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Schistosomiasis

  • 1. Schistosoma mansoni, S. haematobium, S. intercalatum
  • Preferred regimen: Praziquantel 40 mg/kg per day PO in one or two divided doses for one day.
  • Alternative regimen (1): Oxamniquine
  • Alternative regimen (2): Artesmisinin
  • Alternative regimen (3): Mefloquine
  • Note: There is no benefit in associating the alternative therapies to Praziquantel.
  • 2. S. japonicum, S. mekongi
  • Preferred regimen: Praziquantel 60 mg/kg per day PO in two divided doses for one day.
  • Alternative regimen (1): Oxamniquine
  • Alternative regimen (2): Artesmisinin
  • Alternative regimen (3): Mefloquine
  • Note: There is no benefit in associating the alternative therapies to Praziquantel.
  • 3. Katayama Fever
  • Preferred regimen: Prednisone 20-40mg/day PO for 5 days.[1]
  • Note: Praziquantel should be used after 4-6 weeks of exposure, because it cannot kill the larvae stages of the Schistosoma. Praziquantel should be used after acute schistosomiasis syndrome symptoms have resolved always together with corticosteroids, only when ova are detected in stool or urine samples.[2]
  • 4. Neuroschistosomiasis
  • Preferred regimen: prednisone 1-2mg/kg.
  • Note: Praziquantel should only be introduced after a few days of the initiation of corticosteroid therapy, due to the risk of increasing the inflammatory response.


Parasites – Trematodes (Flukes)

  • Preferred regimen: Praziquantel 75mg/kg/day PO tid for 2 days.[3]
  • Alternative regimen (1): Albendazole 10mg/kg/day PO qd for 7 days.[4]
  • Alternative regimen (2): Tribendimidine 400mg PO single dose.[5]
  • This regimen is still under investigation, but it appears to be as effective as Praziquantel.
  • Note: Urgent biliary decompression might be required for patients with acute cholangitis.
  • Note: Praziquantel is not approved for treatment of children less than 4 years old.[7]
  • Alternative regimen (1): Myrrh (commiphora molmol) 12 mg/kg/day PO for 6 days.[8]
  • Alternative regimen (2): Triclabendazole 10 mg/kg PO single dose.[8]
  • Preferred regimen: Triclabendazole 10 mg/kg PO one dose[9]
  • Note: Two-dose (double-dose) triclabendazole therapy can be given to patients who have severe or heavy Fasciola infections (many parasites) or who did not respond to single-dose therapy.
  • Alternative regimen: Nitazoxanide 500mg PO bid for 7 days.
  • Preferred regimen (1): Praziquantel 25 mg/kg PO tid for 3 days[10]
  • Preferred regimen (2): Triclabendazole 10 mg/kg PO qd or bid.
  • Alternative regimen (1): Bithinol 30-50mg/kg PO on alternate days for 10-15 doses.
  • Alternative regimen (2): Niclosamide 2mg/kg PO single dose.


Parasites – Intestinal Nematodes (Roundworms)

  • Eosinophilic Meningitis
    • Preferred regimen: Supportive measures. Anthelminthic therapy might be deleterious by augmenting the inflammation due to the death of the larvae. The use of corticosteroids is generally favored for suppression of the inflammation but there are no clinical trials that prove its efficacy.[11]
  • Cutaneous disease:
  • Preferred regimen[14]
  • Adult: Albendazole 400mg PO qd for 3 to 7 days
  • Pediatric: Albendazole > 2 years 400mg PO qd for 3 days
  • Note: This drug is contraindicated in children younger than 2 years age.
  • Alternative regimen[15]
  • Adult: Ivermectin 200 mcg/kg PO qd for one or two days.
  • Pediatric: Ivermectin >15 kg give 200mcg/kg single dose
  • Preferred: Symptomatic therapy, serial lumber puncture, corticosteroids (prednisone 60mg qd for 2 weeks) and analgesics[16]
  • Note: Albendazole and Mebendazole are generally not recommended due to the risk of exacerbation of neurological symptoms following anthelminthic therapy.[17]
  • Note: Albendazole dose for children of 1-2 years is 200mg instead of 400mg.
  • Alternative regimen (1): Ivermectin 150 to 200 µg/kg PO single dose[19]
  • Alternative regimen (2): Nitazoxanide 500mg bid for 3 days. [20]
  • Alternative regimen (3): Levamisole 150 mg PO single dose. Pediatric dose: 2.5mg/kg single dose. [21]
  • Alternative regimen (4): Pyrantel Pamoate 11mg/kg single dose PO - maximum 1.0g.[21]
  • Alternative regimen (5): Piperazine citrate 75mg/kg qd for 2 days - maximum 3.5g.[21]
  • Preferred regimen: Albendazole 400 mg/day PO for 10-30 days.
  • Alternative regimen: Mebendazole 200 mg PO bid for 20-30 days.
  • Preferred regimen (1): Albendazole 400 mg PO single dose - repeat in 2 weeks.[25]
  • Preferred regimen (2): Mebendazole 100 mg PO single dose - repeat in 2 weeks.
  • Alternative regimen (1): Ivermectin 200 µg/kg PO single dose - repeat in 10 days[26]
  • Alternative regimen (2): Pyrantel pamoate 11 mg/kg up to 1.0g PO single dose - repeat in 2 weeks. [27]
  • Preferred regimen: Albendazole 400 mg PO single dose.[28]
  • Alternative regimen (1): Mebendazole 100 mg PO bid or 500 mg daily for 3 days.
  • Alternative regimen (2): Pyrantel pamoate 11 mg/kg PO qd (maximum 1 g/day) for 3 days[29]
  • Preferred regimen: Albendazole 400 mg PO single dose.[28]
  • Alternative regimen (1): Mebendazole 100 mg PO bid or 500 mg daily for 3 days.
  • Alternative regimen (2): Pyrantel pamoate 11 mg/kg PO qd (maximum 1 g/day) for 3 days[30]
  • Preferred regimen: Ivermectin 200 mcg/kg/day PO qd for 2 days or two doses 2 weeks apart from each other.[31]
  • Alternative regimen: Albendazole400mg PO bid for 3-7 days.[32]
  • Preferred regimen: Albendazole 400 mg PO qd for 3 days.
  • Alternatie regimen (1): Mebendazole 100 mg PO bid for 3 days.
  • Alternative regimen (2): Ivermectin 200 mcg/kg/day PO qd for 3 days.[33]

Entamoeba histolytica

  • 1. Amebic Liver Abscess[34]
  • 2. Amebic Colitis[35]
  • 3. Asymptomatic Intestinal Colonization[36]
  • Preferred regimen: Paromomycin 30 mg/kg/day PO tid for 5-10 days.
  • Alternative regimen (1): Diloxanide furoate 500 mg PO tid for 10 days.
  • Alternative regimen (2): Diiodohydroxyquin 650 mg PO tid for 20 days for adults and 30 to 40 mg/kg per day tid for 20 days for children.

Paracoccidiodomycosis

  • Preferred regimen (1): [37]
  • Adults: Itraconazole 200 mg/day PO.
  • Children: Itraconazole (<30/kg and >5 yr) 5-10 mg/kg/day PO.
  • Note: Treatment duration based on organ involvement:
  • Mild involvement: 6-9 months.
  • Moderate involvement: 12-18 months
  • Preferred regimen (2): [37]
  • Minor involvement: 12 months
  • Moderate involvement: 18-24 months
  • Note (2): Preferred treatment in children due to larger experience.
  • Note (3): Preferred in IV formulation in severe forms of the disease - 2 ampules IV tid until patient condition improves so that oral medication can be given.
  • Preferred regimen (3): Amphotericin B deoxycholate mg/kg/day IV until patient improves and can be treated by the oral route.[37]
  • Note: Preferred in severe forms of the disease.[37]
  • Alternative regimen (5): Voriconazole initial dose 400 mg PO/IV q12h for one day, then 200 mg q12h for 6 months[39]
  • Note: Diminish the dose to 50% if weight is <40 kg.

Coccidioidomycosis

Candidiasis

Aspergillosis

  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, followed by 4 mg/kg IV q12h or PO 200 mg q12h.
  • Alternative regimen (1): Liposomal Amphotericin B(L-AMB) 3–5 mg/kg/day IV qd.
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd.
  • Alternative regimen (3): Caspofungin 70 mg IV single dose followed by 50 mg/day IV qd.
  • Alternative regimen (4): Micafungin 100–150 mg/day PO qd.[41][40]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Alternative regimen (5): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (6): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • 2. Invasive sinus aspergillosis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, followed by 4 mg/kg IV q12h or PO 200 mg q12h.
  • Alternative regimen (1): Liposomal Amphotericin B(L-AMB) 3–5 mg/kg/day IV qd.
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd.
  • Alternative regimen (3): Caspofungin 70 mg IV single dose followed by 50 mg/day IV qd.
  • Alternative regimen (4): Micafungin 100–150 mg/day PO qd.[41][40]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Alternative regimen (5): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (6): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • 3. Tracheobronchial aspergillosis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, followed by 4 mg/kg IV q12h or PO 200 mg q12h.
  • Alternative regimen (1): Liposomal Amphotericin B(L-AMB) 3–5 mg/kg/day IV qd.
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd.
  • Alternative regimen (3): Caspofungin 70 mg IV single dose followed by 50 mg/day IV qd.
  • Alternative regimen (4): Micafungin 100–150 mg/day PO qd.[41][40]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Alternative regimen (5): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (6): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • 4. Chronic necrotizing pulmonary aspergillosis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, followed by 4 mg/kg IV q12h or PO 200 mg q12h.
  • Alternative regimen (1): Liposomal Amphotericin B(L-AMB) 3–5 mg/kg/day IV qd.
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd.
  • Alternative regimen (3): Caspofungin 70 mg IV single dose followed by 50 mg/day IV qd.
  • Alternative regimen (4): Micafungin 100–150 mg/day PO qd.[41][40]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Alternative regimen (5): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (6): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • 5. Aspergillosis of the CNS
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, followed by 4 mg/kg IV q12h or PO 200 mg q12h.
  • Alternative regimen (1): Liposomal Amphotericin B(L-AMB) 3–5 mg/kg/day IV qd.
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd.
  • Alternative regimen (3): Caspofungin 70 mg IV single dose followed by 50 mg/day IV qd.
  • Alternative regimen (4): Micafungin 100–150 mg/day PO qd.[41][40]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Alternative regimen (5): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (6): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • Note: There are drug interactions with anticonvulsant therapy.
  • 6. Aspergillus infections of the heart (endocarditis, pericarditis, and myocarditis)
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, followed by 4 mg/kg IV q12h or PO 200 mg q12h.
  • Alternative regimen (1): Liposomal Amphotericin B(L-AMB) 3–5 mg/kg/day IV qd.
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd.
  • Alternative regimen (3): Caspofungin 70 mg IV single dose followed by 50 mg/day IV qd.
  • Alternative regimen (4): Micafungin 100–150 mg/day PO qd.[41][40]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Alternative regimen (5): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (6): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • Note: endocardial lesions generally require surgical treatment. Aspergillus pericarditis usually requires pericardiectomy.
  • 7. Aspergillus osteomyelitis and septic arthritis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, followed by 4 mg/kg IV q12h or PO 200 mg q12h.
  • Alternative regimen (1): Liposomal Amphotericin B(L-AMB) 3–5 mg/kg/day IV qd.
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd.
  • Alternative regimen (3): Caspofungin 70 mg IV single dose followed by 50 mg/day IV qd.
  • Alternative regimen (4): Micafungin 100–150 mg/day PO qd.[41][40]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Alternative regimen (5): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (6): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • Note: Surgical resection of devitalized bone and cartilage is important for curative intent.
  • 8. Aspergillus infections of the eye (endophthalmitis and keratitis)
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, followed by 4 mg/kg IV q12h or PO 200 mg q12h.
  • Alternative regimen (1): Liposomal Amphotericin B(L-AMB) 3–5 mg/kg/day IV qd.
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd.
  • Alternative regimen (3): Caspofungin 70 mg IV single dose followed by 50 mg/day IV qd.
  • Alternative regimen (4): Micafungin 100–150 mg/day PO qd.[41][40]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Alternative regimen (5): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (6): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • Note: Topical therapy is indicated for keratitis, ophthalmologic intervention and management is recommended for all forms of ocular infection. Systemic therapy may be beneficial when treating aspergillus endophthalmitis.
  • 9. Cutaneous aspergillosis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, followed by 4 mg/kg IV q12h or PO 200 mg q12h.
  • Alternative regimen (1): Liposomal Amphotericin B(L-AMB) 3–5 mg/kg/day IV qd.
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd.
  • Alternative regimen (3): Caspofungin 70 mg IV single dose followed by 50 mg/day IV qd.
  • Alternative regimen (4): Micafungin 100–150 mg/day PO qd.[41][40]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Alternative regimen (5): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (6): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • Note: Surgical resection is indicated when feasible.
  • 10. Aspergillus peritonitis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, followed by 4 mg/kg IV q12h or PO 200 mg q12h.
  • Alternative regimen (1): Liposomal Amphotericin B(L-AMB) 3–5 mg/kg/day IV qd.
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd.
  • Alternative regimen (3): Caspofungin 70 mg IV single dose followed by 50 mg/day IV qd.
  • Alternative regimen (4): Micafungin 100–150 mg/day PO qd.[41][40]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Alternative regimen (5): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (6): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • 11. Prophylaxis against invasive aspergillosis
  • 12. Aspergilloma
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, followed by 4 mg/kg IV q12h or PO 200 mg q12h.
  • Alternative regimen: Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • 13.Chronic cavitary pulmonary aspergillosis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, followed by 4 mg/kg IV q12h or PO 200 mg q12h.
  • Alternative regimen (1): Liposomal Amphotericin B(L-AMB) 3–5 mg/kg/day IV qd.
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd.
  • Alternative regimen (3): Caspofungin 70 mg IV single dose followed by 50 mg/day IV qd.
  • Alternative regimen (4): Micafungin 100–150 mg/day PO qd.[41][40]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Alternative regimen (5): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (6): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • Note: long-term therapy might be needed.
  • 14.Allergic bronchopulmonary Itraconazole aspergillosis
  • Preferred regimen: Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • Alternative regimen (1): Voriconazole PO 200 mg bid.
  • Alternative regimen (2): Posaconazole PO 400 mg bid.
  • Note: Corticosteroids are a cornerstone of the therapy.
  • Allergic aspergillus sinusitis
  • Preferred regimen: None or Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, followed by 400 mg/day PO OR 200 mg q12h IV for 2 days, followed by 200 mg IV qd.
  • Note: Few data available for other agents.
  • Relative indications for surgical treatment of invasive aspergillosis
  • Pulmonary lesion in proximity to great vessels or pericardium;
  • Pericardial infection;
  • Invasion of chest wall from contiguous pulmonary lesion;
  • Aspergillus empyema;
  • Persistent hemoptysis from a single cavitary lesion;
  • Infection of skin and soft tissues;
  • Infected vascular catheters and prosthetic devices;
  • Endocarditis;
  • Osteomyelitis;
  • Sinusitis;
  • Cerebral lesions.

Yellow Fever Virus

  • 1.1. Summary
  • Yellow fever was one of the most lethal diseases before the development of the vaccine. It is a major health concern for unvaccinated travellers to tropical regions in South America and Africa. It is transmitted by mosquitoes (Aedes aegypti) bites in a cycle which involve these mosquitoes biting also monkeys and human beings, which act as hosts for the virus. The yellow fever virus is a member of the Flaviviridae family, which comprises about 70 viruses, most of which are arthropod-borne.
  • 1.2. Epidemiology
  • Up to 5000 cases are reported annually in Africa and 300 annually in South America, although it is believed that numbers are underestimated. In Africa the human population is seasonally exposed in and around villages and small cities so the highest risk of disease are children without naturally acquired immunity. In South America the virus is transmitted in poorly populated forested areas and it occurs mainly with workers and farmers in the borders of the forested areas.
  • 1.3. Clinical Manifestations
  • Yellow fever can present itself in three forms: subclinical infection, nonspecific abortive febrile disease and fatal hemorrhagic fever. The incubation time for the disease is 3-6 days. After this period, the onset of fever, myalgia, lower back pain, irritability, nausea, malaise, headache, fotofobia and dizziness is oftenly abrupt. These findings are not specific to Yellow Fever and can be found in any acute infection. During this period the patient can be a source of virus for mosquitoes.
  • On physical examination the liver can be enlarged with tenderness, Faget sign (slow pulse rate despite high fever) can be found. Skin might appear flushed with reddening of conjunctivae and gums. Between 48-72h after onset and before the jaundice, hepatic enzymes starts to rise. Laboratory studies may show leukopenia with relative neutropenia. This is called period of infection and may last for several days and may be followed by a remission period which last about 48h, with the disappearance of the fever and the symptoms. Patients with the abortive form of the disease recover at this stage.
  • After the third to sixth day of the onset of the symptoms the patient may present return of the fever, vomiting, renal failure (oliguria), jaundice, epigastric pain and hemorrhagic diathesis. The viremia terminates during this stage and the antibodies appear in the blood. The patient may evolve with multiorgan failure during this phase. Also in this stage, AST concentrations might exceed ALT, probably due to myocardial and skeletal muscle damage. Serum creatinine and bilirubin levels also rise at this stage. Hemorrhagic manifestations may include petechiae, ecchymoses, epistaxis, melena, metrorrhagia, haematemesis. Laboratory studies may show thrombocytopenia, reduced fibrinogen levels, presence of fibrin split products, reduced factors II, V, VII, VIII, IX and X, which suggest a multifactorial cause for the bleeding with a consumption coagulopathy. Myocardial disfunction may be demonstrated by abnormalities in the ST-T segment in the electrocardiogram. Encephalitis is very rare.
  • 20-50% of the patients with the hepatorenal disease die after 7-10 days of the onset.
  • 1.4. Diagnosis
  • Diagnosis can be made by serology, detection of viral genome by polymerase chain reaction, immunohistochemistry on postmortem tissues, viral isolation or histopathology. No commercial test is available and diagnostic capabilities are restricted to selected laboratories only. Serologic diagnosis is made by dosing IgM antibodies with ELISA. The virus might be isolated by inoculating it in mice, cell cultures or mosquitoes. PCR is generally used to detect viral genome in clinical samples that were negative by virus isolation or other method.
  • 1.5. Treatment
  • Preferred regimen: No specific treatment is available for yellow fever. In the toxic phase, supportive treatment includes therapies for treating dehydration and fever. Ribavirin has failed in several studies in the monkey model.
  • Note: An international seminar held by WHO in 1984 recommended maintenance of nutrition, prevention of hypoglycemia, maintenance of the blood pressure with fluids and vasoactive drugs, prevention of bleeding with fresh-frozen plasma, dialysis if renal failure, correction of metabolic acidosis, administration of cimetidine IV to avoid gastric bleeding and oxygen if needed.
  • 1.6. Prevention
  • The Yellow fever 17D is highly effective, safe, attenuated vaccine that has been used for over 60 years. It should be taken my travellers who are going to endemic areas of the disease. Revaccination is needed after 10 years from the first dose. The side effects of the vaccines are rare but they include yellow fever associated viscerotropic disease and neurotropic disease. Immunization is contraindicated during pregnancy and in patients with immunodeficiency due to cancers, HIV/AIDS, or treatment with immunosuppressive agents.

Chikungunya Fever

Chikungunya Fever [44]
  • Preferred regimen: no specific therapeutics agents are available and there are no licensed vaccines to prevent Chikungunya Fever.
  • Note: Anti inflammatory drugs can be used to control joint swelling and arthritis.

Rabies

  • Rabies
  • Preferred regimen: no specific therapeutics agents are available once the disease is established.
  • Note: There are vaccines and immune globulins available for postexposure prophylaxis:
  • Postexposure Prophylaxis for non immunized individuals: Wound cleansing, human rabies immune globulin - administer full dose infiltrated around any wound. Administer any remaining volume IM at other site anatomically distant from the wound. Administer vaccine 1,0ml, IM at deltoid area one each on days 0, 3, 7 and 14.
  • Postexposure Prophylaxis for immunized individuals: Wound cleansing, do not administer human rabies immune globulin. Administer vaccine 1,0ml, IM at deltoid area one each on days 0 and 3.

Cryptococcus

  • 1. Cryptococcus neoformans
  • 1.1 Cryptococcus neoformans meningitis in HIV infected patients[45]
  • Preferred regimen for induction and consolidation: (Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction) OR Liposomal AmB 3-4mg/kg IV qd OR Amphotericin B lipid complex (ABLC) 5mg/kg IV qd) PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 2 weeks followed by Fluconazole 400mg (6mg/kg) PO qd for at least 8 weeks.
  • Alternative regimen for induction and consolidation (1): Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd OR Liposomal AmB 3-4 mg/kg IV qd OR AmB lipid complex 5mg/kg IV qd for 4-6 weeks.
  • Alternative regimen for induction and consolidation (2): Amphotericin B deoxycholate 0.7 mg/kg IV qd PLUS Fluconazole 800mg PO qd for 2 weeks, followed by Fluconazole 800mg PO qd for at least 8 weeks.
  • Alternative regimen for induction and consolidation (3): Fluconazole (>800 mg PO qd, 1200mg PO qd is favored) PLUS Flucytosine (100mg/kg/day PO qid) for 6 weeks.
  • Alternative regimen for induction and consolidation (4): Fluconazole PO 800-2000mg qd for 10-12 weeks.
  • Preferred regimen for maintenance and prophylactic therapy: Initiate HAART 2-10 weeks after commencing initial antifungal therapy AND Fluconazole 200mg PO qd.
  • Alternative regimen for maintenance and prophylactic therapy: Itraconazole 200mg PO bid - monitor drug-level OR Amphotericin B deoxycholate (1 mg/kg) per week IV (should be used in azole-intolerant patients).
  • Note (1): Consider discontinuing supressive therapy if CD4 count is higher than 100 cells/uL AND undetectable OR very low HIV RNA level for more than 3 months. Consider reinstitution of maintenance therapy if CD4 count <100 cels/uL.
  • Note (2): Do not use acetazolamide OR mannitol OR corticosteroids to treat increased intracranial pressure, instead it should be used lombar puncture in the absence of focal neurologic signs or impaired mentation (which, if present, patient must be submitted to CT or MRI scan first).
1.2. Cerebral cryptococcomas
  • Preferred regimen for induction and consolidation: (Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction) OR Liposomal AmB 3-4mg/kg IV qd OR Amphotericin B lipid complex (ABLC) 5mg/kg IV qd) PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 2 weeks followed by Fluconazole 400mg (6mg/kg) PO qd for at least 8 weeks.
  • Note: Consider surgery if lesions are larger than 3cm, accessible lesions with mass effect or lesions that are enlarging and not explained by IRIS.
1.3. Cryptococcus neoformans meningitis in HIV negative patients
  • Preferred regimen: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 4 weeks (which may be extended to 6 weeks if there is any neurological complication) followed by Fluconazole 400mg PO qd for 8 weeks. If there's toxicity to AmBd, consider changing to LFAmB in the second 2 weeks.
  • Note (1): After induction and consolidation therapy, start Fluconazole 200mg (3mg/kg) PO qd for 6-12 months.
  • Note (2): If Flucytosine is not given, consider lengthening the induction therapy for at least 2 weeks.
1.4. Cryptococcus neoformans pulmonary disease - immunosupressed
  • Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:
  • Preferred regimen: Fluconazole 400mg PO qd for 6-12 months.
  • Severe pneumonia or disseminated disease or CNS infection:
  • Preferred regimen: treat like CNS cryptococcosis.
  • Note (1): In HIV- infected patients, treatment should be stopped after 1 year if CD4 count is >100 and a cryptococcal antigen titer is <1:512 and not increasing.
  • Note (2): Consider corticosteroid if ARDS is present in a context which it might be attributed to IRIS.
1.5 Cryptococcus neoformans pulmonary disease - non-immunosupressed
  • Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:
  • If there's severe pneumonia, disseminated disease or CNS infection:
  • Preferred regimen: treat like CNS cryptococcosis for 6-12 months.
1.6 Cryptococcus neoformans non-lung, non-CNS infection
  • Cryptococcemia or disseminated cryptococcic disease (involvement of at least 2 noncontiguous sites or cryptococcal antigen titer >1:512):
  • Preferred regimen: treat like CNS infection.
  • If infection occurs at a single site and no immunosupressive risk factors
  • Preferred regimen: Fluconazole 400mg PO qd for 6-12 months.
1.7. Cryptococcosis in Children
  • Preferred regimen for induction and consolidation: Amphotericin B deoxycholate 1.0 mg/kg qd IV PLUS Flucytosine 100mg/kg PO or IV qid for 2 weeks followed by Fluconazole 10-12mg/kg PO qd for 8 weeks.
  • Alternative regimen: patients with renal dysfunction: change Amphotericin B deoxycholate by Liposomal AmB 5mg/kg IV qd or Amphotericin B lipid complex (ABLC) 5mg/kg IV qd.
  • Preferred regimen for maintenance: Fluconazole 6mg/kg PO qd. Discontinuation of maintenance therapy is poorly studied and should be individualized.
  • Cryptococcal pneumonia:
  • Preferred regimen Fluconazole 6-12mg/kg PO qd for 6-12 months.
1.8. Cryptococcosis in Pregnant Women
  • Preferred regimen for induction and consolidation: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction - Liposomal AmB 3-4mg/kg IV qd OR Amphotericin B lipid complex (ABLC) 5mg/kg IV qd. Consider using Flucytosine in relationship to benefit risk basis, since it is a Category C drug for pregnancy. Start Fluconazole after delivery. Avoid use during first trimester and consider use in the last 2 trimesters with the need for continuous antifungal therapy during pregnancy.
  • Note: If pulmonary cryptococcosis: perform close follow-up and administer fluconazole after delivery.
2. Cryptococcus gatti
  • Disseminated cryptococcosis or CNS disease:
  • Preferred regimen: treatment is the same as C. neoformans.
  • Pulmonary disease: single and small cryptococcoma:
  • Preferred regimen: Fluconazole 400mg per day PO for 6-18months.
  • Pulmonary disease: Very large or multiple cryptococcomas:
  • Preferred regimen: administer Flucytosine AND AmB deocycholate for 4-6 weeks, followed by fluconazole for 6-18 months.
  • Note: Surgery should be considered if there is compression of vital structures OR failure to reduce the size of the cryptococcoma after 4 weeks of therapy.

Dermatophytosis

  • 1. Tinea Cruris
  • 2. Tinea Corporis
  • 2.1 Small, well-defined lesions:
  • 2.2 Larger lesions:
  • 3. Tinea Pedis
  • 4. Tinea Capitis
  • Preferred regimen: Griseofulvin PO 10-20mg/kg/day for at least 6 weeks (Preferred for children).
  • Alternative regimens: Terbinafine PO 62.5mg/day if <20kg; 125 mg/day if 20-40kg; 250mg/day if >40kg OR Itraconazole PO 4-6mg/kg pulsed dose weekly.
  • Note: Nistatin is not effective in the treatment of dermatophytosis.
  • 5. Tinea Barbae
  • Preferred regimen: Terbinafine PO 250mg/day for 4 weeks.
  • Alternative regimen: Itraconazole PO 200mg/day for 2 weeks.
  • 6. Tinea Incognito
  • Preferred regimen: Stop topical steroids and treat with topical 1% terbinafine cream for 6 weeks.
  • 7. Tinea Manuum
  • Preferred regimen: topical or systemic terbinafine PO 250 mg/day por 2-4 weeks.
  • 8.Tinea Versicolor
  • 9. Majocchi's Granuloma
  • Preferred regimen: Terbinafine PO 250mg/day for 2-4 weeks or Itraconazole 200mg PO bid for 1 week, per month for 2 months.
  • 10. Onychomycosis[47]
  • 10.1 Fingernails
  • Preferred regimen: Terbinafine PO 250mg/day for 6 weeks OR Itraconazole PO 200mg twice a day for a week a month for 2 months (European guidelines).
  • 10.2 Toenails
  • Preferred regimen: Toenails Terbinafine PO 250mg/day for 12 weeks OR Itraconazole PO 200mg/day for 12 weeks (U.S. guidelines) OR Itraconazole PO 200mg twice a day for a week a month for 3 months (European guidelines).
  • Note (1): There is no evidence that combining systemic and topic treatments has any benefit to the patient.


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