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 216 million Malaria deaths no longer falling: 445 000 Countries targeting elimination by 2020: 11/21 saw an increase in malaria cases 2015-2016
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.. http://travelhealthpro.org.uk/ Always take an EDTA sample for malaria parasites Microscopy (gold standard, quantitative, species) Rapid Diagnostic Test (RDT) dipstick Sensitivity 84-100% No parasite density PCR (high sensitivity, speciation) E.g. P. knowlesi, mixed infection (Serology, LAMP) research tools Notifiable!
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
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
Non-severe falciparum malaria Do you admit?... From Michalakis, Renaud Nature 462, 298 300 (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?
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. 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. 717-725 Dondorp Lancet 376 (2010), pp. 1647-1657
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
Who is at high risk? Pregnant women Children Elderly HIV (globally) + pregnancy Checkley BMJ 2012 (344): e2116
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). 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):1356-1362. doi:10.1093/cid/cir180
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
GLOBAL CONTROL can we eliminate malaria? Co-evolution Rutledge, Nature. 2017 Feb 2; 542(7639): 101 104.
Declining malaria transmission 2000 to 2015 Credit: The Malaria Atlas Project https://map.ox.ac.uk
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)
Prompt and effective case management Images: Nosten, Lancet Infectious Diseases, 2007 Vol7(2):118-125 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
Challenges: Drug resistance Dondorp N Engl J Med 2011; 365:1073-1075 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 antimicrobial resistance Sub-Saharan Africa: ~116 000 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 screening for insecticide resistance 2012 Diana Mrazikova/Networks Senegal, Courtesy of Photoshare Surveillance: Novel screening and reporting systems
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?
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
Thank you!