Complicated and Uncomplicated

Malaria Banadir Hospital-somalia

Pediatric department Emergency ward –CME lectures

Mohamed Adan Aweys (Marwan) dr.awies02@gmail.com

Introduction Malaria continues to be a major global health problem, with

over 40% of the world’s population—more than 3.3 billion people—at risk for malaria to varying degrees in countries with on-going transmission.

Malaria is parasitic infection due to the protozoa of the genius plasmodium, transmitted to humans by bite of Anopheles mosquitoes . Transmission by transfusion of parasite infected blood and transplacental transmission are also possible .

Most infections are due to 5 species : P.vivax , P.ovale P. malaria , P.knowlesi , P. falciparum is the most virulent malaria parasite in the world and also the most common malaria parasite in somalia.

All species may cause uncomplicated malaria ; severe malaria is almost always due to P.falcipaarum .

Uncomplicated Malaria

• A patient who presents with symptoms of malaria and positive parasitological test ( microscopy or RDT) but with no features of severe malaria is defined as having uncomplicated malaria.

• The effect of the presence of malaria parasites in the body varies from person to person. There may be no symptoms (asymptomatic infection), mild illness (uncomplicated malaria), or severe illness (severe malaria). If uncomplicated malaria is not recognized early and treated promptly, it is likely to deteriorate to severe malaria .

• The incubation period of malaria ranges from 10 to 14 days depending on the parasite species .

Clinical features of Uncomplicated Malaria

Fever is the most characteristic symptom of malaria. The fever in malaria is intermittent: it comes and goes many times. Three phases can be distinguished in a typical attack of malaria:

The cold stage is when the patient feels cold and shivers. The hot stage is when the patient feels hot. The sweating stage is associated with sweating and

relief of symptoms.

• When people are frequently exposed to malaria, they develop partial immunity. In such people (with partial immunity), the above classical stages of a malaria attack may not be observed. Also, in people who have had partial treatment with antimalarial medicines, those classical stages may not be pronounced .

Physical examination Always take the temperature, weigh the patient, and carry

out a general examination. Check of Common signs of uncomplicated malaria.

Common signs of uncomplicated malaria Raised body temperature (above 37.5oC as taken from

the axilla) Mild anaemia (mild pallor of palms and mucous

membranes); occurs commonly in children Dehydration (dry mouth, coated tongue, and sunken

eyes). In adults, sunken eyes are usually a sign of severe dehydration.

Enlarged spleen (in acute malaria it may be minimally enlarged, soft and mildly tender

Severe MalariaComplicated malaria Caused by P. falciparum infectionIt is an immediate threat to life and is therefore a medical

emergency which requires hospitalization. Malaria is regarded as severe if there are asexual forms of P. falciparum in blood plus one or more of the following complications:

- Change of behaviour, confusion, or drowsiness - Altered level of consciousness or coma - Convulsions ( siezure , generalized or focal )- Hypoglycemia - Acidosis - Difficulty in breathing - Pulmonary oedema or respiratory distress syndrome ( rapid

and laboured breathing or slow , deep breathing.

- Prostration ( extreme weakness , in children : in ability to sit or drink \ suck ) .

- Acute renal failure ( urine output < 12ml /kg / day in children ) - Severe anaemia Haematocrit <20%, Hb <6g/dL Dizziness, tiredness, pallor - Circulatory collapse ( Shock ) : cold extremities , weak or absent

pulse , slow capillary refill time > 2 seconds , cyanosis . - Haemoglobinuria - Oliguria with very dark urine (coca-cola or coffee- colour) - Jaundice (check mucosal surfaces of the mouth , conjunctive palms - Bleeding tendency ( skin –petechia - Hyperparasitaemia (≥100,000 parasites/μL, MPs +++ or above) - Hyperpyrexia ≥400C - Severe vomiting - Organomegly ( hepatomegaly , splenomegaly )

Danger signs of severe illness

a. Convulsions or fits within the last two days or at present

b. Not able to drink or breastfeed c. Vomiting everything d. Altered mental state (lethargy, drowsiness,

unconsciousness, or confusion) e. Prostration or extreme weakness (unable to stand or

sit without support) f. Severe respiratory distress or difficulty in breathing . g. Severe anaemia (severe pallor of palms and mucous

membranes) h. Severe dehydration (sunken eyes, coated tongue,

lethargy, inability to drink)

Diagnosis Laboratory Parasitological diagnosis of malaria Parasitological diagnosis of malaria requires examination of

blood smear for the presence of malaria parasites. The 'gold standard' of malaria diagnosis is the examination of blood smear for malaria parasites.

Microscopy • Thick blood film: Detection and quantification of parasites • Thin blood film: Species identification Note : blood films may be negative due to sequestration of the

parasitized erythrocyte in peripheral capillary in severe malaria , as well as in placental vessels in pregnant women .

Rapid diagnostic test ( RDTs)aRapid test detect parasite antigens. They give only a

qualitative result ( +ve or –ve ) and may remain positive several days or weeks followig effective treatment.

Note : even with positive diagnostic results ,rule out other causes of fever.

Additional examinations Hemoglobin ( Hb) level or complete blood countBlood glucose level – to be measured routinely to

detect hypoglycemia (<3mmol/l or < 55mg/dl in patients with severe malaria and those with malnutrition .

Where laboratory facilities exist, blood examination for malaria parasites must be done for the following groups of patients:

Patients who present with clinical features of severe malaria

Patients who have taken antimalarial treatment for 2 days and symptoms persist

Children aged less than 4 months with symptoms of uncomplicated malaria

Pregnant women with symptoms of uncomplicated malaria

Management Treatment of uncomplicated F. malaria • the treatment is an artemisinin-based therapy ( ACT)d given by the oral route for 3 days .

The first line ACT is chosen according to the therapeutic efficacy in the area under consideration .

- Coformulations ( 2 antimalarials combined in the same tablet ) are preferred over coblisters

- coblisters ( 2 distinct antimalarials presented in same blister ) .• The recommended first line medicine is Artemether/ Lumefantrine. Any other ACT that

has been recommended by WHO and MOH . • Children below 4 months of age: - Artemether/Lumefantrine or other ACTs are not recommended for children

below 4 months of age or 5kg body weight. Such children should be treated with quinine.

- If vomiting precludes oral therapy , treatment is started using Iv or IM artesunate or IM artemether or rectal artesunate depending on availability , until the patient can tolerate a complete 3-day oral treatment with an ACT

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Efficacy studies on AS+SP and AL in Somalia

General objective– to assess the therapeutic efficacy and safety of

artesunate+sulfadoxine/ pyrimethamine (AS+SP) and artemether- lumefantrine (AL) for the treatment of uncomplicated falciparum malaria in Somalia.

– to measure the clinical and parasitological efficacy of AS+SP and AL in patients aged between 6 months and 60 years suffering from uncomplicated falciparum malaria, by determining the proportion with early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response as indicators of efficacy;

Study Design: – one arm cohorts evaluation of clinical and

parasitological responses to directly observed treatment for uncomplicated malaria.

Study Sites: – AS+SP: Jamame, Janale, Jowhar and Bosaso– AL: Janale, Jowhar and Bosaso

Population:– between 6 months and 60 years, inclusive, – female minors aged 12 to 17 years and unmarried

women aged 18 years and above exclude

Inclusion criteria

• age between 6 months and 60 years with the exception of 12-17years old female minors and unmarried females 18 years and above;

• mono-infection with P. falciparum detected by microscopy;• parasitaemia of 500 - 200000/µl asexual forms;• presence of axillary or tympanic temperature ≥ 37.5 °C or history of

fever during the past 24 h;• ability to swallow oral medication;• ability and willingness to comply with the study protocol for the

duration of the study and to comply with the study visit schedule; • informed consent from the patient or from a parent or guardian in

the case of children aged less than 18 years;• informed assent from any minor participant aged from 12 to age of

majority years; and• consent for pregnancy testing: married female of 18 years and above

Exclusion criteria

• general danger signs in <5 children or signs of severe falciparum malaria;

• weight under 5 kg;• mixed or mono-infection with another Plasmodium species detected

by microscopy;• presence of severe malnutrition (defined as a child who has a mid-

upper arm circumference < 115 mm);• febrile conditions due to diseases other than malaria or other known

underlying chronic or severe diseases;• regular medication, which may interfere with antimalarial

pharmacokinetics;• history of hypersensitivity reactions or contraindications to any of the

medicine(s) being tested or used as alternative treatment(s);• a positive pregnancy test or breastfeeding of married women aged 18

years and above; and• unable /unwilling to take pregnancy test or to use contraception for

women of child-bearing age and who are sexually active.

Conclusion

• Unacceptably high treatment failure in Jamame (22.2%) and in Bosaso (12.3%). – These rates are above the WHO recommended ≥10% threshold for

treatment policy change

• High rate of quadruple or quintuple mutations (41% in Jowhar and 59% in Jamame) confirms that SP resistance is well established.

• Day 3 parasitaemia were zero in all sites confirming the absence of artemisinin resistance.

• The findings indicate that SP is failing.• Sustained use of an ACT with a failing partner drug will eventually

compromise the artemisinin component• There is a need to replace the AS+SP with a more effective ACT.• AL is highly effective and is an appropriate ACT to replace AS+SP.

Treatment of Severe Malaria At hospital level IV line: Establish an IV infusion line Fluids: Correct dehydration by assessing and administering fluid requirements according to body

weight Antipyretic: Reduce body temperature if >38.5oC: Paracetamol 1g max = 4g/day Child: 10mg-15mg /kg every 6 hours Tepid sponging or fanning Anticonvulsant: Treat detectable causes (e.g. hypoglycaemia, hyperpyrexia). Then if necessary, give

an anticonvulsant, e.g. diazepam (IV 0.3mg/ kg (max: 10mg) rectally ( 0.4mg /kg )• If they still persist: Give phenobarbital 200mg IM (child: 10-15mg/kg) then 2.5mg/kg once or

twice daily if still necessary 1st line treatment IV quinine 600mg/2ml - Loading dose 20mg salt/kg to be administrated over 4 hours then keep the vein open - Maintenance dose IV 10mg salt/kg q8 hourly - (Dilute quinine in D5% 5-10ml/kg and run over a 4 hours) - As soon as the patient can tolerate oral treatment , administer either a 3 day of ACT course or

oral quinine to complete 7 days of treatment .• D2-7: IV Quinine 10mg salt/kg q8h AND • Doxycycline (>8yrs) (3.5 mg/kg OD) OR Clindamycin (<8yrs) (10 mg/kg/dose bd) given for 7 days

Treatment of Severe Malaria 2nd line treatment The drugs of choice is artesunate Iv or IM ; if artesunate is not

avalaible , use IM artemether .For the patients in shock : use artesunate Iv or if not avalaible ,

Quinine Iv.Artesunate slow Iv injection ( 3 to 5 minute) or if not possible ,

slow IM injection into Anterior thigh. Children less than 20kg : 3mg/kg/dose Children 20kg and over and adults : 2.4mg/kg/dose .- One dose on admission ( H0)- One dose 12 hours after admission( H12) - One dose 24 hours after admission ( H24) - Then one dose once daily Administer at least 3 doses ,then , if the patient can tolerate oral

route change to an ACT .

Artemether IM ( Anterior thigh ) Children and adults : 3.2mg/kg on admission ( D1) then

1.6mg/kg once daily . As soon as the patient can tolerate oral route , change to

an ACT.For completion of therapy by oral route : - If the duration of parenteral treatment was less than 7

days : treat 3 days with an ACT.- If the duration of parenteral treatment was les7 days:

do not give additional oral treatment.NB : Primaquine for Treatment of chloroquine-resistant P.

vivax, knowlesi or malariae and may cause life threatening haemolysis in individuals with G6PD deficiency. G6PD testing is required before administration of Primaquine..

In severe G6PD deficiency Primaquine is contraindicated.

Symptomatic treatment and Management of complications

Hypoglycaemia: - If the patient is able to swallow : 50ml of 10% glucose or 40ml of water +10ml of 50% glucose or 50ml of water + 5 g (1 teaspoon of granulated sugar or 50ml of milk.- In an unconscious patient : Children : 5ml/kg of 10% glucose by slow IV injection .- Check blood level after 30 minutes. If blood glucose level remains

< 3mmol/l or 55 mg/dl , administer another dose or give glucose by oral route , according to the patient’s clinical condition . Hypoglycemia my recur : maintain regular sugar intake

- The risk of hypoglycemia is higher in patients receiving IV quinine.

Acidosis: Correct fluid & electrolyte balance - If there is severe acidosis without sodium depletion: - Give sodium bicarbonate 8.4% infusion 50mL IV - Monitor plasma pH Pulmonary oedema - Regulate the IV infusion - Prop up the patient - Give oxygen - Give furosemide (1mg/kg or 0.1cc/kg ) Acute renal failure • Urine output: <0.3mL/kg/hour (child) • Check to ensure that the cause of oliguria is not

dehydration or shock .• If due to acute renal failure: Give a challenge dose of

furosemide 20mg slow IV (child: 1mg/kg)

Severe anaemia - Blood transfusion is indicated : • In children with Hb < 4g/dl ( or between 4 and 6 g/dl with signs

of decompensation) - Do blood grouping and cross-matching - Transfuse patient with packed cells 10-15mL/kg or whole blood

20mL/kg especially if the anaemia is also causing heart failure - Repeat Hb/PCV before discharge and preferably on day 28 days

after discharge .Shock: If systolic BP <50mm Hg (child) or if peripheral pulse absent and

capillary refill is slow (>2 seconds) - Raise the foot of the bed - Give sodium chloride 0.9% by fast IV infusion ( 20ml/kg )- Review fluid balance and urinary outputs - Look for evidence of haemorrhage or Septicaemia and treat

accordingly

Coma: Provide intensive nursing care with : - Check / ensure the airway is clear , measure blood glucose

level , and asses level of consciousness ( by GSC ) - IV drip (for rehydration and IV medication - NGT (for feeding and oral medication) - Urethral catheter (to monitor urine output) - Turning of patient frequently every 2 hrs to avoid bedsores. - Exclude meningitis ( lumbar puncture ) or proceed directly

to administration of an Antibiotic . - Monitor vital signs , blood glucose level , level of

consciousness , urine output , hourly until stable and then every 4 hours .

- Monitor fluid blance

Congenital malaria

Congenital malaria is rare. It is acquired from the mother prenatally or perinatally, usually occurring in the newborn of a non-immune mother with P. vivax or P. malariae infection, although it can be observed with any of the human malarial species.. The first sign or symptom most commonly occur between 10 and 30 days of age (range: 14hr to several months of age).

Signs and symptoms include fever, restlessness, drowsiness, pallor, jaundice, poor feeding, vomiting, diarrhea, cyanosis and hepatosplenomegaly. It can mimic a sepsis like illness. Parasitemia in neonates within 7 days of birth implies transplacental transmission

Treatment: Chloroquine, total dose of 25mg base/kg orally divided over 3

days • D1: 10 mg base/kg stat then 5 mg base/kg 6 hours later • D2: 5 mg base/kg OD • D3: 5 mg base/kg OD .

Malaria prophylaxis

• Not recommended for all those living in a highly endemic area like somalia . However, it is recommended for certain high-risk groups but is not 100% effective.

• Pregnancy Give intermittent preventive treatment (IPT) SP single dose (3 tabs) to ensure the well-being of the mother and foetus .

Malaria prevention and control

Give effective treatment and prophylaxis - Eliminate parasites from the human population by early diagnosis and effective

treatment - Protect vulnerable groups with chemoprophylaxis - Give IPT to all pregnant women • Reduce human-mosquito contact • Use insecticide-treated materials (e.g. bed nets) • Destroy adult mosquitoes by residual spraying of dwellings with insecticide or

use of knock-down sprays • Screen houses • Carefully select house sites avoiding mosquito-infested areas • Wear clothes which cover the arms and legs and use repellent mosquito coils

and creams/sprays on the skin when sitting outdoors at night • Control breeding sites • Eliminate collections of stagnant water where mosquitoes breed, e.g. in

empty cans/ containers, potholes, old car tyres, plastic bags, and footprints by disposal, draining, or covering with soil or sand

References

- A practical handbook MANAGEMENT OFSEVERE MALARIA 3rd edition .- Guidelines for the treatment of malaria 3rd edition - UGANDA CLINICAL GUIDELINES 2012 National Guidelines

for Management of Common Conditions . - PAEDIATRIC PROTOCOLS For Malaysian Hospitals 3rd

edition .- MSF clinical guidelines diagnosis and treatment manual

2016 edition.- Updating malaria treatment policy Somalia / Global

malaria program WHO dr marian warsame

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