malaria in childhood

MALARIA IN CHILDHOODDR P.O. ELEMILE

Introduction

• Disease of the Tropics and Subtropics, latitude 64°N and 32°S,but can be taken tothe Temperate regions through Air travel.

Current data show that malaria transmission occurs in about 97 countries in Africa,Central and South America, Asia and Oceania.

• In 2018, nearly half of the world’s population of 7.6 billion (3.8billion) was at risk ofmalaria according to WHO.

• In 2018, there were an estimated 228 million cases of malaria worldwide accordingto the WHO.

•The estimated number of malaria deaths stood at 405,000 in 2018.

Introduction Con’t

• Children < 5 years of age are the most vulnerable group affected by malaria;in 2018, they accounted for 67% (272,000) of all malaria deaths worldwide.

• The WHO African Region carries a disproportionately high share of theglobal malaria burden. In 2018, the region was home to 93% of malaria casesand 94% of malaria deaths.

• P. Falciparum accounts for 80-90% of malaria infection, either alone, or incombination with one or more of the other species. P. Vivax does not occur inindigenous West Africans.

Introduction Con’t (Aetiology )

• Protozoal disease caused by the Plasmodium species discovered by Laveran in1880. 5 species of Plasmodium causing human Malaria are: P. Falciparum, P.Malariae, P. Vivax, P. Ovale and P. Knowlesi.

• Most cases are caused by the bite of the female anopheles mosquito.

• Other modes of transmission of the disease are:

-congenital through the placenta;

-through transfusion of inflected blood;

-perinatally due to blood mingling during delivery;

-through needle prick injuries.

Malaria Endemicity• This describes the amount and severity of malaria in a community or a region.There are 2 systems of classification:

a) based on the use of spleen and parasite rates:

i) Hypoendemicity:0-10%

ii) Mesoendemicity:11-50%

iii) Hyperendemicity:>50% persistently with adult spleen rate >25%

iv) Holoendemicity:>75% persistently with low adult spleen rate.

Malaria Endemicity

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b. Based on transmission rates:

i) High (stable) transmission: (>1 case per 1000 population)

Transmission is all year round

Seasonal variation possible;

Partial immunity occurs in older children and adults who may less likely havesevere disease;

P. Falciparum is the dominant parasite.

Such areas include many countries of sub-Saharan Africa.

MALARIA IN CHILDHOOD CON’T

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-ii)Low(unstable)transmission: (<1 case per 1000 population)

Intermittent transmission;

May be annual, bi-annual or variable;

Transmission varies from year to year or season to season;

Community immunity is low;

Epidemics of malaria may occur;

Both P. Falciparum and P. Vivax are found in such areas.

Life Cycle ofMalaria ParasitesAsexual

This occurs in man in 2 stages:

-Preerythrocytic (5.5-7 days for P.Falciparum):occurs in the liverbeginning from the sporozoitesinjected into man through themosquito bite. This develops intoschizonts and merozoites in thatorder.

Life Cycle of MalariaParasites

Erythrocytic stage (36-48hrs for P.Falciparum): merozoites from theliver enter and develop in the RBCinto trophozoites, merozoites andgametocytes(male and female) inthat order.

Life Cycle of Malaria Parasites Con’t

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Sexual(10-12days):This occurs in the mosquito (the vector) when gametocytesenter its stomach and develop into zygote, ookinete, oocyst and sporozoites, inthat order. Sporozoites are stored in the salivary glands of the mosquito.

• For P. Falciparum:

Incubation period is 9-14 days;

Parasitaemia (cu.ml.): up to 2,000,000;

Febrile paroxysm(hours):16-36 or longer;

Duration of untreated infection (years): up to 1.

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Malaria Immunity

A triad or a combination of:

a)Genetic resistance

b)Natural or Nonadaptive

c)Acquired or Adaptive

Malaria Immunity Con’t

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Genetic Resistance:

Presence of HbS, G6PD deficiency, HbF, HbE, Thallassemia or Duffy-negativegenotype; the presence of the above-named genotypes is known to reduce theability of the malaria parasites to penetrate the red blood cells, thereby reducing theseverity of acute and prevalence of chronic malaria.

In G6PD, in addition, there is increased susceptibility of cells to oxidative damagewhich in turn kills the parasites inside them.


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Natural:

Nonspecific, consisting of

intensive proliferation of the reticuloendothelial system;

macrophages of the liver, spleen and bone marrow, which phagocytize parasitizedand unphagocytized red blood cells during malaria infection.

Acquired:

This can be passive or active:

i) Passive:

Transplacentally transferred IgG antibodies from the maternal to the foetalcirculation;

Offers protection to the new-born and infants up to the age of 6 months.


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Active:

Dependent on circulating IgG in the plasma.

Dependent on active or continuous infection with malaria parasites

Malaria Immunity Con’t•

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-Natural history of this type of immunity in areas of stable malaria transmission:

+death in children under 5 years of age;

+increasingly parasitaemia, albeit asymptomatic, in school aged children;

+declining parasite prevalence and acquisition of immunity to infection in olderage groups.

Both humoral and cellular immunity play a part in the evolution of immunity tomalaria.

Ab responses to various malaria parasite Ags have been associated withprotection against malaria and have for the basis of vaccine development.

Factors Affecting Susceptibility to Malaria andResponse to Treatment

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a)Genetically-determined (innate) resistance as above.

b)Parasite virulence.

c)Socio-economic status.

d)Immunity status and age.

e)Nutritional status.

Curiously malnutrition does not seem to increase the severity of malaria.

Current observation suggests that well-nourished children are more likelyto suffer from severe malaria than malnourished children.

Clinical Manifestations of Malaria

These are divided into

a)Uncomplicated/Non-severe

b)Complicated/Severe

a) Uncomplicated/Non-severe

Symptoms:

Fever, Headache, Vomiting, Convulsions, Jaundice, Pallor, Pain and other aches,

Diarrhoea, Cough. Others: general malaise, anorexia, behavioural changes likefretfulness and unusual outbursts of crying, drowsiness and disturbances of sleep.

These symptoms are virtually exclusive features of acute falciparum malaria.

Clinical Manifestations of Malaria

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Physical Examination:

No significant findings.

Variable degrees of pyrexia (37.5-41°C).

Pallor

Mild jaundice

Hepatomegaly

Splenomegaly or

Hepato-splenomegaly

Lymphadenopathy is never a feature.

Clinical Manifestations of Severe Malaria

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b. Complicated/Severe:

1. Prostration: Generalised weakness or inability to sit/or stand without support.

2. Hyperparasitemia:

>5% of RBCs parasitized by asexual forms of P. Falciparum or parasite count >250,000/cu.ml.

3. Cerebral Malaria:

Unarousable coma for longer than 30mins or a Blantyre coma score of 3 of 5.

Exclusion of other Encephalopathies.

Peripheral, marrow or brain smear parasitaemia.

Ring haemorrhages in the brain and retina haemorrhages or whitening.

Clinical Manifestations of Severe Malaria

4. Hyperpyrexia:

Rectal temperature >40°C

5. Severe Anaemia:

Hb<5.0g/dL or PCV<15%

6. Jaundice, in association with other organ dysfunction: Serum bilirubin >51Umol/L.

7. Hypoglycaemia:

Random blood sugar: <2.2 mmol/L

8. Acute Kidney Injury: Oliguria or anuria.

Serum creatinine: >265/Umol/L

Clinical Manifestations of Severe Malaria9. Shock:

Compensated: capillary refill >3 seconds;

Decompensated: Hypotension – systolic pressure <70mmHg, rapid threadypulse, pallor.

10. Pulmonary Oedema:

Demonstrated clinically: Respiratory rate >30/min, oxygen saturation in room air<92% with diffuse wheeze or crepitation in the lungs or radiologically.

11. Clotting Disturbances: Bleeding episodes.

12. Electrolyte and acid-base imbalances:

Clinically, low serum levels, pH <7.2

Laboratory Diagnosis of Malaria

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This is divided into 2 Categories of tests as follows:

Microscopy based,

Non-microscopy based.

a) Microscopy based:

Thick and thin blood films using the Giemsa stain is the gold standard ofdiagnosis. The thick smear is used to identify the parasites while the thin smearis used to identify the plasmodial species, but both can be used to estimate theparasite densities.


b) Non-microscopy based:

General principles of tests are that they detect any of parasite Ag, parasite Ab orparasite by-product. They include:

i)Rapid Diagnostic Tests (RDTs),

ii)Immune Assays and

iii)Polymerase Chain Reaction (PCR) or Molecular methods. Immune assays andPCR are often used in research settings.


RDTs:

-detect specific Ags (antigens) or proteins produced by malaria parasites.

-are in 3 major classes

•P. Falciparum histidine rich protein 2(PfHRP2) Ags:

+detect P. Falciparum alone.

+produced by trophozoites and young gametocytes and persist after parasite death.

+have high sensitivity but lower specificity since they remain positive up to amonth after infection.

+useful for diagnosis but not for monitoring response to treatment.


Parasite enzyme; Plasmodium lactate dehydrogenase (pLDH):

+closely reflect parasite viability and are produced by both asexual and sexual stages.

-have the potential for monitoring treatment efficacy.

-can detect P. Falciparum, non-plasmodium or mixed infections.

-particularly useful where other plasmodia species contribute significantly to malaria.

-tend to have better specificity than HRP2 although they may not be as sensitive.

•based on aldolase reaction(currently less commonly available).

Treatment of Malaria

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Following the consistent emergence of resistance to every antimalarial drug, the WHO inyear 2000, made a fundamental recommendation to change treatment frommonotherapy to combination therapies.

The preferred therapy is the highly effective artemisinin-based combination therapy(ACTs).

Combination treatment involves the simultaneous use of 2 or more blood schizonticidaldrugs with independent modes of action and different biochemical targets in the parasite.

The mode of therapy is divided into 2 categories:

1.Uncomplicated Malaria,

2.Severe or Complicated.

Treatment of Malaria:Uncomplicated

a)Artemeter-lumefantrine: 1.5/9 mg/kg twice daily x3/7 OR

b)Artesunate+Amodiaquine:

Artesunate4mg/kg dailyx3/7

+Amodiaquine 10mg base/kg on days 1,2 & 3.

Treatment of Malaria:Complicated

a) IM or IV Artesunate for at least 24 hours (including infants) or continue untilpatient is able to tolerate oral medication.

i) Children weighing <20kg: 3mg/kg/dose: the higher dose is to ensure anequivalent drug exposure

ii) Children weighing >20kg:2.4mg/kg/dose at time 0,12hrs & 24hrs, and tocontinue thereafter until patient is capable of tolerating oral medication.

iii) After receiving at least 24hours of parenteral therapy, and is able to tolerateoral therapy, the patient completes treatment with 3 days of the recommendedACT.

b)Symptomatic and Supportive treatment

Malaria Chemoprophylaxis

In the malaria-endemic regions, this is recommended in the following categoriesof children only:

a) Those with sickle cell disease.

b)Visitors to or those who are non-indigenous residents in the regions.

c)Those born to mothers who are known to be non-immune to malaria.

d)Those who are immuno-deficient due to disease or drugs.

Malaria Chemoprophylaxis

Infants and young children outside the above categories should not be givenchemo-prophylaxis. Doing this only amounts to postponing the “evil days”.Efforts should be directed rather to the use of preventive measures ortreating fevers in all children promptly, adequately and appropriately. By sodoing, children will have a chance or opportunity to develop some immunityto malaria at an early age.

Malaria Prevention

This will be considered as follows:

1.Environmental sanitation,

2.Roll Back Malaria Initiative,

3.National Malaria Strategic Plan, and

4.Malaria Vaccine.

1.Environmental sanitation: By destroying and removing all possible sources of thebreeding of the vector(mosquito), contact between it and human beings will bereduced.

Roll Back Malaria Initiative

• This was started by the WHO in 1998.

• A worldwide partnership to fight Malaria, building on existing network of nationalgovernments, international organizations and the private sector.

• Major stakeholders are the WHO, UNICEF, World Bank, UNDP, G8 Nations and the PrivateSector providing the needed resources and coordination.

• The RBM approach involves 6 elements:

a)early detection;

b)prompt and effective treatment

c)multiple prevention including use of Insecticide Treated Nets (ITN/LLINs), indoorresidual spraying (IRS), larviciding and prevention in pregnancy,

d)focused research in order to have evidence based decisions;

e)partnerships and well- coordinated actions and

f)dynamic social movements to mobilize support for malaria control.

National Malaria Strategic Plan (NMSP)

• Consistent with the global focus on Malaria elimination the Government ofNigeria developed a new plan covering the period 2014-2020.

• The vision is to have a Malaria Free Nigeria.

• The goal is to reduce malaria burden to pre-elimination (local prevalence <5%)levels and bring malaria-related mortality to zero.

Malaria Vaccine

• The search for a suitable vaccine against malaria is almost as old as malariaitself dating back to the late 1800s. •RTS,S is the first malaria vaccine to receivea positive scientific opinion from European regulators.

-the name given to this malaria vaccine represents its composition. The ‘R’stands for the central repeat region of Plasmodium (P.) Falciparum

circumsporozoite protein (CSP); The ‘T’ for the T-cell epitopes of the CSP andthe ‘S' for hepatitis B surface antigen (HBsAg).

Malaria Vaccine

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infection is prevented by inducing humoral and cellular immunity, with highantibody titres, that block the parasite from infecting the liver.

RTS,S. RTS,S/AS01 (trade name Mosquirix) is a recombinant protein-basedmalaria vaccine approved for use by European regulators in July 2015.

it is the world's first licenced malaria vaccine and also the first vaccine licencedfor use against a human parasitic disease of any kind.

on 23 October 2015, the WHO recommended a pilot implementation of thevaccine in Africa;

this pilot project for vaccination was launched on 23 April 2019 in Malawi, on 30April 2019 in Ghana, and on 13 September 2019 in Kenya.

the vaccine, when in general use, will be an adjunct to other existing interventionson malaria control.

•Thank you

malaria in childhood

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