Parasitology Lecture notes: Background only:
BS2005 Dr. Clive Bennett Back
Lecture 6 Haemoflagellates : African trypanosomes
Causing African trypanosomiasis or sleeping sickness. In scattered foci throughout the sub-Saharan Tsetse belt.
Trypanosoma brucei rhodesiense
Trypanosoma brucei gambiense
50 Million at risk, 25,000 cases per year
Malaise, lassitude and irregular fevers.
Headache, anaemia, joint pains and swollen tissues, progressing as the parasites invade the CNS to mental deterioration coma and death.
T.b. rhodesiense is usually acute causing severe sickness and death in a few days or weeks.
T.b. gambiense progresses more slowly.
Pentamide: Not effective against the late stage parasites in the CNS and some strains are now resistant to it.
Suramin must be given intravenously and has adverse side effects.
Melarsoprol an arsenical may have fatal side effects.
DFMO an anti-cancer agent is effective against gambiense but less so against rhodesiense.
Reducing contact between humans and Tsetse by using tsetse traps and selective insecticide spraying to reduce numbers, together with vegetation clearance to remove tsetse rseting and breeding sites.
Vickerman K. 1985 Developmental cycles and biology of pathogenic trypanasomes.
British Medical Bulletin 41, 105-114.
Epidemiology and control of African trypanosomiasis. 1986 WHO Technical Report Series 739 (Short Loan Collection)
An incurable disease found only in the New World. Trypanosoma cruzi is transmitted by assassin bugs Triatominae.
90 Million at risk. 16-18 Million clinical cases.
Risk of transmission by transfusion. 4.9% of Central American immigrants to the U.S.A are infected.
This can be avoided by treating blood for storage with a blue dye (Crystal Violet).
Symptoms: A small sore at the site of the bite. If this is at or near the eye it is classically known as Romanas sign.
Within a few days fever and swollen lymph nodes may develop (symptoms similar to malaria). The early acute infection can be fatal but more usually there is a symptomless phase which may last months or years. In this phase the parasites are invading most organs of the body with irreversible damage to the heart and intestine. The patient becomes progressively weaker and may die from heart failure.
Whilst incurable drugs can be used in very early infections if diagnosis is acheived.(Nifurtimox and Benznidazole though there are adverse side effects).
Large scale use of residual insecticide formulations in bug infested houses and peridomestic habitats in endemic areas.
Health education to increase public support for vector control programmes, encourage people to keep their domestic animals outside their houses and sustain community based vigilance to report reappearance of bug vectors.
Housing improvement scheme.
Control of Chagas disease in Brazil.
Dias 1987 P. Today 3 (11) 336-340
Development and interactions of Trypansoma cruzi: Within the Insect Vector.
Garcia 1991 P. Today 7 (9) 249
Malaria Genus Plasmodium
Parasites of primates, with exoerythrocytic schizogony in parenchymal cells of liver; erythrocytic schizonts, large gametocytes in red blood cells are rounded.
Species: P. falciparum Throughout tropical Africa, Asia and Latin America
P. vivax Worldwide in tropical and some temperate zones,
P. malariae Worldwide but patchy distribution
P. ovale Tropical West Africa
2100 Million at risk, 267 Million infected (including a high proportion of infected individuals with aquired immunity who are asymptomatic carriers). 107 Million Clinical cases per year.
Current problems due to both insecticide resistance and drug resistant strains of malaria.
Transmission by females of the Genus Anopheles.
Clinical symptoms: a flu like illness commencing 8-30 days after the bite. Periodic fever cycles depending on the species.
Name Chemistry Clinical use
Primaquine 8-aminoquiniline Post-curative
Chloroquine 4-aminoquinoline Prophylaxis/Treatment
Pyrimethamine 2-4-diamino pyrimidine Treatment
WR 30090 quinoline/methanol Treatment
WR 33063 Phenanthrene-methanol Treatment
Early diagnosis. Promote personal protection measures (bednets etc.) to reduce man-vector contact. Implement cost effective vector control measures.
Diagnosis : Still largely by microscopy.
Barker 1989 Detection of Plasmodium falciparum infection in human patients: a comparison of the DNA probe method to microscope diagnosis. American Journal of Tropical Medicine and Parasitology (Short loan collection).
How much malaria is there worldwide? Sturchler 1989 P. Today 5 (2) 39
Estimates of malaria incidence. Loyola 1989 P. Today 5 (12) 384
Towards a malaria vaccine (Various authors). P. Today 1985 1 (6) 150-158
Nematode structure and physiology of the gut nematodes
Cuticle, hypodermis, pseudocoelom, simple gut without musculature, gut cells with microvilli, glycocalyx.
Reproduction: separate sexes, eggs sperm, egg survival, dispersal and environental resistance. Success as a parasite and as a free living phylum.
Free living to parasitic: Strongyloides.
The parasitic adaptations Trichuris, Ascaris, Trichinella.
The blood suckers in medical parasitology Necator and Ancylostoma
Veterinary parasites: Haemonchus,
A zoonotic nematode:
Toxocara canis an infection where dogs act as definitive hosts and man acts as intermediate hosts. It causes blindness in children and as a result has been highly publicised. There is loss of vision, posterior retinochoroiditis with a hazy, ill defined mass lesion associated with overlying inflammatory cells in the vitreous humour. or a peripheral intra-retinal granuloma in an otherwise clinically normal eye. The infection occurs as a result of children coming across infected faeces from puppies. The infection may therefore occur at home or in public parks. The eggs are separated from soil scrappings in order to determine the level of risk in public places.
Lecture 10 (Mosquito borne nematodes filarial worms)
Filariasis: A billion people are at risk of infection.
Chronic diseases that are rarely life threatening:
Lymphatic filariasis causing elephantiasis:
Filarial worms develop as adult worms several centimetres in length (Macrofilariae) in the afferent lymphatic vessels.
If lodged in the spermatic cord they leads to scrotal damage.
The adult worms give birth to large numbers of microfilariae which circulate in the lymphatics and blood.
905 Million at risk. 90 Million cases.
Wuchereria bancrofti Culex
Brugia malayi Mansonia
Brugia timori Mansonia
River blindness caused by Onchocerca volvulus Vector
90 Million at risk. 17.6 Million cases with 326,000 blinded
Drugs: Diethylcarbamazide difficult to administer and with unpleasant side-effects.
Ivermectin trials in NE Brazil and Africa India SE Asia but this drug only controls microfilariae.
Onchocerciasis: by large scale use of Ivermectin. Control of Blackfly vectors by use of biodegradable insecticides to kill Blackfly larvae\in their riverine breeding sites.
Filariasis: Mass DEC treatment to reduce morbidity. Reduce man-vector contact especially by the use of insecticides.
Chemotherapy of Filariases. Vande Waa 191 P. Today 7 (8) 194-198
Introduction to other nematodes: free living and infectious stages of parasites which penetrate man either through the skin or by mouth: ASCARIS oral infection.
Physiology & Pharmacology of Nematodes.
In these two lectures the physiology and pharmacology of the nervous and neuromuscular systems will be reviewed, with particular reference to Ascaris. There is excellent evidence for acetylcholine as the excitatory transmitter neuromuscular in nematodes. Motoneurones contain choline acetyl transferase and acetylcholine. Acetylcholine depolarizes and excites single body wall muscle cells and induces contractions in strips of body wall muscle. The pharmacology of this acetylcholine receptor will be described from experiments where acetylcholine agonists and antagonists have been used. The receptor resembles the mammalian nicotinic ganglionic receptor. Gamma-aminobutyric acid (GABA) has been demonstrated in inhibitory motoneurones and when these are stimulated, inhibitory junctional potentials (ijps) can be recorded from the muscle cells. GABA will also relax body wall muscle strips. The GABA inhibition is chloride mediated but resistant to block by picrotoxin or bicuculline. The pharmacological profile of this receptor shows that it has similarity with a mammalian GABA-A receptor though it is not modulated by benzodiazepines or barbituates. A number of immunoreactive peptide-like materials have been identified in central neurones and these will be discussed in detail. Two neuroactive peptides have been isolated and sequenced from Ascaris tissue, that is, KNEFIRFamide and KHEYLRFamide. The latter peptide has actions on body wall muscle cells.
Lectures Schistosomiosis (The Blood flukes) causing Bilharzia
Widespread with a low mortality but high morbidity
Causes a serious debilitating illness.
600 Million at risk, 200 Million infected, 200K Mortality per annum
Trematode Digeneans (flukes) Genus Schistosoma
S. mansoni Africa and Latin America
S. haematobium Africa and Middle East
S. japonicum SE Asia and parts of Wesern Pacific
Also S. intercalatum in small areas of Africa
and S. mekongi Mekong basin of SE Asia
Symptoms: Damaged tissues caused by reaction to parasite eggs. S.haematobium results in blood in the urine with further damage to the bladder ureter and kidneys. Bladder cancer common in advanced cases.
Intestinal schistosomiasis (S.mansoni, S. japonicum and S.mekongi) is slower to develop. Progressive enlargement of the liver and spleen as well as damage to the intestine. This is due to fibrotic lesions around the schistosome eggs and hypertension of the abdominal blood vessels.
Metrifonate Requires three spaced doses effective only against S. haematobium. Inexpensive.
Oxamniquine Single dose but only effective against S.mansoni.
Praziquantel Single dose. Effective against all three species.
Simple diagnostic tests e.g. for haematoproteinuria for S.haematobium.
Health Education to discourage people from urinating and defaecation in or near open waters.
Lecture :Protozoan Zoonotic Parasites of AIDS
The human aquired immunodeficiency syndrome (AIDS) is a disease caused by the Human immunodefficiency viruses 1 and 2 HIV1 and HIV2). A number of pathogens including parasites have been recognised which have a prediliction for the immunologically altered host.
We will look at the commonest parasitic infection Cryptosporidium.
Cryptosporidium affects approximately 3-4% of AIDS patients.
There is malabsorbtion and wasting. (cramping pain, anorexia, nausea and vomiting and flatulence) but with no fever.It can cause anorexia and depression without diarrhoea. In AIDS patients prognosis is guarded with mortality reported as over 50% due to the diarrhoea and malnutrition. Besides the protracted enteritis it also causes, in AIDS patients alone, a severe upper quadrant pain. Radiological investigations suggest sclerosing cholangitis and thickening of the gallbladder wall. In the cases of chronic diarrhoea (with no blood or mucus) fluid loss is 3 litres per day (up to 25 litres), with 6-25 bowel movements per day. Hence stool examination is used involving concentration techniques such as salt/sugar flotation or gradients. Oocysts resemble yeast. Ziehl-Nielson stains oocysts brown or red Currently no known cure for cryptosporidial infections
Avoidance of infection
Relies on clean water supplies and good hygiene. However Oocysts are extremely resistant to free chlorine in water. The only conditions under which chlorine is operative are 8-16,000mg/litre for 24 hours at 5C and these levels are not feasible in practice. Removal of oocysts by slow sand filters is the most effective method but this method is on the decline.
1. Parasitic and other infections in AIDS
Transactions of the Royal Society of Tropical Medicine and Hygiene Vol,84 Supplement 1 In the Short Loan Collection BY207 Box. Especially pp17-19 Wakefield et al. and pp19-24 Canning.
2. Parasite infections in AIDS.
Tapeworm zoonotic Infections in the U.K.
Tapeworms will be mainly introduced in the practical. Examples of man carrying mature worms:
Taenia saginatum and solium. The morphology, developmental and reproductive biology will be described and compared with the Schistosome species that have already been introduced in the course A tapeworm in which man solely as an intermediate host: Echinococcus infections is also introduced . This infection found in Kenya and in the U.K. in Wales has a life cycle in which dogs are the definitive hosts carrying the recognisable though short tapeworms. In man the infection is far more serious and is life threatening. The infection in humans is known as HYDATID disease.
(An animal model will be used in the practical Hymenolepis a tapworm of rats which uses beetles
as intermediate hosts).
Lockwood and Weber 1989 P. Today 5 (10) 310-315