![DIAGNOSIS
CLINICAL DIAGNOSIS MICROSCOPIC DIAGNOSIS ANTIGEN DETECTION
MOLECULAR DIAGNOSIS SEROLOGY DRUG RESISTANCE TESTS
• Based on symptoms & on physical
findings (but not specific).
• A complete blood picture & routine
chemistry panel:
- Useful in determining whether the
infection is uncomplicated or severe.
- Can detect severe anemia, hypoglycemia,
renal failure, hyperbilirubinemia, & acid-
base disturbances.
• Blood smear.
• Useful for identifying malaria.
parasites.
• Stain used: Giemsa stain.
• Gold standard for laboratory
confirmation of malaria.
• To detect antigens derived from malaria
parasites.
• Immunochromatographic tests [rapid
diagnostic tests (RDT)]:
-Often use a dipstick or cassette format.
- provide results in 2-15 minutes.
- indicate whether patient is infected with
P. falciparum or one of the other 3 species
of human malaria.
• polymerase chain reactions (PCR):
-Parasite nucleic acids are detected.
- most useful for confirming the species
of malarial parasite after the diagnosis
has been established by either smear
microscopy or RDT.
•either indirect immunofluorescence
(IFA) or enzyme-linked
immunosorbent assay (ELISA).
•Detects antibodies against malaria
parasites.
•Doesnot detect current infection but
rather measures past exposure.
•To assess the susceptibility to
antimalarial compounds of parasites
collected from a specific patient.
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malaria- pharmacotherapy
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- 3. MALARIA PARASITES Malaria parasites are micro-organisms that belong to the genus Plasmodium. There are more than 100 species of Plasmodium, which can infect many animal species such as reptiles, birds, and various mammals. The species infecting humans are the following: •P. falciparum •P. vivax •P. ovale •P. malariae •P. knowlesi 3
- 4. 4 P.falciparum: •Found worldwide in tropical and sub-tropical areas (& especially in Africa) •Can cause severe malaria because it multiplies rapidly in the blood, & can thus cause anemia •Infected parasites can clog small blood vessels. When this occurs in the brain, cerebral malaria results. P.vivax: •Found mostly in Asia, Latin America, & in some parts of Africa. •Most prevalent human parasite. • P.vivax (as well as P.ovale) has dormant liver stages (“hypnozoites”) that can activate & invade blood (“relapse”) several months or years after the infecting mosquito bite. P.ovale: •Found mostly in Africa ( especially west Africa) & the islands of the western pacific. •Biologically & morphologically very similar to P.vivax. P.malariae: •Found worldwide. •Has a quartan cycle (3-day cycle) •Can cause chronic infection that in some cases can last a lifetime. & serious complications such as the nephritic syndrome. P.knowlesi: •found throughout Southeast Asia. •Has a 24-hour replication cycle & so can rapidly progress from uncomplicated to severe malaria. (continued)...
- 5. LIFE CYCLE OF MALARIA PARASITES 5
- 6. INCUBATION PERIOD OF THE PARASITE 6 INCUBATION PERIOD: Interval between inoculation of the sporozoites and appearance of the symptoms. SPECIES INCUBATION PERIOD P.falciparum 7-14 days P.vivax 12-17 days P.Ovale 15-18 days P.malariae 18-40 days
- 7. UNCOMPLICATED MALARIA The classical (but rarely observed) malaria attack lasts 6–10 hours. It consists of •A cold stage (sensation of cold, shivering) •A hot stage (fever, headaches, vomiting; seizures in young children); and •Finally a sweating stage (sweats, return to normal temperature, tiredness). Classically (but infrequently observed) the attacks occur every second day with the “tertian” parasites (P. falciparum, P. vivax, and P. ovale) and every third day with the “quartan” parasite (P. malariae). Symptoms • Fever • Chills • Sweats • Headaches • Nausea and vomiting • Body aches • General malaise Physical findings • Elevated temperatures • Perspiration • Weakness • Enlarged spleen • Mild jaundice • Enlargement of the liver • Increased respiratory rate 7
- 8. Severe malaria is manifestated by one or more of the following: • Cerebral malaria • Severe anemia due to hemolysis • Hemoglobinuria due to hemolysis • Abnormalities in blood coagulation • Low blood pressure caused by cardiovascular collapse • Acute kidney injury • Hyperparasitemia, where more than 5% of the red blood cells are infected by malaria parasites • Metabolic acidosis, often in association with hypoglycemia • Hypoglycemia. (Hypoglycemia may also occur in pregnant women with uncomplicated malaria, or after treatment with quinine). SEVERE MALARIA 8
- 9. DIAGNOSIS CLINICAL DIAGNOSIS MICROSCOPIC DIAGNOSIS ANTIGEN DETECTION MOLECULAR DIAGNOSIS SEROLOGY DRUG RESISTANCE TESTS • Based on symptoms & on physical findings (but not specific). • A complete blood picture & routine chemistry panel: - Useful in determining whether the infection is uncomplicated or severe. - Can detect severe anemia, hypoglycemia, renal failure, hyperbilirubinemia, & acid- base disturbances. • Blood smear. • Useful for identifying malaria. parasites. • Stain used: Giemsa stain. • Gold standard for laboratory confirmation of malaria. • To detect antigens derived from malaria parasites. • Immunochromatographic tests [rapid diagnostic tests (RDT)]: -Often use a dipstick or cassette format. - provide results in 2-15 minutes. - indicate whether patient is infected with P. falciparum or one of the other 3 species of human malaria. • polymerase chain reactions (PCR): -Parasite nucleic acids are detected. - most useful for confirming the species of malarial parasite after the diagnosis has been established by either smear microscopy or RDT. •either indirect immunofluorescence (IFA) or enzyme-linked immunosorbent assay (ELISA). •Detects antibodies against malaria parasites. •Doesnot detect current infection but rather measures past exposure. •To assess the susceptibility to antimalarial compounds of parasites collected from a specific patient. 9
- 10. Blood smear stained with Giemsa, showing a white blood cell (on left side) and several red blood cells, two of which are infected with Plasmodium falciparum (on right side). Indirect fluorescent antibody (IFA) test. The fluorescence indicates that the patient serum being tested contains antibodies that are reacting with the antigen preparation (here, Plasmodium falciparum parasites). 10
- 11. TREATMENT : GENERAL APPROACH 1 The infecting plasmodium species ● P.falciparum & P.knowlesi can cause rapidly progressive severe illness or death. ● P.vivax & P.ovale infections also require treatment for hypnozoite forms. ● P.falciparum and p.vivax have different drug resistance patterns. 2 The clinical status of the patient ● Uncomplicated malaria can be effectively treated with oral antimalarials. ● Severe malaria treated with parenteral anti- malarial therapy. The drug susceptibility of the infecting parasite ● Knowledge of the geographic area where the infection was acquired provides information on the likelihood of drug resistance of the infecting parasite. 3 The previous use of antimalarials. ● If malaria infection occurred despite use of chemoprophylaxis, that medicine should not be a part of the treatment regimen. 4 Treatment should be guided by 4 main factors: 11
- 12. TABLE 1. DOSES OF ANTI-MALARIALS 12 Recommended Adult doses Recommended Pediatric doses Artemether-lumefantrine (Coartem) (1 tab: 20 mg artemether and 120 mg lumefantrine) Adults: 4 tabs po per dose Three-day course: Day 1: Initial dose and second dose 8 h later Days 2 and 3: 1 dose BID Artemether-lumefantrine (Coartem) (1 tab: 20 mg artemether and 120 mg lumefantrine) 5–<15 kg: 1 tab po per dose 15–<25 kg: 2 tabs po per dose 25–<35 kg: 3 tabs po per dose ≥35 kg: 4 tabs po per dose Three-day course: Day 1: Initial dose and second dose 8 h later Days 2 and 3: 1 dose BID Atovaquone-proguanil (Malarone) (Adult tab: 250 mg atovaquone and 100 mg proguanil) 4 adult tabs po QD x 3 days Atovaquone-proguanil (Malarone) (Adult tab: 250 mg atovaquone and 100 mg proguanil; Peds tab: 62.5 mg atovaquone and 25 mg proguanil) 5–<8 kg: 2 peds tabs po QD x 3 days 8–<10 kg: 3 peds tabs po QD x 3 days 10–<20 kg: 1 adult tab po QD x 3 days 20–<30 kg: 2 adult tabs po QD x 3 days 30–<40 kg: 3 adult tabs po QD x 3 days ≥40 kg: 4 adult tabs po QD x 3 days
- 13. Recommended Adult doses Recommended Pediatric doses Quinine sulfate plus doxycycline , tetracycline , or clindamycin Quinine sulfate: 542 mg base (650 mg salt) po TID x 3 or 7 days Doxycycline: 100 mg po BID x 7 days Tetracycline: 250 mg po QID x 7 days Clindamycin: 20 mg/kg/day po divided TID x 7 days Quinine sulfate plus doxycycline , tetracycline , or clindamycin Quinine sulfate: 8.3 mg base/kg (10 mg salt/kg) po TID x 3 or 7 days Doxycycline: 2.2 mg/kg po BID x 7 days Tetracycline: 25 mg/kg/day po divided QID x 7 days Clindamycin: 20 mg /kg/day po divided TID x 7 days Mefloquine Dose 1: 684 mg base (750 mg salt) po Dose 2 at 6 to 12 h: 456 mg base (500 mg salt) po Mefloquine Dose 1: 13.7 mg base/kg (15 mg salt/kg) po Dose 2 at 6 to 12 h: 9.1 mg base/kg (10 mg salt/kg) po Chloroquine phosphate (Arale and generics) Dose 1: 600 mg base (1,000 mg salt) po Doses 2 to 4 (3 additional doses) at 6, 24 and 48 h: 300 mg base (500 mg salt) po per dose; Chloroquine phosphate (Arale and generics) Dose 1: 10 mg base/kg (16.7 mg salt/kg) po Doses 2 to 4 (3 additional doses) at 6, 24 and 48 h: 5 mg base/kg (8.3 mg salt/kg) po per dose; (continued)... 13
- 14. Recommended Adult doses Recommended Pediatric doses Hydroxychloroquine (Plaquenil and generics) Dose 1: 620 mg base (800 mg salt) po Doses 2 to 4 (3 additional doses) at 6, 24 and 48 h: 310 mg base (400 mg salt) po per dose Hydroxychloroquine (Plaquenil and generics) Dose 1: 10 mg base/kg (12.9 mg salt/kg) po Doses 2 to 4 (3 additional doses) at 6, 24 and 48 h: 5 mg base/kg (6.5 mg salt/kg) po per dose Primaquine phosphate 30 mg base po qd x 14 days Primaquine phosphate 0.5 mg base/kg po qd x 14 days Tafenoquine (Krintafel) 300 mg po x 1 dose Tafenoquine (Krintafel) 300 mg po x 1 dose, only for patients ≥16 years old (continued)... 14
- 15. Uncomplicated malaria: Plasmodium falciparum or unknown species Drug Susceptibility Recommended Regimen Chloroquine resistant or unknown resistance (All malariaendemic regions except those in Central America west of Panama Canal, Haiti, and Dominican Republic) Four treatment options are available: A. Artemether-lumefantrine (Coartem) B. Atovaquone-proguanil (Malarone) C. Quinine sulfate plus doxycycline , tetracycline , or clindamycin D. Mefloquine Chloroquine sensitive (All malariaendemic regions except those in Central America west of Panama Canal, Haiti, and Dominican Republic) Chloroquine phosphate (Arale and generics), or Hydroxychloroquine (Plaquenil and generics) NOTE: refer TABLE 1 for dosing. 15
- 16. Uncomplicated malaria: P. vivax or P. ovale Drug Susceptibility (Based on where acquired) Recommended Regimen Acute treatment Antirelapse treatment Chloroquine sensitive (All malaria endemic regions except Papua New Guinea and Indonesia) Chloroquine phosphate (Aralen and generics) Or Hydroxychloroquine (Plaquenil and generics) Primaquine phosphate Or Tafenoquine (Krintafel) Chloroquine resistant (Papua New Guinea and Indonesia) Four treatment options are available: A. Artemether-lumefantrine (Coartem) B. Atovaquone-proguanil (Malarone) C. Quinine sulfate plus doxycycline , tetracycline , or clindamycin D. Mefloquine Primaquine phosphate NOTE: refer TABLE 1 for dosing. 16
- 17. 17 Uncomplicated malaria: P. malariae or P. knowlesi Drug Susceptibility (Based on where acquired) Recommended Regimens Chloroquine sensitive (All malariaendemic regions, no known resistance) Chloroquine phosphate (Aralen and generics) or Hydroxychloroquine (Plaquenil and generics) PLUS Anyone of the following: A. Artemether-lumefantrine (Coartem) B. Atovaquone-proguanil (Malarone) C. Quinine sulfate plus doxycycline , tetracycline , or clindamycin D. Mefloquine NOTE: refer TABLE 1 for dosing.
- 18. Uncomplicated malaria: Pregnant women Species and Drug Susceptibility (Based on where acquired) Recommended Regimens Chloroquine resistant P. falciparum (All malariaendemic regions except Central America west of Panama Canal, Haiti, and Dominican Republic) P. vivax or P. ovale (Papua New Guinea and Indonesia) Preferred for 2nd and 3rd trimesters: Artemether-lumefantrine (Coartem) (1 tab: 20 mg artemether and 120 mg lumefantrine) Adults: 4 tabs po per dose Three-day course: Day 1: Initial dose and second dose 8 h later Days 2 and 3: 1 dose BID All trimesters: Quinine sulfate plus clindamycin Quinine sulfate: 542 mg base (650 mg salt) po TID x 3 or 7 days Clindamycin: 20 mg/kg/day po divided TID x 7 days If no other options, all trimesters: Mefloquine Dose 1: 684 mg base (750 mg salt) po Dose 2 at 6 to 12 h: 456 mg base (500 mg salt) po AND if P. vivax or P.ovale: Chloroquine 500 mg salt (300 mg base) weekly until delivery, then consider antirelapse treatment Antirelapse treatment with either primaquine or tafenoquine contraindicated during pregnancy 18
- 19. Species and Drug Susceptibility (Based on where acquired) Recommended Regimens Chloroquine sensitive P. falciparum (Central America west of Panama Canal, Haiti, and Dominican Republic) P. vivax or P. ovale (All malaria-endemic regions except Papua New Guinea and Indonesia) P. malariae or P. knowlesi A. Chloroquine phosphate (Aralen and generics) ● Dose 1: 600 mg base (1,000 mg salt) po ● Doses 2 to 4 (3 additional doses) at 6, 24 and 48 h: 300 mg base (500 mg salt) po per dose; or Hydroxychloroquine (Plaquenil and generics) ● Dose 1: 620 mg base (800 mg salt) po ● Doses 2 to 4 (3 additional doses) at 6, 24 and 48 h: 310 mg base (400 mg salt) po per dose Options above for chloroquine-resistant malaria parasites AND if P. vivax or P.ovale: Chloroquine 500 mg salt (300 mg base) weekly until delivery, then consider antirelapse treatment Antirelapse treatment with either primaquine or tafenoquine contraindicated during pregnancy 19 (continued)...
- 20. Species and Drug Susceptibility (Based on where acquired) Recommended Regimen All species, drug susceptibility not relevant for acute treatment of severe malaria If P. vivax or P. ovale infections, in addition to acute treatment listed here, antirelapse treatment needed IV artesunate: 1 dose=2.4 mg/kg IV doses (3 in total) at 0, 12 and 24 hours PLUS reassessment and follow-on treatment (in next slide..) If IV artesunate not readily available, give oral antimalarials while obtaining IV artesunate. When IV artesunate arrives, discontinue oral antimalarial and initiate IV treatment. Interim treatment options (Table 1 for dosing): • Artemether-lumefantrine (Coartem) (preferred); or • Atovaquone-proguanil (Malarone); or • Quinine sulfate; or • Mefloquine (only if no other options available) If oral therapy not tolerated, consider administration via nasogastric (NG) tube or after an antiemetic. TREATMENT OF SEVERE MALARIA 20
- 21. Reassessment and follow-on treatment: Reassess parasite density at least 4 hours after the third dose Parasite density ≤1% and patient able to tolerate oral medications: Give a complete follow-on oral regimen. Options include: • Artemether-lumefantrine (Coartem) (preferred), or • Atovaquone-proguanil (Malarone), or • Quinine plus doxycycline or, in children <8 years old and pregnant women, clindamycin, or • Mefloquine (only if no other options available) Parasite density >1%: Continue IV artesunate, same dose, QD up to 6 more days until parasite density ≤1%. When parasite density ≤1%, give complete follow-on oral regimen as listed above. Parasite density ≤1% but patient unable to take oral medication: Continue IV artesunate, same dose, QD up to 6 more days until patient able to take oral therapy. 21
- 22. CHEMOPROPHYLAXIS 22 Considerations when choosing a drug for malaria prophylaxis: • Recommendations for drugs to prevent malaria differ by country of travel and can be found in Malaria Information by Country (source: CDC). • No antimalarial drug is 100% protective and must be combined with the use of personal protective measures, (i.e., insect repellent, long sleeves, long pants, sleeping in a mosquito-free setting or using an insecticide-treated bednet). • For all medicines, also consider the possibility of drug-drug interactions with other medicines that the person might be taking as well as other medical contraindications, such as drug allergies.
- 23. 23 (continued)... • DOSING FOR CHEMOPROPHYLAXIS: Atovaquone/Proguanil (Malarone) Adults: 1 adult tablet daily. Children: 5-8 kg: ½ pediatric tablet daily. 8- 10 kg: ½ pediatric tablet daily. 10-20 kg: 1 pediatric tablet daily. 20-30 kg: 2 pediatric tablets daily.30-40 kg 3 pediatric tablets daily. 40 kg and over: 1 adult tablet daily. Begin 1-2 days before travel, daily during travel, and for 7 days after leaving. Chloroquine Adults: 300 mg base (500 mg salt), once/week. Children: 5 mg/kg base (8.3 mg/kg salt) (maximum is adult dose), once/week. Begin 1-2 weeks before travel, once/week during travel, and for 4 weeks after leaving. Doxycycline Adults: 100 mg daily. Children: ≥8 years old: 2.2 mg/kg (maximum is adult dose) daily. Begin 1-2 days before travel, daily during travel, and for 4 weeks after leaving. Mefloquine Adults: 228 mg base (250 mg salt), weekly. Children: ≤9 kg: 4.6 mg/kg base (5 mg/kg salt), weekly. 10-19 kg: ¼ tablet weekly. 20- 30 kg: ½ tablet weekly. 31-45 kg: ¾ tablet weekly. >45 kg: 1 tablet weekly. Begin 1-2 weeks before travel, weekly during travel, and for 4 weeks after leaving. Primaquine Adults: 30 mg base, daily Children: 0.5 mg/kg base up to adult dose daily Begin 1-2 days prior to travel, daily during travel, and for 7 days after leaving Tafenoquine (Arakoda) Adults only: 200 mg per dose. Begin daily for 3 days prior to travel, weekly during travel, and for 1 week after leaving.
- 24. PREVENTION AND CONTROL 24 Insecticide-Treated Bed Nets (INTs) - only two insecticides classes are approved for use on INTs (pyrroles & pyrethroids). Indoor Residual Spraying (IRS) with DDT. Source reduction: Draining swamps or by ditching marshy areas to remove standing water. Biological control - fungi (E.g., Laegenidium giganteum) - mermithid nematodes (E.g., Romanomermis culicivorax) - mosquito fish (Gambusia affinis) Fogging or area spraying. Wearing of light-colored clothes, long pants, & long- sleeved shirts. Chemical Larviciding - Oils applied to the water surface - Toxins from the bacterium Bacillus thuringiensis var. israelensis (Bti) - Insect growth regulators such as methroprene. INTs IRS Fogging Source reduction
- 25. 25
- 26. REFERENCE 26
- 27. THANK YOU K.APARNA A presentation on MALARIA 27