MBBS, FWACP, FMCP-Infectious disease

Consultant Physician, NDUTH

 LEARNING OBJECTIVES
• At the end of this lecture participants should be able to
– Understand the life cycle, pathogenesis and risk factors for malaria

– Describe the clinical presentation of malaria in adults

– Understand the clinical and laboratory diagnosis of malaria

– Discuss the case management, including drug treatment, of malaria

in adults
– Discuss malaria chemoprophylaxis in non-pregnant adults
 Introduction
• The world’s commonest and most important tropical parasitic
infection
• Commonest cause of fever and out-patient presentation in the
tropics.
• Difficult to control because resistance of parasite to
antimalarial drugs and failure of vector control measures.
• Cost of control drains African economies
• Malaria is the 2nd leading cause of death from infectious
diseases in Africa, after HIV/AIDS
 Epidemiology -1
• In 2017, nearly half of the world's population was at risk of malaria
• In 2017, there were an estimated 219 million cases of malaria in 87
countries.
• The estimated number of malaria deaths stood at 435 000 in 2017.
• The WHO African Region carries a disproportionately high share of the
global malaria burden.
– In 2017, the region was home to 92% of malaria cases and 93% of malaria deaths.
• Total funding for malaria control and elimination reached an estimated
US$ 3.1 billion in 2017.
– Contributions from governments of endemic countries amounted to US$ 900
million, representing 28% of total funding.
 Epidemiology-2
• In 2017, 5 countries accounted for nearly half of all malaria
cases worldwide:
– Nigeria (25%), the Democratic Republic of the Congo (11%),
Mozambique (5%), India (4%) and Uganda (4%).

• Children under 5 years of age are the most vulnerable group

affected by malaria;
– in 2017, they accounted for 61% (266 000) of all malaria deaths
worldwide.
 Malaria in Nigeria

• Malaria is a major public health problem in Nigeria

– 76% of the population living in high and 24% in low malaria transmission areas

• About 50% of the adult population in Nigeria experience at least one

episode yearly while the under five children have up to 2 - 4 attacks of
malaria annually.
• The yearly economic loss due to malaria in Nigeria has been put at
132 Billion Naira
• More than 60% outpatient visits in Nigeria is due to malaria
 Malaria in Nigeria-2

• Malaria accounts for 30% of childhood deaths and 11% of

maternal deaths
• There are an estimated 100 million malaria cases with over
300,000 deaths per year in Nigeria.
• This compares with 215,000 deaths per year in Nigeria from
HIV/AIDS.
 Malaria parasite species
The species that infect humans worldwide:
• –Plasmodium falciparum (15%) –highest burden
• –Plasmodium vivax (80%)
– Plasmodium vivax does not occur in indigenous Nigerians.
• –Plasmodium ovale
• –Plasmodium malariae
• –Plasmodium knowlesi (<1%)
 Transmission
COMMONEST ROUTE: OTHER LESS COMMON ROUTES
•Via bite of a female
anopheles mosquito • Congenital acquired infection.
• Blood transfusion.
• Organ transplantation and
• remotely sharing of
contaminated needles.
 Life Cycle Of Malaria Parasite
2 phases-
• Exogenous phase
(sporogony/sexual cycle) in
definitive host mosquito
• Endogenous phase
(schizogony/asexual cycle) in
intermediate host humans
Animation of malaria life cycle

Copyright: D Ogoina

Sporozoites

Liver stage parasites

Merozoites

Gametocytes

Ring form

Rupturing Trophozoite
schzoint
Life cycle of malaria parasite

48hours
Risk factors for malaria
 Malaria protective factors.
• New born infants- due to high HbF and maternal antibodies.
• Absence of Duffy antigen in west Africans protecting against p.
vivax infection.
• HbAS, Ovalocytosis, beta- thalassemia, G6PD def.- all protect
against severe malaria.
• HLA B53 allele and HLA-DRB1 1302 protect against severe
malaria.
Pathogenesis of malaria
 Clinical features of Malaria
• Spectrum of clinical presentation
–Asymptomatic
–Uncomplicated malaria
–Severe or complicated malaria
Type of presentation dependent on risk and protective
factors
 Uncomplicated malaria
• Defined as symptomatic malaria without signs of severity or
evidence (clinical or laboratory) of vital organ dysfunction.
• The signs and symptoms of uncomplicated malaria are
nonspecific. May include
– Fever-usually acute and intermittent
– Chills and rigors
– Headache, Malaise, Joint pains
– GI symptoms-nausea, vomiting, diarrhoea
• Malaria is, therefore, suspected clinically mostly on the basis
of fever or a history of fever
 Malaria fevers
QUOTIDIAN TERTIAN QUARTAN
mixed infections p.falciparum, p.malariae
/p.falciparum vivax

39

38

37

days
1 2 1 2 3 1 2 3 4
DAILY FEVERS FEVER EVERY 48HOURS FEVER EVERY 72HOURS
 Severe malaria (Complicated malaria)
• Defined as symptomatic malaria with signs of severity or
evidence (clinical or laboratory) of vital organ dysfunction
• More common in children and non-immune adults
• HIV-infection is a risk factor
Further reading-World health organization severe falciparum malaria.
Trans R Soc Trop Med Hyg 2000; 94 (suppl 1): 1-90.
 Clinical diagnosis
WHO recommendations for clinical diagnosis;
• Where the risk of malaria is low – diagnosis based on degree of
exposure, history of fever in previous 3days with no other
features of other severe diseases.
• Risk is high- based on history of fever previous 24hrs and or
presence of anemia( esp. in children.)
 Parasitological diagnosis.
• Gold standard is light microscopy using Giemsa/Leishman
stained blood film. WHO recommends that at least 100 hpf
should be examined before declaring a smear negative.
• In severe malaria a single blood film is not sufficient to exclude
malaria. Serial blood films at 6-12hrs interval are required.
• Others .- rapid diagnostic test- pLdh, HRP-2, QBC, Elisa, PCR.
 Some comments on diagnosis of malaria
• Treatment based on clinical grounds should only be given if
diagnostic testing is not immediately accessible within 2hours
of presentation
• Blood film preferable for diagnosis of severe malaria
• RDT is not useful in follow up of patients – RDT test may
remain positive 2-4weeks after successful treatment
 Treatment objectives.
• Uncomplicated malaria- primary objective is to cure the
infection. The secondary objective is to prevent the emergence
and spread resistance to antimalarials.
• Severe malaria- primary objective is to prevent death.
• To meet this objectives WHO now recommends a follow up
period of 28days as against previous of 14days.
 Treatment .
• Treatment policy should be aimed at offering antimalarials that are
highly effective.
• New guidelines now recommend that first line drugs be changed if cure
rate falls below 90%.
• Chloroquine no longer effective- widespread resistance reported.
• WHO recommends combination therapy using the artemisin based
combinations (ACT)
• Misuse of artemisin as single drugs now fueling resistance.
 The Current National Antimalarial Policy In Nigeria

• ACT recommended as first line therapy for Nigeria (Art/lum or

Ast + AMQ)-January 2005.
• Rational for combination
• Worked in TB, Cancer and HIV therapy
• Increase cure rate beyond that of individual components
• Delay emergence of resistance
• Reduce transmission
 Treatment options
• Artemisinin based Combination Therapy especially
favoured because
– most rapidly schizonticidal anti-malarial drugs known to date
– reduce parasite biomass very fast
– Rapid relief of symptoms
– Good safety profile
– Have short half-lives*
• An additional advantage from a public health perspective is the
ability of the artemisinins to reduce gametocyte carriage and
thus the transmissibility of malaria

* less likely to exert drug pressure

ACT for treatment of uncomplicated malaria

• ■ Artemether Plus Lumefantrine

• ■ Artesunate Plus Amodiaquine
• ■ Artesunate Plus Mefloquine
• ■ Artesunate Plus Sulfadoxine-pyrimethamine
• ■ Dihydroartemisinin Plus Piperaquine
 Drug treatment of severe malaria
• Severe malaria is a medical emergency
• After rapid clinical assessment, full doses of parenteral anti-malarial
treatment should be started without delay
• IV artesunate is the first drug of choice when available
• For adults, artesunate 2.4 mg/kg body weight IV or IM given on admission (time =
0), then at 12h and 24h, then once a day (for 4-5days) is the recommended
treatment
• Quinine is an acceptable alternative if parenteral artesunate is not available:
• Quinine 20 mg salt/kg body weight on admission (IV infusion in 5% dextrose or
divided IM injection), then 10 mg/kg body weight every 8 h; infusion rate should not
exceed 5 mg salt/kg body weight per hour.
• Artemether
• 3.2 mg/kg body weight IM given on admission then 1.6 mg/kg body weight per day
(for 4-5days) should only be used if none of the alternatives are available as its
absorption may be erratic.
 Treatment of severe malaria (contd)
• Give parenteral anti-malarials in the treatment of severe
malaria for a minimum of 24 h, once started (irrespective
of the patient’s ability to tolerate oral medication
earlier), and, thereafter, complete treatment by giving a
complete course of:
• – artemether plus lumefantrine
• – artesunate plus amodiaquine
• – dihydroartemisinin plus piperaquine
• – artesunate plus sulfadoxine-pyrimethamine
• – artesunate plus clindamycin or doxycycline (for7days)
• – quinine plus clindamycin or doxycycline (for 7days)
Case management of malaria
Further reading : www.who.int/malaria/publications
 Treatment failure
• This occurs when fever and parasitaemia fail to resolve, or
recur within 2 weeks of treatment. It must be confirmed
parasitologically preferably by microscopy.
• Recurrence of fever and parasitaemia more than 2 weeks
after treatment could result either from recrudescence or new
infection.
• In an individual patient, it may not be possible to distinguish
recrudescence from re-infection
• Treatment failures may result from
– drug resistance
– poor adherence or inadequate drug exposure (from under-dosing,
vomiting or unusual pharmacokinetic properties in that individual) or
– substandard medicines
 Management of Treatment failure
• The following second-line treatments are recommended, in
order of preference:
– an alternative ACT known to be effective in the region,
– artesunate plus tetracycline or doxycycline or clindamycin (given
for a total of 7 days)
– quinine plus tetracycline or doxycycline or clindamycin (given for a
total of 7 days).
• If the failure is a recrudescence, then the first-line treatment should
still be effective in most cases
• Relapse is a type of treatment failure due to P.vivax/ovale-related hypnozoites in the liver
 Recommendation for Chemoprophylaxis for
non-immune travellers visiting Nigeria
• Mefloquine (Lariam) 5mg base per kg weekly giving an adult
dose of 250mg of base per week.
– It should be started 2-3 weeks prior to arrival and two to three
weeks after departure.
• Atovaquone-Proguanil (Malarone) exist as a fixed dose
combination.
– Commence 1-2 days before travel and continue throughout the stay
and 7 days after return.
• Partial immunity can be lost after 2years out of the endemic
region
 Chemoprophylaxis in Sickle cell
anaemia
• Recent evidences have shown that Proguanil no longer protect
individuals with sickle cell anaemia against malaria; hence this
can no longer be recommended.
• All individuals with Sickle Cell Anaemia are to sleep under
Longer Lasting Insecticidal Nets (LLINs)
• All confirmed cases of malaria should be treated promptly
with ACTs.
 Malaria and HIV
• The effect of HIV-1 on malaria seems to be driven mainly by the
incapacity of the immune system to control parasite load, leading to
• a higher prevalence of infection,
• a higher incidence of clinical malaria,
• higher placenta infection,
• higher risk of severe malaria and
• a risk for treatment failure
• At the current time there is insufficient information to modify the
general malaria treatment recommendations for patients with
HIV/AIDS
 Malaria and HIV
Some treatment concerns
• Treatment or intermittent preventive treatment with
sulfadoxine-pyrimethamine should not be given to HIV-
infected patients receiving cotrimoxazole (trimethoprim plus
sulfamethoxazole) prophylaxis.
• Treatment in HIV-infected patients on Zidovudine or Efavirenz
should, if possible, avoid Amodiaquine containing ACT
regimens- worsens side effects
 Is it Malaria or Typhoid fever?
• Have similar symptoms
• Both common in the tropics
• Can co-exist in one patient
Uncomplicated Malaria fever is usually intermittent and
drops by crisis after treatment

NT
40 TREATME

DROP BY CRISIS
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38
Typhoid fever is usually continuous and drops by
lysis after therapy

Step ladder fever of typhoid

 Treatment errors to avoid
• If laboratory test is negative, don’t treat except you strongly suspect
severe malaria
• Low blood parasite count does not exclude severe malaria
• Don’t treat uncomplicated malaria with artemesinin monotherapy-
e.g. IM Arthemeter (Paluther)
• Always give a pre-referral dose of IM artesunate/arthemeter/quinine
or rectal artesunate before referring any suspected case of severe
malaria
• Don’t give Artemeter intravenously (IV)
• Never give Quinine as bolus IV injection- may cause fatal
hypotension
• Avoid giving IM quinine into the buttocks to prevent sciatic injury-
Give into the anterior thigh
 Malaria Elimination
• Malaria elimination is defined as the interruption of local transmission of a specified
malaria parasite species in a defined geographical area as a result of deliberate
activities
• Malaria eradication is defined as the permanent reduction to zero of the worldwide
incidence of malaria infection caused by human malaria parasites as a result of
deliberate activities
• Countries that have achieved at least 3 consecutive years of 0 local cases of malaria
are eligible to apply for the WHO certification of malaria elimination.
• 9 countries have been certified by the WHO DG as having eliminated malaria:
– United Arab Emirates (2007), Morocco (2010), Turkmenistan (2010), Armenia (2011), Maldives
(2015), Sri Lanka (2016), Kyrgyzstan (2016) Paraguay (2018) and Uzbekistan (2018)
 The WHO Global Technical Strategy for Malaria 2016-
2030
• Reducing malaria case incidence by at least 90% by 2030.
• Reducing malaria mortality rates by at least 90% by 2030.
• Eliminating malaria in at least 35 countries by 2030.
• Preventing a resurgence of malaria in all countries that are
malaria-free.
 Vaccines against malaria
• RTS,S/AS01 (RTS,S) is the first and, to date, the only vaccine to
show partial protection against malaria in young children.
• It acts against P. falciparum, the most deadly malaria parasite
globally and the most prevalent in Africa.
• Among children who received 4 doses in large-scale clinical
trials, the vaccine prevented approximately 4 in 10 cases of
malaria over a 4-year period.
• The vaccine will be introduced in 3 pilot countries – Ghana,
Kenya and Malawi – in 2019.
 Further reading

www.who.int/malaria www.who.int/malaria/publications www.nmcp.gov.ng