CURRENT TRENDS IN THE

MANAGEMENT OF
UNCOMPLICATED MALARIA
BY DCS PAUL BAFFOE-BONNIE AND DCS NANCY EYRAM SALLAH
2023
 OUTLINE
TREATMENT
INTRODUCTION MALARIA IN PREGNANCY
EPIDEMIOLOGY PREVENTION
PATHOPHYSIOLOGY COMPLICATIONS
TYPES OF MALARIA CURRENT TRENDS
SIGNS AND CASE STUDY
SYMPTOMS
REFERENCES
DIAGNOSIS
ACKNOWLEDGEMENT
DIFFERENTIAL
DIAGNOSIS
 INTRODUCTION

Malaria is a parasitic disease endemic to mostly tropical and subtropical regions

of the world, particularly Sub-Saharan Africa.
Caused by Protozoa from Plasmodium genus
Vector and primary host is the female Anopheles mosquito
Particular Health concern in Ghana, as a west African country; significant
morbidity and mortality
 INTRODUCTION

The five human Plasmodium species transmitted from person to person

are P. falciparum, P. vivax, P. ovale, P. knowlesi and P. malariae.

P. falciparum infection is the most severe form of infection.

Major cause of significant morbidity, mortality especially among

vulnerable individuals such as children under 5 years of age, pregnant
women, patients with sickle cell disease and visiting non resident
Ghanaians/foreigners.
 EPIDEMIOLOGY
Malaria is very prevalent globally, at 247 million cases
recorded for 2022 (up from 245 million in 2020)
Patterns of prevalence indicate higher prevalence in tropics and
subtropics generally (Over 95% in African region)
P. falciparum gives greatest disease burden globally, followed
by P. vivax. P. malariae is present with falciparum in Ghana,
and P. vivax more in Americas and western pacific
 EPIDEMIOLOGY IN GHANA

In Ghana, 5.3 million cases in 2022, with 11,557 deaths

Endemic and perennial, with seasonal variations in the north.

Transmission length varies by region, with two distinct rainy
seasons in the southern and middle parts and one rainfall season
in the north.
 PATHOGENESIS, PATHOPHYSIOLOGY
AND LIFE CYCLE
1. Transmission – A malaria-infected female Anopheles mosquito feeds on
a human host and injects/transmits sporozoites.
2.

3. Inoculation - The sporozoites travel through the blood stream to the liver
where they invade the hepatocytes. Bottleneck target for studied vaccines
4.

5. Exo-erythrocytic Stage – Following infection of the hepatocytes, the

sporozoites mature into schizonts. The schizonts then rupture and release
10,000 to 30,000 merozoites into the blood stream. Occurs about 1 to 3
weeks after initial mosquito bite.
PATHOPHYSIOLOGY

4. Erythrocytic Stage – The released merozoites invade RBCs, multiply asexually, and further mature
into trophozoites. Trophozoites mature within infected RBCs to form schizonts, which continue to rupture
and release additional merozoites into the blood stream.
1.

2. Differentiation – Some trophozoites in the blood stream differentiate into male and female gametocytes.
A non-infected Anopheles mosquito feeds on the human host and ingests the gametocytes.
3.

4. Sporogonic Cycle - The gametocytes reproduce in the gut of the Anopheles mosquito and further
mature into sporozoites that migrate to the salivary glands of the mosquito. The mosquito completes the
cycle of transmission by feeding on a new human host and injecting sporozoites.
Pathophysiological effects experienced during
erythrocytic stage
While in the RBC, trophozoites affect the plasticity of the cell, leading to hemolysis,
contributing to anemia
They also cause alterations to the membrane of uninfected cells, leading to increased
clearance of those cells, further contributing to anemia
With each RBC lysis, hemozoin, erythrocyte fragments and toxins from the parasite are
released, causing cytokines release and a fever spike
RBC adherence to endothelial surfaces may occur, leading to obstruction and inflammation
(Immunocompromised individuals at increased risk)
EFFECTS OF GENETIC PREDISPOSITION

Sickle cell Trait - HbAs found to be 90% protective against severe malaria.
Disproportionately present in endemic areas
Native immunity
 TYPES OF MALARIA

Uncomplicated Malaria
Case definition - A person presenting with a history of fever within the preceeding 2-3
days, or found to have fever on examination (peripheral temperature: axillary or infra-red
(≥37.5 oC) or core temperature (e.g. rectal temperature ≥ 38.5°C), in the absence of any
other cause will be considered a suspected case of malaria. In the absence of signs of severe
disease, a case of suspected malaria confirmed by parasitological investigation is
considered to be “uncomplicated” malaria.

Complicated malaria- It is defined as confirmed malaria with life-threatening

complications. It is mostly associated with falciparum, and occurs when infection is
complicated by serious organ failures or abnormalities in the patient's blood or metabolism.
It is an immediate threat to life and is therefore a medical emergency which requires
hospitalization.
 SIGNS ASSOCIATED WITH SEVERE
MALARIA
Altered consciousness (change of behaviour confusion, delirium, unarousable coma).

Repeated generalised convulsions (fits) – 2 or more episodes within 24 hours.

Deep breathing and respiratory distress (Acidotic breathing)

Unexplained abnormal bleeding (Disseminated Intravascular Coagulation)

Recurrent or prolonged bleeding from the nose, gums or venipuncture site, Altered consciousness (change of behaviour
confusion, delirium, unarousable coma).

Repeated generalised convulsions (fits) – 2 or more episodes within 24 hours.

Deep breathing and respiratory distress (Acidotic breathing)

Difficulty in breathing due to acute pulmonary oedema

SIGNS AND SYMPTOMS

Chills Fever (intermittent) (>38.5°C)

Rigors Pallor
Diaphoresis Mild jaundice
Headache Splenomegaly
Generalized body and joint pain In Young children
Nausea or Vomiting Diarrhoea
Loss of Appetite Fits, coma.
Abdominal Pain
Bitterness in mouth
 DIAGNOSIS

History taken from patient

Microscopy –the gold standard

Rapid diagnostic test (parasite factors, gene deletion)

Other labs done to rule out malaria like Cerebrospinal fluid

analysis, stool culture, urine culture.
 DIFFERENTIAL DIAGNOSIS

Influenza
Septicaemia
Viral Hepatitis Pneumonia
In children:
Measles
Typhoid Fever
Otitis media
Tonsillitis
Meningitis

UTIs
 TREATMENT
Objectives of treatment:

Relief of symptoms.
Avoid progression to severe malaria
Limit the duration of illness.
Clear the parasite within the shortest time.
To improve patient quality of life.
Prevent mortality.
 TREATMENT OF UNCOMPLICATED
MALARIA
Treatment of uncomplicated malaria involves the use of the oral
Artemisinin-based Combination Therapy (ACTs).
The first-line ACT options according to the Guidelines on malaria Case
management are:
Artemether + Lumefantrine (AL)
Artesunate-Amodiaquine (AS+AQ)
Artesunate-Pyronaridine
2nd line Management
Dihydroartemisinin-Piperaquine
TREATMENT
Artemisinin derivatives possess an endoperoxide group which binds to heme in the parasite and
results in the generation of highly reactive free radicals which damage parasite membrane via
covalent bonding.
A 3-day course of Artemisinin component of ACTs is recommended as it ensures
that only a small fraction of parasites remain for clearance by the partner drug, thus
reducing the potential development of resistance to the partner drug.
TREATMENT
TREATMENT
TREATMENT
TREATMENT
TREATMENT
 MALARIA IN PREGNANCY

Pregnancy makes women more likely to get malaria or die from malaria. The
infection is more severe in pregnancy and its outcomes may be complicated.
Effects of malaria on mother include anemia, preterm labor, high placental
parasitemia and death.
Effect on the fetus include anemia, prematurity, low birth weight and perinatal
mortality.
Pregnant women are advised to sleep under Insecticide Treated Nets and
strictly adhere to their antenatal care visits and partake in the Intermittent
preventive treatment of malaria in pregnancy (IPTp) at the appropriate time.
 MALARIA IN PREGNANCY
MANAGEMENT
Uncomplicated malaria in first trimester
Oral Artemether-Lumefantrine
Oral Artesunate-Amodiaquine
Oral Quinine and Clindamycin.
In the second and third trimester
Oral Artemether-Lumefantrine or
Oral Artesunate-Amodiaquine or
Oral Dihydroartemisin-Piperaquine
Oral Quinine and Clindamycin
all in their standard dosage regimen .
23/01/2024
TREATMENT
TREATMENT
 NON-PHARMACOLOGICAL PREVENTIVE METHODS

Non-pharmacological
The promotion of widespread use of insecticide-treated bed nets
Maintaining a clean and sanitary environment
The use of mosquito repellents
Avoid stagnant water by promoting drainage
Indoor residual sprays to protect individuals from infective mosquito bites.
 CURRENT TRENDS
Introduction of Artesunate-Pyronaridine (ASPY).
Artesunate-pyronaridine (ASPY) (Pyronaridine tetraphosphate-artesunate) is
recommended as an artemisinin-based combination therapy option for the
treatment of uncomplicated P. falciparum malaria.
It is currently sold under the brand name Pyramax. Pyronaridine (PYR) is an
erythrocytic schizonticide with a potent antimalarial activity against multidrug-
resistant Plasmodium.
PYR functions has an inhibitor of hemozoin (biomineral malaria pigment, by-
product of hemoglobin digestion) formation, blocking the biopolymerization of
β-hematin and thus facilitating the accumulation of toxic hematin into the
digestive vacuole of the parasite.
CURRENT TRENDS

The dose should be taken orally once daily for three consecutive days based on body weight.
 CURRENT TRENDS

Introduction of the malaria vaccine, RTS,S/AS01.

The RTS,S/AS01 vaccine is the first and currently the only malaria vaccine to be
recommended for use by WHO. The RTS,S/AS01 malaria vaccine should be used for the
prevention of P. falciparum malaria in children living in regions with moderate to high
transmission.
The RTS,S/AS01 malaria vaccine should be provided in a four-dose schedule in children
from 5 months of age.
RTS,S/AS01 is a pre-erythrocytic recombinant protein vaccine, based on the RTS,S
recombinant antigen.
It comprises the hybrid polypeptide RTS, in which regions of the P. falciparum
circumsporozoite protein known to induce humoral (R region) and cellular (T region)
immune responses are covalently bound to the hepatitis B virus surface antigen (S).
CURRENT TRENDS

The vaccine is currently produced as a two-dose RTS,S powder to be

reconstituted with a two-dose AS01 adjuvant system suspension. After
reconstitution, the total volume is 1ml (two doses of 0.5 ml). No preservative is
included in either the RTS,S formulation or the AS01 adjuvant system.

The vials should therefore be discarded at the end of the vaccination session, or
within six hours after opening, whichever comes first. The reconstituted 0.5ml
vaccine should be administered by injection into the deltoid muscle in children
aged 5 months or older.

The shelf life of the RTS,S/AS01 vaccine is three years.

CURRENT TRENDS

WHO recommends that the first dose of vaccine be administered from 5 months of
age. There should be a minimum interval of four weeks between doses.
The vaccine should be administered in a three-dose primary schedule, with a
fourth dose provided 12–18 months after the third dose to prolong the duration of
protection.
The RTS,S/AS01 can be given concomitantly with any of the following
monovalent or combination vaccines: diphtheria, tetanus, whole cell pertussis,
acellular pertussis, hepatitis B, Haemophilus influenzae type b, oral poliovirus,
measles, rubella, yellow fever, rotavirus and pneumococcal conjugate vaccines.
However, No co-administration studies have been conducted with RTS,S/AS01
and meningococcus A, typhoid conjugate, cholera, Tick-borne encephalitis, rabies,
mumps, influenza or varicella vaccines.
REFERENCES

Updated Guidelines on Malaria Case Management 2023

Duparc, S., Borghini-Fuhrer, I., Craft, C.J. et al. Safety and efficacy of pyronaridine-
artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data
from six randomized clinical trials. Malar J 12, 70 (2013).
https://doi.org/10.1186/1475-2875-12-70
Journal of Antimicrobial Chemotherapy, Volume 78, Issue 10, October 2023, Pages 2406–
2418, https://doi.org/10.1093/jac/dkad260 Published:28 August 2023
Medical Pharmacology and Therapeutics, (Fifth Edition), Derek G. Waller, Chemotherapy
of infections, 2018.
Ministry of Health/Ghana Health Service. Guidelines for Case Management of Malaria in
Ghana 2020.
REFERENCES

Wang-Yu Chu, Thomas P C Dorlo, Pyronaridine: a review of its clinical pharmacology in

the treatment of malaria, Journal of Antimicrobial Chemotherapy, Volume 78, Issue 10,
October 2023, Pages 2406–2418, http://doi.org/10.1093/jac/dkad260
WHO Guidelines for malaria, 14 March, 2023.
Wong W, Bai XC, Sleebs BE, Triglia T, Brown A, Thompson JK, Jackson KE, Hanssen E,
Marapana DS, Fernandez IS, Ralph SA, Cowman AF, Scheres SHW, Baum J. Mefloquine
targets the Plasmodium falciparum 80S ribosome to inhibit protein synthesis. Nat
Microbiol. 2017 Mar 13;2:17031. doi: 10.1038/nmicrobiol.2017.31
 REFERENCES

Pyronaridine–artesunate real-world safety, tolerability, and effectiveness in malaria patients in 5 African

countries: A single-arm, open-label, cohort event monitoring study. Tona Lutete G, Mombo-Ngoma G, Assi
SB, Bigoga JD, Koukouikila-KoussoundaF, et al. (2021) Pyronaridine–artesunate real-world safety,
tolerability, and effectiveness in malaria patients in 5 African countriesA single-arm, open-label, cohort event
monitoring study. PLOS Medicine 18(6): e1003669. https://doi.org/10.1371/hournak.pmed.1003669
Pryce J, Taylor M, Fox T, Hine P : Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum
malaria. Cochrane Database Syst Rev 2022;6(6): Pubmed Journal
Standard treatment guidelines[2017], Ministry of Health,7 th edition, Pages 482-498
Antimalarial Medicine Policy, Ghana, September, 2022. Ministry of health.
https://who.int/health-topics/.
https://www.who.int/initiatives/malaria-vaccine-implementation-programme
THANK YOU