Malaria Flashcards

Question

Malaria Recurrent Pf

Answer 1

Recurrent can result from reinfection or recrudescence (treatment failure). Treatment failure may be due to drug resistance, suboptimal dosing, poor adherence or vomiting, substandard medicines. Confirm recurrent with microscopy (not PfHRP2 RDTs). May not be possible to distinguish recrudescence from reinfection in individual patients (without PCR for genotyping). Reinfection very common in high transmission areas

Answer 2

Within 28d - alternative ACT to that given first, After 28d consider as a new infection, treat with first line ACT

Answer 3

Patients with Pf malaria can deteriorate rapidly, even with appropriate treatment (esp non-immune), recommend admitting all patients with Pf for initial treatment. Closely monitor patients with hyperparasitaemia >2-10%, if there is any doubt about the species, or there is coinfection, treat as Pf malaria until diagnosis is clear

Answer 4

Artemether-lumefantrine in all trimesters, other ACTs T2-3. Mefloquine safe in T2-3 with artemisinin derivative. Quinine increased risk hypoglycaemia in late pregnancy, only if effective alternatives not available. Primaquine and tetracyclines should not be used

Answer 5

Unsure about species - treat for Pf. If non-Pf in area of chloroquine sens - Rx ACT or CQ, chloroquine resistant Rx ACT.

Answer 6

Primaquine, after checking G6PD status if normal give 0.25mg/kg/d 14d (alternative 0.5mg/kg/d 7d - shorter may improve adherence and thus fewer relapses) Cannot give in pregnant women, infants <6m, breast feeding infants <6m or older infants with unknown G6PD status. Pregnant women get weekly chemoprophylaxis with CQ until delivery and breastfeeding complete, then depending on G6PD, give primaquine. In patients with G6PD deficiency can give primaquine 0.75mg/kg weekly for 8w under close medical supervision for haemolysis

Answer 7

Primaquine kills mature gametocytes of Pf, in endemic low transmission areas, single dose of primaquine (plus ACT) is recommended to reduce the risk of onward transmission. It is not recommended in no-transmission areas as there is no vector (Anopheles mosquito)

Answer 8

Delayed care-seeking, failure of HCW to consider malaria, belief that chemoprevention prevents all malaria, belief that malaria is unlikely if the patient doesn't remember being bitten by mosquitoes, belief that malaria always has classic fever pattern, failure to recognise non-specific symptoms of malaria, failure to immediately obtain a diagnostic test, failure to repeat diagnostic tests if initially negative, failure to prescribe effective treatment immediately, failure to anticipate or treat complications

Answer 9

Sleep under insecticide treated bednet, cover up between dusk and dawn, repellents with 30-50% DEET

Answer 10

Options are Malarone (AQ), Mefloquine, Doxycycline and Primaquine. Pregnant (give Mefloquine), Children (avoid Doxycycline), Depression (avoid Mefloquine). Start 1-2d prior except Mefloquine 2-3 weeks prior. Continue 7d after returning for Malarone and Primaquine, 4w after returning for Mefloquine and Doxycycline. All are given daily except Mefloquine is weekly

Answer 11

After infection, protuberances appear on erythrocyte surface within 12-15h, 'knobs' express PfEMP1 (antigenically variable, strain-specific, adhesive protein), which mediates cytoadherence or attachment of the pRBC to endothelial receptors. pRBCs adhere inside vessels (sequestration) to each other (agglutination) and to non parasitised RBC (rosetting) - in non Pf malaria, significant sequestration does not occur. Most of the major manifestations of severe falciparum malaria are caused by sequestration, microvascular obstruction and organ dysfunction

Answer 12

Africa (9 countries) severe malaria - 4 key predictors of poor outcome: base deficit >8, coma, Ur>20, underlying chronic illness. Mortality artesunate 8.5% quinine 10.9%

Answer 13

SE Asia mortality artesunate 15% quinine 22%

Answer 14

Artesunate IV at 0, 12, 24h. Once received at least 24h parenteral therapy and can tolerate oral, give further 3d ACT. Main objective is to prevent patient from dying, secondary objectives are prevention of disabilities and recrudescent infection. Death from severe malaria often occurs within hours of admission (therapeutic conc of effective antimalaria must be achieved ASAP), severe malaria is a medical emergency, parenteral artesunate is the treatment of choice for all severe malaria. Artesunate rapidly kills ring-stage parasites which are then taken out of the red cells by the spleen, the infected RBC are then returned to circulation but with a shorter life span, resulting in haemolysis. Delayed haemolysis starting >1 week after treatment of severe malaria with artesunate has been reported in hyperparasitaemic, non immune travellers.

Answer 15

The risk for death from severe malaria is greatest in the first 24h (but often the time between referral and start of IV is long, delaying the start of appropriate antimalarial treatment can increase risk of death). Where complete treatment of severe malaria is not possible, but injections are available, adults and children should be given (single IM artesunate & referred to an appropriate facility, if IM artesunate not available, give IM artemether. Where IM injection of artesunate is not available, children <6 should be given a single rectal dose of artesunate and referred immediately

Answer 16

All children presenting with severe malaria in areas of intermediate and high malaria transmission should be given broad spectrum antibiotics in addition to anti-malarial drugs

Answer 17

Coma (maintain airway, exclude other causes such as low BSL, meningitis), Convulsions (diazepam & anticonvulsants, check glucose), hypoglycaemia (recognise and treat), severe anaemia (transfuse), pulmonary oedema (O2, diuretics, I&V), renal failure (dialysis, haemofiltration, PD), metabolic acidosis (exclude/treat hypoglycaemia & septicaemia), spontaneous bleeding (transfuse, give vitK), shock (suspect bacterial coinfection & septicaemia). Additional management: 1 fluid therapy 2 blood transfusion 3 exchange transfusion (no consensus on whether it reduces mortality)

Answer 18

Do not use any of these, they do not work - including dexamethasone, anti-TNFa, IVIg, phenobarbitone, mannitol, NAC etc

Answer 19

Most children who survive make a full recovery, ~15% left with neurological sequelae. Longterm sequelae uncommon in adults (<3%)

Answer 20

Pf sequesters in the intervillous space of the placenta. Cytoadherence is mediated by binding to chondroitin sulphate A (CSA). First time mothers lack immunity to CSA-binding parasites and are highly susceptible to parasitaemia and chronic infection. As a result, this group is an important reservoir of infection. Over successive pregnancies women can acquire antibodies against CSA-binding iRBCs and resistance to placental malaria. Women living in endemic areas develop antimalaria immunity from lifelong exposure to Pf parasites, which controls infection. Thus, total parasite biomass may be low and difficult to diagnose during pregnancy, even in the presence of placental infection. Placental malaria associated with IUGR, preterm birth, LBW, SGA, stillbirth. Worse with 1st pregnancy, reduces with subsequent. Not just Pf, all malaria infections are harmful. Pregnant women are more likely to have severe malaria (T2-3, higher mortality ~50%), at risk of pulmonary oedema & hypoglycaemia (low transmission areas/non-immunes), at risk for fetal death and premature labour. Parenteral artesunate is the treatment of choice in all trimesters. Mechanism is sequestration (mechanical) and pro-inflammatory

Answer 21

Considerable geographic overlap, evidence that HIV coinfection increases malaria severity (higher parasite densities (in partially immune), risk of severe malaria and death (in less immune), in pregnant women - increased adverse effects of placental malaria. HIV patients at higher risk of adverse events and drug interactions: avoid SP if taking SXT, efavirenz increases AQ exposure & risk of toxicity

Answer 22

Defined as for Pf but no density threshold. Severe manifestations include severe anaemia, resp distress, AKI. Less commonly cerebral malaria, pancytopaenia, splenic rupture, haemoglobinuria, jaundice, renal failure, shock. Treat as for severe falciparum and give primaquine after recovery

Answer 23

Defined as for Pf but 2 differences parasite density >100,000/uL and jaundice/parasite density >20,000uL. Associated with high parasite densities. Can present with ARF, shock or resp failure. Treat as for falciparum. Microscopically indistinguishable from Pm but with high parasitaemia and clinical symptoms

Answer 24

Severe malaria is a medical emergency (manifests differently in children and adults). Treat early with an effective antimalarial (Artesunate > artemether > quinine - watch for late haemolysis after artesunate), give broad spectrum antibiotics to children, be careful with fluid replacement and transfusion. Treat complications appropriately. No good evidence to support most other treatment

Answer 25

Capable of transmitting Pf and Pv, unlike other main malaria vectors, it thrives in urban and man-made environments (behaves more like Aedes). Can resist high temperatures thus sustaining malaria transmission in dry seasons. Estimate Pf cases could increase by 50% if no additional interventions are implemented. Usually in Asia, is invading through the horn of Africa. Potential to reverse gains in malaria control - not equipped to handle increased urban malaria burden in Africa, difficult to target the vector with standard control interventions. Interventions in place: increased vector surveillance, increased collaboration between different sectors, bylaws on water storage in urban settings, increase vector control strategies that can target the vector (ie larveciding), ongoing coordination meetings led by WHO

Answer 26

Big problem due to inpatients with circulating gametocytes - advise to sleep under bed net in hospital

Answer 27

Intermittent preventive treatment is recommended in primigravid pregnant women, accessed through antenatal clinics

Answer 28

Sickle cell heterozygous have 10% of the risk of death from Pf compared with those who are homozygous, HbC, thalassaemias, G6PD. O blood type also protective - these probably affect cytoadhesion and splenic clearance, but not straightforward. Haemoglobinopathies prevent the parasite from establishing own actin cytoskeleton within the host cell, impair vesicular transport, reduced cytoadherence and distort trafficking of PfEMP1

Answer 29

Regulation of inflammatory mediators is key to successful resolution of malaria infections. Low levels are beneficial - activation of macrophages to phagocytose infected RBCs and to release toxic radicals that kill the parasite. However, high levels of cytokines cause pathology and disease - instigate fever, increase expression of adhesion molecules on vascular endothelium (higher levels of parasite and leukocyte sequestration), decrease blood glucose levels, inhibit erythropoiesis, promote tissue damage, promote phagocytosis and killing of uninfected RBCs

Answer 30

RTS,S Ag consists of sequences of circumsporozoite, needs 4 doses, low efficacy (26-51%) and not durable, WHO have rolled out from Oct 2021

Answer 31

R21 fused circumsporozoite protein sequences, needs 3 doses plus booster year later, 66% efficacy

Answer 32

Immunity to malaria is acquired following natural infection. The rate of development of immunity depends on the intensity of malaria transmission. Different immune mechanisms operate to decrease parasite prevalence, parasite density and the risk of severe disease and death. Many of the symptoms of malaria are caused by overproduction of inflammatory cytokines. Low levels of these cytokines are required to mediate parasite killing. Malarial immunity involves both antibody-mediated and cell-mediated mechanisms, but these may be directed against different stages of the life cycle and against different antigens. Two modestly efficacious malaria vaccines have been recommended by the WHO

Answer 33

Two subspecies curtisi, wallikeri - highest prevalence in African continent. Clinical: longer latency period, understudied, likely underestimated burden. RDT false negatives are common, molecular diagnosis unreliable

Answer 34

Neglected and commonly benign. Associated with rare kidney pathologies and fatalities. Frequently low parasitaemias, chronic infection suggests immune evasion. Reports of reduced drug susceptibility

Answer 35

There are always some houses without infection (closed, further from water sources), some with low transmission. Hot populations 'hot pops' are at risk because of what they do (not where they live) ie agriculture work, seasonal exposures

Answer 36

1 Prevent the malaria coming out of the mosquito (vaccine targeting sporozoite stage) 2 Chemoprevention - prevent the emergency of parasite from the liver 3 Improved case management 4 Prevent onward transmission through mass drug administration and treat people with primaquine to kill gametocytes (difficult). 5 TBV transmission blocking vaccines, insecticide nets, insecticide residual spraying 6 Stopping the production of mosquitoes

Answer 37

Finances, drug resistance, vector resistance (biochemical, behaviour), diagnostic resistance (HRP2), organisation, climate change - in some places malaria will be too hot to exist and other places will become more susceptible

Answer 38

Reduce vector density (kill, or eliminate breeding sites etc), reduce human-vector contact, reduce the vector's capacity to carry parasite

Answer 39

LLIN long-lasting insecticidal nets, IRS indoor residual spraying, Larviciding, House screening

Answer 40

Evolutionary process leading to decreased sensitivity of a vector population to an insecticide. Resulting from selection pressure due to continuous exposure to an insecticide. Mechanisms: target site, metabolic resistance, behavioural resistance, cuticular resistance/reduced penetration

Answer 41

new insecticides, new modes of action

Answer 42

Climate change alters temperatures and weather patterns in ways that change vector dynamics and increase the risk of malaria. Warmer temperatures can alter vector survival, abundance and increase the geographical spread of malaria vectors. Extensive rainfalls and floods can create more breeding sites extending malaria transmission seasons. Changes in weather can alter mosquito composition, resulting in higher densities of more efficient vectors. Weather changes can affect human behaviour facilitating habits that expose them to vectors eg sleeping outside in hot weather. Temperature changes accelerate changes in vector behaviour, enabling them to escape traditional vector control interventions. Temperature and humidity changes can affect the efficacy of some vector control products.

Answer 43

ITNs are a key malaria prevention strategy with ~2.7 billion nets distributed by 2022. ITN access - not reaching those who need them most. Householders do not sleep under nets, not durable (retention <2y), fabric integrity - insecticide durability. Mitigation strategies: improve ITN allocation eg digitalisation, social and behaviour change campaigns, new metrics to track ITN durability and improve quality. ITNs can lose protective efficacy in the 3rd year post-distribution, including new dual AI ITNs

Answer 44

Outdoor transmission - increase in vectors biting outdoors reduces efficiency of indoor vector control tools like ITNs and IRS. Natural disasters, conflict situations and demographic changes

Answer 45

Bait stations (attractive targeted sugar baits - attract and kill, effective up to 6m, promising for controlling outdoor transmission), spatial repellents (transfluthrin passively emanates using natural airflow), systemic insecticides, genetic manipulation, topical repellents, insecticide treated clothing, housing modification, lethal house lures

Answer 46

Vector control is an important part in the prevention and control of malaria. It was the foundations of the global reductions in malaria burden. Its impact is threatened today by many factors, insecticide resistance, poor durability of nets, reduced funding to boost coverage, invasive species, climate change, outdoor transmission etc. New promising ITNs and IRS have been developed and are being scaled up across Africa. The vector control toolbox is being expanded to go beyond ITNs and IRS eg spatial repellents, ATSBs, Eaves tubes etc – evidence is being generated. Achieving malaria elimination targets will require an integrated and context specific approach which includes vector control

Answer 47

Administration of a full therapeutic courses of antimalaria treatment to a population at risk, whether infected or not, at defined time points separated by periods without drug exposure – for people living in endemic areas, goal is to reduce burden

Answer 48

Administration of an anti-malaria drug to an at risk population in such a way as to achieve protective blood levels over the whole of the period at risk – subtherapeutic doses primarily used by non-immune travellers to malaria endemic areas

Answer 49

Aim: reduce malaria burden in pregnancy. Intervention: from 2nd trimester SP (sulfadoxine-pyrimethamine) at least one month apart, at least 3 doses

Answer 50

Aim: reduce clinical malaria, severe malaria, anaemia and all-cause hospital admission. Intervention: SP or SP+AQ at 10w, 14w, 9m

Answer 51

Aim: reduce severe anaemia in areas of highly seasonal transmission. Intervention: SPAQ monthly starting before rainy season, and continuing one month after

Answer 52

Aim: target school aged children aged 5-15. Intervention depends on school terms

Answer 53

Aim: prevention of malaria following severe anaemia, allows patient to fully recover. Intervention. Outcome: 77% reduction in all-cause mortality, 55% reduction in all-cause readmissions

Answer 54

Chemoprevention target different population at risk in different malaria transmission settings. Recommendations to provide more flexibility to countries to adapt these control strategies to suit their settings and priorities. Generally use non-first or second-line treatments. SP with or without another drug mostly used. Importance to continue to monitor the resistance to the drugs

Answer 55

Vaccines very effective - important additional tools in the fight against malaria. Rapid deployment of the vaccines underway with 20+ countries preparing to roll out, careful introduction and finding optimal delivery methods, combination with other interventions, evaluation of these vaccines in other age groups, next generation of vaccines - combination with transmission blocking and blood stage vaccines.

Answer 56

Effective tool recommended for scaling up global malaria control. Coverage abysmal 11%, pyrethroid resistance resulting in reduced efficacy. High operational cost.

Answer 57

Microscopy capacity is low across Africa, lab diagnosis relies on RDT kits, testing rates are still poor - without testing we do not truly know the burden of malaria. Most RDTs detect Plasmodium falciparum histidine-rich protein 2 (HRP-2) - Threats: gene deletions reduce sens of RDTs causing false negatives, RDTs detecting Pf- or pan-LDH provide less sensitive alternatives and are more expensive. Under-testing - despite recommendation for every case of fever to have a malaria RDT, only 54% are being tested 2015-2023 (improved from 30% 2005-2011)

Answer 58

Emergence of artemisinin resistance in SE Asia and now spreading to Africa, poor access to treatment, especially hard to reach communities, patriarchal barriers (mothers need to wait for husband to return for permission to take child to healthcare), delayed treatment, poor quality of care

Answer 59

IPTp has been implemented at scale for several years, yet coverage is suboptimal, missed opportunities in antenatal clinics, SP resistance now a threat esp East Africa

Answer 60

Low capacity for surveillance, weak systems (inadequate supply of tools, limited number of trained personnel, incomplete reporting - private sector reporting still a huge challenge in most countries), systems are weakest where the burden is heaviest, poor notification and response during emergencies (eg humanitarian crises)

Answer 61

Malaria receptivity is high in most parts of sub-Saharan Africa given the suitable ecology and climate for vector survival. Climate change disruptions including population displacements and mass movement increase malaria risk. Poor integration of real-time meteorological data into national and sub-national malaria monitoring and surveillance systems prevents mitigation planning. Emergence and re-emergence of novel vectors eg Anopheles stephensi

Answer 62

Reaching the 2030 goals of the WHO malaria strategy will require new approaches, new tools nd the better implementation of existing ones. Tailoring existing approaches to prevention, diagnosis an treatment to local contexts. Better and more equitable access to all health services. Strengthening the health systems overall, with a view to achieving universal health coverage. Stepping up both domestic and international investment.

Answer 63

Lots of inefficiencies in domestic financial management and global funding often goes unspent because countries are unable to use the funding 'fast enough' Financing in rich countries is prioritised by the effect upon rich countries (ie impact on military). Genetically modified mosquitoes are innovative, but need community engagement as concept rejected at present. Vaccine and chemoprevention only protect the person, vector control has a bigger community effect.

Answer 64

Awareness of risk, Bite prevention, Chemoprophylaxis, Diagnose promptly and treat without delay

Answer 65

Place: sub-Saharan Africa, areas of deforestation, rural vs urban, type of accommodation. Time; Longer term travellers, seasonality. Person: VFR, extremes of age, pregnancy, immunosuppressed, comorbidities. Awareness of risk: the clinical features of malaria are non-specific - fever, sweats or chills, malaise (vague discomfort), myalgia (muscle pain, tenderness), headache, diarrhoea, cough. Awareness important for you and the patient

Answer 66

Daily 1 d before 7d after. Consider DDI, renal dosing, fatty meal, cannot crush. Preg/BF T2 onwards. SE neuro, GI, hairloss. Malarone is the default option unless pregnant or CrCl<30. It is expensive.

Answer 67

Daily 1d before 4w after. Consider DDI, take with food. Preg/BF not after 15/40, SE gastritis, teratogen, bones/teeth, photosensitivity

Answer 68

Weekly 3w before 4w after. Consider DDI, psych hx, can crush, epilepsy, anticoag, allergy to quinine. Preg/BF safe, SE neuropsych & epilepsy (including 1st degree relatives) - would not use in diving, flying, military, cardiac etc

Answer 69

Long half-life 18d, monthly for 6m, causally protective. Consider G6PD. Access is an issue

Answer 70

Discuss cancelling trip. Increased risk of severe malaria, esp vivax > congenital. Placental sequestration -> difficult/delayed diagnosis. Mefloquine - all trimesters, Doxycycline - if finish 4w post travel by 15w (in practice no), Atovaquone-proguanil - safety data does not suggest any adverse effect but sparse data - take folic acid.

Answer 71

Inform MO 2-3w before travel. Warfarin: Mefloquine ok, others may interact. DOAC: Mefloquine may increase risk of bleeding, Atovaquone may reduce anticoagulation

Answer 72

Choose doxycycline or atovaquone/proguanil

Answer 73

Risk of rapid deterioration, weekly mefloquine easiest >5kg. Atovaquone-proguanil >5kg with milk/yoghurt, Doxycycline >12y

Answer 74

Higher risk of dying from malaria, comorbidities, drug-drug interactions, renal impairment

Answer 75

CrCl <30 avoid malarone - can use mefloquine and doxycycline

Answer 76

All metabolised in liver, Severe use doxycycline

Answer 77

Causal (stop hepatocyte infection) Malarone, Primaquine. Suppressive (kill ring stages - need 30d) doxycycline, mefloquine, chloroquine

Answer 78

Doctors may prescribe SBET in some circumstances such as when the risk of the travellers to get malaria is low (if it is high, consider prophylaxis), the travel destination is remote and medical care may not be available, travellers must be advised and fully understood when and how to use SBET

Answer 79

circumsporozoite protein on parasite surface

Answer 80

L9LS CSP1 major protein of the sporozoite - only a handful of sporozoites during a single cycle of infection, sporozoites are accessible early in infection, 3-6 months protection. Very expensive, not commercially available.

Answer 81

The burden of diseases occurs in VFR population. 70% falciparum malaria patients have not taken chemoprophylaxis. Adherence to advice, BPM and medication is the cornerstone of effective prophylaxis. There are a limited number of prophylactic drugs. Early presentation and diagnosis are part of disease prevention. Malaria risks for travellers are changing.