Lesson 22- Malarialll disease. Very good notes to start with

Take care of loved ones with AFYAPASS! Get health insurance that is accepted at more than 300 hospitals countrywide. Prices start at just Tsh 70,000 per year per person. Buy medical insurance through your M-Pesa App and receive your membership number instantly. Open your M-Pesa App> Services> VodaBima>AFYAPASS

1. THE CATHOLIC UNIVERSITY
OF HEALTH AND ALLIED HEALTH SCIENCES
WEILL BUGANDO SCHOOL OF MEDICINE

DEPARTMENT OF INTERNAL MEDICINE
MD300 - 2013/2014

Prof. Kataraihya JB

2. MALARIA

3. OVERVIEW
•Mal – Aria - Bad air!
•A disease of the blood by the protozoa of
the genus Plasmodium.
•Transmitted by a female mosquito
Genus Anopheles.
•One of the Worlds most common and
serious tropical diseases.

4. 4-Plasmodium species are capable of
infecting man.

P. vivax. ( India, central and south America)

P. falciparum- most deadly and Worldwide

P. ovale- rare outside Africa.

P. malariae- Worldwide- but less common.

5. Transmission

•Mosquito bites;
Female mosquitoes- Anopheles. needs
blood for reproduction.
Others;
• - blood transfusion.
• -congenital malaria.
• -I/V drug abusers.

6. Life cycle of Plasmodium spp.
Mosquitor;
•Take Gametocytes- from man.
•Gametocytes --- fuse into Sporozoites ( in mosq.
Guts sexual cycle).
Man;
•Mosquitor – injects Sporozoites- blood.
•Sporozoites- enter Liver.
•(asexual reproduction-exo- erythrocytic cycle)—
produce Merozoites.
Hypnozoites- dormant stage- P.vivax and P. ovale.

P.Malariae – may remain asymptomatic for years
or even for life.

7. •Merozoites- invade RBCs
(asexual cycle- erythrocytic)

•produce Schizonts.

•Schizonts – rupture to release
More Merozoites into the blood-(fever).

8. •In Rbcs –some Merozoites develop in male
and female Gametocytes.

•Gametocytes. -Wait for the next
mosquito bites.

9. GLOBAL BURDEN OF MALARIA
2010/2011 WHO report.
- Endemic in 106 countries.
- Estimates around 3.3 billion people were at
risk of acquiring Malaria.
- 216 million developed clinical Malaria.
- Resulted in 655,000 deaths.
-91% of the deaths occurred in Africa.
- Has become a global threat due to wide
spread drug resistance.
- Residents of non-endemic areas also at risk.
(Travel malaria – high mortality)

10. MALARIA IN CHILDREN

-A child dies every five seconds from
malaria in Africa.

-71% of deaths occur in children under
five years of age.
-Congenital malaria is increasingly
reported.

11. MALARIA IN TANZANIA
1. A Major Health challenge.

2. Commonest cause of OPD attendances.

3. Contributes 25% of hospital child mortality,
100,000 deaths per annum.

4. Under fives and pregnant mothers most
affected groups.
5. Exerts heavy economic burden to all levels
of society.
6. The poorest section of population most
burdened.

12. CLINICAL FEATURES;
None specific.
Fever – only reliable sign.
Severity depends on

•Type of plasmodium species.
•Individuals body immunity.

General symptoms,7-21 days following an infection.
Ranges – Asymptomatic, moderate symptoms to severe malaria.
•FEVER
•HEADACHE.
•NAUSEA
•VOMITTING
•FLUE LIKE SYMPTOMS
•BODY PAINS.
•Symptoms appear and disappear- in a cyclic manner.

13. SEVERE MALARIA;
WHO GETS IT?
None Immune
•Under fives- loss of maternal immunity.
•Pregnant women- Pregnancy suppresses body
immunity.
•Travelers from none endemic areas to malarious
areas.
•HIV/AIDS Patients.

14. HIV/AIDS AND MALARIA

• Increases frequency and severity of malaria.

• Malaria enhances progression of HIV to
AIDS.
• Acute Malaria episodes temporarily increases viral
replication- ↑Viral load.
•Pts with HIV/AIDS more likely to have symptoms and
higher parasite density.

15. Malaria in Pregnancy.
•Pregnancy lowers immunity to malaria.

•Pregnant mothers at risk of severe malaria –
esp. prime gravide.


•Can result into; low birth wt, still birth,
abortions, or maternal death.

16. Tropical Spleenomegally Syndrome;
•Massive spleenomegally in adults in a malarial
hyperendemic areas.
•Associated with high Ab titres to malaria and low
parasitaemias.
• F >M, with racial and familial predisposition.
•Due to exaggerated immune response to malaria
with over production of IgM.
•The Abs are phagocytosed by R.E.S cells ( spleen
and liver)
Hence confirmation is by liver biopsy.
•on microscopy- sinusoidal lymphocytosis.
•Immunofluorescence of IgM aggregates.
Anaemia, lymphocytosis and portal hypertension may
occur.

17. DIAGNOSIS OF MALARIA;
1.Clinical;
•Unreliable. ! Other causes of fever( the only reliable
symptom) – viral, bacterial, etc.

2.Laboratory;

(i). MICROSCOPY.
Thick film-sensitive.
Thin smear – species identification.
•Problems; Requires a trained Technician and
equipments ( microscopy).
•P. falciparum can be scanty in partially treated.

18. (ii). Malaria Rapid Diagnostic Tests (MRDTS).

Malaria RDTs detect specific antigens (proteins)
produced by malaria parasites, which are
present in the blood of infected or recently infected
individuals.
RDTs are lateral flow “Immuno-chromatographic”
antigen –detection tests, which rely on the capture
of dye-labeled antibodies to produce a visible band
on a strip of nitro-cellulose.

19. Types;
The three main groups of antigens detected by
commercially available RDTs are:

1. Histamine - rich protein 2 (HRP2)

2.Plasmodium lactate dehydrogenase (pLDH)

3. Aldolase.

20. Target antigens of commercially-available malaria rapid
diagnostic tests:


HRP11 pLDH Aldolase
P.
Falciparum -
specific
+ +
Pan specific
(all species)
+ +
P. Vivax
specific
+

21. Advantages:
No need for laboratory facilities
Simplicity and rapidity of the tests.
No need for electricity or laboratory equipment.
Minimal requirement for training (basic skills acquired in 1
day).
Acceptable levels of sensitivity and specificity, and
Feedback of conditions of use can be provided to
manufactures.
Disadvantages:
More expensive than microscopy.
Limitations in species identification, and
Persistent positively of HRP2 tests after effective treatment

Other tests are done as necessary ( cf severe malaria)

22. TREATMENT OF MALARIA;
HISTORY;
•CHQ RESISTANCE IN TANZANIA;
chq dose.
Early 1950s - 2.5mg/kg.
1960 - 10/kg.
1970 - 20 - 25mg/kg
Early 1980s - Resistance reports
Late 1990s High resistance up70%.
(National average 52%)
1999 – Decision to change to S/P as INTERIM Policy
Augost 2001- Change Implementation.
•2006- Changed to Artemisinin based Combination therapy
(CT)

23. TREATMENT
(1) NON COMPLICATED MALARIA
AVAILLABLE OPTIONS

1.“COMBINATION THERAPY”( CT )
DEFINITION OF CT

Simultaneous use of two or more blood
Schizontocidal drugs with independent
mode of action and different biochemical
targets in the malaria parasite.

24. •ADVANTAGES OF CT

• Improved efficacy/Effectiveness.

• Protection of component Drugs and increasing
the useful half life.

•Artemisinin containing CTs may reduce
transmission

25. ARTEMISININ BASED CTs; (ACT);

Advantages of Artemisinin component;

• Rapid reduction of parasite biomass.
Rapid resolution of clinical Symptoms.

•Effective vs multidrug –resistant P. falciparum.

•Action on Gametocytes, hence reduction of
transmission of resistant alleles.

26. •1ST Line;
•Artemether + Lumefantrine (CoartemTM,
Novartis) -ALU
• Available as a co-formulated compound
 good compliance.
Effective (esp. the 6 dose regimen )
Well tolerated.
No adverse reaction ( No Cardio toxicity).

27. •Formulation;
•fixed formulation of -Artemether (20mg)+
Lumefantrine (120mg).- commonest.

•Dosage 1.5/12mg/kg twice daily for 3days.

•Adults; 4tabs twice daily for 3 days.

•Best if taken with a fat meal.
•Second dose at 8hrs.

•2nd Line; Quinine;
•Non response to Quinine; IM Artemether or i/v
artesunate

28. But - ? Safety in pregnancy and lactating
mothers.
-Relatively long dosing schedule- 6 doses.

-COST. At the moment subsidized by
the Governmt.
! COST-- unaffordable.
Coartem - us$ 2.4 (subsidized 2006.)

Art/AQ - us$ 1.59 (subsidized.)

CHQ us$ - 0.12

29. ? Home based therapy
To what level should Cts be stocked.

31. OTHER ANTIMALARIALS
•A. OTHER ARTEMINSININ BASED CTS

•1.Art. + AQ;( Artesunate + Amodiaquine)
-Well tolerated!

•Efficacious., depending on AQ sensitivity in that area.
•Continued monitoring of AQ sensitivity and toxicity is
vital.

32. 2.Art. + Mefloquine;
Mefloquine;
•Has been used for many years in some areas
of low transmission.

-Quite effective.

-Has considerable side effects.

But has a long plasma half life likely to lead to
resistance .
Worry of s/e on unsupervised use.

33. 3. Chlorproguanil + dapsone + Art. (CDATM
or Lapdap plusTM ).
As a fixed combination of Lapdap +Art.

Data available only for the components.

Suggests good potential for a CT.

Avoid use of Lapdap as a Monotherapy if CDA
is contemplated as your future CT.

34. 4.Duo-Cotecxin; Beijing Holly-Cotec

•(Dihydroartemisinin +Piperaquine)

•Co formulated ? Stability.

•Cheep.

•Cross resistance with chloroquine?

35. B. OTHERS;
•1.S/P (Sulfadoxine + Pyrimethamine)-
• no longer recomended due to high resistance to S.P.

•(sulfadoxine -500mg) + pyrimethamine - 25mg)
•a synergistic combination of ant folates.
•Dose – 25mg/kg of sulfa. As single dose.
•Caution; skin reaction –(erythema multiforme,
Steven- Johnson Syndrome or toxic epidermal
necrolysis)
•Do not use in late pregnancy and B/feeding with
infants < two months of age.

36. •2. Amodiaquine.
•Like chloroquine it is a 4- aminoquinoline.
•Has anti- pyretic and anti inflammatory
effect.
• Formulation–200mg.
•Dose – 25mg/kg over three days.
•Adverse effects - nausea, vomiting,
abdominal pain, dirrhoea and itching.
•Rarely hepatotoxicity, agranulocytosis, and
hypotension.
•Not safe for prophylaxis.

37. •3. Quinine

•1640 – Cinchona bark employed for
treatment of Malaria. ( latin America)

•Alkaloid extraction and
purification (QUININE ) occurred in 1820.

•Oral dose. 10mg/kg every 8hrs for a total of 7
days.

38. 4. ARTEMISININ BASED MONOTHERAPIES;

A very old Chinese remedy for malaria.

A product of a plant Qinghao(Artemisia annua)-
described in Chinese literature during the 2nd
Century BC!
-No resistance documented yet with it’s use.
?Few adverse clinical effects.

•?BUT – Short half life – requiring multiple dosages
for seven days, otherwise a/c increased
recrudescence.

39. •-Resistance expected to develop fast if
used as monotherapy.

•Examples; Arteminsinin( qinghaosu),
Artesunate, artemether and
Dihydroartemisinin.

40. •5. MEFLOQUINE;

•First introduced in 1971- a quinoline methanol
derivative (Related to Quinine)

Was effective against malaria strains resistant to all
other forms of ant malarials.

• Due to long plasma half (20days) life was good for
prophylaxis.

•BUT; Wide spread resistance has emerged.
Undesirable side effects, esp. neuropsychiatric.
? Cross resistance with Quinine.

41. 6. HALOFANTRIN;

Belongs to – Phenanthrene methanols.
Introduced in 1980s.

Short half life – not useful for prophylaxis.

BUT. Resistance is developing rapidly.
Concerns about the side effects.esp. cardiotoxicity.
c/I Pregnancy and breast feeding.
! COST.

42. 2. COMPLICATED MALARIA.
•I/V QUININE;
•Dose. 10mg/kg body wt.
•Dilute in 5-10 ml/kg body wt of 5%
Dextrose/d/s.( vol. will depend on fluid balance/
Hb level),
•Infuse over 4hrs , repeated every 8 hrs.
•Drop rate/minute = fluid to be
infused(mls)x20(drop factor)
Time period to be infused (minutes)
Continue with I/V till ptn can take orally. Then
ct with oral quinine till a total of 7 days.

43. •Alternative;
•Once a ptn can take orally give a full
course of Artemether/Lumefantrine(ALu).
ie six doses; except in pregnant women
and babies < 5kg.

•Non response to Quinine

•I/M Arthemeter 3.2mg/km loading dose,
then 1.6mg/kg daily for 6days.

44. •Hypoglycaemia;
•Check blood glucose 4hrly.
•if<2.5mmol/l or consciousness deteriorates.
•Children.
•Give 5mls/kg of 10% dextrose or 2.5mls/kg of
25% or 0.5 – 1ml/kg of 50% dextrose as
bolus.(50% must be diluted in equal vol. of
N/S)
•Adults.
•Give 125mls of 10% or 50mls of 25% or 25mls
of 50% dextrose as bolus.

45. Severe malaria in pregnancy;
Common features;
•High fever.
•Hyperparasitaemia.
•Low blood glucose.
•Severe haemolytic anaemia.
•Cerebral malaria.
•Pulmonary oedema.
•Management; as for severe malaria.

46. IPT (Intermittent presumptive treatment)

•Administration of a drug in full therapeutic
dose at predetermined intervals during
pregnancy even if individuals have no signs
of malaria.

•Aim to prevent the worst effects of malaria
infection in pregnancy. Not to cure.

•Given; 1st dose b/n 20-24wks.
2nd dose b/n 28-32wks.

47. PREVENTION OF MALARIA.
•ITN – Insecticide Treated Nets.

Malaria chemoprophylaxis.
•non immune travelers.
•Non immune pregnant women.
•Ptns with sickle cell aneamia.

48. •Non immune travelers
•Proguanil ( Paludrine) – 200mg daily if staying.

•Mefloquine( Lariam) 250mg wkly.

•Proguanil/Atovaquine (Malarone) 1 tab daily.

•Doxycycline – 100mg daily.

Patients with sickle cell anaemia.
•Chloroquine still recommended.
•Dose – adult 300mg base wkly. Child-5mg/kgwkly.

49. •Non immune pregnant women;
•Advise not to travel to malarious areas.
•Otherwise; 1st trimenster- proguanil.
• 2nd +3rd trimenster- Mefloquine.

•Immune pregnant women – Do not give
prophylaxis. Only IPT recommended with
S/P.

50. Thank you very much