Malaria

Dr.Nashida Ahmed
 Malaria
• Malaria is a potentially life-threatening disease caused by
infection with Plasmodium protozoa transmitted by an
infective female Anopheles mosquito.
• Plasmodium falciparum infection carries a poor prognosis
with a high mortality if untreated, but it has an excellent
prognosis if diagnosed early and treated appropriately
Epidemiology

• Malaria is responsible for approximately 1-3 million deaths per year, typically in
children in sub-Saharan Africa infected with P falciparum. Populations at an
increased risk for mortality due to malaria include primigravida individuals,
travelers without immunity, and young children aged 6 months to 3 years who live
in endemic areas.
• Worldwide, an estimated 300-500 million cases occurring annually. It is most
prevalent in rural tropical areas below elevations of 1000 m (3282 ft) but is not
limited to these climates. P falciparum is found mostly in the tropics and accounts
for about 50% of cases and 95% of malarial deaths worldwide. P vivax is
distributed more widely than P falciparum, but it causes less morbidity and
mortality; however, both P vivax and P ovale can establish a hypnozoite phase in
the liver, resulting in latent infection.
• Human immunodeficiency virus (HIV) and malaria co-infection is a significant
problem across Asia and sub-Saharan Africa, where both diseases are relatively
common. Evidence suggests that malaria and HIV co-infection can lead to worse
clinical outcomes in both disease processes, with malarial infections being more
severe in patients infected with HIV and HIV replication increasing in malaria
infection.
Etiology
• Individuals with malaria typically acquired the infection in an
endemic area following a mosquito bite. Cases of infection
secondary to transfusion of infected blood are extremely rare.
The risk of infection depends on the intensity of malaria
transmission and the use of precautions, such as bed nets,
diethyl-meta-toluamide (DEET), and malaria prophylaxis.
Epidemiological determinants
• 1.Agent factor:
• Agent:
• Malaria in human is caused by five distinct species of the malaria parasite-
• P.vivax
• P.falciparum
• P.malaria
• P.ovale.
• P.knolesi
• Plasmodium vivax has the widest geographic distribution throughout the
world.
• Plasmodium ovale is a very rare parasite of human, mostly confined to
tropical Africa. It also been reported in Vietnam.
Epidemiological determinants
• Life cycle:
• The malaria parasite undergoes 2 cycles of development-
• The human cycle(asexual cycle) and the mosquito cycle(sexual cycle).
• i)Asexual cycle: the asexual cycle begins when an infected mosquito bites a person
and injects sporozites.
• 4 phages are describe in human cycle:
• Hepatic phase:
• the sporozoites disappear within 60 minutes from the peripheral circulation.
• Many of them are destroyed by phagocytes, but some reach the liver cells.
• After 1-2 weeks of development(depending upon the species), they become hepatic
schizonts.
• Which evetualy realease merozoites
• A single plasmodium falciparum sporozoite may form 40,000 merozoites.
• Other species of plasmodium produce 2000 to 15000 merozoites
Epidemiological determinants
• Lifecycle:
• The intrahepatic schizonts of the plasmodium(except p.falciparum) do not
burst all at the same time. Some remain in the dormant stage.
• Once the paracites enter the RBC they do not reinvade liver.
• (b) Erythrocyte Phase:
• Merozoites attach to specific receptor sites on the RBC.
• Merozoite penetrates the RBC and pass through the stages of trophozoite
and scizont.
• The erythocyte stage end with liberation of merozoites.
• (c) Gametogeny: In all species of malaria become male and female
gametocytes. These are sexual form of the parasite which are infective to
mosquito.
Epidemiological determinants
• Lifecycle:
• (ii) Sexual cycle:
• the mosquito cycle(sporogony) begins when gametocytes are ingested by
the vector mosquito when feeding on an infected person.
• In the stomach of the mosquito is exflagellation of the male gametocyte
• The female gametocyte undergoes a process of maturation and become
female gamete or macro gamete.
• Fertilization of the female gamete.
• Resulting zygote
• In 18 to 24 hours it become motile Ookinete,which penetrate the stomach
wall of the mosquito and develops into Oocyte
• The Oocyte grows rapidly and develops numerous sporozoites into the
body cavity of moquito.
• Sporozoite migrate into the salivary gland of the of the mosquito and
become infective to man.
Epidemiological determinants
2.host factor:
I. Age: affect all age
II. sex: male>female
III. Social and economic status: more in under develop country
IV. Housing: more in all ventilated and ill lighted house.
V. Occupation: more in agriculture practitioner
VI. Immunity : the epidemic of malaria influenced by immune status of the
population.
3. environmental factor:
i. Season: maximum prevalence is from July to November.
ii. Temperature: Optimum temperature for the development of malaria parasite in
vector is between 20°C to 30°C.
iii. Humidity:60%
iv. Rainfall: necessary for breeding.
v. Altitude: anopheles are not found at altitudes above 2000-2005 meter.
vi. Man made malaria: Burrow pits, garden pool, irrigation channels have leads to
the breeding of mosquito.
Clinical features

• Plasmodium vivax and Plasmodium ovale

• Causes benign tertian malaria - fever every third day. Incubation period of 12-17
days. Cycle is repeated every 48 hours. Gradually liver and spleen become
enlarge and tender and anaemia develops slowly.

• Plasmodium malariae
• Causes benign quartan malaria - fever every 4th day- but this is frequently not
observed, particularly in early infection. Long incubation period (18-40 days).
With chronic infection, can cause nephrotic syndrome and glomerulonephritis.

• Plasmodium falciparum
• Responsible for severe disease and malaria related deaths. Incubation 7-14 days.
The fever has no particular pattern with headache and vomiting and associated
with jaundice+anaemia develop rapidly and liver+spleen become enlarge and
tender with serious complication.
Incubation

• Each Plasmodium species has a specific incubation period. Reviews of travelers

returning from endemic areas have reported that P falciparum infection typically
develops within one month of exposure, thereby establishing the basis for
continuing antimalarial prophylaxis for 4 weeks upon return from an endemic
area. This should be emphasized to the patient to enhance post travel
compliance.

• Rarely, P falciparum causes initial infection up to a year later. P vivax and P

ovale may emerge weeks to months after the initial infection. In addition, P vivax
and P ovale have a hypnozoite form, during which the parasite can linger in the
liver for months before emerging and inducing recurrence after the initial
infection. In addition to treating the organism in infected blood, treating the
hypnozoite form with a second agent (primaquine) is critical to prevent relapse
from this latent liver stage.

• When P vivax and P ovale are transmitted via blood rather than by mosquito, no
latent hypnozoite phase occurs and treatment with primaquine is not necessary,
as it is the sporozoites that form hypnozoites in infected hepatocytes.
Background

• Malaria, which predominantly occurs in tropical areas

• 4 Plasmodium species known to cause malaria in humans are
P falciparum, P vivax, P ovale, P malariae, .
• The Plasmodium species can usually be distinguished by
morphology on a blood smear. P falciparum is distinguished
from the rest of the plasmodia by its high level of parasitemia
and the banana shape of its gametocytes
Infection and reproduction

• After a mosquito takes a blood meal, the malarial sporozoites

enter hepatocytes (liver phase) within minutes and then
emerge in the bloodstream after a few weeks. These
merozoites rapidly enter erythrocytes, where they develop into
trophozoites and then into schizonts over a period of days
(during the erythrocytic phase of the life cycle). Rupture of
infected erythrocytes containing the schizont results in fever
and merozoite release. The merozoites enter new red cells, and
the process is repeated, resulting in a logarithmic increase in
parasite burden.
Malarial merozoites in the peripheral blood. Note that several of the
merozoites have penetrated the erythrocyte membrane and entered the
cell
Signs and symptoms
• A typical attack comprises three distinct stages:
• Cold stage
• Hot stage and
• sweating stage
• All above three stages are observed in complicated malaria.
• 1. the cold stage: the cold stage consist of sensation of cold
and shivering.
• 2.Hot stage: hot stage consist of fever headache, vomiting,
seizures in young children.
• 3. sweating stage: the sweating stage includes sweets, return
to normal temperature.
Signs and symptoms
• Patients with malaria typically become symptomatic a few weeks after infection, though
the symptomatology and incubation period may vary, depending on host factors and the
causative species. Clinical symptoms include the following:
• Headache (noted in virtually all patients with malaria)
• Cough
• Fatigue
• Malaise
• Shaking chills
• Arthralgia
• Myalgia
• Paroxysm of fever, shaking chills, and sweats (every 48 or 72 hours, depending on species)
• Less common symptoms include the following:
• Anorexia and lethargy
• Nausea and vomiting
• Diarrhea
• Jaundice
Signs and symptoms
• Most patients with malaria have no specific physical findings,
but splenomegaly may be present. Severe malaria manifests as
the following:
• Cerebral malaria (sometimes with coma)
• Severe anemia
• Respiratory abnormalities: Include metabolic acidosis,
associated respiratory distress, and pulmonary edema, chest
retraction, use of accessory muscles for respiration, and
abnormally deep breathing
• Renal failure (typically reversible)
Differential diagnosis
• Typhoid
• Hepatitis.
• Dengue fever.
• Meningitis/encephalitis.
Investigations

• PBF for MP
• CBC
• ELISA
• Probes for parasites DNA
• Immunofluorescence test
• RDT
Management
• Failure to consider malaria in the differential diagnosis of a
febrile illness in a patient who has traveled to an area where
malaria is endemic can result in significant morbidity or
mortality, especially in children and in pregnant or
immunocompromised patients.
• Mixed infections involving more than 1 species of
Plasmodium may occur in areas of high endemicity and
multiple circulating malarial species.
• Occasionally, morphologic features do not permit distinction
between P falciparum and other Plasmodium species. In such
cases, patients from a P falciparum –endemic area should be
presumed to have P falciparum infection and should be treated
accordingly.
Management
• Treatment of uncomplicated malaria:
• P vivax and P. ovale malaria:
• Chloroquine(150 mg)
• 4 tablets in 1st day
• 4 tablets in 2nd day
• 2 tablets in 3rd day.
• For radical cure:
• Chloroquine(150 mg) :
• 4 tablets in 1st day
• 4 tablets in 2nd day + Primaquine(15 mg) daily for 14 days
• 2 tablets in 3rd day.
Management
• In case of chloroquine resistance:
• Quinine 600 mg (8 houorly for 7 days)
+
• Doxycycline 100 mg(12 hourly for 7 days)
+
• primaquine 15 mg (daily for 14 days).
Management
• B) Uncomplicated p. falciparum malaria (confirmed)
• Tab.Co-artem(artemether+Lumenfantrine) 24 tablets in 6 divided dosages
for adults. 00h-4tablets, 08 h-4 tablets,
• 24 h. 4 tablets, 36 h-4 tablets,48 h. 4 tablets,60 h-4 tablets.
Or
• Quinine 600 mg 8 hourly for 7 days.
Or
• Quinine 600 mg 8 hourly for 7 days + Doxycycline 100 mg 12 hourly for 7
days/ tetracycline 250 mg 6 hourly for 7 days.

• C) Uncomplicated P falciparum malaria presumptive:

• Chloroquine(150 mg) 4 tablets In 1st day
4 tablets in 2nd day and
2 tablets in 3rd day.
Chemoprophylaxis
• All plasmodial infections except chloroquine resistant
P.Falciparum---Oral chloroquine(150mg), 2 tablets weekly or
proguanil (100 mg) 1 or 2 tablets daily.

• Infection with moderate chlorquine resistant P.falciparum---

Oral chloroquine(150 mg), 2 tablet weekly + Proguanil (100
mg) 1 or 2 tablets daily.

• High chloroquine resistant area---doxycycline(100 mg) daily.

Management

• Treatment for complicated malaria:

• Quinine:
• Loading dose:Quinine dihydrochlroride 20 mg/kg/weight by IV infusion over 4
hours in 500 ml 5% DA.
• Maintainance dose:
• 8 hourly after the start of the loading dose, quinine salt 10 mg/kg IV over 4 hours
in 500 ml of 5% DA should be given as maintenance dose.
• This maintenance dose should be repeated 8 hourly until the patient can take oral
medication.
• Oral treatment with quinine salt 10 mg/kg should be continued 8 hourly.
• Total duration(Intervenous+oral) of tretmment should be 7 days.

• In severe anaemia packed red cell and for oliguria frusemide or mannitol use.
• For reduce temperature tab paracetamol 500 mg qds.
Management
• Diet and activity
• Patients with malaria should continue intake and activity as
tolerated.
Monitoring

• Patients with non– P falciparum malaria who are well can

usually be treated on an outpatient basis. Obtain blood smears
every day to demonstrate response to treatment. The sexual
stage of the protozoan, the gametocyte, does not respond to
most standard medications (eg, chloroquine, quinine), but
gametocytes eventually die and do not pose a threat to the
individual's health.
Pharmacologic treatment in pregnancy

• Medications that can be used for the treatment of malaria in

pregnancy include chloroquine, quinine, atovaquone-
proguanil, clindamycin, mefloquine (avoid in first trimester),
sulfadoxine-pyrimethamine (avoid in first trimester )
Complications
• Most complications are caused by P falciparum. One of them is cerebral malaria,
defined as coma, altered mental status, or multiple seizures with P falciparum in
the blood. Cerebral malaria is the most common cause of death in patients with
malaria. If untreated, this complication is lethal. Even with treatment, 15% of
children and 20% of adults who develop cerebral malaria die. The symptoms of
cerebral malaria are similar to those of toxic encephalopathy. Other
complications of P falciparum infection include the following:
• Seizures - Secondary to either hypoglycemia or cerebral malaria
• Renal failure - As many as 30% of nonimmune adults infected with P falciparum
suffer acute renal failure
• Hypoglycemia
• Hemoglobinuria (blackwater fever) - Blackwater fever is the passage of dark
urine, described as Madeira wine colored; hemolysis, hemoglobinemia, and the
subsequent hemoglobinuria and hemozoinuria cause this condition .
Complications

• Noncardiogenic pulmonary edema - This affliction is most

common in pregnant women and results in death in 80% of
patients
• Profound hypoglycemia - Hypoglycemia often occurs in young
children and pregnant women; it often is difficult to diagnose
because adrenergic signs are not always present and because
stupor already may have occurred in the patient
• Lactic acidosis - This occurs when the microvasculature
becomes clogged with P falciparum; if the venous lactate level
reaches 45 mg/dL, a poor prognosis is very likely
• Hemolysis resulting in severe anemia and jaundice
• Bleeding (coagulopathy)
Patient education

• Individuals traveling to malarial regions must be provided

with adequate information regarding prevention strategies, as
well as tailored and effective antiprotozoal medications.
Malaria prevention
• People planning to travel to an area with malaria should see
their physician before travel, preferably at least six weeks
before departure.
• Travelers should use mosquito repellent and barrier techniques
(long sleeves and long pants) to reduce the chance of mosquito
bites and take medications to reduce the risk of disease.
• Malaria in pregnancy is very serious and often life-threatening
to both the mother and fetus
• travel to areas where malaria is endemic should be discussed
with a health-care professional and avoided if at all possible
by women who are or may become pregnant.
Malaria Vaccine

• There is no malaria vaccine commercially available to prevent

malaria till now. However, the Centers for Disease Control is
conducting a vaccine trial with the Kenya Medical Research
Institute, and so far the vaccine has had promising results. If
the vaccine continues to perform well, the vaccine could
become available for use within the decade.
• The only malaria vaccine approved for use outside trials as of
2015 is RTS,S. It requires four injections, and has a relatively
low efficacy (26%-50%).
• Research continues into recombinant protein and attenuated
whole organism vaccine
Mortality

• Internationally, malaria is responsible for approximately 1-3

million deaths per year. Of these deaths, the overwhelming
majority are in children aged 5 years or younger, and 80-90%
of the deaths each year are in rural sub-Saharan Africa.
Malaria is the world’s fourth leading cause of death in children
younger than age 5 years.
• Malaria is preventable and treatable. However, the lack of
prevention and treatment due to poverty, war, and other
economic and social instabilities in endemic areas results in
millions of deaths each year.
Roll back malaria:
• By mid-1995 all malaria endemic countries in the region had adopted the
revised malaria control strategy to reduce morbidity and mortality and to
reduce its area of distribution particulars of multi-drug resistance malaria.
Vector resistance to insecticides has necessitated the use of more expensive
pyrethroid, thereby limiting the coverage. Malaria control added impetus
through Roll back Malaria initiative was launched by WHO, Unicef,
UNDP and world bank in 1998.
Roll back malaria
• The main strategies of these initiative are given below:
• Strengthen health system to ensure better delivery of health care,
especially at district and community level.
• Ensure the proper and expanded use of insecticide treated mosquito
nets.
• Ensure adequate access to basic health care and training of health care
workers.
• Encourage the development of simpler and more effective means of
administering medicines such as training of village health workers
and mothers on early and appropriate treatment of malaria, especially
in children.
• Encourage the development of more effective and new anti malaria
drugs and vaccine.