MANAGEMENT_GUIDELINES_OF_MALARIA_IN_MALAYSIA.pdf1_ 2

The life cycle of malaria parasites comprises a sexual phase with multiplication in the mosquito (sporogony) and an asexual phase with multiplication in the human (schizogony).

The four Plasmodium species transmitted from humans-to-humans are P. falciparum, P. vivax, P. ovale, and P. malariae.

The female anopheline mosquito inoculates the malaria parasites into the human host during feeding.

Artesunate + Mefloquine (AS+MQ) is the first line treatment, but it should not be used in pregnancy and may cause seizures in children with epilepsy.

Artemisinin Combination Therapy (ACT) is the standard treatment recommended by WHO for malaria, aimed at alleviating symptoms and preventing relapses and spread of the disease.

P. knowlesi is a simian malaria parasite that has increasingly been reported in human infections, particularly in forested regions of Malaysia and Southeast Asia.

An alternative ACT regimen can be used, such as Oral Quinine with Doxycycline or Primaquine, depending on the patient's condition and G6PD status.

The pre-patent period is the time period before merozoites enter the blood from the liver, which varies by Plasmodium species: about 12 days for P. falciparum and P. knowlesi, 14 days for P. vivax and P. ovale, and 30 days for P. malariae.

Monotherapy is discouraged because it promotes the development of resistant Plasmodium strains.

Do not repeat the AS-MQ regimen within 60 days due to increased risk of neuropsychiatric reactions, and it interacts with Quinine, Chloroquine, and Halofantrine, which may cause arrhythmia.

Malaria Chemoprophylaxis refers to the use of antimalarial drugs to prevent malaria infection, combined with mosquito avoidance measures.

During tissue schizogony, an infected female Anopheles mosquito injects sporozoites that rapidly enter hepatocytes and reproduce by asexual fission to form a pre-erythrocytic schizont, producing no symptoms.

G6PD deficiency testing is important because patients with this deficiency may experience hemolysis when treated with primaquine, necessitating immediate cessation of the drug if symptoms arise.

Riamet is a first-line treatment for non-complicated Plasmodium falciparum malaria, consisting of 20mg artemether and 120mg lumefantrine, administered in a 3-day schedule with a total of 6 doses.

Suppressive prophylaxis refers to the use of drugs like chloroquine, proguanil, mefloquine, and doxycycline that are effective at killing the malaria parasite only after it has entered the erythrocytic stage of its life cycle, requiring continued use for four weeks after leaving the area of risk.

Checking G6PD status is important before using Primaquine to avoid hemolytic anemia in patients with G6PD deficiency.

IV Artesunate 2.4mg/kg at 0 hour, 12 hour, 24 hour and daily subsequently till day 7, along with Oral Doxycycline 100mg BD.

Some people prefer to take a daily medicine; good for short trips and last-minute travelers; tends to be the least expensive; can prevent some additional infections (e.g., Rickettsiae and leptospirosis).

Mosquito avoidance measures include using insect repellant, wearing long sleeves and pants, sleeping in mosquito-free settings, or using insecticide-treated bednets.

Mefloquine is a good choice for long trips because it is taken only weekly, can be used in the second and third trimester of pregnancy, and in the first trimester if there is no other option.

The erythrocytic cycle is the process where merozoites invade erythrocytes, undergo blood schizogony to form trophozoites, evolve to schizonts, and rupture to release new merozoites, occurring every 24, 48, or 72 hours depending on the Plasmodium species.

For patients weighing 15-<25kg, the recommended dosage of Riamet is 2 tablets per dose.

Presumptive treatment is administered to patients with classical malaria symptoms when blood film results are unavailable, particularly in remote areas, and is based on the predominant species in that area.

The incubation period of malaria is variable, averaging 10–14 days, but can be as short as 7 days or, in exceptional cases, up to 20 years in P. malariae infection.

Patients with any features of severe malaria should be referred to a hospital with a HDU or ICU, and all patients with complicated malaria should be referred to the Physician on call for further evaluation and management.

Causal prophylaxis targets both the blood stages and the initial liver stage of malaria, allowing the user to stop taking the drug seven days after leaving the area of risk. Atovaquone/Proguanil (Malarone) and primaquine are examples of causal prophylactics.

Contraindicated in pregnancy and children under 8 years old; photosensitivity requiring avoidance of sun exposure; gastrointestinal upset; vaginal candidiasis.

The incidence of malaria in Malaysia declined from 12,705 cases in 2000 to 4,725 cases in 2012, indicating a significant reduction in malaria cases.

IV Quinine 20mg salt/kg over 4 hours in D5%, or IV Quinine 7mg salt/kg over 1 hour followed by 10mg salt/kg over 4 hours, then IV Quinine 10mg/kg 8 hourly for 7 days.

Uncomplicated malaria is defined as symptomatic malaria without signs of severity or evidence (clinical or laboratory) of vital organ dysfunction.

Diethyltoluamide (DEET) is an effective insect repellent used in concentrations of 20-50% for preventing mosquito bites.

Mefloquine cannot be used in areas with mefloquine resistance, in patients with certain psychiatric conditions, epilepsy, or cardiac conduction abnormalities, and is not a good choice for last-minute travelers or short-duration trips.

Antimalarial drug resistance refers to the ability of malaria parasites, such as P. falciparum, P. malariae, and P. vivax, to survive despite the administration of antimalarial drugs, with varying geographical distributions and rates of spread.

Sulphadoxine/Pyrimethamine should not be used for field treatment due to high levels of resistance observed in malaria parasites.

The Glasgow Coma Scale (GCS) is used to assess the level of consciousness and neurological status of the patient during the physical examination.

EBT is a procedure used in severe malaria to remove infected red blood cells from circulation, lowering parasite burden, and reducing antigen load and toxic mediators, but it requires expertise and monitoring.

The early symptoms of malaria are non-specific and include headache, lassitude, fatigue, abdominal discomfort, muscle and joint aches, followed by fever, chills, perspiration, anorexia, vomiting, and worsening malaise.

The Case Fatality Rate of malaria has been around 0.3 to 0.5 per 100,000 population since 2006, indicating the proportion of deaths among diagnosed cases.

The first-line treatment for P. vivax infection is oral Chloroquine 10mg base/kg (max 600mg) stat, followed by 5mg base/kg (max 300mg) 6 hours later, and then on Day 2 and Day 3. Additionally, Primaquine 0.5 mg/kg (max 30mg) OD for 14 days is recommended.

The patient's blood glucose and ECG should be monitored.

Considerations include checking the risk of exposure to malaria, potential drug-drug interactions, the length of the trip, previous adverse reactions, current medical history, and starting chemoprophylaxis earlier if there are concerns about tolerance.

Good for last-minute travelers; suitable for shorter trips; very well-tolerated with uncommon side effects.

An alternative treatment for Plasmodium falciparum is Artesunate/Mefloquine (AS+MQ), which is administered in a 3-day schedule with varying dosages based on patient weight.

Severe malaria usually manifests with one or more of the following: coma (cerebral malaria), metabolic acidosis, severe anaemia, hypoglycaemia, acute renal failure, or acute pulmonary oedema.

The risk of acquiring malaria is influenced by transmission intensity, duration of stay in endemic areas, and the efficacy of preventive measures.

Resistance in P. falciparum has been observed in all currently used antimalarials, including amodiaquine, chloroquine, mefloquine, quinine, sulfadoxine-pyrimethamine, and more recently, artemisinin derivatives.

For pediatric patients weighing less than 15 kg, the dosage is 5 mg of salt per kg.

Whole blood in EDTA or dried blood spot on filter paper are the preferable specimens for PCR analysis.

Severe malaria is caused by the presence of a high density of asexual forms of Plasmodium in the patient’s body, requiring urgent management at secondary or tertiary hospitals.

The thick and thin film should be prepared on one slide and sent to the laboratory to allow for accurate detection and identification of malaria parasites.

Investigations include Blood for Culture and Sensitivity, Full Blood Count, Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Serum Urea and Electrolytes, Creatinine, Blood glucose, Liver Function Test, Chest X-ray, Arterial Blood gas, and Serum Lactate.

The classical paroxysm begins with a 'cold stage' with rigors, followed by a 'hot stage' with a temperature over 40°C, restlessness, and possible vomiting or convulsions, and ends with a 'sweating stage' when the fever abates.

There is no consensus on the indications, benefits, and risks of EBT in severe malaria, and no randomized clinical trials have been conducted to support its use.

In 2012, 61.6% of the reported malaria cases were human malaria infections.

In patients with mild variants of G6PD deficiency, primaquine should be given in a dose of 0.75 mg base/kg body weight once a week for 8 weeks. If significant haemolysis occurs during treatment, primaquine should be stopped.

In 1993, the overall resistance to chloroquine in Peninsular Malaysia was documented as 63.3%.

The quinine dose should be reduced by one third after 48 hours.

Suppressive prophylactics must be taken for four weeks after leaving the area of risk because they are only effective against the malaria parasite once it has entered the erythrocytic stage, which occurs after the liver stage is complete.

Contraindicated in pregnancy or breastfeeding and in patients with severe renal impairment; expensive.

Primaquine is given at a dosage of 0.75mg/kg (max 45mg) on Day 1 of treatment in addition to the artemisinin regimen and quinine, except for pregnant women and infants under 1 year of age.

Clinical features include impaired consciousness or unrousable coma, prostration, failure to feed, convulsion, respiratory distress, circulatory collapse, clinical jaundice, haemoglobinuria, abnormal spontaneous bleeding, and pulmonary oedema.

Clinical Diagnosis refers to the process of identifying malaria based on symptoms and clinical criteria, which can vary by region and require exclusion of malaria in febrile patients from endemic areas.

Travelers going to West Africa and Oceania have the highest estimated relative risk for malaria infection.

The maximum duration for taking Mefloquine is 1 year.

Patients with manifestations of severe/complicated malaria, those who cannot tolerate orally, those with high parasitaemia (>100,000/μl), patients with G6PD deficiency, all pregnant mothers with acute malaria, patients with severe malnutrition, and children must be admitted.

Whole blood via venipuncture in EDTA should be kept at 4°C within 3-4 hours or minus 20°C if a longer period is needed for transportation.

10% Giemsa stain is used to stain the thick (unfixed) and thin (fixed) films, allowing for better visualization of malaria parasites under the microscope.

If IV Artesunate is not available, IV Quinine should be administered, or IM Quinine if there is no IV access.

Adjunctive treatments such as dexamethasone, iron chelation, and N-acetylcysteine are not supported by evidence of benefit in severe malaria patients.

If prompt and effective treatment is not given, especially in P. knowlesi and P. falciparum malaria, the parasite burden increases every 24 or 48 hours, potentially leading to severe malaria and death.

P. vivax accounted for 50.2% of human malaria infections in 2012.

Limited data on the safety of artemisinin exposure during the first trimester suggests that quinine is recommended, while exposure during the second and third trimesters has shown no adverse effects on the mother or fetus.

Primaquine 0.75mg/kg (max 45mg) should be given on Day 1 of treatment in addition to artemisinin regime and quinine, except for pregnant women and infants under 1 year of age.

If there are concerns about tolerance to malaria medications, it is recommended to start chemoprophylaxis earlier, such as starting mefloquine 3–4 weeks in advance to allow potential adverse events to occur before travel.

The recommended treatment for P. malariae infection is Riamet (1 tablet: 20mg artemether/120mg lumefantrine) for a 3-day schedule with a total of 6 doses. For severe cases, IV Artesunate and Oral Doxycycline 100mg BD for 7 days are advised.

A travel history is crucial in diagnosing malaria, especially in febrile patients, as it helps identify potential exposure to malaria in endemic regions.

Laboratory findings include hypoglycaemia, metabolic acidosis, severe normocytic anaemia, haemoglobinuria, hyperparasitaemia, hyperlactataemia, and renal impairment.

If referral is not possible, the patients must be discussed with Physicians/Infectious Disease Specialists regarding the plan of management.

Patients with severe splenic dysfunction and pregnant women should avoid traveling to endemic areas.

Mefloquine should be started 2 weeks before departure and stopped 4 weeks after travel.

Rapid Diagnostic Tests are based on the detection of circulating parasite antigens and can be supplementary when malaria diagnosis is performed by relatively inexperienced staff.

Minimizing the time between blood collection and film preparation helps to reduce morphological changes in the parasites, ensuring more accurate microscopy results.

Close observation of vital signs and GCS is vital to detect any deterioration in the patient's condition, especially due to complications like pulmonary edema.

Patients must be kept warded until cleared of gametocytes to prevent the spread of malaria, which is a public health concern.

Maintain airways and provide ventilator support if necessary; exclude other treatable causes of coma such as hypoglycaemia and bacterial meningitis; avoid harmful ancillary treatments like corticosteroids, heparin, and adrenaline.

In high-transmission areas, most infections are asymptomatic, and symptomatic malaria occurs primarily in the first few years of life, reflecting a state of imperfect immunity that controls the infection at levels below those causing symptoms.

Imported malaria cases pose a real threat of re-introducing malaria into areas that have eliminated the disease, especially due to frequent travel and influx of workers from endemic countries.

P. malariae and P. knowlesi cannot be distinguished by microscopy. In regions like Sabah and Sarawak, P. malariae is rare, and most cases diagnosed as P. malariae are actually P. knowlesi when tested by PCR.

In exceptional cases where admission is not possible, uncomplicated malaria can be managed at out-patient clinics with close monitoring.

Parasitological diagnosis is essential for confirming clinical suspicion of malaria and involves detecting malaria parasites in the blood.

Mefloquine is the preferred choice for Malaysia due to its efficacy and dosing schedule suitable for long trips.

Complications include cerebral malaria, anaemia, respiratory distress/acute respiratory distress syndrome (ARDS), renal failure, hypoglycaemia, circulatory collapse (shock), and coagulopathy.

To avoid potential hemolytic reactions in patients with G6PD deficiency.

Quantitative malaria microscopy assists doctors in assessing disease severity, monitoring response to treatment, and tracking the patient's progress.

Histidine-rich protein-2 is a water-soluble protein produced by trophozoites and young gametocytes of P. falciparum, and RDTs that use HRP2 detect P. falciparum only.

Patients infected with P. vivax should be followed up monthly for one year after treatment.

Pulmonary edema is a grave complication of severe malaria, particularly in falciparum malaria, with a high mortality rate of over 80%.

Immunity to malaria is modified in pregnancy and is often gradually lost, at least partially, when individuals move out of endemic areas for long durations.

Maintain airways and treat promptly with intravenous or rectal diazepam and/or other anticonvulsants. Check blood glucose, blood urea, and serum electrolytes; prophylactic anticonvulsants are not recommended.

Ensure that a referral letter and BFMP slides are sent along, and that antimalaria treatment is commenced prior to transfer.

For severe P. vivax infection, treatment is similar to that for severe P. falciparum, which includes IV Artesunate and appropriate antimalarial therapy.

A big proportion (78.2%) of the malaria cases in 2012 were among males.

Tests available for laboratory diagnosis include Blood Film for Malaria Parasite (BFMP), Polymerase Chain Reaction (PCR), and Rapid Diagnostic Test (RDT).

Microscopy has high sensitivity, can quantify parasite load, and can distinguish various species and stages of malaria parasites.

RDTs may remain positive for several weeks even after successful treatment, thus they should only be used for the diagnosis of acute malaria infections.

Fluid management should be cautious, maintaining circulation and correcting dehydration, with a urine output goal of > 1ml/kg body weight per hour, avoiding rapid fluid boluses.

If antimalarial drug resistance is suspected, follow-up should be extended beyond one month and reported to state and ministerial levels for further action.

Correct hypoglycaemia and maintain it with a glucose-containing infusion.

The age group of 20 to 29 years accounted for 25% of all malaria cases in 2012.

A limitation of microscopy is that it requires adequately trained laboratory technicians to ensure accurate results.

The BFMP test involves examining thick and thin blood films for malaria parasites, which should be done immediately without waiting for fever peaks.

The laboratory turnaround time for qPCR (real time) is 3 working days.

Exclude pre-renal causes, check fluid balance and urinary sodium; in established renal failure, initiate haemofiltration, haemodialysis, or peritoneal dialysis.

The thick film is more sensitive for detecting malaria parasites as it allows for a greater volume of blood to be examined.

There is considerable variability in performance of the pLDH and aldolase-based tests for non-falciparum species, and none are sufficiently sensitive for P. knowlesi.

Thrombocytopenia is a condition characterized by low platelet count, which is present in more than 90% of non-immune patients with malaria and is a key indicator in diagnosis.

Blood transfusion where indicated.

The thin film helps in the identification of malaria parasite species.

A raised CRP level indicates inflammation and is often elevated in malaria, helping to differentiate it from other causes of fever.

Prop the patient up at an angle of 45°, give oxygen and other respiratory support as indicated, and adjust fluid therapy appropriately; diuretics may be necessary.

The recommended turnaround time for microscopy results in hospitals is within 1 hour after BFMP slides have reached the laboratory.

Monitoring BFMP daily during hospital stay and weekly during follow-up is crucial for assessing the presence of malaria parasites and guiding treatment.

Assess hydration status and provide appropriate fluid therapy; achieve CVP measurement of 8-12 cm H2O. Suspect septicaemia in unexplained clinical deterioration and start parenteral broad-spectrum antimicrobials.

Adjunct therapy refers to any additional treatment that modifies physiological processes caused by malaria, acting directly on specific biological pathways altered by malaria or on end-stage factors produced by various processes.

Look for other causes such as meningitis; a lumbar puncture may be indicated, and antibiotics should be instituted.

There is considerable clinical overlap between septicaemia, pneumonia, and severe malaria, and these conditions may coexist; if secondary infections are suspected, start broad-spectrum IV antibiotics.

High fever can be managed by tepid sponging and administering Paracetamol.