Malaria aicog 2013

JAIDEEP MALHOTRA M.D., F.I.C.O.G., F.I.C.M.C.H.

• Secretary Elect ICOG• Editor Journal SAFOMS• Treasurer IMS (2011 -14)• Executive member Asia Pacific Initiative in Reproductive endocrinology.• Editor ICOG Evidence• Sec UP Chapter ISAR• VICE PRESIDENT FOGSI 2010• Governing council member ISAR,ICOG ,IMS and IFUMB• Chairperson International Academic Exchange Committee FOGSI 2004-2008• Practicing I.V.F. specialist at Agra (Special Interest in Infertility, Laparoscopy, Ultrasound and Genetics)• Member and Fellow of many Indian & International organization • Indumati Zhaveri Award, Jagdeshwari Misra Award three times, Ethicon Fellowship, Outstanding Achievement Award

1999, Chorion Award• Over 50 published and 100 presented papers• Organised many workshops and travel seminars• Co-editor of step by step series of books• Co-editor of manual of operative Obs Gyn• Editor of “Fetus Our Other Patient” and “Step by Step ART”• Credited with producing firsts of U.P. : IVF birth, ICSI birth, IVF Twins, ICSI Twins, IVF Triplets,

TESA-ICSI Pregnancy etc.• Credited for producing first Test Tube Baby of Nepal• Awarded Corion Prize for best original research in “Improving endometrial receptivity and blood flows.”• Technical Advisor to MAMC Delhi and SMS Medical college Jaipur ART Units• Consultant IVF specialist at Ludhiana, Jalandhar, Ambala, Bhiwani, Gorakhpur, Gwalior, Allahabad ,Moga &

Kathmandu & Dhakka

Malaria and Pregnancy

Dr Jaideep MalhotraDr Narendra Malhotra

Malaria Menance

• World wide 107 countries with 2.5 billion people, developing countries worst affected.

• 40 % of world’s population in shadow of Malaria.• Of the 2.5 million reported cases in the South East Asia, India alone

contributes about 70% of the total cases.• Deaths- Under estimated/Unknown,1.1 to 2.7 million per year• 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.

Liver stage

Sporozoites

Mosquito Salivary Gland

Malaria Life Cycle

Gametocytes

Oocyst

Red Blood Cell Cycle

Zygote

Plasmodium falciparum

Plasmodium vivax

Plasmodium ovale

Plasmodium malariae

Why are Malaria and Pregnancy mutually aggravating?

• The physiological changes of pregnancy and the pathological changes due to malaria have a synergistic effect on the course of each other, thus making life difficult for the mother, the child and the treating physician.

• P. falciparum malaria can run a turbulent and dramatic course in pregnant women.

• The non- immune, primigravidae are usually the most affected.

• In areas where malaria is endemic, 20-40% of all babies born may have a low birth weight.

Malaria in Pregnancy :• More common.

– Malaria is more common in pregnancy compared to the general population probably due to Immuno suppression and loss of acquired immunity to malaria.

• More atypical.– In pregnancy, malaria tends to be more atypical in

presentation probably due to the hormonal , immunological and haematological changes of pregnancy.

• More severe.– Probably for the same reason, the parasitemia tends to be 10

times higher and as a result, all the complications of falciparum malaria are more common in pregnancy compared to the non-pregnant population.

Malaria in Pregnancy : • More fatal

– P. falciparum malaria in pregnancy being more severe, the mortality is also double (13 % ) compared to the non-pregnant population (6.5%).

• Selective treatment– Some anti malarials are contra indicated in pregnancy and some may

cause severe adverse effects. – Therefore the treatment may become difficult, particularly in cases of

severe P. falciparum malaria.• Other problems

– Management of complications of malaria may be difficult due to the various physiological changes of pregnancy.

– Careful attention has to be paid towards fluid management, temperature control, etc.

– Decisions regarding induction of labour may be difficult and complex. – Foetal loss, IUGR, and premature labour are common.

Turbulent Course in pregnancy

• Particularly the first and second pregnancies.• These complications are more common and severe

in hyperendemic areas for falciparum malaria. • Physiologic changes of pregnancy contribute to the

aggravation of malarial infection. – Changes in the hormonal milieu, – Increase in the body fluid volume,– Decrease in haemoglobin level and other changes add to

the severity.

Pathology of Malaria in Pregnancy

• There is a 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.

– This makes the pregnant woman more prone for malarial infection and the parasitemia tends to be much higher.

Changes 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 (complete or partial) have been observed.

• All the placental tissues exhibit malarial pigments (with or even without parasites).

11Malaria During Pregnancy

Placental Parasitemia by Pregnancy Number

0

5

10

15

20

25

30

First Pregnancies Second Pregnancies Three or morepregnancies

% p

aras

item

ic

1-999 1000-9,999 >10,000

Parasite density/mm3

772402 479

Source: van Eijk AM et al 2001.

Clinical features

• Fever : – Patient may have different patterns of fever - from

afebrile to continuous fever, low grade to hyper pyrexia. – In 2nd half of pregnancy, there may be more frequent

paroxysms due to Immunosuppression. • 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.

Atypical manifestations of malaria are more common in pregnancy, particularly in the 2nd half of pregnancy.

Clinical features

• Splenomegaly : – Enlargement of the spleen may be variable. It may be absent

or small in 2nd half of pregnancy. – A pre-existing enlarged spleen may regress in size in

pregnancy.

• 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 /

diarrhoea and other complications may be seen.

Atypical manifestations of malaria are more common in pregnancy, particularly in the 2nd half of pregnancy.

Effects on the Pregnant Woman

( +++ =Very Common, ++ =Common, + =Infrequent, -- =Rare)

EffectsPrimigravidae in Stable malaria

areas

All parities in Unstable malaria

areas

High fever

Placental infection

Puerperal sepsis

Complicated malaria

Severe anemia Cerebral malaria Hypoglycemia Pulmonary edema Acute renal failure

Increased maternal mortality

+

+++

++

+++

-

-

-

-

+

+++

+

++

+++

++

++

++

++

++

Complications of Malaria in Pregnancy

• 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.

Anemia


• 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.

Acute pulmonary oedema


• 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


• 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.

Hypoglycaemia


• Hypoglycaemia can be recurrent and therefore constant monitoring is needed.

• In some, it can be associated with lactic acidosis and in such cases mortality is very high.

• Maternal hypoglycemia can cause foetal distress without any signs.

Hypoglycaemia:


• Immunosuppression in pregnancy poses special problems.

• It makes malaria more common and more severe. And to add to the woes, malaria itself suppresses immune response.

• Hormonal changes of pregnancy, reduced synthesis of immunoglobulins, reduced function of reticulo endothelial system are the causes for Immunosuppression in pregnancy.

Immunosuppression


• This results in loss of acquired immunity to malaria, making the pregnant more prone for malaria.

• Malaria becomes more severe with higher parasitemia.

• Patient may have more frequent paroxysms of fever and frequent relapses.

• Secondary infections (U.T.I. and pneumonias) and algid malaria (septicaemic shock) are more common in pregnancy due to Immunosuppression.

Immunosuppression

Quite common Diagnosis can be difficult

Coma scoringExclude other causes of coma

Needs Intensive care1. ABC of coma care

2. Prompt institution of antimalarials3. Treatment of hyperpyrexia

4. Management of other complications

5. Treatment of associated infections

Cerebral malaria

Effects on the Fetus and Newborn

( +++=Very Common, ++=Common, +=Infrequent, -- =Rare)

EffectsPrimigravidae in Stable malaria

areas

All parities in Unstable malaria

areas

Low birth weight

IUGR Prematurity

Abortion Stillbirth Congenital malaria Fetal anemia Infant mortality

+++

+

-

-

-

?

+

+

++

++

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+

+

++

Risks for the foetus

• Malaria in pregnancy is detrimental to the foetus due to: - – high grades of fever, – placental insufficiency, – hypoglycaemia, – anaemia and other complications.

• Both P. vivax and P. falciparum malaria can pose problems for the foetus, with the latter being more serious.

Risks for the foetus• The prenatal and neonatal mortality may vary from 15 to

70%. – neonatal mortality due to P. vivax malaria during pregnancy

was 15.7% while that due to P. falciparum was 33%. – Spontaneous abortion,– pre mature birth,– still birth,– placental insufficiency– I.U.G.R. (temporary / chronic),– low birth weight,– foetal distress are the different problems observed in the

growing foetus.– Transplacental spread of the infection to the foetus can result in

congenital malaria.

Frequency of Low Birth Weight by Placental Malaria Infection

0

5

10

15

20

25

30

35

FirstPregnancy

SecondPregnancy

Three or morepregnancies

With placental parasites

Without placental parasites%

Lo

w B

irth

Wei

gh

t

Source: Steketee 2001.


• It is very rare and occurs in < 5% of affected pregnancies. Placental barrier and maternal Ig G antibodies which cross the placenta may protect the foetus to some extent.

• However, it is much more common in non-immune population and the incidence goes up during epidemics of malaria.

• Fetal plasma Quinine and Chloroquine levels are about one third of simultaneous maternal levels and this subtherapeutic drug level does not cure the infection in the foetus.

Congenital malaria


• All four species can cause congenital malaria, but it is proportionately more with P. malariae.

• The new born child can manifest with fever, irritability, feeding problems, hepato splenomegaly, anaemia, jaundice etc.

• The diagnosis can be confirmed by a smear for M.P. from cord blood or heel prick, anytime within a week after birth (or even later if post-partum, mosquito-borne infection is not likely).

• Differential diagnoses include Rh. incompatibility, infections with C.M.V., Herpes, Rubella, Toxoplasmosis, and syphilis.

Congenital malaria

Diagnosis• High level of awareness • Peripheral blood smear (Gold standard)

thick smear: rapid diagnosisthin : species identification

• other advantages- platelets, anaemia, toxic picture

If negative : repeat blood test 6 hourly for 6 times • Antigen detection techniques : (PfHPR-2) • Fluorescent staining • PCR based assay• Antibody test• Placental blood smear

Why parasites are not detected at times in peripheral smear ?

a. sequestration deep vascular bedb. partially treated patients

c. prophylactic antimalarial Tt d. inexperienced microscopist

e. poor quality staining

Antigen capture tests* Pf-ICT test

* Parasight-F test/ Malacheck etcPrinciple: dipstick antigen capture assay employs a monoclonal

antibody detecting the Pf.HRP-2 antigen in the bloodRapid, simple, sensitive testSpecies specificity

Antibody detection test- RIA

- ELISAantibodies persists for a long

time, so not helpful in acute infection

QBC testSpinning blood in a specialised capillary tubes in which

parasite DNA is stained with acridine orange.Detected by ultraviolet microscope

Sensitive and specific (?) in Experienced hands

PCR testSensitive can identify different species

Takes 48- 72 hoursExpensive

Available in selected places onlyDNA Probes

Indicators of Poor Prognosis

• Hyper parasitemia: - 5% erythrocytes infested.• Peripheral schizotaemia.• Leucocytosis 12,000/ cmm. • Hb 7.1 gm%.• PCV 20 %.• Blood urea 60 mg / dL• Creatinine 3 mg / dL.,• Blood glucose 40 mg / dL.• High lactate and low sugar in CSF. • Low antithrombin III level.

Management of Malaria in Pregnancy

• Management of malaria in pregnancy involves the following three aspects and equal importance should be attached to all the three. 1. Treatment of malaria 2. Management of complications 3. Management of labour

Energetic: • Don't waste any time. • It is better to admit all cases of P. falciparum

malaria. • Assess severity-

– General condition, pallor, jaundice, B.P., temperature, haemoglobin, Parasite count, S.G.P.T., S .bilirubin, S.creatinine, Blood sugar.

Treatment of Malaria in PregnancyShould Be Energetic, Anticipatory and Careful.

Anticipatory: • Malaria in pregnancy can cause sudden and

dramatic complications. Therefore, one should always be looking for any complications by regular monitoring.

• Monitor maternal and foetal vital parameters 2 hourly.

• R.B.S. 4-6 hourly; haemoglobin and parasite count 12 hourly; S. creatinine; S. bilirubin and Intake / Output chart daily.

Treatment of Malaria in Pregnancy

Should Be Energetic, Anticipatory and Careful.

Careful: • The physiologic changes of pregnancy pose special problems in

management of malaria. • In addition, certain drugs are contra indicated 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 contra indicated • Avoid over / under dosing of drugs • Avoid fluid overload / dehydration • Maintain adequate intake of calories.


Should Be Energetic, Anticipatory and Careful.

• All trimesters: – First line - Chloroquine; Quinine; – Second line - Artesunate / Artemether / Arteether

• 2nd / 3rd trimester: with caution– Pyrimethamine + sulphadoxine; Mefloquine

• Contra indicated: – Primaquine; Tetracycline; Doxycycline; Halofantrine

Choice of Anti malarials in pregnancy


• Chloroquine:– 600mg (base) start, 300mg after 6 hours, 24 hours & 48 hours

• 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

Dose of Anti malarials


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. 1x2x1+1x1x4 OR 1x2x3.– 80mg BD X3 days

• Arteether(Emal inj):– One amp (150mg) IM / day for3 consecutive days.

Dose of Anti malarials


Dose of Antimalarials

• Pyrimethamine 25mg+sulphadoxine 500mg tablets:– Three tablets single dose.

• Mefloquine:– 15mg / kg body wt., up to 1 Gm in a single dose. OR

• Tablets of 250mg, 3 tab start, then 2 tab after 6-8 hours. With body wt

>60kg, a third dose of 1 tab after 6-8 hours.

NIMR guidelines 2010

• ACT should be given for treatment of P. falciparum malaria in:

• second and third trimesters of pregnancy,• while quinine is recommended in the first trimester.• P. vivax malaria can be treated with chloroquine• ACT containing mefloquine should be avoided in

cerebral malaria due to neuropsychiatric complications.

General recommendations for the management of uncomplicated malaria

• Avoid starting treatment on an empty stomach.• The first dose should be given under observation.• Dose should be repeated if vomiting occurs within

30 minutes.• The patient should be asked to report back, if there

is no improvement after 48 hours or if the situation deteriorates.

• The patient should also be examined for concomitant illnesses.

SEVERE MALARIA

• Impaired consciousness/coma• Repeated generalized convulsions• Renal failure (Serum Creatinine >3 mg/dl)• Jaundice (Serum Bilirubin >3 mg/dl)• Severe anaemia (Hb <5 g/dl)• Pulmonary oedema/acute respiratory distress syndrome• Hypoglycaemia (Plasma Glucose <40 mg/dl)• Metabolic acidosis• Circulatory collapse/shock (Systolic BP <80 mm Hg, <50 mmHg in children)• Abnormal bleeding and Disseminated intravascular coagulation(DIC)• Haemoglobinuria• Hyperpyrexia (Temperature >106o F or >42o C)• Hyperparasitaemia (>5% parasitized RBCs )

Management of complications

• 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%.

• Renal failure: – Renal 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.

Management of complications

• Septicaemic shock: – Secondary bacterial infections like urinary tract infection, pneumonia etc.

are more common in pregnancy associated with malaria. – Some of these patients may develop septicaemic shock, the so called

'algid 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).

Management of Labour

• Anaemia, hypoglycaemia, pulmonary oedema, and secondary infections due to malaria in pregnancy lead to problems for both the mother and the foetus.

• Severe falciparum malaria in term pregnancy carries a very high mortality.

• Maternal and foetal distress may go unrecognised in these patients.

• Therefore, careful monitoring of maternal and foetal parameters is extremely important.

• Pregnant women with severe malaria are better managed in an intensive care unit.

Management of Labour• Falciparum malaria induces uterine contractions, resulting in

premature labour. The frequency and intensity of contractions appear to be related to the height of the fever.

• Fetal distress is common and often unrecognised. Therefore only monitoring of uterine contractions and fetal heart rate may reveal asymptomatic labour and foetal distress.

• All efforts should be made to rapidly bring the temperature under control,– By tepid sponging (cold sponging causes cutaneous vasoconstriction

and can result in core hyperpyrexia).– Anti pyretics like paracetamol etc.

Management of Labour

• Careful fluid management is also very important. Dehydration as well as fluid overload should be avoided, because both could be detrimental to the mother and/or the foetus.

• In cases of very high parasitemia, exchange transfusion may have to be carried out.

• If the situation demands, induction of labour may have to be considered.

• Once the patient is in labour, foetal or matenal distress may indicate the need to shorten the 2nd stage by forceps or vacuum extraction.

• If needed, even caesarean section must be considered.

Treatment of Vivax Malaria in Pregnancy

• Use of Primaquine & Proguanil are not safe in pregnancy and also in lactating mothers.

• Therefore to prevent the relapse of vivax malaria, suppressive chemoprophylaxis with Chloroquine is recommended.

• Tablet Chloroquine 300 mg (base) weekly should be administered to all such patients until stoppage of lactation.

• At that point, a complete treatment with full therapeutic dose of Chloroquine and Primaquine (7.5mg b.I.d. or 15mg daily, for 14 days) should be administered.

• However in case of resistance, Primaquine or Proguanil may be given with caution in 2nd half of pregnancy.

Radical cure

TREATMENT OF MIXED PLASMODIUM INFECTIONS

• In patients with confirmed or suspected mixed infections i.e. P. falciparum with either P. vivax or P. ovale, the standard therapy for uncomplicated or severe P. falciparum malaria (either quinine or artemether-lumefantrine) plus a follow-up course of primaquine is recommended.

• A mixed infection of P. falciparum and P. malariae should be managed as for P. falciparum malaria. The severity of the P. falciparum infection should dictate choice of initial therapy. Doubt frequently exists about the presence of P. falciparum in addition to other Plasmodium species.

• The patient should then be treated for P. falciparum, as this is the species most frequently associated with severe infections and complications.

COMMON ERRORS IN MANAGEMENT OFSEVERE MALARIA

1. Failure to diagnose associated complications such as bacterialinfections, eclampsia, Gram negative septicemia etc

2. Missed hypoglycaemia

3. Misjudgement of severity

4. Errors of fluid and electrolytic replacement

5. Errors in anti-malarial chemotherapy

6. Delay in starting treatment Unjustified withholding of antimalarial drug for the fear of toxicity e.g. Quinine in pregnant women, in hypoglycaemia-Inadequate dosage administration-Failure to control the rate of IV infusion

7. Delay in considering obstetrics intervention pregnant women suffering from malaria

8. Missed / late diagnosis of ARDS, acute pulmonary oedema

9. Use of inappropriate ancillary therapies e.g. steroids

10. Delay in starting dialysis

Components of Malaria Control During Pregnancy

1.Quality focused antenatal care and health education

2.Intermittent preventive treatment (IPT)3.Use of insecticide-treated nets (ITNs)4.Case management of malaria disease

Health Education on Malaria During Pregnancy: What To Tell Patients

• Pregnant women (especially primigravida, secundigravida and HIV-infected women) are at higher risk of malaria

• Malaria:– Is transmitted through mosquito bites– Can cause severe anemia, with adverse consequences for mother

and baby– Can cause abortions, stillbirths and result in low birth weight

newborns– Can be prevented through the use of IPT and ITNs during

pregnancy– Can be easily treated if recognized early but complicated malaria

requires specialized treatment

Use of Insecticide-Treated Nets (ITNs)

ITNs:• Have been shown to result in reduction of

newborns born with low birth weight or prematurely

• Reduce transmission by physically preventing vector mosquitoes from landing on sleeping persons

• Repel and kill mosquitoes that come in contact with the net

• Kill other insects like cockroaches, lice, ticks and bed bugs

• Should be used by pregnant women as early during pregnancy as possible and use should be encouraged throughout pregnancy and in the postpartum period

58

Impact of ITNs on Maternal and Newborn Health

Among Gravidae 1-4, ITNs were associated with:• During pregnancy

– 38% reduction in peripheral parasitemia– 21% reduction in all causes of anemia (Hb < 11 g/dl)– 47% reduction in severe malarial anemia

• At delivery– 23% reduction in placental malaria– 28% reduction in LBW– 25% reduction in any adverse birth outcome

• No trend towards decreasing efficacy with increasing transmission rate

Source: Shulman 2001.

Intermittent Preventive Treatment (IPT)

• An approach for effectively preventing and controlling malaria during pregnancy

• 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

Chemoprophylaxis in 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 malarious 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. – However, its use may be restricted due to the wide spread resistance

to this drug. – 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.

Malaria During Pregnancy 61

Conception Birth20 3010

Weeks of gestation16

Fetal Growth Velocity

Fetal growth velocity

Source: WHO 2002.

Last month




Fetal Growth Velocity


Quickening

Source: WHO 2002.

Last month




Rationale for the Timing of the Doses


Quickening

Source: WHO 2002.

Last month

RxRx

64

Key Issues About Timing of Doses

• SP should be avoided during the first 16 weeks of pregnancy which is the period of initial development of the fetus

• It is best to clear the placenta of parasites during the period of maximum fetal growth

• IPT allows the mother to recover from anemia by clearing peripheral parasitaemia

Chemoprophylaxis in Pregnancy

• 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.

DOSAGE

Effect of Intermittent Preventive Treatment with SP

Case management

Two-doseSP

MonthlySP p

N=472 N=432 N=431

Mean Hb. 9.9 10.2 10.4 < 0.05

Maternal parasitemia

27% 9% 7% 0.004

Placental parasitemia

27% 12% 9% < 0.001

LBW 14% 8% 8% 0.01

Source: Steketee 2001.

Case Management: Drug Efficacy

• Effective drugs are needed for P. falciparum malaria as it can be fatal to both mother and child

• Drug of choice depends on the geographic drug resistance profile:– Chloroquine is the drug of choice in few areas where it

is still effective– SP often next choice – Quinine is the drug of choice for complicated malaria

Resistance to Drugs

• Resistance of P. falciparum to antimalarial drugs is an ever increasing problem

• To minimize the problem of drug resistance, encourage women to complete their course of antimalarial drugs, even when they feel better

• Drug resistance is inevitable;• WHO recommends these combinations,incase of drug resistance.• Artemether–lumefantrine,• Artesunate– amodiaquine,• Artesunate–mefloquine, • Artesunate–sulfadoxine–pyrimethamine, area dependent• Dihydroartemisinin–piperaquine.

Drugs That Should Not Be Used During 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

the fetus, in animals

Conclusions

• Widely prevalent 36% population exposed• Preventing mosquito bite • Chemoprophylaxis• Drug resistance is a problem.• Energetic anticipatory management • Maternal and neonatal morbidity and

mortality high.

Health & Medicine

Malaria aicog 2013