Sandbox mona

|- | Choriocarcinoma||

• Soft, tan with with hemorrhage and necrosis

http://www.pathologyoutlines.com/topic/ovarytumorchorio.html

Snow storm ultrasound (hydatidiform mole)

Causes by Organ System

Cardiovascular	No underlying causes
Chemical / poisoning	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	No underlying causes
Ear Nose Throat	No underlying causes
Endocrine	No underlying causes
Environmental	No underlying causes
Gastroenterologic	No underlying causes
Genetic	No underlying causes
Hematologic	Chediak-Higashi disease , Extramedullary haemopoiesis, Familial histiocytic reticulosis, Fanconi-Bickel syndrome, Haemochromatosis , Sickle cell crisis , Haemoglobin C disease, Haemoglobin E disease, Haemoglobin SC disease, Haemolytic disease of the newborn, Hereditary spherocytosis , Mastocytosis , Myelofibrosis , Hereditary neutrophilia, Vitamin B12 deficiency.
Iatrogenic	No underlying causes
Infectious Disease	Abscess, Actinomyces, Alveolar hydatid disease, Bartonellosis, Brucellosis, Cat scratch fever, Entamoeba histolytica, Gallbladder empyema, kala-azar, Leishmaniasis, Kaposi sarcoma, Liver abscess, Liver granuloma, Lymphogranuloma venereum, Malaria, Mycobacterium tuberculosis, Oesophagostomiasis, Pancreatic abscess, Pelvic inflammatory disease, Psittacosis, Relapsing fever , Syphilis congenital, Tertiary syphilis, Toxoplasmosis congenital, Yersinia enterocolitica.
Musculoskeletal / Ortho	No underlying causes
Neurologic	No underlying causes
Nutritional / Metabolic	No underlying causes
Obstetric/Gynecologic	Choriocarcinoma, Ectopic pregnancy, Endometriosis, Meigs syndrome, Pelvic inflammatory disease, Pregnancy, Uterine enlargement, Uterine leiomyoma.
Oncologic
Opthalmologic	No underlying causes
Overdose / Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal / Electrolyte	No underlying causes
Rheum / Immune / Allergy	No underlying causes
Sexual	No underlying causes
Trauma	No underlying causes
Urologic	No underlying causes
Miscellaneous	No underlying causes

he main complication of the complete mole is a 2% chance of progression to a cancer called choriocarcinoma.There is also an increased risk of choriocarcinoma, but the risk is lower than with the complete mole. A salvage regimen is instituted if any of the following occur: A plateau of the beta-hCG for 3 weeks (defined as a beta-hCG decrease of 10% or less for 3 consecutive weeks). A rise in beta-hCG of greater than 20% for 2 consecutive weeks. Appearance of metastases.

In women with complete HM, risk of persistence or neoplastic transformation is approximately doubled in the setting of certain characteristics, which include the following:

• Age older than 35 years or age younger than 20 years
• Pre-evacuation serum beta-hCG greater than 100,000 IU/L
• Large-for-date uterus
• Large uterine molar mass
• Large (>6 cm) ovarian cysts
• Pre-eclampsia
• Hyperthyroidism
• Hyperemesis of pregnancy
• Trophoblastic embolization
• Disseminated intravascular coagulation

An effective form of contraception is important during the follow-up period to avoid the confusion that can occur with a rising beta-hCG as a result of pregnancy.

Chemotherapy is necessary when there is the following:

A rising beta-hCG titer for 2 weeks (3 titers). A tissue diagnosis of choriocarcinoma. A plateau of the beta-hCG for 3 weeks. Persistence of detectable beta-hCG 6 months after mole evacuation. Metastatic disease. An elevation in beta-hCG after a normal value. Postevacuation hemorrhage not caused by retained tissues.

If a diagnosis of GTD is made, routine work-up includes the following:

• Serum beta-hCG.
• Blood work of liver, renal, and marrow function.
• Chest x-ray.
• Pelvic ultrasound.
• Head computed tomography or magnetic resonance imaging (in the case of choriocarcinoma or central nervous system signs).

Treatment of GTD depends on the risk category determined by the Modified WHO Prognostic Scoring System as adapted by the International Federation of Gynecology and Obstetrics (see Table 1). Since the very rare placental-site trophoblastic tumors and the even more rare epithelioid trophoblastic tumors are biologically distinct entities, their management is discussed separately.

Gestational trophoblastic disease (GTD) may be classified as follows:[1]

Hydatidiform mole (HM).

Complete HM. Partial HM.

Gestational trophoblastic neoplasia.

Invasive mole. Choriocarcinoma. Placental-site trophoblastic tumor (PSTT); (very rare). Epithelioid trophoblastic tumor (ETT); (extremely rare).

Choriocarcinoma, PSTT, and ETT are often grouped under the heading gestational trophoblastic tumors.

Invasive mole Clinical Features The prognosis for cure of patients with GTDs is good even when the disease has spread to distant organs, especially when only the lungs are involved. Therefore, the traditional TNM staging system has limited prognostic value.[4] The probability of cure depends on the following:

• Histologic type (invasive mole or choriocarcinoma)
• Extent of spread of the disease/largest tumor size
• Level of serum beta-hCG
• Duration of disease from the initial pregnancy event to start of treatment
• Number and specific sites of metastases
• Nature of antecedent pregnancy
• Extent of prior treatment

GTDs contain paternal chromosomes and are placental, rather than maternal, in origin. The most common presenting symptoms are vaginal bleeding and a rapidly enlarging uterus, and GTD should be considered whenever a premenopausal woman presents with these findings. Because the vast majority of GTD types are associated with elevated human chorionic gonadotropin (hCG) levels, an hCG blood level and pelvic ultrasound are the initial steps in the diagnostic evaluation. In addition to vaginal bleeding and uterine enlargement, other presenting symptoms or signs may include the following:

Pelvic pain or sensation of pressure. Anemia. Hyperemesis gravidarum. Hyperthyroidism (secondary to the homology between the beta-subunits of hCG and thyroid-stimulating hormone (TSH), which causes hCG to have weak TSH-like activity). Preeclampsia early in pregnancy.

The most common antecedent pregnancy in GTD is that of an HM.

Choriocarcinoma most commonly follows a molar pregnancy but can follow a normal pregnancy, ectopic pregnancy, or abortion, and it should always be considered when a patient has continued vaginal bleeding in the postdelivery period. Other possible signs include neurologic symptoms (resulting from brain metastases) in a female within the reproductive age group and asymptomatic lesions on routine chest x-ray.

●Choriocarcinoma

●Placental site trophoblastic tumor (PSTT)

●Epithelioid trophoblastic tumor (ETT)

Gestational trophoblastic disease Hydatidiform mole • Complete mole • Partial mole • Invasive mole Placental site trophoblastic tumour Epithelioid trophoblastic tumour Choriocarcinoma

Day	Drug	Dose
1	Etoposide	100 mg/m2 IV for 30 min
	Dactinomycin	0.5 mg IV push
	Methotrexate	300 mg/m2 IV for 12 h
2	Etoposide	100 mg/m2 IV for 30 min
	Dactinomycin	0.5 mg IV push
	Folinic Acid	15 mg or PO every 12 h × 4 doses, beginning 24 h after the start of methotrexate
8	Cyclophosphamide	600 mg/m2 IV infusion
	Vincristine	0.8–1.0 mg/m2 IV push (maximum dose 2 mg

Modified WHO Prognostic Scoring System as Adapted by FIGO
Scores	0	1	2	4
Age	<40	≥40	–	–
Antecedent pregnancy	mole	abortion	term	–
Interval months from index pregnancy	<4	4–6	7–12	>12
Pretreatment serum hCG (iu/1)	<103	103–104	104–105	>105
Largest tumor size (including uterus)	<3	3–4 cm	≥5 cm	–
Site of metastases	lung	spleen, kidney	gastrointestinal	liver, brain
Number of metastases	–	1–4	5–8	>8
Previous failed chemotherapy	–	–	single drug	≥2 drugs"

Stage	FIGO Anatomical Staging
I	Disease confined to the uterus
II	GTN extends outside of the uterus, but is limited to the genital structures (adnexa, vagina, broad ligament)
III	GTN extends to the lungs, with or without known genital tract involvement
IV	All other metastatic sites

'	American Cancer Society (ACS), American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP)1 2012	'
When to start screeningb	Age 21. Women aged <21 years should not be screened regardless of the age of sexual initiation or other risk factors

• Influenza A and B

• Adults

• Preferred regimen:Oseltamivir (Tamiflu)75 mg bid for 5 days OR Zanamivir(Relenza) 10 mg (two 5-mg inhalations)bid for 5 days OR Peramivir(Rapivab) One 600 mg dose, via intravenous infusion for 15-30 minutes for 1 day

• Children

• Preferred regimen:Oseltamivir If younger than 1 yr old: 3 mg/kg/dose bid If 1 yr or older, dose varies by child’s weight: 15 kg or less, the dose is 30 mg bid; >15 to 23 kg, the dose is 45 mg bid ;>23 to 40 kg, the dose is 60 mg bid; >40 kg, the dose is 75 mg bid for 5 days OR

• Zanamivir(Relenza) 10 mg (two 5-mg inhalations)bid
• Note:FDA approved and recommended Peramivir(Rapivab) for use in adults ≥18 yrs

• Dosing in Adult Patients with Renal Impairment
• Oral oseltamivir
• Creatinine clearance 61 to 90 mL/min-75 mg twice a day
• Creatinine clearance 31 to 60 mL/min-30 mg twice a day
• Creatinine clearance 10 to 30 mL/min-30 mg once daily
• ESRD Patients on Hemodialysis
• Creatinine clearance ≤10 mL/min-30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days
• ESRD Patients on Continuous Ambulatory Peritoneal Dialysis-A single 30 mg dose administered immediately after a dialysis exchange

• Intravenous Peramivir (single dose)
• Creatinine clearance >50 mL/min-600mg
• Creatinine clearance 30 to 49 mL/min-200mg
• Creatinine clearance 10 to 29 mL/min-100mg
• ESRD Patients on Hemodialysis-Dose administered after dialysis at a dose adjusted based on creatinine clearance

avian flu

• 1.Preferred regimen:Oseltamivir 75 mg PO qd for a minimum 10 days

• Note:Patients with severe disease may have diarrhea and may not absorb oseltamivir efficiently

• 2.Patients with Avian Influenza who have diarrhea and malabsorption

• Preferred regimen:Zanamivir10 mg inhaled bid for minimum 5 days OR Peramivir600 mg IV as a single dose for1 day
• Note(1)Preliminary evidence demonstrates that neuraminidase inhibitor can reduce the duration of viral replication and improve survival among patients with avian influenza. In cases of suspected avian influenza, one of the following 3 neuraminidase inhibitors should be administered as soon possible, preferably within 48 hours of symptom onset.

• Note(2)The use of corticosteroids is not recommended.
• Note(3): Physicians may consider increasing either the recommended daily dose and/or the duration of treatment in cases of severe disease.
• Note(4):The use of amantadine is not recommended as most H5N1 and H7N9 avian influenza viruses are resistant to it.
• Note(5):Supportive care is also an important cornerstone of the care of patients with avian influenza. Considering the severity of the illness and the possible complications, patients may require fluid resuscitation, vasopressors, intubation and ventilation, paracentesis, hemodialysis or hemofiltration, and parentral nutrition.

• Chronic granulomatous meningitis.

• Preferred regimen: Pentamidine AND (Clarithromycin OR Azithromycin) AND Fluconazole AND Sulfadiazine AND Flucytosine

• Chronic granulomatous meningitis.

• Preferred regimen: Pentamidine AND (Clarithromycin OR Azithromycin) AND Fluconazole AND Sulfadiazine AND Flucytosine

Babesia microti; babesiosis

• 1.Mild/moderate disease.

• Preferred regimen: Atovaquone 750 mg po bid AND Azithromycin 600 mg po qd for 7-10 days

• 2.Severe babesiosis:

• Preferred regimen: Clindamycin 600 mg po tid AND Quinine 650 mg po tid for 7–10 days OR Clindamycin 1.2 gm IV bid.
• Note(1) For overwhelming infection in asplenic patients and immunocompromised patients, treat for 6 or more weeks
• Note(2)Consider transfusion if 􀂕10% parasitemia

CL

IM SbV at 20 mg/kg/day for 14 days for the treatment of L. major, the national standard for the treatment of CL

• ===1.Cutaneous Leishmaniasis===

• 1.1Systemic Therapy (Parenteral)

• Preferred Regimen: Sodium stibogluconate 20 mg/kg IV/IM once qd for 10-20 days OR Meglumine antimoniate 20 mg/kg IV/IM once qd for 10-20 days
• Alternative Regimen: Liposomal amphotericin B 3 mg/kg/day IV infusion for 6-10 days OR Pentamidine 2-3 mg/kg/day IV/IM for 4-7 days
• Note: Data supporting the use of amphotericin B for treatment of cutaneous (and mucosal) leishmaniasis are anecdotal; standard dosage regimens have not been established. In the United States, pentamidine isethionate is uncommonly used for treatment of cutaneous leishmaniasis. Its limitations include the potential for irreversible toxicity and variable effectiveness.
• 1.2 Systemic Therapy (Oral)
• Preferred Regimen: In adults and adolescents at least 12 years of age who weigh from 33-44 kg:-Miltefosine 50 mg PO q12h for 28 days
• Patients who weigh >45 kg:-Miltefosine 50 mg PO q8h for 28 days
• Alternative Regimen:Ketoconazole 600 mg qd for 28 days OR Fluconazole 200 mg qd for 6 weeks
• Note:The FDA-approved indications are limited to infection caused by three particular species, all three of which are New World species in the Viannia subgenus—namely, Leishmania (V.) braziliensis, L. (V.) panamensis, and L. (V.) guyanensis. The "azoles" showed modest activity against some Leishmania species in some cases, but are not FDA approved
• 1.3Local Therapy
• List of possible local therapies
• Cryotherapy (with liquid nitrogen OR Thermotherapy (use of localized current field radiofrequency heat) OR Intralesional administration of SbV OR Topical application of paromomycin (such as an ointment containing 15% paromomycin/12% methylbenzethonium chloride in soft white paraffin)

• 2.Visceral Leishmaniasis

• 2.1Systemic Therapy (Parenteral)
• Preferred Regimen: Liposomal amphotericin B 3 mg/kg/day IV for 5 days, then once on day 14 and once on day 21 (Total dose: 21 mg/kg) ORSodium stibogluconate 20 mg/kg IV/IM once daily for 28 days OR Meglumine antimoniate 20 mg/kg IV/IM once daily for 28 days'
• Alternative Regimen:Amphotericin B deoxycholate 0.5-1 mg/kg IV once daily (Total dose: 15-20 mg/kg)
• Note: In immunosuppressed patients, dose is 4 mg/kg/day for 5 days, then once on day 10, 17, 24, 31, and 38 (Total dose: 40 mg/kg)
• 2.2 Systemic Therapy (Oral)
• Preferred Regimen:In adults and adolescents at least 12 years of age, who weigh from 33-44 kg:Miltefosine 50 mg PO q12h for 28 days Patients who weigh >45 kg:Miltefosine 50 mg PO q8h for 28 days

Plasmodium

• 1. Plasmodium falciparum

• 1.1 Treatment of uncomplicated P. falciparum malaria

• 1.1.1 Treat children and adults with uncomplicated P. falciparum malaria (except pregnant women in their first trimester) with one of the following recommended ACT (artemisinin-based combination therapy)

• Preferred regimen (1): Artemether 5–24 mg/kg bw PO AND Lumefantrine 29–144 mg/ kg bw PO, Both are given bid for 3 days (total, six doses). The first two doses should, ideally, be given 8 h apart.

• Dosage regimen based on Body weight (kg)
• Body weight (kg)-5 to < 15- Artemether 20 (mg) AND Lumefantrine 120(mg) given bid for 3 days;
• Body weight (kg)-15 to < 25- Artemether 40 (mg) AND Lumefantrine 240(mg) given bid for 3 days;
• Body weight (kg)-25 to < 35- Artemether 60 (mg) AND Lumefantrine 360(mg) given bid for 3 days;
• Body weight (kg) ≥ 35- Artemether 80 (mg) AND Lumefantrine 480(mg) given bid for 3 days.

• Preferred regimen (2): Artesunate (2–10) mg/kg bw per day AND Amodiaquine(7.5–15) mg/kg bw per day ,both are given once a day for 3 days. A total therapeutic dose range of 6–30 mg/kg bw per day artesunate and 22.5–45 mg/kg bw per dose amodiaquine is recommended

• Dosage regimen based on Body weight (kg)
• Body weight (kg)-4.5 to < 9- Artesunate 25 (mg) AND Amodiaquine 67.5 (mg) given bid for 3 days;
• Body weight (kg)-9 to < 18 - Artesunate 50 (mg) AND Amodiaquine 135 (mg) given bid for 3 days;
• Body weight (kg)-18 to < 36- Artesunate 100 (mg) AND Amodiaquine 270(mg) given bid for 3 days;
• Body weight (kg) ≥ 36 - Artesunate 200 (mg) AND Amodiaquine 540 (mg) given bid for 3 days.

• Preferred regimen (3): Artesunate (2–10) mg/kg bw per dayAND Mefloquine (2–10) mg/kg bw per day both are given once a day for 3 days

• Dosage regimen based on Body weight (kg)
• Body weight (kg)-5 to < 9- Artesunate 25 (mg) AND Mefloquine 55 (mg) given bid for 3 days;
• Body weight (kg)-9to < 18- Artesunate 50 (mg) AND Mefloquine 110 (mg) given bid for 3 days;
• Body weight (kg)-18 to < 36- Artesunate 100 (mg) AND Mefloquine 220 (mg) given bid for 3 days;
• Body weight (kg)- ≥ 36 - Artesunate 200 (mg) AND Mefloquine 440 (mg) given bid for 3 days;

• Preferred regimen (4): Artesunate (2–10) mg/kg bw per day given once a day for 3 days AND Sulfadoxine-Pyrimethamine 1.25 (25–70 / 1.25–3.5) mg/kg bw given as a single dose on day 1

• Dosage regimen based on Body weight (kg)
• Body weight (kg)-5 to < 10- Artesunate 25 (mg) AND Sulfadoxine-Pyrimethamine 250/12(mg) given bid for 3 days;
• Body weight (kg)-10 to < 25- Artesunate 50 (mg) AND Sulfadoxine-Pyrimethamine 500 / 25 (mg) given bid for 3 days;
• Body weight (kg)-25 to < 50- Artesunate 100 (mg) AND Sulfadoxine-Pyrimethamine 1000 / 50 (mg) given bid for 3 days;
• Body weight (kg)- ≥50- Artesunate 200 (mg) AND Sulfadoxine-Pyrimethamine 1500 / 75 (mg) given bid for 3 days;

• Preferred regimen (5): Dihydroartemisinin (2–10) mg/kg bw per day AND Piperaquine(16–27) mg/kg bw per day

• Dosage regimen based on Body weight (kg)
• Body weight (kg)-5 to < 8- Dihydroartemisinin 20(mg) AND Piperaquine 160 (mg) given bid for 3 days;
• Body weight (kg)-8 to < 11- Dihydroartemisinin30 (mg) AND Piperaquine 240 (mg) given bid for 3 days;
• Body weight (kg)-11 to < 17 - Dihydroartemisinin 40 (mg) AND Piperaquine 320 (mg) given bid for 3 days;
• Body weight (kg)-17 to < 25- Dihydroartemisinin 60 (mg) AND Piperaquine 480 (mg) given bid for 3 days;
• Body weight (kg)-25 to < 36- Dihydroartemisinin 80 (mg) AND Piperaquine 640 (mg) given bid for 3 days;
• Body weight (kg)-36 to < 60- Dihydroartemisinin 120 (mg) AND Piperaquine 960 (mg) given bid for 3 days;
• Body weight (kg)-60 < 80 - Dihydroartemisinin 160 (mg) AND Piperaquine 1280 (mg) given bid for 3 days;
• Body weight (kg)- >80- Dose of Dihydroartemisinin 200 (mg) AND Piperaquine 1600 (mg) given bid for 3 days;

• 1.1.2 Reducing the transmissibility of treated P. falciparum infections In low-transmission areas in patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)

• Preferred regimen: single dose of 0.25 mg/kg bw Primaquine with ACT

• 1.2 Recurrent Falciparum Malaria

• 1.2.1 Failure within 28 days

• Note:The recommended second-line treatment is an alternative ACT known to be effective in the region. Adherence to 7-day treatment regimens (with artesunate or quinine both of which should be co-administered with + tetracycline, or doxycycline or clindamycin) is likely to be poor if treatment is not directly observed; these regimens are no longer generally recommended.

• 1.2.2 Failure after 28 days

• Note: all presumed treatment failures after 4 weeks of initial treatment should, from an operational standpoint, be considered new infections and be treated with the first-line ACT. However, reuse of mefloquine within 60 days of first treatment is associated with an increased risk for neuropsychiatric reactions, and an alternative ACT should be used

• 1.3 Reducing the transmissibility of treated P. falciparum infections In low-transmission areas in patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)

• Note: a single dose of 0.25 mg/kg bw Primaquine with ACT

• 1.4 Treating uncomplicated P. falciparum malaria in special risk groups

• 1.4.1 Pregnancy

• First trimester of pregnancy :Quinine AND Clindamycin PO 10mg/kg bw bid for 7 days
• Second and third trimesters : Mefloquine is considered safe for the treatment of malaria during the second and third trimesters; however, it should be given only in combination with an artemisinin derivative.
• Note: Quinine is associated with an increased risk for hypoglycaemia in late pregnancy, and it should be used (with clindamycin) only if effective alternatives are not available.
• Note: Primaquine and tetracyclines should not be used in pregnancy.

• 1.4.2 Infants less than 5kg body weight : with an ACT at the same mg/kg bw target dose as for children weighing 5 kg.
• 1.4.3 Patients co-infected with HIV: should avoid Artesunate + SP if they are also receiving Co-trimoxazole, and avoid artesunate + amodiaquine if they are also receiving efavirenz or zidovudine.
• 1.4.4 Large and Obese adults: For obese patients, less drug is often distributed to fat than to other tissues; therefore, they should be dosed on the basis of an estimate of lean body weight, ideal body weight. Patients who are heavy but not obese require the same mg/kg bw doses as lighter patients.
• 1.4.5 Patients co-infected with TB: Rifamycins, in particular rifampicin, are potent CYP3A4 inducers with weak antimalarial activity. Concomitant administration of rifampicin during quinine treatment of adults with malaria was associated with a significant decrease in exposure to quinine and a five-fold higher recrudescence rate
• 1.4.6 Non-immune travellers : Treat travellers with uncomplicated P. falciparum malaria returning to nonendemic settings with an ACT.
• 1.4.7 Uncomplicated hyperparasitaemia: People with P. falciparum hyperparasitaemia are at increased risk of treatment failure, severe malaria and death so should be closely monitored, in addition to receiving an ACT

• 2. Treatment of uncomplicated malaria caused by P. vivax, P. ovale, P. malariae or P. knowlesi

• 2.1 Blood Stage infection

• 2.1.1. Uncomplicated malaria caused by P. vivax

• 2.1.1.1 In areas with chloroquine-sensitive P. vivax

• Preferred regimen: Chloroquine PO total dose of 25 mg base/kg bw. Chloroquine is given at an initial dose of 10 mg base/kg bw, followed by 10 mg/kg bw on the second day and 5 mg/kg bw on the third day.

• 2.1.1.2 In areas with chloroquine-resistant P. vivax

• Note: ACTs containing piperaquine, mefloquine or lumefantrine are the recommended treatment, although artesunate + amodiaquine may also be effective in some areas. In the systematic review of ACTs for treating P. vivax malaria, dihydroartemisinin + piperaquine provided a longer prophylactic effect than ACTs with shorter half-lives (artemether + lumefantrine, artesunate + amodiaquine), with significantly fewer recurrent parasitaemias during 9 weeks of follow-up.

• 2.1.2 Uncomplicated malaria caused by P. ovale, P. malariae or P. knowlesi malaria

• Note: Resistance of P. ovale, P. malariae and P. knowlesi to antimalarial drugs is not well characterized, and infections caused by these three species are generally considered to be sensitive to chloroquine. In only one study, conducted in Indonesia, was resistance to chloroquine reported in P. malariae. The blood stages of P. ovale, P. malariae and P. knowlesi should therefore be treated with the standard regimen of ACT or chloroquine, as for vivax malaria.

• 2.1.3 Mixed malaria infections

• Note: ACTs are effective against all malaria species and so are the treatment of choice for mixed infections.

• 2.2 Liver stages (hypnozoites) of P. vivax and P. ovale

• Note: To prevent relapse, treat P. vivax or P. ovale malaria in children and adults (except pregnant women, infants aged < 6 months, women breastfeeding infants < 6 months, women breastfeeding older infants unless they are known not to be G6PD deficient and people with G6PD deficiency) with a 14-day course of primaquine in all transmission settings. Strong recommendation, high-quality evidence In people with G6PD deficiency, consider preventing relapse by giving primaquine base at 0.75 mg base/kg bw once a week for 8 weeks, with close medical supervision for potential primaquine-induced adverse haematological effects.]
• 2.2.1 Primaquine for preventive relapse

• Preferred regimen: Primaquine PO 0.25–0.5 mg/kg bw per day qd for 14 days

• 2.2.2 Primaquine and glucose-6-phosphate dehydrogenase deficiency

• Preferred regimen:Primaquine PO 0.75 mg base/kg bw once a week for 8 weeks.
• Note: The decision to give or withhold Primaquine should depend on the possibility of giving the treatment under close medical supervision, with ready access to health facilities with blood transfusion services.

• 2.2.3 Prevention of relapse in pregnant or lacating women and infants

• Note: Primaquine is contraindicated in pregnant women, infants < 6months of age and in lactating women (unless the infant is known not to be G6PD deficient).

• 3.Treatment of severe malaria

• 3.1 Treatment of severe falciparum infection with Artesunate

• 3.1.1 Adults and children with severe malaria (including infants, pregnant women in all trimesters and lactating women):-

• Preferred regimen: Artesunate IV/IM for at least 24 h and until they can tolerate oral medication. Once a patient has received at least 24 h of parenteral therapy and can tolerate oraltherapy, complete treatment with 3 days of an ACT (add single dose Primaquine in areas of low transmission).

• 3.1.2 Young children weighing < 20 kg

• Preferred regimen:Artesunate (3 mg/kg bw per dose)
• Alternatives regimen: use Artemether in preference to quinine for treating children and adults with severe malaria

• 3.2.Treating cases of suspected severe malaria pending transfer to a higher-level facility (pre-referral treatment)

• 3.2.1 Adults and children

• Preferred regimen: Artesunate IM
• Alternative regimen: Artemether IM OR Quinine IM

• 3.2.2 Children < 6 years

• Preferred regimen: Where intramuscular injections of artesunate are not available , treat with a single rectal dose (10 mg/kg bw) of Artesunate, and refer immediately to an appropriate facility for further care.
• Note: Do not use rectal artesunate in older children and adults.

• 3.3 Pregancy

• Note: Parenteral artesunate is the treatment of choice in all trimesters. Treatment must not be delayed

• 3.4 Treatment of severe P.Vivax infection

• Note: parenteral artesunate, treatment can be completed with a full treatment course of oral ACT or chloroquine (in countries where chloroquine is the treatment of choice). A full course of radical treatment with primaquine should be given after recovery

• 3.5 Additional aspects of management in severe malaria

• Fluid therapy: It is not possible to give general recommendations on fluid replacement; each patient must be assessed individually and fluid resuscitation based on the estimated deficit
• Blood Transfusion :In high-transmission settings, blood transfusion is generally recommended for children with a haemoglobin level of < 5 g/100 mL(haematocrit < 15%). In low-transmission settings, a threshold of 20% (haemoglobin,7 g/100 mL) is recommended
• Exchange blood transfusion: Exchange blood transfusion requires intensive nursing care and a relatively large volume of blood, and it carries significant risks. There is no consensus on the indications, benefits and dangers involved or on practical details such as the volume of blood that should be exchanged. It is, therefore, not possible to make any recommendation regarding the use of exchange blood transfusion

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Toxoplasmosis

• Toxoplasma gondii (treatment)

• 1. Lymphadenopathic toxoplasmosis

• Preferred regimen: Treatment of immunocompetent adults with lymphadenopathic toxoplasmosis is rarely indicated; this form of the disease is usually self-limited.

• 2. Ocular disease

• 2.1 Adults

• Preferred regimen: Pyrimethamine 100 mg for 1 day as a loading dose, then 25 to 50 mg/ day AND Sulfadiazine 1 g m qid AND folinic acid (Leucovorin 5-25 mg with each dose of Pyrimethamine

• 2.2 Pediatric

• Preferred regimen: Pyrimethamine 2 mg/kg first day then 1 mg/kg each day AND Sulfadiazine 50 mg/kg bid AND folinic acid (Leucovorin 7.5 mg per day) for 4 to 6 weeks followed by reevaluation of the patient's condition
• Alternative regimen: The fixed combination of Trimethoprim with Sulfamethoxazole has been used as an alternative.
• Note: If the patient has a hypersensitivity reaction to sulfa drugs, Pyrimethamine AND Clindamycin can be used instead.

• 3. Maternal and fetal infection

• 3.1 First and early second trimesters

• Preferred regimen: Spiramycin is recommended

• 3.2 Late second and third trimesters

• Preferred regimen: Pyrimethamine/Sulfadiazine AND Leucovorin for women with acute T. gondii infection diagnosed at a reference laboratory during gestation.

• 3.3 Infant

• Note: If the infant is likely to be infected, then treatment with drugs such as Pyrimethamine, Atovaquone, Sulfadiazine AND Leucovorin is typical. Congenitally infected newborns are generally treated with pyrimethamine, a sulfonamide, and leucovorin for 1 year.

• 4.Toxoplasma gondii Encephalitis in AIDS

• 4.1 Treatment for acute infection

• Preferred regimen: Pyrimethamine 200 mg PO 1 time, followed by weight-based therapy: If <60 kg, Pyrimethamine 50 mg PO once daily Atovaquone AND Sulfadiazine 1000 mg PO q6h AND Leucovorin 10–25 mg PO once daily, If ≥60 kg, Pyrimethamine 75 mg PO once daily AND Sulfadiazine 1500 mg PO q6h AND Leucovorin 10–25 mg PO once daily. Leucovorin dose can be increased to 50 mg daily or BID. Treatment for at least 6 weeks; longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks.
• Alternative regimen (1) Pyrimethamine Leucovorin AND Clindamycin 600 mg IV/ PO q6h
• Alternative regimen (2)TMP-SMX (TMP 5 mg/kg and SMX 25 mg/kg ) IV/PO BID
• Alternative regimen (3)Atovaquone 1500 mg PO BID )with food ANDPyrimethamine, Leucovorin
• Alternative regimen (4)Atovaquone1500 mg PO BID with food AND sulfadiazine 1000–1500 mg PO q6h (weight-based dosing, as in preferred therapy)
• Alternative regimen (5) Atovaquone 1500 mg PO BID with food
• Alternative regimen (6) Pyrimethamine, Leucovorin AND Azithromycin 900–1200 mg PO daily.

• 4.2 Chronic maintenance therapy

• Preferred regimen: Pyrimethamine 25–50 mg PO daily AND sulfadiazine 2000–4000 mg PO daily (in 2–4 divided doses) AND Leucovorin 10–25 mg PO daily
• Alternative regimen (1): Clindamycin 600 mg PO q8h AND (Pyrimethamine 25–50 mg AND Leucovorin 10–25 mg) PO daily
• Alternative regimen (2): TMP-SMX DS 1 tablet BID
• Alternative regimen (3): Atovaquone 750–1500 mg PO BID AND (Pyrimethamine 25 mg AND Leucovorin 10 mg) PO daily
• Alternative regimen (4): Atovaquone 750–1500 mg PO BID
• Alternative regimen (5): Sulfadiazine 2000–4000 mg PO daily (in 2–4 divided doses ),
• Alternative regimen (6): Atovaquone 750–1500 mg PO BID with food Pyrimethamine and Leucovorin doses are the same as for preferred therapy
• Note: Adjunctive corticosteroids (e.g., Dexamethasone) should only be administered when clinically indicated to treat mass effect associated with focal lesions or associated edema; discontinue as soon as clinically feasible. Anticonvulsants should be administered to patients with a history of seizures and continued through acute treatment, but should not be used as seizure prophylaxis . If Clindamycin is used in place of Sulfadiazine, additional therapy must be added to prevent PCP.

• Toxoplasma gondii (prophylaxis)

• 1. Prophylaxis to prevent first episode of encephalitis in AIDS

• 1.1 Indications

• Toxoplasma IgG-positive patients with CD4 count <100 cells/µL
• Seronegative patients receiving PCP prophylaxis not active against toxoplasmosis should have toxoplasma serology retested if CD4 count decline to <100 cells/µL. Prophylaxis should be initiated if seroconversion occurred.

• 1.2 Prophylactic therapy

• Preferred regimen: TMP-SMX 1 DS PO daily
• Alternative regimen (1): TMP-SMX 1 DS PO three times weekly
• Alternative regimen (2): TMP-SMX 1 SS PO daily
• Alternative regimen (3): Dapsone 50 mg PO daily AND (Pyrimethamine 50 mg AND Leucovorin 25 mg) PO weekly
• Alternative regimen (4): Dapsone 200 mg AND Pyrimethamine 75 mg AND Leucovorin 25 mg PO weekly
• Alternative regimen (5): Atovaquone 1500 mg PO daily
• Alternative regimen (6): Atovaquone 1500 mg AND Pyrimethamine 25 mg AND Leucovorin 10 mg PO daily

African trypanosomiasis

• Sleeping sickness

• 1. East African trypanosomiasis
• 1.1T. b. rhodesiense, hemolymphatic stage

• Adult

• Preferred regimen: Suramin 1 gm IV on days 1,3,5,14, and 21

• Pediatric

• Preferred regimen: Suramin 20 mg/kg IV on days 1, 3, 5, 14, and 21

• 1.2 T. b. rhodesiense, CNS involvement

• Adult

• Preferred regimen: Melarsoprol 2-3.6 mg/kg/day IV for 3 days.After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days.

• Pediatric

• Preferred regimen: Melarsoprol 2-3.6 mg/kg/day IV for 3 days.After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days

• 2. West African trypanosomiasis

• 2.1 T. b. gambiense, Hemolymphatic stage

• Adult

• Preferred regimen: Pentamidine 4 mg/kg/day IM or IV for 7-10 days

• Pediatric

• Preferred regimen: Pentamidine 4 mg/kg/day IM or IV for 7-10 days

• Note(1): Pentamidine should be used during pregnancy and lacation only if the potential benefit justifies the potential risk
• Note(2): IM/IV Pentamidine have a similar safety profile in children age 4 months and older as in adults. Pentamidine is listed as a medicine for the treatment of 1st stage African trypanosomiasis infection (Trypanosoma brucei gambiense) on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.

• 2.2 T. b. gambiense, CNS involvement

• Adult

• Preferred regimen: Eflornithine 400 mg/kg/day in 4 doses for 14 days

• Pediatric

• Preferred regimen: Eflornithine 400 mg/kg/day in 4 doses for 14 days
• Note (1): Eflornithine should be used during pregnancy and lactation, only if the potential benefit justifies the potential risk
• Note (2): The safety of Eflornithine in children has not been established. Eflornithine is not approved by the Food and Drug Administration (FDA) for use in pediatric patients. Eflornithine is listed for the treatment of 1st stage African trypanosomiasis inTrypanosoma brucei gambiense infection on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.

Chagas disease

• Preferred regimen(1):Benznidazole < 12 years5-7.5 mg/kg per day orally in 2 divided doses for 60 days

12 years or older5-7 mg/kg per day orally in 2 divided doses for 60 days

• Preferred regimen(2): Nifurtimox ≤ 10 years15-20 mg/kg per day orally in 3 or 4 divided doses for 90 days

11-16 years12.5-15 mg/kg per day orally in 3 or 4 divided doses for 90 days 17 years or older8-10 mg/kg per day orally in 3 or 4 divided doses for 90 days

• Note: In the United States, nifurtimox and benznidazole are not FDA approved and are available only from CDC under investigational protocols.

varicella zoster

• 1. varicella zoster

• 1.1 Non Immunocompromised person

• Preferred regimen (1): Acyclovir 500 mg PO five times daily for 7-10 days
• Preferred regimen (2):Famciclovir 500mg PO tid daily for 7 days
• Preferred regimen (3):Valacyclovir 1gm PO tid daily for 7 days
• Preferred regimen (4):Brivudin 125mg PO qd daily for 7 days

• 1.2 Immunocompromised person requiring hospitalization or persons with sever neurologic complications

• Preferred regimen (1): Acyclovir 10 mg/ kg IV q8h for 7-10 days
• Preferred regimen (2):Foscarnet 40 mg/ kg IV q8h until lesions are healed

• Note(1): Brivudin is not available in USA and has not been approved by FDA
• Note(2): Foscarnet is not approve by FDA

• Treatment of VZV complications

• HZ ophthalmicus
• Treatment includes the following
• (1) Famciclovir or Valacyclovir for 7–10 days, preferably started within 72 h of rash onset (with IV Acyclovir given as needed for retinitis), to resolve acute disease and inhibit late inflammatory recurrences

(2) pain medications, (3) cool to tepid wet compresses (if tolerated); (4) antibiotic ophthalmic ointment administered bid (e.g.Bacitracin-Polymyxin), to protect the ocular surface;

(5) topical steroids (e.g., 0.125%–1% Prednisolone 2–6 times daily) prescribed and managed only by an ophthalmologist for corneal immune disease, episcleritis, scleritis, or iritis; 

(6) no topical antivirals, because they are ineffective;

(7) mydriatic/cycloplegia as needed for iritis (e.g., 5% Homatropine bid
(8) ocular pressure–lowering drugs given as needed for glaucoma (e.g., Latanaprost qd and/or Timolol maleate ophthalmic gel forming solution every morning). Systemic steroids are indicated in the presence of moderate to severe pain or rash, particularly if there is significant edema, which may cause orbital apex syndrome through pressure on the nerves entering the orbit. The dosage is commonly 20 mg of Prednisone administered (together with an oral antiviral agent) PO tid for 4 days,bid for 6 days, and then once daily every morning for 4 day

• HZ r

Acute retinal necrosis in immunocompetent patients is a less virulent disease and responds better to antiviral therapy. For such patients, acyclovir is clearly beneficial for preserving useful vision [235]. A suggested antiviral regimen for acute retinal necrosis in the otherwise healthy host is intravenous acyclovir (10–15 mg/kg every 8 h for 10–14 days) followed by oral valacyclovir (1 g 3 times daily for 4–6 weeks), although this treatment approach has not been studied in a controlled fashion

• Preferred regimen: Acyclovir IV 10–15 mg/kg q8h for 10–14 days followed by Valacyclovir PO 1 g tid daily for 4–6 weeks

Influenza

• Influenza virus Return to Top

• 1. Adults

• Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg bid
• Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) bid
• Preferred regimen (3): Peramivir (Rapivab®) 600 mg IV for 15-30 minutes (single dose)
• Note: FDA approved and recommended Peramivir (Rapivab®) for use in adults ≥18 yrs

• 2. Children

• 2.1 < 1 yr

• Preferred regimen: Oseltamivir (Tamiflu®) 3 mg/kg/dose bid

• 2.2 > 1 yr

• 2.2.1 ≤ 15 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 30 mg bid

• 2.2.2 > 15 to 23 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 45 mg bid

• 2.2.3 > 23 to 40 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 60 mg bid

• 2.2.4 > 40 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 75 mg bid
• Note: Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) bid may be considered for children > 7 yrs old

• Adult Patients with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis
• Oral Oseltamivir
• Creatinine clearance 61 to 90 mL/min-75 mg twice a day
• Creatinine clearance 31 to 60 mL/min-30 mg twice a day
• Creatinine clearance 10 to 30 mL/min-30 mg once daily
• ESRD Patients on Hemodialysis
• Creatinine clearance ≤10 mL/min-30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days
• ESRD Patients on Continuous Ambulatory Peritoneal Dialysis-A single 30 mg dose administered immediately after a dialysis exchange

• Intravenous Peramivir (single dose)
• Creatinine clearance >50 mL/min-600mg
• Creatinine clearance 30 to 49 mL/min-200mg
• Creatinine clearance 10 to 29 mL/min-100mg
• ESRD Patients on Hemodialysis-Dose administered after dialysis at a dose adjusted based on creatinine clearance

Children- < 1 yr: 3 mg/kg/dose twice daily > 1 yr: dose depends on weight. ≤ 15 kg: 30 mg twice a day > 15 to 23 kg: 45 mg twice a day > 23 to 40 kg: 60 mg twice a day > 40 kg: 75 mg twice a day.

Zanamivir (Relenza®) Adults 10 mg (two 5-mg inhalations) twice daily

For children > 7 yrs old. 10 mg (two 5-mg inhalations) twice daily

Peramivir (Rapivab®) Adults 600 mg IV for 15-30 minutes (single dose)