Sustained funding is crucial to malaria control

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Gladys Logan
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1 Update on Malaria Chi Eziefula Senior Lecturer in Brighton and Sussex Centre for Global Health Research, Brighton and Sussex Medical School Honorary Consultant in Infection, Brighton and Sussex University Hospitals

Sustained funding is crucial to malaria control Unprecedented successes 2000-2015 Malaria cases between 2015-2016: 5 million increase to

2 Sustained funding is crucial to malaria control Unprecedented successes Malaria cases between : 5 million increase to 216 million Malaria deaths no longer falling: Countries targeting elimination by 2020: 11/21 saw an increase in malaria cases

3 Overview Case Management Common pitfalls in management Non-severe malaria Severe malaria Special populations Non-falciparum malaria Global control Successes in malaria control and elimination Threats and challenges to sustained control

Fever in a returning traveller Think of malaria.

uk/ Always take an EDTA sample for malaria parasites

Diagnostic Test (RDT) dipstick Sensitivity 84-100% No

4 Fever in a returning traveller Think of malaria.. Always take an EDTA sample for malaria parasites Microscopy (gold standard, quantitative, species) Rapid Diagnostic Test (RDT) dipstick Sensitivity % No parasite density PCR (high sensitivity, speciation) E.g. P. knowlesi, mixed infection (Serology, LAMP) research tools Notifiable!

5 Non-severe malaria Assessment for signs of severity Speciation dictates treatment Oral treatment Falciparum Artemisinin combination therapy (ACT): Artemether-lumefantrine (Riamet, Coartem ) Dihydroartemisinin-piperaquine Quinine + 2 nd agent (doxycycline or clindamycin) Non-falciparum Artemisinin combination therapy (ACT): Artemether-lumefantrine (Riamet, Coartem ) Dihydroartemisinin-piperaquine Chloroquine Atovaquone-proguanil (Malarone ) Atovaquone-proguanil (Malarone ) Primaquine (if G6PD function normal) UK Malaria Treatment Guidelines 2016, Journal of Infection June 2016 To prevent relapse (vivax, ovale) Expert advice if low G6PD fx

6 Prevention of relapse (P. vivax, P. ovale) Primaquine 30mg/kg daily for 14 days (15mg/kg/d for P. ovale) At the same time as chloroquine Low G6PD function (expert advice) Mild to moderate deficiency: 45mg primaquine weekly for 8 weeks. Monitored Severe deficiency: avoid primaquine Leslie PlosOne 2008;3(8):e2861 Kheng BMC Med 2015; 13: 203 Pregnancy/ breastfeeding Wait until end of pregnancy/ breastfeeding ( X-linked but de novo G6PD mutations) Weekly suppressive chloroquine (500mg/wk) until end of breastfeeding

7 Non-severe falciparum malaria Do you admit?... From Michalakis, Renaud Nature 462, (2009) UK malaria treatment guidelines: 24 hours Deterioration to severity in first 24 hours Can you safely identify high/ low risk? Secure strategies for follow up?

8 Severe malaria Confusion, drowsiness, coma or convulsions Prostration (children) Respiratory distress (acidosis), ARDS, ALI, acute pulmonary oedema Abnormal bleeding (DIC) Haemoglobinuria (v dark coca-cola urine) Jaundice Shock Laboratory: Hyperparasitaemia (> 2%), Severe anaemia (Hb < 8), Acute kidney injury (creatinine > 265 µmol/l), Hypoglycaemia P. falciparum, P. vivax, P. knowlesi

Treatment of severe malaria SEAQUAMAT (SE Asian adults) and AQUAMAT (African children) IV Artesunate reduces mortality compared with quinine Fewer side effects.

9 Treatment of severe malaria SEAQUAMAT (SE Asian adults) and AQUAMAT (African children) IV Artesunate reduces mortality compared with quinine Fewer side effects. Rapid parasite clearance May cause haemolysis (in 10-15%) If unavailable/ any delay in availability: quinine + second agent Follow up with ACT or 2 nd agent (doxycycline or clindamycin) Dondorp Lancet 366 (2005), pp Dondorp Lancet 376 (2010), pp

10 Adjunctive treatments for severe malaria Always in ITU setting Cautious fluid replacement ATN not pre-renal FEAST trial Maitland Lancet 2012 Renal replacement therapy (resolves slowly) ARDS/ acute lung injury (presents late) Treat as standard ITU care DIC Antibiotics in children and in shocked adult (rare) until bacteraemia excluded Platelet transfusion if abnormal bleeding Exchange blood transfusion: no longer indicated

11 Who is at high risk? Pregnant women Children Elderly HIV (globally) + pregnancy Checkley BMJ 2012 (344): e2116

12 Malaria in pregnancy Detection Placental malaria Impact on pregnancy Risk of severe disease: hypoglycaemia, pulmonary oedema/ ALI Maternal anaemia Fetal loss: Miscarriage Still birth Preterm birth Low birth weight Prompt treatment (specialist care (ID + Obs) Uncomplicated malaria: First trimester: quinine and clindamycin 2 nd / 3 rd trimester: ACT Severe malaria: iv artesunate Non-falciparum: delay primaquine The diagnosis and treatment of malaria in pregnancy Green top Guideline No. 54b April 2010

Plasmodium Knowlesi monkey malaria Long-tailed macaques natural human cases Singh Lancet 2004;363:1017 24 Anopheles leucosphyrus mosquitoes (forest feeders).

13 Plasmodium Knowlesi monkey malaria Long-tailed macaques natural human cases Singh Lancet 2004;363: Anopheles leucosphyrus mosquitoes (forest feeders). 1 zoonosis Most common cause of malaria in Sarawak, Malaysia. Microscopic resemblance to malariae Rapid asexual cycle (24 hrs) rapidly severe or fatal if untreated Treat with iv artesunate Figure from: Review of Cases With the Emerging Fifth Human Malaria Parasite, Plasmodium knowlesi Clin Infect Dis. 2011;52(11): doi: /cid/cir180

knowlesi : emerging zoonosis 2 distinct but closely related species: P.

14 GLOBAL MALARIA CONTROL Unrecognisable changes in last 3 decades Six species can infect humans: P. knowlesi : emerging zoonosis 2 distinct but closely related species: P. ovale curtisi, P. ovale wallikeri Drug choices: artemisinins Goal of malaria elimination Figure: Poostchi Translational Research (194) 2018

15 GLOBAL CONTROL can we eliminate malaria? Co-evolution Rutledge, Nature Feb 2; 542(7639):

16 Declining malaria transmission 2000 to 2015 Credit: The Malaria Atlas Project

17 Oxfam.org.uk Pacific Friends of the Global Fund Long-lasting insecticide-treated bed nets Nakawunde Kautharah, Ug Newz 2016 Vector control Elissa Jensen/United States Agency for International Development (USAID) Indoor residual spraying (IRS)

distribution of effective medicines (ACTs) Chemoprevention: Intermittent preventive

18 Prompt and effective case management Images: Nosten, Lancet Infectious Diseases, 2007 Vol7(2): Improved access to care Upscaled distribution of diagnostics Upscaled distribution of effective medicines (ACTs) Chemoprevention: Intermittent preventive treatment in pregnancy (IPTp) Seasonal malaria chemoprophylaxis (SMC) Mass drug administration

19 Challenges: Drug resistance Dondorp N Engl J Med 2011; 365: Devastating consequences if it spreads to regions of high transmission, leaving only inferior treatment options to prevent malaria deaths

Challenges: Counterfeit drugs 1 in 10 medical products in low or middle income countries are falsified or substandard Catastrophic: severe illness, death, spreading

20 Challenges: Counterfeit drugs 1 in 10 medical products in low or middle income countries are falsified or substandard Catastrophic: severe illness, death, spreading antimicrobial resistance Sub-Saharan Africa: ~ additional malaria attributable deaths annually (WHO 2017) Origins: India, China, Hong Kong, Turkey. Organised crime connections

Challenges: Insecticide resistance Resistance affects all four malaria vector species all four recommended insecticide classes Inadequate

21 Challenges: Insecticide resistance Resistance affects all four malaria vector species all four recommended insecticide classes Inadequate screening for insecticide resistance 2012 Diana Mrazikova/Networks Senegal, Courtesy of Photoshare Surveillance: Novel screening and reporting systems

22 Challenges: Inequalities in healthcare access Countries with extreme poverty highest death rates World bank: malaria reduces GDP growth by approximately 1.3% per year in some African countries Conflict and regional crises Can poverty reducing interventions impact malaria burden?

23 Summary Pitfalls in management of returning travellers Assessment Decision to admit Drug of choice for severe malaria: iv artesunate Risk groups: pregnant, children, elderly Developments in non-falciparum malaria: severe Vivax, emerging Knowlesi, awareness of mixed infection Global control: aim to eliminate, progress depends on funding prompt effective case management, vector control prevention with intermittent treatment in pregnancy (IPTp) and childhood (IPTc) Major challenges: drug and insecticide resistance, fake drugs, unequal access to health (poverty), sustained funding and collateral commitment to control

24 Thank you!

Malaria in Children. University Hospitals of Leicester NHS Trust Children's Services Medical Guidelines. Title: Malaria in children

Malaria in Children. University Hospitals of Leicester NHS Trust Children's Services Medical Guidelines. Title: Malaria in children Management of Malaria in Children Malaria is a febrile illness caused by Plasmodium falciparum, vivax, malariae, ovale and knowlesi.delayed diagnosis can be fatal and hence a high index of suspicion is