2.
Serological tests: These are of limited value in the diagnosis of cutaneous
leishmaniasis as the patient has no detectable level of circulating antibodies.
Treatment:
1. Local measures:
Surgical excision especially in single lesions.
Scraping (curettage).
Plastic surgery for scars or disfiguring nodules.
Local heating of lesion by infra-red rays or freezing therapy by carbon
dioxide.
Local injection of 10% atebrine solution.
I.D. injection of interferon gamma around lesions promotes healing of
ulcers.
Cleanliness to prevent secondary bacterial infection.
2. Systemic treatment: Systemic therapy (parenteral)
Pentostam is the drug of choice. (I.M.) + Local around the lesion edge, (3
doses)
If the sores are 1-3 in number, treatment may be facilitated by local
infiltration of the drug into the edges of the ulcers.
Prevention and control:
Preventive and control measures are similar to those of visceral leishmaniasis
MALARIA
Definition
Malaria is an infection caused infected mosquitoes, specifically female
Anopheles mosquitoes.
349
Species:
Four species of Plasmodium cause human malaria:
1. Plasmodium vivax: Benign tertian malaria.
2. Plasmodium ovale: Benign tertian malaria.
3. Plasmodium malariae: Benign quartan malaria.
4. Plasmodium falciparum: Tertian or subtertian malignant malaria.
Geographical distribution:
P. vivax: The most widely distributed species found in tropical, subtropical
and temperate areas.
P. ovale: West Africa.
P. malariae: Tropical Africa and Far East.
P. falciparum: Africa and Far East.
Life cycle:
The life cycle of malaria parasites is heteroxenous (alternation of generations
between two hosts), where an asexual cycle occurs in man (intermediate host),
and sexual cycle occurs in female Anopheles (definitive host).
1. Definitive host: Female Anopheles mosquito.
2. Intermediate host: Man.
3. Reservoir host: No. However, in P. malariae, chimpanzee can be affected and
act as a reservoir of infection.
4. Habitat: In mosquito: Gut, salivary glands.
In man: Intracellular inside the liver cells and RBCs.
5. Infective stage: a. Sporozoites (in mosquito-borne malaria).
b. Merozoites and/or trophozoites (in blood-borne malaria).
350
6. Mode of infection:
1. Bite of infected female Anopheles.
2. Blood-borne transmission:
a. Blood transfusion (whole blood and packed RBCs).
b. Shared syringes among drug addicts.
c. Transplacental transmission.
d. Organ transplantation.
I. Human cycle (Asexual cycle):
- In this cycle the malaria parasites multiply asexually by division; schizogony,
which occurs in 2 sites, in the liver cells (exoerythrocytic schizogony) and in the
RBCs (erythrocytic schizogony).
1. Exoerythrocytic schizogony or merogony (Tissue phase):
a. Initial tissue phase:
During blood meal, a malaria-infected female Anopheles inoculates
sporozoites with saliva into human host, which are carried within 30
minutes, by blood stream to the liver, and form parasitophorous vacuoles
in hepatocytes.
The spindle-shaped sporozoites become rounded and transform into
trophozoites, which multiply by schizogony, resulting in formation of
thousands of pear-shaped merozoites with enlarged infected liver cells.
The mature schizont and the infected liver cells rupture in 6-15 days,
releasing thousands of merozoites into the blood stream, with no clinical
symptoms.
The interval between the inoculation of sporozoites into the human host
and the first appearance of malaria parasite in blood is called the pre-patent
period.
351
b. Latent tissue phase:
In P. vivax and P. ovale, some sporozoites remain dormant in liver cells as
hypnozoites. Months or years later, some hypnozoites are activated, start
exo-erythrocytic schizogony, and release merozoites invading RBCs causing
relapse.
The asexual cycle in man: exo-erythrocytic and erythrocytic
2. Erythrocytic schizogony or merogony:
The merozoites released by exo-erythrocytic schizogony attach to the RBCs
by their apical complex, and then lie within an intra-erythrocytic
parasitophorous vacuoles formed by red cell membrane, by a process of
invagination.
In the infected RBC, the merozoite appears rounded with vacuolated
cytoplasm and the nucleus at one pole. This parasite is called the ring stage
or young trophozoites.
352
Young trophozoite feeds on the haemoglobin of RBC. The degradation
products of haemoglobin appears as residual pigment granules inside the
cytoplasm of the parasite, called malaria pigment or haemozoin pigment.
Also, stippling occurs in the cytoplasm of infected RBCs.
As the ring stage develops, it enlarges in size and becomes irregular in shape.
This is called the old trophozoite.
The nucleus of old trophozoite divides by mitosis followed by division of
cytoplasm to become mature schizonts within 2-3 days.
The mature schizont contains 8-32 merozoites and haemozoin. The
cytoplasm not sharing in the formation of merozoites is called the residual
body.
The mature schizont ruptures releasing the merozoites, haemozoin and
residual body into the circulation. Therefore, the typical malarial paroxysms
occur by the 3rd or the 4th day, and malaria is described as tertian or
quartan.
Erythrocytic merozoites can re-invade new RBCs and repeat the erythrocytic
cycle destroying each erythrocyte they infect, but never re-invade liver cells.
3. Gametogony:
After few erythrocytic cycles, some merozoites invade new RBCs and instead
of developing into trophozoites and schizonts, develop into sexually
differentiated forms, gametocytes, where maturation is completed in 4
days.
The mature gametocytes are round-shaped (P. vivax, P. ovale and P.
malariae) or crescent-shaped (P. falciparum), with prominent pigment
granules.
353
The female gametocyte is large (macrogametocyte) with compact eccentric
nucleus and pale blue cytoplasm, while the male gametocyte is small
(microgametocyte) with large central nucleus and pale blue cytoplasm.
Gametocytes do not cause any febrile illness in the host and individual who
harbours gametocytes is a carrier. They are produced for propagation of
species.
Gametogony starts inside RBCs of intermediate host and is completed in the
mosquito, the definitive host.
The erythrocytic cycle
II. Mosquito cycle (Sexual cycle or Sporogony):
When female Anopheles ingests parasitized RBCs during a blood meal, all
parasitic stages are digested in the stomach, except micro- and macro-
gametocytes, which start a complex cycle of cyclo-propagative
development.
They escape from their RBCs envelope, and from one microgametocyte, 4-8
microgametes are developed by process of division called exflagellation.
354
While, macrogametocyte matures by a process of nuclear reduction division
giving rise to only one macrogamete.
Exflagellation: It is a process in which the male microgametocyte in the
stomach of female Anopheles, undergoes division of its chromatin into 6-8
nuclei that migrate to the periphery of the parasite with part of the
cytoplasm. They form several whip-like actively motile filaments (uninuclear
microgametes), which then detach from the parent cell forming the
individual microgametes.
After half to two hours of the blood meal, one of the male gametes fertilizes
the female gamete forming a rounded zygote.
The zygote elongates and develops into a motile ookinete with an apical
complex.
Ookinete penetrates the gut wall, comes beneath the basement membrane,
secretes a thin wall and develops into a spherical oocyst.
The oocyst undergoes asexual division by sporogony, and thousands of
sporozoites are formed. Rupture of oocyst will release sporozoites into the
body cavity of female Anopheles, where some find their way to salivary
glands.
Sporogony is completed in about 1-4 weeks.
When female Anopheles takes a blood meal from another human, the
sporozoites are injected with the mosquito's saliva and the cycle is repeated.
355
The sexual cycle in female Anopheles mosquito
356
Life cycle of malaria parasites.
Pathogenicity of malaria:
The major clinical manifestations of malaria are due to the products of
erythrocytic schizogony and host´s reaction to them.
I. Destruction of parasitized RBCs:
Rupture of infected RBCs at the end of a schizogony cycle results in:
357
a. Tissue hypoxia because of reduction of blood flow by parasitized RBCs and
subsequent fatty degeneration of liver and spleen.
b. Release of haemozoin and parasite metabolites in blood stream resulting in
hepatosplenomegaly. The soft, large spleen becomes susceptible to
spontaneous rupture and in chronic infection it becomes firm and fibrotic.
Kidneys are also enlarged and congested.
c. Haemolytic anaemia and jaundice.
Causes of anaemia in malaria:
1. Obligatory destruction of RBCs at merogony.
2. Destruction of large number of RBCs by complement-mediated and
autoimmune hemolysis.
3. Increased clearance of both parasitized and non-parasitized RBCs by the
spleen.
4. Decrease erythropoiesis in bone marrow due to increased tumour necrosis
factor.
5. Shortened red cell survival.
6. Failure of the host to recycle the iron bound in haemozoin pigments.
II. Host inflammatory response: Occurs as an immune response of the host to
the liberated parasite metabolites and malaria pigments.
a. Fever coincides with rupture of erythrocytic schizont with release of
merozoites, parasitic pigments, and residual body in the blood stream. These
materials activate tissue macrophages, which in turn produce interleukin-1,
tumour necrosis factor and pyrogens which cause fever.
b. Activation of complement and immune complexes formation as a result of
the antigen excess situation in chronic quartan malaria may lead to the
358
deposition of these circulating antigen-antibody complexes within renal
glomeruli leading to nephrotic syndrome.
III. Additional pathology associated with P. falciparum:
a. In P. falciparum infection, erythrocytic schizogony takes place in capillaries of
internal organs as brain, kidney, spleen, bone marrow, and intestine. Knobs
formation on the surface of RBCs infected with late stages of parasites (during
the second half of the 48 hour life cycle) and the resulting increase in rigidity,
lead to their adherence to receptors on the endothelium of internal capillaries,
a phenomenon termed cytoadherence. Also, infected RBCs adhere to
uninfected RBCs, resulting in rosetting. These lead to sequestration of RBCs
which ultimately block blood flow, with subsequent infarctions and
haemorrhage, mainly in brain and large intestine. All these factors contributing
to the development of severe disease (malignant malaria or pernicious
syndrome).
Sequestration and cytoadherence in P. falciparum
b. Acute renal failure, tubular necrosis from tissue anoxia.
c. Black water fever (malarial haemogloblinuria) due to massive intravascular
haemolysis caused by anti-erythrocyte antibodies, leading to massive
359
absorption of haemoglobin by renal tubules with its passage in urine causing
haemoglobinuria (red urine). Sometimes, the haemoglobin is transformed into
met-haemoglobin in the renal tubules, causing black coloured urine; black
water.
d. Adrenal and retinal haemorrhage.
e. Pulmonary oedema due to disseminated intravascular clotting.
f. Cardiac oedema, blocked capillaries and degenerated foci.
g. Spontaneous abortion.
Clinical picture:
1. Incubation period:
It is the interval between the inoculation of the sporozoites into the human
host and appearance of the earliest manifestation of the disease (1st
paroxysm).
It represents the duration of exo-erythrocytic cycle.
Patient may feel malaise, muscle pain, headache, loss of appetite and fever.
2. Malarial paroxysms: The typical picture of malaria consists of series of febrile
paroxysm, followed by anaemia and splenomegaly. The febrile paroxysm occurs
in 3 successive stages; cold, hot and sweating.
a. Cold stage: Intense cold and uncontrollable shivering for 15-60 minutes.
b. Hot stage: Intense heat, flushing, nausea, vomiting and severe headache,
lasting for 2-6 hours.
c. Sweating stage: Decreased temperature and profuse sweating, lasting for 2-
3 hours.
The paroxysm usually begins in the early afternoon and lasts for 8-12 hours.
360
It synchronizes with the erythrocytic schizogony cycle. With a 48-hour cycle,
the fever recurs every third day; tertian malaria, and with 72-hour cycle, the
fever recurs every fourth day; quartan malaria.
3. Anaemia of microcytic or a normocytic hypochromic type and jaundice.
4. Splenomegaly and hepatomegaly.
5. Tropical splenomegaly syndrome (TSS) or hyper-reactive malarial syndrome
(HMS): A chronic benign condition occurs with any type of plasmodia, seen in
some adults in endemic areas. This results from abnormal immunological
response to malaria and is characterized by:
Hypersplenism and hepatomegaly.
High titers of circulating anti-malarial antibodies.
Hypergammaglobulinemia (IgM).
Presence of circulating immune complex.
Absence of malaria parasites in peripheral blood smears.
Normocytic normochromic anaemia which does not respond to haematinics
or antihelmentics.
Differs from other types of splenomegaly in its response to anti-malarial
drugs.
6. Nephrotic syndrome (oedema, proteinuria and hypo-albuminaemia) in P.
malariae infection.
7. Pernicious malaria (acute falciparum malaria): It is a series of phenomena
occurring in P. falciparum infection, which if not treated, threatens patient´s life.
361
Complications:
1. Cerebral malaria: Manifested by headache, hyperpyrexia, coma and paralysis.
2. Black water fever: It is seen in patients with repeated P. falciparum infection
and inadequate treatment with quinine.
Clinical manifestations include vomiting, prostration with passage of dark red
or black urine.
This condition may be complicated with acute renal failure and circulatory
collapse.
3. Algid malaria: Characterized by peripheral circulatory failure, rapid pulse, low
blood pressure, cold wet skin and profound shock. There may be severe
abdominal pain, vomiting (gastric type), watery diarrhea (choleric type), or
passage of blood in feces (dysenteric type).
4. Septicaemic malaria: It is characterized by high continuous fever with
dissemination of parasite to various organs, causing multiorgan failure.
5. Recurrence of malarial attack:
a. Relapse: It is the recurrence of clinical manifestations of malaria and the
reappearance of peripheral parasitaemia months or years after subsidence of a
previous attack, in the absence of a new mosquito bite.
Species: Relapse occurs in P. vivax and P. ovale (infections last up to 4 years).
Cause: It is due to activation of the dormant hypnozoites initiating exo-
erythrocytic schizogony, with the production of erythrotropic merozoites.
Can be prevented by giving primaquine to eradicate hypnozoites.
b. Recrudescence: It is a recurrence of clinical attack of malaria, few weeks or
many years after apparent clinical cure, without re-infection.
362
Species: Recrudescence can occur in all Plasmodium species, but it is more
common in P. falciparum (up to 2 years) and P. malariae (up to 40 years).
Causes: It results from the persistence of some erythrocytic parasites at a
sub-clinical level, which start to multiply to reach significant numbers.
It may be due to:
a. Incomplete anti-malarial therapy.
b. Anti-malarial drug resistance.
c. Changes of the surface antigens (antigenic variation) of the parasites
resulting in evasion of the host immune response.
d. Splenectomy or immunosuppression.
Can be prevented by adequate drug therapy or use of new antimalarial
drugs in case of drug resistance.
Diagnosis:
I- Clinical diagnosis: In endemic areas, malaria must be suspected in all cases of
typical malarial paroxysm or fever.
II- Laboratory diagnosis:
1. Parasitic diagnosis: Examination of thin and/or thick Leishman or Geimsa
stained blood smears.
All erythrocytic stages can be detected in peripheral blood except in P.
falciparum, only ring form alone or with gametocytes can be detected.
Provocative tests are indicated in chronic infection, when no parasites are
seen in peripheral blood. This may be done by subcutaneous injection of 0.5
ml adrenaline (Ascoli's test), injection of TAB vaccine, milk or cold shower. So,
the spleen contracts and squeezes its blood content to the peripheral
circulation.
363
2. Therapeutic diagnosis: The non-subsidence of the febrile paroxysms after the
administration of anti-malarial drug for 3 days, means that the case is not
malaria.
Images of four species of Plasmodium at different stages
Characteristic features of various forms of the Malaria parasite
Malaria type Stages Infected Trophozoite Schuffer Gametocytes Pigments Schizont
RBC size stippling (haemozoin) nuclei
P. vivax All enlarged small and may present Rounded light brown 12 to 24
become
amoeboid
P. Ovale All enlarged small, with large present Rounded dark brown 6 to 12
chromatin
P. malariae All normal small with dense absent Rounded dark brown 6 to 12
cytoplasm, rarely
band form
P. ring normal smallest, absent banana- Black Rarely
falciparum form multiple, often shaped
double
chromatins
364
3. Serodiagnosis:
a. Circulating antibodies can be detected by IHA, IFA and ELISA.
b. Circulating antigens can be detected by ELISA.
c. Rapid immunochromatographic test for detection of malaria antigens by
using a dipstick impregnated with specific monoclonal antibodies.
4. Molecular diagnosis.
5. Haematological diagnosis: Anaemia and reticulocytosis.
6. Biochemical diagnosis:
Hypergammaglobulinemia and low albumin level.
Hyperglycemia or hypoglycemia.
Hyperkalemia.
Treatment:
I. General and supportive measures: Given to treat symptoms and
complications, e.g. antipyretics, fluids and electrolytes replacement and blood
transfusion.
II. Antimalarial drugs: They are used with various objectives as:
Therapeutic: To eradicate the erythrocytic cycle and produce clinical cure.
Radical cure: To eradicate the exoerythrocytic cycle to prevent relapse.
Gametocidal: To destroy gametes to prevent transmission of infection to
mosquito.
Chemoprophylaxis: To prevent infection in non-immune person visiting
endemic areas.
365
A. Treatment of uncomplicated malaria:
1. Suppressive treatment (Erythrocytic schizonticides): These drugs act on the
erythrocytic stages, e.g. 4-aminoquinoline as chloroquine, quinine, and
atebrine.
2. Prophylactic treatment (Tissue schizonticides): These drugs act on the
exoerythrocytic stages, e.g. 8-aminoquinolines as primaquine.
In blood-borne malaria (no exoerythrocytic stages), one of the anti-
exoerythrocytic drugs should be given because it has a gametocidal effect.
3. Radical treatment: Two drugs are given to eradicate plasmodia, one acting on
the erythrocytic stages, to improve the symptoms (chloroquine), and another
one acting on the exoerythrocytic stages to prevent relapse (primaquine).
B. Treatment of complicated falciparum malaria:
1. Chloroquine-sensitive falciparum malaria: Treated with chloroquine along
with primaquine (gametocidal).
2. Chloroquine-resistant falciparum malaria: Artemisinin combined therapy
(ACT) should be used.
ACT consists of an artemisinin or its derivatives combined with long-acting
antimalarial drug as amodiaquine, mefloquine or sulfadoxine-
pyrimethamine.
Prevention and control:
1. Mass treatment of infected cases.
2. Mosquito control.
3. Chemoprophylaxis: It is used to prevent erythrocytic infections by giving one
of the tissue schizonticides. Primaquine is given for healthy individuals, one
day before visiting a malaria-endemic area and continued for 4 weeks after
the last exposure.
366
4. Vaccination: are the most important part of managing infectious disease; but
nowadays; there is no malaria vaccine. Many vaccines are being tested, and
the most effective vaccine will attack the parasite at each stage of its life
cycle: sporozoites can by blocked by antibodies, T-cell-mediated immunity
can block liver stage, blood stage can easily targeted, and finally transmission
can be blocked by targeting gametocytes.
Taenia solium
(Pork tapeworm)
Geographical distribution: cosmopolitan wherever raw or insufficiently
cooked pork is ingested. Thus it is very rare in Islamic countries.
Morphology:
1. Adult: 4 meters with 1000 segments.
2. Scolex: globular with a rostellum armed with double rows of taenoid hooks.
3. Mature segments contain number of testes about 150.
4. The ovary is trilobed.
5. The gravid segment: the uterus possesses 9-11 lateral branches on
each side.
6. Egg:
Size: 30-
Shape: spheroid.
Shell: thick.
Colour: yellowish-brown.
Contents: hexacanth embryo (onchosphere)
Life cycle:
Habitat: small intestine
Definitive host: man
367
