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1. Malaria
Malaria is the most important of
the transmissible parasitic diseases.
Over 90 million cases occur each year.
DRUG-RESISTANT MALARIA
Hepatic cycle
Sporozoites enter liver cells where they develop into tissue
(liver) schizonts which form large numbers of merozoites
which, usually after 516 days but sometimes after months or
years, are released into the circulation. Plasmodium
falciparum differs in that it has no persistent hepatic cycle.
Erythrocyte cycle
Merozoites enter red cells where they develop into
blood schizonts which form more merozoites which are
released when the cells burst giving rise to the
features of the clinical attack. The merozoites
reenter red cells and the cycle is repeated.
Chloroquine, quinine, mefloquine, halofantrine,
proguanil, pyrimethamine, and tetracyclines (blood
schizontocides)
schizontocides kill these asexual forms. Drugs which
act at this stage in the cycle may be used for:
Treatment of acute attacks of malaria.
Prevention of attacks by early destruction of the
erythrocytic forms. This is called suppressive
prophylaxis as it does not cure the hepatic cycle.
Sexual forms
Some merozoites differentiate into male and female
gametocytes in the erythrocytes and can develop further only if they are ingested by a mosquito where they
form sporozoites and complete the transmission cycle.
Quinine, mefloquine, chloroquine, artesunate,
artemether and primaquine (gametocytocides)
gametocytocides act on
sexual forms and prevent transmission of the infection
because the patient becomes noninfective and the
parasite fails to develop into mosquito.
In summary, drugs may be selected for:
treatment of clinical attacks
prevention of clinical attacks
radical cure.
Life cycle
of malaria
parasites
Pl. falciparum
Pl. malariae
Pl. ovale
Pl. vivax
Antifols
Pyrimethamine (t1/2 4 d) inhibits plasmodial dihydrofolate reductase, for which it has a high affinity. It is
well absorbed from the GIT and is extensively
metabolized. Pregnant women should receive
supplementary folic acid when taking pyrimethamine.
Adverse effects reported include anorexia,
abdominal cramps, vomiting, ataxia, tremor, seizures,
and megaloblastic anaemia.
Pyrimethamine acts synergistically with Sulfadoxine
(as Fansidar) to inhibit folic acid metabolism;
sulfadoxine is excreted in the urine. The combination
is chiefly used with quinine to treat acute attacks of
malaria caused by susceptible strains of Pl. falciparum.
Artesunate and artemether are soluble derivatives of artemisinin which is isolated from the leaves
of the Chinese herb Artemisia annua.
They act against the blood, including sexual forms of
plasmodia and may also reduce transmissibility.
Artesunate (i.v.) and artemether (i.m.) are rapidly
effective in severe and multidrug-resistant malaria.
They are well tolerated but should be used with
caution in patients with chronic cardiac disorders
as they prolong the PR and QT interval in some
experimental animals.
Doxycycline is commonly used in the treatment of falciparum malaria in conjunction with quinidine or quinine,
allowing a shorter and better-tolerated course of quinine.
2. Amoebiasis
Infection occurs when mature cysts of E. histolytica
are ingested and pass into the colon where they
divide into trophozoites. Amoebiasis occurs in two
forms, both of which need treatment.
Bowel lumen amoebiasis is asymptomatic
and trophozoites (noninfective) and cysts
(infective) are passed into the faeces. Treatment
is directed at eradicating cysts with a luminal
amoebicide; diloxanide furoate is the drug of choice;
iodoquinol or paromomycin is sometimes used.
It is caused by the hemoflagellates Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense.
The organisms are transmitted by bites of tsetse flies
(genus Glossina), which inhabit shaded areas along
streams and rivers. The largest number of cases is
in the Congo. Annual incidence estimates are about
100 000 cases and 48 000 deaths.
American Trypanosomiasis (Chagas Disease)
is caused by Trypanosoma cruzi.
4. Leishmaniasis is a zoonosis.
5. Toxoplasmosis
6. Human Trichomoniasis
(Metronidazole or tinidazole
is effective)
Human trichomoniasis caused by Tr. vaginalis,
seen in both females and males. It is usually transmitted by coitus and is sometimes asymptomatic.
The symptomatic condition in females may take the
form of a severe vaginitis associated with discharge,
burning, and pruritus.
In males it may produce urethritis, enlargement of
the prostate, and epididymitis.
7. Giardiasis
It is a common infection of
the human small intestine with
the protozoan Giardia lamblia, spread via
contaminated food or water, or by direct
person-to-person contact.
Treatment:
Metronidazole, mepacrine, or tinidazole
8. Pneumocystis
Treatment:
Co-trioxazole: i.v./p.o. in high daily doses