American Trypanosomiasis

American Trypanosomiasis

Introduction

American trypanosomiasis (Chagas disease) is caused by Trypanosoma cruzi, a protozoan parasite found only in the Americas

-it is transmitted to humans by blood-sucking triatomine bugs (kissing bugs, assassin bugs, reduviid bugs)

-it  is endemic in many rural areas of Central and South America and Mexico

-In many countries in South America, Chagas disease is the most important cause of heart disease

Symptoms & Signs 

American trypanosomiasis progresses in 3 stages.

Stage 1 Acute Phase: asymptomatic or fever lymphadenopathy, mild hepatosplenomegaly, and morbilliform/urticarial rash,  a painful inflammatory reaction at the site of inoculation (Chagoma); unilateral conjunctivitis with palpebral edema (Romaña sign)

Stage 2 Indeterminate Phase: asymptomatic but infectious stage 

Stage 3 Symptomatic Chronic Phase: 

CNS: Meningoencephalitis 

Heart: Acute myocarditis, Dilated cardiomyopathy, arrhythmias, congestive heart failure 

GI: Dysphagia, regurgitation, aspiration, constipation, megaesophagus, and megacolon

Diagnosis: Demonstration of trypomastigotes in blood, smooth muscle biopsy, xenodiagnosis, serologic testing, PCR 

Treatment

Medications: Benznidazole, nifurtimox  


Trypanosomiasis

Introduction

Human African trypanosomiasis (HAT) or African sleeping sickness is a serious infection caused by a protozoan called Trypanosoma 

-the organisms are transmitted by bites of tsetse flies, which are confined to Central Africa  

-the disease is divided into West and East African forms

-Trypanosoma brucei gambiense causes West African sleeping sickness (95% of cases)

-Trypanosoma brucei rhodesiense causes East African sleeping sickness (5% of cases) 

Symptoms & Signs 

-a painful chancre develops at the site of the tsetse bite 

-It consists of a circumscribed, rubbery, indurated, dusky red nodule, often with a central eschar 

-Fever, headache, myalgia, lymphadenopathy, disseminated intravascular coagulopathy, QTc prolongation,pulmonary edema, ARDS, hypotension, and shock

-Involvement of the posterior cervical (Winterbottom sign) and supraclavicular lymph node in Gambian trypanosomiasis

Diagnosis 

Diagnosis is by detection of trypanosomes in blood films, Giemsa-stained thick smears, chancre, lymph node aspirate, bone marrow or CSF 

Treatment 

-Lumbar puncture must always be performed before initiation of therapy for sleeping sickness

-Selection of drugs dependent on whether CNS is involved

-CNS is not invaded: pentamidine, suramin

-CNS is invaded:  eflornithine, nifurtimox, melarsoprol, and fexinidazole 

Prognosis: Without CNS involvement, recovery often complete


Lyme disease

Introduction 

Lyme disease is an infection caused by the spirochete Borrelia burgdorferi, which enters the host after a bite by a tick

-Most cases of Lyme disease occur in the northeast United States between April and November

-It is the most common tick-borne illness and the most common vector-borne zoonotic infection in the United States, 

Symptoms & Signs 

Once a human is infected, disease progression is categorized into three stages: Early localized, Early disseminated, and Late persistent

Stage 1: Early Localized Disease

-Characterized by erythema migrans, which is described as “bull’s-eye” eruption. 

-it is a flat, nonpruritic, erythematous, maculopapular lesion near the site of infection

– Erythema progresses with central clearing 

-it can be accompanied by fever, chills, fatigue, myalgias, arthralgias, and lymphadenopathy

Stage 2: Early Disseminated Disease

-it occurs within a few days to months of the initial infection

-it can involve multiple organs

Fatigue: persistent fatigue is a hallmark of untreated disseminated Lyme disease 

Joints: Asymmetric oligoarticular arthritis of the large joints, particularly the knees; Migratory pains in muscles, joints, and periarticular structures 

Nervous system: it can produce both central and peripheral nervous system disease, acute as well as chronic 

CNS: meningitis or meningoencephalitis, headache, dementia, depression

Cranial nerves:  unilateral or bilateral facial nerve palsy

PNS: painful peripheral radiculopathy 

Heart: Conduction system abnormalities, myocarditis, pericarditis, AV block 

-the most common cardiac manifestation: Atrioventricular blockade

Stage 3: Late Persistent Disease 

-Less than 10% of patients with acute Lyme disease develop chronic manifestations of the disorder

-It can manifest as chronic arthritis, diffuse musculoskeletal pains, myocarditis, subacute encephalopathy, axonal polyneuropathy, chronic insomnia, and leukoencephalopathy

Diagnosis 

Enzyme-linked immunosorbent assay (ELISA), Western blot (immunoglobulin IgM and IgG for B. burgdorferi), CSF analysis (the mononuclear pleocytosis typical of Lyme infection)

Treatment 

Antibiotic treatment is indicated for all stages of Lyme disease

Doxycycline, Amoxicillin, Cefuroxime, Ceftriaxone, Cefotaxime, Penicillin G, erythromycin 

Do not use doxycycline in children under 9 years of age 

Prognosis 

Most manifestations resolve over time even without therapy

Q. What is the most common neurologic manifestation of Lyme disease? Bell palsy (seventh cranial nerve)

Q. What is the hallmark skin lesion of early Lyme disease? Erythema migrans


Leptospirosis

Introduction 

-Leptospirosis is a waterborne zoonosis of worldwide distribution, caused by spirochetes of the genus Leptospira

-it is excreted in urine of reservoir animals, especially rodents

-it is spread by animal urine contaminating lakes and streams

-Hawaii has the highest incidence in the United States

-Leptospira are tightly coiled, thin, flexible spirochetes, with very fine spirals, one end is often bent, forming a hook

-Human infection usually occurs often in bodies of water, entering the body through mucous membranes (mouth, nose, conjunctivae) and breaks in the skin (cuts and abrasions) 

Symptoms & Signs 

-Most human infections are asymptomatic and self-limited

-In symptomatic patients, Leptospirosis is a biphasic illness

Leptospiremic phase:  fever,severe headache, chills, myalgias, hepatitis (with or without jaundice), nausea, vomiting, conjunctival injection without purulent discharge 

Severe leptospirosis (Weil’s syndrome): hemorrhage, jaundice, acute renal injury, aseptic meningitis,uveitis, hepatic failure, renal failure, uveitis, rash, and circulatory collapse

Diagnosis 

Serum agglutination tests are the primary diagnostic method 

Other diagnostic aids: Dark-field examination, whole blood or urine culture

Treatment 

Mild leptospirosis: Oral doxycycline, ampicillin or amoxicillin 

Moderate or severe leptospirosis: intravenous penicillin, ampicillin, or ceftriaxone


Rat-bite fever

Introduction

Rat-bite fever consists of two similar febrile zoonoses caused by the treponeme Spirillum minus (Asia), or the bacteria Streptobacillus moniliformis (North America)

-Streptobacillus moniliformis is a pleomorphic Gram-negative rod

-Spirillum minus is a Gram-negative spirochete

-it is transmitted to humans by the bites from rats, mice, squirrels or gerbils 

-it can also result from exposure to rat feces or urine and ingestion of infected food or drink 

Symptoms & Signs 

-A flu-like illness: Fever, chills, headache, stiff neck, myalgia, nausea and vomiting 

-A rash: macular, morbilliform or petechial rash resembling measles 

-A desquamation: over the palms and soles 

-Arthritis: mostly involving large joints 

Diagnosis 

Gram stains of S. moniliformis:  Gram-negative filamentous branching chains, interspersed with bead-like swellings giving “necklace-shaped” colonies 

Dark field examination reveals Gram-negative spirochete Spirillum minus 

Treatment 

Treatment of choice: Penicillins; amoxicillin-clavulanic acid, Penicillin G

Alternative: Doxycycline


Relapsing fever

Introduction

Relapsing fever is a bacterial infection caused by the spiral-shaped Borrelia species (excluding Borrelia burgdorferi, the causative organism of Lyme disease) transmitted by lice or tick bites.

-it occurs in two forms linked to the mode of transmission and the Borrelia species involved

Louse-borne relapsing fever (LBRF): epidemic; caused by Borrelia recurrentis, transmitted by the body louse 

Tick-borne relapsing fever (TBRF): endemic; caused by multiple Borrelia species, transmitted by ticks 

Symptoms & Signs 

After a louse or tick bite, Borrelia enters the body, multiplies and produces endotoxins which affect the liver, spleen, and capillaries. 

-Abrupt onset of fever, chills, nausea, vomiting, arthralgia, headaches

rashes, hepatomegaly, splenomegaly 

-Delirium, neurologic and psychological abnormalities

-Attacks terminates abruptly after 3-10 days 

-Relapse occurs after an interval of 1-2 weeks 

-Three to ten relapses may occur before recovery

Diagnosis 

Thin or thick blood smears stained with Wright or Giemsa stain reveal large, loosely coiled spirochetes; PCR techniques, serology 

Treatment 

Procaine Penicillin G, tetracyclines, erythromycin


Congenital syphilis

Congenital syphilis is a transplacental fetal infection with T.pallidum 

Symptoms & Signs: 

Early symptoms (within 2 years of life): flu-like syndrome associated with nasal discharge (snuffles), maculopapular rash, anemia, jaundice, hepatosplenomegaly,hydrocephalus, lymphadenopathy, chorioretinitis 

Late symptoms (after 2 years of life): Saddle nose, saber shins, short maxilla, frontal bossing, high palatal arch, eighth nerve deafness, interstitial keratitis, triangular or peglike teeth (Hutchinson teeth)

-The most common eye lesion in congenital syphilis: interstitial keratitis

-treatment of the mother during pregnancy prevents congenital syphilis 

-All infants born to mothers with positive syphilis tests should have RPR or VDRL test 


Neurosyphilis

Neurosyphilis, infection of the CNS by T.pallidum can occur at any stage of infection 

Symptoms & Signs 

Fever,  eye pain, redness, photophobia, vision loss, uveitis, iritis, hearing loss,  cranial nerve abnormalities (especially cranial nerves II, III, IV, VI, VII, and VIII), meningismus 

Tabes dorsalis: It results from damage to the posterior columns of the spinal cord 

It presents with sensory ataxia, impairment of proprioception and vibration sense, a wide-based gait with impaired balance that is exacerbated by eye closure (the Romberg sign), muscular hypotonia, hyporeflexia, paresthesias, analgesia, or sharp, agonizing,  (‘shooting’/ ‘lightning) pains in the muscles of the leg, painful bladder spasms, urinary incontinence, impotence,  footdrop, and loss of reflexes.

-It can be accompanied by an Argyll Robertson pupil (which accommodates, but does not react to, light, light-near disassociation phenomenon) and optic atrophy 

-Painless trophic ulcers may develop over pressure points on the feet. 

-Sensory loss and hypotonicity can lead to the occurrence of hypertrophic (Charcot) joints. 


Tertiary Syphilis

-About one-third of patients with untreated latent syphilis progress to tertiary syphilis 

Manifestations: 

Gummas: granulomatous, erosive, nodular lesions with central necrosis which most commonly affect the skin and bones

-they affect the palate, nasal mucosa, tongue, tonsils, pharynx

-Ulceration of gummas can cause saddle-nose deformity due to erosion of cartilage 

CNS lesions: meningovascular syphilis, paresis, tabes dorsalis 

Cardiovascular lesions: aortitis, aortic valve insufficiency, coronary ostial stenosis, and saccular aneurysm 


Latent Syphilis

Latent syphilis is defined as the asymptomatic period more than 1 year after primary infection with no clinical manifestations but positive serologic tests 

-it is a diagnosis of exclusion after primary, secondary, tertiary and neurosyphilis have been ruled out 

-Patient can be infectious during this period 

-Secondary syphilis relapses often interrupt latent syphilis 

-it can last 20-30 years 

-It should be treated with benzathine penicillin or doxycycline 

Asymptomatic patient + Positive FTA-ABS test + History of syphilis in past medical history = Latent Syphilis 

Syphilis

Primary Syphilis 

Introduction 

Syphilis is a sexually transmitted, systemic disease caused by the spirochete Treponema pallidum 

-It occurs in multiple overlapping stages: Primary, Secondary, Tertiary, and Latent syphilis. 

-Neurosyphilis can occur at any stage.

-It is contracted through direct sexual contact with primary or secondary lesions 

-Congenital syphilis can be contracted across the placenta.

Symptoms & Signs 

Syphilis passes through 4 distinct clinical phases:

  • Primary stage: one or more, usually painless chancres 
  • Secondary stage: rash, condylomata lata, with or without lymphadenopathy, and organ disease
  • Latent syphilis: absence of signs or symptoms of disease, with only reactive serologic tests as evidence of infection
  • Tertiary stage: cutaneous, neurologic, or cardiovascular manifestations.

-Infectious lesions of syphilis can be present anywhere on the body but are typically located in or around the genital, anal, or oral area

-Chancre: Dusky red macule which evolves into a papule, then an ulcer 

Diagnosis 

A diagnosis of syphilis of any stage should be confirmed through the use of two-stage serologic tests

Serologic tests are either nontreponemal, which measure anticardiolipin antibodies, or treponemal , which measure antibodies to T. pallidum

Nontreponemal tests:

  • VDRL—Venereal Disease Research Laboratory.
  • RPR—Rapid plasma reagin.

Treponemal tests:

  • EIA—Enzyme immunoassay.
  • TP-PA—T. pallidum particle agglutination.
  • FTA-ABS—Fluorescent treponemal antibody absorption.
  • MHA-TP—Microhemagglutination assay for T. pallidum.

– Lyme disease may cause a false-positive treponemal test but rarely causes a false-positive nontreponemal test.

-Test all patients with syphilis for HIV.

-Traditionally, a diagnosis of syphilis of any stage should be confirmed through the use of two-stage serologic tests.

-Dark-field microscopy is useful in evaluating moist cutaneous lesions

Treatment 

-Treatment of choice for all stages of syphilis: Benzathine penicillin

-The dose and duration depend on the stage 

-Penicillin allergy: Doxycycline, Ceftriaxone, Azithromycin

-Counsel patients to abstain from sexual activity for 7–10 days after treatment-The Jarisch–Herxheimer reaction: Fever and aggravation of the existing clinical picture in the hours following treatment. The reaction resolves spontaneously within 24 hours


Tuberculous meningitis

-Tuberculous meningitis occurs in persons of all ages

-After primary infection in the lungs, blood-borne bacilli travel to the meninges 

Symptoms & Signs 

-Gradual onset with headache, fever, irritability, vomiting, nuchal rigidity, neck stiffness, cranial nerve palsies 

-Meningeal involvement is prominent at the base of the brain, affecting the pons and optic chiasm, leading to cranial nerve (especially III, IV, and VI) palsies, which results in visual impairment and diplopia 

Diagnosis 

-Cornerstone of diagnosis: Lumbar puncture 

-CSF obeys the ‘500 rule’: Lymphocytic pleocytosis fewer than 500, protein less than 500 mg/dL; glucose less than 45 mg/dL 

-Pathology: Basal meningeal, white gelatinous exudate containing mononuclear cells  

Treatment 

Treatment with isoniazid, rifampin, and pyrazinamide

All three penetrate the cerebrospinal fluid wall 

Add corticosteroids for hydrocephalus.