]

UNIVERSITY OF GHANA
SCHOOL OF PHARMACY
DEPARTMENT OF PHARMACY PRACTICE
DANSO JEPHTHAH KWASI

Personal Information

Patient Initials B.J. Gender MALE Age

80 YRS 3M 7D

Date: 28TH OCTOBER , 2023 Height : N/A Weight; N/A

BMI : N/A

Ward BANDOH WARD Ethnic Origin

Presenting complaint: History of Presenting Complaint:

Fever
Change in behaviour Patient, not known to have diabetes presents
with intermittent fever , associated with
chills, rigors, and loss of appetite. He was taken
to a peripheral facility where he was diagnosed
and treated for malaria. However, he stopped
taking the malarial drugs the next day because
he traveled to his daughter's and left the
medication home. Two days later, he was found
to be quieter, unable to feed on his own,
answer questions correctly, and walk
unassisted as he used to.

So they reported to the polyclinic the next day

where some labs were done. The labs were
ready a day later. -

Social History: Family History:

N/A
He is a christian, Lives in Accra,
stays with daughter

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Past Medical History: Relevant Signs:

BF for Mps 25,110 parasites/mcl, Creatinine
Hypertension, SCD, asthma, 341 umol/l, eGFR 312 mmol/l,
Urine dipstick
Ketone-neg
Nitrite1+
Vital Signs : CalculatedOsmolarity=150mmol/l
TEMP: 37.1 DEGREE CELSIUS
PULSE: 103 BPM ODQ: no early morning facial puffiness,
RR: 26 CPM bipedaledema (seen 3 days ago) , scanty urine
BP: 151/102 MMHG observed , no diarrhea, constipation, no cough,
SPO2: 99% dysuria absent , frequency, urgency, and
nocturia could not be assessed as patient is in
diapers
Abdominal exams:

Soft, mildly distended abdomen bulging in the

sides, MWR

Tenderness in the right iliac and suprapubic

region

No masses palpable

Bowel sounds present

CVS:

Apex beat not visible, palpable at the 5th

intercostal space, MCL

No thrills or parasternal heaves

Muscle bulk reduced bilaterally in both upper
and lower limbs

Tone reduced

Power and sensation-could not be assessed

properly as patient could not follow commands

Reflexes reduced in both upper and lower limbs

Cordination-could not be assessed properly as

patient could not follow commands

Resp:

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No chest deformity

Trachea central

Expansion normal

Tactile fremitus normal

Percussion notes normal bilaterally

Auscultation:

Air entry adequate bilaterally

Vesicular breath sounds in all lung zones

Risk Factors
1.Smoking
2.Drinks alcohol
3. Age (80 years)

Differential diagnosis (if any)

Medication History [Past Six Months ]

Prescription Medications
Medication Dosage/ Start Stop Reason for use Comment
Name / Frequency Date Date
strength/route

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Unknown unknown unknown Treatment of
fever , chills ,
An antimalarial rigor
drug

Non-Prescription Medications/Remedies/Products - Please list any additional non

prescription medications, herbal products, or nutritional supplements used by patient pre-admission.
Medication Dosage/ Start Stop Reason for use Comment
Name / Frequency Date Date
Strength/Route
N/A N/A N/A N/A

No known drugs

Allergies - Please specify what patient is allergic to and the nature of reaction to the allergen
No known allergies

Lifestyle Information- please ask questions which are relevant and appropriate to the patient
(e.g., exercise, use of: tobacco, alcohol, recreational drugs). Quantify information where possible
(e.g., units of alcohol, frequency of exercise).

Takes alcohol and smokes

Does pt self-monitor at home? NO known information

Blood  Yes Peak Flow  Yes Blood  Yes Ketones  Yes
Pressure  No  No Glucose  No  No

Immunisation Information- Has patient had relevant vaccinations and/or does patient require
any additional vaccinations based on disease history?
No Known information

Additional Information

Who organises the patient’s medications at home?

 Patient

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 Carer
 Other: ________________________________________________________________________

Suspected adherence concerns? Please describe.

INVESTIGATIONS
Parameter Reference Range Dates
Urea (SI) 28/10 Flag 1/11 Flag
23 /23
Sodium 135 - 150 mmol/L 134 L 140 N
Potassium 3.5 - 5.5 mmol/L 4.4 N 4.4 N
Chloride 95 - 110 mmol/L 110 N 110 N
Bicarbonate 23-29 mmol/L 22 N 22 N
Anion Gap with 18- 23 mmol/L 18 N 18 N
K+
Urea (SI) 2.6- 6.7 mmol/L 6.8 H 5 N
Creatinine (SI) 53- 97 umol/L 98 H 80 N
Urea / 10 - 20 17 N 18 N
Creatinine ratio
eGFR Stage 1 : > 90 73 L 92 N
ml/min/1.73m2

Stage 2 : 60 - 89
ml/min/1.73m2

Stage 3A : 45- 59
ml/min/1.73m2
Stage 3B : 30 - 44
ml/min/1.73m2
Stage 4 : 15 - 29
ml/min/1.73m2

Stage 5 : < 15
ml/min/1.73m2
Uric Acid 155 - 357 umol/L

Haematology
Parameter RESULTS Dates
28/10 Nor Flags 1/11 flags
/23 mal /23
rang
UNIT e
RBC 5.00 10^6? 3.8 - N 5.1 N
UL 6.5
HB 14.4 G/dL 13 - N 14.5 N
18
HCT 39.3 % 36.0 N 39.4 N
- 54
MCV 78.6 fL 80- N 79 N
100

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MCH 28.8 pG 27 - N 30 N
32
MCHC 36.6 g/dL 32 - H 33 N
36
RDW_SD 42.5 fL 37 - N 43 N
54
RDW_CV 17.1 % 11 - H 15 N
16
PLT 99 10^3/ 150 L 150 N
UL -
400
MPV 11.4 fL 6- H 10 N
11
PDW 14.2 Fl 9_ N 10 N
17
WBC 4.05 10^3 / 3.5 N 5 N
uL _
10.5
NEUT% 65.5 % 40_ N 50 N
75
LYMPH% 25.9 % 21 _ N 25 N
40
MONO% 8.1 % 2_ N 6 N
10
EO% 0.0 % 1-6 L 3 N
BASO% 0.5 % 0.0 - N 0.5 N
1.0
NEUT# 2.65 10^9/L 2-7 N 2.7 N
LYMPH# 1.05 10^9/L 1- 3 N 1.5 N
MONO# 0.33 10^9/L 0.2 - N 0.25 N
1
EO# 0.00 10^9/L 0.04 L 0.05 N
- 0.4
BASO# 0.02 10^9/L 0.02 N 0.02 N
-
0.04

Parameter Reference Range Dates

28/10 1/11
/23 /23
Malaria 25110 Posit nega
parasitaemia parasit ive tive
( trophozoite e /ul
count )

Current Medications (on ward)

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Medication [name/ Dosage Start Date End Date Reason for Comment
strength Route] /Frequency use

Malaria Appropriate
IV ARTESUNATE 150 MG 0, 12 AND 28/10/23 29/10/ 23
24

SC FRAGMIN 2G DAILY 28/10/23 1/11/23 Used as a

thromboproph Appropriate
ylaxis

TAB COARTEM 80/ TWO TIMES DAILY 29/10/11 1 / 11/ 23 Appropriate

480 MG XL 16 FOR THREE DAYS
Malaria

Medical Problems/ Diagnosis being managed as a case of

1. Complicated Malaria

PHARMACEUTICAL CARE PLANS (SOAPO)

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Pharmaceutical care issue / problem 1

OPTIMIZING THE TREATMENT OF COMPLICATED MALARIA IN A PATIENT WHO
WAS NON-COMPLIANT TO HIS ANTIMALARIA MEDICATIONS

SUBJECTIVE DATA
Fever , chills , rigor , loss of appetite , loss of consciousness
OBJECTIVE DATA
Temperature 37.1 Degree Celsius
presence of malaria parasites (25110 parasite /uL)
Assessment
Diagnosis : Complicated Malaria

Malaria is a life-threatening disease primarily found in tropical countries. It is both

preventable and curable. However, without prompt diagnosis and effective
treatment, a case of uncomplicated malaria can progress to a severe form of the
disease, which is often fatal without treatment (World Health Organization,2023)

Malaria is not contagious and cannot spread from one person to another; the
disease is transmitted through the bites of female Anopheles mosquitoes. Five
species of parasites can cause malaria in humans and 2 of these species
– Plasmodium falciparum and Plasmodium vivax – pose the greatest threat. There
are over 400 different species of Anopheles mosquitoes and around 40, known as
vector species, can transmit the disease.( World Health Organization,2023)

This risk of infection is higher in some areas than others depending on multiple
factors, including the type of local mosquitoes. It may also vary according to the
season, the risk being highest during the rainy season in tropical countries. (World
Health Organization, 2023)

Nearly half of the world’s population is at risk of malaria. In 2021, an estimated

247 million people contracted malaria in 85 countries. That same year, the
disease claimed approximately 619 000 lives.( World Health Organization,2023)

Some people are more susceptible to developing severe malaria than others.
Infants and children under 5 years of age, pregnant women and patients with
HIV/AIDS are at particular risk. Other vulnerable groups include people entering
areas with intense malaria transmission who have not acquired partial immunity
from long exposure to the disease, or who are not taking chemopreventive
therapies, such as migrants, mobile populations and travellers (World Health
Organization,2023)

Some people in areas where malaria is common will develop partial immunity.
While it never provides complete protection, partial immunity reduces the risk that
malaria infection will cause severe disease. For this reason, most malaria deaths
in Africa occur in young children, whereas in areas with less transmission and low
immunity, all age groups are at risk (O'Brien, & Wertheimer , 2022)

The first symptoms of malaria usually begin within 10–15 days after the bite from

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an infected mosquito. Fever, headache and chills are typically experienced,

though these symptoms may be mild and difficult to recognize as malaria. In
malaria endemic areas, people who have developed partial immunity may
become infected but experience no symptoms (asymptomatic infections) (White,
2022)

WHO recommends prompt diagnosis for anyone with suspected malaria.

If Plasmodium falciparum malaria is not treated within 24 hours, the infection can
progress to severe illness and death. Severe malaria can cause multi-organ
failure in adults, while children frequently suffer from severe anaemia, respiratory
distress or cerebral malaria. Human malaria caused by
other Plasmodium species can cause significant illness and occasionally life-
threatening disease (World Health Organization, 2023).

Malaria can be diagnosed using tests that determine the presence of the parasites
causing the disease. There are 2 main types of tests: microscopic examination of
blood smears and rapid diagnostic tests. Diagnostic testing enables health
providers to distinguish malarial from other causes of febrile illnesses, facilitating
appropriate treatment (White, 2022).

Malaria is a treatable disease. Artemisinin-based combination therapies (ACTs)

are the most effective antimalarial medicines available today and the mainstay of
recommended treatment for PLASMODIUM FALCIPARUM malaria, the deadliest malaria
parasite globally (World Health Organization, 2023).

ACTs combine 2 active pharmaceuticals with different mechanisms of action,

including derivates of artemisinin extracted from the plant ARTEMISIA ANNUA and a
partner drug. The role of the artemisinin compound is to reduce the number of
parasites during the first 3 days of treatment, while the role of the partner drug is
to eliminate the remaining parasites (World Health Organization,2023)

Falciparum malaria Falciparum malaria is caused by Plasmodium falciparum. Patients

with falciparum malaria should usually be admitted to hospital initially due to the risk of
rapid deterioration even after starting treatment. Artemisinin combination therapy is
recommended for the treatment of uncomplicated P. falciparum malaria. Artemether with
lumefantrine is the drug of choice; artenimol with piperaquine phosphate is a suitable
alternative. Oral quinine or atovaquone with proguanil hydrochloride p. 669 can be used
if an artemisinin combination therapy is not available. Quinine is highly effective but
poorly-tolerated in prolonged treatment and should be used in combination with an
additional drug, usually oral doxycycline p (or clindamycin p. 581 [unlicensed] in
pregnant women and young children)(BNF, 84).

Severe or complicated falciparum malaria should be managed in a high dependency unit

or intensive care setting. Intravenous artesunate (available for ‘named-patient’ use from
infectious disease units or specialist tropical disease centres) is indicated in all patients
with severe or complicated falciparum malaria, or those at high-risk of developing severe
disease (such as if more than 2% of red blood cells are parasitized), or if the patient is

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unable to take oral treatment(BNF,84)

Following a minimum of 24 hours of intravenous artesunate treatment, and when the

patient has improved and is able take oral treatment, a full course of artemisinin
combination therapy should be given. A full course of oral quinine with doxycycline (or
clindamycin [unlicensed]), or atovaquone with proguanil hydrochloride are suitable
alternatives (BNF,84)

Treatment of severe or complicated falciparum malaria should not be delayed whilst

obtaining artesunate. Quinine by intravenous infusion [unlicensed] should be given if
artesunate is not immediately available; it should be continued until the patient can take
oral quinine to complete a full course (BNF,84)

Oral doxycycline (or clindamycin [unlicensed]) should also be given when the patient can
swallow. In most parts of the world, P. falciparum is now resistant to chloroquine p. 669
which should not therefore be used for treatment. Mefloquine p. 671 is also no longer
recommended for treatment because of concerns about adverse effects and non-completion
of courses. Specialist advice should be sought when considering the use of pyrimethamine
with sulfadoxine as an alternative drug in combination with quinine (BNF,84)

Pregnancy Falciparum malaria in pregnancy carries a higher risk of severe disease; it

requires prompt treatment by specialists in hospital and close observation. Uncomplicated
falciparum malaria in the second and third trimesters of pregnancy should be treated with
artemether with lumefantrine p. 668. Quinine with clindamycin [unlicensed indication]
can be used in all trimesters. Quinine can increase the risk of uterine contractions and
hypoglycemia (BNF,84).

Severe or complicated falciparum malaria is associated with a high risk of fatality,

pregnancy loss, and complications. Due to efficacy, treatment with intravenous artesunate
in any trimester of pregnancy is preferred; intravenous quinine (with clindamycin) can be
used as an alternative. Non-falciparum malaria Non-falciparum malaria is usually caused
by Plasmodium vivax and less commonly by P. ovale, P. malariae, and P. knowlesi. P.
knowlesi is present in the Asia-Pacific region (BNF, 84)

Either an artemisinin combination therapy (such as artemether with lumefantrine or

artenimol with piperaquine phosphate or chloroquine can be used for the treatment of
non-falciparum malaria. Chloroquineresistant P. vivax has been reported in the Indonesian
archipelago, the Malay Peninsula, including Myanmar, and eastward to Southern Vietnam.
Chloroquine can still be used for treatment of non-falciparum malaria from these regions
with appropriate follow-up, however artemisinin combination therapy may be preferred.
BNF 84 Malaria Infection 5 Chloroquine alone is adequate for P. malariae and P.
knowlesi infections but in the case of P. vivax and P. ovale, a radical cure (to destroy
parasites in the liver and thus prevent relapses) is required (BNF,84)

For a radical cure, primaquine [unlicensed] is given with chloroquine treatment; the dose
is dependent on the infecting organism. Patients should be screened for G6PD deficiency
before initiating primaquine treatment, as primaquine may cause haemolysis in G6PD

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deficient individuals(BNF, 84)

Severe or complicated non-falciparum malaria should be treated with parenteral artesunate

or quinine [unlicensed] as for treatment of severe or complicated falciparum malaria.
Pregnancy Chloroquine can be given for non-falciparum malaria treatment throughout
pregnancy. Artemisinin combination therapy can be used in the second and third
trimesters, and quinine may be used in the first trimester if there is concern about
chloroquine-resistant P. vivax. In the case of P. vivax or P. ovale however, the radical cure
with primaquine should be postponed until the pregnancy (and breast-feeding) is over;
instead weekly chloroquine prophylaxis should be continued until delivery or completion
of breast-feeding ( BNF, 84)

Over the last decade parasites resistance to antimalarials has emerged as a

threat in the fight against malaria, particularly in the Greater Mekong subregion.
WHO is also concerned about more recent reports of drug-resistant malaria in
Africa. To date, resistance has been documented in 3 of the 5 malaria species
known to affect humans: P. FALCIPARUM, P. VIVAX, and P. MALARIAE. However, nearly
all patients infected with artemisinin-resistant parasites who are treated with an
ACT are fully cured, provided the partner drug is highly efficacious (World Health
Organization,2023)

Confirmation of Diagnosis

The subjective data (Fever , chills , rigor , loss of appetite , loss of consciousness
) and objective data (Temperature 37.1 Degree Celsius , presence of malaria
parasites (25110 parasite /uL)) confirms the diagnosis of severe malaria.

Appropriateness of Therapy

IV ARTESUNATE 150 MG 0, 12 AND 24

Artesunate (AS) is a medication used to treat malaria . The intravenous form is preferred to
quinine for severe malaria. Often it is used as part of combination therapy , such as
artesunate plus mefloquine . It is not used for the prevention of malaria. Artesunate can be
given by injection into a vein, injection into a muscle, by mouth, and by rectum (World Health
Organization , 2018)

Artesunate is the first-line treatment for children or adults with severe malaria, usually in
combination with another antimalarial drug. There is moderate-quality evidence that treatment
with artesunate plus mefloquine is superior to treatment with artesunate plus amodiaquine or
artesunate plus sulfadoxine-pyrimethamine. Artemisinin-based combination therapy may be
used by mouth in persons that can tolerate it after 24 hours by injection ( Peixoto, Marchesini ,
& de Oliveira, 2016)
Artesunate's efficacy is comparable to that of artemether, another artemisinin derivative, in
treating adults for severe malaria caused by Plasmodium falciparum, though artesunate
clears more parasites initially. Artesunate combination drugs have a number of advantages
over artemether-based drugs in terms of its uptake and administration routes and may be
more effective in treatment of severe and complicated malaria in children (The mechanisms of
action of artesunate remains unclear and debatable. Artesunate is a prodrug that is rapidly

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converted to its active form dihydroartemisinin (DHA) ( (Cui L, Su XZ, 2009)
This process involves hydrolysis of the 4-carbon ester group via plasma esterase enzyme. It
is hypothesized that the cleavage of endoperoxide bridge in the pharmacophore of DHA
generates reactive oxygen species (ROS), which increases oxidative stress and causes
malarial protein damage via alkylation. In addition, Artesunate potently inhibits the
essential Plasmodium falciparum exported protein 1 (EXP1), a membrane glutathione S-
transferase. As a result, the amount of glutathione in the parasite is reduced (Cui L, Su XZ,
2009)
In 2016, artemisinin has been shown to bind to a large number targets, suggesting that it acts
in a promiscuous manner. There is evidence suggesting DHA inhibition of calcium-dependent
ATPase on endoplasmic membrane, which disrupts protein folding of parasites (Cui L, Su XZ,
2009 )
In infected individuals, the elimination half-life of artesunate is about 0.22 hours. Its active
metabolite, DHA, has a slightly longer half-life of 0.34 hours. Overall, the average half-life
ranges from 0.5 to 1.5 hours. Because of its short half-life, its use in malaria prevention is
limited (Cui L, Su XZ, 2009 )
DHA is metabolized to an inactive metabolite by the liver enzymes CYP2B6, CYP2C19,
and CYP3A4 (Cui L, Su XZ, 2009 )
Indicated for initial treatment of severe malaria; should always be followed by a
complete treatment course of an appropriate PO antimalarial regimen
2.4 mg/kg IV at 0, 12, and 24 hr, THEN qDay until able to tolerate PO antimalarial
therapy (World Health Organization, 2023)

TAB COARTEM 80/ 480 MG XL 16 TWO TIMES DAILY FOR THREE DAYS
Artemether/lumefantrine, sold under the trade name Coartem among others, is a
combination of the two medications artemether and lumefantrine. It is used to
treat malaria caused by Plasmodium falciparum that is not treatable with chloroquine.[1] It is
not typically used to prevent malaria. It is taken by mouth (Makanga & Krudsood, 2009).

The combination came into medical use in 1992. It is on the World Health Organization's List
of Essential Medicines. It is not available as a generic medication. The combination is an
effective and well-tolerated malaria treatment, providing high cure rates even in areas of multi-
drug resistance (Makanga & Krudsood, 2009).

Artemether is an antimalarial agent used to treat acute uncomplicated

malaria. It is administered in combination with lumefantrine for
improved efficacy. This combination therapy exerts its effects against
the erythrocytic stages of Plasmodium spp. And may be used to treat
infections caused by P. falciparum and
unidentified Plasmodium species, including infections acquired in
chloroquine-resistant areas.

Artemether and lumefantrine combination therapy is indicated for

the treatment of acute uncomplicated malaria caused
by Plasmodium falciparum, including malaria acquired in
chloroquine-resistant areas. May also be used to treat

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uncomplicated malaria when the Plasmodium species has not
been identified. Indicated for use in adults and children greater
than 5 kg.

Involves an interaction with ferriprotoporphyrin IX (“heme”), or

ferrous ions, in the acidic parasite food vacuole, which results in
the generation of cytotoxic radical species (Makanga & Krudsood,
2009).

The generally accepted mechanism of action of peroxide

antimalarials involves interaction of the peroxide-containing drug
with heme, a hemoglobin degradation byproduct, derived from
proteolysis of hemoglobin. This interaction is believed to result in
the formation of a range of potentially toxic oxygen and carbon-
centered radicals (Makanga & Krudsood, 2009).

SC FRAGMIN

Dalteparin is a low molecular weight heparin. It is marketed as Fragmin. Like other low
molecular weight heparins, dalteparin is used for prophylaxis or treatment of deep vein
thrombosis and pulmonary embolism to reduce the risk of a stroke or heart attack. Dalteparin
acts by potentiating the activity of antithrombin III, inhibiting formation of both Factor
Xa and thrombin. It is normally administered by self-injection (Lee A.Y et al.' 2003 )

The CLOT study, published in 2003, showed that in patients with malignancy and
acute venous thromboembolism (VTE), dalteparin was more effective than warfarin in
reducing the risk of recurrent embolic events. Dalteparin is not superior to unfractionated
heparin in preventing blood clots(Lee AY et al.,2003 )

Care Issue

Nil

Recommendation
Nil

Plan

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CURRENT MEDICATIONS

IV ARTESUNATE 0 , 6 , 12 AND 24
Tab Coartem 80/480 two times daily for three days

Goals of Therapy
• To eradicate of the Parasites
• To relief the patient of Symptoms
• To prevent of complications of malaria
• To prevent transmission of malaria parasites
 To improve patients quality of life

Monitoring
Drug Efficacy Toxicity
IV Artesunate Resolution of fever , chills Weakness
, loss of appetitie and loss Loss of appetite
of consciousness tremor

Absence of malaria
parasites
Tab Coartem 80/ 480 Resolution of fever , chills
, loss of appetitie and loss
of consciousness
Severe dizziness
Fainting
Irregular heartbeat

Abscence of malaria
parasites
SC Fragmin No incidence stroke Risk of bleeding
observed

Counselling
 Patient was counselled to prevent mosquito bites when he goes to areas
where malaria is common.
 Patient was counselled to take medicine as prescribed to treat the malaria.
 Patient was counselled to be compliant with his medications and on his
medication side effects
 Patient was counselled to use mosquito nets when sleping to avoid
mosquito bites

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Outcome /Evaluation
Patient has improved and has been discharged

References
Cui, L., & Su, X. Z. (2009). Discovery, mechanisms of action and combination
therapy of artemisinin. Expert Review of Anti-Infective Therapy, 7(8), 999-1013.

Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA,
Haley S, Kovacs MJ, Gent M (2003). "Low-molecular-weight heparin versus a
Coumadin for the prevention of recurrent venous thromboembolism in patients
with cancer". N Engl J Med. 349 (2): 146–53. doi:10.1056/NEJMoa025313. PMID
12853587

Makanga, M., & Krudsood, S. (2009). The clinical efficacy of

artemether/lumefantrine (Coartem). Malaria Journal, 8(Suppl 1), S5.

O'Brien, C. J., & Wertheimer, S. P. (2022). Malaria. In Mandell, Douglas, and

Bennett's principle and practice of infectious disease (Vol. 9, pp. 2884-2909).

Peixoto, H. M., Marchesini, P. B., & de Oliveira, M. R. (2016). Efficacy and safety
of artesunate-mefloquine therapy for treating uncomplicated Plasmodium
falciparum malaria: systematic review and meta-analysis. Transactions of the
Royal Society of Tropical Medicine and Hygiene, 110(11), 626-636.

White, N. J. (2022). Malaria. The Lancet, 399(10372), 617-628.

World Health Organization. (2023). WHO recommendations for testing, treatment

and care for malaria. Geneva: World Health Organization.

World Health Organization. (October 2018). Rectal artesunate for pre-referral

treatment of severe malaria. Global Malaria Programme (Report). World Health
Organization.

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