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INFECTIOUS DISEASE PART II By Camille-Marie A. Go.

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1 INFECTIOUS DISEASE PART II By Camille-Marie A. Go

2 PROTOZOA

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

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

5 AMOEBIC BACILLARY DYSENTERYDYSENTERY Gradual onsetAcute onset (-) Fever, vomiting(+) fever, vomiting Bloody, mucoidWatery, bloody Offensive smellOdorless Acid pHAlkaline pH Few pus cellsMany pus cells (+) Motile amoebae(-) Amoebae

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

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

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

9 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) stools)

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

11 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 - Trophozoite (in diarrheic stools) stools)

12 MASTIGOPHORA (FLAGELLATES)  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

13 MASTIGOPHORA (FLAGELLATES)  GIARDIA lamblia – Diagnosis: Routine Fecalysis Duodenal aspirate Duodenal aspirate Enterotest capsule Enterotest capsule – Treatment: Metronidazole Quinacrine HCl – drug of Quinacrine HCl – drug of choice choice

14 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)

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

16 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)

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

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

19 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 - Via blood transfusion - Transplacental route - Transplacental route

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

21 TRYPANOSOMA cruzi (Zoonosis)  DIAGNOSIS –Peripheral blood smear –Xenodiagnosis –Blood culture –IgM determination  TREATMENT –Nifurtimox, Bezuidazole

22 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

23 LEISHMANIA donovani (Zoonosis)  Infective stage: Promastigotes  Diagnostic stage: Amastigotes in macrophages  Pathology: Blockage and destruction of R.E.S.

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

25 LEISHMANIA donovani (Zoonosis)  TREATMENT –Antimony compounds  e.g. Sodium Stibogluconate – drug of choice  N. methyl – Glucamine  Pentamidine isothionate

26 PLASMODIUM PLASMODIUM

27 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

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

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

30 PLASMODIUM falciparum  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

31 PLASMODIUM falciparum  Treatment: –Quinine, Quinidine –Quinhaosu derivatives: Artemisin, Artesunate, Artemether

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

33 PLASMODIUM vivax  DIAGNOSIS: Enlarged red cells Schuffner’s dots 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

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

35 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

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

37 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

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

39 TOXOPLASMA gondii (Zoonosis)  Clinical forms –Lymphadenopathy –Ocular toxoplasmosis –Myocarditis –Meningoencephalitis –Atypical pneumonia –Congenital toxoplasmosis  Increased IgM  Cerebral calcification

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

41 TOXOPLASMA gondii (Zoonosis)  TREATMENT –Pyrimethamine –Sulfadiazine

42 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

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

44 PNEUMOCYSTIS carinii  TREATMENT –Pentamidine  TMP-SMZ – drug of choice

45 HELMINTHS  PLATYHELMINTHES (Flat worms)  TREMATODA (Digenetic flukes)

46 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

47 FASCIOLOPSIS buski  DIAGNOSIS – Rt. Fecalysis  TREATMENT – Praziquantel

48 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

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

50 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

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

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

53 SCHISTOSOMES  CLASSIFICATION –Superfamily schistosomatoidea  S. haematobium  S. mansoni  S. japonicum  S. mekongi

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

55 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

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

57 SCHISTOSOMA hematobium  Diagnostic stage: urine – egg with terminal spine  Treatment: Praziquantel

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

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

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

61 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

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

63 CESTODA (Tapeworms)

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

65 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 - serological

66 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 lateral uterine branches –Cellophane (Scotch) tape swab

67 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

68 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

69 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

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

71 NEMATHELMINTHES (Round worms)

72 ASCARIS lumbricoides  Large intestinal roundworm  MOT – ingestion of embryonated ova  Dist n  inadequate sanitation; use of night soil

73 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

74 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

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

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

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

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

79 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

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

81 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)

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

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

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

85 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

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

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

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

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

90 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

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

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

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

94 VISCERAL LARVA MIGRANS  ORAL INGESTION OF OVA  Ova carried by blood to: – liver, brain, lungs, heart, and eyes

95 VISCERAL LARVA MIGRANS  Clinical Features: –Eosinophilic granuloma –Hyperglobulinemia

96 Antihelminthic Agents

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

98 Mebendazole 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

99 Mebendazole and Albendazole (Benzimidazoles) 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

100 Mebendazole and Albendazole (Benzimidazoles)  Indications: both drugs effective for Enterobius, Ascaris, Trichiuris, and hookworms *albendazole is more effective against hydatid cysts

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

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

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

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

105 Indications: hookworms pinworms Ascaris *Ineffective against Trichiuris

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

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

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

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

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

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

112 Piperazine Contraindications:  pregnancy  seizures  renal disorders

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

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

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

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

117 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

118 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

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

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

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

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

123 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

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

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

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

127 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

128 CHLAMYDIAL INFECTION

129 Chlamydophila pneumoniae

130 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

131 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

132 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

133 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)

134 Chlamydia Trachomatis Genital Tract Infections

135 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 yr of age exceed 20% in many urban populations but can be as high as 15% in suburban populations as well

136 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

137 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.

138 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).

139 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

140 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

141 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

142 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

143 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

144 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

145 Chlamydia Trachomatis Conjunctivitis and Pneumonia in Newborns

146 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

147 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

148 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/mm 3 )  Chest radiograph: hyperinflation accompanied by minimal interstitial or alveolar infiltrates.

149 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.

150 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

151 Prevention  screening and treatment of pregnant women  Reasons for failure of maternal treatment:  poor compliance  re-infection from an untreated sexual partner

152 THANK YOU :D


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