Malaria diagnosis and management case based study t

P. Vivax schizont
The diagnosis of P. vivax malaria is later confirmed by review of a blood smear available from the first episode (Figure), and by a PCR positive for P. vivax on blood collected during the current episode.
The microscopic diagnosis of P. vivax is based on the following:
The infected red cells are enlarged and deformed;
The schizont shown contains 20 merozoites (schizonts of P. malariae and P. ovale have fewer merozoites; and in P. falciparum, schizonts are not usually seen in the peripheral blood);
The round gametocyte shown, contained in an enlarged red cell. (In this case, the typical Schüffner’s dots were not visible, probably due to staining problems.)

1. Malaria: Effective Drugs Dr. Govind Rankawat (Gold Medalist) MBBS, MD (Medicine), FIDM, FICC Ast . Professor, Department of Medicine SMS Medical College, Jaipur

2. Why only female….

3. A Case of…… A 44-year-old man is seen at a physician’s office in the during a week-end, for suspected malaria. The patient was born in Pakistan but has lived in the India for the past 12 years . He travels frequently back to Pakistan to visit friends and relatives. He did not take malaria prophylaxis then. Five weeks ago, he was diagnosed with malaria and treated at a local hospital. The blood smear at that time was reported by the hospital as positive for malaria, species undetermined. He was then treated with 2 days of IV fluids (nature unknown) and tablets (nature unknown), and recovered .

4. A Case of…… The patient now presents with a history of low grade fever for the past few days, with no other symptoms. A blood smear is taken and examined at a hospital laboratory by the technician (no pathologist is available on this week-end). Through a telephone discussion, the technician states that she sees 4 parasites per 1000 red blood cells, with rings, “other forms with up to four nuclei,” and that some of the infected red blood cells are enlarged and deformed.

5. A Case of…… Question 1: What is your most probable diagnosis? Not Malaria Plasmodium falciparum Plasmodium vivax Plasmodium ovale Plasmodium malariae Babesia

6. Question 2: What treatment approach would you recommend, based on this clinical history and on the fact that the microscopy findings will not be confirmed by a pathologist for at least 24 hours? Ans. Do not start anti-treatment until a formal microscopic diagnosis is made (in 12-24 hours)

7. P. Vivax schizont The diagnosis of P. vivax malaria is later confirmed by review of a blood smear available from the first episode (Figure), and by a PCR positive for P. vivax on blood collected during the current episode. The microscopic diagnosis of P. vivax is based on the following: The infected red cells are enlarged and deformed; The schizont shown contains 20 merozoites ( schizonts of P. malariae and P. ovale have fewer merozoites ; and in P. falciparum, schizonts are not usually seen in the peripheral blood); The round gametocyte shown, contained in an enlarged red cell. (In this case, the typical Schüffner’s dots were not visible, probably due to staining problems.)

8. An 11-year-old boy was admitted to the Hospital due to sustained fever for 10 days prior to admission. He presented with fever and chills, He had a history of unknown partial treatments from a rural Burmese hospital 1 week prior to moving to us. His father remembered that the boy had been given some Lumerax tablets without improvement of his condition. On admission, his physical examination revealed A high-grade fever (39.1°C), heart rate 140 bpm and respiratory rate 30 breaths/minute.

9. He looked sick and had a flushed face. His liver was mildly enlarged with firm and sharp margins without tenderness. His spleen was normal . There were no petechiae or haemorrhages on his skin. He had drowsiness but good orientations to time, place and person. No neurologica deficits were found during admission. INVESTIGATIONS Laboratory studies showed: haemoglobin concentration of 12.2 g/ dL , a haematocrit 38.0% and a white cell count 11 810 cells/mm3 with 70% neutrophils, 11.2 % lymphocytes and 13.7% monocytes. The platelet count was 383 000 cells/mm3.

10. His peripheral blood smear showed normochromic red blood cells with several target cells and few basophilic stipplings , and few ring-form trophozoites of P falciparum in normal-sized red cells. DIAGNOSIS P falciparum malaria. TREATMENT The patient received artesunate as an antimalarial medication intravenously due to poor oral intake for 4 days. Then artesunate was switched to an oral form on the fifth day and was continued for 1 week.

11. He also received mefloquine on the second day of admission, and primaquine to kill gametocytes before he was discharged from the hospital. Owing to poor oral intake, he received a normal saline infusion for hydration for 7 days. OUTCOME AND FOLLOW-UP After the initiation of antimalarial treatment, the patient’s clinical outcome improved. His appetite returned to normal in 1 week. There were no complications from malarial infection, such as cerebral malaria, hyperpyrexia, severe anaemia , hypoglycaemia , metabolic acidosis and seizure in this boy.

12. Algorithm for Management of Malaria CDC GUIDLINES Administer follow on treatment after artesunate complete: † Artemether-lumefantrine or Atovaquone-proguanil or Doxycycline (or clindamycin) or if no other options Mefloquine Atovaquone-proguanil or Artemether-lumefantrine or Quinine plus tetracycline or doxycycline or clindamycin or Mefloquine Atovaquone-proguanil or Artemether-lumefantrine or Quinine plus tetracycline or doxycycline or clindamycin Chloroquine or Hydroxychloroquine Fever and history of travel to malaria- endemic area or clinical suspicion of malaria C onside r al t erna t e diagnosis Perform thick and thin blood smears and read within few hours* Repeat blood films every 12-24 hours (total of 3 times) Admit to intensive care unit . P. vivax In chloroquine resistance Intravenous artesunate Artemether-lumefantrine or Atovaquone-proguanil or Quinine or if no other options Mefloquine Monitor parasitemia ever y 12 – 24 hour s Chloroquine or Hydroxychloroquine Atovaquone-proguanil or Artemether-lumefantrine or Quinine plus tetracycline or doxycycline or clindamycin or Mefloquine No No Y e s Y e s Evaluation Disposi t io n Medica t ion Blood Film Positive From smear: calculate parasitemia and determine species Evaluate clinical status and disease severity Severe malaria and/or patient unable to tolerate oral medication, regardless of species Uncomplicated malaria P. Ovale or P. Vivex (Without chloroquine resistance P. Falciparum in area with no chloroquine resistance P. Falciparum with chloroquine resistance P. Falciparum with mefloquin resistance P . falciparum or species not yet identified P. malariae Blood Film Positive

13. Uncomplicated malaria: Plasmodium falciparum or unknown species Drug Susceptibility (Based on where acquired) Recommended Adult Regimens Recommended Pediatric Regimens 4 Chlo r o q uine resistant or unknown resista nce (All malaria- endemic regions except those in Central America west of Panama Canal, Haiti, and Dominican Republic) Artemether-lumefantrine (Coartem TM ) 5 (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 Atovaquone-proguanil (Malarone TM ) 6 ( Adult tab: 250 mg atovaquone and 100 mg proguanil) 4 adult tabs po QD x 3 days Artemether-lumefantrine (Coartem TM ) 5 (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 TM ) 6 (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 Chl o r o q uine resistant or unknown resistance (All malaria- endemic regions except those in Central America west of Panama Canal, Haiti, and Dominican Republic) C. Quinine sulfate 7 plus doxycycline 8 , tetracycline 8 , or clindamycin 9 Quinine sulfate: 542 mg base (650 mg salt) po TID x 3 or 7 days 7 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 D. Mefloquine 10 Dose 1: 684 mg base (750 mg salt) po Dose 2 at 6 to 12 h: 456 mg base (500 mg salt) po C. Quinine sulfate 7 plus doxycycline 8 , tetracycline 8 , or clindamycin 9 Quinine sulfate: 8.3 mg base/kg (10 mg salt/kg) po TID x 3 or 7 days 7 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 D. Mefloquine 10 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 Chlo r o q uine sensitive 11 ( Centra l America west of Panama Canal, Haiti, and Dominican Republic) 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 TM 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 Chloroquine phosphate (Aralen™ 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; or Hydroxychloroquine (Plaquenil TM 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

14. 3 Uncomplicated malaria: P. vivax or P. ovale Drug Susceptibility (Based on where acquired) Recommended Adult Regimen (BOTH acute and antirelapse treatments recommended) Recommended Pediatric Regimen 3 (BOTH acute and antirelapse treatments recommended) Chlo r o q uine sensitive (All malaria- endemic regions except Papua New Guinea and Indonesia) Acute treatment 4 : 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 TM 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 AND Antirelapse treatment 5 : Primaquine phosphate 6,7,8 30 mg base po qd x 14 days; or Tafenoquine (Krintafel TM ) 6,7,9 300 mg po x 1 dose Acute treatment 4 : Chloroquine phosphate (Aralen™ 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; or Hydroxychloroquine (Plaquenil TM 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 AND Antirelapse treatment 5 : Primaquine phosphate 6,7,8 0.5 mg base/kg po qd x 14 days; or Tafenoquine (Krintafel TM ) 6,7,9 300 mg po x 1 dose, only for patients ≥16 years old Drug Susceptibility (Based on where acquired) Recommended Adult Regimens (BOTH acute and antirelapse treatments recommended) Recommended Pediatric Regimens 3 (BOTH acute and antirelapse treatments recommended) Chlo r o q uine resistant (Pa pu a New Guinea and Indonesia) Acute treatment: Artemether-lumefantrine (Coartem TM ) 10 (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 Atovaquone-proguanil (Malarone TM ) 11 (Adult tab: 250 mg atovaquone and 100 mg proguanil) 4 adult tabs po QD x 3 days Acute treatment: Artemether-lumefantrine (Coartem TM ) 10 (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 TM ) 11 (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

15. 5 (continued) Uncomplicated malaria: P. vivax or P. ovale Drug Susceptibility (Based on where acquired) Recommended Adult Regimens (BOTH acute and antirelapse treatments recommended) Recommended Pediatric Regimens 3 (BOTH acute and antirelapse treatments recommended) Chlo r o q uine resistant (Pa pu a New Guinea and Indonesia) C. Quinine sulfate 12 plus doxycycline 13 , tetracycline 13 , or clindamycin 14 Quinine sulfate: 542 mg base (650 mg salt) po TID x 3 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 D. Mefloquine 15 Dose 1: 684 mg base (750 mg salt) po Dose 2 at 6 to 12 h: 456 mg base (500 mg salt) po AND Antirelapse treatment 16 : Primaquine phosphate 17,18,19 30 mg base po qd x 14 days C. Quinine sulfate 12 plus doxycycline 13 , tetracycline 13 , or clindamycin 14 Quinine sulfate: 8.3 mg base/kg (10 mg salt/kg) po TID x 3 days Doxycycline: 2.2 mg/kg po q12 h 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 D. Mefloquine 10 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 AND Antirelapse treatment 16 : Primaquine phosphate 17,18,19 0.5 mg base/kg po qd x 14 days

16. 6 Uncomplicated malaria: P. malariae or P. knowlesi 1,2 Drug Susceptibility (Based on where acquired) Recommended Adult Regimens Recommended Pediatric Regimens 3 Chlo r o q uine sensitive (All malaria- endemic regions, no known resistance) Chloroquine phosphate (Aralen™ and generics) Dose: 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 TM 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 Artemether-lumefantrine (Coartem TM ) 4 (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 Chloroquine phosphate (Aralen™ 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; or Hydroxychloroquine (Plaquenil TM 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 Artemether-lumefantrine (Coartem TM ) 4 (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 Chlo r o q uine sensitive (All malaria- endemic regions, no known resistance) C. Atovaquone-proguanil (Malarone TM ) 5 ( Adult tab: 250 mg atovaquone and 100 mg proguanil) 4 adult tabs po QD x 3 days D. Quinine sulfate 6 plus doxycycline 7 , tetracycline 7 , or clindamycin 8 Quinine sulfate: 542 mg base (650 mg salt) po TID x 3 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 E. Mefloquine 9 Dose 1: 684 mg base (750 mg salt) po Dose 2 at 6 to 12 h: 456 mg base (500 mg salt) po Atovaquone-proguanil (Malarone TM ) 5 (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 Quinine sulfate 6 plus doxycycline 7 , tetracycline 7 , or clindamycin 8 Quinine sulfate: 8.3 mg base/kg (10 mg salt/kg) po TID x 3 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 9 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

17. 8 Uncomplicated malaria: Pregnant women 1,2 Species and Drug Susceptibility (Based on where acquired) Recommended Adult Regimens Chloroquine resistant 3 P. falciparum (All malaria- endemic regions except Central America west of Panama Canal, Haiti, and Dominican Republic) P. vivax or P. ovale (Papua New Guinea and Indonesia) Preferred for 2 nd and 3 rd trimesters: Artemether-lumefantrine (Coartem TM ) 4 (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 5 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 (Table 2 for options and dosing) Antirelapse treatment with either primaquine or tafenoquine contraindicated during pregnancy 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 TM 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 (Table 2 for options and dosing) Antirelapse treatment with either primaquine or tafenoquine contraindicated during pregnancy

18. 9 Severe malaria Species and Drug Susceptibility (Based on where acquired) Recommended Adult Regimen Recommended Pediatric 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 (Table 2) IV artesunate: Commercially available. If not in stock or available within 24 hours, contact CDC’s Malaria Hotline. 1 dose=2.4 mg/kg IV doses (3 in total) at 0, 12 and 24 hours PLUS reassessment and follow-on treatment below 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. 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 (Table 1 for dosing): 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 (Table 1 for dosing). 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.

19. Finally finished… Thank you!