EXTENDED ESSAY

Effects of Malaria during Pregnancy on Infant

Mortality

Session: May 2021 Biology

Research Question: To what extent does malaria in pregnant women have

an effect on infant mortality and what are some preventive measures that
can be taken against malaria.

Word Count:
Introduction

Malaria is a life-threatening illness caused by parasites that are spread to

humans by the bites of infected female Anopheles mosquitoes. Unlike many
other diseases, malaria is caused by Plasmodium parasites. These parasites
are transferred from person to person by the bite of infected
female Anopheles mosquitoes. These mosquitoes are known as malaria
vectors. There are many different species of this anopheles mosquito and
they are present across the world but they are present most commonly in
tropical countries.1

When an adult contracts malaria and survives its infection they develop a
partial resistance. The immunity that they have built up against malaria
helps them to fight it off if the contract a severe case of the disease once
again. This is not the case for pregnant women. Even if the women has had
malaria before her pregnancy, because of the bodily changes that she goes
through she will lose the immunity the she has built up. The malaria will also
affect a pregnant woman much faster because the new organs such as the
placenta being formed in her body are new place for the malarial parasite to
bind. 2

If a women contracts malaria during her pregnancy it not only affects the
unborn child it also affects. There are many way that the malaria affects the
mother and fetus, some of these ways include maternal anemia, premature
delivery, intrauterine growth retardation and low infant births all of which
are contributing factors in infant mortality. If a woman is in her first or her

1
https://www.healthline.com/health/malaria
2

https://www.cdc.gov/malaria/malaria_worldwide/reduction/iptp.html#:~:text=M
alaria%20infection%20during%20pregnancy%20can,a%20risk%20factor%20for
%20death.
second pregnancy or if she is HIV positive then she is much more prone to
these infections.

The area in which the pregnant woman lives when she contracted malaria is
also a contributing factor to how the infection plays out. This is based of
transmission level. A woman who lives in a high transmission area would
have most likely built up a resistance to a severe case of malaria. Even
though they most likely have a resistance to disease when the parasite
targets the placenta it still leads to an increased risk during pregnancy. On
the contrary a woman who lives in a low transmission, most likely she has
little to no immunity to the malarial infection. This means that she is very
likely to contract a very severe malaria disease, serious maternal anemia,
premature birth or fetal loss.

Another contributing factor to the risk of malaria is HIV. Women who have
been tested HIV positive run a higher risk of infection. HIV affects malaria
because the Human immune deficiency virus affects the T cells of the body.
The T cells of the body are part of the immune system, when they are
affected the immunity levels in the body decrease.

Infant mortality rates also increase when the mother has malaria. A study
was done on maternal malaria during pregnancy and infant mortality rate 3
by Ali A Hagdoost, Neal Alexander and Tom Smith in 2007. The study was
based on the idea that Malaria during pregnancy is a recognized low birth
weight risk factor and is likely to reduce the survival of offspring, particularly
during their first month of life. Acquired maternal immunity, on the other
hand, can protect infants from malaria infection or disease. The data that
they analyzed was taken from a large epidemiological study called the Garki
Project. They used this data to analyze the impact of malaria during
pregnancy and its effect on the survival rates in offspring. The results of this
study showed that in the first year of life, the mortality rate of the infants
3
https://pubmed.ncbi.nlm.nih.gov/17722862/
was independent of maternal malaria infection during pregnancy. The
corresponding incidence ratios were 1.46 and 1.73 for maternal malaria
during the second half of pregnancy. None of these rate ratios is important
statistically. This may be attributed to the small number of casualties with a
complete maternal malaria record in the first year of life (27 deaths). During
the first year of life, there was a positive correlation between malaria during
pregnancy and malaria, which may be attributed to similarity of exposure
threats within a family or confounding socio-economic status impact.
However, in the first four months of life, and in those women who
contracted infection during the second half of pregnancy, this correlation
was weaker. This may mean that in this population, acquired immunity is
stronger and protects babies partially for a few months. From this study we
can conclude that on the whole, malaria during pregnancy does not seem to
have been a significant risk factor for infant mortality in the Garki project.
These findings indicate that the risk of malaria during pregnancy for infant
survival might be overestimated by ignoring acquired maternal immunity.

There many ways that malaria is treated and many different drugs used in
the process. Some of the drugs used to treat malaria include Chloroquine,
quinine, atovaquone-proguanil, clindamycin, mefloquine (avoided in the first
trimester), sulfadoxine-pyrimethamine (avoided in the first trimester) and
artemisininsin. Briand et al contrasted sulfadoxine-effectiveness
pyrimethamines and protection with mefloquine for occasional preventive
care during pregnancy. In their research, 1601 women obtained either
sulfadoxine-pyrimethamine of all gravidities (150. In their report, 1601
women of all ages received either sulfadoxine-pyrimethamine (1500 mg of
sulfadoxine and 75 mg of pyrimethamine) or mefloquine (15 mg/kg) twice
during pregnancy in a single dose. In terms of effectiveness, mefloquine had
a slight benefit, while the frequency of side effects with mefloquine was
higher than with sulfadoxine-pyrimethamine.4

The different drugs used have different ways of reacting and there are four
main drug groups commonly used to treat malaria include quinoline-related
compounds, antifolates, artemisinin derivatives, and antimicrobials. No
single drug has yet been identified or produced that can eliminate all
aspects of the parasite's life cycle.5

Exploration

The first type of drug used for the treating malaria is quinoline-related
compounds. The malarial parasite catabolizes erythrocyte-
derived hemoglobin
to provide bioenergetic support for parasite growth and reproduction.
Antimalarial compounds dependent on quinoline, such as CQ,
hydroxychloroquine (HCQ), quinine (QN), mefloquine (MFQ), and quinacrine
(QNX), are fundamental therapies that effectively destroy parasites of P.
falciparum. Chloroquine, a widely prescribed QBA that has weakly basic
properties, traverses cellular membranes of erythrocytes and P. falciparum
down a pH gradient to accumulate within AFVs and disrupts detoxification of
the heme, causing death of the parasite.6 Since Hydroxychloroquine has
similar anitimalarial activity and it has a lower associated risk of ocular
toxicity it is usually more clinically preferred when higher doses are required
to treat malaria.7

4
. https://www.medscape.com/answers/221134-40845/which-medications-are-
used-to-treat-malaria-during-pregnancy
5
https://emedicine.medscape.com/article/221134-medication#:~:text=The
%204%20major%20drug%20classes,been%20discovered%20or%20manufactured
%20yet.
6
https://thejns.org/focus/view/journals/neurosurg-focus/38/3/article-
pE12.xml#:~:text=Quinoline%2Dbased%20antimalarial%20compounds%2C
%20such,falciparum%20parasites.&text=Mefloquine%20and%20QNX%20have
%20been,efficacious%20in%20CQ%2Dresistant%20malaria.
Another set of compounds that are used as antimalarials are antifolates.
Antifolates are used during the process of chemotherapy. Chemotherapy
remains the most effective method of managing malaria which is one of the
world's deadliest infectious parasitic diseases. Antimalarial antifolates are
essential to malaria prophylaxis and treatment. In the 1940s, during the
Second World War, this drug family was discovered, and molecules that are
now in clinical use were discovered at that time. The discovery of the folate
compound is connected with the understanding of complications of
anaemia. By the 1930s, evidence showed that the addition of yeast or liver
extract could reverse some types of anaemia, mainly megaloblastic anaemia,
leading to the hypothesis that anaemia could be associated with a specific
cause. The name folic acid was given to this element in 1941 when Mitchell
et al isolated it from spinach leaves.8

The WHO recommends artemisinin-based combination therapies (ACTs) as a

first-and second-line treatment for uncomplicated P. falciparum malaria as
well as for P. vivax malaria immune to chloroquine. An artemisinin derivative
and a partner drug are paired with Actions. The role of the artemisinin
compound is to reduce the number of parasites (reduction of parasite
biomass) within the first 3 days of treatment, while the role of the partner
drug is to remove the remaining parasites (cure). Resistance to artemisinin
usually refers to a delay in bloodstream clearance of malaria parasites
following treatment with ACT. As a result, among patients who are infected
with artemisinin-resistant malaria strains, the artemisinin compound is less
successful in clearing all parasites within a 3-day span. 9

7
https://thejns.org/focus/view/journals/neurosurg-focus/38/3/article-
pE12.xml#:~:text=Quinoline-based%20antimalarial%20compounds%2C
%20such,falciparum%20parasites.&text=Mefloquine%20and%20QNX%20have
%20been,efficacious%20in%20CQ-resistant%20malaria.
8
https://academic.oup.com/jac/article/57/6/1043/731405
9
https://www.who.int/malaria/media/artemisinin_resistance_qa/en/#:~:text=Art
emisinin%2Dbased%20combination%20therapies%20(ACTs,1%20with%20a
%20partner%20drug.
Artesunate is the most commonly studied artemisinin derivative in pregnant
women: in a series of more than 400 births, anomalies were no more
common than in the general population; (8) In practice, early combination
therapy based on artemisinin derivatives is frequently prescribed in regions
where P. falciparum malaria is endemic.10

Tetracyclines and macrolides are now well known as anti-malarial drugs and
other antibiotics should also be taken into account. Significant discoveries
could result from chemical modifications with anti-plasmodial properties of
older molecules. Co-trimoxazole is a blend of sulfamethoxazole and
trimethoprim. Trimethoprim is derived from pyrimidine and belongs to a
group of compounds with antibacterial activity that is well characterized. 11

The reduced cost of clinical development is a benefit of using antibiotics

already licensed, such as doxycycline, tigecycline, clindamycin, azithromycin
or co-trimoxazole, as anti-malarial drugs. Furthermore, most of the already
licensed antibiotics are inexpensive and almost universally available.
 
In areas where the parasites are immune to the traditional anti- malarial
drugs, anti-biotics can be used instead. This disparity in modes of action also
means that a combination of antibiotics can be a successful partner. For the
treatment of uncomplicated malaria in pregnant women during the first
trimester, clindamycin is recommended by the WHO in combination with
quinine.
Methodology

The impact of antimalarial drugs is studied using human subjects already infected
with HIV. There are also long-term studies to understand the effect of the
medications on the human subject's reduction in viral load and side effects.

10
https://pubmed.ncbi.nlm.nih.gov/19492494/
11
https://malariajournal.biomedcentral.com/articles/10.1186/s12936-016-1613-
y#:~:text=An%20advantage%20of%20using%20antibiotics,inexpensive%20and
%20almost%20universally%20available.
Due to ethical considerations and time constraints,
the collection of primary data was not sufficient. A secondary research
methodology was then adopted to answer the research issue.

Research reports have been used to gather results. These were selected from the
datasets as they offer more comprehensive details on the process, the attributes
of the study and the possible measurement points. This essay analyses and
evaluates research papers on the impact of antimalarial treatment on foetuses.