Leishmaniasis
Overview
- Definition
Caused by protozoa (Leishmania species) which are transmitted by bites of infected sand flies (various species including Phlebotomus)
- “Neglected tropical disease” mostly affecting poorest populations
Risk factors include malnutrition, weak immune system, poverty, poor housing, populations displacement, and deforestation
Presentation and management vary by species and affected population
- Three forms of disease exist:
Cutaneous (most common) (CL)
Mucosal/mucocutaneous (Espundia) (ML)
Visceral (Kala-azar, black fever, most severe) (VL)
- Symptoms
CL, ML – blurring, pain, redness, light sensitivity
VL – blurring, pain, redness, light sensitivity, floaters
- Laterality
Typically unilateral
- Course
- Subacute onset with chronic self-limiting course
May have permanent sequelae in more severe disease
ML is often seen after untreated or unrecognized CL
- Age of onset
All age groups affected
- Gender/race
Any person in endemic area
- Systemic association
CL – skin lesions mostly in exposed areas, may be diffuse
ML – mucosal erosions
VL – multisystem involvement, potentially fatal
Exam: Ocular
Anterior Segment
CL – lid or periocular ulcers, madarosis, ectropion, trichiasis, exposure keratopathy
ML – lid lesions similar to chalazia, basal cell carcinoma; dacryocystitis; interstitial keratitis
VL – same as in CL, ML; also bilateral anterior uveitis, cataract, phthisis
Posterior Segment
CL, ML – none
VL – panuveitis, RD (retinal detachment) with PVR (proliferative vitreoretinopathy), retinal hemorrhage, glaucoma
Exam: Systemic
CL – single/multiple papules, nodules, ulcers with raised margins and depressed center, may scab; regional lymphangitis
ML – mucosal erosions, perforated nasal septum, oral/pharyngeal ulcers
VL – hepatosplenomegaly, fever, anemia, pancytopenia, lymphadenopathy, hypergammaglobulinemia, hypoalbuminemia; post-VL dermal leishmaniasis with skin lesions involving face, trunk and genitals
Imaging
Fundus photograph, fundus fluorescein angiography, and optical coherence tomography: may be needed to evaluate the involvement of the posterior segment
Laboratory and Radiographic Testing
- Biopsy of involved tissue demonstrating protozoa (amastigotes) with light microscopy (gold standard)
CL, ML – skin and mucosal lesions
VL – bone marrow, splenic aspirate with high yield (latter may have potentially lethal complications and is thus avoided)
VL – culture (Novy-MacNeal-Nicolle medium), deoxyribonucleic acid (DNA) PCR, and serologies (rk39 rapid test, Leishmania IgM/IgG)
Differential Diagnosis
CL – infections including bacterial, fungal, viral; sporotrichosis; dermatologic malignancies including basal cell carcinoma; inflammatory disease including plaque psoriasis
ML – granulomatosis with polyangiitis (previously Wegener’s), lethal midline granuloma, polymorphic reticulosis, lymphoma, nasopharyngeal carcinoma
VL – systemic infections including military tuberculosis (TB), syphilis, brucellosis, endocarditis; malignancy including lymphoma, leukemia
Treatment
- Preventative
Clothing, insect repellent, avoidance of nocturnal activities
Early diagnosis and treatment of infected individuals who may act as reservoir
Control insect breeding
Improvement of living conditions, nutrition, immunocompromised conditions (HIV)
- Therapy
- Pentavalent ammonium compounds
Sodium stibogluconate 20 mg/kg intravenous (IV) for 20 days (CL) or 28 days (VL)
- Liposomal amphotericin B (VL)
Immunocompetent – 3 mg/kg/day IV on days 1–5, 14, and 21
Immunocompromised – 4 mg/kg/day IV on days 1–5, 10, 17, 24, 31, and 38
Conventional amphotericin B deoxycholate 0.5–1 mg/kg/day, total dose 15–20 mg/kg or more
- Miltefosine (>12 yo) 50 mg BID (30–44 kg) or TID (>45 kg) for 28 days
Contraindicated in pregnancy, defer conception by 5 months
CL – ketoconazole 600 mg/day for 28 days; itraconazole 200 mg BID for 28 days; fluconazole 200–400 mg/day for 6 weeks
Pentamidine, allopurinol, topical paromomycin
Topical steroid and cycloplegia for anterior uveitis
Systemic corticosteroid may help posterior ocular findings
Referral/Co-management
Dermatology
Primary Care
Infectious Disease
Malaria
Overview
- Definition
Caused by protozoa Plasmodium and transmitted by mosquito
Intraerythrocytic parasite
Ocular involvement in 20–30%, typically severe malaria
Plasmodium vivax (Pv) causes milder disease than P. falciparum (Pf) which can be lethal (cerebral malaria)
- Symptoms
Blurring
- Conjunctival discoloration
Hemorrhage
Yellowing
Pain
Light sensitivity
Floaters
- Laterality
Unilateral or bilateral
- Course
Typically present only in severe malaria
- Age of onset
All age groups affected
- Gender/race
Any/any person in endemic area
- Systemic association
- Systemic malarial infection
Severe flu-like symptoms
Encephalopathy
May lead to convulsion, coma, or death
Exam: Ocular
Anterior Segment
Subconjunctival hemorrhage
Conjunctival yellowing
Anterior uveitis
Posterior Segment
Retinal hemorrhage, preretinal or intraretinal
Roth spots
Vitreous hemorrhage
Retinal edema
Retinal ischemia
Retinal vasculitis, periphlebitis (poor prognosis)
Papilledema and optic neuritis (poor prognosis)
Exam: Systemic
Fever with chills and rigor at definite intervals
Headache
Fatigue
Muscle ache
Nausea and vomiting
Orthostatic hypotension
Hepatosplenomegaly, anemia, thrombocytopenia
- Severe cases (Pf)
High fever (>40 °C)
Tachycardia
Delirium
- Cerebral malaria with diffuse symmetrical encephalopathy
Potentially fatal
Imaging
OCT: may help to locate the location of hemorrhage
FA: retinal vascular or optic disc leakage, occlusion; blocking defects from hemorrhage
VF: scotomas
Laboratory and Radiographic Testing
Peripheral blood smear showing protozoa (schizonts) within red blood cells (RBCs)
- Rapid diagnostic stick tests
P. falciparum histidine–rich protein 2 (PfHRP2)
Plasmodium lactate dehydrogenase (PLDH) for pan-malaria group
Differential Diagnosis
Infectious – bacterial, fungal, viral, or protozoal
Collagen vascular disease
Malignancy
Heat stroke
Treatment
- Pf
- Quinine-based therapy
Quinine 1 g (600 mg base) PO, then 500 mg (300 mg base) PO 6–8 hours later, then 500 mg (300 mg base) PO at 24 hours and 48 hours after the initial dosewith
Pyrimethamine-sulfadoxine, or doxycycline or clindamycin
Artemether-lumefantrine
Atovaquone-proguanil
Mefloquine
- Pv
Chloroquine with primaquine
Dihydroartemisinin-piperaquine with primaquine
- P. malariae
Chloroquine
Referral/Co-management
Infectious Disease
Primary Care/ICU
SHAPU (Seasonal Hyperacute Panuveitis)
Overview
- Definition
Seasonal severe unilateral inflammation occurring every 2 years in autumn
Suspected relation to tussock moth; exact cause is unknown
Previously called “seasonal endophthalmitis”
- Symptoms
Blurring
White or red eye
Floaters
Lack of pain
- Laterality
Unilateral
- Course
Hyperacute, rapid progression to blindness/phthisis
- Age of onset
Typically pediatric
- Gender/race
No gender predilection
Only reported in Nepal
- Systemic association
None
Exam: Ocular
Anterior Segment
- Severe anterior uveitis
May have hypopyon/fibrinoid reaction
Non-granulomatous or granulomatous
White pupillary reflex
Shallow anterior chamber
Non-dilating pupil
Hypotony (malignant hypotension) very typical
Rapid progression to phthisis in weeks
Posterior Segment
Severe vitritis
Exam: Systemic
No findings
Imaging
Ultrasonography: used to evaluate the vitreous, retina and choroid
Laboratory and Radiographic Testing
Vitreous or aqueous tap showing Streptococcus pneumonia, Acinetobacter spp., varicella-zoster virus, and anellovirus (torque teno virus, torque teno midi, or torque teno mini virus) in some cases
A yet-undiagnosed infectious organism or severe allergic response to moth antigen may be involved in the etiopathogenesis
Differential Diagnosis
Endophthalmitis – endogenous, exogenous, traumatic
Acute retinal necrosis
Intraocular TB
Syphilis
Toxoplasmosis
Sarcoidosis
Behcet’s disease
Treatment
- Early PPV (pars plana vitrectomy) only successful method of salvaging vision reported
Intraocular antibiotic, antiviral can be given after surgery
Supportive care with topical antibiotic, steroid, cycloplegia
Referral/Co-management
Microbiology
Infectious Disease