GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF MALARIA IN VANUATU

Transcription

1 GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF MALARIA IN VANUATU Ministry of Health, Vanuatu 2009

2 FOREWORD These national guidelines for the diagnosis and treatment of malaria in Vanuatu has been prepared by the National Malaria Control rogramme, Ministry of Health, Vanuatu, with technical support from the World Health Organization. 2

3 LIST OF CONTENT FOREWORD LIST OF CONTENT LIST OF ABBREAVTIONS 1. INTRODUCTION 2. KEY RINCILES AND RECOMMENDATIONS ON MALARIA TREATMENT IN VANUATU 3. CLASSIFICATION AND CLINICAL FEATURES OF MALARIA 4. ARASITOLOGICAL DIAGNOSIS OF MALARIA 5. TREATMENT OF LASMODIUM FALCIARUM First line treatment of uncomplicated. falciparum malaria Malaria treatment failure Second line treatment of uncomplicated. falciparum malaria re referral treatment of severe. falciparum cases First line treatment of severe. falciparum malaria Second line treatment of severe. falciparum malaria 6. TREATMENT OF LASMODIUM VIVAX, INCLUDING MIXED INFECTIONS 7. RESUMTIVE TREATMENT OF MALARIA 8. MALARIA TREATMENT AND CHEMOROHYLAXIS OF IN REGNANT WOMEN 9. ATIENT COUNSELLING ANNEX 1: Use of malaria rapid tests (RDTs) ANNEX 2: reparation of artesunate injections and suppositories 3

4 LIST OF ABBREVIATIONS ACT ALU AS CNS CQ ECG G6D h i.m. i.v. f Q R v QN RDT S Artemisinin based Combination Therapy Artemether Lumefantrine Artesunate Central Nervous System Chloroquine Electrocardiogram Glucose 6 phosphate dehydrogenase Hour Intramuscular Injection Intravenous Injection lasmodium falciparum rimaquine er Rectum lasmodium vivax Quinine Rapid Diagnostic Test Sulfadoxine pyrimethamine 4

5 1. INTRODUCTION Despite progress made in reducing malaria in Vanuatu in recent years, malaria still remains a major public health problem in the country. Early diagnosis and effective treatment of malaria at all health facility levels remains a key component of the national malaria control strategy; however, access to early and definitive diagnosis has been constrained by the low diagnostic coverage (malaria microscopy limited to only 10 percent of health facilities in the country in 2007), while provision of effective treatment has been challenged by increasing levels of parasite resistance against previously used antimalarial drugs (chloroquine and sulfadoxine pyrimethamine). Another important barrier to effective malaria control is the burden of lasmodium vivax infections, contributing to approximately half of all confirmed cases of malaria cases in the country, although rarely receiving radical treatment with primaquine due to concerns over sideeffects in patients with possible G6D deficiency. Moreover, the health system in Vanuatu is generally weak, and except for the six provincial hospitals and one private hospital, health facilities from health centre to aid post levels are staffed with nurses and village health workers, who may have received only limited training on the clinical management of malaria. These new national guidelines for the diagnosis and treatment of malaria are developed to ensure the most appropriate and effective treatment for malaria at all levels of the health system in Vanuatu. It describes in simple terms the essentials of malaria diagnostics, emphasising in particular the use of rapid diagnostic tests where malaria microscopy is not available. It also introduces the newly adopted first line antimalarials for uncomplicated malaria, namely artemisinin based combination treatments (ACTs) for both falciparum and vivax malaria, which is now considered the best current treatment for uncomplicated malaria. For the treatment of severe malaria, intravenous treatment with artesunate is introduced in replacement of quinine, while artesunate rectal suppositories are introduced at the peripheral level for pre referral treatment for of severe cases of malaria. Ensuring the widest possible diagnostic coverage and the switch to artemisinin based treatment of malaria, as adopted by the Ministry of Health in 2007, are important steps toward improving clinical management of malaria, and are key elements of the intensified efforts towards controlling and eventually eliminating malaria in Vanuatu. 5

6 2. KEY RINCILES AND RECOMMENDATIONS ON MALARIA DIAGNOSIS AND TREATMENT IN VANUATU With the introduction of the revised guidelines for diagnosis and treatment of malaria in Vanuatu the following key principles and recommendations should be followed, in the public as well as in the private health sector Confirmed malaria diagnosis wherever possible Targeted malaria treatment should always be aimed for, which means using the correct medicine to treat the type of malaria the patient has (. falciparum,. vivax, or both). resumptive treatment of malaria should be avoided to any extent possible. Targeted treatment is achieved by examining every suspected case of malaria with either high quality microscopy (still the most definitive diagnostic technique), or with a malaria rapid test (RDT). resently in Vanuatu, the diagnostic coverage based on microscopy is low (around 10%), therefore to increase diagnostic coverage for malaria in Vanuatu, RDTs are introduced in all health facilities, to be used where and when microscopy is not available. Improved diagnostic coverage will mean that the need to prescribe antimalarials based purely on clinical grounds will be reduced. Unnecessary treatments will thus largely be avoided, while alternative causes of illness and other required treatment should be looked for. Increasing diagnostic coverage also means that reporting of malaria will improve, which will enable more accurate planning and procurement of drugs. Importantly, however, presumptive treatment may still be used where no diagnostic facilities are immediately available, and where delay in treatment is considered unacceptable due to the clinical condition of the patient. Such situations also include cases, where there is a continued strong clinical suspicion of malaria despite a negative RDT test. 2.2 Artemisinin based combination treatment (ACT) for all uncomplicated cases of both falciparum and vivax malaria in all public and private health facilities Due to increasing rates of parasite resistance to previously used first line antimalarials (chloroquine and sulfadoxine pyrimethamine), in Vanuatu as well as in neighbouring countries, a new first line treatment is now introduced: artemether lumefantrine (ALU). This new treatment is administered as a fixed tablet of Coartem twice daily for 3 days. All treatment schedules are shown in this protocol. Importantly, malaria should NEVER be treated with only one drug (i.e. monotherapy). Chloroquine should no longer be used for the treatment of malaria; however, chloroquine should still be used for malaria chemoprophylaxis in pregnancy. 6

7 and trimester. 2.3 Artesunate suppositories for pre referral treatment of patients with severe malaria It is vitally important to treat falciparum malaria early to prevent progression into severe and life threatening disease. atients, who have already developed signs of severe illness when arriving at a peripheral health facility, should be given pre referral treatment in the form of artesunate suppositories, and thereafter immediately be referred for parenteral treatment at a higher level health facility. 2.4 Artesunate injections for the treatment of severe malaria cases Due to its superior efficacy compared to quinine for parenteral treatment of severe malaria, artesunate injections is now the recommended first line treatment for severe malaria for nd rd both children and adults, including pregnant women in Radical treatment for vivax malaria lasmodium vivax remains responsible for a significant burden of malaria in Vanuatu. Wider use of good quality diagnostics, such as RTDs, will identify vivax malaria better and allow more targeted treatment, which needs to include radical treatment with primaquine. Only by use of primaquine can relapsing cases and transmission of vivax malaria be prevented, and thus only by the use primaquine can vivax malaria be effectively controlled and eventually eliminated in Vanuatu. rimaquine treatment is therefore highly recommended for cases of confirmed vivax malaria. However, important exceptions to the use of primaquine for vivax malaria still include the following groups: 1) regnant women, 2) Children below 1 year and/or below the weight 6 kg, and 3) atients with severe G6D deficiency. Therefore, to be able to ensure the widest possible use of primaquine, patient with confirmed vivax malaria and who's G6D deficiency status is unknown, need to be referred to health facilities where testing facilities for G6D deficiency is available. The Ministry of Health aims to make G6D deficiency testing facilities available in all provinces, and it thus the hope to be able to re introduce safe and widespread use of primaquine in Vanuatu in the coming years. 2.6 Early diagnosis and treatment and other measures to prevent transmission The new malaria treatment guidelines emphasize the importance of early diagnosis and prompt treatment. Early diagnosis and treatment of malaria is essential for two main reasons: 1) to minimize malaria morbidity and prevent deterioration and development of severe and life threatening complications e.g. cerebral malaria, and 2) to prevent malaria transmission. Therefore, early diagnosis and treatment is beneficial both for the individual patient and for his/her community. To reduce the risk of malaria transmission further, everyone should also be advised to avoid mosquito bites by sleeping under insecticidetreated bed nets at all times. 7

8 2.7 atient counselling to ensure compliance and correct timing of treatments To ensure effective treatment and to prevent development of drug resistance, patients and caretakers should be carefully instructed in taking the full course of the artemetherlumefantrine treatment and to adhere to correct time intervals. Health workers must pay close attention to ensuring adequate patient counselling about the new treatments, which will be key to maintain effective treatments. 8

9 3. CLASSIFICATION AND CLINICAL FEATURES OF MALARIA The clinical course of malaria may present as uncomplicated or severe, as described below. 3.1 Uncomplicated malaria This condition is usually mild, characterized by fever in the presence of peripheral parasitaemia. Other features may include chills, profuse sweating, fatigue, muscle pains, joint pains, abdominal pain, diarrhoea, nausea, vomiting, irritability and refusal to feed. These features may occur alone or in combination. 3.2 Severe malaria This is a life threatening and complicated manifestation of malaria, defined as the presence of. falciparum in peripheral blood together with any of the following clinical or laboratory features (alone or in combination): rostration (inability or difficulty to sit upright, stand or walk without support in a child normally able to do so, or inability to drink in children too young to sit). Alteration in level of consciousness (ranging from drowsiness to deep coma). Cerebral malaria is defined as unrousable coma not attributable to any other cause in a patient with peripheral. falciparum parasitaemia. Respiratory distress (acidotic breathing or deep breathing). Multiple generalized convulsions (2 or more episodes within a 24 hour period). Circulatory collapse (shock, septicaemia). ulmonary oedema. Abnormal bleeding (Disseminated Intravascular Coagulopathy). Jaundice. Haemoglobinuria (Black Water Fever). Acute renal failure presenting as oliguria or anuria. Severe anaemia (Hb <5g/dl or Hct < 15%). Hypoglycaemia (blood glucose level < 2.2.mmol/l). Hyperparasitaemia (parasitaemia of >100,000/µl). Hyperlactataemia. 9

10 4. ARASITOLOGICAL DIAGNOSIS OF MALARIA Two parasite based methods are available in Vanuatu to confirm the presence of malaria: Standard microscopy, and malaria rapid tests (RDTs). Until recently, the diagnostic coverage in Vanuatu was only low, due to difficulty in maintaining microscopic services in all provinces. With the countrywide distribution of RDTs to all health facilities, access to diagnostic test for malaria is now possible to all patients. However, malaria microscopy still remains the gold standard for malaria diagnosis, and therefore the MOH will ensure continued availability of high quality malaria microscopy services in all provinces. For this purpose, quality assurance systems need to be in place for both malaria microscopy and RDTs, to ensure high sensitivity and specificity of results. 4.1 Malaria microscopy Microscopy is still considered to be the gold standard method for parasitological diagnosis of malaria. 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. Thin films are recommended for species identification and can also be used for parasite quantification. arasites are commonly quantified by counting ring forms against white blood cells. The results are expressed as parasite count/200wbcs or parasite count/µl of blood (assuming a WBC count of 8000/µl or using the measured WBC count of the patient where available). 4.2 Malaria rapid diagnostic tests (RDTs) Malaria rapid diagnostic tets (RDTs), sometimes called "dipsticks", are based on the detection of specific parasite antigens (proteins), which are present in the blood of infected patients. The tests used in Vanuatu can detect both. falciparum and. vivax, including mixed infections. When used correctly, RDTs is a useful tool to guide case management, especially where malaria microscopy is not available. For more detailed information on the practical use of RDTs, please see Annex 1. 10

11 4.3 Diagnostic process for malaria In the case that a patient presents to a health facility, do the following: Take routine medical history and do clinical examination. For any patients suspected with malaria, collect a sample of finger prick blood for examination using either malaria microscopy or RDT. If the malaria diagnosis is confirmed by a positive test, initiate relevant treatment (see treatment protocols). If the malaria diagnosis is not confirmed by a positive test, re evaluate the patient and consider alternative cause of illness. If no other cause of illness is identified, which explains the clinical symptoms of the patient, consider then to treat for malaria, despite the test being negative. Also consider to refer the patient for further examination at a higher level health facility. 11

12 T TREATMENT OF FALCIARUM MALARIA 5.1 First line treatment for uncomplicated. falciparum malaria The recommended first line treatment for uncomoplicated malaria in Vanuatu is oral treatment with tablets of artemether lumefantrine, also known as Coartem. Artemether lumefantrine (ALU) is administered as a fixed combined tablet (artemether 20mg & lumefantrine 120mg) in six s over 3 days (0h, 8h, 24h, 36h, 48h & 60h). Different blister packages exist for different patient weight groups, providing exactly the required number of tablets per for each age group. A dosing table by patient weight group above 5 kg and bigger is shown below. For infants weighing less than 5 kg, it is recommended to use the of 2mg/kg/(A) & 12mg//kg(LU). Artemether lumefantrine (Coartem ) treatment schedules, depending on the time of the day treatment is initiated: When treatment is initiated before 4pm on Day 1: Day 1 st 0 hours nd at 8 hours after 1 Day 2 rd in the morning th in the evening Day 3 th in the morning th in the evening st When treatment is initiated after 4pm on Day 1: Day 1 st at 0 hours Day 2 nd in the morning rd in the evening Day 3 th in the morning th in the evening Day 4 th in the morning 12

13 Artemether lumefantrine dosing table for uncomplicated falciparum malaria (artemether 20mg & Lumefantrine 120mg tablets) ATIENT BODYWEIGHT (KG) < DAY 1 st nd at 0 hours* after 8 hours ½ ½ DAY 2 rd th after 24 hours after 36 hours ½ ½ DAY 3 th th after 48 hours after 60 hours ½ ½ * Note: 0 hours is the time when the 1st of AL treatment is given. The second must be given 8 hours after the 1st. Artemether lumefantrine must be taken together with a small volume of fatty food or milk. Older children and adults must swallow the intact tablets, while infants and younger children can swallow crushed tablets from a spoon. 5.2 What to do if the first line treatment fails Malaria treatment failure is defined as failure to achieve an adequate clinical and parasitological response to treatment. Treatment failure should be suspected if malaria symptoms persist or reappear 3 14 days after initiation of the initial malaria treatment. Although treatment failure could be due to drug resistance, it is more likely the result of inadequate medication, often arising form poor patient compliance with the treatment. Therefore, in evaluating a patient with suspected treatment failure, it is important to determine from the patient s history whether he or she e.g. vomited any of the treatment s, or simply did not complete the full treatment course. Importantly, it should be remembered that a treatment failure could also be explained by a wrong diagnosis in the first place, and therefore the wrong treatment. If reappearance of symptoms occurs 14 days or longer after start of treatment, where there has been initial clearance of symptoms, a new infection should be suspected, and be treated with the same first line treatment, i.e. artemether lumefantrine standard regimen. 13

14 Summary criteria for treatment failure: The patient has completed the full course of artemether lumefantrine The patient did not vomit within 1 hour after taking any of the s resence of malaria parasites in blood confirmed by malaria microscopy within 14 days after finishing a full course of artemether lumefantrine It should be noted that treatment failure within 14 days of receiving a full of artemether lumefantrine is very unusual and should be confirmed by microscopy and documented. Management of suspected treatment failure: Any patient with suspected treatment failure must be referred to the nearest health facility with malaria microscopy available for parasitological confirmation. Use of RDTs is not recommended. Confirmed cases of treatment failure should be treated with the recommended second line treatment drug (see section 5.3). Other potential causes of illness must also be considered and adequately managed. Any patient with signs of severe malaria must be referred immediately to nearest hospital. If the treatment failure is explained by poor treatment compliance, the patient should receive a repeat full course of first line treatment, as well as careful counselling. 5.3 Second line treatment for uncomplicated. falciparum malaria The recommended second line treatment for uncomplicated malaria in Vanuatu is oral quinine combined with oral doxycline, both given daily for 7 days. Quinine is administered in the of 10 mg salt/kg Uthree times a day for 7 daysu (see doing table). Doxycycline is administered in the of 3.5 mg/kg Uonce a day for 7 daysu (see dosing table). IMORTANT NOTE: regnant women and children <8 years (equivalent to a bodyweight of approximately 20 KG) should NOT be given doxycycline. Therefore, these patient groups should receive second line treatment in the form of quinine only! 14

15 Dosing table for quinine salt (300 mg tablets) ATIENT BODYWEIGHT (KG) Quinine salt 300 mg tablets per ¼ ½ ¾ 1 1 ½ 2 Note: For children below the lowest weight category, the dosage of quinine is 10mg /kg and the tablets should be reconstituted into syrup based on the weight of the patient. Dosing table for doxycycline (100 mg tablets) ATIENT BODY WEIGHT (KG) Doxycycline 100 mg tablets per ½ ½ re referral treatment for severe malaria cases Any suspected case of severe malaria must wherever possible be immediately referred to the nearest health centre or hospital for parenteral antimalarial treatment, as well as other supportive treatment and close clinical monitoring. re referral administration of artesunate rectal suppositories to severely ill malaria patients have shown to reduce the risk for complications and death. The advantage of artesunate suppositories is that they can be given easily and rapidly to both children and adults without the need for extra materials or much staff training. Artesunate suppositories should be given as follows: 15 Give artesunate suppository 10mg/kg once; artesunate suppositories are available in 50mg & 200mg strengths (see dosing table below), and can be cut in half (see Annex 2) To ensure absorption, hold the buttocks of the patient together for 10 minutes. If suppository is expelled within 30 minutes, give another suppository. After inserting 3 suppositories, wait at least 10 min. before inserting another one.

16 Repeat the of artesunate suppository after 24 hours if referral has still not been possible. Continue to give artesunate suppository daily until referral becomes possible OR the patient recovers and is able to tolerate oral medications. Change then to a full standard course of oral artemether lumefantrine. Dosing table for artesunate suppositories for pre referral treatment of severe falciparum malaria ATIENT BODYWEIGHT (KG) Using 50 mg artesunate suppositories (10 mg/kg) Using 200 mg artesunate suppositories (10mg/kg) ½ ½ General recommendations for the management and referral of severely ill malaria patients at different health facility levels are as follows: At Aid ost level: Give artesunate suppositories to any patients with suspected severe malaria according to the weight of the patient. Thereafter, refer the patient immediately to the nearest Dispensary, Health Centre or Hospital to initiate parenteral antimalarial treatment, further clinical observation and additional supportive therapy, as necessary. At Dispensary and Health Centre level: If a patient is referred from an Aid ost, and Uif artesunate suppositories have already been administeredu as pre referral treatment, then: Start treatment using artesunate injection (i.v/i.m) as per protocol for severe malaria (see page 17), but only at least 12 hours after the last of artesunate suppository was given. Consider to refer the patient to hospital for closer clinical monitoring and further supportive treatment, as necessary. 16

17 If Uno pre referral treatment has been given yetu, then: Give first of artesunate injection (i.v/i.m) immediately as per protocol for severe malaria. If artesunate or quinine injections are not available in the health facility, start treatment with artesunate suppository and refer the patient immediately to the nearest Health Centre or Hospital to initiate parenteral antimalarial treatment and other supportive treatment. If the patient markedly improves whilst referral is still awaited, then: Continue treatment with artesunate injections (i.v/i.m), or alternatively artesunate suppostitories, to complete at least 3 days of treatment; thereafter continue with a full standard course of oral artemether lumefantrine (6 s over three days). 5.5 First line treatment of severe falciparum malaria USevere malaria is a medical emergencyu. Early recognition, repeated assessment, and appropriate and prompt antimalarial treatment and supportive therapy is key to successful management. Any delay in diagnosis and inappropriate treatment, especially in infants and children, can rapidly lead to a worsening of the patient s condition. In any suspected case of severe malaria, with or without measured fever or a history of fever, parasitological confirmation of the malaria diagnosis is strongly recommended; however, in the absence or delay in obtaining a parasitological diagnosis, antimalarial treatment should not be withheld, but presumptive treatment should be started immediately while efforts to confirm the diagnosis are on going. Other investigations to determine illness severity, complications and prognosis should be undertaken where feasible. Treatment of severe malaria should preferably be given parenteraly, which is more effective than oral treatment. Intravenous drug administration is more effective than intramuscular administration, and should therefore be used wherever possible; however, if i.v. treatment is not feasible, intramuscular drug administration should be applied. The most important is not to waste time in starting the antimalarial treatment. If artesunate injections are not available, quinine injections can be used instead (depending on whether quinine will still be procured to be decided!). If parenteral treatment is not possible, treatment should be given using artesunate suppositories. First line treatment for severe malaria: Artesunate injection followed by a full standard course of artemether lumefantrine tablets. 17 Artesunate 60mg injection, 2.4mg/kg per (see dosing table below)

18 For the preparation of artesunate injections, see Annex 2. While the dosage in mg for i.v. and i.m. administration is the same, the concentration of the mixtures is different because of the different ways in which the mixtures are prepared: o For i.v. use, the mixture is 60mg in 6ml o For i.m. use, the mixture is 60mg in 3ml Artesunate treatment Schedule Commence artesunate injection (i.v. or i.m.) 2.4mg/kg per as follows: st o Give the 1 at the time of on admission, the second 12 hours later, thereafter one daily o Continue parenteral artesunate for a minimum of 3 days or until the patient can take oral medication Follow up with parenteral treatment with a standard of oral artemetherlumefantrine (6 regimen over 3 days, see page 13) 18

19 Dosing table: Artesunate injections (intravenous or intramuscular) for severe falciparum malaria Artesunate injections to be administered at Dispensary, Health Centre or Hospital level, given at the time of admission, 12 hours later and then daily for at least 3 days. ATIENT BODYWEIGHT (KG) Intravenously (using 60mg in 6ml injection)* Day 1: Artesunate 2.4 mg/kg i.v. given twice on day 1 st nd on admission 1ml 2ml 3ml 4ml 6ml 8ml 10ml 12ml 12 hours later 1ml 2ml 3ml 4ml 6ml 8ml 10ml 12ml Day 2+: Artesunate 2.4 mg/kg i.v. given once daily 1ml 2ml 3ml 4ml 6ml 8ml 10ml 12ml Intramuscularly (using 60mg in 3ml injection)* Day 1: Artesunate 2.4 mg/kg i.m. given twice on day 1 st nd on admission 0.5ml 1ml 1.5ml 2ml 3ml 4ml 5ml 6ml 12 hours later 0.5ml 1ml 1.5ml 2ml 3ml 4ml 5ml 6ml Day 2+ : Artesunate 2.4 mg/kg i.v. given once daily 0.5ml 1ml 1.5ml 2ml 3ml 4ml 5ml 6ml * Note that the volume for i.v. and i.m. use is different because of the different ways the drug is prepared. 19

20 5.6 Second line treatment for severe malaria: Quinine injection followed by single of sulfadoxine pyrimethamine tablets when the patient is able to swallow Indications for second line treatment with quinine: 1. Treatment failure of the artemisinin derivatives; or 2. Known patient hypersensitivity to artemisinins; or 3. regnant woman in first trimester. Quinine dihydrochloride injection 600mg in 10ml (see dosing table below) Loading : i.v. 20mg/kg given in dextrose/saline infusion rate controlled over 4 hours, or alternatively i.m. 20mg/kg (to be used at dispendary level, or if i.v. administration is otherwise not possible to give) Maintenance : i.v. 10mg/kg given in dextrose/saline infusion rate controlled over 4 hours, or alternatively i.m. 10mg/kg (to be used at dispendary level, or if i.v. administration is otherwise not possible to give) After the first loading, continue to give quinine injection at maintenance (10mg/kg) every 8 hourly until the patient is able to swallow oral treatment. When the patient can take oral treatment, give a single oral of S (see dosing table on page 15). Treatment option if artesunate injection is not available If artesunate injection is not available, then: Give quinine injection following same dosing schedules as stipulated above for second line treatment of severe malaria. When the patient can take oral treatment, stop quinine injection and give a full course of oral artemether lumefatrine (6 s over 3 days) according to standard dosing schedules (see page 13), unless there are contraindication to artemisinins as indicated above for second line treatment of severe malaria. In case of contra indications to the use of artemisinins, give after quinjine injections a single oral of S (see dosing table on page 15). 20

21 Dosing table: Second line treatment for severe falciparum malaria Volume of quinine injection (600mg quinine in 10ml injection) ATIENT BODYWEIGHT (kg) >50 Loading (20mg/kg) 1ml 2ml 4ml 5ml 8ml 10ml 15ml 20ml Maintenance (10mg/kg) 0.5ml 1ml 2ml 2.5ml 4ml 5ml 7.5ml 10ml Notes on using quinine injection If the volume of quinine injection for i.m. use is more than 3ml, the volume should be halved and one half injected in each thigh. For intravenous administration, quinine must be infused slowly (loading over 4 hours, maintenance over 2 hours) The maintenance is given every 8 hours for adults and every 12 hours for children (commenced 8 hours after the loading in adults, 12 hours after the loading in children) When the patient has improved and can tolerate oral treatment, stop quinine injection and give quinine tablets instead (quinine tablets, 10mg/kg every 8 hours) to complete a total of 7 days. Treatment option if artesunate injection is not available: Quinine injection should be given using the s indicated above; stop quinine injections when the patient can tolerate oral treatment, and give a full course of oral artemether lumefantrine. 21

22 6. TREATMENT OF VIVAX MALARIA and MIXED INFECTIONS lasmodium vivax remains responsible for a large proportion of malaria cases in Vanuatu. The standard treatment is the same as for. falciparum, i.e. artemether lumefantrine. However, due to this parasite's ability to cause relapsing cases following dormant hypnozoite stages in the liver, which are not killed by artemether lumefantrine (or most other antimalarials), additional treatment with primaquine needs to be given after artemether lumefatrine to ensure radical cure. For mixed infections (. falciparum and. vivax together at the same time), treatment recommendations are the same as for. vivax mono infections, i.e. artemether lumefantrine together with primaquine. The treatment of. ovale (as mono infection or mixed infection) is the same as for. vivax, i.e. artemether lumeftantrine + primaquine, while the treatment of. malariae is artemether lumefantrine alone. Standard treatment for. vivax: Artemether lumefantrine (tablets artemether 20mg & lumefantrine 120mg) according to bodyweight (see dosing table page 13, i.e. same treatment as for. falciparum), 6 s over 3 days given at 0h, 8h, 24h, 36h, 48h, & 60h. Artemether lumefabtrine must be taken together with a small volume of fatty food or milk. Radical treatment for. vivax rimaquine (7.5 mg tablets) in the of 0.50 mg/kg once daily for 14 days, to be started on day 3 of artemether lumefantrine treatment (see doing table). rimaquine should always be given together with food. Use of primaquine rimaquine treatment is recommended for any confirmed case of vivax malaria, with the Uimportant exceptions of the following patient groups: regnant women Infants younger than 1 year or with a bodyweight less 6 kg. atients with G6D deficiency 22

23 Administration of primaquine depending on the patient's G6D deficiency status According to patient G6D deficiency status (i.e. level of G6D enzymatic activity), primaquine should be given as follows: atients with normal G6D status: atients with normal G6D staus, based either on G6D testing or based on a history of previous safe and succesful primaquine treatment, should receive the standard primaquine regimen (0.50 mg/kg daily for 14 days) without any specfic precautions in terms of clinical monitoring. However, the patient should be informed that if his/her urine becomes dark (reddish brown) during treatment, the patient must stop taking primaquine and return to the health clinic for advice. atients with known or suspected G6D deficiency: atients with G6D deficiency, either based on G6D testing or based on a history of previous primaquine treatment associated with side effect including haemolysis, should NOT be treated with primaquine. atients with unknown G6D staus: atients with unknovn G6D deficiency status may receive primaquine, provided that direct observed treatment is ensured at Hospital or Health Centre level during the first 3 4 days of treatment. If a patient should be G6D deficient, side effects (in particular haemolysis) will normally appear within the first couple of days. If the patient's urine becomes dark (reddish brown), primaquine treatment must be stopped. Similarly, after the first days of direct clinical observation, the patient must be instructed that if he/she should later observe that his/her urine becomes dark (reddish brown), the primaquine treatment should be stopped and the patient should return to the nearest health facility for advice. 23

24 SUMMARY NOTES ON RIMAQUINE FOR RADICAL CURE OF VIVAX MALARIA resently, primaquine is not widely used in Vanuatu, mainly due to concerns over risk of sideeffects in patients, who could have severe G6D deficiency, although this not common. To facilitate the use of primaquine, patients with confirmed vivax malaria should whereever possible be referred to a health facillity, where G6D testing facilities are available, to exclude the possibility of G6D deficiency. If a patient has already been tested once, testing is not required again later, provided that the patient's G6D deficiency status remains available. Similarly, a patient who is already known to have received primaquine previously without any side efects do not need to be tested for G6D deficiency, but can receive primaquine readily. If a patient is known or suspected to be G6D deficient, based on testing or based on a previous history of side effects (haemolysis) following primaquine treatment, primaquine treatment should NOT be given. If a patient's G6D status is unknown, but where direct clinical observation during the first days of treatment at Hospital or Health Centre level can be ensured, primaquine treatment against vivax malaria is recommended as a standard to ensure radical cure, even if G6D testing may not be available. This recommendation applies in particular in areas where the prevalence of G6D deficiency is known to be low (e.g. in Tafea rovince). 24

25 Dosing table: First line treatment for. vivax, two s a day for 3 days. ATIENT BODYWEIGHT (KG) < Artemether lumefantrine (artemether 20mg & lumefanrine 120 mg) ½ Dosing table: Radical treatment for. vivax, 1 daily for 14 days. ATIENT BODY (KG) rimaquine 0.50 mg base/kg daily for 14 days (using 7.5mg tablets) ½ 1 1½

26 Trimester: and Trimester: 7. RESUMTIVE TREATMENT OF MALARIA resumptive treatment is the same as for uncomplicated f Malaria. resumptive treatment of malaria may be given, if: arasite base diagnostic test are not available, or if A parasite based diagnostic test proves negative, but there is strong clinical evidence for malaria. 8. MALARIA TREATMENT AND CHEMOROHYLAXIS IN REGNANT WOMEN lasmodium falciparum: 1 st Quinine Tablets (QN): Oral at 10mg/kg every 8 hours for 7 days. 2 nd 3 rd Artemether lumefantrine (arrtemether 20mg & lumefantrine 120mg 6 s over 3 days (see page 13) Adult = 4 tablets. lasmodium vivax and mixed infections: As above. rimaquine should NOT be given until after delivery. Chemoprophylaxis during pregnancy: Chloroquine tablets 5mg/kg once a week, from the first antenatal visit and for the remaining pregnancy period. 26

27 9. ATIENT COUNSELLING atient with malaria should be counselled as follows: Take after food. This may be problematic for malaria patients who are often not eating; encourage them to eat as much as they can. Vomiting. If vomiting occurs within 1 hour of taking a, another must be taken or given. Drink plenty of fluids Water, coconut juice, or ORS (Oral Rehydration Solution) can be given. Timing of s This may be a problem for patients taking Coartem due to its unusual dosing pattern. It is important that patients are advised well on when to take their medicine according to the treatment schedule in this protocol. 27

28 line ANNEX 1 ERFOMING A MALARIA RAID TEST (RDT) IMORTANT NOTE The RDT used for malaria diagnosis is to detect biological substances (antigens) derived from malaria parasites. It is qualitative test to detect the existing parasite antigens in the patient with symptoms and signs of malaria. RDTs require important attention to store then properly at temperature, ideally, ranged O O from 4 C to 30 C, either with vaccine cold chain or in a shade area (ensure that they are not directly exposes to sunlight and that the environment exceeded the temperature O range mentioned above. Exposing RDTs to high temperature (e.g. more than 37 C) will reduce their sensitivity, which means a test may be negative even if the patient has malaria. Always check the expiry date on the packet, to make sure it is valid to use. Follow the instructions on the card. Malaria RDT user instructions To perform the malaria RDT, follow the steps below: Step 1: repare all materials needed to perform the test and to record the result, such as the RDT device itself, pipette, reagent, lancet, sterile swab, pencil/marker, timer, and registration book. UWrite the patient ID and date on the back side of the cassette testu. Step 2: Collect a small volume of blood from a finger prick, using pipette. Touch the tip of the st pipette to the blood drop and gently suck up the blood to the 1 (5 micro litters) on the pipette. Step 3: Transfer blood to the test cassette by touching the nozzle to the small sample well and gently squeezing the pipette bulb. Step 4: Holding the Reagent A bottle vertically, slowly add 5 drops of Reagent A to the large round well. 28

29 Step 5: Allow the reaction to proceed for U15 minutesu. Step 6: Read the result through the viewing window at 15 minutes. High level infections may be visible sooner. IMORTANT NOTE: Results read after 15 minutes may be inaccurate and must not be practiced or reported. Interpretation and recording of malaria RDT results The correct interpretation of the RDT result is important to support the diagnostic and treatment decision. The test results are displayed as red bands in the test window. There are several possible red bands, which could be visible in the window. Either one, two or three bands could be visible. There are letters "C" and "T" marked on each end side of the test window. The red line visible at Unear far end of C sideu indicates the Ucontrol line (CU). The red bands visible in the middle and far end side of T side indicate the presence of malaria parasite antigens. UHowever, the results are valid ONLY if the red control band towards the C end is visibleu. There are different possible interpretations regarding the visibility of red band(s) in the test window. To reduce the error of interpreting the test results, follow the steps as below: Step 1: Make sure that the test result is read after no more than 15 after filling the Reagent A into the large round well. In some cases, red test bands may become visible BEFORE 15 minutes, which is OK as long as they as hey remain visible after 15 minutes. If red bands are only temporarily visible for a few minutes, the results are not valid. Step 2: Read carefully the red band(s). The red bands could be highly or poorly visible. Step 3: Record the RDT result into the malaria registration book and complete the Malaria atient Card. Make sure the patient is treated according to the results. Step 4: After performing the blood test, dispose all medical waste appropriately according to the standard operational procedure in place. 29

30 INTERRETATION OF TEST RESULTS BASED ON VISIBILITY OF RED BAND(S): 1) Red "control band" NOT visible. Interpretation: The test is NOT valid, regardless of whether any other red bands are visible or not. CONCLUSION: The patient must be re tested! 2) Red "control band" visible ONLY. Interpretation: The test is valid and the result is negative no parasite antigens detected. CONCLUSION: The patient do not have malaria. Malaria treatment is NOT required! 3) Red "control band" and 1 more red band in the middle of the test window is visible Interpretation: The test is valid and the result is positive for falciparum parasite antigen. CONCLUSION: The patient has falciparum malaria. Malaria treatment is required! 4) Red "control band" and 2 more red bands are visible in the test window (in the middle and at far end of T side of test window). Interpretation: The test is valid and the result is positive for falciparum AND another malaria species (typically vivax malaria). CONCLUSION: The patient has a mixed infection of falciparum and another malaria species, typically vivax malaria. Malaria treatment is required! 5) Red "control band" and 1 more red band at far end of T side of the test window is visible. Interpretation: The test is valid and the result is positive for other parasite species than falciparum (typically vivax malaria). CONCLUSION: The patient has a malaria infection OTHER than falciparum, typically vivax malaria. Malaria treatment is required! 30

31 ANNEX 2 REARATION OF ARTESUNATE INJECTIONS AND SUOSITORIES reparation of ARTESUNATE INJECTIONS: Each pack of artesunate Injection should contain: Vial of 60 mg of artesunate powder; Vial of 1 ml of sterile sodium bicarbonate (5%) fluid; Vial of 5 ml of sterile sodium chloride (0.9%) OR 5ml of sterile dextrose (5%) fluid. reparation: For Intravenous Use: Add 1ml of sterile sodium bicarbonate (5%) to the vial with artesunate powder and SHAKE WELL until the solution becomes clear. Add 5 ml of sterile sodium chloride (0.9%) OR 5 ml dextrose (5%) as available to the same artesunate vial and SHAKE WELL again. This gives a concentration of artesunate 60mg in 6ml of injectable solution. For Intramuscular Use Add 1ml of the sodium bicarbonate (5%) to the vial with artesunate powder and SHAKE WELL until the solution becomes clear. Add 2 ml of sterile sodium chloride (0.9%) OR 2 ml of dextrose (5%) as available to the same artesunate bottle and SHAKE WELL again. This gives a concentration of artesunate 60mg in 3ml of injectable solution. Important points in using artesunate injection (i.v. or i.m.): The prepared Artesunate injection should always be used immediately after mixing. The required amount of injection should be given slowly (over 2 3 minutes). artially used vials should be discarded. Artesunate powder for injection is difficult to dissolve and care must be taken to ensure that it is completely dissolved before i.v. or i.m. injection. If the solution is cloudy or a lump is present, it should be discarded! Artesunate injection will be available in Hospitals, Health Centres and Dispensaries. For severe malaria in Aid osts, artesunate suppositories and refer immediately the patient to the nearest Dispensary, Health Centre of Hospital for treatment with artesunate injections, other supportive treatment and close observation. 31

32 reparation of ARTESUNATE SUOSITORIES and cutting them in half (if required) Remove the suppository from its package. Avoid touching the suppository as much as possible to avoid melting; always use gloves. To cut a suppository in half, place it onto a clean surface. Hold the suppository (using a forceps) in the horizontal position. Using a clean/sterile blade cut on the long axis of the suppository (as shown by the arrow in the illustration below) to get equal halves of the suppository. Administer half of the suppository as required. Discard the unused half NEVER keep it for later use! 32