Respiratory Tract Infections PDF

636 SECTION 8  Respiratory Tract Infections „ BCG has been tried as an adjunctive therapy in Table 63.8: Runyon’s classification of nontuberculous mycobacteria. malignancies, such as bladder carcinoma (Onco Runyon group...

636 SECTION 8  Respiratory Tract Infections „ BCG has been tried as an adjunctive therapy in Table 63.8: Runyon’s classification of nontuberculous mycobacteria. malignancies, such as bladder carcinoma (Onco Runyon group Property Species TICE strain of BCG). I. Photochromogens Produce M. marinum, pigments only in M. asiaticum, M. simiae, M. VPM1002 light kansasii, M. genavense It is a recombinant BCG vaccine, under phase II trial II. Scotochromogens Produce M. scrofulaceum, (2017). It is prepared by replacing the urease C encoding pigments both in M. szulgai, M. gordonae gene from Listeria monocytogenes which improves its dark and light M. celatum, M. flavescens immunogenicity (promotes phagolysosome fusion). III. Non-photochro- Do not produce M. avium-intracellulare mogens pigments complex (MAC), Chemoprophylaxis M. xenopi, M. ulcerans, M. paratuberculosis, Treatment of selected high-risk tuberculin reactors M. malmoense (i.e. people with latent tuberculosis) aims at preventing IV. Rapid growers M chelonae, Grow within one active disease. Isoniazid or ethambutol for six months week M fortuitum, have been tried. However, chemoprophylaxis has several M. smegmatis, shortcomings such as—(1) it is expensive, (2) risk of & M. abscessus developing tuberculosis is minimal in tuberculin reactors, and (3) side eThects of the drugs. Nomogenic ™ M. asiaticum: It is rarely associated with pulmonary Hence, INH preventive therapy (IPT) can be restricted to limited indications such as: disease and bursitis ™ Adults with HIV who are unlikely to have active TB ™ M. simiae: It was originally isolated from monkeys. It is ™ Children with HIV who have no TB symptoms and who principally isolated from pulmonary lesions ™ M. kansasii: It causes chronic pulmonary disease are unlikely to have active TB ™ All children with HIV who have successfully completed resembling tuberculosis ™ M. genavense: It grows very slowly and rarely causes treatment for TB. infection in patients with advanced HIV. NONTUBERCULOUS MYCOBACTERIA 2. Scotochromogens INFECTIONS fiey produce pigments (yellow, orange or red) even when Nontuberculous mycobacteria (NTM) were formerly called cultures are incubated in dark, but intensity of color may atypical mycobacteria or mycobacteria other than tubercle increase on exposure to light. bacilli (MOTT). ™ M. scrofulaceum: It causes scrofula (cervical NTM are diverse group of mycobacteria that are isolated lymphadenitis) in children from birds, animals, and from environmental sources, ™ M. gordonae: It is often found as commensal in tap water such as soil and water. fiey are opportunistic pathogens, and is a common contaminant of clinical specimens. It occasionally associated with human infection. Man-to- is rarely isolated from pulmonary specimens; however man transmission is not known. its pathogenic potential is doubtful Saprophytic mycobacteria are isolated from soil, water ™ M. szulgai: It behaves as a scotochromogen at 37°C and and other environmental sources. fiey do not cause any photochromogen at 25°C. It may occasionally cause disease in humans and are distinct from NTM. Examples pulmonary disease and bursitis include M. phlei (from grass), M. smegmatis (from smegma, ™ M. celatum: It is a rare cause of pulmonary infection. a common contaminant in urine). 3. Nonphotochromogens Classification of NTM fiey do not produce any pigments. Examples include: Nontuberculous mycobacteria (NTM) have been classiffed ™ M. avium-intracellulare complex (MAC): They (Table 63.8) into four groups by Runyon (1959), based on comprise of two related organisms—M. avium (Battey pigment production and rate of growth. bacillus, isolated from birds) and M. intracelluare „ fiey are opportunistic pathogens, especially in HIV- 1. Photochromogens infected people with low CD4 T cell count (2.9 condition. General preventive measures include: ™ Regular hand washing before and after touching animals crore), followed by India, Brazil and Russia ™ Highest cases (%): In terms of total cases per 100 (especially dromedary camels) and should avoid contact with sick animals population, countries such as Czechia (11%), USA (8.8%), ™ Avoid consumption of raw or undercooked camel products, Israel (8.5%), Portugal (7.9%) and Bahrain (7%), were including milk and meat; should be consumed only after worst affected, compared to India (0.8%) pasteurization, cooking or other heat treatment. ™ Mortality rate: The severity of the disease varies among the countries and also across different time CORONAVIRUS DISEASE (COVID)-2019 spans. Countries such as France, Italy, UK and Belgium reported a mortality rate of > 10%, in the early phase of Coronavirus disease-2019 (COVID-19) is an acute the pandemic, which reduced subsequently. In contrast respiratory disease caused by severe acute respiratory USA (1.8%) and India (1.4%) reported lower mortality syndrome coronavirus 2 (SARS-CoV-2). It has caused an rate during the pandemic. The average mortality rate in explosive catastrophic pandemic that affected almost all the world is estimated to be 2.2% part of the world, and produced significant loss of lives ™ China: Rapid rise of cases occurred in China at the and the worst financial crisis recorded ever, since World beginning (over 80,000 cases by end of February 2020). War II. Wuhan accounted for the majority (>80%) of cases in China. However, cases rapidly declined thereafter EPIDEMIOLOGY ™ Italy: Italy was one of those countries which were worst History hit in the early phase of this pandemic. The country was SARS-CoV-2 originated from China and subsequently not prepared when the disease started. As a result, there spread rapidly to affect rest the world over a period of 3-4 was a rapid surge of cases with a mortality rate >10% months—one of the fastest spreading infectious disease ™ USA: Accounts for highest number of cases (>3 crore) recorded in the history of mankind. with a mortality rate of 1.8% ™ Wuhan: It was first identified in December 2019 in ™ Growth curves: The growth curves of COVID-19 cases Wuhan, China, which produced a large cluster of vary among the countries. Different countries are at pneumonia cases— hence, the virus was initially called different stages of pandemic. In countries such as Italy, as the ‘Wuhan Virus’. Subsequently it was named as the Spain and USA, the disease spread quickly reaching its 2019- novel coronavirus (2019-nCoV) peak early; whereas in other countries like India the ™ Origin: In further studies, it was found that it’s a disease had a slower rate of growth (initially) β-Coronavirus, with highly identical genome (96% ™ Variants: The increase number of cases in various parts homology) to SARS-like bat coronavirus, pointing of the world, in the later phase of the pandemic may be towards bat as the natural host (Fig. 67.2) due to emergence of various variants of the SARS-CoV-2 ™ PHEIC: As the cases continued to rise, the outbreak was virus, such as UK variant, Brazilian variant and South declared as ‘Public Health Emergency of International African variant Concern (PHEIC)’ on 30th January 2020 ™ India was one among those countries where the ™ Nomenclature: On 11th February 2020, WHO announced COVID-19 pandemic had a slower growth curve to reach the official name ‘COVID-19’ for this new coronavirus its peak. India accounts for second highest number of disease and also renamed the virus as SARS-CoV-2 cases (>1.1 crore) with a mortality rate of 1.4%. because its genome closely resembled to SARS-CoV. ™ Pandemic: The disease spread rapidly in an explosive MORPHOLOGY manner. On 11th March 2020, WHO declared it as a global The SARS-CoV-2 comprises of a nucleocapsid, surrounded pandemic. By that time, about 114 countries were affected by an envelope. It measures 120 nm in size; has a helical with >118,000 cases and 4,291 deaths symmetry. It possesses 4 structural proteins (N, S, M and  CHAPTER 67  Coronavirus Infections Including COVID-19 663 example, through coughing, sneezing or very close personal contact resulting in the inoculation of entry portals such as the mouth, nose or conjunctiva. Use of mask can prevent droplet transmission. Contact Transmission Transmission of the COVID-19 virus can occur directly by contact with infected people, or indirectly: ™ By contact with the surfaces in the immediate environment or ™ With objects used on or by the infected person (e.g. stethoscope or thermometer) or ™ Through fomites (inanimate objects) in the immediate environment around the infected person such as infected clothes, utensils, furniture. Following contact (direct or indirect), the virus can only be transmitted by touching the contaminated hand to a person’s mouth, nose or conjunctiva. Frequent hand hygiene following potential contact exposure is crucial to Fig. 67.3: Structure of SARS-CoV-2. prevent this type of transmission. Aerosol Transmission E), 16 nonstructural proteins and several other accessory proteins (Fig. 67.3). Aerosol transmission (spread of the infected droplet nuclei ™ Nucleocapsid consists of a positive-sense single- beyond one meter) is not documented yet, although stranded RNA (~30 kb genome size), surrounded by active research is on-going in this regard. However, in nucleocapsid protein (N) specific settings in which aerosol-generating procedures ™ The envelope is lipoprotein in nature; the lipid part are performed (e.g. endotracheal intubation), aerosol is host-derived into which a number of proteins are transmission of the COVID-19 virus may be possible embedded such as: (Chapter 21). Use of N95 respirator is important to prevent „ Spike protein (S): Helps in the attachment to the this type of transmission. host cells. Neutralizing antibodies are produced against S protein are protective in nature. It has two Pre-symptomatic Transmission subunits. It is defined as the transmission of the COVID-19 virus from  S1 subunit possesses the receptor-binding domain a person who is infected and shedding the virus but has (RBD), which binds to a specific receptor in the not yet developed symptoms. This type of transmission has host cell surface been observed in people 1-3 days before the onset of their  S2 subunit facilitates virus-cell membrane fusion symptom, with the highest viral loads detected around the „ Membrane glycoprotein (M): It is the most abundant day of symptom onset, followed by a gradual decline over structural protein, gives the shape to the virus time. „ Envelope protein (E): It is a transmembrane protein and with ion channel activity; found in small Host Cell Entry quantities. SARS-CoV-2 enters into the target host cells by binding of ™ Non-structural proteins: They include several enzymes its spike glycoprotein (S) antigen with the host cell receptor, which help in replication of the virus, e.g. RNA-dependent i.e. angiotensin converting enzyme-2 (ACE-2). This is also RNA polymerase (RdRp), helicase, etc. the receptor for SARS-CoV. ™ Spike protein cleavage: For virus entry into a host cell, PATHOGENESIS its S protein needs to be cleaved, which is mediated by host cell proteases; of which TMPRSS 2 (transmembrane Transmission protease serine 2) is important COVID-19 virus is primarily transmitted via respiratory ™ Fusion: Cleavage of S protein produces S1 subunit which droplets and contact routes. binds to ACE-2 and S2 subunit which causes fusion of viral envelope with host cell membrane. Then follows Droplet Transmission the entry of the virus via endosomal pathway Droplet transmission occurs when a person is in close ™ ACE-2 receptors are highly expressed on type- II alveolar contact (within 1 meter) with an infected person. Exposure cells in lungs and on the epithelial cells of oral mucosa; to potentially infective respiratory droplets occurs, for also found on cells of heart, kidney, endothelium and 664 SECTION 8  Respiratory Tract Infections intestine. Therefore, the patients develop extrapulmonary perturbed which leads to fluid retention in the interstitial manifestations in addition to respiratory symptoms. space Note: The primary function of ACE-2 is that, it helps to ™ To prevent collapse, the muscular movement of reduce blood pressure and has anti-inflammatory action. inspiration becomes hyperactive, which results in increased lung volume in the interstitial space. The "low Development of ILI pressure area" created in the interstitial space attracts ACE-2 receptors are highly expressed on the epithelial cells liquid, which further contributes to edema in the lungs. of oral mucosa. Therefore, at the initial stage, SARS-CoV-2 infects the pharyngeal epithelium, induces inflammation. Cytokine Storm This accounts for the influenza-like illness (ILI) which occurs The presence of SARS-CoV-2 in lung induces an uncontrolled at the beginning stage of most of the symptomatic cases. generalized immune response. Several immune cells like neutrophils, T-lymphocytes, macrophages are recruited to Development of ARDS the lungs (Fig. 67.4). The leading cause of mortality in patients with COVID-19 ™ Acute cytokine influx: These immune cells release pro- is hypoxemic respiratory failure which can result in acute inflammatory cytokines—IL-2, IL-2R, IL-6, IL-7, IL-8, IL- respiratory distress syndrome (ARDS). 10, G-CSF, IFN- , IP-10, MCP-1, MCP-3, TNF- and others ™ Host injury: The elevated cytokines leads to various Reduced Surfactants consequences such as: In lungs, ACE-2 receptors are highly expressed on type- „ Tissue damage and necrosis II alveolar cells. These cells normally produce pulmonary „ Further recruitment of leukocytes surfactants which lower the alveolar surface tension. In „ Impaired gas exchange, which leads to reduced COVID-19 patients the following events take place. blood oxygenation and tissue hypoxia ™ Damage to the type-II alveolar cells leads to reduced „ Endothelial damage of pulmonary vasculature, production of pulmonary surfactants; as a result of which leading to vasodilation, microvascular thrombosis alveoli tend to collapse. The air-liquid-interphase is and hemorrhage, and hypercoagulability Fig. 67.4: Cytokine storm seen in COVID-19 patients.  CHAPTER 67  Coronavirus Infections Including COVID-19 665 „Dilatation of blood vessels underlying the alveoli: Table 67.2: Clinical severity of COVID-19 disease. This allows passage of fluid from the blood vessels Clinical stage Clinical presentations to lungs which leads to pulmonary edema. These Mild disease infiltrates in the lungs appear as ‘ground-glass’ in ILI ((influenza-like Patients with uncomplicated upper chest imaging illness) respiratory tract infection, may have mild „ Fibrosis: In the later stage, there occurs recruitment symptoms such as fever, cough, sore throat, of fibroblast, which causes lung fibrosis, and nasal congestion, malaise, headache ultimately, leads to respiratory failure. Without evidence of breathlessness or hypoxia (normal saturation) This stage is called as acute respiratory distress syndrome Moderate disease (ARDS), eventually leading to respiratory failure ™ Multiorgan failure: Cytokines can also induce damage to Pneumonia with Dyspnea, fever and cough no signs of severe Hypoxia, SpO2 30 /min or (ii) SpO2 „ Age > 60 years (risk increases with age) 200 IU/mL) in most of the streptococcal all streptococci, but exhibits the following biochemical infections except pyoderma and PSGN. It is detected by properties that differentiate it from group A Streptococcus latex agglutination test and nephelometry method (Table 52.4). ™ Anti-DNase-B antibodies: Titer more than 300–350 IU/ ™ Colonies: The colonies of GBS are -hemolytic, similar to mL is diagnostic of PSGN and pyoderma. that of S. pyogenes; however they are mucoid and slightly larger (2 mm) (see Fig. 52.5C) Antimicrobial Susceptibility Test (AST) ™ CAMP positive: CAMP factor (named after the AST is performed by disk diffusion method (on Mueller– discoverers—Christie, Atkins-Munch-Petersen) is a Hinton agar with 5% sheep blood) or by automated MIC phospholipase produced by GBS that enhances the detection method by microbroth dilution (e.g. VITEK). Table 52.5: Treatment of S. pyogenes skin and soft-tissue T REATMENT S. pyogenes infections infections. Penicillin is the drug of choice for pharyngeal infections as well as Conditions Treatment recommended for suppurative infections. Resistance to penicillin is not reported Impetigo and PSGN Benzathine penicillin G, IM single dose; yet. or Oral penicillin V for 10 days However, failure to penicillin treatment may occur due to: (i) Erysipelas/cellulitis Mild: Procaine penicillin noncompliance, if discontinued before 10 days of full course Severe: Penicillin G of oral penicillin V, (ii) -lactamases produced by normal throat flora such as Moraxella Necrotizing fasciitis Surgical debridement (most crucial) + Penicillin G + Clindamycin Macrolide, such as erythromycin is given to patients allergic to penicillin. However, resistance to macrolides is common Streptococcal toxic Penicillin G + Clindamycin + Intravenous Treatment shortens the clinical syndrome, at least modestly, shock syndrome immunoglobulin (against streptococcal reduces transmission to others, decreases the risk of pyrogenic exotoxin) Contd... Abbreviations: IM, intramuscular; PSGN, poststreptococcal glomerulonephritis. 526 SECTION 7  Skin, Soft Tissue and Musculoskeletal System Infections hemolysis of S. aureus. When GBS is streaked on blood Streptococcus MG is an α-hemolytic strain belonging to this agar plate perpendicular to S. aureus, an enhanced group. Demonstration of antibodies to Streptococcus MG in the arrowhead-shaped hemolysis is produced at their patient’s sera has been used for diagnosis of primary atypical junction, pointing towards S. aureus streak line (see Fig. pneumonia (caused by Mycoplasma pneumoniae). 52.5E) Group D Streptococci ™ Bacitracin resistant (see Fig. 52.5D) Group D streptococci comprise of enterococci (fecal streptococci, ™ Species identification can be confirmed by Lancefield described below) and non-enterococci (S. gallolyticus and S. serogrouping and automations such as MALDI-TOF. equinus). Both groups possess the common group D lipoteichoic acid antigen and give positive bile esculin hydrolysis test; but T REATMENT S. agalactiae infections differ in many properties. Compared to Enterococcus, non- Penicillin/ampicillin plus gentamicin are the drug of choice for all enterococcal Group D are: GBS infections. ™ More susceptible to antibiotics such as penicillin ™ Do not grow in presence of 6.5% salt Group C and G Streptococci ™ Less pathogenic to humans ™ Not a part of human intestinal flora. Group C and G streptococci comprise of the following species. S. gallolyticus (formerly S. bovis) and S. infantarius are ™ S. dysgalactiae subsp. equisimilis: It carries both group C commensal of intestine of animals. In humans, they occasionally and G antigens. This is the most common species to infect cause endocarditis associated with colorectal cancer or polyps. humans, causes pharyngitis, cellulitis and soft tissue infections, Penicillin is the drug of choice. pneumonia, bacteremia, endocarditis, and septic arthritis, UTI, meningitis and puerperal sepsis ™ S. equi: It carries group C antigen; has two subspecies equi ENTEROCOCCUS AND OTHER STREPTOCOCCI and zooepidemicus Enterococcus and other streptococci principally cause infections „ Both cause infections animals, especially horses and cattle; of various body sites; therefore, they are discussed under the rarely cause human infections through consumption of respective infective syndromes. unpasteurized milk or contact with infected animals ™ Enterococcus: It is non or -hemolytic, found as normal flora „ Spectrum of disease include pneumonia, bacteremia, of human intestine; causes widespread infection including endocarditis, meningitis and septic arthritis. UTI (Chapter 76), meningitis, intra-abdominal infection and ™ Diagnosis: They produce -hemolytic colonies on blood agar endocarditis of >0.5 mm size. Species identification is made by Lancefield ™ Viridans streptococci: They are α-hemolytic, found as normal serogrouping and automations such as MALDI-TOF flora in oral cavity; may occasionally cause dental caries and ™ Treatment: Penicillin is the drug of choice. endocarditis (subacute bacterial endocarditis) (Chapter 28) ™ Streptococcus pneumoniae: It is α-hemolytic, primarily causes Group F Streptococci pneumonia (Chapter 61), spreads further to cause various They are also called minute streptococci. They grow poorly on invasive diseases such as bacteremia and meningitis. It can blood agar, occasionally cause suppurative infection. also cause local infections such as otitis media and sinusitis. EXPECTED QUESTIONS I. Write essay on: II. Write short note on: 1. Chinu, a 3-year-old girl from Mangaluru presented 1. Necrotizing fasciitis. with tender, bright red, subcutaneous swelling on III. Multiple Choice Questions (MCQs): malar area of the face with indurated peau d’orange 1. Serotyping of Streptococcus pyogenes is based on texture of involved skin along with fever and chills. A which of the following protein? clinical diagnosis of cellulitis was made. The culture a. M protein b. T protein of the aspirated pus revealed beta-hemolytic pin c. R protein d. Carbohydrate antigen point colonies. 2. Streptococcus pyogenes can be differentiated a. What is the most likely etiologic agent? from S. agalactiae by testing susceptibility to: b. Describe the virulence factors and the other a. Optochin b. Bacitracin clinical manifestations produced by the c. Polymyxin d. Novobiocin etiological agent? 3. CAMP test is useful in identification of: c. Briefly discuss the laboratory diagnosis of this a. S. pyogenes b. S. agalactiae clinical condition. c. S. pneumoniae d. Viridans streptococci Answers 1. a 2. b 3. b  CHAPTER 49  Parasitic Infections of Hepatobiliary System 493 Prevention Includes avoidance of ingestion of food and water contaminated with human feces and treatment of asymptomatic persons. HUMAN ECHINOCOCCOSIS Human echinococcosis is a zoonotic disease that is caused by a cestode of the genus Echinococcus. It occurs in 4 forms: ™ Cystic echinococcosis, also known as hydatid disease or hydatidosis, caused by Echinococcus granulosus ™ Alveolar echinococcosis, caused by E. multilocularis ™ Two forms of neotropical echinococcosis: „ Polycystic hydatid disease, caused by E. vogeli „ Unicystic hydatid disease, caused by E. oligarthrus. Cystic Echinococcosis It is caused by Echinococcus granulosus; also called as dog tapeworm. Fig. 49.3: Life cycle of Echinococcus granulosus. Morphology 2. Intermediate hosts: Sheep and other herbivores are It is a tissue cestode, exits in three morphological forms— the usual intermediate host. Man acts as an accidental adult, larva (called hydatid cyst), and egg. intermediate host (dead end). ™ fle adult worm resides in dog’s intestine. It measures Infective form: Eggs are the infective form. 3–6 mm long, consists of head, neck and a strobila or body made up of three proglottids/segments (Fig. 49.2A) Mode of transmission: Man (and other intermediate hosts) ™ The larval form is called as hydatid cyst. It is the acquires the infection by ingestion of food contaminated pathogenic form, forms cystic lesions in liver and other with dog’s feces containing E. granulosus eggs. viscera of man and other herbivores (Fig. 49.2B) Development in Man/Sheep ™ Eggs: E. granulosus eggs are morphologically similar to Taenia eggs, consists of an embryo with six hooklets ™ In duodenum, the embryo or oncosphere is released, surrounded by an embryophore. which penetrates the intestinal wall, enters the portal circulation and carried to the liver (60–70% of cases) or Life Cycle (Fig. 49.3) lungs or rarely to other organs Host: E. granulosus passes its life cycle through two hosts: ™ Although majority of embryo are destroyed by host 1. Deffnitive host: Dogs and other canine animals immune response, few escape and develop into Thuid fflled bladder-like cyst called as hydatid cysts ™ fle hydatid cyst undergoes maturation increases in size at a rate of 1 cm/month. Full development takes 10–18 months in sheep ™ flis stage is infective to dog and other deffnitive hosts ™ Man is a dead end, as dogs do not feed on human viscera and therefore the cycle stops there. Development in Dog Dog and other canine animals acquire infection by consumption of the contaminated viscera of intermediate hosts (sheep) containing mature hydatid cysts. fle hydatid cyst (larva) transforms into adult worm in dog’s intestine. fle adult worms sexually mature, self- fertilize to produce eggs which are passed in feces and are A B infective to man. Figs 49.2A and B: Echinococcus granulosus: A. Adult worm Pathogenicity (schematic); B. Hydatid cyst, gross specimen. Source: B. Head, Department of Microbiology, Sri Siddhartha Medical Pathogenicity is related to the deposition of the hydatid College, Tumkur, Karnataka (with permission). cysts (larval form of the parasite) in various organs. 494 SECTION 6  Hepatobiliary System Infections Hydatid cyst (Figs 49.2B and 49.5A) ™ World: Higher incidence has been reported from Central It is a Thuid-fflled bladder-like cyst; unilocular, subspherical Asia (>10 per 1 Lakh population); which may be up to 27 in shape and average size measures 5–8 cm (from few mm per 1 lakh population in Tajikistan to >30 cm). ™ India: Hydatid disease has been reported from various ™ Cyst wall consists of three layers: outer pericyst (host places in India like Andhra Pradesh, Tamil Nadu, derived), middle ectocyst and inner endocyst Chandigarh, Kashmir, Maharashtra and West Bengal ™ Brood capsule: fle inner side of the endocyst gives rise ™ Genotypes: E. granulosus comprises of 10 genotypes; to brood capsule, and also secretes the hydatid Thuid. fle which difier in their intermediate host, and geographic brood capsule contains number of protoscolices (future distribution. Genotypes G1-G3 cause 88% of human head) cases. In India, G1 (sheep strain) is more common, ™ Hydatid fluid: It is clear, pale yellow colored Thuid, which followed by G5 (cattle strain). is antigenic, toxic and anaphylactic L ABORATORY DIAGNOSIS Hydatid disease ™ Hydatid sand: Some of the brood capsules and protoscolices break ofi and get deposited at the bottom Hydatid fluid microscopy (direct mount or staining with as hydatid sand acid-fast stain)—detects brood capsules and protoscolices ™ Fate: fle hydatid cyst may undergo—(i) spontaneous res- Histological examination (H & E)—demonstrates cyst wall and attached brood capsules olution, or (ii) rupture of the cyst, which may lead to either Antibody detection—ELISA (using B2t antigen), DIGFA (dot formation of secondary cysts (carried to other organs) or immunogold filtration assay) and western blot anaphylactic reaction to the hydatid Thuid antigens. Imaging methods—X-ray, USG (demonstrates Water lily sign), CT scan, MRI Clinical Features Molecular methods—PCR, PCR-RFLP and molecular typing Infection usually occurs in childhood but gets manifested (10 genotypes, most common in India is type 1) in adult life. Skin test (Casoni test)—demonstrates type I hypersensitivity ™ Site: Most common site of the cyst is liver (60–70%, right reaction (obsolete now). lobe) or lung (20%), followed by kidney, muscle, spleen, soft tissue, brain, bone and others Laboratory Diagnosis ™ Asymptomatic: fle cysts grow up to 5–10 cm in size Hydatid Fluid Microscopy within the ffrst year and can survive for years or even After surgical removal of the cyst (Fig. 49.4), the hydatid decades, without any symptoms fluid is aspirated and examined by direct microscopy ™ Symptoms: Few patients develop symptoms which may or staining with acid-fast stain for presence of hydatid be due to: sand. „ Pressure effect of the enlarging cyst: Leads to palpable ™ Diagnostic aspiration is not usually recommended abdominal mass, hepatomegaly, abdominal because of the risk of Thuid leakage which may lead to tenderness, portal hypertension and ascites anaphylaxis or dissemination of infection „ Obstruction: Daughter cysts may erode into the biliary tree or a bronchus and enter into the lumen to cause cholestasis, cholangitis, and dyspnea „ Secondary bacterial infection, causing pyogenic abscess in liver „ Anaphylactic reactions: Cyst leakage or rupture may be associated with a severe allergic reaction to hydatid Thuid antigens; leading to hypotension, syncope and fever. ™ Outcome of the disease: It depends on the cyst size and location ™ Younger children are more associated with extrahepatic cysts in lungs, brain and orbital sites and multi-organ involvement ™ Allergy: Patient sometimes develops hypersensitivity (atopy and anaphylaxis); which is attributed to release of various allergens from the cyst such as 12-kDa AgB (protease inhibitor), Ag5 serine protease, etc. Fig. 49.4: Surgically resected hydatid cyst from liver. Epidemiology Source: Head, Department of Pathology, Meenakshi Medical College, E. granulosus is worldwide in distribution. Chennai (with permission).  CHAPTER 49  Parasitic Infections of Hepatobiliary System 495 A B C Figs 49.5A to C: Microscopy of hydatid cyst: A. Schematic; B and C. Histopathological section (hematoxylin and eosin stain) showing (B) all three layers of cyst wall—pericyst, ectocyst and endocyst, (C) endocyst with attached brood capsules. Source: B and C. Head, Department of Pathology, Meenakshi Medical College, Chennai (with permission). ™ Drop of centrifuged Thuid is placed between two slides Imaging Methods and the slides are rubbed over the Thuid Imaging methods play an important role as they are non- ™ Hydatid sand is felt as grating of the sand grains in invasive methods, which can detect the cysts inciden- between the slides. The hydatid sand comprises of tally in asymptomatic individuals and in seronegative protoscolices and brood capsules. cases. ™ X-rays: It is simple, inexpensive, yet useful technique Histological Examination to detect hepatomegaly and calciffed cysts and cysts in Surgically removed cysts (Fig. 49.4) can be subjected to lungs histopathological stains like Giemsa, hematoxylin and ™ Ultrasound (USG): It is the imaging method of choice eosin (H & E) and periodic acid–Schiff (PAS) stain to because of its low cost and high diagnostic accuracy of demonstrate the three layers of the cyst wall and attached 90% brood capsules (Figs 49.5A to C). „ It detects both single and multiple cysts „ WHO classification of USG imaging: WHO has Antibody Detection classified the USG images of cysts into six types Serodiagnosis of hydatid disease follows a two-step according to its activity (CL and CE1 to CE5) (Table approach; ffrst, a more sensitive test (for screening) such 49.1). flis is useful in determining whether the cyst as ELISA or DIGFA (dot immunogold ffltration assay) is is active or not carried out. If found positive, should be conffrmed with „ USG is used to monitor the response to treatment more speciffc test such as immunoblot. „ It is also used for epidemiological studies to detect ™ ELISA using crude E. granulosus cyst Thuid antigen or the prevalence of hydatid cyst in population. recombinant B2t antigen are available. fle later shows better results. It is also used as an indicator of cure in surgically treated patients Table 49.1: WHO international classification of ultrasound ™ DIGFA: Dot immunogold ffltration assay (DIGFA) can images of hydatid cyst. simultaneously detect serum antibodies against four Types Activity USG finding native antigens; three from E. granulosus (cyst Thuid, AgB and protoscolex antigens) and one from E. multilocularis CL Active Cystic lesion and no visible cyst wall (Em2 antigen) CE1 Active Visible cyst wall and internal echoes ™ Immunoblot (Western blot): Immunoblot is the most (snowflake sign) speciffc serological method; detects antibodies to hydatid CE2 Active Visible cyst wall and internal septation cyst Thuid antigen or antigen B fragment. (honeycomb appearance) Antibody methods are useful for sero-epidemiological CE3 Transitional Have detached laminar membranes or study but cannot difierentiate recent and past infection. may be partially collapsed, and floating Antigen B is the antigen of choice used for sero- within the cyst cavity (known as Water lily sign) epidemiological study for the detection of antibody. Patients with liver cysts show better results than CE4 Inactive Non-homogeneous mass extrahepatic cysts. Pulmonary cysts do not produce CE5 Inactive Cyst with a thick calcified wall detectable antibodies. Alveolar echinococcosis shows Abbreviations: WHO: World Health Organization; CE- cystic echinococcosis. better results than cystic echinococcosis. Note: This classification is also applicable for CT scan and MRI images. 496 SECTION 6  Hepatobiliary System Infections Contd... T REATMENT Hydatid disease 3. Infusion of scolicidal agents like hypertonic saline, cetrimide, or ethanol 4. Re-aspiration of the fluid after 5 minutes PAIR claims higher cure rate, less recurrence rate, less complications and hospitalization compared to surgery PAIR is recommended for a single hepatic cyst (CE1 lesion and uncomplicated CE3 lesion) PAIR is contraindicated for: Superficially located cysts (because of the risk of rupture) CE2: Cyst with multiple thick internal septal division (honeycomb appearance) Inaccessible cyst or extrahepatic cysts Cysts communicating to the biliary tree CE4 and CE5 lesions: These are inactive lesions; should be managed with observation only Surgery Though surgery is the definitive method of treatment, it should be reserved for: Fig. 49.6: CT scan showing calcified hydatid cyst in the liver. Cases where PAIR is contraindicated or refractory Source: Dr A Subathra, Department of Radiodiagnosis, JIPMER, Puducherry Secondary bacterial infection (with permission). Advanced disease Disadvantages of surgery are high recurrence rate (2–25%) ™ Computed tomography (CT scan): It can detect 90– and postoperative complications (10–25%) 100% of cases (Fig. 49.6) Preoperative use of albendazole is effective in reducing size „ It detects more accurately the number, location of the and to prevent recurrence cyst and the complications Antiparasitic agents „ It is superior to detect the calciffed lesions Albendazole is the drug of choice, given to prevent recurrence „ It is superior to USG to detect smaller cysts, and to reduce the size of the cyst before surgery or PAIR and is given at 15 mg/kg daily in two divided doses; 1 week before to 4 extrahepatic cysts and to difierentiate hydatid cyst weeks after the procedure from other cystic lesions Complicated and multivesicular cysts may require longer „ CT scan can also be used as a prognostic marker. duration ™ Magnetic resonance imaging (MRI): It has a higher Pulmonary cyst, preoperative albendazole should be avoided; contrast resolution, which makes cysts clearer. It can praziquantel is given alternatively be used as an alternate to CT scan. However, it poorly Percutaneous thermal ablation detects the calciffed cysts. It is a noninvasive method, involves percutaneous radiofrequency ablation of the germinal layer of the cysts. Molecular Methods ™ PCR targeting mitochondrial DNA has been developed Prevention ™ PCR-RFLP can be used to detect genotypes of E. granulosus. Cystic echinococcosis can be prevented by: ™ Administering praziquantel to infected dogs Skin Test (Casoni Test) ™ To improve personal hygiene to reduce contamination It is an immediate hypersensitivity reaction (wheal and of food and water with dog’s feces Thare), which develops following injection of hydatid Thuid ™ Vaccinating the sheep antigens. It was developed by Casoni in 1911. Now this test ™ Limitation of stray dog population. is obsolete. Alveolar Echinococcosis T REATMENT Hydatid disease Echinococcus multilocularis is the agent of alveolar hydatid Therapy for cystic echinococcosis is based on viability, size and disease. location of the cyst; guided by USG and overall health of the ™ Life cycle: Life cycle is similar to that of E. granulosus. patient. Only the hosts are difierent PAIR (puncture, aspiration, injection and re-aspiration) „ Deffnitive host: Foxes and wolves (and also dogs and It is an alternative method recommended instead of surgery. It cats) involves four basic steps: „ Intermediate hosts: Small wild rodents like squirrels, 1. Percutaneous puncture of the cyst voles, mice, etc. Man is an accidental intermediate host. 2. Aspiration of 10–15 mL of cyst fluid ™ Clinical features: It produces alveolar (or multilocular) Contd... hydatid disease. So named because the cysts have  CHAPTER 49  Parasitic Infections of Hepatobiliary System 497 multiple locules resembling lung alveoli. The cysts ™ Morphology: Similar to other trematodes, they have are usually sterile, do not produce brood capsule and adult worm (leaf-like), operculated eggs, and larvae (in protoscolices ffve stages) „ Liver is the most common organ afiected (98% of ™ Hosts: Liver Thukes have three hosts cases) „ Definitive host: Humans are the definitive host. „ Symptoms developed are similar to that of E. granu- Other animals can also act as deffnitive host such as— losus such as hepatomegaly and portal hypertension sheep for F. hepatica (also called as sheep liver Thuke) „ Cyst has an ability to migrate rapidly to other organs and dogs and cats for Clonorchis and Opisthorchis mimicking a malignant tumor. However, there is no „ Intermediate hosts: Snails are the ffrst intermediate malignant potential. fle rapid invasion is due to a host, whereas the second intermediate host is aquatic surface protein 14-3-3 found on the cyst wall. plant (for Fasciola) and cray ffsh (for Clonorchis, and ™ Geographical distribution: flis disease is found more Opisthorchis) frequently in Russia, Kazakhstan, China, South-Central ™ Transmission: Man gets infection by ingestion of second Europe and North America intermediate host carrying metacercaria larvae (infec- ™ Laboratory diagnosis: It is similar to as described for tive form) cystic echinococcosis ™ fle larvae excyst and penetrate through the intestinal „ Imaging methods can detect the number and size of wall to migrate to their habitat (liver or bile duct), where the cyst, extension of the lesion they develop into adult worms „ Antibody detection tests: Different ELISA formats ™ Adult worms undergo fertilization to produce eggs. Eggs are available using cyst Thuid antigen, recombinant are passed from the bile duct or liver to intestine and Em-10 and Em-18 antigens. flese tests are sensitive excreted in feces (diagnostic form). but gives false positive results, in cross-reacting E. granulosus infection Fascioliasis „ Histopathology: Detects the multi-loculated sterile Fascioliasis (caused by Fasciola hepatica), although cyst and associated necrosis reported worldwide is particularly endemic in sheep- „ Molecular method: PCR can differentiate various raising countries such as Peru, Bolivia, and Chile. In India, Echinococcus species. it is extremely rare. ™ Treatment: fle treatment modalities are as described for E. granulosus. Clinical Features ™ Liver: Migration of metacercaria larvae into liver Neotropical Echinococcosis causes fever, right upper quadrant pain, hepatomegaly It comprises of two forms—polycystic hydatid disease and eosinophilia. Liver parenchyma is inThamed with (caused by E. vogeli) and unicystic hydatid disease (caused formation of multiple subcapsular abscesses (called as by E. oligarthrus). liver rot) ™ Host: Wild felids like wild cats, jaguars and pumas (E. ™ Bile duct: fle adult worm can cause obstruction of the oligarthrus) or bush dogs (E. vogeli) are the deffnitive bile duct and dilatation of the biliary tract and biliary host, whereas rodents are the intermediate host cirrhosis. It does not cause malignancies ™ Clinical features: E. vogeli infects most commonly liver ™ Halzoun or Marrara syndrome: In endemic areas (e.g. (80%) followed by lungs and other viscera. Symptoms Lebanon or Sudan) where uncooked goat and sheep are similar to cystic echinococcosis livers may be eaten, the adult worms may attach to ™ Epidemiology: Till date, over 200 cases of polycystic the pharyngeal wall; causing severe pharyngitis and hydatid disease have been reported, mainly from South laryngeal edema. America. Only three cases of E. oligarthrus are reported so far Laboratory Diagnosis ™ Laboratory diagnosis and treatment are similar to that ™ Stool microscopy reveals characteristic operculated eggs, of E. granulosus. measuring130–150 μm × 63–90 μm in size (Fig. 49.7A). Concentration techniques (by sedimentation methods) TREMATODE INFECTIONS OF LIVER can be followed to increase the sensitivity. Floatation Fasciola, Clonorchis, Opisthorchis are together called as methods are not useful. Egg of F. hepatica is similar to liver Thukes. Fasciola infect liver and bile duct, whereas the that of Fasciolopsis buski others infect only the bile duct. ™ Antibody detection: ELISA or western blot are available to detect serum antibodies against excretion secretion Life Cycle antigen. It helps in the early diagnosis before the eggs Life cycle of liver Thukes is similar to as described for other are detected in stool, useful for the seroepidemiological trematodes, except schistosomes (Chapter 46, Figure 46.12). study and to monitor the response to treatment  CHAPTER 75  Parasitic and Fungal Infections of Central Nervous System 735 ™ Treatment: Artesunate, artemether, arteether and water containing eggs of T. solium, and (2) autoinfection quinine are the drugs used for treatment of cerebral (described below) malaria (Chapter 35). Autoinfection AFRICAN SLEEPING SICKNESS Eggs excreted in the feces reinfect the same individual. Autoinfection can be of two types: Trypanosoma brucei (T.b.) gambiense and T. b. rhodesiense 1. External autoinfection: Due to unhygienic personal are the causative agents of Western and Eastern African habit, e.g. contaminated ffnger. sleeping sickness respectively (Chapter 36). It is transmitted 2. Internal autoinfection: Due to reverse peristaltic by tsetse Thy, inoculating the infective form—metacyclic movements by which the gravid segments throw the trypomastigotes. eggs back into the stomach (equivalent to swallowing ™ Pathogenesis: It begins with hemolymphatic stage (i.e. of the eggs). Note: A prior episode of intestinal taeniasis is a prerequisite dissemination of the parasite through the lymphatics for development autoinfection. Intestinal taeniasis and bloodstream), which proceeds to the next stage is transmitted by ingestion of uncooked pork meat with invasion of CNS particularly pons, medulla and contaminated with larvae (cysticercus cellulosae), which frontal; which leads to steady progressive chronic develop into adult worms that sexually mature (self- meningoencephalitis fertilize) to produce eggs in the gut. ™ Clinical manifestations: Patients develop characteristic progressive daytime somnolence (hence called as ™ Human cycle: μe embryo or oncosphere is released “sleeping sickness”), with restlessness and insomnia at from the eggs, penetrates the intestine and enters into night which may be related to increased prostaglandin the portal circulation or mesenteric lymphatics and D2 level in the body reaches to various organs like subcutaneous tissue, „ Behavioral and personality changes with apathy, muscle, eye and brain where it is transformed to the confusion, fatigue and loss of coordination may be larval stage; cysticercus cellulosae in 7–9 weeks and observed deposited as cyst. Full development to mature cysts „ Other features include listless gaze, loss of spontaneity, takes 2–3 months of time. and abnormal speech with few extrapyramidal Cysticercus Cellulosae signs like choreiform movements, tremors and fasciculations A mature cysticercus cellulosae measures 5 mm long „ In the terminal stage, the patient becomes emaciated and 8–10 mm wide, spherical (or slightly oval), yellowish progressing to coma and death, usually from white, separated from the host tissue by a thin collagenous secondary infection. capsule. ™ Duration: West African form is a chronic disease, lasting ™ It contains two chambers: Outer one is a bladder like for months to years; whereas East African disease runs sac fllled with 0.5 mL of vesicular Thuid and the inner an acute course with duration 20 cm), containing in the difierential diagnosis of CNS infections in these 60 mL of vesicular Thuid patients. „ They do not contain scolices within the bladder, resemble metastatic tumor Other Forms of Cysticercosis „ Mainly found in brain (fourth ventricle and ™ Subcutaneous cysticercosis : It is frequently subarachnoid space), and cervical spinal cord asymptomatic but may manifest as palpable nodules „ It is associated more frequently with HIV infected ™ Muscular cysticercosis: Manifest as muscular pain, patient weakness or pseudohypertrophy „ Patients present with increased intracranial pressure ™ Ocular cysticercosis: Can involve eyelids, conjunctiva and frequently require surgery and sclera. Common symptoms like proptosis, diplopia, „ μe prognosis of racemose cysticerci is poor. loss of vision and slow growing nodule with focal inThammation. Clinical Manifestations (Cysticercosis) Clinical spectra of the disease depend upon the localization Epidemiology of the cyst. μough it is discovered from any site of the World body, but the common sites are CNS, subcutaneous tissue, Cysticercosis is a major public health problem, especially skeletal muscle and eyes. in the developing world. ™ T. solium infection is endemic in Mexico, Central Neurocysticercosis America, South America, Africa, Southeast Asia, India, Neurocysticercosis (NCC) is the most common form of Philippines, and Southern Europe cysticercosis; accounts for 60–90% cases of cysticercosis. ™ NCC is the most frequent preventable cause of epilepsy ™ NCC is considered as the most common parasitic CNS worldwide. According to WHO, 30% of all epilepsy cases infection of man and the most common cause of adult in endemic countries and 3% epileptic cases globally may onset epilepsy throughout the world be due to NCC ™ Age: Adults of 30–50 years of age are afiected commonly ™ However, it is reported less from the Muslim countries ™ Types: Based on the site of involvement, NCC is of two (as pork eating is not allowed). types: 1. Parenchymal: Involves brain parenchyma ; India considered as the most common site of NCC Cysticercosis is highly prevalent in the northern states such 2. Extraparenchymal sites are meninges, ventricles, as Bihar, Odisha, Uttar Pradesh and Punjab. spinal cord and subarachnoid space. ™ It is believed that NCC is largely underreported in India, ™ Asymptomatic NCC: Sometimes NCC remains in the accounting for 2–3% of epileptic cases brain without causing any apparent symptoms ™ The underreporting is because of lack of systematic ™ Seizure is the most common manifestation (70% of population-based studies and unavailability of imaging cases). NCC accounts for 50% cases of late-onset epilepsy techniques in rural areas. ™ Hydrocephalus: It is the most common extra parenchy- mal feature. Its presence carries a bad prognosis L ABORATORY DIAGNOSIS Cysticercosis ™ Other clinical features include: ‰ Radiodiagnosis—CT scan and MRI (useful for detecting „ Increased intracranial pressure and hypertension- number, location, size of the cysticerci and the stage of the presented as headache, vomiting and vertigo disease) „ Chronic meningitis ‰ Antibody detection in serum or CSF— „ Focal neurological deflcits ¾ ELISA (using crude extract of cysticerci) „ Psychological disorders and dementia ¾ Western blot (using 13 kDa LLGP Ag) „ Cerebral arteritis (associated with subarachnoid ‰ Antigen detection in serum or CSF—ELISA cysticercosis) ‰ Lymphocyte transformation test „ Basal and ventricular involvement: Carries poor ‰ Histopathology of muscles, eyes, subcutaneous tissues or prognosis. brain biopsies—can detect cysticerci ‰ FNAC of the cyst and then staining with Giemsa ™ NCC exists in four morphological stages: It starts as ‰ Fundoscopy of eye—detects larvae vesicular form, gradually develops into necrotic, followed portant ‰ Modiffed Del Brutto diagnostic criteria. by nodular and flnally into calcifled stage ™ μe clinical presentation is variable and depends on Laboratory Diagnosis number, location and size of the cyst, the morphological stage of the cyst and the host immune response Radiodiagnosis (Imaging Methods) ™ NCC and HIV: NCC co-infection is likely to be increasingly CT scan and MRI are the two important imaging methods recognized in patients with HIV and should be included used to detect cysticerci in brain.  CHAPTER 75  Parasitic and Fungal Infections of Central Nervous System 737 ™ Because of the vesicular structure, live cysticerci its speciflcity is low as it gives false positive results in cross appear hypodense (low signal intensity) area and the reacting helminthic infections such as echinococcosis scolex is present eccentric inside the vesicle and gives a ™ QuickELISA: It is a quantitative ELISA, available hyperdense (high signal intensity) area commercially. It detects antibodies in serum against ™ Imaging methods are useful to identify: T24H recombinant antigen. Results are comparable to „ μe number of cysts (single or multiple cysticerci) western blot, has a sensitivity of 96% and speciflcity 99%. „ Location of the cyst (parenchymal or extra- Western blot: Western blot assay [also called as enzyme parenchymal) immune transfer blot (EITB)] uses highly speciflc 50-13 kDa „ Size of the cyst (small—cysticercus cellulosae and big lentil lectin-purifled seven glycoprotein (LLGP) antigenic cyst—cysticercus racemosus) fractions; hence its speciflcity approaches 100%. „ μe stage of the disease (vesicular, necrotic, nodular ™ Presence of one to seven Gp bands confirms the and calcifled) diagnosis „ Extent of the lesion ™ It can be performed on serum, blood, dried blood spot „ Active or dormant lesion: Associated inThammation or CSF and edema gives a ring-like enhancement surroun- ™ The sensitivity and specificity are 98% and 100% ding the cysts, indicates acute infection. respectively in persons with multiple viable cyst ™ CT scan is useful to detect calcifled cysts (appears as ™ μe sensitivity is directly proportional to the number of hyperdense dots) (Fig. 75.12) live cysticerci. ™ MRI has a higher contrast resolution, which makes the However, antibody detection methods have lesion clearer. It is superior than CT scan to detect the: disadvantages—(1) cannot difierentiate active and past „ Extraparenchymal cysts in ventricle and cisterns infection, (2) antibodies persist even after recovery of the „ InThammatory changes patient. „ Vesicular and necrotic lesions „ Noncystic lesions. 2. Antigen Detection Antigen detection in CSF or serum by ELISA has been Immunodiagnosis developed using monoclonal T. solium antibodies. Antigen It has the advantage of lower cost than CT and MRI and disappears following treatment hence, can be used for conflrms the etiology. monitoring. 1. Antibody Detection Histopathology ELISA: ELISA detects antibodies in serum and CSF by Cysticerci can be detected in muscles, eyes, subcutaneous using crude extract of cysticerci or vesicular Thuid. tissues (or brain during postmortem) by biopsy following ™ It is highly sensitive (75–90%) in serum. CSF ELISA also surgical removal or fine needle aspiration of the cyst gives better results followed by microscopic demonstration of the parasite ™ Moreover, recent ELISA method using purified (Fig. 75.13). glycoprotein antigens has shown better sensitivity but Fine-needle Aspiration Cytology (FNAC) Fine-needle aspiration of the cyst can be done followed by staining with Giemsa, or Ryan’s modiflcation of trichrome stain. ™ Microscopically, it can differentiate between viable, necrotic and calcified cysticerci through their morphological pattern ™ Cholesterol crystals are frequently seen which may be attributed to the high lipid content of the lesions. Charcot-Leyden crystals are characteristically absent. Fundoscopy Ocular cysticercosis can usually be diagnosed by fundoscopy for the visual identiflcation of the movements and morphology of the larval worm. Fig. 75.12: CT scan of brain showing multiple ring enhancing Revised DelBrutto’s Diagnostic Criteria lesions with eccentric scolex (neurocysticercosis). Source: Dr A Subathra. Department of Radiodiagnosis, JIPMER, Puducherry DelBrutto’s criteria has been widely used for the diagnosis (with permission). of NCC in endemic countries since 2001. It has been revised 738 SECTION 9  Central Nervous System Infections and T. ovis recombinant antigens are attempted for vaccination of pigs. μey are under development. RARE PARASITIC INFECTIONS OF CNS μe following are the rare parasitic agents infecting CNS. μey are either—(1) common human pathogens producing infections elsewhere and occasionally infect CNS (e.g. E. histolytica, Strongyloides) or (2) primary pathogens of lower animals and human infection is rare (e.g. Angiostrongylus). Rare Protozoan Infections of CNS Entamoeba histolytica: Hematogenous spread of trophozoites can occur from liver afiecting brain causing brain abscess and secondary amoebic encephalitis (Chapter 45). Fig. 75.13: Cysticercus cellulosae in biopsy from the brain (hematoxylin and eosin stain)—An entire cysticercus seen within Rare Cestode Infections of CNS the bladder walls, [Parenchymatous portion of the cysticercus can ™ Taenia multiceps: It is a cestode, infecting dog and other be better observed. The extensive folding of the spiral canal and animals one sucker of the scolex (Arrow)]. „ Human infection is rare, producing space occupying Source: Head, Department of Pathology, Meenakshi Medical College, Chennai (with permission). lesion in CNS similar to NCC due to deposition of larval stage called as coenurus in CNS. μerefore, the in 2016. It is based on clinical, imaging, immunological and disease is called as coenurosis epidemiological data. „ Nearly 175 cases have been reported in humans so far; mainly from developing countries where the T REATMENT Cysticercosis dog population is not controlled such as African Antiparasitic agents: countries. ‰ For brain parenchymal lesions: ™ Spirometra: It is another cestode of dogs and cats ¾ Albendazole (15 mg/kg per day for 8–28 days) or „ Human infection is extremely rare, results in deposition ¾ Praziquantel (50–100 mg/kg daily in three divided doses of its larva (called sparganum) in various tissues such for 15–30 days) as subcutaneous tissues, muscles, eyes and visceral ‰ Longer courses are often needed in patients with multiple organs like brain (frontal and parietal lobes) and subarachnoid cysticerci lymphatics. μe disease is called as sparganosis Symptomatic treatment of: „ Presents with various neurological symptoms ‰ Seizures by antiepileptic drugs including weakness, headache, seizure, and abnormal ‰ High-dose glucocorticoids should be used to reduce the skin sensations, such as numbness or tingling. inμammatory reactions caused by dead cysticerci ™ Echinococcus: Hydatid cyst may get deposited in brain ‰ Hydrocephalus: Attempts should be made to reduce intrac- ranial pressure. In the case of obstructive hydrocephalus, very rarely (3% of cases) and spinal cords. (discussed in cysticerci can be removed by endoscopic surgery or ventricu- detail in Chapter 49). loperitoneal shunting. Surgery: Rare Trematode Infections of CNS ‰ Open craniotomy to remove cysticerci is rarely required ™ Neuroschistosomiasis: It is rare complications seen with nowadays Schistosoma infection (Chapter 46). Myelopathy of the ‰ Surgery is indicated for ocular, spinal and ventricular lumbosacral region is the most common neurological lesions because antiparasitic drugs can provoke irreversible manifestation of S. mansoni or S. haematobium infection, inμammatory damage. whereas acute encephalitis is the most common feature Prevention of S. japonicum μe prevention of cysticercosis involves: Cerebral Schistosomiasis ™ Good personal hygiene to prevent autoinfection with Acute encephalitis is the common CNS presentation of S. eggs japonicum infection. ™ Efiective fecal disposal to prevent contamination of food ‰ It occurs in 2–4% of cases due to migration of eggs and water with eggs ‰ Parietal lobe is the most common site ™ Treatment and prevention of human intestinal taeniasis ‰ Symptoms include Jacksonian convulsions and grand mal seizures ™ Vaccines to prevent porcine cysticercosis: Various antigens like T. solium oncosphere antigen, T. crassiceps Contd...  CHAPTER 75  Parasitic and Fungal Infections of Central Nervous System 739 Contd... Other rare nematode infections of CNS are: ™ Loa loa: It is a filarial nematode causing cutaneous ‰ The higher incidence of CNS involvement of S. japonicum and ocular infections (Chapter 57). It rarely can cause compared to other schistosomes is attributed to their meningoencephalitis small size eggs; which are released in higher numbers „ It occurs in DEC treated patients with higher from the worm, and can be carried easily to CNS. microfilaremia; antigens released from the dead ™ Cerebral paragonimiasis: It is the most severe form of larvae may induce inThammatory reaction paragonimiasis (Chapter 69). Encapsulated cysts in the „ It can be prevented by administration of anti- brain parenchyma present as space-occupying lesions. inThammatory drugs along with DEC Symptoms include fever, headache, vomiting, motor „ DEC should be stopped if any neurological symptoms weakness or epilepsy. appear. ™ Trichinella spiralis: It is a somatic nematode that Rare Nematode Infections of CNS usually produce cystic lesions in muscle (Chapter 57). Hyperstrongyloidiasis Syndrome Occasionally the larvae may migrate to CNS producing encephalitis In Strongyloides infection, repeated autoinfection cycles ™ Toxocara: It is a parasite of lower animals, causes visceral occur occasionally which result in generation of large larva migrans, mainly afiects liver, occasionally involve number of filariform larvae, which penetrate the GIT brain, resulting in seizures (Chapter 49) and migrate to various organs including CNS causing ™ Baylisascaris procyonis: It is also parasite of lower disseminated strongyloidiasis. animals, and also a rare cause of neural larva mi- ™ CNS invasion causes brain abscess and meningitis. grans, producing fatal eosinophilic meningoen- Larvae can be seen in the CSF occasionally cephalitis ™ CSF examination shows pleocytosis, elevated protein, ™ Gnathostoma spinigerum: It is also a parasite of lower normal glucose and negative for bacterial culture animals that rarely infects man. It usually produces ™ μe mortality rate in untreated patients approaches 100% cutaneous swellings. Rarely, the larvae may spread to and even with treatment it may exceed 25% CNS producing eosinophilic meningoencephalitis. ™ Risk factors: Glucocorticoid therapy is the main risk factor. Other risk factors include immunosuppressive conditions such coinfection with human T cell FUNGAL INFECTIONS OF CNS lymphotropic virus type-1 (HTLV-1). Various fungal agents can cause CNS infections Strongyloidiasis is discussed in detail in Chapter 46. (mainly chronic meningitis), out of which Cryptococcus neoformans is the most important. Other fungi infecting Angiostrongylus cantonensis Infection CNS predominantly cause infections of other systems and Also called as the rat lung worm, produces a form of therefore discussed elsewhere (Table 75.3). visceral larva migrans (Chapter 49) afiecting CNS called, eosinophilic meningitis. μis infection occurs principally CRYPTOCOCCAL MENINGITIS in Southeast Asia. Cryptococcal meningitis is caused by a capsulated yeast ™ Human acquires infection by ingestion of L3 larvae in called Cryptococcus neoformans, which is capable of undercooked intermediate host or in contaminated producing potentially fatal meningitis in HIV infected water. μe larvae penetrate the intestine and through people. the blood circulation, migrate to the CNS and develop into adult worms Species and Serotypes ™ As man is an abnormal host, the life cycle gets arrested, Cryptococcus has two species, C. neoformans and C. gattii worms die producing a local eosinophilic inThammation and four serotypes A, B, C and D. and granuloma formation around the dying worms ™ Patients usually present with headache, neck stifiness, Table 75.3: Fungal agents causing CNS infections. nausea and vomiting, and paresthesia ™ Diagnosis: Examination of CSF can reveal—increased Primary CNS pathogen: Cryptococcus neoformans CSF pressure, protein and WBC count, eosinophilic Fungi which primarily cause infections of other body sites, pleocytosis of more than 20%, and normal glucose level rarely cause CNS infections Agents of systemic mycoses: Blastomyces dermatitidis, „ Larvae or young adult worms can often be recovered Histoplasma capsulatum and Coccidioides immitis in the CSF Agents of subcutaneous mycoses: Sporothrix schenckii, „ Peripheral blood eosinophilia may be mild. Pseudallescheria boydii and Cladophialophora bantiana ™ Treatment: Management consists of supportive mea- Opportunistic fungal agents : Candida albicans, Aspergillus sures, including analgesics, sedatives and glucocorti- species and Mucor (rhinocereberal mucromycosis) Others: Microsporidia coids. 570 SECTION 7  Skin, Soft Tissue and Musculoskeletal System Infections ™ Provision of clean drinking water from boreholes or wells (was a major source of infection) ™ Health education about boiling or filtering of drinking water ™ Treatment of cases. TRICHINELLOSIS A B Trichinella spiralis causes trichinellosis (or trichinosis), Figs 57.4A and B: Dracunculiasis: A. Blister formed; B. Adult female which is a zoonotic infection acquired from domestic pigs worm of Dracunculus medinensis emerging from the blister. or other carnivores. Source: DPDx Image Library, Centers for Disease Control and Prevention (CDC), Atlanta (with permission). Epidemiology ™ Characterized by painful blister from which the female Human trichinellosis is widely prevalent in the pork eating worm emerges, accompanied by local erythema, fever, countries (more in temperate zone than tropics) like nausea and pruritus (Fig. 57.4A) Europe and America. It is very rare in India, except for the ™ The most common sites—lower leg, ankle and foot outbreak in 2010, which occurred in Uttarakhand aflecting ™ Secondary bacterial infections may occur at the bister 18 people eating roasted wild boar meat called kachmoli. site. Morphology Laboratory Diagnosis Like other somatic nematodes, it has an adult worm (1.5– Dracunculiasis is diagnosed by: 3 mm long), and four stages of larvae. There is no egg stage. ™ Detection of adult worm: This is possible when the L1 larva is the infective form, which forms cysts in muscles. gravid female worms appear in the blisters (Fig. 57.4B). Life Cycle (Fig. 57.5) The calcified adult worms from the deeper tissue can be detected by X-ray The life cycle involves one host— usual host is pig (or other ™ Detection of L1 larvae: When the leg with ulcer is placed animals); man is an accidental host and acts as dea