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Mlr

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Mlr

  1. 1. Presented by : Dr Abhay Pota Guided by : Dr Dilip Singh www.dnbpediatrics.com
  2. 2. epidemiology www.dnbpediatrics.com
  3. 3. EPIDEMIOLOGY WORLD INDIA 350-500 million /year 1.84 million cases annually 1 million deaths 1000 deaths 2.48 million from south asia and 75% of them are from india Mainly sub saharan africa and africa are endemic belts 1) Stable transmission 2) Unstable transmission www.dnbpediatrics.com
  4. 4. Malaria maps www.dnbpediatrics.com
  5. 5. ETIOLOGY – protozoal infection • 5 species of plasmodium 1- P. vivax – most common 2- P. Falciparum – most serious 3- P. ovale – illness similar to 4- P.malarie - P.vivax 5- P. Knowlesi – monkey parasite www.dnbpediatrics.com
  6. 6. • Caused by bite of infected female anopheles mosquito 1- A. culcifacies – rural 2- A. Fluviatilis 3- A. stephenesi – urban 4- A. minimus 5- A. Phillipinesis - A. sundaicus www.dnbpediatrics.com
  7. 7. Malarial parasite www.dnbpediatrics.com
  8. 8. Pathophysiology and immunopathology • 1) – innate resistance - Where the distance is endemic - Sickle cell trait, thalessemia and G6PD deficiency • 2) Acquired resistance - Cell mediated immunity - Protective antibodies - Complemental system - Protection to fetus www.dnbpediatrics.com
  9. 9. • Immune evasion by parasite - Some pathological lesions in malaria are explained as being due to immunological mechanism - 1- anemia - 2- hemolysis a/w blackwater fever - 3- Damage to kidneys www.dnbpediatrics.com
  10. 10. • Autoimmunity in malaria - Auto-antibodies are increasingly seen in people living in endemic zones • Immunosuppressive effects - Malaria patient respond poorly to treatment - RA and SLE uncommon in malaria endemic zones www.dnbpediatrics.com
  11. 11. • Relapse - Recurrence of asexual parasitemia in P. vivax (and P. ovale) delivering from persisting liver stages • Recrudescence - Recurrence of asexual parasitemia after treatment of the infection with the same infection that caused the original illness • Recurrence - Recurrence of asexual parasitemia following treatment www.dnbpediatrics.com
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  14. 14. CLINICAL PRESENTATION ENDEMIC ZONE NON ENDEMIC REGIONS Minimal parasitamia High parasitemia Mild symptoms Acute presentations Rapid progression Temperature rises only occasionally Epidemics of malaria can occur Insidious presentation may cause delay in diagnosis Chronic repeated infection causes malnutrition, anaemia and intermittent bacterial infections Marked hepato-splenomegaly www.dnbpediatrics.com
  15. 15. CLINICAL FEATURES • Incubation period- 9-30 days - Shortest for P.falci and longest for P.malarie • Onset of disease - Headache - Fever - Loss of appetite - Pain in limbs www.dnbpediatrics.com
  16. 16. • Fever may become continuous or remittant before it becomes classical intermittent, then, 1- Cold stage (chills, rigors, with headache, nausea, anorexia) 2 Hot stage (dry flushed skin, rapid breathing and increased thirst) 3-Sweating stage • There is no fever for next 24-48 hours and then cycle recurrs – quatidian - tertian www.dnbpediatrics.com
  17. 17. Diagnosis • Prompt parasitological confirmation by microscopy or alternatively by RDTs is recommended in all patients suspected of malaria before treatment is started. • Treatment solely on the basis of clinical suspicion should only be considered when a parasitological diagnosis is not accessible. www.dnbpediatrics.com
  18. 18. Choosing a RDT • Depends upon- 1)plasmodium species to be detected 2)Sensi and speci 3)Shelf life and temperature stability 4)Ease of use and format of test 5)Cost 6)RDT specific www.dnbpediatrics.com
  19. 19. Investigations to detect complications of severe malaria • BLOOD - Parasite count - Blood glucose level - Complete hemogram (hemoglobin estimation, white cell count and platelet count) - Blood group determination and cross match - Blood gas analysis - Serum electrolyte estimation - Blood urea and creatinine level - Blood culture - Coagulation indices - Estimation of serum/plasma levels of liver enzymes www.dnbpediatrics.com
  20. 20. • CSF - Microscopic examination including cell count - Estimation of CSF levels of glucose and protein (to exclude other infections of the central nervous system) • URINE - Determination of specific gravity - Microscopic examination including cell count • CHEST X-RAY - Evidence of pulmonary edema or pneumonia www.dnbpediatrics.com
  21. 21. Quantitative buffy coat • Staining the centrifuged red cell layer with acridine orange and its examination under UV light. • Requires 60ul of blood from capillary prick • RBCs with plasmodias are less dense and concentrate above normal RBCs • Parasites take up the dye & fluorescete • Fast,easy and more sensitive than PSMP www.dnbpediatrics.com
  22. 22. RDT • Detect malaria antigens(PfHRP2/PMA/pLDH) • Detected by color changes on antibody coated lines on the strip test such as OptiMAL and Para sight F tests • Detection limits are >100-200 parasites per ul for p.falciparum and p. vivax;higher for other two species www.dnbpediatrics.com
  23. 23. PERIPHERAL SMEAR RAPID DIAGNOSTIC TESTS Format Slides with blood smear Test strip Equipment Microscope Kit only Training Trained microscopist Anyone with a little training Test duration 20-60 minutes or more 5-30 minutes Test result Derect visualization of the parasites Color changes on antibody coated lines Capability Detects and differentiates all plasmodia at different stages Detects malaria antigens PfHRP2/PMA/pLDH from asexual and sexual forms of parasite Detection threshold 5-10 parasites/UL of blood 100-500/ Ul for P. falciparum, higher for non- falciparumwww.dnbpediatrics.com
  24. 24. PERIPHERAL SMEAR RAPID DIAGNOSTIC TESTS Species differentiation Possible Cannot differentiate among non-falciparum species; mixed infections of P.falciparum and non- falciparum appear as P.falciparum Quantification Possible Not Possible Differentiation between sexual and asexual stages Possible Not Possible Disadvantages Availability of equipment and skilled microscopist, particularly at remote areas and odd hours Unpredictable efficiency at low and very high parasitemia; cross reaction among plasmodial species and with autoantibodies; persistence of antigens Status Gold standard Not yet approved by FDA www.dnbpediatrics.com
  25. 25. Summary of recommendations on parasitological diagnosis • prompt parasitological confirmation by microscopy, or rdts, is recommended in all patients suspected of malaria before treatment is started. • treatment solely on the basis of clinical suspicion should only be considered when a parasitological diagnosis is not accessible. www.dnbpediatrics.com
  26. 26. Characteristics of severe malaria; features associated with a poor diagnosis Physical findings Laboratory abnormalities Prostration Severe anaemia; hematocrit<15, hemoglobin <5 g/dL Impaired consciousness, coma Hypoglycemia; glucose <40 mg/dL Respiratory distress; tachypnea, dyspnea Metabolic acidosis (bicarbonate <15 mEq/L, pH < 7.25) Pulmonary edema Hyperlactatemia; venous lactate > 36 mg/dL Repeated seizures >- 3 seizures in 24 hr Hyperparasitemia; >500,000 parasites/mm3, or >5-10 % red cell Abnormal bleeding, retinal hemorrhages Parasitized Systolic pressure< 80 mm/Hg after volume repletion Disseminated intra-vacular coagulation Jaundice Elevated aminotransferase levels > 3 times normal Acute renal failure Bilirubin level > 3 mg/dL Renal insufficiency; creatinine> 2.5 – 3 mg/dLwww.dnbpediatrics.com
  27. 27. DIFFERENTIAL DIAGNOSIS • Early invasive phase- typhoid, hepatitis and septicemia • Paroxysmal phase-UTI,G(-) septicemia,liver abscess • Cerebral malaria- meningitis, encephalitis,lead encephalopathy, heat stroke • GI form-non specific AGE,cholera,surgical abdomen • Algid-shock due to septicemia • Chronic malaria with splenomegaly-TB,kala azar,leukemia www.dnbpediatrics.com
  28. 28. PREVENTION • Vector control strategies • 1) anti adult measures- a) Residual spraying-DDT,melathion - indoor house spraying -repeated applications needed b) Space spraying- with a special instrument in fog or mist form c) Individual protection-mosquito repellents, protective clothing, screening of houses, coils www.dnbpediatrics.com
  29. 29. • 2) Anti larval measures- a)Larvicides-oiling or dusting with paris green on surface of water b)Source reduction-drainage,feeling,changing salt content of water c)Integrated control-Health education,community participation besides above www.dnbpediatrics.com
  30. 30. NAMP • Present strategies for prevention and control: • 1) ED+T –DDC/FTD/MLV -100million cases examined/year -drugs and funds by GOI -involvement of private labs,supply of RDTs,combo of blister packs • 2)Integrated vector management-selective indoor residual spraying in high risk areas -insecticide treated bed nets -synthetic pyrethroid formulations for impregnation of bed nets • 3)Larvivorous fish • 4)IEC for generating awareness www.dnbpediatrics.com
  31. 31. • Intensfied Malaria Control Programme- -by WHO with global fund for AIDS,TB and malaria in NE states -same measures with enhanced funding • Anti malaria month- June -prior to onset of malaria season -to enhance awareness & encourage community participation through mass media & intersectoral colloboration with other govt,private & NGOs www.dnbpediatrics.com
  32. 32. VACCINES • Currently, no commercially available vaccines • RTS, SASO/1 against P.falci by GSK - Most advanced vaccine candidate - In 6-12 years and 6-14 weeks age group – 3 doses at 1 month intervals - To come into practice by 2015 - 40-50% efficacy against clinical and severe malaria • Other vaccine candidates are Circumsporozoite protein vaccine, polyepitope DNA EP1300, PfSPZ, adeno virus encoded ME TRAP, SERA5, JAIVAC, GMZ2 etc • Other measures : - Irradiated mosquitoeswww.dnbpediatrics.com
  33. 33. • Timeline of Anti Malaria Programmes- • NMCP-1953 • NMEP-1958 • MPO-1977 • MAP-1995 • EMCP-1997 • NAMP-1999 www.dnbpediatrics.com
  34. 34. • Blood film Examination-Stained with Romanowsky stains like giemsa, field, wright, leishman • Thick blood film-Even low levels of parasitemia can be detected • Thin blood film-for identification of parasite species www.dnbpediatrics.com
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  36. 36. Management • The aims of the Malaria case management are: - To provide prompt and complete treatment to all suspected/ confirmed cases of malaria - To prevent progression of mild cases of malaria in to severe or complicated from of malaria - To prevent deaths from severe and complicated malaria - To prevent transmission of malaria - To minimize risk of spread of drug resistant parasites by use of effective drugs in appropriate dosage by everyone. www.dnbpediatrics.com
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  40. 40. Treatment of uncomplicated P. vivax malaria • Chloroquine combined with primaquine is the treatment of choice for chloroquine-sensitive infections. • In mild-to-moderate G6PD deficiency, primaquine 0.75 mg base/kg body weight given once a week for 8 weeks. In severe G6PD deficiency, primaquine is contraindicated and should not be used. • Where ACT (exception AS+SP) has been adopted as the first-line treatment for P. Falciparum malaria, it may also be used for P. vivax malaria in combination with primaquine for radical cure. • Artesunate plus sulfadoxine-pyrimethamine is not effective against P. vivax in many places. www.dnbpediatrics.com
  41. 41. Treatment of uncomplicated P. vivax malaria • In areas with chloroquine resistant P. vivax, artemisinin-based combination therapies (particularly those whose partner medicines have long half-lives) are recommended for the treatment of P. vivax malaria. • At least a 14-day course of primaquine is required for the radical treatment of P. vivax. www.dnbpediatrics.com
  42. 42. recommendations on treatment of uncomplicated malaria in epidemic situations • the following acts are recommended for antimalarial treatment in P. falciparum or mixed P. falciparum/ P. vivax malaria epidemics: – artemether plus lumefantrine – artesunate plus amodiaquine – artesunate plus mefloquine – dihydroartemisinin plus piperaquine. • the 14-day anti-relapse therapy for vivax malaria patients (where applicable) should be postponed to the post-epidemic period. • treatment of severe malaria: – artemether by the IM route is an acceptable and practical alternative for treatment of severe falciparum malaria during an epidemic. As soon as intensive case monitoring becomes possible, artesunate (IV or IM route) is the treatment of choice. Quinine can be used where artesunate is not available. www.dnbpediatrics.com
  43. 43. Summary of recommendations on the treatment of uncomplicated vivax malaria• chloroquine 25 mg base/kg body weight divided over 3 days, combined with primaquine 0.25 mg base/kg body weight, taken with food once daily for 14 days is the treatment of choice for chloroquine-sensitive infections. in oceania and south east asia, the dose of primaquine should be 0.5 mg/kg body weight. • ACTs combined with primaquine for chloroquine-resistant vivax malaria. • In mild-to-moderate G6pd deficiency, primaquine 0.75 mg base/kg body weight should be given once a week for 8 weeks. in severe G6PD deficiency, primaquine is contraindicated and should not be used. • Where act (exception as+sp) has been adopted as the first-line treatment for P. falciparum malaria, it may also be used for P. vivax malaria in combination with primaquine for radical cure. artesunate plus sulfadoxine-pyrimethamine is not effective against P. vivax in many places. www.dnbpediatrics.com
  44. 44. recommendation: primaquine for the radical treatment of vivax malaria • at least a 14-day course of primaquine is required for the radical treatment of P. vivax - A 14-day course of primaquine significantly reduces the relapse rate of P. vivax compared to a 5-day course • Other considerations - In addition, in clinical trials, CQ plus 14 days of primaquine has been shown to be superior to CQ alone in reducing relapses.No difference has been shown between CQ plus 5 days of primaquine and CQ alone. www.dnbpediatrics.com
  45. 45. Treatment of uncomplicated P. falciParum malaria- • Artemisinin-based combination therapies (ACTs) are the recommended treatments for uncomplicated P. falciparum malaria. • The following ACTs are recommended: artemether plus lumefantrine, artesunate plus amodiaquine, artesunate plus mefloquine, and artesunate plus sulfadoxine-pyrimethamine. • The choice of ACT in a country or region will be based on the level of resistance of the partner medicine in the combination. • Artemisinin and its derivatives should not be used as monotherapy. • Second-line antimalarial treatment: - alternative ACT known to be effective in the region; - artesunate plus tetracycline or doxycycline or clindamycin; any of these combinations to be given for 7 days; - quinine plus tetracycline or doxycycline or clindamycin; any of these combinations should be given for 7 days. www.dnbpediatrics.com
  46. 46. Treatment of uncomplicated P. falciparum malaria • Artemisinin-based combination therapies should be used in preference to sulfadoxinepyrimethamine (SP) plus amodiaquine (AQ) for the treatment of uncomplicated P. Falciparum malaria. - ACTs should include at least 3 days of treatment with an artemisinin derivative. - Dihydroartemisinin plus piperaquine (DHA+PPQ) is an option for the first-line treatment of uncomplicated P. falciparum malaria worldwide. • Addition of a single dose primaquine (0.75 mg/kg) to ACT treatment for uncomplicated falciparum malaria as an antigametocyte medicine, particularly as a component of pre-elimination or an elimination programme. www.dnbpediatrics.com
  47. 47. treatment of severe P. falciparum malaria • intravenous(IV) artesunate should be used in preference to quinine for the treatment of severe P. falciparum malaria in adults. www.dnbpediatrics.com
  48. 48. Treatment of severe malaria • Severe malaria is a medical emergency. After rapid clinical assessment and confirmation of the diagnosis, full doses of parenteral antimalarial treatment should be started without delay with whichever effective antimalarial is first available • For children, artesunate IV or IM( artemether or quinine is an acceptable alternative if parenteral artesunate is not available) • Give parenteral antimalarials in the treatment of severe malaria for a minimum of 24 h, once started (irrespective of the patient’s ability to tolerate oral medication earlier) and, thereafter, complete treatment by giving a complete course of: www.dnbpediatrics.com
  49. 49. Treatment of severe malaria - an ACT; - artesunate plus clindamycin or doxycycline; - quinine plus clindamycin or doxycycline. • If complete treatment of severe malaria is not possible, patients should be given pre-referral treatment and referred immediately to an appropriate facility for further treatment. The following are options for pre-referral treatment : rectal artesunate, quinine IM, artesunate IM, artemether IM. www.dnbpediatrics.com
  50. 50. Summary of recommendations on the treatment of Severe Falciparum malaria • Severe malaria is a medical emergency. After rapid clinical assessment and confirmation of the diagnosis, full doses of parenteral antimalarial treatment should be started without delay with any effective antimalarial first available. www.dnbpediatrics.com
  51. 51. immediate clinical management of severe manifestations and complications of P. falciparum malaria Manifestation/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 treatment, such as corticosteroids, heparin and adrenaline; intubate if necessary. Hyperpyrexia Administer tepid sponging, fanning, a cooling blanket and antipyretic drugs. Paracetamol is preferred over more nephrotoxic drugs (e.g. NSAIDs). convulsions Maintain airways; treat promptly with intravenous or rectal diazepam or intramuscular paraldehyde. Check blood glucose. www.dnbpediatrics.com
  52. 52. Manifestation/complication immediate management Hypoglycaemia Check blood glucose, correct hypoglycaemia and maintain with glucose containing infusion. severe anaemia Transfuse with screened fresh whole blood. acute pulmonary oedema Prop patient up at an angle of 45°, give oxygen, give a diuretic, stop intravenous fluids, intubate and add positive end expiratory pressure/ continuous positive airway pressure in life-threatening hypoxemia. acute renal failure Exclude pre-renal causes, check fluid balance and urinary sodium; if in established renal failure add hemofiltration or haemodialysis, or if unavailable, peritoneal dialysis. 8. Treatment of severe P.falciparum malaria www.dnbpediatrics.com
  53. 53. Manifestation/complication immediate management spontaneous bleeding and coagulopathy Transfuse with screened fresh whole blood (cryoprecipitate, fresh frozen plasma and platelets, if available); give vitamin K injection. metabolic acidosis Exclude or treat hypoglycaemia, hypovolaemia and septicaemia. If severe, add haemofiltration or haemodialysis. shock Suspect septicaemia, take blood for cultures; give parenteral broad-spectrum antimicrobials, correct haemodynamic disturbances. www.dnbpediatrics.com
  54. 54. Recommendation: pre-referral treatment for severe P. falciparum malaria • if complete treatment for severe malaria (as recommended in Section 8.4) is not possible, patients with severe malaria should be given pre-referral treatment and referred immediately to an appropriate facility for further treatment. • – The following are options for pre-referral treatment: • rectal artesunate • quinine IM • artesunate IM • artemether IM. – In young children of less than 5 years of age, the use of rectal artesunate (10 mg/kg) has been shown to reduce the risk of death and permanent disability. www.dnbpediatrics.com
  55. 55. Criteria for admission of patients with severe malaria to ICU Acidosis Base excess<-8 Parasitemia Endemic areas : >20% Non-endemic areas : >10% Coma Glasgow coma scale <_ 8 Hypoglycemia Blood glucose level <2.2 mmol/l Renal dysfunction Urine output < 0.5 ml/kg/hr Pulmonary edema www.dnbpediatrics.com
  56. 56. recommendations: treatment for HIV- infected patients with uncomplicated P. falciparum malaria • patients with Hiv infection who develop malaria should receive prompt, effective antimalarial treatment regimens as recommended in the relevant sections of these guidelines. • treatment or intermittent preventive treatment with sulfadoxine-pyrimethamine should not be given to Hiv- infected patients receiving cotrimoxazole (trimethoprim plus sulfamethoxazole) prophylaxis. • treatment in Hiv-infected patients on zidovudine or efavirenz should, if possible, avoid amodiaquine- containing act regimens. www.dnbpediatrics.com
  57. 57. recommendations on the treatment of falciparum malaria in special Groups • Pregnancy • First trimester: – quinine plus clindamycin to be given for 7 days (artesunate plus clindamycin for 7 days is indicated if this treatment fails); – an ACT is indicated only if this is the only treatment immediately available, or if treatment with 7-day quinine plus clindamycin fails or if there is uncertainty of compliance with a 7-day treatment. • Second and third trimesters: – ACT known to be effective in the country/region or artesunate plus clindamycin to be given for 7 days or quinine plus clindamycin to be given for 7 days. www.dnbpediatrics.com
  58. 58. • lactating women – Lactating women should receive standard antimalarial treatment (including ACTs) except for dapsone, primaquine and tetracyclines, which should be withheld during lactation. • infants and young children – ACTs for first-line treatment in infants and young children with attention to accurate dosing and ensuring the administered dose is retained. – Referral to a health centre or hospital is indicated for young children who cannot swallow antimalarial medicines reliably. If referral is expected to take more than 6 hours, pre-referral treatment with rectal artesunate is indicated. www.dnbpediatrics.com
  59. 59. • travellers returning to non-endemic countries • Uncomplicated falciparum malaria: – atovaquone plus proguanil, – artemether plus lumefantrine, – dihydroartemisinin plus piperaquine, – quinine plus doxycycline or clindamycin; all drugs to be given for 7 days. www.dnbpediatrics.com
  60. 60. recommendations: treatment of uncomplicated falciparum malaria in pregnancy • first trimester: - Quinine plus clindamycin to be given for 7 days (artesunate plus clindamycin for 7 days is indicated if this treatment fails). - An ACT is indicated only if this is the only treatment immediately available, or if treatment with 7-day quinine plus clindamycin fails, or if there is uncertainty about patient compliance with a 7-day treatment. • second and third trimesters: - ACT known to be effective in the country/region or artesunate plus clindamycin to be given for 7 days or quinine plus clindamycin to be given for 7 days. Pharmacovigilance programmes need to be established to continually monitor safety of antimalarial medicines in all trimesters, including inadvertent exposures in the early first trimester. www.dnbpediatrics.com
  61. 61. recommendations on treatment for uncomplicated P. falciparum malaria • the treatment of choice for uncomplicated falciparum malaria is a combination of two or more antimalarial medicines with different mechanisms of action. • acts are the recommended treatments for uncomplicated falciparum malaria. • the artemisinin derivative components of the combination must be given for at least three days for an optimum effect. • the following acts are recommended: artemether plus lumefantrine, artesunate plus amodiaquine, artesunate plus mefloquine, artesunate plus sulfadoxine-pyrimethamine, and dihydrortemisinin plus piperaquine. • fixed-dose combinations are highly preferable to the loose individual medicines co-blistered or co-dispensed. www.dnbpediatrics.com
  62. 62. • the choice of act in a country or region will be based on the level of resistance of the partner medicine in the combination: - in areas of multidrug resistance (east Asia), artesunate plus mefloquine, or artemether plus lumefantrine or dihydroartemisinin plus piperaquine are recommended; and - in other areas without multidrug resistance (mainly Africa), any of the ACTs including those containing amodiaquine or sulfadoxine- pyrimethamine may still be effective. • artemisinin and its derivatives should not be used as monotherapy. www.dnbpediatrics.com
  63. 63. • second-line antimalarial treatment: - alternative ACT known to be effective in the region; - artesunate plus tetracycline or doxycycline or clindamycin, any of these combinations should be given for 7 days; - quinine plus tetracycline or doxycycline or clindamycin, any of these combinations should be given for 7 days. www.dnbpediatrics.com
  64. 64. • Criterias for selection of RDTs • For Pf: sensi & speci >95% at parasite density level of 200 asexual parasites/ul of blood • For Pv: -Sensi >= 75% at density of 200 parasites/ul -Speci>= 90% Type of RDT-HRP2 and pLDH based RDTs,not aldose based ones www.dnbpediatrics.com
  65. 65. • Dipsticks,cassettes & cards • Histidine rich protein 2,specific to Pf.Soluble,heat stable Ag in cytoplasm of infected RBCs • Plasmodium lactate dehydrogenase currently available in all 3 forms • Aldolase is a major enzyme in glycolytic pathway of parasites Ag HRP2 pLDH Aldolase Pf specific + + Pan specific + + Pv specific + www.dnbpediatrics.com
  66. 66. • PCR-High sensi and speci(10x than microscopy), esp. in case of low parasite load and mixed infections • Immunofluorescence and enzyme immunoassay-useful in epidemio survey and screening blood donors • Best and cheaper way is ELISA augmented PfHRP2 RDT www.dnbpediatrics.com
  67. 67. TREATMENTS NOT RECOMMENDED • ANTIPYRETICS • Studies in non severe malaria showed that their use prolonged parasite clearance. • Ibuprofen more effective than pcm in non severe uncomplicated malaria • STEROIDS • No use in cerebral malaria • Adr,DEXTRAN,CYCLOSPORIN A,HYPER IMMUNE SERUM,ANTI TNF ANTIBODIES IN CEREBRAL MALARIA www.dnbpediatrics.com
  68. 68. COMPLICATIONS 1) cerebral malaria : - Sudden or gradual - Convulsions – unconscious - CSF – Normal - Due to sequestration and thrombosis of capillaries by parasitized RBCs 2) anemia : - Severe and out of proportion to degree of parasitemia 3) gastrointestinal illness : - Vomiting - Diarrhoea - dehydration www.dnbpediatrics.com
  69. 69. 4) algid malaria in P.falci : - Peripheral circulatory failure and shock 5) blackwater fever –hypersensitivity to drugs : - Sudden severe hemolysis - hemoglobinuria - renal faolure 6) renal lesions : in P.malarie - Acute transient nephritis - Chronic nephritic syndrome www.dnbpediatrics.com
  70. 70. • For children, artesunate 2.4 mg/kg BW iv or im given on admission (time = 0), then at 12 h and 24 h, then once a day is the recommended treatment. artemether, or quinine, is an acceptable alternative if parenteral artesunate is not available: artemether 3.2 mg/kg BW im given on admission then 1.6 mg/kg BW per day ; or quinine 20 mg salt/kg BW on admission (iv infusion or divided im injection), then 10 mg/kg BW every 8 h; infusion rate should not exceed 5 mg salt/ kg BW per hour. • Give parenteral antimalarials in the treatment of severe malaria for a minimum of 24 h, once started (irrespective of the patient’s ability to tolerate oral medication earlier), and, thereafter, complete treatment by giving a complete course of: • – artemether plus lumefantrine, • – artesunate plus amodiaquine, • – dihydroartemisinin plus piperaquine, • – artesunate plus sulfadoxine-pyrimethamine, • – artesunate plus clindamycin or doxycycline, • – quinine plus clindamycin or doxycycline. www.dnbpediatrics.com
  71. 71. Various factors determine the propensity for antimalarial drug resistance to develop • The intrinsic frequency with which the genetic changes occur • The degree of resistance (the shift in the concentration effect relationship, conferred by the genetic change • The number of parasites exposed to the drug • The concentrations of drug to which these parasites are exposed • The pharmacokinetic and pharmaco-dynamic properties of the anti-malarial www.dnbpediatrics.com
  72. 72. • Individual (dosing, duration, adherence) and community (quality, availability, distribution) patterns of drug use • The immunity profile of the community and the individual • The simultaneous presence of other antimalarials or substances in the blood to which the parasite is not resistant. www.dnbpediatrics.com
  73. 73. Drug resistance www.dnbpediatrics.com
  74. 74. Essential nuggets • 1- the standard oral regimen of chloroquine of 25mg base/ kg body weight given over 3 days plus primaquine at either a low (0.25 mg base/ / kg body weight per day for 14 days) or high (0.5- 0.75 mg base/kg body weight per day for 14 days) dose is effective and safe for the radical cure of chloroquine sensitive P. vivax malaria in patients with no G6PD deficiency. • 2- In areas where infections of drug resistant P. falciparum and/or P. vivax are common, drug regimens to treat both species effectively must be used. An artemisin based combination treatment (particularly dihydroartemisimin plus piperaquine) that does not include sulfadoxine pyrimethamine would be a good choice. www.dnbpediatrics.com
  75. 75. • 3- the use of high dose primaquine (0.5-0.75 mg base/kg body weight per day for 14 days), with either chloroquine or another effective antimalarial, is essential for trying to prevent relapses of primaquine resistant or primaquine tolerant P.vivax. • 4- A primaquine regimen of 0.75 mg base/kg body weight once per week for 8 weeks is recommended as anti-relapse therapy for P.vivax and P.ovale malaria in patients with mild G6PD deficiency. www.dnbpediatrics.com
  76. 76. Resources • 1- O.P. Ghai- 8th edi. • 2- malaria sites.org • 3-NVBDCP.gov.co.in • 4- WHO guidelines • 5- IAP guidelines www.dnbpediatrics.com
  77. 77. THANK YOUwww.dnbpediatrics.com

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