Sandbox m ex

antrax

Bacillus anthracis
Photomicrograph of Bacillus anthracis (fuchsin-methylene blue spore stain). Photomicrograph of Bacillus anthracis (fuchsin-methylene blue spore stain).
Scientific classification
Kingdom: Bacteria Phylum: Firmicutes Class: Bacilli Order: Bacillales Family: Bacillaceae Genus: Bacillus Species: B. anthracis
Binomial name
Bacillus anthracis Cohn 1872

File:B anthracis diagram en.png

Structure of Bacillus anthracis.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2]

Overview

Bacillus anthracis is a Gram-positive, facultatively anaerobic, rod-shaped bacterium of the genus Bacillus. An endospore forming bacterium, B. anthracis is a natural soil-dwelling organism, as well as the causative agent of anthrax.

Each cell is about 1 by 6 μm in size.

Historical background

B. anthracis was the first bacterium conclusively demonstrated to cause disease, by Robert Koch in 1877. The species name anthracis is from the Greek anthrakis (ἄνθραξ), meaning coal and referring to the most common form of the disease, cutaneous anthrax, in which large black skin lesions are formed.

Pathogenicity

Under conditions of environmental stress, B. anthracis bacteria naturally produce endospores which rest in the soil and can survive for decades in this state. When ingested by a cattle, sheep, or other herbivores, the bacteria begin to reproduce inside the animal and eventually kill it, then continue to reproduce in its carcass. Once the nutrients are exhausted, new endospores are produced and the cycle repeats.

B. anthracis has at least 89 known strains, ranging from highly virulent strains with biological warfare and bioterrorism applications (Ames and Vollum) to benign strains used for inoculations (Sterne). The strains differ in presence and activity of various genes, determining their virulence and production of antigens and toxins. The form associated with the 2001 anthrax attacks produced both toxin (consisting of three proteins: the protective antigen, the edema factor and the lethal factor) and a capsule (consisting of a polymer of glutamic acid). Infection with anthrax requires the presence of all three of these exotoxins.

The bacterium can be cultivated in ordinary nutrient medium under aerobic or anaerobic conditions.

Treatment

Main article: Anthrax

Infections with B. anthracis can be treated with β-lactam antibiotics such as penicillin, and others which are active against Gram-positive bacteria.

Gallery

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

• 

  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

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  Bacillus anthracis. From Public Health Image Library (PHIL).

References

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Antibiotic Treatment

Cutaneous Anthrax without Systemic Involvement

Choice of Antibiotics

• Uncomplicated cutaneous anthrax has been successfully treated with a single oral antimicrobial drug.
• Oral fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) and doxycycline are equivalent first-line agents.
• Clindamycin is an alternative option if fluoroquinolones and doxycycline are contraindicated or unavailable.
• Given the long history of successful treatment of localized uncomplicated cutaneous anthrax with penicillin, amoxicillin and penicillin VK are also alternative therapeutic options if the isolate is known to be susceptible to penicillin. However, adequate dosages must be used because of the potential for development of drug resistance during treatment with subtherapeutic dosing.

Duration of Treatment

• Duration of treatment for localized or uncomplicated cutaneous disease depends on the B. anthracis exposure source:
  • Naturally acquired (e.g., animals with anthrax, products such as hides from animals with anthrax): 7–10-day course
  • Bioterrorism-related exposure or an aerosol exposure is suspected: 60 days (because the patient is likely to have also inhaled spores.)

Systemic Anthrax When Meningitis Has Been Excluded

Choice of Antibiotics

• The initial treatment should include ≥2 antimicrobial drugs with activity against B. anthracis:
  • ≥1 should have bactericidal activity, and
  • ≥1 should be a protein synthesis inhibitor

• Intravenous ciprofloxacin is preferred as the primary bactericidal component in the treatment of systemic disease. Linezolid or clindamycin are the preferred as the first-line protein synthesis inhibitor.

• If the B. anthracis strain is susceptible to penicillin, then penicillin G is considered equivalent to the fluoroquinolone options for primary bactericidal treatment.

• Treatment with antimicrobial drugs that have good central nervous system (CNS) penetration is not a crucial factor. Thus, meropenem is recommended as an acceptable alternative option than as a first-line antimicrobial drug, and vancomycin is also an acceptable alternative. Clindamycin and linezolid are considered equivalent first-line choices for protein synthesis inhibitors. Doxycycline is added as an alternative protein synthesis inhibitor option if linezolid or clindamycin are contraindicated or unavailable.

Duration of Treatment

• Initial intravenous combination treatment should be given for ≥2 weeks or until the patient is clinically stable, whichever is longer.

Follow–up Oral Treatment for Systemic Disease

Once patients with systemic illness who were exposed to aerosolized spores have completed initial combination treatment, they should be transitioned to single-agent oral treatment to prevent relapse from surviving B. anthracis spores.

Systemic Anthrax with Possible/Confirmed Meningitis

Choice of Antibiotics

• Empiric treatment for anthrax in which anthrax meningitis is suspected or cannot be ruled out should include ≥3 antimicrobial drugs with activity against B. anthracis:
  • ≥1 drug should have bactericidal activity
  • ≥1 should be a protein synthesis inhibitor
  • All should have good CNS penetration

• Hospitalized patients for systemic anthrax should be immediately treated with a combination of broad-spectrum intravenous antibiotic drug treatment pending confirmatory test results because any delay may prove fatal. Because meningitis and hemorrhagic brain parenchymal infection was observed in ≤50% of cases, meningitis must be considered in all cases of systemic anthrax. Therefore antibiotics to treat possible meningitis must have good penetration of the central nervous system (CNS).

• Intravenous ciprofloxacin is preferred as the primary bactericidal component in the treatment of systemic disease on the basis of efficacy in non-human primates (NHP) infection models and recent use for anthrax cases. Levofloxacin and moxifloxacin are considered equivalent alternatives to ciprofloxacin. The fluoroquinolones have adequate CNS penetration and there are no reports of natural resistance.

• The carbapenem class of antimicrobial drugs is highly resistant to β-lactamases and provides good CNS penetration. Meropenem is preferred as the second antimicrobial drug in the combination antimicrobial drug regimen for anthrax meningitis. If meropenem is unavailable, doripenem and imipenem/cilastatin are considered equivalent alternatives. Imipenem/cilastatin is associated with increased seizure risk and should be used with caution in patients with suspected meningitis. If the B. anthracis strain is susceptible to penicillin (MIC <0.125 µg/mL), penicillin G or ampicillin are acceptable alternatives to carbapenems.

• At least 1 antimicrobial drug that inhibits protein synthesis should be used to reduce exotoxin production. Linezolid is preferred as the first-line protein synthesis inhibitor. It is preferred over clindamycin because it is likely to provide better CNS penetration, although randomized controlled trials on treatment for CNS infections with either agent are lacking. However, linezolid toxicity issues must be taken into consideration. Myelosuppression, peripheral and optic neuropathies, and serotonin syndrome have been reported in patients receiving linezolid. Linezolid should be used cautiously in patients with pre-existing myelosuppression. In patients receiving monoamine oxidase inhibitors or serotonin reuptake inhibitors, the benefit of linezolid treatment should be weighed against the risk for serotonin toxicity and an alternative should be considered. If patients experience visual impairment, prompt ophthalmic evaluation is recommended. If patients have contraindications to linezolid use or it is unavailable, clindamycin is an acceptable alternative. Rifampin, although not a protein synthesis inhibitor, has been widely used for its synergistic effect with a primary drug and could also be used in this capacity if linezolid or clindamycin are unavailable. The protein synthesis inhibitor chloramphenicol has good CNS penetration and has historically been used to successfully treat anthrax. Where available, it could be an acceptable alternative if linezolid, clindamycin, and rifampin are unavailable. Doxycycline should not be used if meningitis is suspected because it does not adequately penetrate the CNS.

Duration of Treatment

• Intravenous combination treatment for systemic anthrax with possible meningitis should be provided for ≥2 weeks or until the patient is clinically stable, whichever is longer.
• Given the high mortality rate associated with meningitis, some expert panelists favored 3 weeks of treatment for patients in whom meningitis could not be ruled out.

Follow–up Oral Treatment for Systemic Disease

Once patients with systemic illness who were exposed to aerosolized spores have completed initial combination treatment, they should be transitioned to single-agent oral treatment to prevent relapse from surviving B. anthracis spores.

Dosage of Antibiotics

▸ Click on the following categories to expand treatment regimens.

Cutaneous Anthrax Without Systemic Involvement   ▸  Adult Patients   ▸  Pediatric Patients   ▸  Pregnant Patients Systemic Anthrax with Possible/Confirmed Meningitis   ▸  Adult Patients   ▸  Pediatric Patients   ▸  Pregnant Patients Systemic Anthrax Without Meningitis   ▸  Adult Patients   ▸  Pediatric Patients   ▸  Pregnant Patients

Cutaneous Anthrax, Adult Patients Preferred Regimen ▸ Ciprofloxacin 500 mg PO q12h OR ▸ Levofloxacin 750 mg PO q24h OR ▸ Moxifloxacin 400 mg PO q24h OR ▸ Doxycycline 100 mg PO q12h Alternative Regimen ▸ Clindamycin 600 mg PO q8h OR ▸ Penicillin VK 500 mg PO q6h OR ▸ Amoxicillin 1 g PO q8h Cutaneous Anthrax, Pediatric Patients Preferred Regimen ▸ Ciprofloxacin 30 mg/kg/day PO q12h, max: 500 mg/dose OR ▸ Levofloxacin 16 mg/kg/day PO q12h, max: 250 mg/dose (<50 kg) OR ▸ Levofloxacin 500 mg PO q24h (≥50 kg) OR ▸ Doxycycline 4.4 mg/kg/day PO q12h, max: 100 mg/dose (<45 kg) OR ▸ Doxycycline 100 mg/dose PO q12h (≥45 kg) Alternative Regimen ▸ Clindamycin 30 mg/kg/day PO q8h, max: 600 mg/dose OR ▸ Penicillin VK 50–75 mg/kg/day PO q6–8h OR ▸ Amoxicillin 75 mg/kg/day PO q8h, max: 1 g/dose Cutaneous Anthrax, Pregnant Patients Preferred Regimen ▸ Ciprofloxacin 500 mg PO q12h Systemic Anthrax with Meningitis, Adult Patients Preferred Regimen ▸ Ciprofloxacin 400 mg IV q8h OR ▸ Levofloxacin 750 mg IV q24h OR ▸ Moxifloxacin 400 mg IV q24h PLUS ▸ Meropenem 2 g IV q8h OR ▸ Imipenem 1 g IV q6h OR ▸ Doripenem 500 mg IV q8h PLUS ▸ Linezolid 600 mg IV q12h OR ▸ Clindamycin 900 mg IV q8h OR ▸ Rifampin 600 mg IV q12h OR ▸ Chloramphenicol 1 g IV q6–8h Alternative Regimen ▸ Ciprofloxacin 400 mg IV q8h OR ▸ Levofloxacin 750 mg IV q24h OR ▸ Moxifloxacin 400 mg IV q24h PLUS ▸ Penicillin G 4 MU IV q4h OR ▸ Ampicillin 3 g IV q6h PLUS ▸ Linezolid 600 mg IV q12h OR ▸ Clindamycin 900 mg IV q8h OR ▸ Rifampin 600 mg IV q12h OR ▸ Chloramphenicol 1 g IV q6–8h Systemic Anthrax with Meningitis, Pediatric Patients Preferred Regimen ▸ Ciprofloxacin 30 mg/kg/day IV q8h, max: 400 mg/dose OR ▸ Levofloxacin 20 mg/kg/day IV q12h, max: 250 mg/dose (<50 kg) OR ▸ Levofloxacin 500 mg IV q24h (≥50 kg) OR ▸ Meropenem 60 mg/kg/day IV q12h, max: 2 g/dose OR ▸ Imipenem/Cilastatin 100 mg/kg/day IV q6h, max: 1 g/dose OR ▸ Vancomycin 60 mg/kg/day IV q8h PLUS ▸ Clindamycin 30 mg/kg/day PO q8h, max: 600 mg/dose OR ▸ Linezolid 30 mg/kg/day IV q8h, max: 1 g/dose (<12 yr) OR ▸ Linezolid 30 mg/kg/day IV q12h, max: 600 mg/dose (≥12 yr) OR ▸ Doxycycline 4.4 mg/kg/day IV q12h, max: 100 mg/dose (<45 kg) OR ▸ Doxycycline 200 mg IV x1 then 100 mg IV q12h, max: 200 mg/dose (≥45 kg) OR ▸ Rifampin 20 mg/kg/day IV q12h, max: 300 mg/dose Alternative Regimen ▸ Penicillin G 0.4 MU/kg/day IV q4h, max: 4 MU/dose OR ▸ Ampicillin 200 mg/kg/day IV q6h, max: 900 mg/dose PLUS ▸ Clindamycin 30 mg/kg/day PO q8h, max: 600 mg/dose OR ▸ Linezolid 30 mg/kg/day IV q8h, max: 1 g/dose (<12 yr) OR ▸ Linezolid 30 mg/kg/day IV q12h, max: 600 mg/dose (≥12 yr) OR ▸ Doxycycline 4.4 mg/kg/day IV q12h, max: 100 mg/dose (<45 kg) OR ▸ Doxycycline 200 mg IV x1 then 100 mg IV q12h, max: 200 mg/dose (≥45 kg) OR ▸ Rifampin 20 mg/kg/day IV q12h, max: 300 mg/dose Systemic Anthrax with Meningitis, Pregnant Patients Preferred Regimen ▸ Ciprofloxacin 400 mg IV q8h PLUS ▸ Clindamycin 900 mg IV q8h OR ▸ Rifampin 600 mg IV q12h Alternative Regimen ▸ Levofloxacin 750 mg IV q24h OR ▸ Meropenem 2 g IV q8h OR ▸ Penicillin G 4 MU IV q4h OR ▸ Ampicillin 3 g IV q6h PLUS ▸ Clindamycin 900 mg IV q8h OR ▸ Rifampin 600 mg IV q12h Systemic Anthrax Without Meningitis, Adult Patients Preferred Regimen ▸ Ciprofloxacin 400 mg q8h OR ▸ Levofloxacin 750 mg q24h OR ▸ Moxifloxacin 400 mg PO q24h OR ▸ Meropenem 2 g q8h OR ▸ Imipenem 1 g IV q6h OR ▸ Doripenem 500 mg q8h OR ▸ Vancomycin 60 mg/kg/day IV q8h, trough: 15–20 μg/mL PLUS ▸ Clindamycin 900 mg q8h OR ▸ Linezolid 600 mg q12h OR ▸ Doxycycline 200 mg x1 then 100 mg IV q12h OR ▸ Rifampin 600 mg q12h Alternative Regimen ▸ Penicillin G 4 MU IV q4h OR ▸ Ampicillin 3 g IV q6h PLUS ▸ Clindamycin 900 mg q8h OR ▸ Linezolid 600 mg q12h OR ▸ Doxycycline 200 mg x1 then 100 mg IV q12h OR ▸ Rifampin 600 mg q12h Systemic Anthrax Without Meningitis, Pediatric Patients Preferred Regimen ▸ Ciprofloxacin 30 mg/kg/day IV q8h, max: 400 mg/dose OR ▸ Levofloxacin 16 mg/kg/day IV q12h, max: 250 mg/dose (<50 kg) OR ▸ Levofloxacin 500 mg IV q24h (≥50 kg) OR ▸ Moxifloxacin 12 mg/kg/day IV q12h, max: 200 mg/dose (3 mo–2 yr) OR ▸ Moxifloxacin 10 mg/kg/day IV q12h, max: 200 mg/dose (2 yr–5 yr) OR ▸ Moxifloxacin 8 mg/kg/day IV q12h, max: 200 mg/dose (6 yr–11 yr) OR ▸ Moxifloxacin 8 mg/kg/day IV q12h, max: 200 mg/dose (12 yr–17 yr, <45 kg) OR ▸ Moxifloxacin 400 mg IV q24h (12 yr–17 yr, ≥45 kg) PLUS ▸ Meropenem 120 mg/kg/day IV q8h, max: 2 g/dose OR ▸ Imipenem/Cilastatin 100 mg/kg/day IV q6h, max: 1 g/dose OR ▸ Doripenem 120 mg/kg/day IV q8h, max: 1 g/dose OR ▸ Vancomycin 60 mg/kg/day IV q8h PLUS ▸ Linezolid 30 mg/kg/day IV q8h, max: 600 mg/dose (<12 yr) OR ▸ Linezolid 30 mg/kg/day IV q12h, max: 600 mg/dose (≥12 yr) OR ▸ Clindamycin 40 mg/kg/day IV q8h, max: 900 mg/dose OR ▸ Rifampin 20 mg/kg/day IV q12h, max: 300 mg/dose OR ▸ Chloramphenicol 100 mg/kg/day IV q6h Alternative Regimen ▸ Ciprofloxacin 30 mg/kg/day IV q8h, max: 400 mg/dose OR ▸ Levofloxacin 16 mg/kg/day IV q12h, max: 250 mg/dose (<50 kg) OR ▸ Levofloxacin 500 mg IV q24h (≥50 kg) OR ▸ Moxifloxacin 12 mg/kg/day IV q12h, max: 200 mg/dose (3 mo–2 yr) OR ▸ Moxifloxacin 10 mg/kg/day IV q12h, max: 200 mg/dose (2 yr–5 yr) OR ▸ Moxifloxacin 8 mg/kg/day IV q12h, max: 200 mg/dose (6 yr–11 yr) OR ▸ Moxifloxacin 8 mg/kg/day IV q12h, max: 200 mg/dose (12 yr–17 yr, <45 kg) OR ▸ Moxifloxacin 400 mg IV q24h (12 yr–17 yr, ≥45 kg) PLUS ▸ Penicillin G 0.4 MU/kg/day IV q4h, max: 4 MU/dose OR ▸ Ampicillin 400 mg/kg/day IV q6h, max: 3 g/dose PLUS ▸ Linezolid 30 mg/kg/day IV q8h, max: 600 mg/dose (<12 yr) OR ▸ Linezolid 30 mg/kg/day IV q12h, max: 600 mg/dose (≥12 yr) OR ▸ Clindamycin 40 mg/kg/day IV q8h, max: 900 mg/dose OR ▸ Rifampin 20 mg/kg/day IV q12h, max: 300 mg/dose OR ▸ Chloramphenicol 100 mg/kg/day IV q6h Systemic Anthrax Without Meningitis, Pregnant Patients Preferred Regimen ▸ Ciprofloxacin 400 mg IV q8h PLUS ▸ Clindamycin 900 mg IV q8h OR ▸ Rifampin 600 mg IV q12h Alternative Regimen ▸ Levofloxacin 750 mg IV q24h OR ▸ Meropenem 2 g IV q8h OR ▸ Penicillin G 4 MU IV q4h OR ▸ Ampicillin 3 g IV q6h PLUS ▸ Clindamycin 900 mg IV q8h OR ▸ Rifampin 600 mg IV q12h

piss

Psittacosis Microchapters
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [4]

Overview

Psittacosis is an infection caused by the obligatory intracellular bacterium Chlamydia psittaci. It is apparently acquired from the birds (parrots).

Causes

Psittacosis is an infection caused by the obligatory intracellular bacterium Chlamydia psittaci. It is apparently acquired from the birds (parrots). Ornithosis is infection from any kind bird.

References

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plam

Malaria Microchapters
Home
Patient Information
Overview
Historical perspective
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Pathophysiology
Causes
Differentiating Malaria from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
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Xray
Ultrasound
CT scan
MRI
Other Diagnostic Studies
Treatment
Medical Therapy
Primary Prevention
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Cost-Effectiveness of Therapy
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Case #1
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American Roentgen Ray Society Images of Sandbox m ex All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
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Directions to Hospitals Treating Malaria
Risk calculators and risk factors for Sandbox m ex

This page is about clinical aspects of the disease.  For microbiologic aspects of the causative organism(s), see Plasmodium.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [5]; Associate Editor(s)-In-Chief: Yazan Daaboul, Serge Korjian, Alison Leibowitz [6]

Overview

Malaria is a vector-borne infectious disease caused by protozoan parasites. P. vivax is the most common cause of infection, responsible for about 80% of all malaria cases. P. falciparum, the most significant cause of disease, is responsible for about 15% of infections and 90% of deaths.

Causes

P. vivax is the most common cause of infection, responsible for about 80% of all malaria cases. P. falciparum, the most significant cause of disease, is responsible for about 15% of infections and 90% of deaths. The remainder of human malaria infections are caused by P. ovale, P. malariae, and P. knowlesi.

The following table distinguishes between the different strains of Plasmodium species, all of which are causative agents of malarial infection.

Comparison of Plasmodium Species Implicated in Human Malaria ("Malaria". Center for Disease Control and Prevention. Center for Disease Control and Prevention (CDC). Nov. 29 2013. Retrieved Jul 24 2014. )

Strain	Clinical Significance
P. falciparum	Tertian/subtertian fever (every 48 hours), causes severe malaria in up to 24% of cases, and is frequently drug resistant.
P. vivax	Tertian fever (every 48 hours), results in severe malaria in up to 22% of cases, and is frequently drug resistant. Relapse is common due to the dormant liver phase.
P. ovale	Tertian fever (every 48 hours), rarely causes severe malaria or drug resistance. Relapse is common due to dormant liver phase.
P. malariae	Quartan fever (every 72 hrs), rarely results in severe malaria or drug resistance. Although dormant liver phase is uncommon, infection persistence is frequently demonstrated.
P. knowlesi	Daily fevers, may result in severe malaria in up to 10% of cases, although resistance is rare.

^{Adapted from Center for Disease Control and Prevention (CDC) - Malaria}

q fever microb

Coxiella burnetii
C. burnetii, the causative agent of Q fever C. burnetii, the causative agent of Q fever
Scientific classification
Kingdom: Bacteria Phylum: Proteobacteria Class: Gamma Proteobacteria Order: Legionellales Family: Coxiellaceae Genus: Coxiella Species: C. burnetii
Binomial name
Coxiella burnetii (Derrick 1939) Philip 1948

Coxiella burnetii is a species of intracellular, pathogenic bacteria, and is the causative agent of Q fever. The genus Coxiella is morphologically similar to the rickettsia, but with a variety of genetic and physiological differences. C. burnetii are small Gram negative bacteria with two growth phases, as well as a spore form which lies idle in soil. It can survive standard disinfectants, and is resistant to many other environmental changes.

Pathogenesis

The ID₅₀ (the dose needed to infect 50% of experimental subjects) is one via inhalation— i.e. inhalation of one organism will yield disease in 50% of the population. Disease occurs in two states: An acute state presents with headaches, chills, and respiratory symptoms, and an insidious chronic stage.

While most infections clear up spontaneously, treatment with tetracycline or doxycycline appears to reduce the symptomatic duration and reduce the likelihood of chronic infection. A combination of erythromycin and rifampin is highly effective in curing and prevention of disease and so is vaccination with Q-vax vaccine (CSL).

References

Anti-malarial Agents

Recommended Indications and Doses of Common Anti-malarial Agents

Anti-malarial Agent	Indication	Dosing
Chloroquine phosphate	P. falciparum from chloroquine-sensitive areas P. vivax from chloroquine-sensitive areas All P. ovale All P. malariae	1g oral load, followed by 500 mg orally at 6, 24, and 48 h
Hydroxychloroquine	Same as chloroquine (second line agent)	800 mg oral load, followed by 400 mg orally at 6, 24, and 48 h
Atovaquone-Proguanil	P. falciparum from chloroquine-resistant areas	250 mg atovaquone/100 mg proguanil (1 tab) orally 4 times daily for 3 days
Primaquine phosphate	Cure of P. vivax and P. ovale (to eliminate hypnozoites)	30 mg orally once daily for 14 days
Clindamycin*	P. falciparum or P. vivax from chloroquine-resistant areas	20 mg/kg/day orally for 3 days or 10 mg/kg IV load, followed by 5 mg/kg IV every 8 hours
Doxycycline*	P. falciparum or P. vivax from chloroquine-resistant areas	100 mg orally twice daily for 7 days or 100 mg IV every 12 hours for 7 days (can switch from IV to PO)
Tertacycline*	P. falciparum or P. vivax from chloroquine-resistant areas	250 mg orally 4 times daily for 7 days or 250 mg IV 4 times daily for 7 days (can switch from IV to PO)
Mefloquine	P. falciparum or P. vivax from chloroquine-resistant areas except Thailand-Burmese and Thailand-Cambodian border regions	750 mg oral load, followed by 500 mg orally 6-12 hours after initial dose
Quinine sulfate	P. falciparum or P. vivax from chloroquine-resistant areas	650 mg orally 3 times daily for 3 days or 7 days if acquired from Southeast Asia
Quinidine gluconate	Severe malaria (all species Unable to tolerate oral agents Parasitemia>10%	10 mg/kg IV load over 1-2 hours, then 0.02 mg/kg/min continuous infusion for at least 24 hours
Artemether-lumefantrine	All P. falciparum (outside USA)	1.5 mg/kg - 9 mg/kg orally twice daily for 3 days
Dihydroartemisinin–piperaquine	All P. falciparum (outside USA)	2·5 mg/kg – 20 mg/kg orally once daily for 3 days
Artesunate	All P. falciparum (outside USA) First line IV agent for severe malaria (outside USA)	In severe malaria: 2.4 mg/kg IV or IM load, followed by 2.4 mg/kg at 12 h and 24 h; continue injection once daily if necessary In uncomplicated malaria: Monotherapy not recommended, 4mg/kg orally once daily for 3 days combined with a single oral dose of sulfadoxine–pyrimethamine 25/1.25 mg/kg or mefloquine 8 mg/kg orally daily for 3 days

^{*Used in combination with quinine or quinidine}

mx The treatment approach in patients with suspected or confirmed malaria varies according to several factors namely travel history, species of Plasmodium, severity of presentation, and availability of certain therapeutic agents.

Initial Assessment & Severe Malaria

The first step in the management of patients with malaria is to conduct a clinical assessment of status and disease severity, as well as determination of the degree of parasitemia. Signs of severe malarial disease include any of the following: Prostration, impaired consciousness/coma, respiratory distress, convulsions, shock, pulmonary edema, acute respiratory distress syndrome (ARDS), jaundice, abnormal bleeding, severe anemia, hemolysis, hemoglobinuria, acute kidney injury, metabolic acidosis, disseminated intravascular coagulopathy, parasitemia >5%. Patients with severe disease require rapid resuscitation and medical therapy. The most vital step in the management is immediate initiation of appropriate parenteral treatment. Unlike patients who appear stable clinically, patients with severe malaria do not require speciation prior to initiation of medical therapy.

The therapeutic regimen in patients with severe malaria consists of intravenous quinidine gluconate plus either tetracycline, doxycycline, or clindamycin. Other supportive measures include admission to the intensive care unit, continuous monitoring of cardiac function, glycemia, parasitemia, hemoglobin and electrolytes. Exchange transfusions may also be considered in patients with a degree of parasitemia >10%.

Uncomplicated Malaria

In patients with clinically and bacteriologically uncomplicated malaria, speciation is required to tailor medical therapy. For most non-falciparum species, chloroquine remains the first line therapeutic agent. It is important to add primaquine to the treatment regimen in patients with documented P. vivax and P. ovale infections to eradicate liver hypnozoites (dormant liver spores that are responsible for recurrence). Care should be taken in patients with G6PD deficiency as large doses of primaquine can cause significant hemolysis. Patients infected with P. malaria do not require primaquine as the species is not capable of forming hypnozoites. Patients diagnosed with P. falciparum malaria require hospitalization given the risk of progression to severe malaria. These patients have to be monitored on daily basis with a blood film and a full physical exam. The choice of drug in these patients depends on two main factors: the area of acquisition of the parasite, and the center at which the patient is being treated.

Despite being the mainstay of therapy since its introduction, empiric treatment with chloroquine in patients with P. falciparum is no longer recommended due to a sharp increase in resistance. A detailed travel history is important to determine where the infection was acquired. Most malaria endemic countries have reported chloroquine resistant strains, with the exception of Central America west of Panama Canal, Mexico, Hispaniola, certain parts of China, and the Middle East (see figure below). If acquired in any of the latter sites then treatment with chloroquine is adequate. Acquisition from all other endemic countries requires other therapeutic regimens such as oral quinine with either tetracycline, doxycycline, or clindamycin as a first line therapy in the United States, otherwise atovaquone-proguanil or mefloquine if the primary regimen is unavailable.

Worldwide, the treatment of both complicated and uncomplicated P. falciparum malaria requires a combination therapy that includes artemisinin derivatives. According to the 2010 WHO guidelines on the treatment of malaria, the following regimens are first line for the treatment of uncomplicated P. falciparum: artemether plus lumefantrine, artesunate plus amodiaquine, artesunate plus mefloquine, and artesunate plus sulfadoxine-pyrimethamin. It is important to note that artemisin monotherapy in not recommended due to increasing resistance. For patients with severe P. falciparum malaria, artesunate IV or IM is first line followed by IV quinidine. The artemisinin derivatives clear parasites very rapidly have been shown to reduce mortality in severe malaria compared with parenteral quinine. Artemisins are not widely available in the United States and their use is not common practice. Only oral artemether plus lumefantrine is available, while IV atresunate can be obtained through the CDC part of an investigational drug protocol.