Week 9 Flashcards

Question

VTE Why treat?

Answer 1

If DVT remains untreated, 15-24% of these patients will develop pulmonary embolism (PE). PE during pregnancy may be fatal in almost 15% of patients, and in 66% of these, death will occur within 30 minutes of the embolic event

Answer 2

Anticoagulation (can prevent potentially fatal PE, increases risk of bleeding - especially around time of delivery), LMWH (safest but expensive), UFH (can be used in pregnancy but needs some APTT monitoring and risk of heparin-induced thrombocytopaenia and thrombosis (HITT) and osteoporosis), Warfarin (teratogenic in T1, increased risk of fetal bleeding throughout pregnancy, needs stopping at least 2/52 prior to delivery as crosses placenta -> unacceptable bleeding risk for fetus during delivery) Not enough evidence yet to recommend direct oral anticoagulants (DOACS - Rivaroxaban shows fetal toxicity in animal studies, apixaban does not)

Answer 3

VTE is common but the management remains very difficult in low-income settings. Management is especially difficult in pregnancy. Pragmatic decision making is often required.

Answer 4

Anaemia is a serious public health problem requiring a multi-sectorial approach. Blood transfusion services are challenging and expensive (research capacity building and creating local solutions is essential, always think about alternatives to transfusion). Partnerships can provide a useful means for approaching resource shortages.

Answer 5

Are you a floor mopper or a tap turn offer

Answer 6

Needs referral patterns, supply lines, skilled physicians, skilled nurses, surgical services, laboratory (pathology, haematology, blood transfusion, microbiology, biochemistry), radiology, radiotherapy, palliative care, prevention

Answer 7

There are two solutions to every problem - the one for now, and the one for the future. Need to look after the patient in front of you, whilst planning for the long-term sustainable option.

Answer 8

Clinical protocols and SOBs, chemotherapy guidelines (procurement, storage, distribution, reconstitution), chemotherapy automated prescribing, network database, pocket guides for nurse/doctors/pharmacists, play-therapy manuals and tools, parents handbook, NGO guidelines, early warning signs awareness campaigns, outreach and national network management guide. Childhood cancer survivors

Answer 9

Leukopaenia (neutropaenia, fever, infections), Thrombocytopaenia (bruising, bleeding), Anaemia (pallor, fatigue, weakness, shortness of breath), Leukocytosis (bone pain, stroke, cranial nerve palsy, renal failure), extra-medullary sites (generalised lymphadenopathy, hepatosplenomegaly), B-symptoms (weight loss, drenching night sweats, unexplained fever, bone pain)

Answer 10

Rapidly growing. Most common between age 5-15, almost never <3y. Symptoms usually rapid in onset <3m. Rapidly growing mass most commonly affecting (jaw, retro-orbital LNs, mediastinum, abdomen - liver, LNs, spleen, kidney), B symptoms (night sweats, bone pain, weight loss, unexplained fever), CNS/PNS signs (central nerve palsy, lower limb weakness, constipation, incontinence - urine/stool) Signs of bone marrow failure (anaemia, neutropaenia, leucopaenia)

Answer 11

Slow growing mass. Swollen LN (groin, neck, chest, armpit), hepatosplenomegaly, B symptoms (night sweats, bone pain, weight loss, unexplained fever), recurrent infections

Answer 12

Symptoms involving one eye or both include: leucocoria (white pupil that does not reflect the light), strabismus (eye to become crossed because of loss of vision), painful red eye, decreased vision in one eye, eye swelling or proptosis. Most common in infants and young children. (Almost all diagnoses before age six years)

Answer 13

Symptoms/signs include: child is generally well, abdominal mass +/- pain, haematuria, urinary tract infection, hypertension

Answer 14

Children who present with a short history and obvious symptoms are likely to have aggressive disease in comparison with those who have a long history of subtle symptoms. Symptoms include: persistent headache, new onset seizures, raised ICP signs/symptoms (headache and vomiting on waking or early morning), visual disturbances, cranial nerve abnormalities, gait abnormalities (eg ataxia), changes in continence, deteriorating school performance or developmental milestones, behaviour changes - lethargy, aggression

Answer 15

Larger lymphocytes with darker cytoplasm

Answer 16

Usually large, high nuclear-cytoplasmic ratio. Scanty cytoplasm (+/- granules or Auer rods), Immature chromatin (fine, open - rather than mature cells which have clumped nuclear material), prominent nucleoli

Answer 17

buku medicine - valuable tool

Answer 18

Anaemia, hypersegmented neutrophil, schistocytes, tear drop, anisopoikilocytosis. Diagnosis: severe B12 deficiency (macrocytic anaemia with hypersegmented neutrophils - fragments in severe cases)

Answer 19

Bite cells (degmacytes), polychromasia. Diagnosis: G6PD deficiency

Answer 20

Thrombocytopaenia. Diagnosis: ITP (

Answer 21

Hypochromic anaemia, anisopoikilocytosis (different shapes and sizes), microcytic anaemia, target cells. Diagnosis: Iron deficiency anaemia

Answer 22

Sickle cells, polychromasia

Answer 23

Normal blood film

Answer 24

mature lymphocytosis, smear cells. Diagnosis: CLL

Answer 25

promyelocyte, promyelocyte, metamyelocyte, neutrophil precursors, myelocytes. Diagnosis: CML

Answer 26

vacuoles within cytoplasm. Diagnosis: Burkitt lymphoma

Answer 27

Blast cells, smear cells. Diagnosis: AML

Answer 28

All ages: infection (H pylori, giardia, tapeworm), malabsorption (pernicious anaemia), comorbidities (gastric resection/banding, coeliac, tropical sprue, Crohn's). Infants (congenital - transcobalamin deficiency, Imerslud Gasbeck Syndrome), Pregnancy (due to higher requirements), Older (malabsorption - achlorhydria secondary to PPI or atrophic gastritis)

Answer 29

X-linked, female carriers have increased resistance to malaria. Variable phenotype (Mild in African, Moderate in Asian, Severe in Mediterranean patients). Pathophysiology: G6Pd reduces nicotinamide adenine dinucleotide phosphate (NADP) to NADPH. This is the only source of NADPH for the red cell. NADPH is needed to reduce glutathione. Reduced glutathione clears free oxidants -> deficiency results in increased susceptibility to oxidative stress. Clinical features: Neonatal jaundice (peaks at 2-3d after birth, variable severity), Acute haemolysis (triggered by 'oxidant' drugs/food/infections), Chronic non-spherocytic haemolytic anaemia (CNSHA)

Answer 30

Primary ITP: acquired immune-mediated disorder characterised by a platelet count <100 and absence of any obvious initiating or underlying disorder. It can be newly diagnosed, persistent (2-12 months), chronic (>12 months). Treatment: 1st line steroids, IVIg, anti-D. 2nd line rituximab, splenectomy, TPO agonists, steroid-sparing immunosuppressants

Answer 31

~15,000 people with SCD in UK (~9% on long-term transfusion programme). ~300 infants born with SCD in UK each year. Caused by inheritance of the sickle mutation on the HBB gene (Glu6Val, bs). Sickle cell trait = HbAS, Sickle cell anaemia = HbSS, Sickle cell disease = HbSS or sickling compound heterozygotes = HbSC, HbS/b0, HbS/b+, HbSC, HbSOArab. In West Africa, SCD responsible for 16% of all deaths <5 year olds. In Jamaica, 10% of SCD infants die between 6-12 months of age. In the UK, 99% survival to age of 16 years. Pathophysiology: In hypoxic states, erythrocytes become rapidly, but reversibly, deformed. Intracellular polymerisation of the abnormal HbS molecule stretches cell into rigid sickle form. Sickled cells cause vaso-occlusion, along with many other cellular and plasma factor interactions -> cycle of repeated ischaemia and inflammation. Re-oxygenation restores the normal red cell shape. Cells cycle in and out of this state until forced into intravascular haemolysis or extravascular removal by the reticuloendothelial system. HbS is a low oxygen affinity haemoglobin -> right shift on the oxygen dissociation curve -> partly explains the chronic anaemia in SCD (which is not all due to haemolysis)

Answer 32

Incidence 4.2 per 100,000 per year. Median age of presentation 72, Men>women. Caucasian > other ethnic groups. >80% incidental diagnosis. Diagnosis >5x10^9/L circulating clonal B cells persisting for >3 months and of characteristic immunophenotype

Answer 33

Pathophysiology: part of ABL from 9 moves to the BCR on 22 (and part of 22 moves to 9). Philadelphia (Ph) chromosome = abnormal 22 that carries the BCR-ABL 1 fusion gene. BCR-ABL 1 fusion gene codes for a protein with excess tyrosine kinase activity. Ph chromosome is an acquired abnormality of a haemopoietic stem cell and so found in cells of both myeloid and lymphoid lineages. Clinical presentation: median age at diagnosis = 57 years. 20% of patients >70 years, <5% of patients <18. 50% diagnosed on incidental FBC finding. B symptoms, splenomegaly, symptoms of anaemia/thrombocytopaenia. Blast phase vs chronic phase. Treatment: tyrosine kinase inhibitor

Answer 34

Aggressive B-cell non-Hodgkin's lymphoma, uniformly associated with MYC translocations. Doubling time of 25 hours - probably fastest growing of any cancer. WHO-HAEMS Classification: EBV positive vs EBV negative - this replaces previous classification of endemic/sporadic/immunodeficient. Endemic (African) BL - uniformly EBV positive, 3-6 cases per 100,000 children per year in equatorial Africa. Incidence is increasing in line with increasing HIV and malaria. Classically presents with jaw or facial bone tumours. Sporadic BL - 2-3 cases per million per year in Europe. 30% of paediatric lymphomas, 1% of adult NHL, Men>women (4:1). Immunodeficiency-associated BL - essentially HIV, occurs independently of CD4 count and so incidence has not fallen with introduction of HAART.

Answer 35

Medan age 70y. Age <65: 3-8 cases per 100,000 adults per year, 40% 5-year survival. >65y 0.17 cases per 100,000 adults per year, 10% 5 year survival. Adults 18-60y induction therapy achieves clinical remission in 60-80% of adults, allograft in first clinical remission offers significant overall survival benefit. Allograft long-term survival for adverse AML is 30% (but chemo alone is much worse)

Answer 36

First cases described in Hisponalia (Domenican Republic) 1495 - first epidemic described in Guadeloupe in 1647. Feared disease at the turn of the 19th Century - Western Hemisphere and the coastal regions of West Africa (Ships 'Yellow Jack' flag. Now commonly believed YFV originated in Africa, taken to the Americas on ships carrying anopheles eggs.

Answer 37

Flavivirus, enveloped virus, ssRNA, surface proteins are important for infecting cells (E dimer used for cell surface attachment) - pantropic virus (affects many cells), predilection for the liver also. Internalised by endocytosis, replication cycle starts in endothelial reticulum and finishes in the golgi apparatus. pH dependent phenomenon. Genotypes 1 & 2 West Africa, 3, 4, 5 East/central Africa. 6 & 7 South America

Answer 38

HCQ increases the pH within the cell, but is not able to get inside cells at levels required to increase the pH so does not work for any viral infection

Answer 39

Global distribution: Tropical belt of Africa and South America (around rainforests).

Answer 40

Vector is Aedes aegypti and A albopictus have the potential to carry YF - these go around the globe - why isn't there any YF in SE Asia or Pacific region? Noone really knows, but a number of theories. 1 Absence of centuries of slave trade with Africa. 2 Less competent vectors? 3 Relatively low viral loads of handful of imported cases - care in urban centres, less likelihood of establishment of sylvatic cycle. 4 Cross-protective immunity between flaviviruses?

Answer 41

1 Sylvatic (jungle) cycle - this is the maintenance cycle, 2 Anthropogenic sylvatic cycle (humans go into forest, get infected, and then take it back to the urban or village environment), 3 Village epidemic 4 Urban epidemic (this is the most feared, where mosquitoes are able to thrive and many non-immune get massive epidemics). 1-4 in Africa, 1 and 4 only in South America

Answer 42

Short incubation period 3-6d (may be longer <21d). Asymptomatic or mild febrile illness in many cases. Some progress to 'toxic' phase of infection (0.8-7.5% will progress to this stage and often come to the attention of medical facilities - 30-60% CFR)

Answer 43

d3-6 Clinical features: headache, myalgia, lumbosacral pain, nausea, malaise, prostration, dizziness, conjunctival infection, furred tongue, red at tip, Bradycardia (Faget's sign). Lab features: leukopaenia, neutropaenia, AST>>ALT, proteinuria. Then immune response to E protein, neutralising - symptoms abate for 2-24h

Answer 44

d7-12 'period of intoxication' CFR 30-60% antibody-complex mediated disease. Clinical features: headache, epigastric pain, vomiting, prostration, malaise, jaundice, olig/anuria, tender liver, hypotension -> shock, stupor -> coma, haemorrhage, convulsions, hypothermia, Lab: leukocytosis, AST>ALT, proteinuria, hypoglycaemia, acidosis.

Answer 45

Older age >45y, neutropaenia, AST >3500, hyperbilirubinaemia, high YFV RNA levels, renal dysfunction

Answer 46

No reported outcomes from liver transplantation in severe yellow fever. UK do not have a cohort of immunised surgeons. YF virus known to infect many organs, death often rapid and multifactorial., Virus remained detectable by PCR, therefore risk of graft infection

Answer 47

No effective antiviral therapy established. Unclear if effective antiviral therapy could alter disease course of established toxaemic phase. Ribavirin (activity in vitro and small animal models at high doses, no benefit in several non-human primate models. The doses required to have any intracellular effect are likely to be toxic). Sofosbuvir (relatively weak activity in vitro, some protection in small animal model when administered prior to yellow fever virus challenge).

Answer 48

Max Theiler - Nobel Prize in Physiology or Medicine "for discoveries concerning yellow fever and how to combat it" - the only time Nobel has been awarded for a vaccine. YF-Vaccine (17D). Live attenuated YFV. Has no ability to infect vectors - low level replication in humans (important when given in areas where vectors are available but no YF). >90% protection after 10d, >99% protection after 30d, single-dose probably provides life-long protection. Requirement of a cold-chain. Many countries (national vaccination programme, many others a requirement for travel/entry)

Answer 49

Absolute CI: under six months old, confirmed anaphylactic reaction to. A previous dose or any components of vaccine, or egg, those who have a history of thymus disorder and thymectomy following a thymus disorder. Patients with primary or acquired immunodeficiency due to a congenital condition, disease process, or treatment.

Answer 50

Small molecule antiviral, nucleoside (adenosine) analogue. Broad-spectrum activity in vitro against RNA viruses - blocks viral polymerase similar to sofosbuvir but only IV. Survival benefits in animal models of Ebola, Marburg, Zika, Yellow fever. Survival benefit in Syrian golden hamster model of YF - when treatment initiation 4d after lethal challenge

Answer 51

Yellow fever remains a large burden disease. High morbidity/mortality in subsets (no decent data on the predictors of morbidity and mortality at the onset of the illness). 17D vaccine highly effective (know your contraindications, for travelers (especially short travel) consider risk vs benefit). No licensed therapy (sofosbuvir and galidesivir heading into clinical trials)

Answer 52

Bartonella spp are Gram-negative, facultative intracellular pathogens, emerging and reemerging human diseases. Associated with a range of human and animal infections. Emerging zoonotic pathogen and affects humans, domestic animals and wildlife. Bartenellosis is characterised by a prolonged intraerythrocytic bacteraemia within a diverse array of reservoir hosts. The severity of the clinical manifestations is often correlated with the immune status of the patient (other factors: the species infecting the host, virulence factors, and bacterial load)

Answer 53

Bartonella invades endothelial cells and erythrocytes. Induces angiogenesis via VEGF and other growth factors. Avoids immune clearance by intracellular localisation. Chronic infection through persistent bacteraemia. Subversion of immune system: inhibition of apoptosis in host cells. Bacterial virulence factors.

Answer 54

Adhesion (infection of the primary niche in mammalian reservoir host, infection waves seeded from the primary niche, antibody response that limits the bacteraemia), Invasion, Replication, Persistence

Answer 55

Neuropathy (varied), aneurysm, bacillary peliosis (hepatic), epithelioid haemangioendothelioma, arthritis, Verruga peruana (Peruvian warts), endocarditis, myocarditis, vasoproliferative and lymphatic tumours, bacillary angiomatosis, vasculitis/thrombosis

Answer 56

Lutzomyia verrucarum sandfly = B bacilliformis, Cat = B henselae, B clarridgiae, Human body louse = B quintana, Rat = B elizabethae, Vole = B vinsonii

Answer 57

Carrion disease = B bacilliformis, Cat scratch disease = B henselae, B clarridgiae, Trench fever = B quintana, Bacteraemia/endocarditis = B henselae, B elizabethae, B vinsonii, B quintana, Bacillary angiomatosis = B henselae, B quintana, Peliosis hepatis = B henselae, B quintana

Answer 58

Primary cause of cat scratch disease. Associated diseases: bacillary angiomatosis (in immunocompromised host), Parinaud's oculoglandular syndrome (granuloma in eye). Transmission via scratches or bites from infected cats (fleas play a role in cat infection cycles). Clinical presentation: immunocompetent - cat scratch disease (regional LN, fever, fatigue and headache), immunosuppressed - bacillary angiomatosis (affected patients present with vascular lesions that most frequently involve the skin but can affect other organs, such as bone and LN, can be life-threatening if untreated, mimic Kaposi sarcoma in HIV). Diagnosis: Clinical history and exposure to cats. Lab: Serology for B henselae, PCR, Biopsy for angiomatous lesions (Warthin Starry stain). Treatment: LN Azithromycin 5d (or Clari, Rif, SXT), Bacillary angiomatosis: Erythromycin or doxycycline 12w minimum - if response not satisfactory, duration can be extended (optimal duration not determined, but longer with invasive disease)

Answer 59

Trench fever (also can cause bacillary angiomatosis, endocarditis). Associated with homelessness and poor hygiene (transmission: Pediculus humanus corporis - human body louse, no known animal reservoir). Worldwide distribution (sporadically reported in US, EU, Russia, Brazil, and East Africa). Outbreaks reported in homeless, refugees and prisoners (HIV, EtOH, IVDU higher risk). Seroprevalence studies of homeless population in USA and France found 8-53% had B quintana infection compared with 0-2% of healthy blood donors. Incubation 5-20d. Clinical: Trench fever (cyclical fever every 5-6d, severe headache, bone pain (esp shins), relapsing, chronic form in some cases), Immunocompromised: Bacillary angiomatosis (vascular lesions affecting skin and internal organs - occurs in patients with advanced HIV CD4<100, Bq more likely to have lytic bone lesions), Culture negative endocarditis (20-43% of patients with B quintana have endocarditis, causes up to 15% of CNE Bq>Bh causing endocarditis), Chronic infection can persist asymptomatically or with mild nonspecific symptoms. Bacillary peliosis hepatitis (occurs in patients with HIV CD4<100, present with abdo pain, hepatosplenomegaly with or without systemic symptoms, elevated ALP) Lab: BC (difficult due to fastidious growth), Serology (IgM/G), PCR, histopathology for vascular lesions. Treatment: Doxycycline 28d + Rif 14d. Bacillary angiomatosis and endocarditis need prolonged doxy or erythro with gent in severe cases - treatment of BA depends on the presence of bacteraemia and severity of illness

Answer 60

Carrion's disease, Oroya's fever two phases: acute and chronic. Geographically confined to Andean region (mostly Peru). Transmission: vector-borne Lutzomyia verrucarum sandfly but not clear. Pathogenesis: infects erythrocytes and endothelial cells, physical damage and introduction of antigens into the erythrocyte membrane, producing intense erythrophagocytosis -> haemolytic anaemia. Virulence factors (adhesin, flagellin, hemi) evade the host immune response. Acute phase: increased IL-10 secretion by RBC, decrease cytokine production -> suppresses T helper cells, macrophages, and dendritic cells (favours persistent B bacilliformis infection and increase the risk of secondary infection)

Answer 61

Characterised by fever and haemolytic anaemia and has a reported mortality of 44-88% untreated (acute bacteraemia for 60d) Complications are common and include super-infections such as Salmonella spp (also Toxoplasma, Histoplasma, and others). Other complications are haematological, gastrointestinal, cardiovascular and neurological. Young children are the most affected in endemic communities (presumptive protective immunity that develops with repeated infection means adults are more protected). High mortality without antibiotic therapy. RF: >45y, history of alcohol use, shock, pulmonary oedema, pericarditis, seizures, coma, anasarca, petechiae, and altered mental status. Complications: more common cardiovascular (heart failure, pericardia effusion, pulmonary oedema etc) also coagulation disorders (requires ICU))

Answer 62

Malaria, dengue, typhoid, viral hepatitis, leptospirosis, brucellosis, Zika, Chikungunya, TB, haem malignancy, Parvovirus B19, haemolytic anaemia, aplastic anaemia

Answer 63

Bacillary angiomatosis, yaws, pyogenic granuloma, angioma, cutaneous lymphoma, capillary malformation, Kaposi sarcoma, NTM, leprosy, lymphomatoid papillomatosis, fibrosarcoma, reticuloendotheliosis, Molluscum contagiosum, Chickenpox, Spitz naevaus, cutaneous TB

Answer 64

May occur weeks to months after the acute illness (and there may or may not be a history of antecedent illness). Characterised by the eruption of miliar, mular or nodular skin lesions, or verrugas ('warts'), containing serosanguinous fluid which exudes on contact. Blood-filled nodular haemangiomas of the skin - Peruvian warts (bacterial invasion of capillary endothelium and generates bacteria-filled vacuoles and localised cellular proliferation, leading to formation of warts). Warts are cutaneous, usually on the head and extremities (can persist for several weeks to months). Lesions are classified as miliary (multiple red papules <3mm), mular (blood-filled nodules), diffuse (groups of subdermal nodules >5mm). Chronic phase is a more common manifestation of inhabitants of endemic regions. Seropositive people who are asymptomatic or in chronic phase can have blood culture positive for B bacilliformis (hypothesis - this population can serve as reservoir). Younger age, higher incidence/severity/recurrent infection/chronic phase (hypothesis - humoral immunity, as a result of recurring or chronic infections, confers partial immunological protection).

Answer 65

Acute phase: blood smears (cheapest, most used but low sensitivity), culture (>70% are positive, but it takes a long time (>14d) and is logistically complicated), PCR (expensive and not available in rural areas), Immunological tests sens and spec (but can reflect persistent humoral immune response, the indirect fluorescence antibody (IFA) test, immunoblot-based protocol). An ELISA using two different antigen combinations porin B plus autotransporter E - combination is sufficient to detect anti-B bacilliformis IgG Ab. Chronic phase: clinical diagnosis with or without skin biopsy - overlap with cutaneous leishmania. Culture BC positive 13-47% (however can be asymptomatic or transient)

Answer 66

All evidence of poor quality. Acute phase: Cipro, CRO (severe cases in children and pregnant women), Amox/Clav (uncomplicated cases). Chronic phase: Azithromycin, Rif (some reports showed failure), Cipro. All are expert opinion (no RCT). But ciprofloxacin resistance is being described.

Answer 67

Pathophysiology (single gene disorder, different levels of severity, common symptoms, pain, infection, anaemia), Epidemiology (common genetic disorder, annual SCD births 300,000, high morbidity and mortality in Africa). Interventions (Interventions reduce childhood mortality by 70%, disease modifying medicines, curative interventions)

Answer 68

Disproportionately affects Africa >5.7m and South Asia >1.3m, with cases in Middle East >620,000 and Jamaica 57,000

Answer 69

HbS polymerisation -> sickling and haemolysis. Sickling -> vasoocclusion (impaired rheology, adhesion between sickled erythrocytes, neutrophils, endothelium and plt -> ischaemia-reperfusion injury -> sterile inflammation -> vasoocclusion (feed forward). Haemolysis -> endothelial damage -> oxidation -> abnormal heme -> sterile inflammation -> vaso-occlusion

Answer 70

Severe: HbSS (the most common form of sickle cell disease, also called sickle cell anaemia, HbSbetao thalassaemia (Most prevalent in the eastern Mediterranean region and India (also includes severe beta+ with <5% HbA present), HbSDpunjab (predominant in northern India but occurs worldwide), Moderate HbSC (25-30% of cases of SCD in populations of African origin), Hbsbeta+ thalassaemia (Most cases found in the eastern Mediterranean region (6-15% HbA present), Mild: HbSbeta++ thalassaemia (Mostly in populations in Africa (16-30% HbA present)) Very mild sickle cell disease HbS/HPFH (Group of disorders caused by large deletions of the beta-globin gene. Typically >30% HbF)

Answer 71

Blood film with sickled cells. Sickle solubility test. Hb electrophoresis (alkaline pH), high performance liquid chromatography

Answer 72

Sickle cell disease: SS sickle cell anaemia, SC, SD-, Sbeta+, Sbeta0, mild disease - S-HPFH. Sickle cell trait: heterozygous state for HbS (HbAS), no serious clinical consequences, sudden death during intensive training. Haematuria, isotheuria (renal papillary necrosis) protection vs malaria

Answer 73

Acute: Acute pain episodes, acute anaemia, acute chest syndrome, infection inc sepsis, meningitis, stroke, priapism, aplastic crisis, bone marrow infarction, osteomyelitis, splenic infarction & sequestration, dactylitis (children), gallstones, papillary necrosis, post-hyphaema glaucoma, retinal infarction. Chronic: chronic pain, chronic anaemia, leukocytosis, sickle nephropathy, sickle retinopathy, sickle hepatopathy, functional asplenia, leg ulcers, pregnancy, cardiac - pulmonary hypertension, cardiomegaly, diastolic heart failure, sickle lung disease, neurocognitive dysfunction, delayed puberty, erectile dysfunction, avascular necrosis, complications of pregnancy

Answer 74

Acute: Pain causes up to 95% of hospital admissions for SCD patients. ~30% of adult patients have some pain 95% of the time. ~14% of adult patients are in pain <5% of the time. Characteristics: acute pain unpredictable, mild to severe. Lasts hours to days, migrates, waxes and wanes. As intense as post-operative pain (SCD women have reported labour pain less in intense than sickle crisis). Precipitating factors (triggers): infection, dehydration, stress, hypoxia, temperature, physical exertion, alcohol, unknown. Predicting pain: patient and families can often tell when a severe sickle pain is coming on by jaundice, irritability, malaise and numbness or sensation change in area about to be affected. Management: warmth increases blood flow, massaging and rubbing, rest and relax, analgesia.

Answer 75

The first effective drug treatment for adults with severe sickle cell anaemia reported in 1995. Daily doses reduced the frequency of painful crises, acute chest syndrome. Side effects: well tolerated, effect on male fertility (offer sperm banking), occasional gut discomfort take at night, transient reduction in blood counts (monitor), no cases of leukaemia attributable to treatment in SCD. Increase in nail and skin pigmentation - cosmetic, dose-dependent and reversible. Pregnancy: very high doses may affect fetus development in animals, no effect reported in humans. Stop 3 months before pregnancy. Multiple modes of action: increases HbF production, improved red cell hydration, reduced neutrophil count, modifies endothelial cell interactions, acts as a nitric oxide donor.

Answer 76

Malaria infection in SCD is associated with morbidity and mortality. Anti-malaria prophylaxis and insecticide treated nets should be provided to all SCD in malaria endemic areas. Prompt diagnosis and treatment of malaria

Answer 77

SCD have functional or anatomical asplenia and are at high risk of infection with encapsulated organisms. Prophylaxis vaccination and penicillin - reduces incidence of infections but doesn't remove risk completely. Penicillin and prompt referral for further treatment may be life saving in the event of infection. Other infections: Parvovirus and aplastic anaemia.

Answer 78

signs and symptoms of respiratory distress (chest pain, fever, wheeze, SOB or cough). New radiological evidence of consolidations. Haematological emergency: SaO2<94, Rx CRO and Clarithromycin, high flow oxygen/CPAP, IV hydration, incentive spirometry, thromboprophylaxis, regular monitoring, discussion with ICU, exchange transfusion. Can be difficult to distinguish from LRTI. Usually occurs during painful crisis, chest/abdominal/back pain, pleurisy, cough, dyspnoea. Raised inflammatory markers. Fever. Hypoxia, tachypnoea, tachycardia. Infiltrates on CXR: bilateral, bibasal. Causes of hypoxia in SCD: chest infection, acute chest syndrome, pulmonary embolism, opioid toxicity (?Type 2 respiratory failure), fat embolism syndrome, pulmonary hypertension (?Type 2 respiratory failure)

Answer 79

Devastating complication of SCD. SCD children >200 fold risk of peers for stroke. 11% of HbSS have an apparent stroke by age 20 years. Risk factors: Hb<70, LDH>2000, transcranial doppler velocity >200m/s, evidence of silent infarct on MRI, previous painful crises, renal failure, retinopathy, hypertension. Management: haematological emergency, exchange blood transfusion, identify precipitating cause, management with multi-D team, manage in ICU when possible. Prevention: Investigations for high risk or silent infarcts: transcranial doppler US (children), neuroimaging, neurocognitive assessment, psychosocial assessment. Prophylactic therapy: hydroxyurea, chronic exchange blood transfusion

Answer 80

Problems: red cell antibodies, delayed transfusion reactions, iron overload, infections. 'Hyperhaemolysis': rare, severe delayed transfusion reaction. Rarely without existing or newly formed red cell alloantibodies, haemolyse own as well as transfused cells, poorly understood mechanism, heme toxicity. Avoid future red cell transfusion. If transfusion unavoidable, consider pre-emptive IVIg and methylprednisolone +/- Rituximab. Automated red cell exchange transfusion: Aim to lower HbS to <30%, Hb ~100. Cross match 8-12 sickle negative, phenotyped (Rh and Kell as minimum), <5 days old. Indications: Acute chest syndrome (severe clinical features, progression despite top up transfusion), acute multi-organ failure, hepatic or splenic sequestration, intrahepatic cholestasis, severe sepsis. Emergency and elective surgery (individual considerations). Acute ischaemic stroke (primary and secondary stroke prevention). Vasoocclusive episodes/current/previous complications in pregnancy. Repeated severe VOC despite HU or if HU contraindicated. Pulmonary hypertension, leg ulcers (usually temporary indication)

Answer 81

Numerous advances in the understanding of sickle cell disease have allowed the development of curative therapies through allogeneic stem cell transplantation, with the promise of gene therapy-based treatment in the future. Drug treatment (aim to allow more cells to transit the microcirculation before sickling), Allogeneic transplant (an established curative strategy using bone marrow stem cells from a donor without SCD), Ex vivo gene therapy (the patient's bone marrow cells are modified by adding a beta-globin gene, using a retroviral vector or with gene editing, to reactivate fetal Hb (HbF) or correct the disease mutation). In vivo gene therapy (direct gene editing in patients could circumvent the need for transplantation of modified patient cells if sufficient efficiency and safety can be achieved).

Answer 82

A genetic disorder of public health significance. Diverse and complex disorder. Associated with numerous acute and chronic medical complications. Limited treatment options. Evolving therapeutic landscape. Gene and cellular therapies are available and developing for cure

Answer 83

The commonest skin diseases that occur in the 'tropics' are not the 'classical tropical' ones'. It can be difficult to pick out the NTD from the common conditions.

Answer 84

Barrier, Immune function, Temperature regulation, Attraction/display, Sensing the environment, Metabolic, Homeostasis of water, electrolytes

Answer 85

Prevalence of skin disease is high, varies depending on where study done 40-90% have a skin disease - case definition and methodology alters prevalence. Skin disease is common, at least 1 in 4 have it worldwide, and it is often neglected by doctors. Skin disease is a public health issue, economic burden for individuals and families. Lack of dermatologists. Need to train more health workers (but LMIC they are already overworked with managing childbirth, acute illness etc). The majority of skin disorders seen in resource limited settings are those that are seen all over the world, in all skin types.

Answer 86

Scabies, bacterial skin infection, fungal infection (superficial infection), eczema, acne, HIV-associated skin diseases, pigmentary disorders, wounds. These are defined by the International Foundation for Dermatology and WHO

Answer 87

Ectopic mite, Sarcoptes scabiei var hominis. Designated a NTD by WHO in 2017. Symptoms are thought to be due to hypersensitivity to the mite, eggs or faeces - sensitisation by continuous exposure. Epi: 565 million incident cases, 4.84 million DALYs. Transmission: close physical contact, fomites and bedding (less than physical contact), outbreaks in closed communities, incubation period 4-6w - asymptomatic and transmit which is why outbreaks in closed communities are perpetuated. No immunity.

Answer 88

Intense itch, burrows, papules/nodules/vesicles/pustules. Web spaces of hands, axilla, areola, umbilicus, genitals. Excoriations. The pattern may differ in infants (feet), children and the elderly (mimics xerotic dermatitis). Unmasking IRIS in HIV occurs. Crusted scabies (hyperkeratosis, itch may not be a prominent feature (and may contribute to worsening due to lack of scratching the mites out), HIV serology, HTLV1 serology)

Answer 89

Clinical, Identification of the mite (or eggs) (sens <30%), dermatoscope (delta wing sign), microscopy, no serological, molecular or point of care tests, peripheral eosinophilia

Answer 90

Treat the whole 'family'. Topical treatment (5% permethrin cream, benzylbenzoate lotion 25%, 12.5%, 6.25%, 0.5% malathion lotion), oral ivermectin, moxidectin under investigation, keratolytics. Practical steps in treating: Information (diagnosis, transmission, fomites). Treatment advice: Benzyl benzoate 3 consecutive days concentration determined by age, OR two treatments 7 days apart (Permethrin 5% or Ivermectin 200ug/kg) and treat household contacts treated simultaneously (economic - cheaper to treat everyone now - need to take the time to explain this). Expectations from treatment and management of post-treatment symptoms. Cannot give Ivermectin <15kg in children (although consensus from France suggests you probably can give it)

Answer 91

Advice about post-scabies itch, dermatitis, psychological support, sexual health screen. Resistance vs Relapse vs Reinfestation - challenging, demonstration of 'tolerance' rather than resistance to permethrin in Europe. Ivermectin resistance in two cases in Australia.

Answer 92

Secondary bacterial infection, post-streptococcal glomerulonephritis, rheumatic heart disease, bullous disease, erythroderma, widespread skin loss

Answer 93

Health care in detention - managing scabies outbreaks in prison settings ICRC have a good document

Answer 94

WHO informal consultation 2019: Community prevalence of scabies is >10%, two doses of oral ivermectin delivered 7-14d, 3-5 rounds of MDA, stop if prevalence of scabies falls <2%.

Answer 95

Eukaryotes. Heterotrophic - absorb nutrition from the environment. Most are saprophytes. Growth forms: moulds and yeast. Moulds are multicellular, filamentous (hyphae), reproduce by sporulation. Yeasts are unicellular, reproduce by budding, some produce hyphal structures. Dimorphic fungi are both.

Answer 96

Classification based on morphology, dual nomenclature - mode of reproduction. Anamorph phase (asexual state) form that occurs in infection, observed in tissue and culture. Teleomorph phase (sexual state) basis of taxonomy, rarely observed in laboratory. Most fungi are heterothallic - require 2 mating strains. Some are homothallic (self-fertile).

Answer 97

Recognition of fungi in asexual state. In tissue (direct examination) - phylum/genera level (characteristics of hyphae and yeasts). In culture - species level (asexual production of spores). Asexual spore production (conidiogenesis). Thallic (conidium produced from existing hyphal cell). Blastic conidiogenesis (budding process, large numbers of spores from single conidiogenous cell. Holoblastic - conidium contains both cell layers, chains may branch. Enteroblastic - outer wall ruptures, inner layer becomes new spore wall, chains do not branch)

Answer 98

Tinea, ringworm. Keratinophilic moulds (digest keratin from hair, skin and nails). Very common 20-25% global population. Anthropophilic, Zoophilic tend to be more aggressive (tend to affect face more often), Geophilic (soil). Direct microscopy: KOH 20% wet mount

Answer 99

Endothrix = Trichophyton sp.- may consider Terbinafine. Ectothrix = Microsporum sp - may consider Griseofulvin or azole

Answer 100

Highly virulent and multidrug resistant Trichophyton indotineae. T mentagrophytes genotype VIII. Mutation in squalene epoxidase (SQLE) gene. Resistance to terbinafine. Emergence due to widespread use of combination topical steroid and antifungal/bacterial. Chronic, recurrent, recalcitrant infection. Severe and atypical presentations. History of travel. Identification by molecular methods.

Answer 101

Not only T mentagrophytes. Also seeing T rubrum, T interdigitale, T tonsurans. M canis, M audouinii, N gypsea. Resistance to terbinafine, itraconazole, fluconazole, griseofulvin.

Answer 102

Deep dermatophyhtosis (immunosuppressed) T rubrum, Extensive dermatophytosis T indotineae. Sexually transmitted dermatophytosis T mentagrophytes VII

Answer 103

Hortaea werneckii. Saprophyte - soil, wood, compost. Asymptomatic infection of skin (esp acral palms >soles). Rare (adults > children) associated hyperhydrosis. Rx topical azole (ketoconazole)

Answer 104

N dimidiatum, N hyalinum. Infection of skin and nails. Caribbean, West Africa, SE Asia. Dryness, scaling - palms and soles. Onychomycosis (distal and lateral nail edges), onycholysis, brown pigmentation. No effective treatment

Answer 105

Black piedra (Piedraia hortae, hard, black nodules, scalp >> facial, genital). White piedra (Trichosporon spp, soft, white - light brown nodules. Facial, genital >>scalp)

Answer 106

Implantation mycoses. Tropical distribution. Environmental organisms - saprophytes. Immunocompetent individuals. Exposed body sites. Chronic/progressive. Disabling.

Answer 107

1 Mycetoma (eumycetoma (fungal), actinomycetoma (bacterial). 2 Chromoblastomycoma. 3 Other deep mycoses (sporotrichosis, phaeohyphomycosis, lobomycosis, rhinosporidiosis, entomophthoromycosis)

Answer 108

Clinical triad: 1 (painless) subcutaneous mass, 2 sinus formation, 3 discharge containing grains. Majority feet but shoulder can be common as people carry things over the shoulder have recurrent exposure. Excise mass - grains within tissue. Distribution largely within latitude 30o north, 15o south. Acacia exposure in Sudan is classic. Aetiology fungal: dark (Madurella mycetomatis, Falciformispora senegalensis, Trematosphaeria grisea), pale (Scedosporium boydii, Fusarium spp, Neotestudina rosatii, Sarocladium spp). Bacterial (Actinomadura madurae, Streptomyces somaliensis, Actinomadura peletieri, Nocardia brasiliensis, Nocardia asteroides). Diagnosis: grains from sinus tract - direct microscopy of grains. XR/MRI: tissue and bone destruction. Treatment: Eumycetoma (fungal): antifungal and surgery (itraconazole), recurrence >1/3, posaconazole - refractory disease, Fusarium. Actinomycetoma (bacterial): combination antibiotics SXT, Amikacin, Rifampicin, Amox/Clav, CR<90%. Itraconazole (daily) better than Fosravuconazole (weekly). Comment: for small lesions surgery up front, for lesions >5cm consider pre-surgical antimicrobial, then debulking surgery.

Answer 109

Cutaneous sporotrichosis - ulcerating nodules, plaques, purulent discharge, exposed body sites esp upper limbs. Two forms: 1 Lymphocytnaeous form (75%) 'sporotrichoid' distribution of skin lesions. 2 Fixed cutaneous 25% variable morphology of skin lesions, papulopustular, nodular, verrucous. Systemic disease may occur in immunosuppressed patients - can have extensive skin involvement, bones and joints, as well as pulmonary, ocular and CNS. Differential diagnosis: Cutaneous leishmaniasis, atypical mycobacterium (M marinum), cutaneous nocardiosis. Aetiology: S schenckii (most common), S brasiliensis, S globosa. Dimorphic fungi. Distribution: mainly occurs in tropics and subtropics. Prevalence <0.5%. Hyperendemic foci - Brazil, Mexico. Aetiology - S schenckii (most common), S brasiliensis, S globosa. Dimorphic fungi - saprophytic mould 25-28oC, pathogenic yeast 36-37oC. Distribution: mainly occurs in tropics and subtropics. Prevalence <0.5%. Hyperendemic foci - Brazil, Mexico, China, humid environments. Neglected tropical disease - cases not reported. Sporadic cases in Europe. Source of infection: widely distributed in nature. Soil and decaying organic matter = trauma. Cat bite/scratch in Brazil -> S brasiliensis. Histopathology: granulomatous reaction. Suppurative with neutrophil foci. Cigar-shaped or oval yeasts (3-5um) PAS and Grocott stains. Asteroid bodies. Treatment: Itraconazole, Terbinafine or Potassium iodide. Treat until clinical resolution. Surgical excision or drainage (cystic lesions). Thermotherapy, cryotherapy, photodynamic therapy may be used.

Answer 110

Chronic infection of skin and SC tissue. Dematiaceous (brown-pigmented) fungi (Fonsecaea pedrosoi, Cladophialophora carrionii, Phialophora verrucosa, Exophiala spp). Produce thick-walled murform or sclerotic cells. Multiply by binary fission. Presentation: verrucous plaque, polymorphic, slowly progressive, dissemination extremely rare. Distribution tropical with hyperendemic foci, Mexico, Brazil and China. Diagnosis: skin scraping (direct microscopy). Complications: swelling, scarring, ectropions, joint contracture, squamous cell carcinoma from longstanding inflammation. Treatment: Variable response (Itraconazole, Terbinafine), Severe disease (itraconazole and terbinafine/flucytosine), Refractory (posaconazole). Excision of small lesions, thermotherapy, cryotherapy, PDT (photodermotherapy).

Answer 111

Lacazia loboi. Central and South America. Keloid-like skin lesions. Ears, arms and legs. Dx: microscopy, histopathology - very difficult to culture. Rx survival excision. Does not respond well to antifungal therapy

Answer 112

Slowly progressive, subcutaneous swelling and fibrosis. Basidiobolus ranarum (SE Asia, Africa, limb swelling, children (boys)), Conidiobolus coronatus (Africa, India, West Indies, S America, facial swelling, young adults (males))

Answer 113

Caused by dimorphic pathogens. Infection usually by inhalation. Asymptomatic <-> disseminated infection. Occupy specific ecological niche. Hazardous to laboratory staff. Geographic distribution is quite limited (other than Histo)

Answer 114

H capsulatum - var capsulatum (Wide geographic distribution, soil enriched with bird or bat droppings, caves, roosting sites, attics - asymptomatic infection common in endemic areas, but may have acute pulmonary, disseminated or chronic presentation, cutaneous in HIV with low CD4 presents as papules, nodules - umbilicated, necrotic on the face and body. Mucocutaneous granulomas and ulcers may occur in acute and chronic disseminated forms) - var duboisii (African histoplasmosis - intracellular parasitic yeast, infection by inhalation, often involves skin, bone and lymph nodes). Risk factors: male agricultural workers, occupational/environmental exposure, immunosuppression esp lymphoma, HIV. Diagnosis: Direct examination or histopathology Hcc small 2-5um oval yeasts, Hcd larger 10-15um. Culture: tan-white, cottony colonies, tuberculate macroconidia. Treatment Itraconazole, Amphotericin in severe disease

Answer 115

B dermatitidis, B gilchristii. Saprophytes. Epi: US (Mississippi valley), Africa, Asia. Soil, organic matter - close to rivers. Infection in dogs. Infection by inhalation, primary skin infection can occur (very rare). Risk factors: rural and agricultural work, Males>females 5:1, uncommon in HIV/AIDS. Clinical presentation: primary cutaneous blastomycosis (rare, laboratory workers at risk), pulmonary (variable symptoms, lung cavity, abscess, often disseminates if untreated), disseminated (skin involvement common, nodules, abscesses, pustules, warty lesions, often on torso). Diagnosis: Direct examination (thick-walled, spherical yeasts, broad-based buds). Culture (mould at 30C, white-tan cottony). Treatment itraconazole, disseminated disease Amphotericin

Answer 116

C immitis, C posadasii. Endemic in SW USA, Mexico, Central and South America. Semi-desert areas, low rainfall, found in soil. Infection by inhalation of spores - humans and animals. Spores -> spherules in lung. Risk factors: Latin, Native American, African American, immunosuppression, pregnancy - dissemination, exposure to soil/dust. Clinical presentation: Acute pulmonary infection (variable severity, can be influenza or TB-like), acute disseminated coccidiodomycosis (rare <0.5% (immunosuppressed), multi-system involvement, skin: verrucous plaques, abscesses, ulcers, high mortality), progressive pulmonary disease with dissemination. Direct examination (large spherules 30-80um containing endospores). Culture (fast growing, white-tan, cottony colonies. Thick-walled arthroconidia, alternate empty cells. Management: not necessary to treat pulmonary infection. Itraconazole or fluconazole. Amphotericin B.

Answer 117

P brasiliensis, P lutzii. Brazil - 80% of cases, Colombia, Venezuela, Ecuador. Soil and animal reservoirs, humid forest regions, coffee/tobacco crops. Acute form (juvenile - prominent lymphadenopathy, fever, hepatosplenomegaly, skin lesions in 50%, mucosal invasion rare) and chronic form (adult - >90% of cases, vegetative lesions, ulcers, oral mucosa (muriform stomatitis), macrocheilitis, skin - face, upper body). Direct examination large yeast 20-60um with multiple budding. Culture slow growing, white-brown colonies. Management: Itraconazole, Amphotericin, Voriconazole, SXT.

Answer 118

T marneffei, SE Asia esp Thailand, Vietnam, Southern China. Associated with bamboo rats. Risk factors: rural agricultural workers, strong association with AIDS, increased incidence in rainy season. Disseminated mycosis in immunocompromised and healthy. Skin lesions present in 70% of cases - face, chest, extremities. Oral lesions - papules, erosions. Genital ulcers. Systemic features: fever, weight loss, hepatosplenomegaly. Mortality <1 in 3. Direct examination oval yeast cells with transverse septa. Culture: fast growing suede-like white-yellow. Flask shaped phialides, globose conidia. Management: early diagnosis >> reduces mortality. Amphotericin B and itraconazole. Long duration to prevent relapse.

Answer 119

New genus 2017, reservoir in soil, infection by inhalation, opportunistic infection. Es africanus - South Africa. Individuals with advanced HIV disease. Clinical presentation overlap with Histo and Talaromycosis. Skin and mucosal involvement ++ (96% have skin lesions at presentation, overlap with histoplasmosis, 86% have abnormal CXR). Histopathology not specific (similarities H capsulatum, B dermatitidis). Culture: growth in 7-30d, yellow-white to tan, powdery. Slender conidiophores, florets. Management: Amphotericin B, Itraconazole, voriconazole, posaconazole. Avoid fluconazole (high MICs)

Answer 120

Common things occur commonly

Answer 121

Can mimic fungating SCC

Answer 122

Thailand (xerosis, seborrheic dermatitis, PPE, folliculitis, zoster, alopecia, drug eruptions, tinea corporis, onychomycosis, penicilliosis), Uganda (seborrheic dermatitis, scabies, PPE, melasma, tinea corporis, onychomycosis, allergic contact dermatitis, tinea pedis, atopic dermatitis, nummular dermatitis), Nigeria (PPE, seborrhoeic dermatitis, zoster, xerosis, tinea manuum/unguium, Molluscum, warts, drug eruptions, scabies), Brazil (seborrheic dermatitis, xerosis, tineas, onychomycosis, PPE, Kaposi sarcoma, Histoplasmosis, hyperpigmentation, psoriasis, scabies)

Answer 123

Very common in HIV, worse at lower CD4 counts, will improve with ART. Can mimic dandruff. Erythema/fine scale: scalp, eyebrows, alar crease, axillae, groin. Rx: Clotrimazole 1% cream, Hydrocortisone. Other treatments: econazole cream, ketoconazole cream/shampoo

Answer 124

Particularly bad at low CD4 counts, may not improve with ART (can be recalcitrant). Gentle skin care: emollients are first line (whatever is available and affordable). Topical steroids. Treatment: betametamethasone valerate, hydrocortisone. Other treatments: triamcinolone, mometasone, fluocinonide, clobetasol.

Answer 125

Low CD4, high viral load, symmetric excoriated papules on extremities, exaggerated bug bite response. ART may be helpful. Topical steroids and anti-itch medications. Treatment: Betamethasone. Other treatments: fluocinonide, clobetasol, sedating antihistamines. Comment: dysregulated immune response, with pruritis and scratching perpetuates this

Answer 126

Common in HIV, painful vesicular lesions. Dermatomal and/or grouped. Pain/itch precedes rash 2-3 days. Vesicles, crusting - different stages of morphology within the evolution. Treat with antivirals acutely. TCAs/Gaba for PHN. Treatment: Aciclovir, amitriptyline. Other treatment: valaciclovir, gabapentin. Comment: post-herpetic neuralgia is not commoner in HIV - most HIV with post-herpetic neuralgia have V1 distribution.

Answer 127

Four forms: Classical (old men Jewish heritage), Endemic (Central and East Africa), HIV/AIDS (Epidemic), Transplant. In HIV: Severe disease at low CD4, consider if lungs/gut involved, need ART (in mild disease may be sufficient, but in severe disease need chemotherapy). If disease severe will need additional chemo, best is liposomal doxorubicin. Treatment: ART, doxorubicin/adriamycin, bleomycin, vincristine (ABV). Other treatment: Liposomal doxorubicin (Doxil), Taxol, PD1 inhibitors, Pomalidomide. Comment: lungs and gut (mucocutaneous), skin - classically involves feet and lower limbs. Assess for oedema, look in the mouth. Giving steroids in setting of unmasking IRIS with KS - this may tip the balance to death

Answer 128

Genital and common warts very common in HIV. Worse with low CD4 count. May not get better with ART. Increased risk of neoplastic transformation so need to monitor for AIN/VIN/CIN. Treatment same as HIV negative patients although Imiquimod less effective in HIV. Treatment: Salicylic acid, podophyllum. Other treatment: cryotherapy, surgery does have some benefits but may not be available

Answer 129

Paradoxically worse disease at low CD4 counts (despite it being immune-mediated disease). Will improve with ART. Well demarcated silvery scaly plaques: extensor surfaces. May affect nails and joints. Treatment: Betamethasone, ART. Other treatments: clobetasol, fluocinonide, UV light. Comment: look at nails, may see pits. Demarcated lesion with no central sparing. Consider non-adherence or ART resistance if HIV patient develops psoriasis/flare

Answer 130

CD4 count <20, Pts within 3-6 months of initiating ART. Rx Itraconazole 200-400mg/d (despite this not being a fungal disease). Permethrin from waist up (despite this not being a parasitic disease). Photo therapy. Wait for immune reconstitution to settle (3-6 months after starting ART). Treatment: Permethrin, Itraconazole. Other treatments: UV light, isotretinoin

Answer 131

Transmission and acquisition 4 times more likely in PLWH. Ulcerated lesions with scalloped borders. Genital/perioral location. Treatment: aciclovir. Other treatment: valaciclovir, famciclovir. Comment; can be subtle in HIV, impetigo. Verrucous nodules in very low CD4 ACV resistant herpes - rare in immunocompetent (0.1-0.6% resistance), 10% more common in immunocompromised. Think about it unresponsive lesions or atypical presentations including verrucous lesions - can be difficult to distinguish from SCC - can give IV cidofovir (or intralesional), foscarnet, pretellovir (only available in Japan - DNA helicase inhibitor)

Answer 132

Low CD4, may be extensive, often facial involvement. "Molluscum has never killed a patient, but has saved a good number of patients" - may be the reason a patient takes ART (when previously unwilling) - pearly umbilicated papules. Differential diagnosis: Cryptococcosis, Histoplasmosis, Talaromycosis

Answer 133

Clade 2B mimics syphilis, but painful (can cause proctitis). Symptoms: Rash 90%, Fever 58%. Polymorphic exanthem: pustules, vesicles, pseudopustules (solid, not full of fluid), ulcers (mouth, genital - can have chancreform appearance, some have punched out appearance), papules can all occur. Exanthem/morbilliform rash can be seen (harder to see in darker skin tones)

Answer 134

No two refugee/asylum seeker/patient's stories are the same. No two refugee/asylum seekers/patients profile of health needs are the same

Answer 135

1 Physiological needs (air, water, food, shelter, sleep, clothing, reproduction) 2 Safety needs (personal security, employment, resources, health, property) 3 Love and belonging (friendship, intimacy, family, sense of connection) 4 Esteem (respect, self-esteem, status, recognition, strength, freedom) 5 Self-actualisation (desire to become the most that one can be)

Answer 136

Factors that affect the health of migrants and their host communities: Social determinants of health, migration, host country policy, living and working conditions and discrimination. Increased vulnerability to infections and medical conditions. Population movement and infection transmission across boarders. Global health implications. Cultural and socioeconomic barriers. Integration of health services. Public health policy.

Answer 137

Movement of people from one place to settle in another as an individual, family unit or large groups. 1 Voluntary 2 Forced. Why do people leave (environment, social, economic, political factors) Push factors (leave poverty, fear, disasters, unemployment) Pull factors (safety, opportunity, stability, freedom)

Answer 138

Forced; civil unrest/natural disaster/political, religious or other persecution. Internally displaced (often religious within own country). Asylum seeker: a formal application for refuge in another country. Refugee: if application successful, the legal status becomes that of a refugee. Migrant health: health status and issues faced by migrants. Vulnerable migrants: specific groups such as undocumented migrants, children, women and elderly. Global context is that 75% are hosted in a LMIC, 69% within border countries (not what the mainstream EU/Aus media would make us believe)

Answer 139

Key components: epidemiological data (morbidity and mortality), access to healthcare services (screening, vaccination, mental health support), Cultural and language considerations. Examples of complex health needs: Infectious diseases (malaria, TB, HIV), Mental health and trauma-related issues. Maternal and child health concerns. Mental health symptoms were documented in 77% of unaccompanied asylum seeking children, physical assault and abuse was reported in 67%, IDs warranting treatment were identified in 41%, 28% reported body aches and pains. 24% presented with GI symptoms.

Answer 140

People who are socially excluded: risk factors for poor health, multiple complex health issues, stigma and discrimination, limited capture in records, barriers to access (socioeconomic, legal and policy, cultural and linguistic, and geographical). Strategies for improvement: community engagement and outreach programmes, training healthcare providers on cultural competency and language services, policy recommendations for improving access to healthcare for migrants. Six essential strategies for inclusive engagement: 1 Build personal relationships with target population 2 Create a welcoming atmosphere 3 Increase accessibility 4 Develop alternative methods for engagement 5 Maintain a presence within the community 6 Partner with diverse organisations and agencies

Answer 141

Trauma-informed methods of working are based upon an understanding of the harmful effects of traumatic experiences together with fundamental principles of compassion and respect. Any form of professional communication with a person who has suffered human trafficking or slavery should be treated as an opportunity to help them to progress towards a long-term situation of safety, stability and well-being

Answer 142

At any professional encounter, in all professional communication: Understand the harmful effects of trauma - Compassion and Respect. create safe environment, minimise re-traumatisation through repeated history taking, no such thing as a 'classic victim'. Create the 'illusion of time', be realistic and honest when discussing care. Briefly and respectfully acknowledge distressing information. Always clearly introduce yourself and role. Ask preferred name choice.

Answer 143

The emotional impact of being exposed to the traumatic experiences of others. Risk reduction strategies: Peer support/supervision (buddy system, reflective practice), work/life balance (physical health, mental health), Parasympathetic nervous system (Cold water swimming, meditation). Symptoms of vicarious trauma: intrusive thoughts, emotional distress, empathy fatigue, physical symptoms. cognitive changes, changes in worldview, hypervigilance, avoidance behaviours. Treatment: self-care and stress management, psychoeducation, supportive relationships.

Answer 144

To grow and develop optimally, children need adequate nutrition, they need to be healthy, they must feel safe and secure, and have opportunities for learning starting from birth. Mothers too, need to be healthy prior to conception and they should receive quality antenatal care.

Answer 145

Pushed from a country where things are not going well - health care, education, safety have not been able to be a priority, have a journey that may be months, may be years, invariably traumatic, and then encounter a new environment where they are again, exposed to challenges in accessing health care, education, safety etc - coming from something difficult, through something difficult and to something difficult - that tends to be universal.

Answer 146

Maternal: Nutrition, Safe delivery, neonatal care, screening for BBV. Babies: neonatal care (high period of disability, key period for vaccines and building immune system - likely to suffer lifelong), Childhood: nutrition, dental health. Adolescence: sexual , reproductive and mental health

Answer 147

At every age, safety, security and financial stability are key to achieving self-actualisation and a happy life in the destination country. If there is no family or community that is very difficult. Need to have a sense of who you are and where you are going to develop to full potential. Some of this is education, role models and education. All of these are impacted by migration experience

Answer 148

Long before child born. If mother or parents have not been access basic education, less likely to access healthcare with vaccines and safe delivery. Childhood: informal education, on being secure, being fed and not hungry), Childhood: formal education, school, longterm opportunities for studying and learning

Answer 149

Trafficked women, family groups (enormous history of physical and sexual trauma), Family groups (including children, often both parents, young children who have either under organised resettlement, or overland by long and tortuous process). Unaccompanied young people (usually boys, eldest child, to establish life, gain legal status and send money home, eventually bring family members over)

Answer 150

High frequency of congenital difficulties that have not been detected, undertreated paediatric problems, nutrition (often obesity more than under nutrition), lack of immunisation, dental work

Answer 151

Often asymptomatic TB 18%, Parasitic 7%, HBV 3%, Schistosomiasis 12%

Answer 152

Rare situation where someone doesn't have a mental health challenge. Ability to do something about it is limited, resource constrained, particularly lacking continuity of care in mobile population. Unaccompanied children 80-90% sexual assault, 60-70% physical trauma (2/3 deliberate torture) - these will leave longterm mental health problems. Smaller children have delayed development, behavioural upset, children struggling with toilet training, integration and separation. Remember that mental health kills - risk of self harm is incredibly high, and suicide is considerable.

Answer 153

Stop child trafficking (still common in London in Albanian communities, but young women from Vietnam and a few other key areas) consider RF even if history does not disclose it. FGM - consider daughters born here may still be at risk (Mother may not have full agency over this), Age dispute project (boys are subject to difficult process as 'aged as children or adults' - adults automatically lose rights to the safety nets. Remember if you are asked to 'age' someone, remember as a healthcare professional the impact this may have and is not to benefit the child

Answer 154

We all need to belong, need family, community, education (formal and informal), having hobbies, interests and doing things we enjoy (think about the bigger picture of what you need to be happy)

Answer 155

If you are not safe, you cannot learn or be part of a community. Safe is essential - may mean being fed, safety from physical threat, and means stability - knowing where you will be this week, next week, next year, and where your children will grow up.

Answer 156

What you do or don't get in early childhood impacts longterm social, cognitive and emotional development - this is lifelong. Intergenerational effect of trauma, the effect of trauma and displacement may be felt several generations down the line. Some is narrative, sharing, stories, some of it has more biological basis - epigenetics and how trauma might affect the expression of genes and phenotype you end up with. Adverse childhood experiences -> disrupted neurodevelopment -> social, emotional and cognitive impairment -> adoption of health-risk behaviours -> disease, disability and social problems -> early death.

Answer 157

Awareness, Advocate (for our patient, thinking about policy, the culture of the place we work, the teaching and training we want to give, work on developing services) , Research (start thinking about how to build the evidence), Innovate. If you don't put patient voice at the centre of this, you will miss

Answer 158

Refugees and migrants are a diverse group and have a variety of health needs, which may differ from those of the host populations.

Answer 159

1 Access to healthcare (language and cultural barriers, legal and immigration status [asylum/refugee have full access to NHS, but if asylum rejected, then only have emergency care], financial challenges, limited knowledge of host country health system, cultural differences, transportation issues) 2 Healthcare system preparedness (lack of training and awareness of healthcare professionals, resource allocation: gaps in infrastructure and services. Fragmentation of services: navigating complex healthcare systems) 3 Stigma and discrimination (impact on healthcare seeking behaviour, examples of discrimination in healthcare and broader societal context) 4 Public health challenges (addressing infectious diseases in migrant populations: screening, vaccination and treatment. Chronic diseases and late presentations, No standardised approach)

Answer 160

Health check-up by healthcare authorities in transit countries. Urgent care provided by medical authorities in detention centres or refugee centres. NGOs medical centres in refugee camps or informal settlement in transit countries. Use of healthcare system existent in the host country (different type of access based on legal status)

Answer 161

Screening interview (Placed in initial accommodation - Home office gathers personal information and decides whether to detain). Asylum interview (full detailed interview, can last several hours) Decision (usually received by post within 6 months) if refused (reason for refusal letter states why claim is, rejected, no reasons given if claim is accepted). Appeal within 14d to first tier tribunal. If rejected again - removal or voluntary return to country.

Answer 162

During the pandemic, an unprecedented number of asylum-seekers were placed in 'contingency accommodation' across North Central London. July 2021, the respond outreach assessment service pilot was initiated in five primary care practice and three contingency hotels across the London boroughs of Barnet, Camden, Haringey and Islington

Answer 163

1 Active identification of ASR via liaison with GPs and accommodation providers. 2 Inclusion health nurse completes outreach health screening appointment at hotel or GP 3 Inclusion health nurse initiates appropriate local referrals and signposting 4 Targeting care planning with local GP and/or respond GP 5 Consultation to support complex case management at the respond MDT 6 Integrated care plan developed and distributed (aim to avoid trauma through repeated asking of same questions)

Answer 164

1 Physical health including infections diseases (physical health symptom survey, medical, drug and vaccination history. Screening for HIV, TB, viral hep, schisto, strongy, and other relevant gut parasites and infections. Actions: referral for catch-up immunisations. Specialist review of positive ID screening results. Signposting to accessible vision and hearing screening. Booking of targeted GP appointments). 2 Emotional and psychological welling (mental health symptom survey. Actions: referral to local primary and secondary care mental health services. Signposting to community support groups and useful wellbeing resources). 3 Sexual and reproductive health (sexual health screening, STI testing and access contraception. Actions: Referral to antenatal services, Referral to sexual health services. Booking of targeted primary care input for contraception). 4 Child development and family functioning (key developmental domain screening and observation, exploring current access to local play and education resources. Actions: Referral to local child development services, allocation of a family support worker with local authority early help services. Engagement with specialist health visitor and school nursing teams). 5 Trauma and safeguarding (targeted screening questions to uncover history of trafficking, sexual exploitation, torture, FGM, modern slavery, and domestic violence. Consideration of impact and parental trauma on parenting capacity. Referral to early help and safeguarding services. Referral to third sector organisations for victims of trauma and torture). 6 Oral and dental health (Dental pain, access to toothbrushes and toothpaste, referral to urgent, and non-urgent dental services. Oral health promotion packs, facilitation of access to emergency dental care, signposting to accessible local dental services, referral for specialist).

Answer 165

CBE, EUC, LFT, HbA1c, Vit D, IGRA, HBV, HCV, HIV, Syphilis, Schistosoma, Strongyloides serology. If from Central and South America T cruzi serology. Urine NG/CT, Stool microscopy for OCP and Novodiagnostics Stool parasites assay. E histolytica/giardia, cryptosporidium PCR. H pylori Ag

Answer 166

Health needs for this population are diverse and complex. Importance of holistic approach following trauma informed practice. An outreach health assessment service dedicated for asylum-seekers is acceptable, feasible and achievable within the NHS. Good links with other services in the community are of paramount importance. In the future: standardised approach to health needs assessment for newly arrived migrants, asylum seekers and refugees across HIC, better communication across host countries to avoid duplication and re-traumatisation. Collaboration with services in the community and introduction of peers in the service. Universal health coverage. Leave no migrant behind.

Answer 167

A group or communities of people that are under threat in terms of safety or health to the extent to which it requires a response. IRC watch list 20 top countries

Answer 168

Conflict drives 80% of displacement, the climate crisis is also a humanitarian crisis, 12 of the 15 countries at most risk of climate, are also at conflict, risk of economic shocks, intertwined. Resulted in almost doubling of people who have been displaced globally. Fueleld by Sudan, but also Gaza 90% of population is displaced, and ongoing displacement monthly

Answer 169

Important idea, refugees are protected under international humanitarian law, but the vast majority of people who are impacted with displacement are internally displaced (forced to leave homes, and seek refuge within their own country, they are under their own government which is complicated. Two other people: entrapped (unable to move, but subject to same humanitarian threats) and host communities who are also impacted by displacement. Important: excess mortality in internally displaced people compared with baseline, whereas refugee populations were much less affected (more access to care), important to note host populations (resident in area of displacement) are also impacted

Answer 170

Camp-like settings: (refugee camps in Kenya, Nepal, IDP camps in Dafur or Camps in Jordan and Lebanon. Urban settings: Urban refugees in Nairobi, IDPs in Pesawar, Refugees in Damascus, IDPs in Tbilisi, Bogota. Rural dispersed settings: IDPs and host in eastern DRC, host population in Darfur. These populations have different demographic and epidemiological risk profiles. Present different challenges for humanitarian health service provision

Answer 171

Crude mortality rate (CMR) no deaths per 10,000 per day. Historically crisis threshold >=1/10,000 persons per day. Does not take into account that mortality has been dropping since the threshold was created in the 60s. Moving towards Sphere guidance - CMR and under-5 mortality doubling of 'norm'. Mortality measurement helps classify emergency and signal humanitarian need: it is therefore deeply political.

Answer 172

Consider how high is mortality, the timeline and number of people involved to assess EXCESS mortality. Within humanitarian healthcare, cannot address previous healthcare needs, but to address the EXCESS mortality (either directly or indirectly)

Answer 173

Common domains of health effects of crisis: infectious disease, malnutrition (and associated morbidities), mental and psychosocial health, reproductive maternal and child health, sexual and gender-based violence, non-communicable diseases, injuries from fighting, landmines.

Answer 174

Baseline disease burden x crisis emergent factors - this evolves over time, and needs to be predicted to consider what funding is required. Several multiplicative crisis emergent risk factors can plausibly affect burden AND epidemiology. Potential to shift to different age groups than usually think of (younger acquisition but also more carriage and disease among older kids)

Answer 175

Underlying factors (Poverty, structural barriers to development and wellbeing. Epidemiological conditions and demographic profile. Vaccination coverage. Access to health services and strength of the health system. Nutrition levels and food security) -> characteristic of conflict (Intensity, duration, type of war) -> impact of conflict (Reduced access to health services/delayed treatment. Disrupted vaccination and disease control programmes. Damage to broader health system. Less agriculture, food supply, and nutritional intake. Poor water, sanitation and hygiene conditions. Inadequate shelter, overcrowding. Environmental decay. Population displacement. Exposure to violence and traumatic events. Poverty) -> Direct health effects (Injuries. Worse mental health. Mortality) and Indirect health effects (Infectious disease. Malnutrition. Poor reproductive health. Worse mental health. Worse NCDs. Mortality). Health system effects of crisis: Prior conflict in West Africa weakened health systems' ability to respond to Ebola crisis. Conflicts in the middle east have allowed previously controlled diseases to recur (polio, leishmaniasis).

Answer 176

Many crises are chronic; acute on chronic. Average length of displacement >10 years and more for refugees. Even after crises have ended, their public health effects may persist for decades (due to: disability following trauma injuries. Long-term mental health problems. Alterations to disease epidemiology eg increased TB transmission, setbacks in disease control programmes. Worse health due to increased poverty, reduced social protection mechanisms. Damage to the health system). Long term impacts can be intergenerational and especially differentiated by gender and age.

Answer 177

In principle - nothing: humanitarian action should support people to be at least no worse off than before the crisis (could entail restoring thalassaemia treatment in Syria, or resuming routine EPI. Nothing is 'just not part of humanitarian work' but some things may not be feasible (skills, funds, prioritisation etc). In reality - a lot: in crisis settings, and especially during the acute emergency phase, interventions need to be adapted to: (Achieve their effect within a very short time window to avert preventable mortality. Cope with reduced access and security. Rely on a potentially smaller and less skilled health workforce. Deal with unprecedented co-existent risk factors or health problems. Function in spite of a disrupted health system. Limited data). Plus rapid impact: population and prevention measures, coping with reduced access and security, functioning despite a disrupted health system, dealing with unprecedented risk factors.

Answer 178

For disaster or war-affected populations within their country borders (including internally displaced persons) Donations need to come through Government, whereas refugees funding comes through UNHCR. The only two actors who are able to have money for response are MSF and ICRC - enable rapid response.

Answer 179

Needs assessment and analysis -> strategic planning -> resource mobilisation -> implementation and monitoring -> operational peer review and evaluation. Significant delays to instituting interventions. Central to this is coordination and information management.

Answer 180

Builds on existing data sources. Rapid needs assessment (MIRA - Multi-sector initial rapid assessment) usually leading on to a more detailed PHSA (Public Health Situation Analysis +/- specific rapid assessments eg Mental Health Rapid Needs Assessment). Assessments of existing service provision and capacity: 4W (Who does what, when and where) and HeRAMS (Health Resources and Services Availability Monitoring System). These assessments ideally should be repeated at each change in context)

Answer 181

Adequate and appropriately spaced shelter. Sufficient and safe food. Sufficient and safe water. Adequate sanitation facilities. Mass vaccination (especially measles). Access to primary health care and referral hospitals. Disease surveillance, outbreak preparedness and control, vector control. Health education and social mobilisation. Reproductive health (MISP). Psychosocial care. Treatment for chronic conditions (eg HIV/AIDS, diabetes, CVD)

Answer 182

Potential to address main health problems. Feasibility, Maximum opportunity benefit, minimum opportunity cost. Maximum effectiveness/cost-effectiveness. Timeliness. Sustainability. Issue is that by the time resources are mobilised, many issues have already compounded

Answer 183

Most agencies dependent on flash appeals to raise funds to intervene. Can take just 2 weeks (eg Ukraine) or 2 months (eg Tigray). Factors increasing speed and likelihood of successful appeal; (The crisis poses a threat to global health security. Availability of data/testimonies/high profile champions. Robust joined up donor approach together with a trusted government. WHO Grade3 emergency (means high level support in Geneva)). A few agencies (eg MSF) have sufficient unallocated funds to intervene immediately. Transitional funding from humanitarian to development donors is challenging. Many promising pilot projects are not continued.

Answer 184

Health effects of displacement depend on the intersection between all hazards, population vulnerabilities, and capacities/resilience in that population. A key indicator of harm (or risk of harm) is the crude mortality rate which directs of lot of aid resources. The characteristics of the displacement context, the health system and the background epidemiology determine the types of healthcare interventions that can and should be delivered. Timely assessment of humanitarian need, systematised monitoring of humanitarian health interventions, and robust programme evaluation are vital to ensure appropriateness and quality of humanitarian response.

Answer 185

Libya detection centres, complicated to maintain access, complicated to keep to MSF's principle of speaking out. Pull out at times when access restricted or too dangerous. Clinic for survivors of torture, MSF also works on the Geo Barents Boat in the Mediterranean - rescuing 91,000 people, attention to the difficult journeys across the Mediterranean. Shrinking of the humanitarian space - only allowed to rescue one boat at a time, detained at the port for 60d, resource heavy and limited. Decolonisation is also important.

Answer 186

MSF has been declared as a terrorist organisation by the Syrian government, which significant affects the ability to access or provide. North East Syria 'stability unstable' There remains a USA and Russian presence - geopolitical instability. Significant security issues for MSF staff. Living in the dessert, very hot and very cold. Staff travel from Hassakeh ~1h away. Hassakeh has its water access disconnected from Turkey, only comes in on trucks, and therefore lots of water-borne illness.

Answer 187

Violence on the border of Europe. Sanctions put on Belarus by Europe after plane made to land to release Russian leaders in Belarus . Belarus response was to give lots of tourist visas and encourage people to migrate into Europe through borders with Latvia, Lithuania, Poland. People freezing on the border. Injuries from trying to climb over the border. Dog bites, beatings, sexual assaults. GI illness and trench foot during Summar, and frostbite in the Winter

Answer 188

Mobile clinic, large containment site for asylum seekers. Houses 600 men seeking asylum, with plan to increase to 800. Ex-military base, large chain fences, people are in barracks, 6 to a room, some people find it very re-traumatising. There is a firing range next to the site. Advocating for their rights, large burden of social needs.

Answer 189

Obligate intracellular Gram negative coccobacilli bacteria. Does not stain on Gram, but does on Giemsa. Fastidious and difficult to grow (cell lines). One of the top causes of non-malarial febrile illness among returned travellers. Tropism for vascular endothelial cell. Can cause mild to life-threatening infections. Underpinning the pathogenesis of rickettsia is vasculitis causing rashes and disseminated features.

Answer 190

Underdiagnosed due to challenges in diagnostics - hard to culture, short rickettsaemic period, delayed seroconversion). Inoculation d-7, Eschar d-4, fever d0, rash d4. Culture, Ag & DNA detectable d-4 to 14. Serology not useful until at least d7. Rash is common feature. Gold standard in the diagnosis of rickettsial infections is indirect immunofluorescence IgG antibody assay of paired serum samples.

Answer 191

All spread by arthropods (vectors: fleas, mites, lice, ticks), often act as reservoir (small mammals/birds). Present all around the world. Worldwide distribution eg murine typhus. Geographically restricted eg scrub typhus. Specific environmental conditions of hosts and vectors. Incubation 6-14d (<21d). Fever, malaise, headache, myalgia. No apparent focus of infection. Eschar? Rash? Severe - vasculitic syndrome. Variable severity. Bloods: normal WCC, normal or low Plt, CRP elevated. Normal or slightly elevated ALT/Bili. Renal failure and DIC late

Answer 192

Still widely used in resource-limited areas where more advanced methods are unavailable. Certain serotypes of Proteus bacterial display antigenic cross-reactivity with Rickettsia IgM Ab produced from 5-10d in response to the infection. Low sens 33% and spec 46%.

Answer 193

Doxycycline is gold standard (alternatives macrolides (no in vivo data in Rocky Mountain Spotted Fever or murine typhus), chloramphenicol (side effects), fluoroquinolones (not all species are susceptible). CDC recommend Doxycycline for suspected rickettsial infections in patients of all ages. New research shoes no evidence of tooth staining when used in short courses. High mortality if rickettsia untreated.

Answer 194

Spotted fever, Typhus (Epidemic, endemic/murine), Scrub typhus groups

Answer 195

Fever, headache, rash +/- local lymphadenopathy +/- inoculation eschar (if present then diagnostic). Incubation 6-10d (<21d). Tickborne (mostly) - environment in which humans become infected depends upon the habitat and biting behaviour of the tick species.

Answer 196

African tick typhus/tick bite fever. Vector: Amblyomma varigatum hard tick (Ixodidae), with climate change are biting more - seeing patients with multiple eschars - aggressively seek host. Geographical confines: Africa/Caribbean. Commonest cause of non-malarial fever post travel to South Africa. Usually mild disease: fever, headache, myalgia, eschars common (may be multiple), mortality <1% Lots of other Spotted group in Africa (does it matter? - all will respond to doxycycline)

Answer 197

R rickettsia, R conorii, Syphilis, Enterovirus = hand foot and mouth, Streptobacillus moniliformis, Mpox, Human monocytic ehrlichiosis, Drug reaction

Answer 198

Mediterranean spotted fever/Boutonneuse fever, Vector: Brown dog tick Rhipicephalus sanguineus. Sporadic cases, often in urban/suburban areas. Distribution Africa, Mediterranean, South Asia. Eschar common, usually single. Complications: multiorgan dysfunction, hepatomegaly, confusion, meningitis, pneumonia, DIC. Moderate severity, mortality 3-30% untreated.

Answer 199

Queensland tick typhus, spotted fever - severe associated with vasculitis, gangrene. Vector: Ixodes holocyclus.

Answer 200

Rocky mountain spotted fever. Vector: American Dog Tick Dermacentor variablis/andersoni. Not confined to the Rockies. Geographically restricted to North and South Americas. Seasonal - peak in Summer. Clinical: Fever, headache, macular rash -> petechial. Eschar rare. Severe vasculitis process with haemorrhagic complications. Severe disease mortality 30-80% untreated. Deteriorate rapidly. Risk Male>female, >40yo highest cases, children <10yo highest reported deaths. RF: G6PD deficiency, immunocompromised, dark skin -> delayed diagnosis and is extremely high risk. Cases rising internationally due to climate change, increased tick activity and spread.

Answer 201

Rickettsialpox. Vector: mite Liponyssoides sanguineus (not a tick!). Clinical 7d fevers, chills, headaches, rash. Thrombocytopaenia. Probably worldwide, urban setting, house mouse. Painless red papule -> vesicular -> eschar: generalised rash, fever, regional lymphadenopathy. Mild illness, self-limited.

Answer 202

R rickettsiae USA Rocky Mountain Spotted Fever Tick vector. R africae Africa/Caribbean Africa tick bite fever Tick vector. R conorii Worldwide (Europe, Africa, Asia) Mediterranean spotted fever/Boutonneuse fever Tick vector. R akari Worldwide Rickettsia pox. MITE vector.

Answer 203

Murine typhus, Endemic typhus. Vector Oriental rat flea - Xenopsylla cheopis. Transmitted by faeces. Human infection from contamination of broken skin or inhalation of flea faeces. Worldwide distribution. Clinical: fever, headache, myalgia, rash (starts central and moves out), no eschar, difficult to distinguish from other spotted fevers. Relatively mild and self-limiting with non-specific features <15% cases present with 'classic' triad of fever, headache and rash. Mortality 1-2%

Answer 204

Epidemic typhus. Vector human body louse Pediculus hemanus. Risk: crowded, unhygienic conditions, transmitted by louse faeces, fever, headache, myalgia, rash. Humans only hot, transmission by body lice - associated with war, conflict, famine, natural disasters eg during civil war in Burundi 1990s. Clinical: nonspecific prodrome, followed by fever, headache, myalgia and wide range of other symptoms. Most patients develop macular, maculopapular, or petechial rash. Complications: meningoencephalitis, myocarditis, splenomegaly. Once febrile it does not fluctuate. Can have a very non-specific spotted rash, with peripheral gangrene (severe small vessel vasculitis). Mortality 4% (recent series) to 80%. Brill Zinsser disease late relapse - organism remains in endothelial cells and reemerge as a milder form and lead to secondary infection (unique to R prowazekii). Rp 3-5 million deaths in the USSR after WWII. Bioterror used against nazi - jewish scientists to make typhus vaccine

Answer 205

R typhi Worldwide Murine typhus or endemic typhus. Vector: Flea faeces - Xenopsylla cehopsis. R prowazekii Worldwide. Epidemic typhus. Louse faeces - Pediculus humanus corporis.

Answer 206

Tsutsugamushi triangle, there are some non-tsutsugamushi Orientia outside of the triangle. Incubation period 1-3w, 1 million cases per year, 1 billion at risk. Vector: Trombiculid mite transmitted zoonosis. Larvae in high density 'mite islands' in jungle clearing. Incubation period 6-21d. Clinical presentation: fever, fatigue, frontal headaches, myalgia, cough. 55% painless eschar. Delayed generalised maculopapular rash. Lymphadenopathy. Pregnancy (stillbirth, prematurity, low birth weight in >40%). Difficult to distinguish from sever dengue. Subtleties - WCC, Plt, LFTs, alter sensorium. Pathogenesis: widespread vasculitis and perivasculitis, accompanied by infiltration of mononuclear cells into affected organs. 34% end organ failure. Diagnosis: Immunofluorescence assay (IFA) is the 'gold standard' sens 70% spec 95%. Serological testing: ELISA, latex agglutination and Western blot could be used for serological diagnosis. Patients presenting early into the illness may have low antibody levels (false negative) - hence empiric therapy in suspected severe cases. PCR can be carried out on eschar or blood. Spec 100%. Sens 74-97%. Weil-Felix test uses a crossreacting Proteus OXK strain, low sens 50% in the second week. Mortality 1-8% (40% untreated). Immunity short lived and strain specific.

Answer 207

Climate change will increase temperature, longer warm season will cause increased range of ticks and reservoir hosts, increased rick abundance and activity, and increased transmission. Will increase Lyme disease, Anaplasmosis, Babesiosis, Powassan virus, Borrelia miyamotoi disease. May increase Rocky Mountain spotted fever, Colorado tick fever virus, other Borrelia infections. How to manage: Increase awareness, prevent exposure, diagnose when present, treat promptly, assess/monitor risks.

Answer 208

Wear long clothing. Check for ticks after outdoor activities. DEET. Promptly/safely remote ticks to prevent transmission of some infectious diseases. Tick removal: Remove upwards, grab from mouth part - they are intrinsically linked to the transmission. Other good reasons to avoid ticks: Babesiosis, borreliosis, CCHF, Lyme disease, Tick-borne encephalitis, Tularaemia. Lone-star tick: Alpha gal - mammalian meat anaphylaxis

Answer 209

Rickettsial infections - Gram negative intracellular coccobacilli. A major cause of non-malaria febrile illnesses among returned travellers. Some found worldwide - others, restricted geographical areas. Diagnosis modalities are similar for all. Most present with fever, myalgia, headache +/- rash +/- eschar +/- variable signs of severity (vasculitic syndrome, CNS disease). Treatment: Doxycycline. No vaccines available.

Answer 210

The health of human civilisation and the state of the natural systems on which it depends

Answer 211

Socioeconomic trends (world population, real GDP, foreign direct investment, urban population, primary energy use, fertiliser consumption, large dams, water use, paper production, transportation, telecommunication, international tourism) Earth system trends (CO2, NO, methane, stratospheric ozone, surface temperature, ocean acidification, marine fish capture, shrimp aquaculture, coastal nitrogen, tropical forest loss, domesticated land, terrestrial biosphere degradation) - all have increased

Answer 212

Increased CO2 and SLCPs (short-lived climate pollutants) -> increased temperature, rising sea levels, extreme weather events. Demographic, socioeconomic, environmental etc factors that influence patterns of risk

Answer 213

New cases, new places, more severe infections. Urbanisation - unplanned and precarious urbanisation can allow invasive vectors and novel pathogens to spread widely. The rationale for an association between climate change and infectious disease is clear. Changed socioecological systems (humans, vectors livestock, and pathogens are forced into increasingly closer contact). Extreme weather events. More international travel and trade. Increased global connectivity (allows invasive vectors and novel pathogens to spread widely). These changes create the potential for pandemics with devastating public health, social and economic consequences. Ultimately leading to increased morbidity and mortality

Answer 214

Floods and drought as a result of precipitating patterns. Drought -> water shortages, impacts on livelihoods including loss of crops, livestock, fisheries etc. Increased food prices, migration -->Indirect health effects --> nutrition related effects, mental health effects, vector-borne disease, airborne and dust-related disease, water-related disease. Other: injuries, migration-related health issues, fires, health care system and infrastructure impacts

Answer 215

Direct effects (heat - crops, animals and labour productivity, CO2 concentrations). Indirect effects (water availability, salinity and sea level rise, pests, soil fertility), Socioeconomic (food demand, dietary patterns, trade/food price, food system policies) all lead to climate change adaptation and mitigation strategies for agriculture -> crop and livestock productivity and vulnerability. Although plants grow bigger in the setting of higher CO2, there is the risk of growing faster than the micronutrients can keep up - leading to lost zinc, iron and protein. Also increased heat reduces pollination, and has impacts in other ways increasing non-communicable diseases in Global North and Malnutrition and communicable disease in the Global South.

Answer 216

In the low latitude developing nations, human nutrition is most dependent on wild fish, and fisheries are most at risk from illegal fishing, weak governance, poor knowledge of stock status, population pressures and climate change. These countries urgently need effective strategies for marine conservation and fisheries management to rebuild stocks for nutritional security. In developing small island states of the Pacific, wild fisheries will move poleward because of a rise in sea temperature, and aquaculture in deltas and floodplains will be affected by rising sea levels. Sub-Saharan Africa regions still largely depend on domestic, subsistence and artisanal fishing. In Bangladesh, much farmed high-value fish is exported to wealthier nations. Smallholder systems, including fish farmed in flooded rice fields, have improved local food security.

Answer 217

Mitigation: action to reduce emissions that cause climate change. (sustainable transportation, clean energy, energy efficiency). Adaptation: action to manage the risks of climate change impacts (disaster management and business continuity, flood protection, infrastructure upgrades). Both (water conservation, new energy systems, local food, education, complete communities, urban forest)

Answer 218

Leadership and governance. Health workforce. Health information systems (vulnerability capacity and adaptation assessment. Integrated risk monitoring and early warning, Health climate research). Essential medical products and technologies (Climate resilient and sustainable technologies and infrastructure). Service delivery (emergency preparedness and management, climate-informed health programmes, management of environmental determinants of health). Financing (climate & health financing)

Answer 219

Vested interests, organised denialism, political short-termism, divided public opinion, perception that change is expensive and difficult.