Malaria

• Malaria is an acute protozoan anthroponous

endemic infectious disease caused by
malarial plasmodia, transmitted through bites
of an infected female Anopheles mosquito and
is characterized by intoxication, febrile attacks
(paroxysms) in definite intervals, anaemia,
pathological involvement of the liver, the
brain, the kidneys, other organs and frequent
early and late relapses.
 Malaria endemic areas in India
According to the
World Malaria Report
2017, in the year 2016,
more than half of the
population (698 million)
was at risk of malaria.
India accounted for 6%
of all malaria cases in
the world, 6% of the
deaths, and 51% of the
global P. vivax cases.
The total cases in India
are 1.31 million with
23990 deaths.
Proportion of P. falciparum distribution in India
• New features are:
• resistance to
insecticide(s);
• extensive vector breeding
grounds created
principally by the water
resource development
projects,
• urbanization and
industrialization;
• change in parasite formula
in favour of P. falciparum;
• resistance in P. falciparum
to chloroquine and other
antimalarial drugs.
 Iraq
• The incidence of malaria in Iraq is low. Seasonality is
March-November. Prevalence is in the north, below 1500 m.
 ETIOLOGY
• There are five types of Plasmodium that infect
humans:
▫ Plasmodium vivax causes three-day malaria
▫ Plasmodium falciparum - tropical malaria
▫ Plasmodium malariae - four-day malaria
▫ Plasmodium ovale is the cause of three-day
ovale malaria
▫ Plasmodium knowlesi - described recently,
was previously pathogenic only for apes.
▫ All plasmodia have the same life cycle:
▫ asexual development (schizogony) takes place in the
human body of an intermediate host (human);
▫ sexual
▫ development
▫ (sporogony)
▫ - in the body
▫ of the final
▫ host, the
▫ female
▫ mosquito
▫ of the genus
▫ Anopheles.
• Anopheles mosquitoes, infected with malarial
plasmodia, introduce sporozoites with their saliva
into the human organism while sucking the blood of
a healthy person. Sporozoites rapidly disappear out
of the blood, travel to the liver and penetrate into
hepatocytes, where they develop so-called tissue
schizonts, which produce large number of tissue
merozoites. Tissue or preerythrocytic (exerythrocytic)
phase lasts for 6—9 days. But in malaria caused by
P.vivax and P.ovale, some tissue parasites may
remain dormant and later become active and be
released into the blood. These forms, called
hypnozoites, cause no symptoms during 6—11
months or more after the initial infection but are
 EPIDEMIOLOGY
• The source of the infection is a sick person or a
parasite carrier, whose blood contains
gametocytes. The mechanism of transmission is
vectorborne. Under natural conditions, malaria
vectors are mosquitoes of the genus Anopheles.
• Other ways of transmitting malaria are possible:
from the mother to the fetus or newborn
(vertical transmission during delivery);
transfusion pathway - in case of transfusion of
donor blood containing the pathogen, organ
transplantation; drug addiction through a
common syringe. Рarenteral infection is
possible with medical
procedures.
 Pathogenesis
• Malaria clinic is caused by erythrocyte
schizogony — the growth and reproduction in
the blood of asexual erythrocyte forms of the
parasite. Tissue schizogony is not clinically
manifested. Malarial attack is associated with
the completion of erythrocyte schizogony, mass
disintegration of red blood cells and release in
the blood of merozoites and their toxins that
cause fever. Due to cyclicity of the erythrocytic
schizogony paroxysms recur every 48 hours in
vivax, ovale and falciparum malaria and 72
hours in P. malariae.
• The human body gets infected with a
heterogeneous population of parasites, and
schizogony in the initial period occurs
asynchronously, because of this the fever may
be wrong.
• In the process of immunity formation the ability
to parasitize in red blood cells remains in one
main generation of parasites, which determines
the characteristic type of fever.
• Only in tropical malaria there can be several (2-
3) major generations of plasmodia, so the fever
is often wrong.
• P. vivax and ovale develop in the reticulocytes, P.
malariae - in older erythrocytes, but P. falciparum
invades red cells of all ages. Anaemia as one of the
most common signs of malaria is the result of
haemolysis erythrocytes. Indirect-reacting serum
bilirubin increases in the blood and unconjugated
jaundice is frequently present.
• In the liver and spleen lymphoid and reticuloendothelial
hyperplasia occur. Jaundice develops as a result of
hemolysis of erythrocytes and lesions of hepatocytes.
• Reduced absorption of carbohydrates and inhibition of
gluconeogenesis in the liver causes hypoglycemia.
Activation of anaerobic glycolysis leads to lactate
acidosis, which is one of the causes of severe tropical
malaria.
• In tropical malaria, the pathogen multiplies in the
vessels of the brain, where microthrombs appear
(plasmodia, their toxins, destroyed red blood cells
stick together). Blockage of vessels causes ischemia.
Нypoxia develops due to insufficient function of
infected red blood cells. The least resistant to hypoxia
is brain tissue, what leads to cerebral malaria (its
specific meningoencephalitis). Renal failure is a
frequent complication of severe P. falciparum
infection with development of proteinuria,
haemoglobihuria, and elevated serum creatinine and
urea levels. Also pulmonary edema are due to tissue
anaemia and hypoxia. In severe falciparum malaria
DIC-syndrome occurs.
• There is a high risk of death in patients with
high rate of parasitaemia, especially among
nonimmune persons. Young children and
pregnant women also have a more severe
course and frequent complications.
• After clinical convalescence relapses may
sometimes occur. Late relapses after vivax and
ovale malaria are the result of infection of
erythrocytes by merozoites derived from
persistent liver forms (hypnozoites). Early
relapses are the result activation of slow
asymptomatic erythrocite cycle.
• Malaria does not produce long immunity. But if
a person lives in the area and is infected with
malaria every year, the clinic does not occur.
Immunity fades in 5-6 years, and when he
returns to the area the symptoms are as
severe as for the first time.
 CLINICAL PICTURE
• The incubation period depends on the species of
plasmodium and state of the immunity and lasts from
several days to several months.
• Prodromal symptoms are common (several hours or 2
—3 days).
▫ Headache
▫ Malaise
▫ Fatigue
▫ Nausea
▫ Muscular pains
▫ Slight diarrhea
▫ Slight fever, usually not intermittent
 Malarial Paroxysm
cold stage
•feeling of intense cold
•vigorous shivering
•lasts 15-60 minutes
hot stage
•intense heat
•dry burning skin
•throbbing headache
•lasts 2-6 hours
sweating stage
•profuse sweating
•declining temperature
•exhausted and weak → sleep
•lasts 2-4 hours
P. falcipa-
rum:

P. vivax,
P. ovale

P.
malariae
• After 2-3 temperature attacks, the liver and
spleen clearly increase. Hemolytic anemia
appears, skin of the patient has a lemon color.
 Vivax malaria
• The incubation period lasts from 10 days to 14 months.
Prodromal period usually lasts up to 5 days. Subsequently
the typical paroxysms develop which last 6—10 hours
ending with profuse sweating. Anaemia develops after the
disease but it is not often severe. ESR increases. The
spleen and liver are often enlarged.
• However, after 2 weeks—2 months, early relapses appear,
characterized by a synchronous temperature curve,
increased liver and spleen, anemia.
• Subsequently, with the increase of immunity parasites
disappear from the blood and the latent period begins.
• If during this time histoshizotropic drugs are not given,
then in 6-8 months (and sometimes after 1-3 years) the
activation of slumbering tissue forms of the parasite
 Ovale malaria
• The incubation period usually lasts 11—16
days, but may be longer (from 2 months to 2
years). Ovale malaria is usually characterized
by slight clinical symptoms. Paroxysms
frequently develop in the evening and are not
severe. For this form early and late relapses
are common.
 Falciparum malaria
• In most patients, tropical malaria begins
acutely, without a prodromal period, with a rise
in body temperature to 38-39 °C. In some
cases, the onset of tropical malaria is
accompanied by nausea, vomiting, diarrhea.
Catarrhal symptoms from the upper respiratory
tract sometimes are registered. In the acute
stage, patients have conjunctival hyperemia, in
the severe course it can be accompanied by
petechial or larger subconjunctival
hemorrhages. The fever lasts for days, periods
of apyrexia are rarely recorded.
• The duration of individual paroxysms (and in
fact the combination of several ones) with
tropical malaria reaches 30-40 hours. The
wrong type of temperature curve prevails, less
often the remitting type is observed,
occasionally — intermittent and constant ones.
Enlargement of the liver and spleen is usually
determined from 3d day of the disease. More
than a three-fold increase in the activity of
aminotransferases is regarded as an indicator
of an unfavorable forecast.
• In falciparum malaria a great number of
erythrocytes (as a rule approximately 20—30%)
are infected. In this form severe normocytic
anaemia, trombocytopenia and decrease in
hemoglobin are common.
• The recurrent course is due to inadequate
etiotropic treatment, or the presence of P.
falciparum resistance to chemotherapy.
• The natural course of tropical malaria with a
favorable outcome lasts not more than 2
weeks. In the absence of etiotropic therapy,
relapses occur after 7-10 days.
• Pregnancy and early childhood are risk factors
for severe tropical malaria. Children under 3-4
years do not have the most striking symptom —
malarial paroxysm. Symptoms such as cramps,
vomiting, diarrhea, abdominal pain are
observed, with a progressive deterioration of
the child's condition. Parasitemia
is usually high. The disease can
quickly acquire a malignant
course and lead to death of the
child.
 Сomplications
– Cerebral malaria (unrousable coma not attributable to
other causes).
– Generalised convulsions (> 2 episodes within 24
hours)
– Severe normocytic anaemia (Ht<15% or Hb < 50 g/l)
– Hypoglycaemia (blood glucose < 2.2 mmol/l )
– Fluid and electrolyte disturbances
– Acute renal failure (urine <400 ml/24 h in adults; 12
ml/kg/24 h in children)
– Acute pulmonary edema and adult respiratory distress
syndrome
– Abnormal bleeding
– Jaundice
– Haemoglobinuria
– Circulatory collapse, shock, septicaema (algid malaria)
– Rupture of the spleen
 Сerebral malaria
• develops in P. falciparum (plasmodia multiply in the
blood vessels of the brain where they disrupt the blood
circulation).
• The onset of coma may be preceded by headache,
drowsiness, stupor or excitation. The patients become
unconscious. In a comatose state various neurological
signs may be present. In untreated cases mortality
reaches 100%.
 Blackwater fever
• Blackwater fever develops due to massive
intravascular hemolysis in intensity of infection
or in treatment with some antimalarial drugs.
Intense jaundice, severe hemorrhagic
syndrome, anemia and anuria develop,
accompanied by chills, fever (40 °C), lower
back pain, vomiting, myalgia, arthralgia.
• Urine becomes dark brown or black due to the
presence of oxyhemoglobin. The number of red
blood cells deacreases to 1×1012 /l, and
hemoglobin — to 20-30 g/l. Parasites in the
blood may not be determined.
• With the rapid abolition of
antimalarial drug, the condi-
tion improves. In severe
cases, the prognosis may
be unfavourable due to the
development of ARF.
 Renal failure
• is due to reduction of intrarenal blood flow and
microcirculation. Renal damage is manifested
by increasing creatinine and urea in the blood.
Uremia and coma may develop.
 Diagnosis
• Epidemiological and clinical data;
• microscopic examination of thick or thin blood’s
smear.
• The thick drop contains more blood therefore
the probability of finding Plasmodia is much
greater than in the smear.
• Rapid diagnostic tests (RDTs) are quick tests
that use a drop of blood from the finger tip to
identify whether parasites are present in the
patient.
• PCR for determination of parasite DNA.
 Laboratory diagnosis of malaria

CCMOVBD
Plasmodium falciparum CCMOVBD
Plasmodium vivax

CCMOVBD
Plasmodium malariae Malaria Tutorials, Wellcome Trust Plasmodium ovale
 Antimalarial drugs
• 1. Hematoshizotropic drugs (affecting erythrocyte
schizonts): chloroquine, mefloquine, quinine,
artesunate (i/v), artemether (i/m), artenser +
lumefantrine (Riamet), pyrimethamine,
pyrimethamine + sulfadoxine (Fansidar).
• 2. Histoshizotropic drugs: affecting preerythrocytic
(primary tissue) forms: pyrimethamine, proguanil,
proguanil + atovaquone (Maloron); affecting
exoerythrocytic (secondary tissue) forms –
primaquine.
• 3. Gamontotropic drugs (affect sexual forms):
gamontocide – primaquine; gamontostatistic –
pyrimethamine (sporontocide action).
• 4. Doxycycline, clindamycin.
 Treatment
• Drugs such as chloroquine and primaquine
are recommended
• 10 mg/kg/day at 1-st and the second days.
• During the third day 5 mg/kg/day
• Currently, Plasmodium has resistance to
quinine preparations, therefore artemisinin
and its analogues are recommended.
Differential diagnosis of
diseases with fever
syndrome
• Fever, accompanied by intoxication, is
characteristic of most bacterial, viral and protozoal
infectious diseases, generalized mycoses. It is
possible with helminthic invasions (opisthorchiasis,
etc.). Fever-intoxication syndrome does not appear
in cholera, botulism, HBV and HCV, uncomplicated
amebiasis, cutaneous leishmaniasis, giardiasis,
localized mycoses and many helminthic invasions.
The level of fever reflects the overall severity of the
disease. Fever may be absent or be subfebrile
with mild course of many diarrheal and acute
respiratory infections.
 Sepsis
• is often manifested by paroxysms of fever, resembling
malaria, pallor and subictericity of the skin,
hepatolienal syndrome, anemia. But there are not
observed pronounced periods of apyrexia. Hemorrha-
gic syndrome is more pronounced. Sepsis is
characterized by the presence of a gate infection;
multiple pyogenic foci are possible. Laboratory testing
confirms the diagnosis: isolation of the germs from the
blood, urine, pus.
• Neutrophilic leukocy-
• tosis is in the hemog-
• ramma, ESR is high.
 Croupous pneumonia
• begins with chills and high fever, followed by coughing
with sputum, chest pain, dyspnеa. During
auscultation, the
doctor hears
crepitus, wheezing.
X-ray examinations
help determine the
final diagnosis.
 Leptospirosis
• begins with hyperthermia, vomiting, weakness.
Then such pathognomonic sign as myalgia
(especially gastrocnemius muscles) appears.
Rash (petechial, roseolous), jaundice, kidney
damage with oliguria may occur. Of importance
are the epidemiological situation, the detection
of leptospira in the blood and urine, the
agglutination reaction with cultures of
leptospirae.
 Meningococcal meningitis
• The acute onset of meningococcal meningitis with
severe chill, headache, the temperature curve may
resemble that of malaria. The diagnosis is confirmed by
parasitological examination of the blood, changes in the
general blood test and the characteristics of the
cerebrospinal fluid (purulent character, meningococcus
detection).
 Typhoid fever
• Severe forms of typhoid fever, especially in
children, occurring from the 1st day with high fever,
typhoid status, hepatolienal syndrome,
tachycardia, leukopenia, sometimes with clinical
picture are similar to tropical malaria.
• In these conditions, epidemiological data are
important. In typhoid fever when measuring the
temperature every 2 hours during the day, its
monotony is determined.
• The diagnosis is established on the basis of
laboratory data: positive blood culture, Vidal
reaction in typhoid fever, and plasmodia found in
malaria.
 Yersiniosis
• Infection with Y. enterocolitica occurs most often in
young children. The infection is thought to be
contracted through the consumption of undercooked
meat products, unpasteurized milk, or water
contaminated by the bacteria, and raw vegetables.
Common symptoms are fever, abdominal pain, and
diarrhea, which is often bloody. In older children and
adults, right-sided abdominal pain and fever may be
the predominant symptoms, and appendicitis,
mesadenitis may develop. In generalized form such
symptoms as high fever, skin rash, joint pains, ileitis,
erythema nodosum, and sometimes sepsis, acute
arthritis can occur.
 HIV-infection
When initially infected, many people
have no noticeable symptoms, but
within 1 to 4 weeks, fever, rashes, sore
throat, lymphoadenopathy, fatigue,
and hepatosplenomegaly develop in
some people. Opportunistic infections
may cause various symptoms with
long fever.
 Brucellosis
• In the acute period of brucellosis, fever changes
periods of aperixia, chilling, sweating, hepato- and
spleenomegaly, and leukopenia suspect malaria.
• But in brucellosis, there is a lesion of the
musculoskeletal system (arthritis, bursitis, etc.).
• Patients feel satisfactory during fever. Accounting for
the epidemiological situation (contact with sick
animals, eating infected foods) helps to differentiate
diseases.
• Serological tests (Wright and Headdlson reactions),
the Byrne test in brucellosis and blood tests in malaria
confirm the diagnose.
 Yellow fever
• Yellow fever is an acute hemorrhagic transmission
disease of viral etiology, a tropical zoo anthroponosis
in Africa and South America. It is transmitted through
Aedes aegypti mosquito bites.
• A severe course is characterized by a sudden onset,
fever up to 39–41 ° C, chills, severe headache, back
and limbs myalgia, nausea, vomiting. The patient’s
look it is typical: jaundice due to liver damage; red,
puffy face, swollen eyelids.
• After a short light period, shock can occur,
hemorrhagic syndrome with ARF, AHF develops.
Patients can die in 3-4 days. Mortality of the disease is
5-60%.
 Nipah fever
• For the first time the Nipah virus was detected in 1999.
It spreads in South Asia. The sources of the infection
are flying foxes and pigs. Transmission factors are
urine, saliva, animal tissue. Ways of transmission are
airborne, contact.
• The disease begins with flu-like symptoms. Then acute
encephalitis or SARS may appear. In severe cases,
encephalitis leads to coma in 24-48 hours. The
mortality is 40-75%.
 Dengue fever
• Dengue fever occurs in countries of South and
Southeast Asia, Africa, Oceania and the
Caribbean. The annual incidence is about 50
million people. The source of infection is a sick
person, monkeys and bats. Aedes aegypti
mosquitoes transmit infection from a sick
person.
• It occurs with fever, intoxication, myalgia,
arthralgia, rash, and swollen lymph nodes.
When re-infection happens dengue
hemorrhagic fever with DIS develops.
 Zika fever
• Zika fever is an infectious disease caused by the
Zika virus. Symptoms may include fever, red eyes,
joint pain, headache, and a maculopapular rash.
Symptoms generally last less than seven days.
Mother-to-child transmission during pregnancy can
cause microcephaly and other brain malformations in
some babies.
• Zika fever is mainly spread via the bite of mosquitoes
of the Aedes type. It can also be sexually transmitted
and potentially spread by blood transfusions.
Infections in pregnant women can spread to the
baby. Diagnosis is by testing the blood, urine, or
saliva for the presence of the virus's RNA, or the
blood for antibodies.
Serological surveys have indicated that Zika virus is
endemic in most areas of Asia, though at a low level.
 Japanese encephalitis
• Japanese encephalitis is an infection of the brain
caused by the Japanese encephalitis virus. Signs
which develop during the acute encephalitic stage
include headache, vomiting, neck rigidity, cachexia,
hemiparesis, convulsions and a raised body
temperature between 38–41 °C.
• The disease occurs in Southeast Asia and the
Western Pacific. JEV is generally spread by
mosquitoes, specifically those of the Culex type.
Pigs and wild birds serve as a reservoir for the virus.
The disease mostly occurs outside of cities.
Diagnosis is based on blood or cerebrospinal fluid
testing.
Ebola hemorrhagic
fever
• is a viral hemorrhagic fever of humans and other
primates caused by ebolaviruses. The natural
reservoir for Ebola is bats. Primary signs are fever,
sore throat, muscular pain, and headaches. Vomiting,
diarrhea and rash usually follow, along with decreased
function of the liver and kidneys. The disease has a
risk of death about 50% due to DIC.
• The virus spreads through direct contact with blood
from infected humans or other animals. Semen or
breast milk of a person after recovery may carry the
virus for several weeks to months.
Thanks to those who attended
my lectures!