramatic but not required for diagnosis. A patient can be in life-threatening Ebola shock because of diarrhoeal fluid loss, capillary leak, acidosis and organ failure before visible bleeding appears. Clinical presentation 1. Early dry phase Early features are nonspecific: sudden fever, severe headache, fatigue, weakness, myalgia, arthralgia, backache, sore throat, conjunctival injection and anorexia. Malaria, typhoid, COVID-19 and other febrile infections may look identical at this stage. 2. Gastrointestinal/wet phase Nausea, repeated vomiting and watery diarrhoea. Abdominal pain, dysphagia, hiccups and profound weakness. Dehydration, postural dizziness, oliguria and electrolyte disturbance. Rash, red eyes and worsening transaminases. Confusion, agitation or reduced consciousness from shock, encephalitis or metabolic abnormalities. 3. Haemorrhagic and multiorgan disease Bleeding may include petechiae, ecchymoses, bleeding from venepuncture sites, gums, nose, gastrointestinal tract, vagina or urinary tract. Severe cases can develop shock, acute kidney injury, hepatitis, hypoglycaemia, respiratory distress, encephalopathy, seizures and multiorgan failure. The amount of external bleeding does not reliably predict severity. 4. Pregnancy and newborn considerations Pregnancy is associated with high maternal and fetal risk. Virus can be present in placenta, amniotic fluid, breast milk and other tissues. Pregnant patients require obstetric, infectious-disease and public-health coordination. Avoid unsafe obstetric procedures; use dedicated protocols for delivery, miscarriage, stillbirth and disposal of contaminated material. Case definition and exposure assessment Ask about Examples Why it changes risk Geography/time Residence or travel in an outbreak area within 21 days Links symptoms to an active transmission chain Contact Care for a suspected case, funeral attendance, blood/body-fluid contact Identifies high-risk exposure and contacts Healthcare Needlestick, unsafe injection, unprotected procedure May require urgent occupational-risk management Animal exposure Hunting, butchering or handling wildlife/primates/bats Possible index-case exposure Symptoms Fever, headache, vomiting, diarrhoea, rash, bleeding, weakness Determines triage and isolation urgency Investigations Routine severity assessment in a safe setting Capillary glucose, pulse oximetry, temperature, respiratory rate, blood pressure and mental state. Full blood count and platelets; leukopenia or thrombocytopenia may occur. Electrolytes, urea, creatinine, bicarbonate, liver tests, bilirubin and albumin. PT/INR, aPTT, fibrinogen and lactate where available. Malaria testing, blood cultures and other differential tests only through safe procedures and approved pathways. Specific Ebola tests RT-PCR: the main acute diagnostic test in blood, usually positive after viraemia develops. Antigen-detection tests: useful in approved field or reference-laboratory settings. Serology: IgM may support recent infection; IgG supports previous exposure or

Rift Valley Fever: Zoonotic Transmission, Clinical Features, Diagnosis and Control Clinical Medicine Year 3 • a One Health viral zoonosis affecting people, livestock, mosquitoes and food systems Clinical safety note: Suspected Rift Valley fever (RVF) requires urgent notification, public-health coordination and safe specimen handling. Do not handle blood, aborted tissues, placentas, raw meat or animal carcasses without appropriate PPE and veterinary/public-health guidance. Human treatment is mainly supportive; specialist and reference-laboratory input is essential. Why Rift Valley fever matters Rift Valley fever is a mosquito-borne viral zoonosis that mainly affects livestock but can infect humans. It is clinically important for two reasons: it can cause explosive abortion and neonatal death in sheep, goats and cattle, and it can produce human disease ranging from a short febrile illness to retinitis, meningoencephalitis, haemorrhagic fever, liver failure and death. In Uganda and other African settings, a cluster of livestock abortions, sudden animal deaths and human fever after animal contact should trigger a One Health investigation. The “animal story” is often the clue that distinguishes RVF from malaria, dengue or ordinary viral hepatitis. Learning outcomes Explain RVF virology, vector ecology, animal reservoirs and human exposure routes. Recognise the clinical spectrum from uncomplicated fever to ocular, neurologic and haemorrhagic disease. Construct a safe diagnostic and differential-diagnosis plan. Describe supportive treatment, infection prevention and outbreak control. Apply the One Health relationship between animal vaccination, mosquito control and human protection. Definition and virology RVF virus is an enveloped, segmented, negative-sense RNA virus in the genus Phlebovirus. Modern taxonomy places it in the family Phenuiviridae; older teaching materials may describe it under the former family Bunyaviridae. Its segmented genome allows reassortment, and its ecology is closely linked to mosquitoes, rainfall and livestock amplification. The disease was first recognised in Kenya’s Rift Valley in 1931. It is established in sub-Saharan Africa and has also caused outbreaks in Egypt, the Arabian Peninsula and other regions. The virus primarily circulates between mosquitoes and animals, with humans infected as incidental hosts. Animal hosts and transmission cycle Source/vector How infection occurs Clinical implication Floodwater Aedes mosquitoes Eggs can survive dry periods and hatch after heavy rain/flooding Explains sudden outbreaks after unusual rainfall Other mosquitoes Anopheles, Culex, Mansonia and other genera can amplify and spread virus Outbreak control cannot rely on one mosquito species only Infected livestock Sheep, goats, cattle and camels develop viraemia; pregnant animals may abort Handling blood, placenta, foetus, meat or milk is a major occupational risk Humans Usually a dead-end host; infection follows mosquito bites or animal exposure Human cases can signal an ongoing animal outbreak Routes of human infection Contact with blood, tissues, organs, placenta, aborted foetuses or vaginal secretions of infected animals. Inoculation through cuts, abrasions or contaminated needles. Aerosol exposure during slaughtering, necropsy, butchering or laboratory manipulation. Consumption of raw or inadequately pasteurised milk and possibly undercooked animal products. Bites from infected mosquitoes. There is no evidence of sustained ordinary person-to-person transmission. Nevertheless, blood and tissues from a viraemic patient may expose healthcare workers, laboratory staff and caregivers, so standard precautions and outbreak-specific PPE are essential. Incubation and pathogenesis The human incubation period is commonly about 2–6 days. Virus first replicates at the entry site and lymphoid tissue, followed by viraemia. The liver is a major target, and hepatic necrosis, thrombocytopenia, endothelial injury and inflammatory responses explain fever, jaundice, bleeding and organ failure. In some patients the virus or immune response affects the retina or central nervous system. Exposure through mosquito or infected animal material. Viraemia and systemic inflammatory response. Most patients develop a self-limited influenza-like illness. A small minority develop localised ocular disease, meningoencephalitis or haemorrhagic/hepatic disease. Clinical presentation in humans 1. Uncomplicated febrile illness Many infections are asymptomatic or mild. Symptomatic patients may develop abrupt fever, severe headache, malaise, weakness, myalgia, arthralgia, backache, nausea, vomiting, photophobia and dizziness. Conjunctival injection and mild hepatitis can occur. 2. Ocular disease Retinal vasculitis, macular lesions or retinitis may appear after the systemic illness. Blurred vision, scotomata, photophobia, floaters and reduced visual acuity require urgent ophthalmologic assessment. Visual loss may be permanent even when the fever resolves. 3. Meningoencephalitis Neurologic disease may develop later, with severe headache, neck stiffness, photophobia, confusion, drowsiness, seizures, focal deficits, weakness or coma. Consider RVF in a patient with encephalitis and a compatible livestock/mosquito exposure, while urgently excluding bacterial meningitis, malaria, HSV, TB and other viral infections. 4. Haemorrhagic and hepatic disease Jaundice, hepatomegaly and marked transaminase elevation. Bleeding from gums, nose, gastrointestinal tract or injection sites. Easy bruising, petechiae, haematuria and disseminated intravascular coagulation. Shock, renal failure, hypoglycaemia, encephalopathy and multiorgan failure. Severe-disease alert Persistent vomiting, jaundice, altered mental state, visual symptoms, seizures, active bleeding, hypotension, oliguria, severe thrombocytopenia or rapidly worsening liver tests require admission and specialist escalation. Animal clues that support human RVF During an outbreak, veterinarians may observe sudden large numbers of abortions, high neonatal mortality, fever, weakness, diarrhoea and hepatic necrosis in young livestock. Pregnant ewes and goats can abort at very high rates. These findings are epidemiologically important even if human patients have only mild fever. History and examination History/exam focus Questions and findings Why it matters Animal contact Slaughtering, butchering, assisting births, handling abortions, veterinary work, farming Direct tissue exposure is a major route Animal outbreak Abortion storms, neonatal deaths, livestock illness or unexplained animal deaths Strongly raises suspicion and guides public-health response Mosquito/rainfall exposure Flooding, heavy rains, outdoor work, mosquito abundance Supports vector-borne acquisition Eyes Visual loss, floaters, scotoma, photophobia May indicate retinal disease Neurologic state Headache, neck stiffness, seizures, weakness, confusion Identifies meningoencephalitis Bleeding/liver/kidney Jaundice, bleeding, abdominal pain, urine output, bruising Identifies severe haemorrhagic/hepatic disease Investigations and specimen safety Routine assessment Full blood count and platelets. AST, ALT, bilirubin, albumin, glucose, urea, creatinine and electrolytes. PT/INR, aPTT, fibrinogen and lactate where available. Malaria test, blood cultures and other febrile-illness investigations. CSF studies and brain imaging only when safe and when meningitis/encephalitis is suspected. Ophthalmologic examination for any visual complaint. Specific diagnosis RT-PCR: detects viral RNA early in blood or tissue and is particularly useful during

Dengue Fever: Clinical Features, Warning Signs, Diagnosis and Management Clinical Medicine Year 3 • dengue illness, dengue with warning signs, severe dengue and dengue shock Clinical safety note: Dengue can deteriorate rapidly when fever settles and the critical phase begins. Treatment is mainly careful fluid management and monitoring. Avoid aspirin, ibuprofen, diclofenac and intramuscular injections until significant bleeding risk has been excluded. Use current national/WHO/CDC guidance for fluid volumes, admission and paediatric care. Why dengue matters Dengue is an acute infection caused by one of four closely related dengue virus serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). It is transmitted mainly by infected female Aedes aegypti mosquitoes. Most illness is self-limited, but plasma leakage, shock, severe bleeding, liver failure, myocarditis and encephalopathy can develop—often around the time the fever improves. The key bedside skill is to classify the patient repeatedly. A patient who looks stable during the febrile phase may become critically ill during the 24–48-hour critical phase. Serial examination, haematocrit, urine output, pulse pressure and mental state are more useful than a single platelet count. Learning outcomes Explain dengue serotypes, transmission, pathogenesis and the risk of secondary infection. Distinguish undifferentiated dengue, dengue with warning signs and severe dengue. Recognise the febrile, critical and recovery phases. Interpret CBC, haematocrit, liver tests, NS1/PCR and dengue serology. Manage hydration, shock, bleeding, organ dysfunction and safe discharge. Definition, virology and epidemiology Dengue virus is an enveloped, positive-sense single-stranded RNA flavivirus. Infection with one serotype usually gives long-lasting immunity to that serotype but only temporary and incomplete protection against the others. A later infection with a different serotype can be more severe in some patients because pre-existing non-neutralising antibodies may facilitate viral entry into Fc-receptor-bearing cells—an immunologic process called antibody-dependent enhancement. Dengue is endemic in many tropical and subtropical regions. Risk increases with urban crowding, water storage, climate conditions that support mosquito breeding, population movement and low community immunity. Transmission and incubation An infected female Aedes mosquito acquires virus while feeding on a viraemic person. After an extrinsic incubation period in the mosquito, it can transmit dengue during later bites. Mosquitoes commonly bite during daylight, especially in the early morning and late afternoon. Human incubation is usually about 4–10 days. Rare non-vector transmission can occur through blood products, organ transplantation or vertical transmission. Pathophysiology: why severe dengue causes shock Virus replicates in dendritic cells, monocytes and macrophages and triggers innate immune responses. Cytokines, complement and endothelial mediators alter vascular permeability. In severe disease, plasma leaks from the intravascular space into the pleural and abdominal cavities while red cells remain intravascular. Intravascular volume falls even though the patient may appear oedematous. Haematocrit rises because plasma is lost but red cells are concentrated. If leakage is untreated, tissue perfusion fails, causing metabolic acidosis, organ injury and shock. Platelet destruction, marrow suppression and coagulopathy contribute to mucosal or gastrointestinal bleeding. Interpretation principle: In a patient with warning signs, a rising haematocrit with a falling platelet count suggests ongoing plasma leakage. A falling haematocrit in a shocked patient may instead indicate bleeding or haemodilution after fluids. Clinical phases Phase Typical timing What to look for Febrile Usually 2–7 days High fever, headache, retro-orbital pain, myalgia, arthralgia, nausea, vomiting, rash, mild bleeding and leukopenia Critical Often around defervescence; about 24–48 hours Capillary leakage, rising haematocrit, narrow pulse pressure, shock, fluid accumulation, severe bleeding or organ dysfunction Recovery After leakage stops Reabsorption of fluid, improved appetite/urine, slowing pulse, convalescent rash and sometimes transient bradycardia Clinical manifestations Uncomplicated dengue Sudden high fever, chills and severe headache. Retro-orbital pain, photophobia and marked muscle, bone or joint pains (“breakbone fever”). Nausea, vomiting, anorexia and abdominal discomfort. Macular or maculopapular rash, facial flushing and pruritus during recovery. Mild gum or nose bleeding, petechiae or a positive tourniquet test may occur. Leukopenia and thrombocytopenia are common; not every low platelet count means severe disease. Warning signs Severe abdominal pain or abdominal tenderness. Persistent vomiting or inability to maintain oral fluids. Clinical fluid accumulation: ascites, pleural effusion or pericardial effusion. Mucosal bleeding, haematemesis, melaena, haematuria or heavy vaginal bleeding. Lethargy, restlessness, irritability, confusion or reduced Glasgow Coma Scale. Enlarged tender liver. Progressively rising haematocrit, especially with rapidly falling platelets. Reduced urine output, cold extremities, tachycardia or narrowing pulse pressure. Severe dengue Severe dengue is diagnosed when there is one or more of: Severe plasma leakage causing shock or respiratory distress from fluid accumulation. Severe bleeding judged clinically important, especially with haemodynamic compromise. Severe organ involvement: AST/ALT often very high, encephalitis/encephalopathy, myocarditis, arrhythmia, acute kidney injury or other organ failure. History and examination Assess Questions/examination Clinical decision Timing Day of illness, day fever settled, prior dengue and travel/outbreak exposure Predicts the transition into the critical phase Hydration Oral intake, vomiting, thirst, mucosa, capillary refill, urine volume Determines oral versus IV fluids Circulation Pulse, systolic/diastolic BP, pulse pressure, extremity temperature, mental state Detects compensated shock before hypotension Leakage/bleeding Abdominal tenderness, ascites, pleural signs, gums, stool, urine, menstrual loss Guides admission and blood-product decisions Organ function Glucose, liver size, jaundice, neurologic state, chest findings, ECG Identifies severe dengue and ICU needs Special groups Pregnancy, infancy, elderly age, obesity, renal/cardiac disease Requires lower threshold for observation and careful fluid titration Investigations Baseline and serial tests Full blood count: leukopenia, thrombocytopenia and serial haematocrit. Haematocrit should be interpreted with the fluid history and bleeding assessment. Urea, creatinine, electrolytes, glucose, AST/ALT, bilirubin and albumin. Coagulation profile when bleeding, liver failure or severe illness is suspected. Chest radiograph or ultrasound for pleural effusion, ascites and pulmonary oedema. ECG/troponin/echocardiography when myocarditis or arrhythmia is suspected. Malaria testing and cultures when clinically indicated; dengue and malaria can coexist. Specific dengue tests RT-PCR: detects viral RNA early in illness and can identify serotype. NS1 antigen: useful in the early febrile period, although sensitivity varies by serotype and whether infection is primary or secondary. IgM: usually becomes detectable after approximately day 4–5 and remains detectable for weeks to months. IgG: a single positive result often indicates previous flavivirus exposure; paired sera or a fourfold rise is more

Yellow Fever: Clinical Features, Diagnosis, Management and Prevention Clinical Medicine Year 3 • an African arboviral disease with hepatic, renal and haemorrhagic complications Clinical safety note: Suspected yellow fever is a notifiable public-health emergency. Isolate the patient from mosquitoes, notify the health authorities, obtain expert laboratory advice and manage in hospital. There is no routine specific antiviral cure; survival depends on early recognition, careful supportive care and prevention of complications. Why yellow fever matters Yellow fever is an acute mosquito-borne viral haemorrhagic disease caused by yellow fever virus, a flavivirus. It ranges from an asymptomatic or mild febrile illness to a toxic phase with jaundice, coagulopathy, shock, renal failure, encephalopathy and death. Because early yellow fever can look like malaria, viral hepatitis, dengue or sepsis, the diagnosis is often missed unless the clinician asks about mosquito exposure, travel, vaccination and outbreaks. The word “yellow” refers to jaundice from hepatic injury. The disease is not spread by ordinary casual contact, but a patient with circulating virus can infect a mosquito that later bites another person. Early mosquito precautions therefore protect both the patient and the community. Learning outcomes Describe the virus, vectors, reservoirs and jungle, intermediate and urban transmission cycles. Explain the clinical phases from incubation through acute and toxic disease. Recognise jaundice, bleeding, shock, renal failure and encephalopathy as danger signs. Choose appropriate laboratory tests and distinguish yellow fever from malaria, hepatitis, dengue and other severe febrile diseases. Provide safe supportive management and explain vaccination, mosquito control and outbreak response. Definition and virology Yellow fever virus is an enveloped, positive-sense single-stranded RNA virus in the genus Flavivirus. It is an arbovirus because it is transmitted by arthropods. The virus has a strong tropism for hepatocytes, reticuloendothelial cells and other tissues. Viral replication, apoptosis and inflammatory injury can produce midzonal hepatic necrosis, cholestasis, coagulopathy and multiorgan dysfunction. Epidemiology and transmission cycles Yellow fever remains endemic in tropical parts of Africa and South America. Uganda is within the African risk zone, so a febrile jaundiced patient with mosquito exposure or an outbreak connection requires serious consideration of yellow fever alongside malaria and viral hepatitis. Cycle Reservoir and vector Clinical/public-health meaning Sylvatic (jungle) Non-human primates and forest mosquitoes; humans enter the cycle when they work or travel in forest Occupational and travel-related cases; primate deaths may precede human cases Intermediate (savannah) Forest-edge mosquitoes infect monkeys and humans in rural or semi-rural areas Can cause rural outbreaks and bridge infection toward towns Urban Infected humans and peridomestic Aedes mosquitoes, especially Aedes aegypti Rapid explosive outbreaks where population immunity is low An infected mosquito becomes capable of transmission after an extrinsic incubation period. Humans are most infectious to mosquitoes around the early viraemic days of illness. A person does not normally infect another person directly by touch, coughing or sharing food. Risk factors Living in or visiting a yellow-fever-endemic area without vaccination. Forest work, farming, hunting, logging, fishing or outdoor night/day exposure depending on the vector. Low community vaccine coverage, urban crowding and abundant breeding sites. Immunosuppression or advanced age, which may increase the risk of severe vaccine adverse effects or severe natural disease. Pregnancy and young infancy require careful vaccine-risk decisions in a travel or outbreak context. Pathophysiology After a mosquito bite, virus replicates locally and enters lymphatic tissue. Viraemia disseminates virus to the liver, spleen, lymph nodes, kidney and bone marrow. Hepatocyte injury causes jaundice, raised aminotransferases, impaired clotting-factor synthesis and hypoglycaemia. Systemic endothelial injury, cytokines and coagulation abnormalities produce bleeding, capillary leak and shock. Acute kidney injury results from shock, direct injury and pigment/volume effects; encephalopathy may reflect hepatic failure, shock or metabolic derangement. Teaching link: In yellow fever, jaundice is not simply a liver-test abnormality. It is a visible marker of a disease process that can simultaneously disturb clotting, glucose control, kidney perfusion and brain function. Clinical course 1. Incubation phase Symptoms commonly begin about 3–6 days after an infective mosquito bite. The patient is usually well during incubation. 2. Acute febrile phase This phase usually lasts several days and may include sudden fever, chills, severe headache, backache, myalgia, arthralgia, nausea, vomiting, photophobia, weakness and facial flushing. Conjunctival injection and relative bradycardia may be present. Laboratory findings can include leukopenia, thrombocytopenia, raised transaminases and mild proteinuria. 3. Remission phase Many patients improve after the initial fever. A short remission does not always mean cure; clinicians must warn patients to return if jaundice, bleeding, severe abdominal pain, reduced urine, confusion or recurrent fever appears. 4. Toxic phase A minority progress to severe disease, often after apparent improvement. Findings include: Jaundice, dark urine, pale stool and tender hepatomegaly. Persistent vomiting, epigastric or right-upper-quadrant pain. Bleeding from gums, nose, gastrointestinal tract, injection sites or uterus; petechiae and ecchymoses. Hypotension, narrow pulse pressure, cold extremities, oliguria and metabolic acidosis. Acute kidney injury, haematuria and reduced urine output. Hypoglycaemia, agitation, drowsiness, seizures or hepatic encephalopathy. Myocarditis, arrhythmias, respiratory failure, disseminated intravascular coagulation and multiorgan failure. Bedside danger signs Jaundice plus bleeding, persistent hypotension, altered mental state, oliguria, hypoglycaemia, severe abdominal pain, rapidly rising INR, severe thrombocytopenia or worsening creatinine should be treated as toxic yellow fever until proven otherwise. History and examination Ask or examine Why it matters Onset, travel and residence Links illness to endemic area or a known outbreak and estimates incubation. Vaccination card and prior yellow fever A documented vaccine or past infection greatly changes probability, but does not replace testing in a compatible outbreak. Mosquito and forest exposure Identifies sylvatic or urban risk. Malaria tests and treatment Failure to improve after appropriate antimalarial therapy should prompt a wider differential. Bleeding and urine output Detects coagulopathy and kidney injury early. Neurologic state and glucose Encephalopathy and hypoglycaemia are potentially reversible emergencies. Jaundice, hydration, shock, hepatosplenomegaly Assesses severity and need for admission/critical care. Investigations Initial severity assessment Full blood count with platelet count and haematocrit. Urea, creatinine, electrolytes, glucose and urinalysis. AST, ALT, bilirubin, albumin and alkaline phosphatase. PT/INR, aPTT, fibrinogen and lactate where available. Blood group and cross-match if bleeding or severe

Cytomegalovirus (CMV) Infection: Clinical Features, Diagnosis and Management Clinical Medicine Year 3 • CMV in immunocompetent people, pregnancy, newborns, HIV and transplant patients Clinical safety note: CMV treatment is specialist-directed. Doses, duration, renal adjustment, pregnancy decisions and newborn treatment must follow the current Uganda Clinical Guidelines, local laboratory capability and infectious-disease/paediatric advice. Ganciclovir, valganciclovir, foscarnet and cidofovir can cause serious marrow, renal and reproductive toxicity. Why CMV matters Cytomegalovirus is a ubiquitous human herpesvirus that usually produces silent or mild infection in an immunocompetent host but can cause destructive disease when cellular immunity is immature or impaired. The same virus therefore has very different meanings in a healthy adult, a pregnant woman, a newborn, a person with advanced HIV, and a transplant recipient. The important clinical question is not simply “Is CMV present?” Many healthy adults remain CMV-IgG positive for life. The clinically useful question is: Is there evidence of recent infection, viral replication, tissue-invasive disease, or congenital infection in a vulnerable patient? Learning outcomes Explain CMV classification, latency, reactivation and the major routes of transmission. Distinguish primary infection, reinfection, reactivation, congenital infection and perinatal infection. Recognise CMV mononucleosis, congenital CMV, retinitis, pneumonitis, gastroenteritis, encephalitis and disseminated disease. Select and interpret PCR, serology, antigen testing, histology, ophthalmology and newborn tests. Plan supportive care, antiviral induction/maintenance, monitoring, prevention and follow-up. Definition and virology CMV, also called human herpesvirus type 5 (HHV-5), is an enveloped double-stranded DNA virus in the Herpesviridae family and Betaherpesvirinae subfamily. It has a large genome and replicates slowly. Infected cells enlarge and may show basophilic intranuclear inclusions surrounded by a clear halo—the classic “owl-eye” appearance—although immunohistochemistry and molecular tests are now more sensitive in many settings. Like other herpesviruses, CMV persists after the first infection. Latent virus remains mainly in cells of the monocyte/macrophage lineage and other tissues. Immunosuppression, inflammation, transplantation, HIV immune failure or severe illness can allow reactivation and renewed viral replication. Epidemiology and risk groups CMV infection is common worldwide, with seroprevalence varying by age, crowding, breastfeeding, sexual exposure and socioeconomic conditions. A positive CMV-IgG result is therefore common and does not by itself prove active disease. Patient group Why disease may be severe Typical clinical concern Immunocompetent adult Usually effective T-cell control Asymptomatic infection or heterophile-negative mononucleosis Pregnant woman and fetus Placental transmission can injure the developing brain, ear, eye and growth pathways Congenital CMV, fetal growth restriction, sensorineural hearing loss Newborn, especially preterm Immature cellular and humoral immunity Sepsis-like illness, pneumonitis, hepatitis, thrombocytopenia Advanced HIV Low CD4-mediated immunity permits tissue invasion Retinitis, colitis, oesophagitis, encephalitis and disseminated disease Solid-organ or stem-cell transplant recipient Immunosuppressive drugs and donor/recipient mismatch Viral syndrome, pneumonitis, graft dysfunction and opportunistic coinfection Transmission CMV is present in saliva, urine, blood, semen, vaginal secretions, cervical secretions, breast milk and transplanted tissues. Transmission normally requires close or repeated contact rather than casual contact across a room. Congenital: transplacental infection during pregnancy after maternal primary infection, reinfection or reactivation. Primary infection generally carries the greater fetal risk, but reactivation can still transmit. Perinatal: exposure to genital secretions during delivery and breast milk. In a term infant this is often asymptomatic; very premature infants can develop clinically important disease. Child-to-child: saliva and urine from toddlers are important sources. Sharing utensils, kissing on the mouth and contact with nappies can transmit virus. Sexual: semen and cervical/vaginal secretions. Blood and organs: transfusion of infected cellular products and transplantation from a CMV-positive donor. Pathogenesis: how latent virus becomes disease CMV enters mucosal or damaged tissue cells and spreads locally and through blood leukocytes. The immune system usually suppresses replication but does not eradicate the virus. Latency is maintained in monocytes and progenitor cells; inflammation or immunosuppression activates viral gene expression. New virions infect endothelial, epithelial, stromal and neural tissues. The resulting tissue injury may be direct viral cytopathy plus immune-mediated inflammation. In pregnancy, placental infection can impair fetal growth and neurodevelopment. In advanced HIV, inadequate T-cell control permits high viral load and destructive retinitis, colitis or encephalitis. Clinical reasoning: CMV disease is most likely when a compatible organ syndrome occurs in a patient with impaired cellular immunity and there is evidence of viral replication or tissue invasion. Detecting CMV DNA in blood alone does not prove that CMV caused a particular symptom. Clinical presentations 1. Asymptomatic infection Most infections in children and healthy adults are silent. The patient may have no illness but can intermittently shed CMV in saliva or urine for months or years. A positive IgG often represents remote infection rather than current disease. 2. CMV mononucleosis in an immunocompetent host After an incubation period commonly measured in weeks, some adolescents and adults develop prolonged fever, profound fatigue, malaise, myalgia, headache, sore throat, cervical or generalised lymphadenopathy and mild hepatitis. Atypical lymphocytosis and raised transaminases are common. Unlike Epstein–Barr virus mononucleosis, prominent exudative tonsillitis and heterophile antibody positivity are less typical. Usually self-limited over several weeks. Possible complications include hepatitis, haemolysis, thrombocytopenia, myocarditis, pneumonitis, meningoencephalitis and Guillain–Barré syndrome, but these are uncommon in healthy people. 3. Congenital CMV Congenital CMV means infection acquired before birth. Some infants are normal at birth but later develop hearing loss or developmental difficulty. Symptomatic disease may include: Intrauterine growth restriction, prematurity and poor feeding. Microcephaly, seizures, hypotonia or abnormal neurologic examination. Periventricular calcifications, ventriculomegaly, white-matter abnormalities or cortical malformations. Petechiae and purpura (“blueberry muffin” appearance), thrombocytopenia and anaemia. Jaundice, hepatosplenomegaly, hepatitis and cholestasis. Chorioretinitis, optic abnormalities and sensorineural hearing loss. Congenital versus perinatal infection Testing after the first few weeks becomes difficult because urine or saliva PCR may reflect postnatal acquisition. To confirm congenital infection, test saliva or urine by PCR as soon as possible and ideally within the first 21 days of life. A positive test beyond this window cannot reliably distinguish congenital from perinatal infection without stored newborn samples or additional evidence. 4. CMV disease in advanced HIV CMV disease is classically associated with severe immune suppression, particularly a very low CD4 count, although effective ART has reduced its frequency. Presentations include: Retinitis: painless

HIV/AIDS and Opportunistic Infections: Comprehensive Clinical Diagnosis and Management Clinical Medicine Year 3 • a future-doctor chapter for HIV care in Uganda Clinical safety note: Antiretroviral regimens, opportunistic-infection doses, prophylaxis thresholds, pregnancy care and timing of ART must follow the current Uganda Clinical Guidelines, national HIV treatment guidelines, resistance results and specialist advice. Doses below are learning examples—not a substitute for a current prescription chart. Why HIV and opportunistic infections require one integrated approach HIV is not simply a positive test or a low CD4 number. It is a chronic viral infection that progressively impairs cellular and humoral immunity, allowing organisms that are harmless or easily controlled in healthy people to cause severe disease. A patient may present with pneumonia, chronic diarrhoea, meningitis, visual loss, weight loss, fever, lymphadenopathy, malignancy or a combination of several conditions. Successful care has five linked components: confirm HIV safely; assess the stage, viral load, CD4 count and comorbidities; identify and treat active opportunistic infections (OIs); start and monitor effective antiretroviral therapy (ART); and prevent recurrence through prophylaxis, vaccination, screening, adherence, nutrition and social support. Learning outcomes Define HIV infection, AIDS, immune failure, opportunistic infection and immune reconstitution inflammatory syndrome. Explain HIV structure, CD4-cell infection, viral replication, immune activation and progressive immune dysfunction. Describe transmission, prevention, testing, counselling, disclosure, stigma and the principle of undetectable = untransmittable. Stage disease using symptoms, WHO clinical staging, CD4 count, viral load and OI patterns. Take a complete HIV/OI history and perform a system-based examination. Order and interpret HIV tests, viral load, CD4, resistance testing, cultures, imaging, CSF, ophthalmology and tissue studies. Recognise the clinical presentation and emergency management of major fungal, bacterial, protozoal and viral OIs. Plan ART initiation, drug interactions, adherence, monitoring, prophylaxis, pregnancy/paediatric care and IRIS management. Prevent OIs through cotrimoxazole and other appropriate prophylaxis, TB preventive treatment, vaccination, safe water, food safety and screening. 1. Definitions Human immunodeficiency virus (HIV) is an enveloped RNA retrovirus that targets cells expressing CD4, especially CD4 T lymphocytes, macrophages and dendritic cells. HIV-1 causes most global disease; HIV-2 is less common and has different geographic and resistance considerations. AIDS describes advanced HIV infection with severe immune suppression, an AIDS-defining condition or both. A patient can have advanced disease despite a single apparently acceptable CD4 result, and a person with a high CD4 can still develop an OI if another immune or structural problem exists. Opportunistic infections are infections that occur more often, are more severe or behave atypically when host immunity is weakened. The organisms and body sites vary with CD4 level, ART exposure, prophylaxis, geography and local prevalence. The supplied SlideShare sources group OIs into bacterial, fungal, protozoal and viral categories and emphasise that falling CD4 increases OI risk. See the organ-based OI overview. 2. HIV microbiology and replication Attachment and entry: viral gp120 binds CD4 and a co-receptor (usually CCR5 early or CXCR4 later), while gp41 mediates fusion. Reverse transcription: viral RNA is converted into DNA by reverse transcriptase; errors create genetic diversity and drug resistance. Integration: integrase inserts viral DNA into the host genome, creating a long-lived reservoir. Transcription and translation: infected cells produce viral RNA and proteins. Assembly and budding: immature virions bud from the cell membrane. Maturation: protease cleaves polyproteins into functional components; the new virion becomes infectious. ART targets these stages using nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs), non-nucleoside reverse-transcriptase inhibitors (NNRTIs), integrase inhibitors, protease inhibitors, entry/fusion inhibitors and pharmacokinetic boosters. Combination therapy prevents one drug from selecting resistant variants. 3. Natural history and pathogenesis 3.1 Acute retroviral syndrome Two to four weeks after infection, viraemia can cause fever, rash, sore throat, lymphadenopathy, myalgia, headache, diarrhoea, oral/genital ulcers, aseptic meningitis or hepatitis. Symptoms are non-specific and may resemble malaria, EBV, influenza or COVID-like illness. Antibody tests can be negative during the window period; laboratory testing must follow the current algorithm. 3.2 Clinical latency is not viral latency After acute infection, viral replication continues in lymphoid tissues even when the patient is asymptomatic. CD4 cells are progressively lost through direct infection, apoptosis, immune-mediated killing, exhaustion and damage to gut-associated lymphoid tissue. Without ART, viral load, immune activation and opportunistic disease risk eventually rise. 3.3 Advanced disease When cellular immunity fails, latent organisms reactivate and new pathogens cause invasive disease. Mucosal barriers, neutrophil function, antibody responses and macrophage activation are also impaired. ART can restore immune function, but rapid immune recovery against a hidden pathogen can trigger inflammatory disease—IRIS. 4. Transmission, prevention and counselling 4.1 Routes of transmission Sexual exposure to infected genital/rectal/pharyngeal secretions. Blood exposure through shared needles, unsafe injections, unscreened blood or unsterile procedures. Vertical transmission during pregnancy, delivery or breastfeeding. Occupational exposure to infected blood; casual contact, hugging, sharing food, mosquitoes and intact skin do not transmit HIV. 4.2 Prevention package Condoms, lubricants, HIV testing and treatment of STIs. PrEP for eligible HIV-negative people and PEP after significant exposure, started urgently according to national policy. Safe blood, sterile instruments, injection safety and harm-reduction services. Universal ART and support for viral suppression: sustained undetectable viral load prevents sexual transmission (U=U), but does not prevent other STIs. Prevention of mother-to-child transmission through antenatal testing, maternal ART, safe delivery, infant prophylaxis/diagnosis and breastfeeding guidance under Uganda’s programme. 4.3 Counselling essentials Obtain consent, protect privacy, use non-judgemental language, assess safety and disclosure risk, involve a chosen treatment supporter, discuss partner testing and screen for depression, violence, substance use, food insecurity and stigma. “Disclosure” is a supported clinical process, not an instruction to tell everyone immediately. 5. HIV diagnosis and staging 5.1 Testing algorithm Use the national serial or parallel testing algorithm with validated assays. A reactive screening test is not the same as a confirmed diagnosis. Resolve discordant or indeterminate results through the reference algorithm, repeat testing at the correct interval and assess recent exposure. Window period: recent exposure may precede detectable antibodies; antigen/antibody or nucleic-acid testing may detect infection earlier. Confirmatory testing: never diagnose or label a patient from one unconfirmed reactive test. Infants under 18 months: maternal antibody makes antibody testing unreliable; use virological early-infant

Chlamydial Infections: Complete Clinical Guide to Urogenital, Rectal, Ocular and Systemic Disease Clinical Medicine Year 3 • sexually transmitted, perinatal and intracellular infection Confidentiality and partner care are part of treatment. Obtain consent, protect privacy, test for other STIs, treat partners according to local policy and prevent reinfection. Use the current Uganda STI guidelines for drug choice, pregnancy and neonatal treatment. Why chlamydia matters Chlamydia trachomatis is frequently asymptomatic but can silently damage the upper genital tract. Untreated infection may cause pelvic inflammatory disease, infertility, ectopic pregnancy, chronic pelvic pain, epididymitis and neonatal conjunctivitis or pneumonia. Rectal infection, lymphogranuloma venereum (LGV), trachoma and respiratory chlamydial disease require different questions and treatment durations. Learning outcomes Describe chlamydial structure, elementary/reticulate bodies and the intracellular life cycle. Relate serovars to trachoma, urogenital infection and LGV. Recognise cervical, urethral, rectal, pharyngeal, ocular, neonatal, PID and epididymal syndromes. Choose NAAT specimens from every exposed site and understand test-of-cure indications. Provide pregnancy-safe treatment, partner management, retesting, screening and prevention. Identify PID, tubo-ovarian abscess, testicular torsion, neonatal pneumonia and LGV complications requiring referral. 1. Organism and life cycle Chlamydiae are obligate intracellular bacteria with a biphasic life cycle: Elementary body (EB): small, metabolically inactive, extracellular and infectious; attaches to columnar epithelial cells. Endocytosis and inclusion: the EB enters a host cell and remains within a membrane-bound inclusion. Reticulate body (RB): metabolically active form that divides inside the inclusion. Reorganisation: RBs convert back to infectious EBs. Release: host-cell lysis or extrusion spreads EBs to neighbouring cells and new hosts. Persistence can occur during immune stress or antibiotic pressure, helping explain chronic inflammation and recurrent symptoms. 2. Serovars and related species Organism/serovar Main syndrome Clinical focus C. trachomatis A–C Trachoma Repeated conjunctival infection, scarring and blindness C. trachomatis D–K Urogenital, rectal, pharyngeal and neonatal infection PID, infertility, epididymitis and infant disease C. trachomatis L1–L3 Lymphogranuloma venereum Invasive lymphatic infection, proctitis and buboes C. pneumoniae Respiratory infection Pharyngitis, bronchitis and atypical pneumonia C. psittaci Psittacosis Bird exposure, atypical pneumonia, hepatitis/myocarditis/encephalitis 3. Transmission and risk factors Urogenital, rectal and pharyngeal infection spreads through vaginal, anal or oral sexual contact. Perinatal transmission occurs during delivery. Reinfection is common when partners are untreated. Risk is increased by a new/multiple partner, inconsistent condom use, previous STI, limited screening access, sexual violence, young age and lack of partner treatment. Trachoma spreads through close contact, secretions, hands, clothing and flies in settings with inadequate water and sanitation. 4. Clinical syndromes 4.1 Cervicitis Many women are asymptomatic. Possible findings include mucopurulent endocervical discharge, easily induced cervical bleeding, post-coital bleeding, dysuria, intermenstrual bleeding and lower abdominal discomfort. Untreated ascending infection may be silent until infertility or ectopic pregnancy occurs. 4.2 Urethritis in men and women Dysuria, urethral irritation, scant mucous discharge and urinary frequency may occur. Gonorrhoea often produces more purulent discharge, but co-infection is common and cannot be excluded clinically. 4.3 Pelvic inflammatory disease Lower abdominal pain, cervical motion tenderness, uterine/adnexal tenderness, fever, dyspareunia, abnormal bleeding, nausea and vomiting indicate possible PID. Chlamydia may coexist with gonorrhoea and anaerobes. Delay increases tubal damage, ectopic pregnancy and infertility. 4.4 Epididymitis and male upper-tract disease Unilateral scrotal pain, epididymal tenderness/swelling, dysuria and fever can occur. Always exclude testicular torsion in sudden severe pain, high-riding testis, absent cremasteric reflex or vomiting. 4.5 Rectal and pharyngeal infection Rectal infection may be asymptomatic or cause proctitis—pain, discharge, bleeding, tenesmus and painful defecation. Pharyngeal infection is often asymptomatic but can contribute to transmission; test the site when exposed. 4.6 LGV L1–L3 infection may begin with a small painless genital/rectal papule or ulcer that resolves, followed by painful inguinal/femoral lymphadenopathy (“buboes”), fever and proctitis. Chronic infection can cause strictures, fistulas, lymphoedema and genital/rectal destruction. 4.7 Neonatal infection Conjunctivitis typically begins 5–14 days after birth with eyelid swelling and mucopurulent discharge. Pneumonia may develop at several weeks with an afebrile staccato cough, tachypnoea and wheeze. Topical drops alone do not eradicate nasopharyngeal infection. 4.8 Trachoma and respiratory chlamydiae Repeated trachoma causes conjunctival follicles, scarring, entropion and corneal damage. C. pneumoniae causes pharyngitis/atypical pneumonia; C. psittaci follows bird exposure with fever, headache, myalgia, dry cough, interstitial pneumonia and occasional hepatitis, myocarditis or encephalitis. Urgent referral: severe pelvic pain, fever and vomiting, pregnancy with suspected PID, adnexal mass/tubo-ovarian abscess, acute scrotum, visual threat, neonatal respiratory distress, meningitis or disseminated infection. 5. History and examination Ask sensitively Symptoms, onset, sites of sexual exposure and condom use; ask separately about vaginal, anal and oral exposure. Partners in the previous 60 days, previous STI/PID, infertility, ectopic pregnancy, contraception, pregnancy possibility and antibiotics. Consent, safety, sexual violence, confidentiality and ability to notify/treat partners. HIV, syphilis, hepatitis and gonorrhoea risk; bird exposure for atypical pneumonia; water/sanitation for trachoma. Examination Inspect external genitalia, discharge, ulcers and nodes. Perform speculum examination where indicated, looking for mucopurulent cervicitis and contact bleeding. Bimanual examination assesses cervical motion, uterine and adnexal tenderness. Examine testes/epididymis and inguinal nodes. Assess rectum, pharynx, eyes, chest and neurological system according to symptoms. Obtain consent and protect privacy throughout. 6. Diagnosis 6.1 NAAT is preferred Nucleic acid amplification testing is the most sensitive routine test. Use first-catch urine or a vaginal/cervical swab, and obtain rectal or pharyngeal swabs from every exposed site. Self-collected vaginal swabs are acceptable where validated. A negative urine test does not exclude rectal or pharyngeal infection. 6.2 Other tests Culture is specialised and mainly useful for research or selected resistance/forensic questions. Microscopy is not sensitive for chlamydia; intracellular inclusions are not a reliable routine diagnosis. Test for gonorrhoea, HIV, syphilis and hepatitis according to risk and local policy. Pregnancy test before selecting treatment; urine dip/culture when UTI is a competing diagnosis. PID: diagnosis is clinical; ultrasound supports tubo-ovarian abscess or ectopic pregnancy but a normal scan does not exclude early PID. Neonate: conjunctival swab/NAAT and respiratory assessment; evaluate for pneumonia and sepsis. 7. Differential diagnosis Syndrome Differentials Key distinction Cervicitis/urethritis Gonorrhoea, Mycoplasma genitalium, trichomoniasis, BV, candidiasis, HSV, UTI NAAT/culture and discharge pattern; co-infection common Pelvic pain/PID Ectopic pregnancy, appendicitis, ovarian torsion, endometriosis, UTI Pregnancy test, pelvic examination,