Author name: doctorsrevision@gmail.com

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,

Diarrhoeal Diseases: Comprehensive Clinical Assessment, Rehydration, Diagnosis and Management Clinical Medicine Year 3 • acute, persistent and chronic diarrhoeal syndromes The first emergency is dehydration. Replace fluid and electrolytes immediately while investigating the cause. A stool result must never delay resuscitation in shock, severe dehydration, cholera or sepsis. Why diarrhoea is a clinical syndrome, not one diagnosis Diarrhoea can be caused by viruses, bacteria, protozoa, helminths, toxins, medicines, malabsorption, inflammation, endocrine disease or malignancy. The same patient may move from watery secretory diarrhoea to hypovolaemic shock, dysentery, haemolytic uraemic syndrome or severe malnutrition. Management starts with physiology—mental state, perfusion, urine and dehydration—then identifies the organism and the reason the illness persists. Learning outcomes Define acute, persistent and chronic diarrhoea and classify watery, inflammatory, fatty and osmotic patterns. Explain secretory, osmotic, invasive, malabsorptive and motility mechanisms. Assess dehydration and shock in adults, children, older people, pregnancy and severe malnutrition. Use Plan A, Plan B and Plan C rehydration principles and calculate ongoing losses. Recognise cholera, shigellosis, amoebiasis, enteric fever, C. difficile, giardiasis and HIV-associated diarrhoea. Choose stool, blood, electrolyte, imaging and endoscopic investigations appropriately. Use antibiotics, zinc, nutrition and infection-control measures selectively and safely. 1. Definition and classification Diarrhoea is passage of three or more loose or liquid stools in 24 hours, or more frequent stools than is normal for that person. In infants, stool frequency must be judged against the child’s usual pattern; breastfed infants normally pass soft stools. Classification Duration/appearance Main clinical question Acute diarrhoea Less than 14 days Is there dehydration, dysentery, cholera or sepsis? Persistent diarrhoea 14 days or more Is there malnutrition, HIV, parasite, post-infectious injury or inflammatory disease? Chronic diarrhoea More than four weeks Is there malabsorption, IBD, endocrine disease, malignancy or medication effect? Watery Large-volume liquid stool without visible blood Secretory toxin, virus, osmotic cause or cholera Dysentery Visible blood ± mucus, fever and tenesmus Invasive bacteria, amoebiasis, IBD or ischaemia Fatty/malabsorptive Bulky, greasy, foul, difficult-to-flush stool Giardia, pancreatic, bile or small-bowel disease 2. Causes 2.1 Infectious causes Viral: rotavirus, norovirus, adenovirus and other viruses—common in children and outbreaks. Invasive bacteria: Shigella, Campylobacter, non-typhoidal Salmonella, diarrhoeagenic E. coli, Yersinia and occasionally Vibrio. Secretory bacteria: toxigenic Vibrio cholerae, ETEC and other toxin-producing organisms. Protozoa: Entamoeba histolytica, Giardia duodenalis, Cryptosporidium, Cyclospora and Cystoisospora. Helminths and other infections: worms, HIV-associated infections, TB, CMV colitis and disseminated fungal disease. 2.2 Non-infectious causes Antibiotics and C. difficile, metformin, laxatives, magnesium, chemotherapy, inflammatory bowel disease, coeliac disease, lactose intolerance, pancreatic insufficiency, hyperthyroidism, adrenal disease, colorectal cancer, microscopic colitis, bile-acid diarrhoea, short bowel and functional disorders. 3. Pathophysiology 3.1 Secretory diarrhoea Enterotoxins activate chloride and bicarbonate secretion; water follows osmotically. Stool volume remains high even when the patient stops eating. Cholera produces massive secretory losses with bicarbonate and potassium depletion. 3.2 Osmotic diarrhoea Unabsorbed solute—lactose, poorly absorbed carbohydrates, magnesium or laxatives—retains water. Symptoms improve during fasting, although fasting is unsafe in children with acute infection. 3.3 Inflammatory/invasive diarrhoea Organisms invade mucosa or trigger cytotoxic injury, producing fever, abdominal pain, urgency, mucus, leukocytes and blood. Mucosal damage reduces absorption and can cause protein loss. 3.4 Malabsorptive diarrhoea Damage to villi or pancreatic/bile function causes bulky fatty stools, weight loss and deficiencies. Persistent infection can cause temporary lactose intolerance after mucosal injury. 3.5 The dehydration pathway Loss of water, sodium, chloride, bicarbonate and potassium reduces circulating volume. Tachycardia and thirst progress to poor perfusion, acute kidney injury, metabolic acidosis, hypoglycaemia, altered consciousness, shock and death. 4. History and examination 4.1 History Onset, frequency, volume, nocturnal symptoms, blood/mucus, tenesmus, pain and vomiting. Fever, thirst, urine amount, dizziness, fainting, confusion, seizures and weight change. Water source, sanitation, food, travel, outbreaks, sick contacts, raw milk/meat, antibiotics and healthcare exposure. HIV, pregnancy, malnutrition, diabetes, kidney/heart disease, immunosuppressants and previous bowel disease. Medication, laxative, metformin, chemotherapy and dietary history; relation to fasting or particular foods. 4.2 Examination Assess mental state, thirst, pulse, blood pressure, capillary refill, respiratory rate, temperature, oxygen saturation, mucous membranes, eyes, tears, skin pinch, peripheral temperature, abdominal tenderness/distension and bowel sounds. Record weight, urine output and stool losses. Examine for pallor, jaundice, oedema, oral thrush, perianal disease and signs of malnutrition. 5. Dehydration assessment Category Typical findings Action No dehydration Alert, drinks normally, moist mouth, normal eyes/skin, normal perfusion Plan A: extra fluids, nutrition, zinc for children, safety-net Some dehydration Restless/irritable, thirsty, sunken eyes, dry mouth, reduced tears, skin pinch slow Plan B: ORS under observation, reassess after four hours Severe dehydration/shock Lethargy/unconsciousness, unable to drink, very sunken eyes, weak pulse, cold extremities, very slow skin pinch, hypotension, oliguria Plan C: immediate IV/IO isotonic fluid, glucose/electrolytes, urgent monitoring Older people, obese patients, malnourished children and pregnant patients may not show classic skin-pinch or eye signs. Use perfusion, mental state, urine, weight change and response to fluids. 6. Rehydration plans Plan A: no dehydration Give extra safe fluid after each stool, continue breastfeeding and normal feeding, provide low-osmolarity ORS, and teach the caregiver the four rules: extra fluids, zinc for eligible children, continued feeding and when to return. Return urgently for persistent diarrhoea, increasing frequency/volume, repeated vomiting, increasing thirst, inability to drink/feed, fever, blood in stool, lethargy or worsening dehydration. Plan B: some dehydration Give ORS over approximately four hours according to the current IMNCI/WHO weight-band table, using frequent small sips and reassessing regularly. Replace ongoing stool losses, continue breastfeeding and restart normal feeds. If vomiting occurs, pause briefly and resume slowly; persistent vomiting or deteriorating mental state requires tube/IV management. Plan C: severe dehydration Start IV Ringer’s lactate or normal saline immediately. A commonly taught child protocol uses 100 mL/kg divided into 30 mL/kg then 70 mL/kg, with faster administration in older children; follow the current IMNCI table precisely for age. Give ORS by mouth or nasogastric tube as soon as the child can drink, reassess perfusion every 15–30 minutes initially and hourly thereafter, and treat hypoglycaemia, electrolyte disturbance and sepsis. If IV access is delayed: refer urgently, give ORS by mouth or nasogastric tube according to the current protocol if the airway is

Relapsing Fever: Complete Clinical Guide to Borrelia Infection Clinical Medicine Year 3 • louse-borne and tick-borne relapsing fever Clinical safety note: The first effective antibiotic dose can trigger a serious Jarisch–Herxheimer reaction. Monitor high-risk patients closely after treatment begins, especially those with hypotension, pregnancy, cardiac disease, high spirochaete burden or CNS involvement. Why the fever returns Relapsing fever is an acute infection caused by antigenically variable Borrelia spirochetes. A high-density bloodstream episode produces abrupt fever; antibodies clear one surface-antigen variant, but a new variant emerges and causes another episode. The patient may appear well between attacks, making the history of fever cycles crucial. Learning outcomes Distinguish louse-borne from tick-borne relapsing fever in organism, reservoir and transmission. Explain spirochaetaemia, antigenic variation and recurrent febrile episodes. Recognise haemorrhage, jaundice, myocarditis, shock, meningitis and pregnancy complications. Diagnose during fever using blood film, PCR or reference tests and distinguish malaria/sepsis. Start effective therapy, anticipate Jarisch–Herxheimer reaction and control vectors. 1. Organisms and epidemiological forms Feature Louse-borne relapsing fever Tick-borne relapsing fever Main organisms Borrelia recurrentis Several species; African examples include B. duttonii and B. crocidurae Vector Human body louse, Pediculus humanus corporis Soft ticks, especially Ornithodoros Reservoir Humans; louse-borne cycle is human-to-human Rodents and other animals maintain a zoonotic cycle Risk setting Overcrowding, displacement, homelessness, prisons, poor hygiene Rural/tick-infested sleeping areas, animal burrows and rodent exposure Public-health priority Delousing, hygiene, clothing/bedding and outbreak control Tick avoidance, rodent control, housing and environmental measures 2. Microbiology and transmission Borrelia are slender, actively motile spirochetes with loose coils and axial filaments. Louse-borne organisms infect lice; when an infested louse is crushed, organisms in its tissues contaminate abraded skin or mucosa. Tick-borne organisms are transmitted during the brief feeding of an infected soft tick. Unlike Lyme disease, this African relapsing-fever syndrome is often an acute high-spirochaete-burden illness. Transmission is favoured by poverty, overcrowding, poor access to bathing and laundry facilities, displacement, sleeping in rodent/tick habitats and lack of vector control. Ordinary casual contact without vector or contaminated blood exposure is not the usual route. 3. Pathogenesis and antigenic variation Inoculation through skin or mucosa is followed by rapid multiplication. High spirochaetaemia produces cytokine release, endothelial injury and the first fever. Neutralising antibodies clear the dominant surface-antigen variant, so fever falls. A new antigenic variant escapes the antibodies and multiplies, causing another febrile episode. Repeated cycles can produce three to five relapses; severe inflammation injures the myocardium, liver, brain and coagulation system. The rapid fall in organisms after antibiotics releases inflammatory products and can produce a Jarisch–Herxheimer reaction, sometimes more dangerous than the original fever. 4. Clinical presentation 4.1 Incubation and first attack Incubation is commonly 5–10 days. Fever begins abruptly, often 39–40°C, with rigors, severe headache, myalgia, arthralgia, nausea, vomiting, weakness and photophobia. Dry cough and abdominal discomfort may occur. 4.2 Physical signs Tachycardia, hypotension or a transient fall in blood pressure after rigors. Hepatomegaly, splenomegaly, jaundice and abdominal tenderness. Petechiae, epistaxis, gingival bleeding or subconjunctival haemorrhage. Confusion, meningism, cranial-nerve signs or seizures in CNS disease. Myocarditis, heart failure, arrhythmia or pulmonary oedema in severe infection. 4.3 The relapse After 3–7 days of fever, the temperature may fall with dramatic improvement. A symptom-free interval is followed by another abrupt fever when an antigenic variant emerges. Relapses may be milder or more severe and should not be mistaken for malaria treatment failure without testing. 4.4 Pregnancy and children Severe fever and spirochaetaemia may cause miscarriage, preterm birth, fetal infection or neonatal disease. Children may present with irritability, poor feeding, vomiting, seizures or shock. Use age/pregnancy-compatible treatment and refer severe cases. Danger signs: hypotension, altered consciousness, meningism, seizures, jaundice, bleeding, dyspnoea, pulmonary oedema, severe abdominal pain, oliguria, pregnancy with systemic illness or recurrent fever with shock. 5. History and examination Ask about Number, duration and spacing of fever attacks; rigors and recovery between episodes. Lice, overcrowding, homelessness, prison/displacement, infested bedding, rodents, ticks, rural sleeping and animal burrows. Bleeding, jaundice, headache, photophobia, confusion, weakness, chest pain, dyspnoea and reduced urine. Pregnancy, HIV, malaria treatment, antibiotics and contact with similar febrile patients. Examine Measure temperature repeatedly, pulse, blood pressure, respiratory rate, oxygen saturation, capillary refill, mental state, hydration and urine output. Look for lice/nits, petechiae, jaundice, hepatosplenomegaly and subconjunctival haemorrhage. Perform cardiac, respiratory and neurological examinations, including meningism and focal deficits. 6. Diagnosis 6.1 Blood during the fever Demonstration of spirochetes is most likely during a febrile episode, when organism density is high. Thick and thin blood films examined by experienced staff may show long, motile organisms; repeat films can be needed. PCR and reference laboratory methods improve confirmation. 6.2 Supporting tests FBC and platelets for anaemia, thrombocytopenia and severe disease. Glucose, electrolytes, urea/creatinine, liver tests, bilirubin and coagulation. Malaria testing, blood cultures and sepsis work-up according to local epidemiology. ECG/troponin/echo for myocarditis; chest imaging for pulmonary oedema; LP and neuroimaging for CNS signs after safety assessment. 6.3 Do not over-rely on serology Serological tests may support retrospective diagnosis but often cannot distinguish current from previous infection early enough to guide emergency care. A compatible febrile illness with exposure and spirochaetaemia deserves treatment even while confirmatory testing is pending. 7. Differential diagnosis Condition Why it resembles relapsing fever Useful distinction Malaria Rigors, fever cycles, splenomegaly, anaemia Repeated malaria tests, parasite morphology and exposure; co-infection possible Enteric fever Prolonged fever, abdominal symptoms Blood culture, bowel complications and exposure history Leptospirosis Fever, myalgia, jaundice, renal injury Water/animal urine exposure, conjunctival suffusion, renal pattern Rickettsial disease Fever, headache, vector exposure, rash Eschar/rash and serology/PCR where available Meningitis/sepsis Fever, confusion, hypotension Acute microbiology, CSF and source examination Viral haemorrhagic fever Fever, bleeding, shock Outbreak/travel history, isolation/public-health pathway and specific tests 8. Treatment Admit patients with severe disease, pregnancy, CNS signs, bleeding, hypotension, organ dysfunction or diagnostic uncertainty. Start a locally recommended effective antibiotic—options used in different protocols include doxycycline, penicillin-class therapy, ceftriaxone or another active agent—after considering pregnancy, age, CNS involvement and regional guidance. Do not delay life-saving therapy for a negative initial film. Uncomplicated adult disease Use the national recommended oral or parenteral antibiotic

Anthrax: Complete Clinical Chapter on Cutaneous, Inhalational and Gastrointestinal Disease Clinical Medicine Year 3 • zoonosis, toxin-mediated sepsis and outbreak control Anthrax is a notifiable high-consequence infection. Isolate contaminated materials, notify public health/veterinary authorities, alert the laboratory before sending specimens and begin specialist-guided therapy when clinical suspicion is high. Do not incise, biopsy or surgically debride a classic eschar before expert review. Why anthrax must be recognised early Anthrax is caused by spore-forming Bacillus anthracis. Most human disease is cutaneous and may begin with a painless itchy papule, but inhalational, gastrointestinal, oropharyngeal and injectional disease can progress rapidly to oedema, bacteraemia, meningitis, shock and death. The patient’s occupation and recent contact with livestock, hides, wool, carcasses or contaminated soil may be more diagnostic than the first physical sign. Learning outcomes Describe the organism, spores, capsule, toxins, reservoirs and routes of exposure. Recognise the clinical sequence of cutaneous, inhalational, gastrointestinal/oropharyngeal and injectional anthrax. Distinguish anthrax from cellulitis, necrotising fasciitis, plague, tularemia and other eschars. Collect specimens safely and understand laboratory confirmation. Start urgent antimicrobial, antitoxin, supportive and exposure-management measures. Plan vaccination, post-exposure prophylaxis, livestock control and outbreak communication. 1. Causative organism and virulence B. anthracis is a large, gram-positive, non-motile, non-haemolytic, spore-forming bacillus. Vegetative bacilli multiply in nutrient-rich tissues and produce a poly-D-glutamic acid capsule that inhibits phagocytosis. Spores survive for years in soil, animal products and contaminated equipment. The tripartite toxin consists of: Protective antigen: binds host cells and permits entry of the other toxin components. Edema factor: an adenylate-cyclase activity that increases intracellular cAMP and produces marked oedema. Lethal factor: disrupts signalling pathways, macrophage function and vascular stability, contributing to shock and death. 2. Reservoir and transmission Herbivores acquire spores from contaminated soil, pasture, feed or carcasses. Humans are accidental hosts. The supplied teaching deck emphasises contact with cattle, sheep, goats, horses or pigs dying of disease; contaminated hair, wool, hides, drums, brushes, rugs, bone meal and soil; inhalation during hide/wool processing; ingestion of contaminated undercooked meat; and laboratory accidents. Ordinary person-to-person spread is not expected. Route Typical exposure Resulting form Cutaneous inoculation Handling carcass, hide, wool, meat, soil or infected animal tissue Cutaneous anthrax Inhalation Aerosolised spores in tanning, wool, bone processing or laboratory work Inhalational anthrax Ingestion Contaminated undercooked meat or animal products Oropharyngeal or gastrointestinal anthrax Injection Contaminated injected drugs Severe injectional soft-tissue/systemic anthrax 3. Pathogenesis Spores enter through skin, respiratory or gastrointestinal mucosa. Macrophages transport spores to regional lymph nodes, where germination produces encapsulated bacilli and toxins. Local oedema and necrosis are followed by lymphatic spread, bacteraemia and metastatic seeding. Inhalational disease causes haemorrhagic mediastinitis and pleural effusions; meningeal invasion causes haemorrhagic meningitis. Toxin-driven capillary leak and myocardial/vascular dysfunction lead to shock. 4. Incubation and clinical forms Incubation is commonly one to seven days, but inhalational spores may remain dormant longer and illness can appear weeks after exposure. Clinical disease has a short prodrome followed by local and systemic manifestations. 4.1 Cutaneous anthrax Usually begins as an itchy, painless papule on an exposed area. It progresses to vesicle, ulcer/malignant pustule and a depressed black eschar surrounded by non-pitting gelatinous oedema. Fever, malaise, headache, regional lymphadenopathy and lymphangitis may occur. Pain out of proportion, rapidly progressive necrosis or crepitus should raise concern for an alternative or coexisting necrotising infection. Many localised lesions heal over two to six weeks, but untreated disease can progress to bacteraemia, oedema of the face/neck, respiratory compromise, meningitis and death. Facial lesions are particularly dangerous because oedema can obstruct the airway. 4.2 Inhalational anthrax The first phase resembles influenza: fever, malaise, myalgia, fatigue, dry cough, chest discomfort, nausea or mild breathlessness. After a short improvement, the patient can abruptly deteriorate with severe dyspnoea, hypoxia, cyanosis, stridor, haemoptysis, shock, confusion, widened mediastinum and pleural effusions. The absence of productive cough does not reassure. 4.3 Oropharyngeal and gastrointestinal anthrax Oropharyngeal disease produces sore throat, dysphagia, neck oedema, cervical nodes and airway risk. Intestinal disease causes severe abdominal pain, fever, vomiting, bloody diarrhoea, ascites, bowel oedema, ileus, perforation and sepsis. It may be mistaken for surgical abdomen, cholera, dysentery or food poisoning. 4.4 Injectional anthrax Injection sites may show extensive painful oedema, necrosis, bullae and systemic toxicity without the classic eschar. It progresses rapidly and requires aggressive surgical/infectious-disease assessment. Anthrax red flags: painless black eschar with disproportionate oedema; unexplained widened mediastinum; severe fever after hide/wool exposure; bloody diarrhoea with animal-meat exposure; rapidly progressive injection-site necrosis; meningism or shock. 5. History and examination 5.1 Exposure questions Was there a sudden animal death, carcass opening, home slaughter, livestock outbreak or unexplained animal bleeding? Did the patient handle hide, wool, hair, bone meal, meat, placenta, carcass or contaminated soil? Was meat eaten raw/undercooked, or was a household member exposed? Does the patient work in farming, veterinary practice, abattoirs, leather/tanning, wool, laboratories or waste disposal? Any injection-drug exposure, travel or previous anthrax vaccination/prophylaxis? 5.2 Examination Assess airway, breathing and circulation first. Inspect all skin including hidden sites; describe lesion stage, pain, oedema, vesicles, eschar, lymphangitis and regional nodes. Examine oral cavity and neck, chest for hypoxia/pleural signs, abdomen for tenderness/ascites/peritonism, skin/soft tissue, mental state and neurological function. 6. Diagnosis 6.1 Clinical diagnosis In a compatible exposure, treatment should not wait for confirmation. Anthrax is confirmed by isolation of B. anthracis, detection by validated molecular/immunofluorescence methods or a significant antibody response in an appropriate case. Tell the laboratory in advance because handling cultures can generate dangerous aerosols. 6.2 Specimens Unopened vesicle fluid or swab from beneath the lesion edge, not an aggressively scraped eschar. Multiple blood cultures before antibiotics if this does not delay life-saving treatment. Pleural fluid, CSF, respiratory specimens or tissue only with specialist guidance and safe transport. Serum for paired antibody testing in selected cases. 6.3 Imaging and severity tests Chest radiograph/CT may show widened mediastinum, pleural effusions, hilar adenopathy or infiltrates. Ultrasound/CT evaluates abdominal disease and ascites. FBC, renal/liver profile, coagulation, lactate, glucose, blood gas, ECG and cultures stage sepsis and guide supportive care. 7. Differential diagnosis Anthrax presentation Important differential Clues favouring the alternative