4SARCODINA (AMOEBAE) ENTAMOEBA histolytica Distribution 1. Inadequate sanitation2. Poor personal hygieneInfective state – mature 4-nucleated cystDiagnostic stage – cyst and trophozoiteDifferent from E. coliDDx – bacillary dysentery
9CILIOPHORA (CILIATES) BALANTIDIUM coliOnly ciliate that parasitizes manNH-pigs; MOT- ingestion of cystInfective stage – cyst (No incubation)Diagnostic stage – cyst (formed and semiformed stool)- Trophozoite (dysentericstools)
10CILIOPHORA (CILIATES) BALANTIDIUM coliCauses bloody mucoid diarrheaDiagnosis by Rt. FecalysisTreatmnent – drug of choice – Iodoquinol
11MASTIGOPHORA (FLAGELLATES) GIARDIA lamblia Humans as only reservoir infectionMOT – ingestion of cystInfective stage – cyst (no incutation)Diagnostic stage – cyst (formed and semiformed stool)- Trophozoite (in diarrheicstools)
12MASTIGOPHORA (FLAGELLATES) GIARDIA lambliaDuodenum, jejunumPrevalent among childrenCauses Villous Atrophy – Malabsorption and lactose intolerance; steatorrheaPredisposition: GIT disorders, bacterial infection of intestine; hypochloridia, pancreatic disease
14TRICHOMONAS vaginalis MOT -sexually transmittedcommon cause of acute vaginitis with yellow–green purulent discharge in females (urinary frequency)Causes urethritis and purulent discharge in malesInfective stage: Flagellates (No cyst stage)
15TRICHOMONAS vaginalis Treatment: MetronidazoleBoth partners* T. hominis* T. intestinalis
16TRYPANOSOMA b. rhodesiense (zoonosis) TRYPANOSOMA b TRYPANOSOMA b. rhodesiense (zoonosis) TRYPANOSOMA b. gambiense (humans mostly)Cause African sleeping sicknessM.O.T. – bite of tsetse fly (Glossina) and blood transfusionInfective stage – Metacyclic trypomastigoteDiagnostic stage – Trypomastigote (peripheral blood)
18TREATMENT Pentamidine Drug of Choice: Suramine (Early hemolymphatic stage)Metarsoprol (Late stage) – CNS Involvement
19TRYPANOSOMA cruzi (Zoonosis) Endemic in S. AmericaCauses Chaga’s diseaseMOT- Bite wound made by kissing bug (Triatoma or Rhodnius) is contaminated by rubbing bug’s feces containing metacyclic trypomastigote- Via blood transfusion- Transplacental route
22LEISHMANIA donovani (Zoonosis) Endemic in S. and C. America, Europe, Africa, Asia (esp. India); Local cases (OCW’s)Causes visceral Leishmaniasis/KalaazarMOT – bite of sandfly (Phetobotomus or Lutzomyia)Congenital/transplacentalSexual contactBlood transfusion
23LEISHMANIA donovani (Zoonosis) Infective stage: PromastigotesDiagnostic stage: Amastigotes in macrophagesPathology: Blockage and destruction of R.E.S.
24LEISHMANIA donovani (Zoonosis) DIAGNOSISPeripheral blood monocytesAspirate of bone marrow, lymph node, spleenFormol get test (non-specific; increased IgG (+)Gelling and Whitening of serum
25LEISHMANIA donovani (Zoonosis) TREATMENTAntimony compoundse.g. Sodium Stibogluconate – drug of choiceN. methyl – GlucaminePentamidine isothionate
27PLASMODIUM falciparum Causes malignant tertian malariaMost prevalent in the world, in the Phil.Most pathogenic- CytoadherenceMOT – bite of Anopheles mosquito1° vector- A.minimus flavirostris2° vector- A. balabacencisA. littoralisA. mangyanus*Potential vector: A. maculatus
28PLASMODIUM falciparum Parasitizes red cells of all agesSchizogony, sporogonySevere Falciparum MalariaCerebral malariaAnemiaBlackwater feverDiarrhea/Vomiting (GIT)Pulmonary edema ± renal failureHypoglycemia
29PLASMODIUM falciparum In pregnancy – abortion, premature labor, stillbirth, neonatal death, low-birth weight infantsHyperactive malaria splenomegalyRecrudescenceVaccine production fails because of antigenic variation
30PLASMODIUM falciparum Diagnosis:Clinical: History of travel, SSxLaboratory:Thick and thin blood smearsMaurer’s dotsRing forms (young trophozoites), Accoele formsCrescent/Banana-shaped gametocytesImmunofluorescent (Q.B.C.)Serological
32PLASMODIUM vivax Causes benign tertian malaria Parasitizes young red cells (reticulocytes)Rarely found in E. Africa (-) Duffy blood group antigen Fya and FybRelapses due to hypnozoitesCommon etiology of transfusion malaria
33PLASMODIUM vivax DIAGNOSIS: Enlarged red cells Schuffner’s dots TREATMENT: Chloroquine + Primaquine* Plasmodium malariaeQuartan malaria, nephrotic syndromeOlder red cells; Ziemann’s stippling, daisy schizont; band form; bird’s eye formRecrudescence
34* Plasmodium ovale Causes Ovale Tertian Malaria Relapses Young cells; red cells become slightly enlarged, oval-shaped with fimbriated (ragged) ends; James dots
35CRYPTOSPORIDIUM sp. (Zoonosis) Common among AIDS patientsCommon cause of diarrhea in children <5 y/o and non-breast fed infantsHabitat: small intestineMOT – ingestion of oocystInfective and Diagnostic stage: oocyst
37TOXOPLASMA gondii (Zoonosis) Nat. host/Def. host – catHumans. Other mammals – Int. hostCommon among immunocompromised individuals, e.g. AIDS patientsMOT – ingestion of oocystEating uncooked meat of IHBlood transfusion
42PNEUMOCYSTIS carinii Common cause of death in AIDS patients Common among malnourished childrenMOT – droplet infectionInfective and Diagnostic stage: Cyst/TrophozoitePathology: Interstitial (viral-like) pneumonia
51PARAGONIMUS westermani Habitat – BronchiolesCauses PTB–like SSxCough, night sweats , chest pains, hemoptysisDIAGNOSIS: Eggs in sputum, fecesTreatment: Praziquantel
52PARAGONIMUS westermani Clonorchis sinensis –Chinese Liver FlukeCholangiocarcinomaMetagonimus yokogawai – smallest fluke that parasitizes manHeterophyes heterophyes – causes cardiac beriberiDicrocoelium dendriticum – IH2 is an ant
53SCHISTOSOMES CLASSIFICATION Superfamily schistosomatoidea S. haematobiumS. mansoniS. japonicumS. mekongi
54SCHISTOSOMES FEATURES Adult habitat – venous plexuses Sexes- separate Shape – cylindricalDefinitive host – humans only1st I.H. – snails; NO 2nd I.H.Transmission – skin penetrationLab. diagnosis – eggs in urine, feces, rectal scrapings
55SCHISTOSOMA hematobium Endemic in Africa, Middle EastCauses urinary SchistosomiasisSpread and construction of irrigation channels and dams for hydroelectric power and flood controlMOT – skin/mucosal penetration by cercariae
64TAENIA soliumTaeniasis – ingestion of measly pork containing cysticerciCysticercosis – ingestion of eggsRegurgitation of gravid proglottid into the stomach
65TAENIA solium Diagnosis: Scolex with 4 suckers and 2 rows of hooks Taeniasis – finding of adult segments or eggs in the stoolCysticercosis – radiological (radiolucent or radio-opaque cysts along limb soft tissue parts- serological
66TAENIA saginata More prevalent worldwide; in R.P. MOT – ingestion of cysticerci in undercooked, infected beefCysticercosis bovis not seenScolex with 4 suckers and no hooksDiagnosis: FecalysisAdult proglottid - >13 mainlateral uterine branchesCellophane (Scotch) tape swab
67ECHINOCOCCUS granulosis (Zoonosis) Endemic in sheep-raising countriesCauses hydatid disease/hydatidosisMOT – ingestion of eggsInfective stage – eggsDiagnostic stage – eggs and adultDH – dogsAccidental host – manIH - sheep
68ECHINOCOCCUS granulosis (Zoonosis) Pathology:Hydatid cyst: 60% in ® liver, others in lungs, bone, brain, kidney, spleenRupture of cyst – Anaphylactic shockDiagnosis:X-rayCyst fluidSerologicalCasoni skin test – intradermal testMx: Surgical removal/extirpation
69DIPHYLOBOTHRIUM latum Largest fish tapewormMOT – ingestion of plerocercoidInfective stage: Plerocercoid in undercooked or raw freshwater fishDH – humans and fish–eating animalsIH 1 – crustaceans (procercoid) cyclops DiaptomusIH 2 – freshwater fish
77STRONGYLOIDES stercoralis Pathology: Heavy infection malabsorption with steatorrhea,Larva currens; free-living phaseDiagnosis: FecalysisHarada-Mori culture tech.EnterotestTreatment: AlbendazoleThiabendazole
78TRICHURIS trichiura Whipworm MOT – ingestion of bipolar-plugged ova Pathology: Chronic cases rectal prolapse; prone to 2ndy E. histolytica infectionDiagnosis: Fecalysis, ProctoscopyTreatment: Albendazone, Mebendazole, O. pyrantel
79HOOKWORMSMOT – skin penetration by filariform larva; mucosal; transmammary; transplacentalHookworm infection vs. Hookworm diseasePathology:A. duodenale – more blood loss (0.15 ml/day)Ground itchRespiratory problems – petechial hemorrhagesHookworm anemia – iron deficiency, hypochromic, microcytic; hypoalbuminemia* Creeping Eruption by non-human hookworms
80HOOKWORMS Diagnosis: Fecalysis Harada Mori culture tech Treatment: MebendazolePyrantel pamoate
81CAPILLARIA philippinensis Small whipworm, Pudoc wormNat. host – fish-eating birdsEndemic in N. Luzon, Bohol, Leyte, MindanaoM.O.T. – ingestion of infective eggs in undercooked or raw fish (Bacto, Bagsit, Bagsan)
97Mebendazole and Albendazole (Benzimidazoles) MOA: inhibit microtubule polymerization by binding to beta- tubulin → immobilization → death
98Mebendazole and Albendazole (Benzimidazoles) 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
99Mebendazole and Albendazole (Benzimidazoles) Pharmacokinetics –Albendazole:variably and erratically absorbedabsorption enhanced by a fatty mealmetabolized to albendazole sulfoxide which has potent antihelminthic activity70% bound to plasma proteinsexcreted through urine
100Mebendazole and Albendazole (Benzimidazoles) Indications:both drugs effective forEnterobius,Ascaris,Trichiuris,and hookworms*albendazole is more effective againsthydatid cysts
101Adverse Effects:allergic reactions alopecia reversible neutropenia agranulocytosis hypospermia teratogenic in experimental animals *Albendazole has lesser ADRs
102Contraindicationspregnant patients children below 2 years old * Albendazole is contraindicated in hepatic cirrhosis
103Pyrantel pamoateMOA: depolarizing neuromuscular blocking agent releases acetylcholine and inhibits cholinesterase induces marked, persistent activation of nicotinic receptors spastic paralysis of worms
104Pyrantel PamoatePharmacokinetics: poorly absorbed from the GIT (selective action on the GIT nematodes) excreted in urine and feces
105Indications:hookwormspinwormsAscaris*Ineffective against Trichiuris
106Adverse effects:transient and mild GIT upset headache dizziness rash fever
107Drug interaction:pyrantel + piperazine = antagonismContraindications:pregnancychildren less than 2 years old
108Oxantel pamoateeffective against Trichiuris Oxantel-pyrantel combination (Quantrel) is available in a fixed dose of each drug
109Piperazine citrateMOA: blocks the response of Ascaris muscle to acetylcholine causes flaccid paralysis of Nematodes
110Piperazine Pharmacokinetics: absorbed rapidly from the GIT 20% excreted unchanged in the urineIndications:EnterobiusAscaris
111PiperazineAdverse Effects: GIT upset neurotoxicity urticaria Drug interaction with pyrantel: antagonism
113(also an imidazole derivative) Levamisole(also an imidazole derivative)as efficacious as Piperazinealso an immunomodulant
114Diethylcarbamazine citrate used mainly in lymphatic filariasis and loaisisPharmacokinetics:readily absorbed in the GIT,skin, and conjunctivawidely distributedexcreted in urine
115Adverse effectss:nausea, vomiting, headache, drowsinessallergic reactions arise from the death of the filariae or microfilariaePrecaution:adjust doses in renal failure
116PraziquantelMOA: increases cell membrane permeability to calcium resulting in marked contraction, followed by paralysis of worm musculature
117PraziquantelPharmacokinetics: 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
118PraziquantelAdverse 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
130ETIOLOGY obligate intracellular pathogens established a unique niche in host cellsgram-negative envelope without detectable peptidoglycanshare a group-specific lipopolysaccharide antigenuse host ATP for the synthesis of chlamydial proteinsencode 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. psittaciC. psittaci is the cause of psittacosis, an important zoonosisThe MOMP is the major determinant of the serologic classification of C. trachomatis and C. psittaci isolates.
131Clinical Manifestations classic atypical (or nonbacterial) pneumonia characterized by mild to moderate constitutional symptoms, includingfever, malaise, headache, cough, pharyngitisAsymptomatic respiratory infection has been documented in 2-5% of adults and children and can persist for ≥1 yrcannot be readily differentiated from those caused by other respiratory pathogens, especially M. pneumoniae.
132Diagnosis Auscultation: rales,wheezing Chest radiograph: appears worse than the patient's clinical statusmild, diffuse involvement or lobar infiltrates with small pleural effusions.CBC: may be elevated with a left shift but is usually unremarkableSpecific diagnosis:isolation of the organism in tissue culturegrows best in cycloheximide-treated HEp-2 and HL cellsoptimum site for culture is the posterior nasopharynx
133Treatmenteffective for eradication of C. pneumoniae from the nasopharynx of children with pneumonia in approximately 80% of caseserythromycin (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), andazithromycin (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
135EtiologyC. 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. trachomatisprevalence 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 wellChildren 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.
136Clinical Manifestations Up to 75% of women asymptomaticdischarge that is usually mucoid rather than purulentcan cause urethritis (acute urethral syndrome), epididymitis, cervicitis, salpingitis, proctitis, and pelvic inflammatory diseaseAsymptomatic urethral infection is common in sexually active men.Autoinoculation from the genital tract to the eyes can lead to conjunctivitisThe symptoms of chlamydial genital tract infections are less acute than those of gonorrhea,
137DiagnosisDefinitive diagnosis: isolation of the organism in tissue culture and as confirmation of the characteristic intracytoplasmic inclusions by fluorescent antibody stainingC. trachomatis can be cultured in cycloheximide-treated HeLa, McCoy, and HEp-2 cells.
138Treatmentuncomplicated C. trachomatis genital infection in men and nonpregnant womenazithromycin (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.
139Treatment 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
140Treatment Empirical treatment only for patients at high risk for infection who are unlikely to return for follow-up evaluation,including adolescents with multiple sex partnerstreated empirically for both C. trachomatis and gonorrheaSex partners of patients with nongonococcal urethritis should be treatedEspecially if they have had sexual contact with the patient during the 60 days preceding the onset of symptomsThe most recent sexual partner should be treated even if the last sexual contact was more than 60 days from onset of symptoms
141Complicationsperihepatitis (Fitz-Hugh-Curtis syndrome) and salpingitisup to 40% will have significant sequelae:17% will suffer from chronic pelvic pain,17% will become infertile9% will have an ectopic (tubal) pregnancyAdolescent girls at higher risk for complications:tubal scarring,subsequent obstruction with secondary infertility,increased risk for ectopic pregnancy
142Complications50% of neonates born to pregnant women with untreated chlamydial infection will acquire C. trachomatis infectionWomen with C. trachomatis infection have a 3-5-fold increased risk for acquiring HIV infection
143Prevention Timely treatment Sex partners should be evaluated and treated if they had sexual contact during the 60 days preceding onset of symptoms in the patientThe most recent sex partner should be treated even if the last sexual contact was >60 days
144Complications Patients and partners: abstain from sexual intercourse until 7 days after a single- dose regimen or after completion of a 7-day regimenAnnual routine screening for C. trachomatis forsexually active female adolescents,women years of age,older women with risk factors such as new or multiple partners or inconsistent use of barrier contraceptivesSexual risk assessment might indicate more frequent screening of some women.
145Chlamydia Trachomatis Conjunctivitis and Pneumonia in Newborns
146Epidemiology 5-30% of pregnant women 50% risk for vertical transmission at parturition to newborn infantsinfected at 1 or more sites, (conjunctivae, nasopharynx, rectum, and vagina)Transmission is rare following cesarean section with intact membranessystematic prenatal screening and treatment of pregnant women decreased the incidenceHowever, 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.
147Inclusion Conjunctivitis 30-50% of infants born to mothers with active, untreated chlamydial infectiondevelop 5-14 days after delivery,from mild conjunctival injection with scant mucoid discharge to severe conjunctivitis with copious purulent discharge,chemosis,pseudomembrane formationconjunctiva may be very friable and miight bleed when stroked with a swab50% of infants with chlamydial conjunctivitis also have nasopharyngeal infectionChlamydial conjunctivitis must be differentiated from gonococcal ophthalmia, which is sight threatening.
148Pneumonia10-20% of infants born to women with active, untreated chlamydial infection25% of infants with nasopharyngeal chlamydial infection develop pneumoniaOnset:1 and 3 mo of agePresentation: insidious, with persistent cough, tachypnea, and absence of feverAuscultation: ralesLaboratory 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.
149DiagnosisDefinitive 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% andspecificities of ≥95% for conjunctival specimens compared with culture.Accuracy for nasopharyngeal specimens is not as good.
150Treatment: 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 pertussisThe 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 toThe 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.
151Prevention screening and treatment of pregnant women Reasons for failure of maternal treatment:poor compliancere-infection from an untreated sexual partnerNeonatal 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.