INFECTIOUS DISEASE PART II

INFECTIOUS DISEASE PART II
By Camille-Marie A. Go

PROTOZOA

SARCODINA (AMOEBAE) ENTAMOEBA histolytica
90% commensal strain – Amoebic infection (asymptomatic) 10% invasive strain – Amoebic disease MOT – ingestion of mature cyst

SARCODINA (AMOEBAE) ENTAMOEBA histolytica Distribution
1. Inadequate sanitation 2. Poor personal hygiene Infective state – mature 4-nucleated cyst Diagnostic stage – cyst and trophozoite Different from E. coli DDx – bacillary dysentery

AMOEBIC BACILLARY DYSENTERY DYSENTERY Gradual onset Acute onset
(-) Fever, vomiting (+) fever, vomiting Bloody, mucoid Watery, bloody Offensive smell Odorless Acid pH Alkaline pH Few pus cells Many pus cells (+) Motile amoebae (-) Amoebae

SARCODINA (AMOEBAE) Extraintestinal Amoebiasis
Liver – most common site (post ® lobe) Adults; men (3:1) Skin, CNS, Lungs

SARCODINA (AMOEBAE) DIAGNOSIS Fecalysis – cyst – formed and semiformed
-troph.–dysenteric (w/in15”) - Rectal smear (Prostoscopy) Rectal biopsy Liver (Abscess wall) biopsy Serological (Extraintestinal)

SARCODINA (AMOEBAE) Treatment Metronidazole Iodoquinol
*NAEGLERIA fowleri–Primary Amoebic Meningoencephalitis (PAM)

CILIOPHORA (CILIATES)
BALANTIDIUM coli Only ciliate that parasitizes man NH-pigs; MOT- ingestion of cyst Infective stage – cyst (No incubation) Diagnostic stage – cyst (formed and semiformed stool) - Trophozoite (dysenteric stools)

CILIOPHORA (CILIATES)
BALANTIDIUM coli Causes bloody mucoid diarrhea Diagnosis by Rt. Fecalysis Treatmnent – drug of choice – Iodoquinol

MASTIGOPHORA (FLAGELLATES)
GIARDIA lamblia Humans as only reservoir infection MOT – ingestion of cyst Infective stage – cyst (no incutation) Diagnostic stage – cyst (formed and semiformed stool) - Trophozoite (in diarrheic stools)

GIARDIA lamblia Duodenum, jejunum Prevalent among children Causes Villous Atrophy – Malabsorption and lactose intolerance; steatorrhea Predisposition: GIT disorders, bacterial infection of intestine; hypochloridia, pancreatic disease

GIARDIA lamblia Diagnosis: Routine Fecalysis Duodenal aspirate Enterotest capsule Treatment: Metronidazole Quinacrine HCl – drug of choice

TRICHOMONAS vaginalis
MOT -sexually transmitted common cause of acute vaginitis with yellow–green purulent discharge in females (urinary frequency) Causes urethritis and purulent discharge in males Infective stage: Flagellates (No cyst stage)

TRICHOMONAS vaginalis
Treatment: Metronidazole Both partners * T. hominis * T. intestinalis

TRYPANOSOMA b. rhodesiense (zoonosis) TRYPANOSOMA b
TRYPANOSOMA b. rhodesiense (zoonosis) TRYPANOSOMA b. gambiense (humans mostly) Cause African sleeping sickness M.O.T. – bite of tsetse fly (Glossina) and blood transfusion Infective stage – Metacyclic trypomastigote Diagnostic stage – Trypomastigote (peripheral blood)

DIAGNOSIS Peripheral Blood Smear Aspirate of lymph node Chancre fluid
CSF Morula (MOTT) cells TP (IgM)

TREATMENT Pentamidine Drug of Choice:
Suramine (Early hemolymphatic stage) Metarsoprol (Late stage) – CNS Involvement

TRYPANOSOMA cruzi (Zoonosis)
Endemic in S. America Causes Chaga’s disease MOT- Bite wound made by kissing bug (Triatoma or Rhodnius) is contaminated by rubbing bug’s feces containing metacyclic trypomastigote - Via blood transfusion - Transplacental route

Infective stage – Metacyclic trypomastigote Diagnostic stage – Trypomastigote (C-shaped) SSx: Early – Chagoma (Romana’s sign) Late – Cardiomegaly Mega-esophagus Mega-colon

DIAGNOSIS Peripheral blood smear Xenodiagnosis Blood culture IgM determination TREATMENT Nifurtimox, Bezuidazole

LEISHMANIA donovani (Zoonosis)
Endemic in S. and C. America, Europe, Africa, Asia (esp. India); Local cases (OCW’s) Causes visceral Leishmaniasis/Kalaazar MOT – bite of sandfly (Phetobotomus or Lutzomyia) Congenital/transplacental Sexual contact Blood transfusion

Infective stage: Promastigotes Diagnostic stage: Amastigotes in macrophages Pathology: Blockage and destruction of R.E.S.

DIAGNOSIS Peripheral blood monocytes Aspirate of bone marrow, lymph node, spleen Formol get test (non-specific; increased IgG (+) Gelling and Whitening of serum

TREATMENT Antimony compounds e.g. Sodium Stibogluconate – drug of choice N. methyl – Glucamine Pentamidine isothionate

PLASMODIUM

PLASMODIUM falciparum
Causes malignant tertian malaria Most prevalent in the world, in the Phil. Most pathogenic- Cytoadherence MOT – bite of Anopheles mosquito 1° vector- A.minimus flavirostris 2° vector- A. balabacencis A. littoralis A. mangyanus *Potential vector: A. maculatus

Parasitizes red cells of all ages Schizogony, sporogony Severe Falciparum Malaria Cerebral malaria Anemia Blackwater fever Diarrhea/Vomiting (GIT) Pulmonary edema ± renal failure Hypoglycemia

In pregnancy – abortion, premature labor, stillbirth, neonatal death, low-birth weight infants Hyperactive malaria splenomegaly Recrudescence Vaccine production fails because of antigenic variation

Diagnosis: Clinical: History of travel, SSx Laboratory: Thick and thin blood smears Maurer’s dots Ring forms (young trophozoites), Accoele forms Crescent/Banana-shaped gametocytes Immunofluorescent (Q.B.C.) Serological

Treatment: Quinine, Quinidine Quinhaosu derivatives: Artemisin, Artesunate, Artemether

PLASMODIUM vivax Causes benign tertian malaria
Parasitizes young red cells (reticulocytes) Rarely found in E. Africa (-) Duffy blood group antigen Fya and Fyb Relapses due to hypnozoites Common etiology of transfusion malaria

PLASMODIUM vivax DIAGNOSIS: Enlarged red cells Schuffner’s dots
TREATMENT: Chloroquine + Primaquine * Plasmodium malariae Quartan malaria, nephrotic syndrome Older red cells; Ziemann’s stippling, daisy schizont; band form; bird’s eye form Recrudescence

* Plasmodium ovale Causes Ovale Tertian Malaria Relapses
Young cells; red cells become slightly enlarged, oval-shaped with fimbriated (ragged) ends; James dots

CRYPTOSPORIDIUM sp. (Zoonosis)
Common among AIDS patients Common cause of diarrhea in children <5 y/o and non-breast fed infants Habitat: small intestine MOT – ingestion of oocyst Infective and Diagnostic stage: oocyst

CRYPTOSPORIDIUM sp. (Zoonosis)
DIAGNOSIS: Rt. Fecalysis - Sugar floatation technique Fecal smear stained with: Modified (Kinyoun’s) Acid Fast staining technique Safranin-Methylene Blue TREATMENT: Spiramycin

TOXOPLASMA gondii (Zoonosis)
Nat. host/Def. host – cat Humans. Other mammals – Int. host Common among immunocompromised individuals, e.g. AIDS patients MOT – ingestion of oocyst Eating uncooked meat of IH Blood transfusion

TOXOPLASMA gondii(Zoonosis)
Transplacental/Congenital: Most serious form Pathology Acute stage: Tachyzoites – phagocytes Late stage: Bradyzoites – visceral organs (pseudocyts)

Clinical forms Lymphadenopathy Ocular toxoplasmosis Myocarditis Meningoencephalitis Atypical pneumonia Congenital toxoplasmosis Increased IgM Cerebral calcification

DIAGNOSIS: Aspirate of lymph node, bone marrow, spleen CSF, pleural or peritoneal fluid, sputum Serological: IgM Sabin-feldman dye test (Live toxoplasms)

TREATMENT Pyrimethamine Sulfadiazine

PNEUMOCYSTIS carinii Common cause of death in AIDS patients
Common among malnourished children MOT – droplet infection Infective and Diagnostic stage: Cyst/Trophozoite Pathology: Interstitial (viral-like) pneumonia

PNEUMOCYSTIS carinii DIAGNOSIS: Transbronchial Lung Biopsy;
Cell Imprint Stains: Methenamine Silver or Gram–Weigert Giemsa

PNEUMOCYSTIS carinii TREATMENT Pentamidine TMP-SMZ – drug of choice

HELMINTHS PLATYHELMINTHES (Flat worms) TREMATODA (Digenetic flukes)

FASCIOLOPSIS buski Largest intestinal fluke
MOT – ingestion of metacercaria Infective stage: Metacercaria Diagnostic stage: Immature egg DH – man, pigs, buffalo IH 1 – Segmentina, Hippeutis IH 2 – Water caltrop, water chestnut

FASCIOLOPSIS buski DIAGNOSIS – Rt. Fecalysis TREATMENT – Praziquantel

ECHINOSTOMA ilocanum Garrison’s fluke
Endemic in the Phil. (N. Luzon, Leyte, Samar, Mindanao) Adult Habitat – Small intestine DH – man IH 1 – Gyraulus, Hippeutis IH 2 – Pila luzonica

ECHINOSTOMA ilocanum Diagnosis: Eggs in feces
Treatment: Praziquantel, Hexylresprcinol

PARAGONIMUS westermani
Oriental lung fluke MOT – ingestion of metacercaria Infective stage: Metacercaria Diagnostic stage: Immature egg DH – man, rodents, domesticated animal IH 1 – Semisulcospira, Thiara IH 2 – Crab, crayfish, shrimps

Habitat – Bronchioles Causes PTB–like SSx Cough, night sweats , chest pains, hemoptysis DIAGNOSIS: Eggs in sputum, feces Treatment: Praziquantel

Clonorchis sinensis – Chinese Liver Fluke Cholangiocarcinoma Metagonimus yokogawai – smallest fluke that parasitizes man Heterophyes heterophyes – causes cardiac beriberi Dicrocoelium dendriticum – IH2 is an ant

SCHISTOSOMES CLASSIFICATION Superfamily schistosomatoidea
S. haematobium S. mansoni S. japonicum S. mekongi

SCHISTOSOMES FEATURES Adult habitat – venous plexuses Sexes- separate
Shape – cylindrical Definitive host – humans only 1st I.H. – snails; NO 2nd I.H. Transmission – skin penetration Lab. diagnosis – eggs in urine, feces, rectal scrapings

SCHISTOSOMA hematobium
Endemic in Africa, Middle East Causes urinary Schistosomiasis Spread and construction of irrigation channels and dams for hydroelectric power and flood control MOT – skin/mucosal penetration by cercariae

Infective stage: cercaria Diagnostic stage: mature egg D.H. – man Adult habitat – Urinary bladder I.H. – Bulinus Pathology: Granulomata formation Hematuria Squamous cell carcinoma

Diagnostic stage: urine – egg with terminal spine Treatment: Praziquantel

SCHISTOSOMA mansoni Causes intestinal schistosomiasis
MOT – skin penetration by cercariae Infective stage: cercariae Diagnostic stage: mature egg D.H. – Man I.H. - Biomphalaria

SCHISTOSOMA mansoni Adult habitat – Inf. mes. veins
Pathology: Granulomata formation Bloody mucoid diarrhea Rectal polyps Claypipe-stem fibrosis  Portal HPN; Esophageal varices, Splenomegaly

SCHISTOSOMA mansoni Diagnosis: Fecalysis- egg with prominent lateral spine Treatment: Praziquantel

SCHISTOSOMA japonicum
Causes intestinal schistosomiasis MOT – skin penetration by cercaria Infective stage – cercaria Diagnostic stage – mature egg DH – man, rodents,etc. IH – Oncomelania quadrasi Adult habitat – sup. mes. veins

SCHISTOSOMA japonicum
Pathology – similar to S. mansoni Katayama reaction Egg output – 1500 – 3500 eggs/day Diagnosis: Feces – egg w/ vestigial lateral spine Serum – C.O.P.T. Treatment: Praziquantel S. mekongi – Mekong River Basin (Laos, Kampuchea, Thailand Swimmers’ itch

CESTODA (Tapeworms)

TAENIA solium Taeniasis – ingestion of measly pork containing cysticerci Cysticercosis – ingestion of eggs Regurgitation of gravid proglottid into the stomach

TAENIA solium Diagnosis: Scolex with 4 suckers and 2 rows of hooks
Taeniasis – finding of adult segments or eggs in the stool Cysticercosis – radiological (radiolucent or radio-opaque cysts along limb soft tissue parts - serological

TAENIA saginata More prevalent worldwide; in R.P.
MOT – ingestion of cysticerci in undercooked, infected beef Cysticercosis bovis not seen Scolex with 4 suckers and no hooks Diagnosis: Fecalysis Adult proglottid - >13 main lateral uterine branches Cellophane (Scotch) tape swab

ECHINOCOCCUS granulosis (Zoonosis)
Endemic in sheep-raising countries Causes hydatid disease/hydatidosis MOT – ingestion of eggs Infective stage – eggs Diagnostic stage – eggs and adult DH – dogs Accidental host – man IH - sheep

ECHINOCOCCUS granulosis (Zoonosis)
Pathology: Hydatid cyst: 60% in ® liver, others in lungs, bone, brain, kidney, spleen Rupture of cyst – Anaphylactic shock Diagnosis: X-ray Cyst fluid Serological Casoni skin test – intradermal test Mx: Surgical removal/extirpation

DIPHYLOBOTHRIUM latum
Largest fish tapeworm MOT – ingestion of plerocercoid Infective stage: Plerocercoid in undercooked or raw freshwater fish DH – humans and fish–eating animals IH 1 – crustaceans (procercoid) cyclops Diaptomus IH 2 – freshwater fish

DIPHYLOBOTHRIUM latum
Pathology: Mechanical intestinal obstruction Megaloblastic/Pernicious anemia Treatment: Praziquantel *Sparganosis (Spirometra)

NEMATHELMINTHES (Round worms)

ASCARIS lumbricoides Large intestinal roundworm
MOT – ingestion of embryonated ova Distn  inadequate sanitation; use of night soil

ASCARIS lumbricoides Pathology:
Loffler’s syndrome (Heart–lung migration) Malnutrition Intestinal obstruction Erratic behavior or adult Diagnosis: Eggs and adult worm in feces Treatment: Pyrantel pamoate, Mebendazole

ENTEROBIUS vermicularis
Pinworm, Seatworm, Threadworm MOT Ingestion of D-shaped embryonated eggs/fecal-oral route Airborne/Inhalation of embryonated eggs Autoinfection via mouth and/or anus (retroinfection) Adult Habitat – caecum, appendix

ENTEROBIUS vermicularis
Cepahalic alae Pathology: Nocturnal anal pruritus in children Diagnosis: Cellophane(Scotch)tape swab Urinalysis (occasionally) Treatment: Pyrantel pamoate Mebendazole

STRONGYLOIDES stercoralis
Dwarf threadworm MOT – skin penetration by filariform larva, transmammary route, internal autoinfection Infective stage – Filariform larva Diagnostic stage – Rhabditiform larva

STRONGYLOIDES stercoralis
Pathology: Heavy infection  malabsorption with steatorrhea, Larva currens; free-living phase Diagnosis: Fecalysis Harada-Mori culture tech. Enterotest Treatment: Albendazole Thiabendazole

TRICHURIS trichiura Whipworm MOT – ingestion of bipolar-plugged ova
Pathology: Chronic cases  rectal prolapse; prone to 2ndy E. histolytica infection Diagnosis: Fecalysis, Proctoscopy Treatment: Albendazone, Mebendazole, O. pyrantel

HOOKWORMS MOT – skin penetration by filariform larva; mucosal; transmammary; transplacental Hookworm infection vs. Hookworm disease Pathology: A. duodenale – more blood loss (0.15 ml/day) Ground itch Respiratory problems – petechial hemorrhages Hookworm anemia – iron deficiency, hypochromic, microcytic; hypoalbuminemia * Creeping Eruption by non-human hookworms

HOOKWORMS Diagnosis: Fecalysis Harada Mori culture tech
Treatment: Mebendazole Pyrantel pamoate

CAPILLARIA philippinensis
Small whipworm, Pudoc worm Nat. host – fish-eating birds Endemic in N. Luzon, Bohol, Leyte, Mindanao M.O.T. – ingestion of infective eggs in undercooked or raw fish (Bacto, Bagsit, Bagsan)

CAPILLARIA philippinensis
Pathology: Internal autoinfection Intestinal gurgling (Borborygmi) Chronic watery diarrhea; F/E IMB Diagnosis: Eggs in feces Treatment: Mebendazole

WUCHERERIA bancrofti Causes Bancroftian lymphatic filariasis
Most prevalent worldwide, in the Phil. Microfilaremia and periodicity Mosquito vectors: Anopheles, Aedes, Culex MOT – mosquito bite

WUCHERERIA bancrofti Pathology: Diagnosis: Thick & Thin Smears (12 MN)
Recurrent lymphangitis, fever Elephantiasis (Whole lower limb) Hydrocoele Chyluria Tropical pulmonary eosinophilia Diagnosis: Thick & Thin Smears (12 MN) Treatment: Diethylcarbamazine (DEC)

BRUGIA malayi Causes Malayan lymphatic filariasis
Mosquito vectors- Anopheles,Aedes, Culex, Mansonia MOT – mosquito bite More seen in children More rapid course Elephantiasis – below knee

BRUGIA malayi Diagnosis: Thick& Thin smears (12 MN) Treatment: DEC
* Loa loa – Calabar swellings * Onchocerca volvulus – River blindness and hanging groin

DRACUNCULUS medinensis
Guinea worm Cyclops contain the infective larvae No reservoir host Mx: Manual extraction Rx: Steroid, Antibiotic, Anti-tetanus

TRICHINELLA spiralis (Zoonosis)
Nat.Hosts – pigs, wild boar MOT – ingestion of undercooked pork, sausage meat containing larvae Man – accidental IH

TRICHINELLA spiralis (Zoonosis)
Pathology: GIT (Diarrhea, nausea, vomiting, abdominal pain) Migration – fever allergic reaction, myalgia, headache Diagnosis: Muscle biopsy Serological Treatment: Steroids

ANISAKIS sp.  fondness for raw fish (Japanese restaurants)
Present as gastritis, gastric ulcer, gastric cancer Mx: Fiberoptic gastroscopy with forceps extraction of mass containing the worm

CUTANEOUS LARVA MIGRANS
Ancylostoma brasiliense – Dog/Cat hookworm larva Ancylostoma caninum – Dog hookworm larvae Larva migrate to superficial layers of the skin Feet, legs, hands, thigh, and back

CUTANEOUS LARVA MIGRANS
Clinical Features: Allergic reaction Irritation Inflammation Secondary infection

VISCERAL LARVA MIGRANS
Toxocara canis/cati- larvae of dog and cat roundworms cause granuloma formation - Common in children up to 3 years

ORAL INGESTION OF OVA Ova carried by blood to: liver, brain, lungs, heart, and eyes

Clinical Features: Eosinophilic granuloma Hyperglobulinemia

Antihelminthic Agents

Mebendazole and Albendazole (Benzimidazoles)
MOA: inhibit microtubule polymerization by binding to beta- tubulin → immobilization → death

Pharmacokinetics – Mebendazole: poorly and erratically absorbed rapid first-pass hepatic metabolism (these two cause low systemic bioavailability) 95% bound to proteins excreted in the bile and in the urine *mebendazole is the active drug form and not its metabolites

Pharmacokinetics – Albendazole: variably and erratically absorbed absorption enhanced by a fatty meal metabolized to albendazole sulfoxide which has potent antihelminthic activity 70% bound to plasma proteins excreted through urine

Indications: both drugs effective for Enterobius, Ascaris, Trichiuris, and hookworms *albendazole is more effective against hydatid cysts

Adverse Effects: allergic reactions alopecia reversible neutropenia agranulocytosis hypospermia teratogenic in experimental animals *Albendazole has lesser ADRs

Contraindications pregnant patients children below 2 years old * Albendazole is contraindicated in hepatic cirrhosis

Pyrantel pamoate MOA: depolarizing neuromuscular blocking agent  releases acetylcholine and inhibits cholinesterase  induces marked, persistent activation of nicotinic receptors  spastic paralysis of worms

Pyrantel Pamoate Pharmacokinetics: poorly absorbed from the GIT (selective action on the GIT nematodes) excreted in urine and feces

Indications: hookworms pinworms Ascaris *Ineffective against Trichiuris

Adverse effects: transient and mild GIT upset headache dizziness rash fever

Drug interaction: pyrantel + piperazine = antagonism Contraindications: pregnancy children less than 2 years old

Oxantel pamoate effective against Trichiuris Oxantel-pyrantel combination (Quantrel) is available in a fixed dose of each drug

Piperazine citrate MOA: blocks the response of Ascaris muscle to acetylcholine  causes flaccid paralysis of Nematodes

Piperazine Pharmacokinetics: absorbed rapidly from the GIT
20% excreted unchanged in the urine Indications: Enterobius Ascaris

Piperazine Adverse Effects: GIT upset neurotoxicity urticaria Drug interaction with pyrantel: antagonism

Piperazine Contraindications: pregnancy seizures renal disorders

(also an imidazole derivative)
Levamisole (also an imidazole derivative) as efficacious as Piperazine also an immunomodulant

Diethylcarbamazine citrate
used mainly in lymphatic filariasis and loaisis Pharmacokinetics: readily absorbed in the GIT, skin, and conjunctiva widely distributed excreted in urine

Adverse effectss: nausea, vomiting, headache, drowsiness allergic reactions arise from the death of the filariae or microfilariae Precaution: adjust doses in renal failure

Praziquantel MOA: increases cell membrane permeability to calcium resulting in marked contraction, followed by paralysis of worm musculature

Praziquantel Pharmacokinetics: rapidly and almost completely absorbed from the GIT peak serum concentration is reached in 1-2 hours penetrates the BBB first pass metabolism in liver excretion: renal

Praziquantel Adverse effects: most common – malaise, headache, dizziness, anorexia others – drowsiness, nausea, vomiting, abdominal pain, low grade fever, pruritus Contraindication: ocular cysticercosis children under 4 years old pregnant and lactating mothers

Niclosamide MOA: inhibits oxidative phosphorylation Pharmacokinetics:
minimally absorbed following oral administration

Niclosamide Adverse effects: mild and transient nausea, vomiting, diarrhea, abdominal discomfort; Contraindications/precautions: consumption of alcohol children below 2 years old pregnancy

Niridazole MOA: not established Pharmacokinetics: absorbed slowly peak serum concentration attained in 6 hours mainly excreted in the urine, some in feces

Niridazole Adverse effects: GIT – nausea, vomiting, diarrhea, abdominal pain headache, dizziness myalgia hematologic and neuropsychiatric effect

DRUGS OF CHOICE & ALTERNATE DRUGS Ascaris lumbricoides
Pyrantel pamoate, Mebendazole Piperazine citrate Trichiuris trichiura (whipworm) Mebendazole *Updated from: Handbook of Pediatric Infectious Diseases, 2004, a PPS Publication

DRUGS OF CHOICE & ALTERNATE DRUGS
Necator americanus & Ancylostoma duodenale Mebendazole Pyrantel pamoate Enterobius vermicularis (pinworm) *Updated from: Handbook of Pediatric Infectious Diseases, 2004, a PPS Publication

DRUGS OF CHOICE & ALTERNATE DRUGS Strongyloides stercoralis
Albendazole Thiabendazole Schistosoma japonicum Praziquantel *Updated from: Handbook of Pediatric Infectious Diseases, 2004, a PPS Publication

DRUGS OF CHOICE & ALTERNATE DRUGS Taenia saginata & Taenia solium
Niclosamide Praziquantel Paromomycin Cysticercosis *Updated from: Handbook of Pediatric Infectious Diseases, 2004, a PPS Publication

DRUGS OF CHOICE & ALTERNATE DRUGS Wuchereria bancrofti & Brugia malayi
Diethylcarbamazine citrate Capillaria philippinensis Mebendazole Paragonimus westermani Praziquantel Bithionol *Updated from: Handbook of Pediatric Infectious Diseases, 2004, a PPS Publication

CHLAMYDIAL INFECTION

Chlamydophila pneumoniae

ETIOLOGY obligate intracellular pathogens
established a unique niche in host cells gram-negative envelope without detectable peptidoglycan share a group-specific lipopolysaccharide antigen use host ATP for the synthesis of chlamydial proteins encode an abundant surface exposed protein called the major outer membrane protein (MOMP, or OmpA) The most significant human pathogens are: C. pneumoniae ; C. trachomatis ; C. psittaci C. psittaci is the cause of psittacosis, an important zoonosis The MOMP is the major determinant of the serologic classification of C. trachomatis and C. psittaci isolates.

Clinical Manifestations
classic atypical (or nonbacterial) pneumonia characterized by mild to moderate constitutional symptoms, including fever, malaise, headache, cough, pharyngitis Asymptomatic respiratory infection has been documented in 2-5% of adults and children and can persist for ≥1 yr cannot be readily differentiated from those caused by other respiratory pathogens, especially M. pneumoniae.

Diagnosis Auscultation: rales,wheezing Chest radiograph:
appears worse than the patient's clinical status mild, diffuse involvement or lobar infiltrates with small pleural effusions. CBC: may be elevated with a left shift but is usually unremarkable Specific diagnosis: isolation of the organism in tissue culture grows best in cycloheximide-treated HEp-2 and HL cells optimum site for culture is the posterior nasopharynx

Treatment effective for eradication of C. pneumoniae from the nasopharynx of children with pneumonia in approximately 80% of cases erythromycin (40 mg/kg/day PO divided twice a day for 10 days), clarithromycin (15 mg/kg/day PO divided twice a day for 10 days), and azithromycin (10 mg/kg PO on day 1, and then 5 mg/kg/day PO on days 2-5) Tetracyclines, erythromycin, the macrolides (azithromycin and clarithromycin), and quinolones show in vitro activity. The ketolides also have promising in vitro activity. Like C. psittaci, C. pneumoniae is resistant to sulfonamides

Chlamydia Trachomatis
Genital Tract Infections

Etiology C. trachomatis is a major cause of epididymitis and is the cause of 23-55% of all cases of nongonococcal urethritis, 50% of men with gonorrhea may be co-infected with C. trachomatis prevalence of chlamydial cervicitis among sexually active women is 2-35% Rates of infection among girls 15-19 yr of age exceed 20% in many urban populations but can be as high as 15% in suburban populations as well Children who have been sexually abused can acquire anogenital C. trachomatis infection, which is usually asymptomatic. Culture is the only method that should be used for diagnosis of C. trachomatis from these sites when a prepubertal child is being tested for suspected sexual abuse. However, because perinatally acquired rectal and vaginal C. trachomatis infections can persist for ≥3 years, the detection of C. trachomatis in the vagina or rectum of a young child is not absolute evidence of sexual abuse.

Clinical Manifestations
Up to 75% of women asymptomatic discharge that is usually mucoid rather than purulent can cause urethritis (acute urethral syndrome), epididymitis, cervicitis, salpingitis, proctitis, and pelvic inflammatory disease Asymptomatic urethral infection is common in sexually active men. Autoinoculation from the genital tract to the eyes can lead to conjunctivitis The symptoms of chlamydial genital tract infections are less acute than those of gonorrhea,

Diagnosis Definitive diagnosis: isolation of the organism in tissue culture and as confirmation of the characteristic intracytoplasmic inclusions by fluorescent antibody staining C. trachomatis can be cultured in cycloheximide-treated HeLa, McCoy, and HEp-2 cells.

Treatment uncomplicated C. trachomatis genital infection in men and nonpregnant women azithromycin (1 g PO as a single dose) doxycycline (100 mg PO twice a day for 7 days) erythromycin base (500 mg PO 4 times a day for 7 days), erythromycin ethylsuccinate (800 mg PO 4 times a day for 7 days), ofloxacin (300 mg PO twice a day for 7 days), levofloxacin (500 mg PO once daily for 7 days). The high erythromycin dosages might not be well tolerated. Doxycycline and quinolones are contraindicated in pregnant women, and quinolones are contraindicated in persons younger than 18 yr.

Treatment For pregnant women
erythromycin base (500 mg PO twice a day for 7 days) amoxicillin (500 mg PO 3 times a day for 7 days) erythromycin base (250 mg PO 4 times a day for 14 days), erythromycin ethylsuccinate (800 mg PO 4 times a day for 7 days or 400 mg PO 4 times a day for 14 days), azithromycin (1 g PO in a single dose) Amoxicillin at a dosage of 500 mg PO 3 times a day for 7 days is as effective as any of the erythromycin regimens

Treatment Empirical treatment
only for patients at high risk for infection who are unlikely to return for follow-up evaluation, including adolescents with multiple sex partners treated empirically for both C. trachomatis and gonorrhea Sex partners of patients with nongonococcal urethritis should be treated Especially if they have had sexual contact with the patient during the 60 days preceding the onset of symptoms The most recent sexual partner should be treated even if the last sexual contact was more than 60 days from onset of symptoms

Complications perihepatitis (Fitz-Hugh-Curtis syndrome) and salpingitis up to 40% will have significant sequelae: 17% will suffer from chronic pelvic pain, 17% will become infertile 9% will have an ectopic (tubal) pregnancy Adolescent girls at higher risk for complications: tubal scarring, subsequent obstruction with secondary infertility, increased risk for ectopic pregnancy

Complications 50% of neonates born to pregnant women with untreated chlamydial infection will acquire C. trachomatis infection Women with C. trachomatis infection have a 3-5-fold increased risk for acquiring HIV infection

Prevention Timely treatment
Sex partners should be evaluated and treated if they had sexual contact during the 60 days preceding onset of symptoms in the patient The most recent sex partner should be treated even if the last sexual contact was >60 days

Complications Patients and partners:
abstain from sexual intercourse until 7 days after a single- dose regimen or after completion of a 7-day regimen Annual routine screening for C. trachomatis for sexually active female adolescents, women years of age, older women with risk factors such as new or multiple partners or inconsistent use of barrier contraceptives Sexual risk assessment might indicate more frequent screening of some women.

Chlamydia Trachomatis
Conjunctivitis and Pneumonia in Newborns

Epidemiology 5-30% of pregnant women
50% risk for vertical transmission at parturition to newborn infants infected at 1 or more sites, (conjunctivae, nasopharynx, rectum, and vagina) Transmission is rare following cesarean section with intact membranes systematic prenatal screening and treatment of pregnant women decreased the incidence However, in countries where prenatal screening is not done, such as the Netherlands, C. trachomatis remains an important cause of neonatal infection, accounting for >60% of neonatal conjunctivitis.

Inclusion Conjunctivitis
30-50% of infants born to mothers with active, untreated chlamydial infection develop 5-14 days after delivery, from mild conjunctival injection with scant mucoid discharge to severe conjunctivitis with copious purulent discharge, chemosis, pseudomembrane formation conjunctiva may be very friable and miight bleed when stroked with a swab 50% of infants with chlamydial conjunctivitis also have nasopharyngeal infection Chlamydial conjunctivitis must be differentiated from gonococcal ophthalmia, which is sight threatening.

Pneumonia 10-20% of infants born to women with active, untreated chlamydial infection 25% of infants with nasopharyngeal chlamydial infection develop pneumonia Onset:1 and 3 mo of age Presentation: insidious, with persistent cough, tachypnea, and absence of fever Auscultation: rales Laboratory finding: peripheral eosinophilia (>400 cells/mm3) Chest radiograph: hyperinflation accompanied by minimal interstitial or alveolar infiltrates. The absence of fever and wheezing helps to distinguish C. trachomatis pneumonia from respiratory syncytial virus pneumonia.

Diagnosis Definitive diagnosis: isolation of C. trachomatis in cultures of specimens obtained from the conjunctiva or nasopharynx. Nonculture methods including direct fluorescent antibody (DFA) sensitivities of ≥90% and specificities of ≥95% for conjunctival specimens compared with culture. Accuracy for nasopharyngeal specimens is not as good.

Treatment: C. trachomatis conjunctivitis or pneumonia in infants
erythromycin (base or ethylsuccinate, 50 mg/kg/day divided 4 times a day PO for 14 days). results of 1 small study: short course of azithromycin (20 mg/kg/day once daily PO for 3 days) is as effective as 14 days of erythromycin. An association between treatment with oral erythromycin and infantile hypertrophic pyloric stenosis has been reported in infants <6 wk of age who were given the drug for prophylaxis after nursery exposure to pertussis The rationale for using oral therapy for conjunctivitis is that 50% or more of these infants have concomitant nasopharyngeal infection or disease at other sites, and studies have demonstrated that to The failure rate with oral erythromycin remains 10-20%, and some infants require a 2nd course of treatment. pical therapy with sulfonamide drops and erythromycin ointment is not effective.

Prevention screening and treatment of pregnant women
Reasons for failure of maternal treatment: poor compliance re-infection from an untreated sexual partner Neonatal gonococcal prophylaxis with topical erythromycin or tetracycline ointment, or silver nitrate, does not appear to prevent chlamydial ophthalmia or nasopharyngeal colonization with C. trachomatis or chlamydial pneumonia.

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INFECTIOUS DISEASE PART II

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INFECTIOUS DISEASE PART II

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