Islamic Republic of Afghanistan

Ministry of Public Health

General Directorate of Preventive medicine

Communicable Disease Control Directorate

National Malaria and Leishmaniasis Control Program

National Malaria Treatment

Guideline

September 2017

Table of Contents

........................................................................................................... 1

Acknowledgment: .......................................................................................... Error! Bookmark not defined.

Acronyms ...................................................................................................................................................... 5

........................................................................................................... 7

......................................................................................................... 10

Symptom-Based (Clinical or probable) Diagnosis ................................................................................... 10

Parasitological Diagnosis ......................................................................................................................... 10

Microscopy .............................................................................................................................................. 11

Rapid Diagnostic Tests (RDT) .................................................................................................................. 11

......................................................................................................... 13

Uncomplicated malaria ........................................................................................................................... 13

Probable (clinical) uncomplicated malaria .......................................................................................... 13

Confirmed uncomplicated falciparum malaria ................................................................................... 13

Confirmed uncomplicated vivax malaria ............................................................................................ 13

Confirmed uncomplicated mixed infection ........................................................................................ 13

Severe malaria ........................................................................................................................................ 13

Probable severe malaria ..................................................................................................................... 14

Confirmed severe malaria ................................................................................................................... 14

......................................................................................................... 17

UNCOMPLICATED MALARIA .................................................................................................................... 17

First line drug treatment ......................................................................................................................... 17

Probable uncomplicated malaria ........................................................................................................ 17

Confirmed uncomplicated falciparum malaria ................................................................................... 17

Confirmed uncomplicated vivax malaria: ........................................................................................... 18

Confirmed uncomplicated Mix (Pf + Pv) malaria: ............................................................................... 19

Second line drug treatment .................................................................................................................... 19

SEVERE MALARIA .................................................................................................................................... 20

Antimalarial drug treatment of severe malaria ...................................................................................... 21

SUMMARY

I NTRODUCTION.

D IAGNOSIS

CASE DEFINITIONS

TREATMENT

Hospital level ....................................................................................................................................... 21

Health center level .............................................................................................................................. 21

Health Post level ................................................................................................................................. 22

MANAGEMENT OF COMPLICATIONS ...................................................................................................... 22

Malaria treatment in pregnancy ............................................................................................................. 23

Treatment of probable uncomplicated malaria:................................................................................. 23

Treatment of confirmed uncomplicated falciparum malaria ............................................................. 23

Treatment of confirmed uncomplicated vivax malaria ...................................................................... 23

Treatment of confirmed uncomplicated Mix malaria ......................................................................... 23

Treatment of probable or confirmed severe malaria ......................................................................... 23

Malaria drug dosage chart: (Parenteral drug) ............................................................................................ 25

.......................................................................................................... 27

REFERRANCE

1

Malaria case management, consisting of early diagnosis and prompt effective treatment, remains a vital

component of malaria control and elimination strategies. The National Treatment Guidelines ensures that

the best evidence based treatment is provided for management of malaria in the country.

Recommendations:

All cases of suspected malaria should have a parasitological test (microscopy or Rapid diagnostic test (RDT))

to confirm the diagnosis. Therefore, it is necessary to scale-up malaria diagnostics facilities to ensure the

feasibility of parasitological diagnosis. Both microscopy and RDTs should be supported by a quality assurance

programme.

Treatment of Malaria UNCOMPLICATED MALARIA

First line treatment

Uncomplicated P. falciparum malaria: Treat children and adults with uncomplicated P. falciparum malaria

(including infants, lactating women and pregnant women in their second and third trimester; except pregnant

women in their first trimester) with recommended ACT (artemether + lumefantrine) for 3 days, with giving a

single dose of 0.25 mg/kg bw Primaquine to P. falciparum patients (except pregnant women, infants aged <

6 months and women breastfeeding) to reduce transmission. Testing for glucose-6-phosphate

dehydrogenase (G6PD) deficiency is not required.

Infants weighing < 5 kg with uncomplicated P. falciparum malaria should be treated with recommended ACT

(AL) at the same mg/kg bw target dose as for children weighing 5 kg.

P. vivax malaria

Blood stage infection: Treat all patients with P. vivax malaria with Chloroquine.

Preventing relapse: To prevent relapse, treat P. vivax malaria in children and adults (except pregnant women,

infants aged < 6 months, women breastfeeding) with Primaquine as following

In patients with normal G6PD level: consider giving a 14-day course of Primaquine base at 0.25 mg/kg bw

daily.

In patients with mild-to-moderate G6PD deficiency: consider preventing relapse by giving Primaquine base

at 0.75 mg/kg bw once a week for 8 weeks, with close medical supervision for potential Primaquine-induced

hemolysis.

In patients with known sever G6PD deficiency: Primaquine is contraindicated and must not be given.

When G6PD testing is not available: consider preventing relapse by giving Primaquine base at 0.75 mg/kg bw

once a week for 8 weeks, with close medical supervision for potential Primaquine-induced hemolysis.

SUMMARY

2

In female patients: In the absence of quantitative testing, all females should be considered as potentially

having intermediate G6PD activity (mild-to-moderate deficiency) and given the weekly dose of Primaquine

with close medical supervision.

Primaquine is contraindicated in pregnant women, infants aged < 6 months and breastfeeding women

Clinically diagnosed malaria

It is strongly recommended to parasitologically confirm all cases with microscopy or RDT and then treat them

based on parasitological confirmation. Only in exceptional cases where parasitological confirmation is not

available (nor microscopic neither RDT) the patient can be treated based on clinical sign and symptoms, if

any other cause was not found.

Clinical cases should be treated with Chloroquine and patient should be referred to facility for confirmation

of diagnosis and follow-up treatment.

Second line treatment

Quinine should be used as second line treatment when treatment failed with first line. Quinine can be given

as: (10mg salt/kg orally three times daily) plus Doxycycline (3.5mg/kg once a day) or Clindamycin (10mg/kg

twice a day); all drugs to be given for 7 days. All cases must be parasitological confirmed before treatment.

Note: NMLCP has plan to test the therapeutic efficacy and safety of (Di hydro artemesinine + Piperaquine) in

the country to introduce this ACT as a second line therapy for uncomplicated confirm malaria cases.

Treating severe malaria

Health Post level: The Community Health Workers (CHWs) at the Health Post (HP) level, should be trained

on major signs of sever malaria and they should refer any sever malaria case to the health center/or hospital

for proper diagnosis and treatment.

Health center level: At health centers (BHC, CHC, mobile team, SHC) where complete treatment of severe

malaria is not possible, all severe malaria patients (adults and children) should be given the initial single

intramuscular dose of Artesunate (as pre-referral treatment) and then refers the patient to an appropriate

facility for further care. Where intramuscular Artesunate is not available; use artemether in preference to

Quinine.

Hospital level: Treat adults and children with severe malaria (including infants, pregnant women in all

trimesters and lactating women) with intravenous or intramuscular Artesunate for at least 24 h and until they

can tolerate oral medication. Once a patient has received at least 24 h of parenteral therapy and can tolerate

oral therapy, complete treatment with 3 days AL (add single dose Primaquine).

Children weighing < 20 kg should receive a higher dose of Artesunate (3 mg/kg bw per dose) than larger

children and adults (2.4 mg/kg bw per dose) to ensure equivalent exposure to the drug.

If parenteral Artesunate is not available, use artemether in preference to Quinine, but if both Artesunate and

artemether are not available, use Quinine for treating children and adults with severe malaria.

3

Malaria treatment in pregnant women

Uncomplicated P. falciparum

First trimester: Treat pregnant women with uncomplicated P. falciparum malaria during the first trimester

with 7 days of Quinine + Clindamycin.

Second and third trimesters: uncomplicated falciparum malaria in the second and third trimesters of

pregnancy should be treated same as common uncomplicated P. falciparum patients with artemether +

lumefantrine 3 days.

Primaquine and Doxycycline are contraindicated and should not be used in pregnancy.

P. vivax malaria: Only blood stage of the infection should be treated with Chloroquine during pregnancy.

Primaquine is contraindicated in pregnant women.

Sever malaria: Treatment of sever malaria in pregnant women is same as treatment of sever malaria in other

patient at each level. Parenteral Artesunate is the treatment of choice in all trimesters. If Artesunate is

unavailable, intramuscular artemether should be given, and if this is unavailable then parenteral Quinine

should be given. Treatment must not be delayed.

4

5

Acronyms ACT Artemisinin-based Combination Therapy

AL Artemether + Lumefantrine

AS Artesunate

CBMM Community Based Management of Malaria

CHW Community Health Worker

CQ Chloroquine

G6PD Glucose 6 Phosphate Dehydrogenase

HRP Histamine - Rich Protein

NMSP National Malaria Strategic Plan

NTG National Treatment Guideline

PLDH Plasmodium Lactate Dehydrogenase

RDT Rapid Diagnostic Test

6

NTG Chapter 1

Malaria Introduction

7

Malaria is caused by infection of red blood cells with protozoan parasites of the genus Plasmodium inoculated

into the human host by a feeding female anopheline mosquito. The five human Plasmodium species

transmitted from person to person are P. falciparum, P. vivax, P. ovale (two species) and P. malariae.

Increasingly, human infections with the monkey malaria parasite (P. knowlesi) are being reported from the

forested regions of South-East Asia and particularly the island of Borneo.

In Afghanistan of the four-human species, at present, P. vivax malaria is the most prevalent species

accounting for almost 95% of all parasitological confirmed cases, with less than 5% of total cases attributed

to P. falciparum with a decrease in its proportion over the past years.

In Afghanistan, malaria occurs at altitudes below 2000 meters and its transmission is seasonal from June to

November. The P. falciparum peak is in August to October, a few months after the summer peak of P. vivax.

Many Plasmodium vivax infections relapse during the spring season and this may give rise to a vivax peak

around July. Transmission of P. falciparum, at the edge of its geographical range, is unstable, and can

fluctuate markedly from year to year.

Malaria is a complex disease and its distribution in Afghanistan varies largely from place to place, and is

dependent upon a variety of factors related to parasites, vectors and human populations under different

geographical, ecological and socio-economic conditions. Based on revised National strategic plan from

malaria control to elimination, 2018 – 2022 by using five-year malaria data and combination of available

malaria and environmental information, all districts in Afghanistan were classified into three main strata with

high, medium and low risk of malaria areas:

Stratum Population Districts Criteria

1 6,960,987 123 Those districts with API >1 (confirm

cases) and the TPR above or equal 9%

2 21,738,456 213

Those districts with API (confirm

cases) equal or less than one (<1) and

the TPR below 9%

3 3,392,611 63 Those districts with API =0 and the

TPR zero

INTRODUCTION

8

The goal of National Strategic Plan on Malaria Control and Elimination is to contribute to the improvement

of the health status in Afghanistan through the reduction of morbidity and mortality associated with

malaria with a vision to completely interrupt transmission of P. falciparum by 2020.

Malaria case management consisting of early diagnosis and prompt effective treatment, remains a vital

component of malaria control and elimination strategies. It is one of the key strategic interventions and a

major cornerstone of malaria control and elimination in Afghanistan.

It is recommended to parasitologically confirm all cases of suspected malaria (with microscopy or Rapid

Diagnostic Test, RDT) and then promptly treat according to the National Treatment Guideline (NTG). To

ensure parasitological confirmation at all levels RDTs are introduced through wide-scale implementation of

Community Based Management of Malaria (CBMM) through the extensive CHW network; and awareness of

the general population increased regarding the prompt recognition, appropriate care-seeking behavior and

effective prevention of malaria through community-level and mass media support.

This National Malaria Treatment Guidelines has been revised and updated to ensure that health care workers

are provided with clear evidence-based recommendations on the diagnosis and treatment of malaria adapted

to the specific malaria epidemiology and drug profile in Afghanistan.

9

NTG Chapter 2

Malaria Diagnosis

10

Prompt, accurate diagnosis of malaria is part of effective Case management. All patients with suspected

malaria should be treated on the basis of a confirmation by microscopic examination or RDT testing of a blood

sample. Correct diagnosis in malaria-endemic areas is particularly important for the most vulnerable

population groups, such as young children and non-immune populations, in whom falciparum malaria can be

rapidly fatal. High specificity of diagnosis will reduce unnecessary treatment with antimalarial drugs and

improve the diagnosis of other febrile illnesses in all settings.

Symptom-Based (Clinical or probable) Diagnosis

Malaria is suspected clinically primarily on the basis of fever or a history of fever. There is no combination of

signs or symptoms that reliably distinguishes malaria from other causes of fever; diagnosis based only on

clinical features has very low sensitivity, specificity and results in overtreatment. The common signs and

symptoms (fever, chills, headache and anorexia) are non-specific and are common to many diseases and

conditions. The appropriateness of particular clinical diagnostic criteria varies from area to area according to

the intensity of transmission, the prevalent species of malaria parasite and other prevailing causes of fever.

The symptoms of malaria which are nonspecific and similar to those of a minor systemic viral illness comprise

headache, lassitude, fatigue, abdominal discomfort and muscle and joint aches, usually followed by fever,

chills, perspiration, anorexia, vomiting and worsening malaise. Many of the key symptoms and signs of

malaria in one area may not be applicable elsewhere. Other possible causes of fever and whether alternative

or additional treatment is required must always be carefully considered. The focus of malaria diagnosis

should be to identify patients who truly have malaria, to guide rational use of antimalarial medicines.

In very exceptional settings where parasitological diagnosis is not possible and other causes of fever are rolled

out, a decision to provide antimalarial treatment can be based on the probability that the illness is malaria.

Parasitological Diagnosis

In all settings, suspected malaria should be confirmed with a parasitological test. The commonly used

confirmatory tests to detect the presence of malaria parasites in blood are microscopy or rapid diagnostic

tests (RDTs). The benefit of parasitological diagnosis relies entirely on an appropriate management response

of health care providers. Antimalarial treatment should be limited to cases with positive tests, and patients

with negative results should be reassessed for other common causes of fever and treated appropriately.

The results of parasitological diagnosis should be available within a short time (< 2 h) of the patient

presenting.

If both the slide examination and the RDT results are negative, malaria is unlikely, and other causes of the

illness should be sought and treated.

Quality assurance of microscopy and RDTs is vital to ensure high sensitivity and specificity of results.

DIAGNOSIS

11

Microscopy

Microscopy not only provides a highly sensitive, specific diagnosis of malaria when performed well but also

allows quantification of malaria parasites and identification of the infecting species. This is done by examining

a stained thick and/or thin blood film for the presence of malaria parasites. Thick films are recommended for

parasite detection and quantification and can be used to monitor response to treatment, while, thin films are

recommended for species identification and can also be used for parasite quantification.

In nearly all cases of symptomatic malaria, examination of thick and thin blood films by competent

microscopes will reveal malaria parasites, but the accuracy of diagnosis is strongly dependent on the

competence of the microscopist. High-quality light microscopy requires well- trained, skilled staff, good

staining reagents, clean slides and, often, electricity to power the microscope. It also requires a continuous

quality assurance system.

The important advantages of Microscopy are:

Low direct costs, if laboratory infrastructure to maintain the service is available;

High sensitivity, if the performance of microscopy is high;

Differentiation of Plasmodia species;

Determination of parasite densities – notably identification of hyperparasitaemia;

Detection of gametocytaemia;

Allows monitoring of responses to therapy and

Can be used to diagnose many other conditions.

Although nucleic acid amplification-based tests are more sensitive, light microscopy is still considered the

“field standard” against which the sensitivity and specificity of other methods must be assessed. A skilled

microscopist can detect asexual parasites at a density of < 10 per µL of blood, but under typical field

conditions, the limit of sensitivity is approximately 100 parasites per µL.

Good performance of microscopy can be maintained through adequate training and supervision of laboratory

staff to ensure competence in malaria diagnosis, good quality slides and stains, provision and maintenance

of good microscopes and maintenance of quality assurance and control of laboratory services.

Rapid Diagnostic Tests (RDT)

Rapid diagnostic tests (RDTs) are immuno-chromatographic tests for detecting parasite-specific antigens in a

finger-prick blood sample. Malaria RDTs should be used if quality-assured malaria microscopy is not readily

available.

Some RDTs can detect only one species (P. falciparum); others allow detection of one or more of the other

species of human malaria parasites (P. vivax, P. malariae and P. ovale).

RDTs for detecting PfHRP2 can also be useful for patients who have received incomplete antimalarial

treatment, in whom blood films can be negative.

RDTs cannot be used for parasite quantification.

12

Current tests are based on the detection of histidine-rich protein 2 (HRP2), which is specific for P. falciparum,

and Plasmodium lactate dehydrogenase (pLDH) which is specific for P. vivax and other species.

The tests have many potential advantages, including:

Rapid provision of results and extension of diagnostic services to the lowest-level health facilities and

communities;

Fewer requirements for training and skilled personnel (for instance, a general health worker can be

trained in 1 day); and

Reinforcement of patient confidence in the diagnosis and in the health service in general.

Several studies have shown that health workers, volunteers and private sector providers can, with adequate

training and supervision, use RDTs correctly and provide accurate malaria diagnoses. RDTs are relatively

simple to perform and to interpret, and they do not require electricity or special equipment, but are not

sensitive in detecting low parasitaemia. Use of RDTs is not recommended for follow-up assessment after an

initial antimalarial treatment, as most tests, especially HRP2 based tests; remain positive for 1–5 weeks

following effective antimalarial treatment and clearance of parasites.

13

Uncomplicated malaria

A patient who presents with symptoms of malaria and a positive parasitological test (microscopy or RDT) but

has no signs of severity or features of severe malaria and no evidence of vital organ dysfunction is defined as

having uncomplicated malaria.

Probable (clinical) uncomplicated malaria

In malaria-endemic areas, malaria should be suspected in any patient presenting with a history of fever or

temperature ≥ 37.5 °C without any other obvious cause.

A patient who presents with symptoms of malaria, mainly fever with no any other obvious cause, without

signs of severity or evidence of vital organ dysfunction, and is treated presumptively as malaria without

parasitological confirmation by a diagnostic test (due to unavailability of diagnostic test in a very rare

situation), is defined as probable (clinical) uncomplicated malaria case.

Confirmed uncomplicated falciparum malaria

A patient who presents with symptoms of malaria and a positive parasitological test (microscopy or RDT) of

P. falciparum, but with no features and sign of severe malaria

Confirmed uncomplicated vivax malaria

A patient who presents with symptoms of malaria and a positive parasitological test (microscopy or RDT) of

P. vivax, but with no features and sign of severe malaria

Confirmed uncomplicated mixed infection

A patient who presents with symptoms of malaria and a positive parasitological test (microscopy or RDT) of

P. falciparum and P. vivax, but with no features and sign of severe malaria

Severe malaria

Severe malaria is defined as acute falciparum malaria with signs of severe illness and/or clinical or laboratory

evidence of vital organ dysfunction.

Severe falciparum malaria should be diagnosed if there are asexual forms of P. falciparum in a blood film

from a patient showing any of the following clinical features or laboratory findings (singly or in combination).

Clinical features of severe malaria:

Impaired consciousness: A Glasgow coma score < 11 in adults or a Blantyre coma score < 3 in children

(including unrousable coma);

Prostration, i.e. generalized weakness so that the patient is unable to sit, stand or walk without

assistance;

CASE DEFINITIONS

14

Multiple convulsions: more than two episodes within 24h;

Deep breathing and respiratory distress (acidotic breathing);

Acute pulmonary edema and acute respiratory distress syndrome;

Circulatory collapse or shock, systolic blood pressure < 80mm Hg in adults and < 50mm Hg in children;

Clinical jaundice plus evidence of others vital organ dysfunction; and

Abnormal spontaneous bleeding

Laboratory and other findings:

Hypoglycemia (< 2.2mmol/l or < 40mg/dl);

Metabolic acidosis (plasma bicarbonate < 15mmol/l);

Severe normocytic anemia (hemoglobin < 5g/dl, packed cell volume < 15% in children; <7g/dl, packed

cell volume < 20% in adults);

Hemoglobinuria;

Hyperlactatemia (lactate > 5mmol/l);

Renal impairment (serum creatinine > 265μmol/l); and

Pulmonary edema (radiological).

Hyperparasitaemia

Acute kidney injury (serum creatinine 265mmol/litre or greater).

Probable severe malaria

A patient with suspected malaria (fever or history of fever, with no other obvious cause) presenting with one

or more clinical features or laboratory findings of severe malaria, and requiring hospitalization that is not

confirmed parasitologically

However, this should be kept in mind that all suspected severe malaria cases must be parasitological

confirmed by microscopy and/or RDT.

Confirmed severe malaria

A patient with parasitological confirmation of P. falciparum (either by microscopy or RDT) presenting with

one or more clinical features or laboratory findings of severe malaria.

Below definition is mainly for elimination program:

Autochthonous: A case locally acquired by mosquito-borne transmission, i.e. an indigenous or introduced

case (also called ‘locally transmitted’).

Indigenous case: A case contracted locally with no evidence of importation and no direct link to transmission

from an imported case

Induced case: A case the origin of which can be traced to a blood transfusion or other form of parenteral

inoculation of the parasite but not to transmission by a natural mosquito-borne inoculation

15

Imported case: Malaria case or infection in which the infection was acquired outside the area in which it is

diagnosed

Introduced case: A case contracted locally, with strong epidemiological evidence linking it directly to a known

imported case (first-generation local transmission)

Locally acquired case: A malaria case that is acquired locally by mosquito-borne transmission

Note: Locally acquired cases can be indigenous, introduced, relapsing or recrudescent; the term

“autochthonous” is not commonly used.

16

NTG Chapter 3

Malaria Treatment

17

UNCOMPLICATED MALARIA

First line drug treatment

Probable uncomplicated malaria

All suspected malaria cases should first be tested by microscopy or RDT for parasitological confirmation and

then treated properly. Where confirmation by microscopy or RDT is not available, probable uncomplicated

malaria should be treated as possible vivax malaria with Chloroquine.

Confirmed uncomplicated falciparum malaria

Treat children and adults with uncomplicated P. falciparum malaria (except pregnant women in their first

trimester) with Artemether + lumefantrine.

Standard tablets containing 20 mg artemether and 120 mg lumefantrine, 40 mg artemether and 240 mg

lumefantrine, 60 mg artemether and 260 mg lumefantrine and 80 mg artemether and 480 mg lumefantrine

and in a fixed-dose combination formulation. A total dose of 5–24 mg/kg bw of artemether and 29–144

mg/kg bw of lumefantrine. Artemether + lumefantrine is given twice a day for 3 days (total, six doses). The

first two doses should, ideally, be given 8 h apart.

An advantage of this ACT is that lumefantrine is not available as a monotherapy and has never been used

alone for the treatment of malaria.

Absorption of lumefantrine is enhanced by co-administration with fat. Patients or caregivers should be

informed that this ACT should be taken immediately after food or a fat containing drink (e.g. milk),

particularly on the second and third days of treatment.

Artemether–lumefantrine has a wide therapeutic index and is generally well tolerated, with reported side

effects such as nausea, dizziness and headache that are not easily distinguishable from symptoms of acute

malaria.

Artemether–lumefantrine should not to be administered to patients with known hypersensitivity to either

artemether or lumefantrine.

Decreased exposure to lumefantrine has been documented in young children (<3 years) as well as pregnant

women, large adults, patients taking mefloquine, rifampicin or efavirenz and in smokers. As these target

populations, may be at increased risk for treatment failure, their responses to treatment should be

monitored more closely and their full adherence ensured.

TREATMENT

18

Artemether–lumefantrine has not been studied extensively in patients > 65 years or children weighing < 5

kg. So, these patients should be monitored closely when taking this medication.

Gametocytocidal therapy in confirmed uncomplicated falciparum malaria: A single dose of Primaquine at

0.25 mg base/kg is both effective in blocking transmission and unlikely to cause serious toxicity in individuals

with any of the G6PD-deficiency variants. Therefore; single dose of 0.25 mg/kg bw Primaquine with ACT

should be given to patients with confirmed P. falciparum malaria to reduce transmission. G6PD testing is not

required. The safety of Primaquine as a P. falciparum gametocytocide is reviewed and it is concluded that a

single dose of 0.25 mg/kg bw of Primaquine base is unlikely to cause serious toxicity, even in people with

G6PD deficiency. Thus, a single dose of 0.25mg/kg bw Primaquine base should be given on the first

day of treatment, in addition to an ACT, to all patients with parasitological confirmed P. falciparum

malaria (except pregnant women, infants aged < 6 months and women breastfeeding) because there are

insufficient data on the safety of its use in these groups.

Tolerability can be improved by taking Primaquine with food.

Confirmed uncomplicated vivax malaria:

The objectives of treatment of vivax malaria are: 1) to cure the acute blood stage infection and, 2) to clear

hypnozoites from the liver to prevent future relapses which is known as “radical cure”.

Chloroquine remains an effective treatment for the blood stage of vivax malaria in Afghanistan. Oral

Chloroquine at a total dose of 25 mg base/kg bw in three days, is effective and well tolerated treatment of

P.vivax malaria, and is considered safe in pregnancy. Chloroquine is given at an initial dose of 10 mg base/kg

bw, followed by 10 mg/kg bw on the second day and 5 mg/kg bw on the third day. Lower total doses are not

recommended, as these encourage the emergence of resistance.

Anti-relapse treatment for confirmed vivax malaria:

The relapses originating from liver hypnozoites can be prevented by giving Primaquine. To achieve radical

cure and prevent relapse, treat P. vivax malaria in children and adults (except pregnant women, infants aged

< 6 months, women breastfeeding and people with known G6PD deficiency) with a 14-day course of 0.25 mg

base/kg Primaquine per day.

Primaquine causes dose-limiting abdominal discomfort when taken on an empty stomach; they should

therefore always be taken with food. Primaquine should be given only to patients with parasitological

confirmed vivax malaria. If feasible, determine the G6PD status of patient before administration of

Primaquine.

Where it is not feasible to determine the G6PD status, Primaquine should be given at a dose of 0.75mg

base/kg once a week for 8 weeks under close medical supervision to detect and manage possible cases of

haemolysis. At this dose and schedule, severe hemolysis in-patient with mild to moderate G6PD deficiency is

rare.

19

Anti-relapse treatment and G6PD status:

Patient with normal G6PD level should be treated with 0.25 mg/kg bw per day Primaquine once a day

for 14 days,

Patient with intermediate deficiency can be treated with weekly dose of Premaquine (0.75mg base/kg

once a week for eight weeks) with close clinical follow up, since severe haemolysis in-patient with

moderate G6PD deficiency is rare.

Some heterozygote females who test as normal or not deficient in qualitative G6PD tests may have

intermediate G6PD deficiency and can still haemolyse substantially. Intermediate deficiency (30–80% of

normal) and normal enzyme activity (> 80% of normal) can be differentiated only with a quantitative test.

When the quantitative testing is not available, all females should be considered as potentially having

intermediate G6PD and should be treated with weekly dose of Primaquine (0.75mg base/kg once a week

for eight weeks) with close clinical follow up.

Primaquine should not be given to patients with known severe G6PD deficiency

Confirmed uncomplicated Mix (Pf + Pv) malaria:

Treatment of confirmed uncomplicated mix malaria (P. falciparum + P. vivax) is same as treatment of

confirmed uncomplicated P. falciparum with Artemether + lumefantrine (as mentioned in section 5.1.1.2),

with adding Primaquine for anti-relapse treatment of P. vivax infection (as mentioned in section 5.1.1.3).

Second line drug treatment

Quinine should be considered as second line treatment for patients with recurrent malaria, after completing

the first line treatment, due to treatment failure.

Recurrence of malaria can result from re-infection or recrudescence (treatment failure). Treatment failure

may result from drug resistance or inadequate exposure to the drug due to sub-optimal dosing, poor

adherence, vomiting, unusual pharmacokinetics in an individual /or substandard medicines.

Before starting the second line treatment, it is important to determine:

Whether the patient vomited previous treatment or did not complete a full course of treatment

Adequate dose and course of 1st line treatment was given according to the National Guidelines

If there are other causes of febrile illness to be excluded

Parasitological confirmation of malaria (whether or not this was confirmed before the initial treatment).

The patients initially treated for falciparum malaria that return with confirmed vivax infections should be

treated with CQ as for first line treatment, and similarly, patients initially treated for vivax malaria that return

with confirmed falciparum infections should be treated with recommended ACT as for first line treatment.

These are not treatment failures and the 2nd line treatment should not be given to these groups of patients.

Treatment failure must be confirmed parasitologically. This may require referring the patient to a facility with

microscopy. In individual patients, it may not be possible to distinguish recrudescence (treatment failure)

20

from re-infection, although lack of resolution of fever and parasitaemia or their recurrence within 4 weeks

of treatment are considered failures of treatment. Patients should be asked whether they received

antimalarial treatment within the preceding 1–2 months.

Recurrence of fever and parasitaemia > 4 weeks after treatment may be due to either recrudescence or a

new infection. The distinction can be made only by PCR genotyping of parasites from the initial and the

recurrent infections. As PCR is not routinely used in patient management, all presumed treatment failures

after 4 weeks of initial treatment should, from an operational standpoint, be considered new infections and

be treated with the first-line.

Additional Considerations for Clinical Management

Give first dose under supervision and observe for half an hour. Repeat if vomits within half an hour. Patients

with repeated vomiting require admission. Check for dehydration and treat if necessary.

In young children, high fevers are often associated with vomiting, regurgitation of medication and seizures.

They are thus treated with antipyretics and, if necessary, fanning and tepid sponging. Antipyretics should

be used if the core temperature is > 38.5 ºC. Paracetamol (acetaminophen) at a dose of 15 mg/kg bw every

4 h is widely used; it is safe and well tolerated and can be given orally or as a suppository.

Give second and third dose of medicine for treatment at home. Explain how to give the treatment. Explain

to caregivers that it is important for infants to breastfeed frequently, and older children to drink plenty of

fluids, to prevent dehydration.

Explain to caregivers that if someone is abnormally sleepy or difficult to wake, or has convulsions, or has

difficulty in breathing these are danger signs of severe illness. Seek treatment immediately. Ask the patient

to return after 2 days if there is no improvement.

Some patients cannot tolerate oral treatment and will require parenteral administration for 1–2 days, until

they can swallow and retain oral medication reliably. Although such patients do not show other signs of

severity, they should receive the same initial antimalarial treatments recommended for severe malaria. The

initial parenteral treatment must always be followed by a full 3-day course of ACT.

Anti-emetics are potentially sedative and may have neuropsychiatric adverse effects, which could mask or

confound the diagnosis of severe malaria. They should therefore be used with caution.

SEVERE MALARIA

Severe malaria is a medical emergency, with a very high fatality if not managed urgently and appropriately.

The management involves the use of specific antimalarial medicines and secondly the adjuvant management

of the features of severity or accompanying complications.

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Antimalarial drug treatment of severe malaria

Hospital level

Artesunate IV/IM: Treat adults and children with severe malaria (including infants, pregnant women in all

trimesters and lactating women) with intravenous or intramuscular (IV or IM) Artesunate for at least 24 h

and until they can tolerate oral medication. The recommended parenteral dose of Artesunate is 2.4mg/kg

body weight given intravenously or intramuscularly at admission (time = 0), then at 12h, 24h, then once a

day. Children weighing < 20 kg should receive a higher dose of Artesunate (3 mg/kg bw per dose) than larger

children and adults to ensure equivalent exposure to the drug. Artesunate is dispensed as a powder of

Artesunic acid, which is dissolved in sodium bicarbonate (5%) to form sodium Artesunate. The solution is

then diluted in approximately 5 mL of 5% dextrose and given by intravenous injection or by intramuscular

injection into the anterior thigh. The solution should be prepared freshly for each administration and should

not be stored.

Artemether IM: If parenteral Artesunate is not available, use intramuscular artemether in preference to

Quinine for treating children and adults with severe malaria. The initial dose of artemether is 3.2 mg/kg bw

intramuscularly at time of admission. The maintenance dose is 1.6 mg/kg bw intramuscularly daily.

Artemether is dispensed dissolved in oil and given by intramuscular injection into the anterior thigh.

Intramuscular artemether may be absorbed more slowly than water-soluble Artesunate, which is absorbed

rapidly and reliably after intramuscular injection.

Quinine IV: Last option is Quinine treatment for severe malaria when parenteral Artesunate and artemether

is not available. Studies of pharmacokinetics show that a loading dose of Quinine (20 mg salt/kg bw) provides

therapeutic plasma concentrations within 4h. The maintenance dose of Quinine (10mg salt/ kg bw) is

administered at 8h intervals, starting 8h after the first dose. If there is no improvement in the patient’s

condition within 48h, the dose should be reduced by one third, i.e. to 10mg salt/kg bw every 12h.

Rapid intravenous administration of Quinine is dangerous. Each dose of parenteral Quinine must be

administered as a slow, rate-controlled infusion (usually diluted in 5% dextrose and infused over 4 h). The

infusion rate should not exceed 5 mg salt/kg bw per h. Quinine must never be given by intravenous bolus

injection, as lethal hypotension may result.

Antimalarial drugs should be given parenterally for a minimum of 24h and replaced by oral medication as

soon as it can be tolerated. Anytime, after 24h parenteral treatment, the patient can start swallowing, the

parenteral treatment should be stopped and full treatment course of 3 days oral Artemether + Lumefantrine

with single dose Primaquine as gametocide, must be giver to the patient. Intramuscular injections should be

given into the anterior thigh and not the buttock. Do not attempt to give oral medication to unconscious

children.

Health center level

At health centers (BHC, CHC, mobile team, SHC) where complete treatment of severe malaria is not possible,

all severe malaria patients (adults and children) should be given the initial single intramuscular dose of

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Artesunate (as pre-referral treatment) and then refers the patient to an appropriate facility for further care.

Where intramuscular Artesunate is not available; use artemether in preference to Quinine.

Health Post level

The Community Health Workers (CHWs) at the Health Post (HP) level, should be trained on major signs of

sever malaria and they should refer any sever malaria case to the health center/or hospital for proper

diagnosis and treatment.

MANAGEMENT OF COMPLICATIONS

Severe malaria is associated with a variety of manifestations and complications, which must be

recognized promptly and treated as shown below.

Manifestation or

complication Immediate management

Coma

(cerebral malaria)

Maintain airway, place patient on his or her side, exclude other treatable

causes of coma (e.g. hypoglycaemia, bacterial meningitis); avoid harmful

ancillary treatments, intubate if necessary.

Hyperpyrexia Administer tepid sponging, fanning, a cooling blanket and paracetamol.

Convulsions Maintain airways; treat promptly with intravenous or rectal diazepam,

lorazepam, midazolam or intramuscular paraldehyde. Check blood glucose.

Hypoglycaemia

Check blood glucose, correct hypoglycaemia and maintain with glucose-

containing infusion. Although

hypoglycaemia is defined as glucose < 2.2

mmol/L, the threshold for intervention is

< 3 mmol/L for children < 5 years and <

2.2 mmol/L for older children and adults

Severe anaemia Transfuse with screened fresh whole blood.

Acute pulmonary

edema

Prop patient up at an angle of

45o, give oxygen, give a diuretic,

Stop intravenous fluids, intubate and add positive end-expiratory pressure or

continuous positive airway pressure in life-threatening hypoxaemia.

Acute kidney injury

Exclude pre-renal causes, check fluid balance and urinary sodium; if in

established renal failure, add haemofiltration or haemodialysis, or, if

not available, peritoneal dialysis.

Spontaneous bleeding

and coagulopathy

Transfuse with screened fresh whole blood (cryoprecipitate, fresh frozen plasma

and platelets, if available); give vitamin K injection.

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Malaria treatment in pregnancy

Treatment of probable uncomplicated malaria:

All pregnant women with probable uncomplicated malaria should be treated with CQ and referred for a

parasitological diagnosis.

Treatment of confirmed uncomplicated falciparum malaria

First trimester of pregnancy: Quinine (oral) 10 mg salt /kg (maximum 600mg) three times a day plus

Clindamycin 10mg/kg 2 times a day. All medicines should be given for seven days.

Second and third trimester: AL as above.

Treatment of confirmed uncomplicated vivax malaria

All trimesters: CQ as above.

Treatment of confirmed uncomplicated Mix malaria

Treatment of Mix (P. falciparum + P. vivax) malaria during pregnancy is same as treatment of

confirmed uncomplicated falciparum malaria in different trimesters of pregnancy.

Primaquine is contraindicated.

Treatment of probable or confirmed severe malaria

Same as treatment of severe malaria among others; see above (treatment of severe malaria).

Primaquine is contraindicated and should not be given during pregnancy or to breastfeeding

mothers.

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Chloroquine dosage by mg/bw in Kg

Days Day 1 Day 2 Day 3 Total dose

Dose 10 mg/kg 10 mg/kg 5 mg/kg 25 mg/kg body weight

Chloroquine dosage by number of tablets (150mg base) according to age years

Age Day 1 Day 2 Day 3 Total number of tablets

<1 1/2 1/2 1/4 1.25

1 – 4 1 1 1/2 2.5

5 – 8 2 2 1 5

9 – 14 3 3 1.5 7.5

15 & above 4 4 2 10

Primaquine dose based on 0.25 mg/kg bw according to body weight

Age One dose 7.5 mg base 15 mg base

10 to < 25 3.75 1/2 (0.5)

25 to < 50 7.5 1 1/2 (0.5)

50 to 100 15 2 1

Primaquine dose chart based on 0.75 mg/kg bw according to age years

Age One dose 7.5 mg base 15 mg base

1 - 4 7.5 1 1/2 (0.5)

5 - 8 15 2 1

9 – 14 30 4 2

15 & above 45 6 3

Artemether + Lumefantrine dose given twice daily for 3 days

Body weight (Kg) Dose (mg) 20 mg + 120 mg /tablet

40 mg + 240 mg /tablet

80 mg + 480 mg /tablet

5 to < 1 4 20 + 120 1 1/2 (0.5)

15 to < 25 40 + 240 2 1 1/2 (0.5)

25 to < 3 60 + 360 3 1.5

≥ 35 80 + 480 4 2 1

Quinine dose (10 mg/kg) given three time in a day for 7 days

Age and weight Number of tablets (300 mg) – one dose Total dose for 7 days

5 months to < 2 years/7 to 12 kg 1/4 5.25

2 to < 8 years/12 to < 25 kg 1/2 10.5

8 to < 14 years/25 to <35 kg 1 21

11 to < 14 years/35 to <50 kg 1.5 31.5

≥ years/ ≥ 50 kg 2 42

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Malaria drug dosage chart: (Parenteral drug)

Artesunate injection dose: 2.4 mg/kg (3 mg/kg bw for children under 20 kg bw)

Powder for injection, in 60 mg-vial, with one 1 ml-ampoule of 5% sodium bicarbonate and one 5 ml ampoule

of 0.9% sodium chloride, for slow IV (3 to 5 minutes) or slow IM injection.

Dissolve the powder in the entire volume of 5% sodium bicarbonate and shake the vial until the solution

become clear. then, add the 0.9% sodium chloride into the vial (for IV injection: 5 ml of 0.9% sodium chloride

to obtain 6 ml of Artesunate solution containing 10 mg/ml; and for IM injection: 2 ml of 0.9% sodium

chloride to obtain 3 ml of Artesunate solution containing 20 mg /ml)

Body weight (kg) IV injection

(Artesunate solution 10 mg/ml

IM injection

(Artesunate solution 20 mg/ml

<3 1 ml 0.5 ml

3 to <4 1.2 ml 0.6 ml

4 to <5 1.5 ml 0.8 ml

5 to <6 2 ml 1 ml

6 to <8 2.5 ml 1.2 ml

8 to <10 3 ml 1.5 ml

10 to <13 4 ml 2 ml

13 to <15 4.5 ml 2.5 ml

15 to <17 5 ml 2.5 ml

17 to <20 6 ml 3 ml

20 to <25 6 ml 3 ml

25 to <29 7 ml 3.5 ml

29 to <33 8 ml 4 ml

33 to <37 9 ml 5 ml

37 to <41 10 ml 5 ml

41 to <45 11 ml 6 ml

45 to <50 12 ml 6 ml

50 to <55 13 ml 7 ml

55 to <62 15 ml 8 ml

62 to <67 16 ml 8 ml

67 to <71 17 ml 9 ml

71 to <76 18 ml 9 ml

76 to <81 20 ml 10 ml

Artemether injection dose: 80 mg /ml ampoule, oily solution for IM injection (3.2 mg/kg by IM injection on the first

day followed by 1.6 mg/kg once daily)

when dose required is less than 1 ml, use a 1 ml syringe graduated in 0.01 ml

Body weight (kg) 80 mg ampoule

Loading dose Maintenance dose

3 -4 kg 0.2 ml 0.1 ml

5-6 kg 0.3 ml 0.15 ml

7-9 kg 0.4 ml 0.2 ml

10-14 kg 0.6 ml 0.3 ml

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15-19 kg 0.8 ml 0.4 ml

20-29 kg 1.2 ml 0.6 ml

30-39 kg 1.6 ml 0.8 ml

40-49 kg 2 ml 1 ml

50-59 kg 2.5 ml 1.2 ml

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1. Guidelines for the treatment of malaria – 3rd edition – World Health Organization (2015)

2. Management of Severe Malaria, A Practical Handbook– 3rd Edition – World Health Organization (2013)

3. Policy brief on single-dose Primaquine as a gametocytocide in Plasmodium falciparum malaria, World

Health Organization, 2015

4. WHO malaria terminology, Global Malaria Programme, WHO, 2017

5. National Strategic Plan “From Malaria Control to Elimination in Afghanistan” (2018-2022)

6. Malaria Program Review (MPR), report, in Afghanistan (2016)

7. Therapeutic Efficacy Study of Artemether - Lumefantrine in Afghanistan, study report (2015)

REFERRANCE

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