Medical Parasitology in the Philippines PDF

Medical Parasitology in the Philippines Medical Parasitology in the Philippines Vicente Y. Belizario, Jr. Winifreda U. de Leon Editors The University of the Philippines Press Diliman, Quezon City The University of the Philippines Press E. de los Santos St., UP Campus, Diliman, Quezon City 1101 Tel. Nos.: 925-3243, 926-6642 / Telefax No.: 928-2558 E-mail: [email protected] Website: uppress.com.ph © 2013 by University of the Philippines Manila ???? (Vicente Y. Belizario, Jr., Winifreda U. de Leon ???????) All rights reserved. No copies can be made in part or in whole without prior written permission from the author and the publisher. The data in this book have been verified with reliable sources, and treatment modalities suggested have been utilized in clinical practice. However, new researches and changes in the medical sciences should be considered. Readers are advised to consult other sources such as drug information sheets and dosage, contraindications to administration, and other relevant data. The National Library of the Philippines CIP Data Recommended entry: ISBN 978-971-542-________ Book Design by Zenaida N. Ebalan Printed in the Philippines To our fellow Filipinos, from whom we derive inspiration and learning, especially those who are poor and neglected, suffering from the burden of parasitic diseases vi Medical Parasitology in the Philippines Table of Contents Foreword.....................................................................................................................................x Foreword to the Second Edition..............................................................................................x Foreword to the First Edition..................................................................................................x Preface.........................................................................................................................................x Acknowledgments.......................................................................................................................x List of Figures.............................................................................................................................x List of Plates...............................................................................................................................x List of Tables...............................................................................................................................x Chapter 1: Introduction to Medical Parasitology..................................................................x General Considerations.......................................................................................................x Host-Parasite Relationships.................................................................................................x Immunology of Parasitic Infections.....................................................................................x Groups of Parasites with Medical and Public Health Importance........................................x Chapter 2: Protozoan Infections...............................................................................................x Intestinal Amebae...............................................................................................................x Commensal Amebae...........................................................................................................x Free-living Pathogenic Amebae...........................................................................................x Ciliates and Flagellates........................................................................................................x Coccidians..........................................................................................................................x Other Intestinal Protozoans................................................................................................x Plasmodium spp..................................................................................................................x Babesia spp..........................................................................................................................x Blood and Tissue Flagellates................................................................................................x Chapter 3: Nematode Infections................................................................................................x Intestinal Nematodes..........................................................................................................x Tissue Nematodes...............................................................................................................x vii viii Medical Parasitology in the Philippines Chapter 4: Cestode Infections...................................................................................................x Intestinal Cestodes..............................................................................................................x Extraintestinal Cestodes......................................................................................................x Chapter 5: Trematode Infections...............................................................................................x Blood Flukes.......................................................................................................................x Lung Flukes........................................................................................................................x Intestinal Flukes..................................................................................................................x Liver Flukes........................................................................................................................x Chapter 6: Arthropods and Mollusks of Medical Importance.................................................x Introduction to Arthropods of Medical Importance............................................................x Arthropods as Direct Causes of Injury................................................................................x Arthropods as Vectors of Disease.........................................................................................x Introduction to Medical Malacology...................................................................................x Chapter 7: Diagnostic Parasitology..........................................................................................x Examination of Stools and Body Fluids...............................................................................x Examination of Tissues.......................................................................................................x Recent Advances in Diagnosis of Parasitic Infections...........................................................x Quality Assurance in a Parasitology Laboratory...................................................................x Chapter 8: Special Topics in Parasitology..................................................................................x Parasitic Zoonoses...............................................................................................................x Immunocompromised Hosts and Parasitic Infections..........................................................x Neglected Tropical Diseases.................................................................................................x Preventive Chemotherapy...................................................................................................x Emporiatrics for the Filipino Traveler..................................................................................x Appendices....................................................................................................................................x WHO Bench Aids for the Diagnosis of Intestinal Parasites.................................................x WHO Bench Aids for the Diagnosis of Filarial Infections...................................................x WHO Bench Aids for the Diagnosis of Malaria Infections..................................................x Treatment of Parasitic Infections.........................................................................................x List of More Recent National Policies and Guidelines on Parasitic Diseases........................x Index...........................................................................................................................................x List of Figures Figure 2.1 Life cycle of Entamoeba histolytica......................................................................x Figure 2.2 Life cycle of commensal amebae.........................................................................x Figure 2.3 Life cycle of Acanthamoeba spp..........................................................................x Figure 2.4 Life cycle of Naegleria fowleri.............................................................................x Figure 2.5 Life cycle of Balantidium coli.............................................................................x Figure 2.6 Life cycle of Giardia duodenalis Figure 2.7 Life cycle of Trichomonas vaginalis Figure 2.8 Life cycle of Cryptosporidium spp. Figure 2.9 Life cycle of Cyclospora cayetanensis Figure 2.10 Life cycle of Cystoisospora belli Figure 2.11 Life cycle of Toxoplasma gondii Figure 2.12 Life cycle of Sarcocystis spp. Figure 2.13 Life cycle of Dientamoeba fragilis Figure 2.14 Life cycle of Plasmodium spp. Figure 2.15 Diagram of the course of malaria infections showing the primary attack, relapses, and recrudescence Figure 2.16 A WHO field test for response of malaria parasites to chloroquine Figure 2.17 Global distribution of malaria Figure 2.18 Distribution of malaria in the WHO Southeast Asia Region Figure 2.19 Distribution of malaria in the WHO Western Pacific Region Figure 2.20 Malaria cases per 100,000 population in the Philippines from 2000 to 2009 Figure 2.21 Malaria-related deaths per 100,000 population in the Philippines from 2005 to 2009 Figure 2.22 Macrostratification of provinces in the Philippines according to category by average malaria cases Figure 2.23 Life cycle of Babesia spp. Figure 2.24 Life cycle of Trypanosoma cruzi Figure 2.25 Life cycle of Trypanosoma brucei ix x Medical Parasitology in the Philippines Figure 2.26 Life cycle of Leishmania spp. Figure 3.1 Life cycle of Ascaris lumbricoides Figure 3.2 Global distribution of soil-transmitted helminth (STH) infections and proportion of children requiring preventive chemotherapy for STH infections in each country Figure 3.3 Schematic life cycle of soil-transmitted helminths Figure 3.4 Comparison of cumulative prevalence in San Vicente Elementary School (SVES) and sentinel schools in Biñan, Laguna from 1999 to 2010 Figure 3.5 Life cycle of Trichuris trichiura Figure 3.6 Life cycle of hookworms Figure 3.7 Life cycle of Strongyloides stercoralis Figure 3.8 Life cycle of Enterobius vermicularis Figure 3.9 Life cycle of Capillaria philippinensis Figure 3.10 Life cycle of Wuchereria bancrofti Figure 3.11 Distribution and status of preventive chemotherapy for lymphatic filariasis, worldwide, 2010 Figure 3.12 Map of lymphatic filariasis-endemic provinces in the Philippines, distribution in the three major island groups, and provinces declared lymphatic filarisis-free by the Department of Health Figure 3.13 Life cycle of Parastrongylus cantonensis Figure 3.14 Life cycle of Trichinella spiralis Figure 3.15 Life cycle of Anisakis spp. Figure 3.16 Life cycle of Toxocara canis Figure 4.1 Life cycle of Taenia spp. Figure 4.2 Life cycle of Taenia solium (cysticercosis) Figure 4.3 Life cycle of Hymenolepis nana Figure 4.4 Life cycle of Hymenolepis diminuta Figure 4.5 Life cycle of Dipylidium caninum Figure 4.6 Life cycle of Diphyllobothrium latum Figure 4.7 Life cycle of Echinococcus spp. Figure 4.8 Life cycle of Spirometra spp. Figure 5.1 Life cycle of Schistosoma spp. Figure 5.2 Map of Schistosoma japonicum-endemic provinces in the Philippines Figure 5.3 Life cycle of Paragonimus westermani Figure 5.4 Life cycle of Fasciolopsis buski Figure 5.5 Life cycle of Echinostoma spp. Figure 5.6 Life cycle of heterophyids List of Figures xi Figure 5.7 Life cycle of Fasciola spp. Figure 5.8 Life cycle of Clonorchis sinensis Figure 5.9 Life cycle of Opisthorchis spp. Figure 6.1 A generalized diagram of an adult Cyclorraphan fly Figure 6.2 Parts of an insect head Figure 6.3 Chewing type of mouthparts Figure 6.4 Sponging type of mouthparts Figure 6.5 Piercing-sucking type of mouthparts Figure 6.6 Chewing-lapping type of mouthparts Figure 6.7 Walking leg of an insect Figure 6.8 Spiracle Figure 6.9 Cercus Figure 6.10 Diagram of an insect showing the arrangement of the circulatory system Figure 6.11 Diagram showing an insect spiracle and trachea Figure 6.12 Diagram of an insect showing the arrangement of the nerve cord Figure 6.13 The digestive and excretory systems Figure 6.14 Reproductive systems of an insect Figure 7.1 SYBR Green detection in real-time PCR Figure 7.2 TaqMan real-time PCR Figure 7.3 Mode of action of antigen-detecting malaria rapid diagnostic tests (RDTs) Figure 7.4 The importance of ensuring quality of laboratory diagnosis of parasitic infections Figure 8.1 Direct zoonoses Figure 8.2 Cyclozoonoses subtype 1: man as an obligatory (definitive) host Figure 8.3 Cyclozoonoses subtype 2: man as a non-obligatory (optional) host Figure 8.4 Metazoonoses subtype 1: one vertebrate host (definitive) and one invertebrate host (intermediate) Figure 8.5 Metazoonoses subtype 2: more than one invertebrate host (first and second intermediate host) and one vertebrate host Figure 8.6 Metazoonoses subtype 3: one invertebrate host (intermediate) and two invertebrate hosts (one definitive and one intermediate) Figure 8.7 Zaprozoonoses Figure 8.8 Life cycle of microsporidia Figure 8.9 Distribution of malaria Figure 8.10 Global distribution of neglected tropical diseases (NTDs) by number of NTDs per country xii Medical Parasitology in the Philippines Figure 8.11 School teachers administering deworming tablets to students in a public elementary school in Biñan, Laguna Figure 8.12 Cumulative STH prevalence and heavy intensity infections in school-age children in Aklan, Antique, and Capiz, 2007-2009 Figure 8.13 Process, performance, and impact indicators for helminth control Figure 8.14 Checking for tongue discoloration after administration of deworming tablets to school children to ensure compliance Figure 8.15 Former DOH Secretary Francisco Duque III and former Antique Governor Salvacion Perez administering anthelminthics to school children in Pandan Central Elementary School, Antique during the launch of the War on Worms—Western Visayas Figure 8.16 Parade of school children and teachers during the launch of War on Worms—Biñan, Laguna List of Plates Plate 2.1 Entamoeba histolytica cyst Plate 2.2 Entamoeba histolytica trophozoite Plate 2.3 Entamoeba histolytica quadrinucleate cyst Plate 2.4 Charcot-Leyden crystal observed in stool specimen of a patient suffering from amebiasis Plate 2.5 Agarose gel showing the 100bp PCR products of Entamoeba histolytica-positive stool specimens (lanes 2–15) Plate 2.6 Ultrasound showing a solitary hypoechoic mass at the right lobe of the liver suggesting ALA Plate 2.7 Entamoeba coli trophozoite Plate 2.8 Iodamoeba bütschlii cyst Plate 2.9 Acanthamoeba trophozoite exhibiting characteristic acanthopodia Plate 2.10 Naegleria fowleri trophozoites in ameboid and ameboflagellate forms Plate 2.11 Giardia duodenalis trophozoite Plate 2.12 Giardia duodenalis cysts Plate 2.13 Immature oocyst of Cystoisospora belli recovered from stool sample, showing a single sporoblast Plate 2.14 Toxoplasma tachyzoites Plate 2.15 Binucleate forms of trophozoites of Dientamoeba fragilis stained with trichrome Plate 2.16 Plasmodium falciparum ring forms Plate 2.17 Ixodes sp. Plate 2.18 Trypanosoma cruzi trypomastigote in thin blood smears stained with Giemsa Plate 3.1 Ascaris unfertilized egg, fertilized egg, and embryonated egg Plate 3.2 Ascaris in the liver Plate 3.3 Intestinal obstruction with Ascaris Plate 3.4 Ascaris in the brain Plate 3.5 Trichuris male and female Plate 3.6 Trichuris egg xiii xiv Medical Parasitology in the Philippines Plate 3.7 Rectal prolapse in a 9-year old female seen at the Philippine General Hospital with heavy Trichuris infection Plate 3.8 Buccal capsules of hookworms Plate 3.9 Hookworm filariform larvae Plate 3.10 Hookworm egg Plate 3.11 Cutaneous larva migrans Plate 3.12 Strongyloides stercoralis rhabditiform larva Plate 3.13 Enterobius cephalic alae Plate 3.14 D-shaped eggs of Enterobius vermicularis Plate 3.15 Male Capillaria philippinensis Plate 3.16 Female Capillaria philippinensis Plate 3.17 Capillaria philippinensis egg Plate 3.18 Capillaria philippinensis second stage larva from the feces of a person with intestinal capillariasis Plate 3.19 31-year old female with intestinal capillariasis before treatment and 1 year after treatment Plate 3.20 Proper excreta disposal is important for prevention and control of intestinal helminthiases including capillariasis Plate 3.21 Brugia malayi microfilaria Plate 3.22 Wuchereria bancrofti microfilaria Plate 3.23 Dermatolymphangioadenitis (acute lymphatic filariasis) Plate 3.24 Elephantiasis Plate 3.25 Hydrocele Plate 3.26 Small and big hydroceles in 2 patients suffering from filariasis Plate 3.27 Farmer in abaca plantation Plate 3.28 An axil of abaca: a breeding site of Aedes poecilus Plate 3.29 Parastrongylus adults Plate 3.30 Achatina fulica, the intermediate host of Parastrongylus cantonensis Plate 3.31 Trichinella spiralis larvae in muscle Plate 4.1 Taenia saginata scolex Plate 4.2 Taenia saginata gravid segment Plate 4.3 Taenia egg Plate 4.4 Taenia solium scolex Plate 4.5 Cysticercus cellulosae from pork Plate 4.6 Hymenolepis spp. scolex Plate 4.7 Hymenolepis spp. gravid segment List of Plates xv Plate 4.8 Hymenolepis nana egg Plate 4.9 Hymenolepis diminuta egg Plate 4.10 Dipylidium caninum gravid segment Plate 4.11 Dipylidium caninum egg capsule Plate 4.12 Raillietina garrisoni adult Plate 4.13 Flour beetle (Tribolium spp.), the intermediate host of Raillietina garrisoni Plate 4.14 Diphyllobothrium latum scolex Plate 4.15 Diphyllobothrium latum egg Plate 4.16 Hydatid sand Plate 5.1 Schistosoma japonicum male and female Plate 5.2 Schistosoma japonicum egg Plate 5.3 Schistosoma japonicum adults in copula Plate 5.4 A boy from Leyte with portal hypertension and ascites secondary to schistosomiasis Plate 5.5 Schistosoma egg in the brain Plate 5.6 Oncomelania h. quadrasi, intermediate host of Schistosoma japonicum Plate 5.7 Paragonimus westermani adult Plate 5.8 Paragonimus westermani egg; note the flattened operculum and the abopercular portion Plate 5.9 Antemelania asperata, first intermediate host of Paragonimus westermani Plate 5.10 Sundathelphusa philippina, the second intermediate host of Paragonimus westermani Plate 5.11 Paragonimus westermani metacercaria in crab heart muscle Plate 5.12 Trapa bicornis, second intermediate host of Fasciolopsis buski Plate 5.13 Pila luzonica, second intermediate host of Echinostoma ilocanum Plate 5.14 Echinostoma ilocanum adult Plate 5.15 Artyfechinostomum malayanum adult Plate 5.16 Heterophyid fluke adult Plate 5.17 Heterophyid egg Plate 5.18 Fasciola egg Plate 5.19 Opistorchis viverrini adult Plate 6.1 Bee (Bombus sp.) Plate 6.2 Wasp Plate 6.3 Bee stinger Plate 6.4 Kissing bug (Triatoma sp.) Plate 6.5 Caterpillar, dorsal view Plate 6.6 Caterpillar head and thorax, lateral view xvi Medical Parasitology in the Philippines Plate 6.7 Centipede Plate 6.8 Centipede head Plate 6.9 Scorpion Plate 6.10 Black widow spider (Latrodectus hasselti) Plate 6.11 Blackfly (Simulium sp.) Plate 6.12 Midge (Culicoides spp.) Plate 6.13 Sandfly (Phlebotomus spp.) Plate 6.14 Horsefly (Tabanus spp.) Plate 6.15 Louse (Pediculus humanus capitis) Plate 6.16 Pubic louse (Phthirus pubis) Plate 6.17 Bedbug (Cimex sp.) Plate 6.18 Butterfly scales Plate 6.19 Dust mite (Blomia tropicalis) Plate 6.20 Dust mite (Glycyphagus sp.) Plate 6.21 Dust mite (Dermatophagoides pteronyssinus) Plate 6.22 Dust mite (Cheyletus malaccensis) Plate 6.23 Maggots Plate 6.24 Mosquito (Aedes aegypti) Plate 6.25 American cockroach (Periplaneta americana) Plate 6.26 German cockroach (Blatella germanica) Plate 6.27 Oriental cockroach (Blatta orientalis) Plate 7.1 Cysticercus in brain Plate 7.2 Ovary with incidental finding of Schistosoma japonicum ova Plate 7.3 Fallopian tube with incidental finding of Schistosoma japonicum ova Plate 7.4 Colon with adenocarcinoma and Schistosoma ova Plate 7.5 Adult filaria with microfilaria in an inguinal lymph node Plate 7.6 Adult Trichuris identified by ova in genital tract Plate 7.7 Cysticercus with calcareous corpuscles Plate 7.8 A fungal spore in a wet mount stool may look like a cyst of Entamoeba spp. Plate 7.9 A mite egg in a formalin-concentrated stool specimen may look like a hookworm egg Plate 7.10 A plant cell in a concentrated wet mount of stool may look like a helminth egg Plate 7.11 A pollen grain in a concentrated wet mount of stool may look like a fertilized egg of Ascaris lumbricoides Plate 7.12 Plant hair in a concentrated wet mount of stool may look like a hookworm or Strongyloides stercoralis larva List of Plates xvii Plate 7.13 Howell-Jolly bodies in a thin blood smear stained with Giemsa may look like malaria parasites Plate 7.14 A nucleated red blood cell may look like a schizont of Plasmodium spp. Plate 7.15 Fungal spores of Helicosprorium may be mistaken as microfilariae in stained blood smears Plate 8.1 Balantidium coli from pig Plate 8.2 Sarcocyst in sectioned esophageal muscle of water buffalo Plate 8.3 Cysticercus cellulosae freed from muscle of pig Plate 8.4 Strobilocercus fasciolaris freed from liver of field rat Plate 8.5 Anisakis larva from fish Plate 8.6 Fasciola gigantica and F. hepatica from water buffalo Plate 8.7 Fasciola metacercariae Plate 8.8 Schistosoma cercariae Plate 8.9 Dipylidium caninum from dog Plate 8.10 Dirofilaria immitis from dog Plate 8.11 Macracanthorhynchus hirudinaceus from pig Plate 8.12 Echinostoma lindoense from field rat Plate 8.13 Eurytrema pancreaticum from cattle Plate 8.14 Philophthalmus gralli from duck Plate 8.15 Plagiorchis philippinensis from rat Plate 8.16 Sparganum of Spirometra from muscle of frog Plate 8.17 Gnathostoma doloresi from pig Plate 8.18 Gnathostoma larva from frog muscle Plate 8.19 Toxacara canis from dog Plate 8.20 Toxocara canis embryonated egg (infective) Plate 8.21 Mammomonogamus laryngeus in copula from water buffalo xviii Medical Parasitology in the Philippines List of Tables Table 1.1 Classification of protozoan parasites Table 1.2 Classification of metazoan parasites Table 2.1 Comparison of bacillary and amebic dysentery Table 2.2 Selected Philippine data on giardiasis Table 2.3 Selected Philippine studies on trichomoniasis Table 2.4 Millennium development goals: eight goals for 2015 Table 2.5 Comparison of morphological features of malaria parasites Table 2.6 Clinical features and laboratory findings in severe malaria infection Table 2.7 Comparison of sign and symptoms of sever malaria in adults and children Table 2.8 Macrostratification of malaria endemic provinces according to annual incidence Table 2.9 Treatment of malaria infection Table 2.10 Summary of human cases of babesiosis reported in some Asian countries Table 3.1 Core indicators of mass drug administration for soil-transmitted helminth infections Table 3.2 The WASHED framework for a comprehensive control of soil-transmitted helminth infections Table 3.3 Comparison of microfilaria of Wuchereria bancrofti and Brugia malayi Table 3.4 Algorithm for the diagnosis of the probability of acute trichinellosis in humans Table 4.1 WHO classification for hepatic echinococcal cysts Table 5.1 Prevalence of schistosomiasis stratified by province (2005-2007) Table 6.1 List of immediate diagnostic features of arthropods Table 6.2 Specific injuries and their causative agents Table 6.3 Principal differences between mites and ticks Table 6.4 Arthropods as pests of stored products, food and water sources Table 6.5 Identifying characteristics of some myiasis-producing larva Table 6.6 List of arthropod-associated diseases and their corresponding agents and vectors Table 7.1 WHO classification of intensity of infections with soil-transmitted helminths and Schistosoma spp. Table 7.2 Organs and parasites isolated xix xx Medical Parasitology in the Philippines Table 7.3 Special stains and corresponding parasites Table 7.4 Antibody detection tests offered at CDC Table 7.5 Commercially available parasite antigen detection tests Table 7.6 Recommended stool examination techniques for specific situations Table 8.1 Philippine fishes found harboring anisakine larvae (from various authors) Table 8.2 Philippine fishes found harboring metacercariae of heterophyid species Table 8.3 Protozoans and helminthic organisms of special importance to immunocompromised patients Table 8.4 Microsporidial infections in immunocompromised patients Table 8.5 Neglected tropical diseases targeted by the WHO Table 8.6 Target population, drug recommended, and mass drug administration frequency of health programs in the Philippines Table 8.7 Categories, usage, and frequency of collection of indicators Table 8.8 Vaccines for travelers Table 8.9 Vaccines for selective use by travelers Table 8.10 Recommended drugs used in the prophylaxis for malaria Table 8.11 Specific infectious diseases involving potential health risks for travelers Foreword N o other book published by the University of the Philippines Manila (UPM) has been as widely patronized both by UPM constituents the book all the more relevant to policy makers, practitioners, students, and health workers involved in eradicating parasitism in highly and other health students and professionals affected communities. throughout the country than the Philippine To this day, parasitic infections are still Textbook on Medical Parasitology, now entitled considered a major public health problem in Medical Parasitology in the Philippines. the Philippines and the rest of the Asian region. That the response to the first two editions For a developing and tropical country like the of the book has been overwhelming affirms Philippines, the prevalence of parasitic diseases the value and significance of the material in is worsened by high population density, hot complementing meager publications on medical and humid climate and other environmental parasites with special focus on the local setting. factors, poverty, and socioeconomic conditions Dr. Vicente Y. Belizario, Jr. and the that provide a conducive setting to the parasites. contributors of the book for both editions Notwithstanding the difficulties and deserve commendation for responding to the struggles of fighting parasitism, all sectors need for a locally compiled comprehensive should come together and join efforts to material on parasitology through their combat the disease because of its grave effects painstaking work on this book. on the health, productivity, and well-being of It is good to know that the book that first the people. came out in 1998 has been updated again I am confident that his latest edition of through this third edition. The additional the book will serve as an accurate and valuable data and information, fresh insights, and reference material in the continuing war against new experiences shared by the authors at the parasites. global, regional, and national settings, make Thank you again for this gem of a textbook. MANUEL B. AGULTO Chancellor University of the Philippines Manila xxi xxii Medical Parasitology in the Philippines Foreword to the Second Edition T he preparation of this Philippine Textbook of Medical Parasitology merits commendation for many reasons. It is a precious health in the Philippines. It must be a valuable reference for those involved in the eradication of parasitism in communities especially among product of collaborative effort among the school children and for all with interest in top parasitologists in the country, including tropical diseases. faculty members from different medical and Our teachers have been used to prescribing science colleges. The comprehensive biological foreign textbooks in tertiary education and presentation (gross, microscopic and molecular) professional courses. This is primarily due to and the extensive and updated epidemiological a mindset that we are not capable of making data on each parasite speak of the rigorous our own. This textbook is proof that Filipino scholarship of the contributors and the editors. authors can and should provide the information It should have a special place in all public and needed by our students, professionals and policy private health libraries. makers. Learning, practice and policy making This book makes accessible to medical, should, after all, be in the context of what is public health and other paramedical students obtaining in the life and the environment of and to various health professionals and policy the learner and user. makers important and relevant scientific UP Manila is particularly proud to be the information on parasites that impact on human publisher of this textbook. MARITA V. T. REYES Chancellor University of the Philippines Manila xxiii xxiv Medical Parasitology in the Philippines Foreword to the First Edition I t is a great pleasure and honor to write the foreword of a book which addresses a significant need for information. Definitely, Parasitic infections constitute a major public health problem in the Philippines and many parts of the world. No geographic there is a need to make information on area is spared from colonization by parasites. medically important parasites more accessible. The seriousness of the problem is not only The first Philippine Textbook of Medical confined to the morbidity and mortality that Parasitology is relevant because it is focused on parasites can cause. Its effects are also linked to medical parasites which are found in our local different aspects of societal life such as decreased setting. It is therefore an excellent complement productivity and growth, mental retardation, to existing books on parasitology which are and malnutrition. foreign in orientation. All attempts should be made to control This book is a welcome addition to parasitic diseases because of their overwhelming locally published learning resources which at ill effects. These have to be a multidisciplinary the moment are quite meager. We realize the undertaking requiring, contributions from difficulties and travails of editors and authors. parasitologists, anthropologists, ecologists, I congratulate Dr. Vicente Y. Belizario, Jr. and immunologists, clinicians and economists, to his team for their commitment and dedication name a few. to our countrymen. It is timely that this book It is my wish that this book receive the is published in 1998, the 100th year of the attention it deserves because the knowledge Republic and the 90th year of the University it contains is a powerful means to combat of the Philippines Manila. parasitism in our country. PERLA D. SANTOS-OCAMPO Chancellor University of the Philippines Manila xxv xxvi Medical Parasitology in the Philippines Preface P arasitic infections remain as a major challenge to public health especially in developing countries like the Philippines. While Health Organization are included for reference purposes. For the first time, relevant policies and guidelines from the Department of Health are there have been significant advances in terms listed for the guidance of the readers. of a better understanding of the epidemiology The production of this book would not of these infections, improved diagnostic tools have been possible if not for the major efforts and newer approaches to control, in many of the members of the Editorial Team as well areas where these infections are encountered, as the various contributors of the chapters and barriers to early diagnosis, treatment, control sections who are themselves experts in their and prevention remain. own respective fields. Prof. Winifreda de Leon, The development of this learning resource, with her long experience in parasitic infections, Medical Parasitology in the Philippines, is a remains the Co-Editor of this book, while Dr. response to these continuing challenges. More Edsel Maurice Salvaña and Dr. Francis Isidore than providing basic information for students Totañes served as Associate Editors. Mr. Paul and trainees in medicine, public health, nursing, Lester Chua provided vital assistance to push medical technology, and other allied health this book writing project forward. The Editorial professions, this book provides important Team is very grateful to Johnson & Johnson updates of chapters included in the first two Corporate Contributions Committee that editions of the Philippine Textbook of Medical provided a grant for the book writing initiative Parasitology as well as an introduction to in a similar way that it provided support for important subject areas like neglected tropical the development of the first two editions of and parasitic infections and emporiatrics. This the book. book therefore may be considered as the third With the launching of this book, may there edition of the book. be hope that parasitic infections in this beloved In this edition, the life cycles developed by country would be better understood, diagnosed, the United States Centers for Disease Control treated, controlled and prevented for a healthier and Prevention are utilized, and as in the other and more productive populace. earlier editions, Bench Aids developed by World VICENTE Y. BELIZARIO, JR. xxvii xxviii Medical Parasitology in the Philippines Acknowledgments T he Third Edition of the Philippine Textbook of Parasitology was made possible through a generous educational grant will lay the foundation for a life of learning in medical parasitology for the next generation of leaders in this field. Working with you has been from Johnson & Johnson (Philippines) Inc., a great honor and privilege. through its pharmaceutical division, Janssen Our deepest gratitude to the University of Pharmaceutica, our stalwart partners in this the Philippines Press for providing the technical undertaking. expertise and know-how to produce an excellent The editors would like to acknowledge the learning resource. invaluable contributions of the new associate Very special thanks to the Chancellor of editors, Dr. Edsel Maurice Salvaña and Dr. the University of the Philippines Manila, Dr. Francis Isidore Totañes for their able assistance in Manuel B. Agulto, for his wholehearted support this revision. We would also like to acknowledge of this book writing initiative that will provide the herculean efforts of the Editorial Team for a valuable reference and guide for students the countless hours spent revising, reviewing, and health professionals in the service of the and re-revising manuscripts as well as meeting Filipino people. the tight deadlines. In addition, we recognize We are most grateful to our respective the contributions of Dr. Carlos Miguel Perez, families for their understanding and Dr. Timothy Ting, Dr. Ernesto Balolong, Jr., encouragement in the course of preparing this and Amelia Breyre in providing inputs for the book. Thank you for allowing us to work more improvement of selected articles. than the usual office hours and beyond the We are tremendously indebted to the confines of our workplace. individual chapter and section contributors. And finally, we give thanks for the Your expertise and dedication to your profession enlightenment and guidance from the Almighty, of teaching and research are the heart and soul to Whom this work is humbly offered. of this book. The chapters and sections herein VICENTE Y. BELIZARIO, JR. WINIFREDA U. DE LEON xxix Chapter 1 Introduction to Medical Parasitology General Considerations Vicente Y. Belizario, Jr. P arasitology is the area of biology concerned with the phenomenon of dependence of one living organism on another. Medical Parasitology protected from harm, while it does not cause any damage to the tissues of its host. Mutualism is a symbiosis in which two organisms mutually is concerned primarily with parasites of humans benefit from each other like termites and the and their medical significance, as well as their flagellates in their digestive system, which importance in human communities. Tropical synthesize cellulase to aid in the breakdown Medicine is a branch of medicine that deals of ingested wood. Parasitism is a symbiotic with tropical diseases and other special medical relationship where one organism, the parasite, problems of tropical regions. A tropical disease lives in or on another, depending on the latter is an illness, which is indigenous to or endemic for its survival and usually at the expense of the in a tropical area but may also occur in sporadic host. One example of a parasite is Entamoeba or epidemic proportions in areas that are not histolytica, which derives nutrition from the tropical. Many tropical diseases are parasitic human host and causes amebic dysentery. diseases. Parasites Biological Relationships Parasites are often described according to Organisms may develop unique relationships their habitat or mode of development. A parasite due to their habitual and long associations living inside the body of a host is known as an with one another. These relationships are very endoparasite, whereas a parasite living outside important to their survival. Symbiosis is the the body of a host is an ectoparasite. The living together of unlike organisms. It may also presence of an endoparasite in a host is called an involve protection or other advantages to one infection, while the presence of an ectoparasite or both organisms. on a host is called an infestation. A parasite is Different forms of symbiosis may be considered erratic when it is found in an organ distinguished on the basis of whether or not which is not its usual habitat. Most parasites the association is detrimental to one of the are obligate parasites in that they need a host two organisms. Commensalism is a symbiotic at some stage of their life cycle to complete relationship in which two species live together their development and to propagate their and one species benefits from the relationship species. Obligate parasites such as tapeworms without harming or benefiting the other. depend entirely upon their host for existence. For example, Entamoeba coli in the intestinal A facultative parasite may exist in a free-living lumen are supplied with nourishment and are state or may become parasitic when the need 1 2 Medical Parasitology in the Philippines arises. A parasite, which establishes itself in a Vectors host where it does not ordinarily live, is called Vectors are responsible for transmitting the an accidental or incidental parasite. A permanent parasite from one host to another. A biologic parasite remains on or in the body of the host vector transmits the parasite only after the for its entire life, while a temporary parasite lives latter has completed its development within on the host only for a short period of time. A the host. A biologic vector is therefore an spurious parasite is a free-living organism that essential part of the parasite’s life cycle. When passes through the digestive tract without an Aedes mosquito sucks blood from a patient infecting the host. with filariasis, the parasite undergoes several Hosts stages of development from first stage larva to third stage larva before the latter (infective Hosts can be classified into various types stage) is transmitted to another susceptible based on their role in the life cycle of the host. A mechanical or phoretic vector, on the parasite. A definitive or final host is one in other hand, only transports the parasite. Flies which the parasite attains sexual maturity. In and cockroaches that feed on fecal material taeniasis, for example, humans are considered may carry enteric organisms and transfer these the definitive host. An intermediate host harbors to food, which could be ingested by humans. the asexual or larval stage of the parasite. Pigs or cattle serve as intermediate hosts of Taenia spp., Exposure and Infection while snails are hosts of Schistosoma spp. If there Majority of parasites are pathogens is more than one intermediate host, these can be which are harmful and which frequently classified as first and second intermediate hosts. cause mechanical injury to their hosts. A A paratenic host is one in which the carrier harbors a particular pathogen without parasite does not develop further to later stages. manifesting any signs and symptoms. Exposure However, the parasite remains alive and is able is the process of inoculating an infective agent, to infect another susceptible host. For example, while infection connotes the establishment of Paragonimus metacercaria in raw wild boar meat the infective agent in the host. can pass through the intestinal wall of humans The incubation period is the period between and complete its development. In this case, the infection and evidence of symptoms. It is wild boar serves as a paratenic host transferring sometimes referred to as the clinical incubation the infective stage to humans. Paratenic hosts period. The pre-patent period, also known as the are important because they widen the parasite biologic incubation period, is the period between distribution and bridge the ecological gap infection or acquisition of the parasite and between the definitive and intermediate hosts. evidence or demonstration of infection. There are also other animals that harbor Autoinfection results when an infected the parasite other than definitive, intermediate, individual becomes his own direct source of and paratenic hosts. These are known as infection. In enterobiasis, infection may occur reservoir hosts. They allow the parasite’s life through hand-to-mouth transmission. Infective cycle to continue and become additional eggs may end up in the hands by scratching sources of human infection. Pigs are reservoirs the perianal areas where the gravid females lay of Balantidium coli, field rats of Paragonimus their eggs. Alternatively, parasites may multiply westermani, and cats of Brugia malayi. internally, such as Capillaria philippinensis. Humans are not always the final host. Superinfection or hyperinfection happens when Humans may be the most important host in the already infected individual is further the spread of the disease or an incidental host of infected with the same species leading to massive parasites prevalent in other animals. Chapter 1: Introduction to Medical Parasitology 3 infection with the parasite. An alteration in of infection. Autoinfection where the infected the normal life cycle of Strongyloides results in person himself is the source of infection is seen a large increase in worm burden, which may in the life cycles of Capillaria philippinensis, lead to severe debilitation or even death due to Enterobius vermicularis, Hymenolepis nana, and an increase in the proportion of rhabditiform Strongyloides stercoralis. larvae that transform into filariform larvae while Modes of Transmission in the gut. Since the most common source of parasitic Sources of Infection infection is contaminated food and water, There are various sources of parasitic the most likely portal of entry is the mouth. infections. The most common sources are Majority of infections with cestodes, trematodes, contaminated soil and water. Lack of sanitary and intestinal protozoans are foodborne: Taenia toilets and the use of night soil or human solium, Taenia saginata, and Diphyllobothrium excreta as fertilizer allow the eggs to come in latum from eating food harboring the infective contact with the soil and favor the development larval stages; Entamoeba histolytica and Giardia of Ascaris lumbricoides, Trichuris trichiura, lamblia from drinking water contaminated with Strongyloides stercoralis, and hookworm. Water cysts; and Clonorchis, Opistorchis, and Haplorchis may be contaminated with cysts of amebae or through ingesting raw or improperly cooked flagellates, as well as cercariae of Schistosoma. freshwater fish containing infective larvae. Another possible source of infection is food, Skin penetration is another route of which may contain the infective stage of transmission. Hookworms and Strongyloides the parasite, as exemplified by a number of enter via exposure of skin to soil, while trematode and cestode infections. Consumption Schistosoma species enter skin via water. of undercooked or raw freshwater fish can Arthropods also serve as vectors and result in several intestinal and liver fluke transmit parasites through their bites. Examples infections. Raw crabs are considered a delicacy are agents of malaria, filariasis, leishmaniasis, in areas where paragonimiasis is endemic, trypanosomiasis, and babesiosis. while raw Bullastra snails are associated with Another way of acquiring infection is Artyfechinostomum malayanum infection. through congenital transmission. Toxoplasma Arthropods can also transmit infection. gondii trophozoites can cross the placental Mosquitoes are vectors of malaria and filarial barrier during pregnancy. In transmammary parasites. Triatoma bugs are carriers of infection with Ancylostoma and Strongyloides, Trypanosoma cruzi causing Chagas disease. the parasites may be transmitted through Sand flies (e.g., Phlebotomus spp.) are the mother’s milk. natural vectors of all types of Leishmania. Other Other ways of acquiring the infection animals, whether wild or domesticated, may include inhalation of airborne eggs of Enterobius also harbor parasites. Cats are direct sources of and sexual intercourse as in the case of Toxoplasma infection, while rats may be infected Trichomonas vaginalis. with Hymenolepis nana. Nomenclature Other sources of infection include another person, his beddings and clothing, as well as the Animal parasites are classified according immediate environment he has contaminated, to the International Code of Zoological or even one’s self. Asymptomatic carriers of Nomenclature. Each phylum is divided into Entamoeba histolytica working as food handlers classes, which are further subdivided into orders, in food establishments may be important sources families, genera, and species. At times, the 4 Medical Parasitology in the Philippines further divisions of suborder, superfamily, and number of worms per infected person. This may subspecies are employed. Scientific names are be measured directly or indirectly and is also latinized; family names are formed by adding referred to as the worm burden. In the case of -idae to the stem of the genus type; generic soil-transmitted helminths, it can be measured names consist of a single word written in initial directly by counting expelled worms during capital letter; the specific name always begins treatment, or indirectly by counting helminth with a small letter. The names of the genera eggs excreted in feces. The latter is expressed as and species are italicized or underlined when the number of eggs per gram (epg). written. Clinical consequences of infections or diseases that affect an individual’s well-being Life Cycle refer to morbidity. Through adaptation to their hosts and the Treatment external environment, parasites have developed life cycles, which may be simple or complicated. Deworming is the use of anthelminthic Most parasitic organisms attain sexual maturity drugs in an individual or a public health in their definitive hosts. Some spend their program. Cure rate refers to the number entire lives within the host with one generation (usually expressed as a percentage) of previously after another, while others are exposed to the positive subjects found to be egg negative external environment before being taken up on examination of a stool or urine sample by an appropriate host. The larval stage of the using a standard procedure at a set time after parasite may pass through different stages in an deworming. Egg reduction rate (ERR) is the intermediate host before it reaches a final host. percentage fall in egg counts after deworming As the life cycle becomes more complicated, the based on examination of a stool or urine sample lesser the chances are for the individual parasite using a standard procedure at a set time after to survive. the treatment. The perpetuation of a species of parasite Selective treatment involves individual-level depends upon its ability to ensure transmission deworming with selection for treatment based from one host to the next. The parasite must, on a diagnosis of infection or an assessment of the therefore, adapt to protect itself from the host’s intensity of infection, or based on presumptive defenses and the external environment, and it grounds. This strategy can be used in whole must overcome the attrition in the species by populations, or in defined risk groups. Targeted producing numerous progeny. treatment is group-level deworming where the (risk) group to be treated (without prior Epidemiologic Measures diagnosis) may be defined by age, sex, or other Epidemiology is the study of patterns, social characteristics irrespective of infection distribution, and occurrence of disease. status. Universal treatment is population-level Incidence is the number of new cases of deworming in which the community is treated infection appearing in a population in a given irrespective of age, sex, infection status, or other period of time. Prevalence is the number social characteristics. Preventive Chemotherapy is (usually expressed as percentage) of individuals the regular, systematic, large-scale intervention in a population estimated to be infected with involving the administration of one or more a particular parasite species at a given time. drugs to selected population groups with the Cumulative prevalence is the percentage of aim of reducing morbidity and transmission of individuals in a population infected with at selected helminth infections. least one parasite. Intensity of infection refers Coverage refers to the proportion of the to burden of infection which is related to the target population reached by an intervention. It Chapter 1: Introduction to Medical Parasitology 5 could be the percentage of school-age children reservoirs of disease. It also covers the provision treated during a treatment day. of safe drinking water and food safety; housing Efficacy is the effect of a drug against an that is adequate in terms of location, quality of infective agent in ideal experimental conditions shelter, and indoor living conditions; facilities and isolated from any context. Effectiveness for personal and domestic hygiene; as well as is a measure of the effect of a drug against safe and healthy working conditions. an infective agent in a particular host, living Sanitation is the provision of access to in a particular environment with specific adequate facilities for the safe disposal of human ecological, immunological, and epidemiological excreta, usually combined with access to safe determinants. Effectiveness is usually measured drinking water. by means of qualitative and quantitative Eradication versus Elimination diagnostic tests which detect eggs or larvae in feces or urine after an optimal time interval, Disease eradication is defined as a permanent which is variable for each parasite. Cure rate reduction to zero of the worldwide incidence of and egg reduction rate are indicators that are infection caused by a specific agent, as a result commonly used to measure the reduction of deliberate efforts. Once this is achieved, in prevalence and reduction in intensity of continued measures are no longer needed. On infection, respectively. the other hand, disease elimination is a reduction Drug resistance is a genetically transmitted to zero of the incidence of a specified disease in a loss of susceptibility to a drug in a parasite defined geographic area as a result of deliberate population that was previously sensitive to the efforts. Continued intervention or surveillance appropriate therapeutic dose. measures are still required. Prevention and Control References Morbidity control is the avoidance of illness Beaver PC, Jung RC, Cupp EW. Clinical caused by infections. It may be achieved by parasitology. 9th ed. Philadelphia: Lea and periodically deworming individuals or groups, Febiger; 1984. known to be at risk of morbidity. Markell EK, John DT. Medical parasitology. Information-education-communication 8th ed. Philadelphia: W. B. Saunders (IEC) is a health education strategy that aims Company; 1999. to encourage people to adapt and maintain Markell EK, Voge M, John DT. Medical healthy life practices. parasitology. 7th ed. Philadelphia: W. B. Environmental management is the planning, Saunders Company; 1992. organization, performance, and monitoring Muller R. Worms and disease: a manual of of activities for the modification and/or medical helminthology. London: William manipulation of environmental factors or their Heinemann Medical Books Limited; 1975. interaction with human beings with a view to Neva FA, Brown HW. Basic clinical parasitology. preventing or minimizing vector or intermediate 6th ed. Connecticut: Appleton and Lange; host propagation and reducing contact between 1994. humans and the infective agent. Walter-Beck J, Davies J. Medical parasitology. Environmental sanitation involves 3rd ed. Missouri: The C. V. Mosby interventions to reduce environmental health Company; 1981. risks including the safe disposal and hygienic World Health Organization. Prevention and management of human and animal excreta, control of schistosomiasis and intestinal refuse, and waste water. It also involves the nematodes. Geneva: World Health control of vectors, intermediate hosts, and Organization; 2002. 6 Medical Parasitology in the Philippines Host-Parasite Relationships Vicente Y. Belizario, Jr. T he relationship between parasite and host has gradually evolved through the ages. The process has produced changes in the parasite spp. are hermaphroditic, that is, they contain a complete set of male and female organs capable of producing thousands of ova. Furthermore, and in its life cycle, consequently affecting the flukes undergo asexual reproduction in the life of its host. intermediate hosts to increase the number of Adaptation causes changes in the molecular progeny. biology, biochemistry, immunology, and Parasitic existence may also result in structure of the parasite. Parasites that are more profound biochemical adaptations. Such specialized have shown the greatest changes, changes include loss of certain metabolic most of which are essential for survival. pathways common to free-living organisms. The most noticeable adaptations are This process is called streamlining, that is the found in the locomotory and digestive inability of the parasite to synthesize certain organs. Protozoans belonging to the Phylum cellular components and the need of the parasite Apicomplexa have no locomotory organelles, to obtain these from a host. Streamlining and these organisms are mostly parasitic. Free- is exemplified by hemoflagellates and other living flatworms have cilia on their epidermis, helminth parasites. These changes in metabolic while parasitic cestodes and trematodes do pathways may become the target of future not have any. Cestodes and trematodes obtain chemotherapeutic strategies. nutrients through their tegument, which is Some parasites have developed specialized provided with microvilli. Flatworms have mechanisms needed for entry into the body highly specialized organs of attachment, such or tissues. The trophozoites of Entamoeba as hooks and suckers, which anchor the parasite histolytica secrete cysteine proteinases, which inside the body of the host and facilitate tissue allow the parasite to penetrate the mucosa and migration. The size and shape of the parasite adhere to the underlying layer and surrounding are also adapted for maintaining its hold in tissues. No such enzyme has been found in the the host. Adult Ascaris worms maintain their commensal Entamoeba coli. The cercariae of position inside the intestinal wall by constant Schistosoma contain penetration glands, which movement. The integument is thickened to produce an enzyme capable of digesting the skin resist enzymes and juices in the digestive tract allowing entry into the body of the host. All of humans and to protect against dessication cestode embryos have six hooklets, which aid and physical injury. In intestinal flukes, the them in tissue penetration before developing tegument is covered with spines to prevent into encysted larvae. abrasion. Special coverings of ova, larvae, and Effects of the Parasite on the Host cysts protect the parasite during its free-living stage. These coverings also aid in resisting Some organisms may live inside the body digestive juices once the parasite is ingested by of the host without causing any damage, but the host. in most instances, they have the ability to Reproductive systems of flatworms are inflict damage to their host. There are several highly elaborate and complicated. All tapeworms mechanisms by which parasites cause injury and flukes, with the exception of Schistosoma to the host. The most common mechanism Chapter 1: Introduction to Medical Parasitology 7 is by interference with the vital processes of blood factor increases the susceptibility of an the host through parasitic enzymes. Secretory individual to Plasmodium vivax infection. and excretory products elaborated by many Another important aspect is the nutritional parasites allow them to metabolize nutrients status of the host. A diet rich in protein is obtained from the host and store these for not suitable for the development of intestinal energy production. This is best exemplified by protozoans, while a low-protein diet favors Entamoeba histolytica trophozoites that secrete the appearance of symptoms of amebiasis cysteine proteinases, which do not only digest and complications of the disease. A high cellular materials but also degrade epithelial carbohydrate diet favors the development of basement membrane facilitating tissue invasion. some tapeworms. Another mechanism is through invasion Immune processes play an important role in and destruction of host tissue. One example host-parasite relationships. Absolute immunity is Plasmodium, which invades red blood cells. to reinfection occurs rarely following protozoan After multiplication, the host’s red blood cells infections, and probably never happens with rupture resulting in the release of merozoites. helminth infections in humans. Acquired In Schistosoma japonicum infection, cumulative immunity may be very important in modifying deposition of eggs in the liver stimulates an the severity of disease in endemic areas. immune response mechanism resulting in References granuloma formation and then fibrosis which leads to portal hypertension and massive Beaver PC, Jung RC, Cupp, EW. Clinical hemorrhage in the venules. Hookworms have parasitology. 9th ed. Philadelphia: Lea and cutting plates, which can attach to the intestinal Febiger; 1984. mucosa and destroy the villi. Large numbers of Crompton DW, Savioli L. Intestinal parasitic worms such as Ascaris form tangled masses that infections and urbanization. Bull World can lead to intestinal obstruction. An Ascaris Health Organ. 1993;71(1):1–7. worm in the intestine may invade other organs Markell EK, John DT. Medical parasitology. like the appendix and bile ducts and may cause 8th ed. Philadelphia: W. B. Saunders a surgical emergency. Company; 1999. Parasites can also deprive the host of essential Markell EK, Voge M, John DT. Medical nutrients and substances. Heavy hookworm parasitology. 7th ed. Philadelphia: W. B. infection causes massive intestinal bleeding which Saunders Company; 1992. results in chronic blood loss and iron deficiency Muller R. Worms and diseases: a manual of anemia. Diphyllobothrium latum competes with medical helminthology. London: William its host for the available supply of Vitamin B12, Heinemann Medical Books Limited; 1975. thus resulting in megaloblastic anemia. Neva FA, Brown HW. Basic clinical parasitology. 6th ed. Connecticut: Appleton and Lange; Effects of the Host on the Parasite 1994. There are several factors which determine Que X, Reed SL. The role of extracellular the outcome of an infection. The genetic make- cysteine proteinases in pathogenesis of up of the host may influence the interaction Entamoeba histolytica invasion. Parasitol between host and parasite. In falciparum Today. 1997;13(5):190–3. malaria, possession of sickle-cell trait confers Walter-Beck J, Davies J. Parasitology. 3rd ed. some protection, while the presence of Duffy Missouri: The C. V. Mosby Company; 1981. 8 Medical Parasitology in the Philippines Immunology of Parasitic Infections Edsel Maurice T. Salvaña, Winifreda U. de Leon, Katerina T. Leyritana T he function of the immune system is to protect the body from invasion by potential pathogens. It is a tightly-controlled The ability of the parasites to cause infections has evolved through the process of natural selection, since only a proportion of balancing act, in the sense that dysfunction parasites are able to accomplish this. In the same of the immune system can lead to either a way, the host’s ability to defend itself against a permissive environment for infection on one parasite’s invasion is also selected for. Some life hand, or to unchecked activation which can cycles are so complicated that the parasite has harm the organism on the other. Immunity adapted means to survive immune assault in to parasites, especially eukaryotes such as not just one but a variety of hosts, including helminths and protozoans, is complicated the definitive host, intermediate hosts, and by the fact that, unlike bacterial pathogens, reservoir hosts. eukaryotic organisms are similar in make- The host-parasite relationship remains up and physiology. Moreover, parasites have dynamic, and while some parasites become evolved strategies to evade the immune system specific to some hosts over time, accidental over millions of years, and some are so successful infection of erstwhile non-susceptible hosts that these organisms not only survive but thrive may eventually lead to establishment of a new in the bloodstream (e.g., Schistosoma sp.) where reservoir, intermediate, or definitive host which they are subjected to constant and intimate in time may even become the dominant host for exposure to the body’s immune system. that organism. This is exemplified by zoonoses Parasitic infections in humans and animals such as infections with Trypanosoma sp., and occur when the parasite successfully establishes the newly discovered human malaria parasite itself in the host and is not eliminated by many Plasmodium knowlesi. host defense systems and is able to continue its Host-Parasite Interactions life cycle. However, not all interactions between the host and parasite relationship result in injury Natural physical barriers to the entry of the and pathology. It can result in the following parasite into the body constitute the first line outcomes: of defense against pathogens. The skin provides effective surface protection against invasion Parasite fails to become established in from parasites that initiate infection through the host. skin penetration. Adaptive mechanisms of Parasite becomes established and the some helminths allow them to overcome these host eliminates the infection. defenses. The filariform larvae of hookworms Parasite becomes established, and the and Strongyloides can synthesize a protein that host begins to overcome the infection aids in the entry through the skin. Schistosoma but is not totally successful. spp. cercariae are capable of skin penetration Parasite becomes established and because of the presence of glands in the anterior the host, in trying to eliminate the part of the parasite that secrete lytic enzymes. organism, becomes damaged itself. The mucous membranes lining the Parasite becomes established and kills respiratory, gastrointestinal, and genitourinary the host. tracts provide external barriers to parasite entry Chapter 1: Introduction to Medical Parasitology 9 as well. Tight junctions between epithelial cells defenses rely on humoral and cell-mediated serve to prevent passage of all but the smallest mechanisms of action. molecules. The low pH of vaginal secretions The innate response happens when the and gastric juices present a hostile environment body detects and eliminates pathogens through to many microorganisms. For instance, the non-specific mechanisms that use mechanical, trophozoites of Trichomonas vaginalis are unable chemical, and cytokine-mediated methods to to survive the acidic environment of the vagina, destroy or disrupt invading organisms with and once intestinal secretions envelope Giardia little or no delay from the time of invasion. One lamblia, its motility is greatly diminished method is through phagocytosis by macrophages reducing injury to the host. To evade this type and dendritic cells with subsequent pathogen of host defense, the infective stages of helminths elimination through oxidative killing and use of that are ingested, like embryonated eggs of toxic peptides. Some intracellular pathogens are Ascaris, Trichuris, and Taenia spp. are protected able to invade and multiply inside macrophages, from the acidic environment by thick egg shells. like Leishmania spp., Toxoplasma gondii, and The cystic wall of intestinal protozoa like the Trypanosoma cruzi, in which case cell-mediated Entamoeba and Giardia are also resistant to immune mechanisms (whether non-specific acidic pH. such as natural killer cells, or acquire cell- Chemical components of body fluids play mediated immunity through T-lymphocytes) a major role in the protection of the host. The are required to identify and destroy them. lipase content of breast milk, for example, has Toll-like receptors (TLRs) recognize been found to be toxic to Giardia lamblia in specific molecules that are non-native to the vitro. Lysozyme found in tears and saliva is able body and so represent some of the earliest to destroy microorganisms, along with secreted recognition mechanisms for pathogens. To IgA immunoglobulins in these fluids. date, ten TLRs have been identified and each Physiologic functions of the body also is activated by a bacterial components [e.g., inhibit parasite invasion. Peristalsis, motion LPS (TLR4), diacylated lipoprotein (TLR2 of cilia, and human reflexes all serve to expel and 6) and triacylated lipoprotein (TLR 1 parasites. Coughing enables expectoration of and 2), flagellin (TLR5)], viral RNA (TLR3), aberrantly situated adult Ascaris lumbricoides and other unfamiliar components. Binding of and eggs of Paragonimus westermani, and the a specific ligand to a TLR causes a cascade of flushing action of urine decreases the numbers reactions down a common signaling pathway of Trichomonas vaginalis. which produces cytokines such as interferon In the event that the parasite is able to gamma and interleukin-1. These cytokines overcome physical barriers, a second host activate natural killer cells and macrophages, defense comes into play. The penetration of stimulation of which leads to further production the body’s barriers results in a series of events of inflammatory cytokines, and co-stimulatory that facilitate sensing of the invading parasite molecules. TLRs are therefore largely responsible via pathogen-associated molecular patterns, or for triggering the initial inflammatory response. through pattern recognition responses which They function as pyrogens and synthesize enable the body to mount an immune response inflammatory response proteins, which then that acts towards eliminating or limiting the increase the number and function of phagocytic infection. cells. The host, once infected, is exposed to the Host-Immune Response parasite antigens, which in turn can stimulate The host possesses both innate and the host to mount an acquired specific response acquired immune defenses. Both kinds of against the antigen. The expression of acquired 10 Medical Parasitology in the Philippines immunity is the result of a complex series of Th1 lymphocytes produce gamma immunoregulatory events: activation, induction interferon and interleukin-2 which activate through proliferation, differentiation, and cytotoxic lymphocytes (with CD8 surface effector function. The effector function may molecules) and macrophages. This brings about be at the end point of a response or it might the cell-mediated immune response. serve a regulatory function that modulates other Cell-mediated immunity has been observed functions. in many parasitic infections. Parasite-specific The parasitic antigens may originate from antigens induce clonal expansion of parasite- the surface, from secretions and excretions, and specific T-lymphocytes. They may act by direct from somatic tissues of the parasite. Following cytotoxicity on the parasite or indirectly by initial contact with antigen (immunologic acting on natural killer cells or the antibody priming), subsequent antigen exposure leads producing B-lymphocytes. Migrating larvae of to more rapid and vigorous immune responses, Toxocara canis are killed through cell-mediated leading to immunologic memory. The response activity. of acquired immunity is either antibody- Th2 lymphocytes produce interleukins dependent or cell-mediated. 4, 5, and 6 that enhance the proliferation and Most of the time, immunity is directed differentiation of B-lymphocytes into plasma against the antigen that induced the response. cells, which are responsible for immunoglobulin Cross-reactivity does occur. The antigen may production. The antibodies that are produced be present in just one developmental stage or bind with specific parasite antigens and can in just one species of the parasite. There are activate complement and include the following antigens, however, that have been detected in classes: IgE, IgG, IgM, and IgA. all of the stages of parasite development or in all In helminthic infections, the most common members of a genus. It is therefore important responses include eosinophilia and elevated to remember that an immune response does serum IgE. With lumen-dwelling Ascaris not always equate with protection, and that lumbricoides and Trichuris trichiura, however, conversely, immunity to one pathogen may the immune response is not as intense compared confer immunity to another closely related with lymphatic dwelling Wuchereria bancrofti species. and Brugia malayi since contact with both recognition and effector elements of the Acquired Immune Response immune system is less intimate. Immunologic The immune response to parasitic response is also marked in visceral larval infections is under well-defined genetic control infections with Parastrongylus cantonensis and and has a strong influence over the outcome of Toxocara canis which are less likely to have infection in terms of resistance, susceptibility, immune-evading mechanisms since they are not and pathology. The major histocompatibility specifically adapted to the human host. complex (MHC) gene products help regulate IgE antibodies that are bound to the T-lymphocyte activities. Human leukocyte mucosal mast cells, eosinophils, and goblet antigen (HLA) is also a factor. cells can mediate the eventual expulsion of The specific immune response to the adult gastrointestinal helminths. IgE has also parasite begins when parasitic antigens are been identified on inflammatory cells involved processed and presented to the CD4 T-helper in the cytotoxic action on some parasites lymphocytes, which either belong to the Th1 like Schistosoma spp. referred to as antibody or Th2 subset. These subsets of T-helper dependent cell-mediated cytotoxicity (ADCC). cells are responsible for producing different There are a variety of activating molecules lymphokines. expressed by the eosinophils that mediate Chapter 1: Introduction to Medical Parasitology 11 ADCC. Among these are eosinophil activating parasite life cycles, location within body sites factor (EAF), interleukin-5, and granulocyte- that are relatively protected from the immune monocyte colony stimulating factor (GM-CSF). response, and antigenic complexity. Destruction of microfilariae among patients In addition, natural selection and with tropical pulmonary eosinophilia has been adaptation have resulted in deployment by attributed to ADCC mediated by IgE and the parasite of various mechanisms to avoid eosinophils. Cells like neutrophils and platelets the destructive effect of the host response. have been found to participate in ADCC as well. These major mechanisms include induction of With homocytotrophic IgG1, IgE can immune suppression, antigenic variation, host act on mast cells and basophils, which can mimicry, and sequestration among others. lead to degranulation and eventual release A. Resistance to Immune Response of pharmacologically active substances. Unregulated activation can result in an Protozoa and helminthic parasites that anaphylactic Type 1 hypersensitivity reaction enter the blood stream or tissue are often as seen during the rupture of Echinococcus able to survive and replicate because they are granulosus hydatid cysts. The same immediate resistant to the host innate immune response. hypersensitivity reaction has been observed at Parasites in humans are usually resistant to the site of the bite of several arthropods like complement. Macrophages can phagocytose mites and ticks. protozoa, but the cuticle and integument of The combined activity of IgG and IgM helminthic parasites make them resistant to can prevent penetration of erythrocytes by the cytotoxic effects of both neutrophils and Plasmodium spp. and Babesia spp., but are macrophages. This may be due to the loss of generally ineffective against gastrointestinal surface molecules that bind complement or helminths. In the presence of complement acquisition of host regulatory proteins such as activity, these antibodies can mediate lysis of decay accelerating factor. Trypanolytic factors trypomastigotes of Trypanosoma cruzi and, even such as apolipoprotein L-1 (APOL1) destroy in the absence of the complement, are involved non-human trypanosomes except Trypanosoma in the rapid phagocytosis of the same parasites. brucei which has evolved resistance through Secretory IgA in the intestines protect against expression of serum resistance-associated metacestode and gastrointestinal infections. IgM protein. A frameshift mutation in the APOL1 with secretory IgA mediate ADCC in Giardia gene enables a non-human trypanosome (T. lamblia infection. Among immunocompetent evansi) to infect a human, and addition of individuals, Cryptosporidium infection is self- recombinant APOL1 restored trypanolytic limited due to the combined action of IgA and activity. lgG with cell-medicated immunity, which helps B. Immune Suppression cleave the parasite from the enterocytes. In many infections, be it microbial or There are parasites that can reduce parasitic, the host can activate its non-specific, the immune function of macrophages that specific, humoral, and cell-mediated defenses result in lower capacity of phagocytosis and all at the same time. defective processing of antigen, as in the case of Plasmodium spp. infection. In Trypanosoma Parasite Evasion Mechanisms brucei infection, the trypomastigotes can Parasites have several characteristics that produce large amounts of surface glycoproteins. make it difficult for the host to detect and This affects the processing of the proteins eliminate them: parasite size, complicated due to antigenic competition and at the 12 Medical Parasitology in the Philippines same time impairs the B- and T-lymphocyte Malarial parasites, especially Plasmodium activities resulting in diminished production of falciparum, exhibit antigenic diversity. The lymphokines and immunoglobulins. mechanism is through repeat variation of the Entamoeba histolytica suppresses macrophage encoded polypeptides, which contain tandem respiratory burst and consequent nitric oxide sequences of amino acids, as observed in production, produces a suppressor factor that merozoite surface antigen (MSA) and ring- can inhibit movement of monocytes to the site infected erythrocyte surface antigen (RESA). of invasion (monocyte locomotion inhibitory These repeat sequences are antigenic epitopes, factor), and inhibits complement assembly. In which stimulate antibody production. With Fasciola infection, there is down regulation of variation, therefore, antibodies fail to recognize Th1 lymphocytes. In filarial infections with the antigen. Wuchereria bancrofti and Brugia malayi, there D. Host Mimicry is polyclonal hypergammaglobulinemia where antibodies lack specificity against these parasites. The larval stage of Echinococcus granulosus This has also been observed in Plasmodium spp. in the hydatid cyst has been found to carry infection. P blood group antigen, and the tegument of Blocking antibodies produced by several Schistosoma spp. adult can acquire antigenic parasites like Wuchereria bancrofti can also molecules from the host. Antibodies produced dampen the effect of immune responses. In against the parasite then fail to recognize non- Necator americanus infection, the immune self from self-antigens. response is directed against the deeper layers E. Intracellular Sequestration of its cuticle but the immune response is diverted to the rapidly changing surface of its Amastigotes of Trypanosoma cruzi and integument. Leishmania spp. proliferate in macrophages Immune complexes produced in cysticercus in various organs. Toxoplasma gondii multiply cellulosae infection suppress inflammatory inside macrophages as well as in other nucleated response through inhibition of complement cells. Once intracellular, they are able to evade activity. Infection with Plasmodium spp. the host immune response. and Trypanosoma cruzi can also lead to The late intracellular stages of Plasmodium immunosuppression through the production falciparum are sequestered from the circulation of immune complexes. In Schistosoma spp. in deep vasculature beds. This is mediated by infection, complement cannot participate in the the presence of knobs on infected erythrocytes destruction of the parasite; it has been found that enable them to attach to endothelial cells of that the complement is consumed by the soluble capillaries. This sequestration process excludes antigens of the Schistosoma spp. the parasitized red blood cells from splenic filtration and the action of antibodies. C. Antigenic Variation Adverse Effects of the Immune Response In Trypanosoma brucei infection, the initial in the Host host response against the surface glycoproteins of the trypomastigotes is very effective. But in Under normal circumstances, orderly the subsequent releases of trypomastigotes, the progression of host defenses through the immune response is no longer effective since different phases results in a well-controlled the parasites have changed the antigenic profile immune and inflammatory response that of their surface coat through variant surface protects the host from the offending antigen. glycoproteins (VSG). Surface protein variation However, dysfunction of any of the host defense has also been observed in Giardia lamblia. systems can result in damage to host tissue and Chapter 1: Introduction to Medical Parasitology 13 produce clinical disease. The normal immune The main clinical manifestations of response itself might contribute substantially to Schistosoma spp. infection are related to the tissue damage as one of four types of reactions: host immune response to eggs that are trapped Type 1 (Immediate type hypersensitivity), in various organs of the host. This usually Type 2 (Immune complex formation), Type 3 results in hepatosplenomegaly, fibrosis, portal (Cytotoxic reactions of antibody), and Type 4 hypertension, and esophageal varices. High (Delayed-type hypersensitivity). levels of Schistosoma spp. circulating antigen in In acute infection with Trypanosoma cruzi, immune complexes can produce a condition the intense immune response to the parasite is very similar to serum sickness. T-cell mediated accompanied by massive damage not only to the delayed-type of hypersensitivity lymphocytes, infected cells but also to the surrounding cells when stimulated such as in Schistosoma spp. including nerve cells and myocytes. It is believed infection, can produce attractants and activators that this is partially responsible for heart failure of other cells that form destructive granulomas and meningoencephalitis. Moreover, it has around Schistosoma spp. eggs. In Leishmania been postulated that antibodies to T. cruzi may spp. infections, more macrophages are damaged, activate adrenergic and muscarinic receptors be it the cutaneous, mucocutaneous, or visceral because of similarities between these and parasite type of infection. antigens, leading to autonomic dysfunction and Practical Applications predisposition to arrhythmias. In Wuchereria bancrofti, there is an overproduction of IgM Understanding the host immune response to (polyclonal hypergamma-globulinemia) due parasitic invasion is useful in immunodiagnosis, to the functional T-suppressor cell (T8) defect, and predicting the resulting patholog

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