plasmodium falciparum infection malaria management / pregnancy

1. MALARIA
Op. Dr. Kivanc KAYHAN
Obs & Gyn

6. ude birth rate
icates the number
ive births
curring during the
ar, per 1,000
pulation. Crude
ath rate indicates
number of deaths
urring during the
ar, per 1,000
pulation estimated
midyear. Subtracting
crude death rate
m the crude birth
e provides the rate
natural increase
Age dependency
ratio is the ratio of
dependents--
people younger
than 15 or older
than 64--to the
working-age
population--those
ages 15-64.

7. SAME

8. IMPROVEMENT

9. INCREASING

10. INCREASING

11. SAME

13. SAME

14. GDP per capita is gross domestic product divided by
midyear population.
same

17. Better??

18. better

23. better

44. • Malaria threatens the lives of 40% of the world’s population – over
2 200 million people. Each year, there are an estimated 300-500 million
clinical cases. Malaria is estimated to kill more than 1 million people
annually, the majority of whom are young children.
• Ninety percent of malaria cases in the world occur in Africa south of
the Sahara. Children under 5 years of age and pregnant women are
the worst affected by malaria.
• Africa, malaria is responsible for about 20-30% of hospital admissions
and about 30-50% of outpatient consultations.
• Widespread drug resistance against commonly used antimalarial
drugs such as chloroquine and pyrimethamine/sulfadoxine (Fansidar)
has been reported all over the world.

45. ATTENTION ON;
1-insecticide treated
• mosquito nets and other materials such as curtains and screens on
windows and doors. The success of three large trials on insecticide-
treated mosquito nets conducted in the Gambia, Kenya and Ghana
and another one using treated curtains in Burkina Faso, have
demonstrated that the use of insecticide-treated materials can reduce
all-cause child mortality by about 25%.
• 2-changes in treatment regimen in areas of chloroquine resistance are
possible. Alternative drugs, such as pyrimethamine/sulfadoxine,
mefloquine, quinine and artemisinin derivatives, provide effective
cure
• 3-increase the general care skills of parents, caregivers and health
workers

46. > When a mosquito bites a person it sucks up blood. If the person has
malaria, some of the parasites in the blood will be sucked into the
mosquito. The malaria parasites multiply and develop in the mosquito.
After 10-14 days they are mature and ready to be passed on to
someone else.
Re-bite > liver (multiplies 10 times in every2 day) > bloodstream >
destroying RBC’ entering to a new one

50. >Plasmodium falciparum which causes the severest type of malaria,
>Plasmodium vivax/ovale/malariae which cause less severe symptoms.
INC PERIOD: week to several months after infection, but usually in 7-21
days.
VECTOR: female Anopheles mosquitoes, can be recognized by its
upturning tail. (2-5mm wide) black spots on the surface of water,
chooses stagnant or slow-flowing water, 2-3 days later larva comes out.
Turns to pupa, hatches and mosq flies away, lays eggs around. All takes
7-14 days.
egg, larva or pupa does not have malaria parasites inside it. Lifespan
of mosq is equal to growth time of parasite
lifespan is shorter in cooler environments and lengthens as the
temperature rises. Thus the survival of the parasite depends upon the
weather. Once the average temperature drops below a certain point,
the mosquito tends to die before it can transmit malaria.

52. UNCOMPLICATED MALARIA
• Like a minor systemic viral illness.
• headache, lassitude, fatigue, abdominal discomfort, and muscle and joint
aches, usually followed by fever, chills, perspiration, anorexia, vomiting and
worsening malaise, sometimes cough and diarrhea,
• Any child who presents with fever in a malaria endemic region or who
recently visited such a region, must be assumed to have malaria until
proven otherwise, and requires urgent treatment.
• frequently over-diagnosed,
• FEVER IS EQUAL TO MALARIA
• >Ask the patient, or the adult accompanying a young patient, whether
there has been any fever at any time during the past 2-3 days
• Early diagnosis and treatment will save lives

53. SEVERE OR COMPLICATED MALARIA
• Untreated malaria in a young child or in a non-immune individual may
become complicated
• very high body temperature, drowsiness, convulsions and coma
indicating heavy parasitaemia and cerebral malaria
• AND bleeding, jaundice, diminished urine output, all signifying liver
and/or kidney failure, pulmonary edema, metabolic acidosis
• By this stage of the disease, the case fatality in people receiving
treatment is typically 10–20%. However, if left untreated, severe
malaria is fatal in the majority of cases.

55. NOKTURNAL ATTACK: last several hours,
shivering (body shaking) >> period of fever >> finally there is profuse
sweating.
>Feels headache and pain in the back, joints and all over the body. loss
of appetite, vomiting and diarrhea
Children may present as loss of consciousness, drowsiness and/or
convulsions, diarrhoea, dark urine and reduced urine output (anuria).
If untreated (or inadequately treated), malaria may cause several
weeks or months
It is particularly important to make an early diagnosis of malaria in
young children and in pregnant women.
 Malaria during pregnancy is more difficult to treat, because the
parasites tend to hide in the placenta

57. DISEASE IMMUNITY ???
>where populations are continuously exposed to a high rate of malarial
inoculations partial immunity to the clinical disease and to its severe
manifestation is acquired early in childhood.
>sub-Saharan Africa and parts of Oceania, the acute clinical disease
described above is mostly confined to young children, who suffer high
parasite densities and acute clinical disease. If untreated, this can
progress very rapidly to severe malaria; adolescents and adults are
partially immune and seldom suffer clinical disease, although they may
continue to harbour low blood-parasite densities.
>Immunity is, however, modified in pregnancy, and it is often gradually
lost, at least partially, when individuals move out of the endemic areas
for long durations (usually many years).

58. >>Asia and Latin America, and the remaining parts of the world where
malaria is endemic, the rates of inoculation fluctuate greatly over
seasons and years. Entomological inoculation rates are usually <5 per
year and often <1 per year. This retards the acquisition of immunity and
results in people of all ages, adults and children alike, suffering acute
clinical malaria, with a high risk of progression to severe malaria if
untreated.

59. BLOOD TESTS: Examining a stained blood film under a microscope will
show whether a patient has malaria parasites in the blood (parasitaemia).
>Prompt parasitological confirmation by microscopy or alternatively by RDTs
is recommended in all patients suspected of malaria before treatment is
started.
>Treatment solely on the basis of clinical suspicion should only be considered
when a parasitological diagnosis is not accessible
>The two methods in routine use for parasitological diagnosis are light
microscopy and rapid diagnostic tests (RDTs).
>Microscopy has further advantages in that it can be used for speciation and
quantification of parasites, and to assess response to antimalarial treatment.
>In the diagnosis of severe malaria cases, microscopy is a preferred option

64. DISTINGUISHING MALARIA FROM
OTHER SERIOUS CONDITIONS
> lumbar puncture may distinguish malarial coma from meningitis;
careful examination of the chest may distinguish malarial breathing
from pneumonia.
>Other conditions which may present with similar symptoms to malaria
include:
hepatitis – causing jaundice;
acute renal (kidney) failure – causing diminished urine output;
diabetes – causing deep acidotic breathing.

65. WHO GUIDELINE
>>> Since the publication of the first edition of the guidelines in 2006,
most of the countries where P.falciparum is endemic have progressively
updated treatment policies from the failing chloroquine (CQ) and
sulfadoxine-pyrimethamine (SP) to the recommended artemisinin
based combination therapies (ACTs); this is the best current treatment
for uncomplicated falciparum malaria. high costs???!!!

66. MALARIA DRUG RESISTANCE
>Reports of chloroquine resistant strains of P. falciparum are being
documented in all regions of the world where malaria is Endemic.
>Malawi and Kenya recently changed their first line anti-malaria drug
treatment from chloroquine to pyrimethamine/sulfadoxine (Fansidar)
At least %30 resistance is seen…

68. TREATMENT
chloroquine is no longer effective in treating malaria, hence second line
antimalarial drugs are often used. Artemisin comb therapy,
pyrimethamine/sulfadoxine (Fansidar) or mefloquine(expensive) may be
used as first line drugs
resistance to mefloquine is growing in South East Asia
> vomiting soon after medication may require more treatment
fever which persists during treatment or which returns after a few days of
completed anti-malaria treatment may indicate treatment failure.
FAILURE: incomplete treatment (e.g. vomited or forgot to take pills) or
because the malaria might be resistant

69. >Artemisinin is a natural product developed by Chinese scientists from
the wormwood plant, Artemisia annua.
>Artemisinin clears the parasite from the body more quickly than
chloroquine or quinine. It is also considered to be less toxic than
quinine.
>Combination drug therapies are being advocated for treatment of
malaria, e.g. mefloquine plus artemisinin

70. TREATMENT OF
SEVERE OR COMPLICATED MALARIA
>intravenous quinine or artemisinin derivatives. IV infusion of quinine
should be given slowly over 8 hours to avoid cardiac complications. This
should be followed by oral quinine tablets for a total of 7 days
Artemisinin, if available, can be given in suppository form
fever, give paracetamol or aspirin

72. CHILDREN - TREATMENT
> The child should be observed for 1 hour. If the child vomits during
that time, treatment should be repeated (full dose if the drug is
vomited before 30 minutes, half dose if vomited between 30 minutes
and 1 hour). If the child vomits repeatedly, he or she must be
hospitalized.
> Children with malaria may have other infections at the same time,
such as meningitis or pneumonia. If coma and fever persist, it may be a
result of the common association of severe malaria with meningitis,
pneumonia or sepsis

73. OTHER DRUGS USED IN THE TREATMENT
OF MALARIA

74. (artemisinin-combination therapies, ACTs)

82. MALARIA IN PREGNANCY
In some countries, national policies recommend routine use of anti-
malarial drugs during pregnancy.
>Pyrimethamine/sulfadoxine (Fansidar) has been used as
prophylaxis/intermittent treatment in Malawi and in Kenya with good
preliminary results.
Chloroquine, amodiaquine, quinine can all be safely given during
pregnancy.
Artemisinin and its derivatives are also safe from the fourth month of
pregnancy onwards, though it is not recommended during the first 3
months of pregnancy.
Mefloquine ??? Not known about safety, maybe after 1st tri

83. CHEMOPROPHYLAXIS AGAINST MALARIA
during pregnancy, all migrants and travelers
>Chemoprophylaxis is an effective strategy for a limited time (ranging
from a few weeks to a few years). However, it does not offer lifelong
protection
chloroquine resistance in many countries, chloroquine is no longer
the drug of choice for prophylaxis in many regions of the world.
Mefloquine is the first drug of choice. The recommended dose is 1
tablet (250mg) weekly starting 1-2 weeks before departure to malaria
endemic regions and continued for 4 weeks after return.

84. >For children the dose is:
Weight over 45kg 1 tablet weekly
31-45kg three-quarters of a tablet weekly
20-30kg half a tablet weekly
5-19kg quarter of a tablet weekly
again continued for 4 weeks after leaving a malaria area.
Side effects of mefloquine are: nausea, vomiting, abdominal pain,
diarrhoea, headache, dizziness, abnormal heart rhythm and liver
dysfunction.

85. ALTERNATIVE DRUGS FOR CHEMOPROPHYLAXIS
Doxycycline: Dosage 100mg daily for 2 days before departure and
continued for 4 weeks after return from a malaria zone. It is
contraindicated in children under 8 years of age. Side effects include
nausea, vomiting, abdominal pain and in women it may cause
frequent vaginal candida infections. It is contraindicated during
pregnancy.
> Pyrimethamine/sulfadoxine (Fansidar), is no longer recommended for
routine weekly prophylaxis, because of the danger of severe cutaneous
reaction and sudden death.

87. Artemisinin-based combination therapy(ACT)
>These are combinations in which one of the components is
artemisinin and its derivatives (artesunate, artemether,
dihydroartemisinin).
artemisinin and its derivatives are eliminated rapidly, when given
alone or in combination with rapidly eliminated compounds
(tetracyclines, clindamycin), a 7-day course of treatment
in combination with slowly eliminated antimalarials. With this shorter
3-day course
To eliminate at least 90% of the parasitaemia, a 3-day course of the
artemisinin is required to cover up to three post-treatment asexual
cycles of the parasite. This ensures that only about 10% of the
parasitamia is present for clearance by the partner medicine, thus
reducing the potential for development of resistance.

90. many countries,
emether plus
mefantrine(COARTEM),
esunate plus
floquine or
ydroartemisinin plus
eraquine may give the
hest cure rates
The low levels of
resistance to AQ and SP in
some parts of Africa still
makes artesunate plus
amodiaquine or
sulfadoxine-
pyrimethamine effective
options.

95. TREATMENT FAILURE OF ACT
if fever and parasitaemia fail to resolve or recur within two weeks of
treatment then this is considered a failure of treatment. 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.
Wherever possible, treatment failure must be confirmed parasitologically
– preferably by blood slide examination
In many cases, failures are missed because patients who present with
malaria are not asked whether they have received antimalarial treatment
within the preceding 1–2 months. This should be a routine question in
patients who present with malaria.

96. TREATMENT FAILURE OF ACT
Treatment failure within 14 days of receiving an ACT is very unusual,
with the majority of treatment failures occurring after two weeks of
initial treatment.
failure rates at day 14 ranged from 1–7%.
 Treatment failures within 14 days of initial treatment should be
treated with a second-line antimalarial

101. Artemether plus lumefantrine (COARTEM)
containing 20 mg of artemether and 120 mg of lumefantrine.
The dosing is based on the number of tablets per dose according to
pre-defined weight bands (5–14 kg: 1 tablet; 15–24 kg: 2 tablets; 25–
34 kg: 3 tablets; and >34 kg: 4 tablets), given twice a day for 3 days.
1.4–4 mg/kg of artemether and 10–16 mg/kg of lumefantrine.
 Lumefantrine absorption is enhanced by co-administration with fat,
take after a meal

103. Artesunate plus amodiaquine
> A target dose of 4 mg/kg/day artesunate and 10 mg/kg/day
amodiaquine once a day for 3 days, with a therapeutic dose range
between 2–10 mg/kg/day artesunate and 7.5–15 mg/kg/dose
amodiaquine.

104. Artesunate plus mefloquine
50 mg of artesunate and 250 mg base of mefloquine tablets
respectively
A target dose of 4 mg/kg/day artesunate given once a day for 3 days
and 25 mg/kg of mefloquine either split over 2 days as 15mg/kg and
10mg/kg or over 3 days as 8.3 mg/kg/day once a day for 3 days. The
therapeutic dose range is between 2–10 mg/kg/dose/day of
artesunate and 7–11 mg/kg/dose/day of mefloquine.
Mefloquine is associated with an increased incidence of nausea,
vomiting, dizziness, dysphoria and sleep disturbance
 the 25 mg/kg dose is usually split and given either as 15 mg/kg
(usually on the second day) followed by 10 mg/kg one day later, or as
a daily dose of 8.3 mg/kg for 3 days.

105. Artesunate plus sulfadoxine-pyrimethamine
> separate scored tablets containing 50 mg of artesunate and tablets
containing 500 mg of sulfadoxine and 25 mg of pyrimethamine
>A target dose of 4 mg/kg/day artesunate given once a day for 3 days
and a single administration of 25/1.25 mg/kg sulfadoxine-
pyrimethamine on day 1, with a therapeutic dose range between 2–10
mg/kg/day artesunate and 25–70/1.25–3.5 mg/kg sulfadoxine-
pyrimethamine.

106. Dihydroartemisinin plus piperaquine
> fixed-dose combination with tablets containing 40 mg of
dihydroartemisinin and 320 mg of piperaquine.
> A target dose of 4 mg/kg/day dihydroartemisinin and 18 mg/kg/day
piperaquine once a day for 3 days, with a therapeutic dose range
between 2–10 mg/kg/day dihydroartemisinin and 16–26 mg/kg/dose
piperaquine

107. Artesunate plus tetracycline or doxycycline or
clindamycin
> Artesunate (2 mg/kg once a day) plus tetracycline (4 mg/kg four
times a day or doxycycline (3.5 mg/kg once a day) or clindamycin (10
mg/kg twice a day). Any of these combinations should be given for 7
days.

108. COMBINATION THERAPYYYYYYYYYYY
• With the exception of lumefantrine, the partner medicines of all
other ACTs have been used previously as monotherapies, and
amodiaquine, mefloquine and SP continue to be available as
monotherapy in many countries. Despite recommendations and
warnings, artemisinin derivatives are available as monotherapy in the
market place in many countries, and they are being used as such for
the treatment of uncomplicated malaria

112. PREGNANCY & MALARIA
Malaria in pregnancy is associated with low birth weight, increased
anaemia and, in low-transmission areas, an increased risk of severe
malaria and death.
antimalarial medicines considered safe in the first trimester of
pregnancy are quinine, chloroquine, clindamycin and proguanil.
Pregnant women in the first trimester with uncomplicated falciparum
malaria should be treated with quinine plus clindamycin for seven
days (and quinine monotherapy if clindamycin is not available).
Artesunate plus clindamycin for seven days is indicated if this
treatment fails.
ACT exposed pregnancies in the first trimester (n=123) indicate no
adverse effects of artemisinins (and the partner drugs) on pregnancy
or on the health of the fetus and neonates

113. >There is increasing experience with artemisinin derivatives in the second
and third trimesters (over 1500 documented pregnancies). There have been
no adverse effects on the mother or fetus.
>Mefloquine monotherapy has been associated with an increased risk of
stillbirth
>There is no published information about the combination of amodiaquine
and artesunate.
> six-dose artemether plus lumefantrine regimen has been evaluated in 125
women in the second and third trimesters in a controlled trial for the
treatment of uncomplicated falciparum malaria on the Burmese-Thai border.
It was well tolerated and safe, but efficacy was inferior to seven days of
artesunate monotherapy.
>Clindamycin is also considered safe, but it must be given for seven days in
combination with quinine. Quinine is associated with an increased risk of
hypoglycaemia in late pregnancy, and it should be used only if effective
alternatives are not available.

114. ways dilute IM quinine to a
entration of 60mg/ml. Dilute
ampoules containing
mg/ml with 3ml 0.9% sodium
ide injection. Dilute 2ml
oules containing 300mg/ml
8ml 0.9% sodium chloride
tion. Give 10mg/kg, repeat
4 hours, repeat again 4 hours
then repeat dose every
ours until the patient can
ow oral medication
10mg/kg 3 times daily for
ys (including time on IV or IM
apy)
ge: Protect from light

118. • > Withdrawal of oral artemisinin-based monotherapies
• The continued use of oral artemisinin-based monotherapies is considered to
be a major contributing factor to the development of resistance to
artemisinin derivatives. WHO urges regulatory authorities in malaria-endemic
countries to take measures to halt the production and marketing of these oral
monotherapies, and promote access to quality-assured artemisinin-based
combination therapies (ACTs).
• For oral artemisinin-based monotherapies to be effective in eliminating
malaria parasites, they need to be taken as a full seven-day treatment course.
However, due to the rapid clinical response – i.e. clearance of signs and
symptoms within 2-3 days – most patients do not complete the full regimen.
On day three, the cure rates of all artemisinin derivatives are as low as 52%,
leaving the parasite exposed to sub-therapeutic blood levels.
• >2007, WHO Member States adopted World Health Assembly resolution WHA
60.18 which calls for a progressive removal of oral artemisinin-based
monotherapies from markets.

120. Additional considerations for clinical
management
Can the patient take oral medication?
Treatment is with antipyretics and, if necessary, fanning and tepid
sponging.
Vomiting is common in acute malaria and may be severe. Antiemetics
are widely used
Management of seizures: patients with repeated seizures (more than
two seizures within a 24h period) should be treated as for severe
malaria. This suggests an overlap between the cerebral pathology
resulting from malaria(seizure that is not relieving after 30 min) and
febrile convulsions.

121. TRAVELLERS
> When within the malaria endemic country, they should be treated
according to national policy, provided this has a recent proven cure rate
exceeding 90%.
> if the patient has taken chemoprophylaxis, then the same medicine
should not be used for treatment.

124. PERSONAL PROTECTION AND SELECTIVE
VECTOR CONTROL MEASURES
• rainfall patterns, temperature and humidity. In many places,
transmission is seasonal, with the peak period during and just after
the rainy season.
USE OF INSECTICIDE-TREATED MOSQUITO NETS
insecticide treated mosquito nets and other materials such as
curtains and screens on windows and doors.
>The success of three large trials on insecticide-treated mosquito
nets conducted in the Gambia, Kenya and Ghana and another one
using treated curtains in Burkina Faso, have demonstrated that the
use of insecticide-treated materials can reduce all-cause child
mortality by about 25%.

125. VECTOR CONTROL-INSECTICIDE SPRAYING
>Many countries in Europe and North America have already banned
the use of DDT.
> The health worker plays an enormously important role in
early diagnosis and prompt treatment of malaria cases

126. • WHO has initiated several key preventive and curative interventions that
include:
• prompt and effective treatment with artemisinin-based combination
therapies
• rolling out long-lasting insecticide-treated bed net distribution to protect
pregnant women and children
• indoor residual spraying with insecticide.
• In 2010, about 9500 malaria cases were reported in Somalia, compared to
over 49 000 cases reported in 2006. This significant decrease was a result
of prompt treatment, indoor household spraying campaigns and the
distribution of bednets.
• UNICEF has distributed 732,000 long lasting insecticide treated nets over
the last two years in malaria prone districts across Somalia. This has
contributed to reduction of malaria morbidity. A recent survey indicates
that distribution of nets has enhanced coverage to about 45 per cent of
households.

127. • “In some instances the true cause of fever may not be malaria and by
not getting tested for malaria, individuals can miss the opportunity to
treat the real cause of fever,” says Ahmed Jama - Malaria Coordinator
for the Global Fund Programme in Northwest Somalia (“Somaliland”).
“Generally we see that 1 per cent of persons tested in Northwest
Somalia actually have malaria while the others are suffering from
other illnesses that require different treatment.