EPIDEMIOLOGY • 40 % of world’s population affected by Malaria. (WHO) • Of the 2.5 million reported cases in the South East Asia, India alone contributes about 70% of the total cases. • >25million woman are at risk of malaria(WHO) • Maiaria is 2nd most common cause of infectious death after T.B. • Deaths- Under estimated/Unknown,1.1 to 2.7 million per year • India most affected area are UP,Bihar,Karnataka,Rajasthan MP • Gender related mortality - Females more
Transcript
EPIDEMIOLOGY
• 40 % of world’s population affected by Malaria.(WHO)
• Of the 2.5 million reported cases in the South East Asia, India alone contributes about 70% of the total cases.
• >25million woman are at risk of malaria(WHO)• Maiaria is 2nd most common cause of infectious
death after T.B.• Deaths- Under estimated/Unknown,1.1 to 2.7 million
per year• India most affected area are
UP,Bihar,Karnataka,Rajasthan MP• Gender related mortality - Females more
Malaria in Pregnancy:
•Mutually aggravating •Mortality is double•Primigravidae - 60-70%•Highest prevalence in second half. •Plasmodium Falciparum – More common
Gravidity and malaria
• Primigravida have no pre-existing immunity to placental parasites and are highly susceptible.
• In high transmission areas, primigravida develop immunity to placental parasites and are protected in subsequent pregnancies.
• In low transmission areas, multigravida are unexposed and unprotected
CAUSATIVE ORGANISM
• Malaria vector borne disease caused by protozoan plasmodium
1.P.falciparum(most dangerous account for 90%death d/t malaria)
2.P.vivax(most widely spread species)3.P.malariae4.P.ovale5.P.knowlesi(malaria in macaques but can
infect human)
• Malaria transmitted by mosquito female Anopheles
1.Bite of infected mosquito
2.Congenital infection
3.Blood transfusion
4.Contaminated needle
5.Organ transplantation
SOME FACTS ABOUT ANOPHELES
They choose their victim by odor. Males are more frequently bitten. Most common time of bite is late evening to early
morning with peak at midnight. Stylets cut & proboscis probe for tiny blood vessels in
the skin. If it does not strike blood proboscis is withdrawn and struck again at different angle.
They can fly for few Km. Their life span is 2–3 weeks. Human blood is needed to lay eggs and nourish eggs.
LIFE CYCLE OF PLASMODIUM
• Human - intermediate host(asexual cycle)• Mosquito-definitive host(sexual cycle)• Infective form for human-sporozoite(in
salivary gland of mosquito)
• P.vivax affect young RBC
• P.falciparum- all stages RBC
• P.malariae-old RBC
Malaria in Pregnancy : Double Trouble• Malaria is more common in pregnancy
compared to the general population.
• Malaria in pregnancy tends to be more atypical in presentation. This could be due to the hormonal, immunological and hematological changes of pregnancy.
• The parasiteamia tends to be 10 times higher.• P. falciparum malaria in pregnancy being
more severe, the mortality is also double (13 %) compared to the non-pregnant population (6.5%).
• During normal pregnancy, the cellular immune response (Th1) is suppressed to prevent fetal rejection.
• Malaria stimulates the Th1 response intrauterine growth retardation.
• Malaria stimulates expression of an HIV co-receptor (CCR5) in the placenta.
• Generalised immunosuppression in pregnancy with reduction in gamma globulin synthesis and inhibition of reticulo endothelial system, resulting in– Decrease in the levels of anti malarial antibodies and
loss of acquired immunity to malaria. -more prone for malarial infection and the parasitemia
tends to be much higher.
Change in placenta
• Placenta is the preferred site of sequestration and development of malarial parasite.
• Intervillous spaces are filled with parasites and macrophages, interfering with oxygen and nutrient transport to the foetus.
• Villous hypertrophy and fibrinoid necrosis of villi
• All the placental tissues exhibit malarial pigments
TYPES OF MALARIA
1.UNCOMPLICATED
2.COMPLICATED
CLINICAL FEATURESFEVER• Stage 1-Cold stage• Chills for 15 mt to 1 hour• Caused due to rupture from the host red cells escape
into Blood• Preset with nausea, vomitting,headache
– Stage 2-Hot stage• Fever may reach upto 400c may last for several hours
starts invading newer red cells.• Stage 3-Sweating stage Patent starts sweating, concludes the episode. Cycles are frequently Asynchronous Paroxysms occur every 48 – 72 hours In P.malariae pyrexia may last for 8 hours or more and
temperature my exceed 410C
• Interval between fever
• 48hrs -Malaria tertiana (P.vivax,P.ovale)
• 72hrs -Malaria quartiana(P.malariae)
• Irregular high grade fever(P.falciparum)
• Anemia : – In developing countries, where malaria is most
common, anemia is a common feature of pregnancy. – Malnutrition and helminthiasis are the commonest
causes of anemia. – In such a situation, malaria will compound the
problem. » Anemia may even be the presenting feature
of malaria and therefore all cases of anemia should be tested for M.P.
– Anemia as a presenting feature is more common in partially immune multigravidae living in hyper endemic areas.
ANAEMIA
• Malaria can cause or aggravate anaemia due to: – Hemolysis of parasitised red blood cells.
– Increased demands of pregnancy.
– Profound hemolysis can aggravate folate deficiency.
• Anemia due to malaria is more common and severe between 16-29 weeks.
• It can develop suddenly, in case of severe malaria with high grades of parasitemia.
• Pre existing iron and folate deficiency can exacerbate the anemia of
malaria and vice versa.
• Splenomegaly : – Enlargement of the spleen may be variable.
• Complications : – Complications tend to be more common and more severe in
pregnancy. – A patient may present with complications of malaria or they may
develop suddenly. – Acute pulmonary edema,– hypoglycemia – anemia are more common in pregnancy. – Jaundice, convulsions, altered sensorium, coma, vomiting /
autotransfusion &increased peripheral vascular resistance)• Fluid and electrolyte imbalance• Cerebral malaria• Circulatory collapse• Black water fever
ACUTE PULMONARY EDEMA
• Acute pulmonary oedema is also a more common complication of malaria in pregnancy compared to the non-pregnant population.
• It may be the presenting feature or can develop suddenly after several days. It is more common in 2nd and 3rd trimesters.
• It can develop suddenly in immediate post-partum period. This is due to – Auto transfusion of placental blood with high proportion of
parasitised RBC’s – Sudden increase in peripheral vascular resistance after delivery.
• It is aggravated by pre existing anaemia and hemodynamic changes of pregnancy.
• Acute pulmonary oedema carries a very high mortality.
HYPOGLYCEMIA
• This is another complication of malaria that is
peculiarly more common in pregnancy.
• The following factors contribute to hypoglycemia:
– Increased demands of hypercatabolic state and
infecting parasites.
– Hypoglycaemic response to starvation.
– Increased response of pancreatic islets to secretory
stimuli (like quinine) leads to hyperinsulinemia and
hypoglycemia..
• Hypoglycaemia in these patients can remain asymptomatic and may not be detected, because: – all the symptoms of hypoglycemia are also caused by
malaria viz. tachycardia, sweating, giddiness etc. – Some patients may have abnormal behaviour,
convulsions, altered sensorium, sudden loss of consciousness etc.
– These symptoms of hypoglycemia may be easily confused with cerebral malaria.
– Therefore, in all pregnant women with falciparum malaria, particularly those receiving quinine, blood sugar should be monitored every 4-6 hours.
CEREBRAL MALARIA
Needs Intensive care1. ABC of coma care2. Prompt institution of antimalarials3. Treatment of hyperpyrexia4. Management of other complications
5. Treatment of associated infections
Effect of malaria on foetus
Malaria in pregnancy detrimental to foetus due to-
a.high grade fever
b.placental insufficiency
c.hypoglycemia
d.anaemia
• There is interesting fact that primigravidas may develop more clinical symptoms of malaria, woman with higher immunity may not demonstrate sympt. but they may have more placental burden so more fetal complications
Resulting in-
• Spontaneous abortion
• Premature birth
• I.U.G.R.
• Still birth
• Low birth weight
• Congenital malaria<5%(b/c of protection by maternal IgG) more with P.malariae
• Currently available rapid diagnotic tests are as follows-• Histidine rich protein two (HRP 2) – asexual stages &
young gametocyte of Pfalciparum• Parasite lactate dehydrogenas – for all 4 types• Plasmodium aldolase – for all four types
sample collection-any time irrespective to fever but before administration of antimalarial drugs
Advantage:-• can diagnose 5-
10parasites/ml• identificatin of species
&stage of parasite
• parasite density• malarial pigment in
neutrophils &monocyte
• Disadvantage:-• time consuming• skilled technician• in mixed infection one
species suppress
THICK AND THIN SMEAR
• parasites are not detected at times in peripheral smear :-a. sequestration deep vascular bedb. partially treated patientsc. prophylactic antimalarial t/td. inexperienced techniciane. poor quality staining
RAPID DIAGNOSTIC TEST
Currently available rapid diagnotic tests are as follows-Histidine rich protein two (HRP 2) – asexual stages & young gametocyte of
PfalciparumParasite lactate dehydrogenas – for all 4 typesPlasmodium aldolase – for all four types
WHO- A MINIMUM STANDARD OF 95% SENSITIVITY FOR P.FALCIPARUM DENSITIES OF 100 PARASITES/L OF BLOOD AND A SPECIFICITY OF 95%
HRP-II with parasite density 100/ml of blood -90% - with 10/ml -75%
HRP-II remain positive for 1-3wk.p LDH remain positive for 5 days.
Antigen detection tests
Principle: dipstick antigen capture assay employs a monoclonal antibody detecting the Pf.HRP-2 antigen in the bloodRapid, simple, sensitive testSpecies specificity
Optimal Assay
ControlPlasmodium pan specific
monoclonal antibody
P. falciparum specific
monoclonal antibody
Antibody detection (not for acute infection)
a.RIA
b.ELISA
=
Antigen-antibodycomplex
Patient’s serumcontains specificand non-specific
antibodies
+
Antigen
QBC TEST
Spinning blood in a specialised capillary tubes in which parasite DNA is stained with acridine orange.Detected by ultraviolet microscope
PCR TEST:-
SENSITIVE CAN IDENTIFY DIFFERENT SPECIES
WITHin 48-72 hrs but expensive
Diagnosis of
• untreated acute malaria -blood smear
• Chronic malaria-serology
- blood smear
-PCR
Treated recent malaria-serology
-blood smear
MANAGEMENT
Management of malaria in pregnancy involves the following three aspects and equal importance should be attached to all the three.
• Treatment of malaria• Management of complications• Management of labour
TREATMENT OF MALARIA
• Treatment of malaria in pregnancy should be energetic, anticipatory and careful.
• Energetic:• Don't waste any time.• It is better to admit all cases of P. falciparum malaria.• Assess severity- General condition, pallor, jaundice, BP,
temperature, hemoglobin, Parasite count, SGPT, S. bilirubin, S. creatinine, Blood sugar.
• Anticipatory:• one should always be looking for any complications by regular
monitoring.• Monitor maternal and fetal vital parameters 2 hourly.• RBS 4-6 hourly; hemoglobin and parasite count 12 hourly; S.
creatinine; S. bilirubin and Intake / Output chart daily.
• Careful:
• The physiologic changes of pregnancy pose special problems in management of malaria.
• Certain drugs are contraindicated in pregnancy or may cause more severe adverse effects. All these factors should be taken into consideration while treating these patients.
• Choose drugs according to severity of the disease/ sensitivity pattern in the locality.
• Avoid drugs that are contraindicated.• Avoid over / under dosing of drugs• Avoid fluid overload / dehydration• Maintain adequate intake of calories.
MANAGEMENT OF MALARIA IN PREGNANCY
• Treatment depends on -
a.severity of disease
b.getational age
• WHO recommended -in endemic area t/t should started within 24hrs after 1st symptom.
a.uncomplicated malaria -OPD basis t/t
b.complicated malaria-Hospitalisation
• DOC in pregnancy(WHO)a. All trimester
1st line- chloroquine,quinine 2nd line -artesunate,artemether.arteetherb.2nd &3rd trimester pyrimethamine+sulphadoxine,mefloquine
NIMR GUIDLINE 2010• Quinine in 1st trimester• chloroquine for P.vivax• ACT for t/t of P.falciparum in 2nd &3rd trimester• ACT containing mefloquine should avoided in cerebral
malaria d/t neuropsychiatric complication
Drugs contraindicated in pregnancy
• Tetracycline– Cause abnormalities of skeletal and muscular growth, tooth
development, lens/cornea• Doxycycline
– Risk of cosmetic staining of primary teeth is undetermined – Excreted into breast milk
• Primaquine– Harmful to newborns who are relatively Glucose-6-Phosphatase-
Dehydrogenase (G6PD) deficient• Halofantrine
– No conclusive studies in pregnant women– Has been shown to cause unwanted effects, including death of
• Quinine:– IV - 20mg/kg infusion over 4 hours, repeat 8 hourly.– Maintenance: 10mg over 4 hours, 8 hourly.
Follow with oral medication after clinically stable.
• Oral – 600mg 8hourly ( maximum 2 gm / day) for 7 days. • Presently fixed dose combinations of
• Artesunate + amodiaquine
• Blister pack of artesunate +mefloquine
Artemisinin compounds(rapid Schizonticidal)
• Artesunate(Falcigo):– Oral-100mg BD on day 1, then 50mg BD for 4-6 days (Total
dose 10mg/kg).– IM / IV-120mg on Day 1 followed by 60mg daily for 4 days. In
severe cases an additional dose of 60mg after 6 hours on Day 1.
• Artemether(Larither):– Six amp (480mg) IM in 5 / 3 days
– 80mg BD X3 days
• Arteether(Emal inj):– One amp (150mg) IM / day for3 consecutive days.
UNCOMPLICATED MALARIA• Oral quinine 600mg 8hrly for 7days OR• Chloroquine 10mg/kg f/b 10mg/kg at 24 hrs & 5mg/kg at 48 hrs
• Avoid starting t/t on empty stomach• 1st dose given under observation• repeat dose if vomitting within 30min• ask to report back if no improvement/deteriorate
COMPLICATED MALARIA
• Signs of uncomplicated malaria, plus:• Dizziness• Breathlessness• Sleepy/drowsy• Confusion/coma• Sometimes fits, jaundice, severe dehydration
COMPLICATED MALARIA
• Artesunate i.v. 2.4mg/kg at 0,12,24hrs f/b daily when pt able to take orally artesunate2mg/kg daily for 7days
• Quinine i.v.20mg/kg in D5% over 4hrs f/b 10mg/kg over 4hrs 8hrly (max dose of quinine 1.4gm) when pt able to take orallly quinine 600mg tds for 7 days
DRUG RESISTANCE
• Resistance of P. falciparum to antimalarial drugs is an ever increasing problem
• WHO recommends these combinations,incase of drug resistance.
• Artemether–lumefantrine,• Artesunate– amodiaquine,• Artesunate–mefloquine, • Artesunate–sulfadoxine–pyrimethamine, area dependent• Dihydroartemisinin–piperaquine.
VIVAX MALARIA
• Chloroquine sensitivechloroquine base 10mg/kg OD for 2 days f/b
5mg/kg on day 3• Chloroquine resistant Quinine salt 10mg/kg BD for 7daysorMefloquine 15mg/kg single doseor Artesunate 4mg/kg in divided loading dose
f/b 2mg/kg OD for 6 days
FALCIPARUM MALARIA
• Chloroquine sensitive Chloroquine base 10mg/kg OD for 2days f/b 5mg/kg on
day 3• Chloroquine Resisantsulfadoxine(500mg)/pyrimethamine(25mg) 3tab single doseorQuinine salt 10mg/kg TDS for 7daysorquinine salt 10mg/kg TDS for 3 days+
sulfadoxine/pyrimethamine 3 tab single dose on 1st day
MANAGEMENT OF COMLICATION OF MALARIA • Acute Pulmonary Oedema:
– Careful fluid management; back rest; oxygen; diuretics; ventilation if needed.• Hypoglycaemia:
– 25-50% Dextrose, 50-100 ml I.V., followed by 10% dextrose continuous infusion. – If fluid overload is a problem, then Inj. Glucagon 0.5-1 mg can be given intra
muscularly. – Blood sugar should be monitored every 4-6 hours for recurrent hypoglycemia.
• Anemia: – Packed cells should be transfused if haemoglobin is <5 g%.
• Rnal failure: • Reenal failure could be pre-renal due to unrecognised dehydration or renal due to severe
parasitemia. – Treatment involves careful fluid management, diuretics, and dialysis if needed.
etc. are more common in pregnancy associated with malaria. . – Treatment involves administration of 3rd generation cephalosporins,
fluid replacement, monitoring of vital parameters and intake and output.• Exchange transfusion:
– Exchange transfusion is indicated in cases of severe falciparum malaria to reduce the parasite load.
– It is especially useful in cases of very high parasitemia (helps in clearing) and impending pulmonary oedema (helps to reduce fluid load).
• Radical Cure:-
for prevention of relapse of P.vivax
Tab chloroquine 300mg/wk untill stoppage of lactation,complete therapeutic t/t given at that time chloroquine & primaquine given for 14 days
• Mixed infection :-
std therapy for uncomplicated/complicated malaria f/b course of primaquine
DURING LABOUR
• Careful monitoring of maternal &fetal parameters because fetal distress common and remained unrecognised
• All efforts should made to bring temp. under control by cold sponging,antipyretics
MALARIA CONTROL DURING PREGNANCY
• Antenatal care & health education
• Intermittent preventive treatment
• Use of insecticide treated net
• case management of malarial disease
Intermittent preventive treatment
INTERMITTENT PRESUMTIVE TREATMENT• Based on an assumption that every pregnant woman in
a malaria-endemic area is infected with malaria• Recommends that every pregnant women receive at
least two treatment doses of an effective antimalarial drug
• Sulfadoxine-pyrimethamine (SP) currently considered the most effective drug for IPT
sp should avoid during first 16weeks
Doses for IPT
• Chloroquine: - 300mg base, administered once every week.
• Pyrimethamine-25mg + Sulphadoxine-500mg: - One tablet once weekly.
• Mefloquine: -250mg weekly.– Dose may have to be increased in the last trimester,
in view of the accelerated clearance of the drug.
• Proguanil: - 150-200mg / day.
Chemoprophylaxis during pregnancy
• Malaria being potentially fatal to both the mother and the foetus, this should be an important part of antenatal care in areas of high transmission. – All pregnant women, who remain in the malarial endemic area :
during their pregnancy, should be protected with chemoprophylaxis.
• Choice of anti malarials for chemo prophylaxis– Chloroquine being the safest drug in pregnancy, should be the
first choice – In areas with known resistance to Chloroquine
• Pyrimethamine + Sulpha, Mefloquine or Proguanil can be used.
• But these drugs should be started only after 1st trimester only.
Doses for chemoprophylaxis
• Chloroquine: - 300mg base, administered once every week.
• Pyrimethamine-25mg + Sulphadoxine-500mg: - One tablet once weekly.
• Mefloquine: -250mg weekly.– Dose may have to be increased in the last trimester,
in view of the accelerated clearance of the drug.
• Proguanil: - 150-200mg / day.
VACCINE
• Malaria vaccines in development.• No licensed vaccine against malaria
currently exists• The parasite has evolved a series of
strategies that allow it to confuse, hide, and misdirect the human immune system.
• The parasite changes through several life stages even while in the human host, presenting a different subset of molecules for the immune system to combat at each stage.
