Epidemiology

 The adult worms reside in the pulmonary artery and right side of the heart. Eggs shed by the female lodge in

the pulmonary capillaries, where the larvae hatch and migrate up the trachea. The larvae are swallowed and

passed in the rodent feces. Once released the larvae infect the intermediate host, mollusks. The mollusks are

consumed by a variety of paratenic hosts such as shrimp, fish, crabs, or frogs. The rodents then consume the

paratenic hosts and the larvae penetrate the intestine, enter the circulation, and migrate to the central nervous

system. Following two successive molts, the larvae then reenter the circulation and migrate to the pulmonary

artery. Humans are infected by ingestion of either the intermediate or the paratenic host.

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Pathogenesis and spectrum of disease

 The pathogenesis correlates with the worm burden and the site of infection. The larvae may migrate to the

central nervous system, causing meningitis or meningoencephalitis.

Symptoms include headache, fever, eosinophilia, increased cerebrospinal fluid (CSF) protein, and neurologic

manifestations. Occasionally, the larvae may migrate to the eye, causing blindness. Most often the disease is

self-limiting.

Laboratory diagnosis

 Definitive diagnosis relies on histologic identification of the adult female worm. The adult female worm has a

distinctive morphologic appearance with spiral, winding, “barber pole” appearing uterus. Highly specific

serologic assays are available.

Therapy:

Anthelmintic therapy may be helpful, such as mebendazole. It is important to closely monitor therapy, because

the therapy may actually exacerbate the inflammatory response of the host and cause more systemic damage. If

larvae are located within the eye, surgical removal is recommended.

Parastrongylus costaricensis

(Abdominal angiostrongyliasis):

General characteristics

Parastrongylus costaricensis is found primarily in the cotton rat and the black rat.

Pathogenesis and spectrum of disease

The life cycle is very similar to that of Parastrongylus cantonensis. Human infection is typically by ingestion

of salad contaminated with infected slugs or snails. The larvae create inflammatory lesions in the wall of the

bowel, resulting in tissue inflammation, necrosis, vomiting, and diarrhea. The patient may experience lower

right quadrant abdominal pain similar to that manifested in appendicitis.

Laboratory diagnosis

Histologic identification of larvae or eggs in tissue sections results in definitive diagnosis. Patients often present

with leukocytosis and eosinophilia. Radiologic imaging may be useful.

Therapy

Traditional anthelmintic therapy is recommended.

Gnathostoma spinigerum.

General characteristics

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Gnathostoma spp., a gastric Spirurida, is found in a variety of mammals worldwide. Dogs and cats serve as the

definitive host for G. spinigerum.

Epidemiology

The adult worms reside in the stomach of the definitive host where they mate and produce eggs that are passed

in the feces. When the feces are deposited in water, the larvae hatch and infect copepods. The larvae mature in

the copepods and are then ingested by a variety of hosts including fish, snakes, and frogs. Inside the paratenic

host the larvae then migrate to the musculature and encyst until the tissue is ingested by the definitive host.

Once in the definitive host, the larvae excyst and penetrate the gastric wall, migrating and maturing in the

stomach. Humans act as accidental hosts when they ingest larvae in contaminated fish.

Pathogenesis and spectrum of disease

The worms are incapable of maturation within the human host and migrate aimlessly, causing tissue damage

and inflammation. The infection is not typically fatal; however, it depends on the migration pattern and organs

infected.

Laboratory diagnosis

The identification of the larvae in tissue is definitive for diagnosis. The head contains four rows of cephalic

hooklets. The body is covered with transverse rows of spines that diminish anteriorly to posteriorly.

Therapy

Supportive corticosteroid treatment is recommended. Although anthelmintics are not lethal, they are often

recommended. Surgical excision of the larvae is optimal treatment.

Blood and Tissue (Filarial) Nematodes:

Nematodes Blood and Tissues (Filarial Worms):

Wuchereria bancrofti

Brugia malayi

Brugia timori

Loa loa

Onchocerca volvulus

Mansonella ozzardi

Mansonella streptocerca

Mansonella perstans

Blood and tissue filarial nematodes are roundworms that infect humans. These organisms are transmitted

via a blood-sucking arthropod vector such as a mosquito, midge, or fly. The filarial nematodes infect the

subcutaneous tissues, deep connective tissues, body cavities, and lymphatic system. The life cycles of the

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filarial nematodes are complex , The infective larval stage resides in the insect vector with the adult worm

stage, which is the pathogenic form in humans. When the arthropod vector feeds on a human blood meal, the

infective larvae are injected into the bloodstream. The larvae are motile and migrate to the lymphatic vessels.

The infective larvae grow and develop into the adult gravid worm in the human host over a period of months.

The male and female adult worms mate in the definitive human host. The female worm produces large numbers

of larvae called microfilariae.

Depending on the species, the microfilariae may maintain the egg membrane as a sheath or may rupture the egg

membrane, resulting in an unsheathed form. These parasites can reside in the host for many years and cause

chronic, debilitating conditions and severe inflammatory responses. Identification of the various species is

based on the morphology of the microfilaria, the periodicity (defined circadian rhythm), and the location within

the human host. Microfilariae morphologic characteristics are important in the identification and include the

presence or absence of the sheath and the presence and arrangement of the nuclei in the tail of the worm , A

comparison of the morphologic characteristics of the pathogenic filarial worms is depicted in, Diagnosis of

infection is based on the identification of the microfilariae in the blood or tissue of the host.

Wuchereria bancrofti:

Epidemiology

W. bancrofti is the most common identified species of filarial worms that infect humans. The

mosquito vectors have complex life cycles that include laying eggs and developing larvae on the surface of a

water source. When the larvae mature into adult mosquitos, the male and females will swarm in the evening and

mate. The female requires feeding on a blood meal in order to reproduce. The mosquito becomes the

intermediate host for the microfilaria parasite. Humans are the definitive host and the reservoir for W. bancrofti.

The parasite has two forms that demonstrate different periodicities. The nocturnal periodic form is found in the

peripheral blood during the night between 10 pm and 4 am. The second form is found only in the Pacific

Islands and is present in the blood at all times, but more frequently during the day in the afternoon hours.

Pathogenesis and spectrum of disease

Microfilaria clinical disease varies geographically based on the species of nematode causing the infection.

The disease may present as acute or asymptomatic for many years. W. bancrofti causes bancroftian filariasis

and elephantiasis. The adult worm resides in the lymphatic vessels distal to the lymph nodes. The presence of

the organisms within the host results in an immunologic response including inflammation, hyperplasia,

lymphedema, and hyperplasia.

Lymphedema most often occurs in the lower extremities. Elephantiasis is a crippling condition that results from extended

periods of filarial infection. The obstruction of the lymphatic vessels causes fibrosis and proliferation of dermal and

connective tissue, resulting in the wrinkled, dry appearance of an “elephant” extremity. Lymphedema may also occur in the

arms, female breasts, and scrotum of infected males.

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Acute lymphatic filariasis results from worms residing within the lymph nodes. The lymph nodes swell and

lymphangitis may appear peripherally from the infected node.

.Laboratory diagnosis

 Definitive laboratory diagnosis is based on the identification of the parasites in blood, fluids, or tissue.

 Serologic assays that measure antibody response have limited utility in the diagnosis of infections with

microfilariae.

The antibodies tend to demonstrate a high cross reactivity with other antibodies made in response to a wide

variety of parasitic worm infections. The absence of an antibody reaction would, however, indicate the lack of

infection by a microfilaria species. Laboratory detection of W. bancrofti-circulating antigens has demonstrated

high specificity and sensitivity in detecting parasitic infections. However, the commercial testing formats

available are not FDA-approved. Polymerase chain reaction (PCR) amplification is available in reference

laboratories for the rapid diagnosis of an infection .

Brugia malayi and brugia timori

General characteristics

The Brugia spp. are lymphatic filarial parasites resembling W. bancrofti

Epidemiology

The organism is transmitted via mosquitos included in the genus Anopheles and Mansonia.

Pathogenesis and spectrum of disease

As in infections with W. bancrofti, two periodic forms exist. The nocturnal form is the most common and

located near areas of coastal rice fields, whereas the nonperiodic form is associated with infections in areas near

swampy forests. The pathogenesis and spectrum of disease is essentially the same as for W. bancrofti, with the

exception that involvement of the genital lymphatic vessels is predominantly associated with W. bancrofti.

Figure 45:Microfilaria of Wuchereria bancrofti in thick blood film

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Clinical disease progresses faster following infection with B. malayi than with W. bancrofti. Microfilariae may

appear in the blood in as little as 3 to 4 months. Brugia spp. have been implicated in zoonotic infections of

dogs, cats, rabbits, and raccoons worldwide. Cases of human infection have occurred in the United States in the

northeastern region. Clinical disease is typically asymptomatic but may present with a tender region in the

cervical, axillary, or inguinal region. The lymphatic mass may contain either a live or a dead worm. If the worm

is no longer viable, the mass may be surrounded by a granulomatous reaction.

Laboratory diagnosis

Definitive diagnosis is generally by the identification of the adult worms in the blood of infected individuals.

The adult worms can be distinguished from W. bancrofti morphologically. The B. malayi microfilariae are

sheathed and contain 4 to 5 subterminal and 2 terminal nuclei in the tail. B. timori also contains 5 to 8

subterminal and terminal nuclei in the tail, but they are much larger than B. malayi. The B. malayi sheath will

stain bright pink with Giemsa, whereas the B. timori sheath does not stain. The microfilariae of B. timori tend to

be somewhat longer. High-frequency ultrasound has been useful in identifying adult worms in various locations

within the patient, such as lymphatic vessels of the legs, inguinal area (groin or lower abdomen), lymph nodes,

and female breasts. Nucleic acid-based methods have been developed but are not widely used in clinical

laboratories.

Therapy

Diethylcarbamazine (DEC) is the treatment of choice for lymphatic filarial parasites including W. bancrofti and

Brugia spp. Additionally, ivermectin and albendazole may be used. Death of the microfilarial worms may result

in an increased hypersensitive reaction requiring the need for treatment with antihistamines to limit the

inflammatory symptoms.

Prevention

The use of insect repellent is recommended for travelers in areas where the parasites are endemic. DEC has also

been used for prophylactic treatment before travel. Vector control studies in combination with mass drug

administration of DEC and ivermectin have successfully decreased the population of the arthropod vectors and

decreased filarial infection in the human hosts.

LOA LOA

General characteristics

Loa loa, commonly referred to as the eye worm, is a microfilaria that circulates in the bloodstream and resides

in the subcutaneous tissue in the human host. The worm may grow up to 300 μm.

Epidemiology

The parasite is found within the rain forests of West and Central Africa. The organism is transmitted through a

bite of the tabinid fly or deer fly of the genus Chrysops. The female lays her eggs on the leaves of small plants

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near the water. The larvae feed on small insects and develop in wet soil. The male fly feeds on pollen and the

female feeds on a blood meal.

Pathogenesis and spectrum of disease

The organism is often associated with asymptomatic infection. The larvae develop into adult worms in

approximately 6 to 12 months, but can persist in the human host for up to 17 years. The infection is typically

identified when the adult worm is seen migrating within the subconjunctiva of the host. Symptoms associated

with infection include episodic “calabar swelling,” which are localized areas of transient angioedema in

response to the production of parasitic metabolic products. Predominant swelling on the extremities with

inflammation of nearby joints and peripheral nerves may occur. Immunemediated encephalopathy,

nephropathy, and cardiomyopathy may occur.

Laboratory diagnosis

Infections with Loa loa may be asymptomatic for many years before the appearance of microfilariae in the

peripheral blood. Therefore, patient diagnosis is often made on the basis of the patient’s clinical symptoms

including calabar swelling, eosinophilia, and travel or residency in an endemic area.

Direct Detection

Definitive diagnosis is made by identification of the adult worm from the eye, in tissue or in the peripheral

blood. The organism contains a sheath that does not stain with Giemsa. The adult females are larger than the

adult males. The nuclei extend to the tail in an irregularly arranged fashion.

Serologic Detection

As with other filarial infections, serologic assays have limited use for diagnosis. A Loa-specific recombinant

protein has been used in the development of an enzymelinked immunosorbent assay (ELISA) and has

demonstrated improved specificity but limited sensitivity.

Molecular Diagnostics

PCR assays are currently available but are limited to research laboratories.

Therapy

DEC is the treatment of choice. In heavy infections, inflammation and allergic reactions may occur, requiring

the administration of antiinflammatory medications. Allergic responses can result in central nervous system

damage, encephalitis, coma, and death.

Prevention

Prophylactic treatment with DEC has been used to prevent infection.

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Onchocerca volvulus

General characteristics

Onchocerca volvulus predominantly resides in tissue nodules within the host. Adult worms measure

approximately 300 μm long by 5-9 μm wide.

Epidemiology

O. volvulus is found throughout Africa, Central America, and South America. The parasite is transmitted by the

black fly, Simulium spp. The black fly lays its eggs in running water where the larvae attach to the rocks. The

larvae feed on algae and bacteria. The adults emerge as a flying insect. The females require a blood meal,

whereas the males are nectar feeders. The flies feed predominantly during the day.

Pathogenesis and spectrum of disease

Onchocerciasis, commonly referred to as river blindness, is a result of subcutaneous infection with the parasite.

The infections are typically localized to the skin, lymph nodes, and eyes. Skin infections result in pruritus,

edema, and erythema. Hypo- or hyperpigmentation can occur following a lengthy infection. Nodules,

containing the adult worm, vary in size and are firm and tender. Lymphadenopathy may be found in the

inguinal or femoral regions. Enlargement of the lymph node may result in a condition referred to as “hanging

groin” that may result in a hernia. Onchocercal eye disease may be seen in moderate to heavy infections.

Infections of the eye may lead to serious damage and blindness. Mortality increases in adults that experience

blindness and systemic infection.

Laboratory diagnosis

Direct Detection

Definitive diagnosis is made from the identification of the adult worm from tissue such as in a nodule or skin

snip. Skin samples are placed in physiologic buffered saline for up to 24 hours. Following incubation, the

Figure 46 Microfilaria of Onchocerca volvulus.

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worms will emerge from the tissue and can be visualized microscopically. Occasionally the adult worms may

be found in blood or urine following treatment. Microfilariae may also be visible in the cornea of the eye. The

microfilariae lack a sheath. The tail is tapered, appears bent or flexed, and does not include nuclei (Figure 46).

Serologic Detection

Although serologic tests generally lack specificity, recombinant ELISAs using multiple antigens have

demonstrated increased sensitivity and specificity for the diagnosis of onchocerciasis.

Molecular Diagnostics

PCR amplification assays have been developed and are currently limited to research laboratories.

Therapy

Ivermectin is the recommended treatment. However, in Africa, where O. volvulus and L. loa are coendemic,

ivermectin treatment is often associated with encephalopathy in patients with heavy microfilaria infections.

Surgical excision of nodules containing adult worms is recommended when they are located on the head.

Prevention

Mosquito control using insecticides in endemic areas has been used to assist in the control of transmission of O.

volvulus. In addition, a mass-treatment program with ivermectin is effective in preventing infection.

MANSONELLA SPP. (M. OZZARDI,

M. STREPTOCERCA, M. PERSTANS)

General characteristics

Mansonella spp. are generally not associated with serious infections. The adult worms of all species are very

similar in size, ranging from approximately 200-225 μm long.

Epidemiology

The parasites are transmitted by biting midges of the genus Culicoides. The female requires a blood meal for

the maturation of eggs and typically bites in the early evening or morning hours. Transmission of M. ozzardi

has also been associated with bites from the black fly (Simulium amazonicum).

Pathogenesis and spectrum of disease

M. streptocerca may be found in the skin; however, most infected individuals appear asymptomatic. Patients

may present with a pruritic rash and pigmentation changes. In addition, lymphadenitis may occur. M. perstans

resides in the pericardial, pleural, and peritoneal cavities. Symptomatic patients present with swelling of the

arms or face similar to infection with L. loa. M. ozzardi and M. perstans are found in the blood.

M. perstans and M. ozzardi do not demonstrate periodicity when circulating within the bloodstream. M. ozzardi

infections are not well characterized.

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Laboratory diagnosis

Mansonella spp. microfilariae do not possess sheaths. M. streptocerca and M. perstans tails contain nuclei that

extend to the end of the tail. The tail of M. streptocerca is often referred to as a “shepherd’s crook.” M. ozzardi

have tails with nuclei that do not extend to the tip.

Therapy

Ivermectin is effective in the treatment of M. streptocerca and M. ozzardi infections. Treatment of M. perstans

infections has not been effective in most cases.

Prevention

Prevention relies on the use of insect repellents and adequate clothing.

Intestinal Cestodes:

Intestinal Cestodes (Tapeworms):

Diphyllobothrium latum

Dipylidium caninum

Hymenolepis nana

Hymenolepis diminuta

Taenia solium

Taenia saginata

The intestinal cestodes are commonly referred to as tapeworms. Tapeworms have a long, segmented, ribbonlike

body with a specialized structure for attachment, or scolex, at the anterior end. The adult tapeworm consists of a

chain of egg-producing units called proglottids, which develop posteriorly from the neck region of the scolex.

The crown of the scolex, rostellum, may be smooth or armed with hooks. The body of the worm (proglottids)

varies in the geometric characteristics or number of segments according to the genus and species of the cestode.

The mature cestode is hermaphroditic.

In other words, the organism contains both male and female reproductive organs. Food is absorbed from the

host through the worm’s integument, the outer covering or skin of the organism. Adult worms typically inhabit

the small intestine; however, humans may be host to either the adult or the larval forms, depending on the

infecting species. Humans infected with a cestode pass the eggs in the feces. The embryo may be visible within

the tapeworm egg as an oncosphere (larva tapeworm within an embryonic envelope, infective stage) or

hexacanth embryo. The intermediate host ingests feces containing the adult tapeworm eggs, which further

develop into the larva of the cestode. Cestodes generally require one or more intermediate hosts for the

completion of their life cycle. Intestinal tapeworm infections are generally asymptomatic. However, if the larval

stage develops in human organs outside the intestine, they may cause additional life-threatening complications.

Serologic tests are not available for the diagnosis of tapeworm infections, therefore requiring skilled

laboratorians for proper morphologic identification of the organism. Fresh or preserved stools are the specimen

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of choice for ova and parasites (O&P) examination and cestode identification. Preserved stool containing adult

worm segments (strobila) or the scolex may also be used for Diagnosis.

Diphyllobothrium latum

General characteristics

Diphyllobothrium latum, the freshwater broad fish tapeworm, is the largest human tapeworm. Adults have been

known to reach up to 10 m in length, with more than 3000 to 4000 proglottids, and reside within a host for 30

years or more. The proglottids are characteristically wider than long with a central rosette-shaped uterine

structure (Figure 47). The scolex is spatulate and contains two shallow sucking grooves referred to as bothria

(Figure 47). D. latum has unembryonated eggs. The eggs are operculated with a terminal knob, similar to

trematode eggs (Figure 47). The intermediate hosts include crustaceans and freshwater fish.

Pathogenesis and spectrum of disease

Diphyllobothrium latum is the only cestode to have an aquatic life cycle (Figure 54-2). Fish serve as the

reservoir host, with humans serving as the definitive host. D. latum eggs are found in the feces of infected

humans and other fish-eating mammals. Once passed into a water source, such as a lake, the life cycle requires

two intermediate hosts. After incubation in freshwater for approximately 2 weeks, the mature eggs release the

first larval stage (coracidium). The coracidia are ingested by

Figure 47, A ,Diphyllobothrium latum scolex. B,. latum scolex, bothria visible. C,. latum ovum, Diphyllobothrium

latum scolex,

bothria visible.

A B C

Figure 48: Proglottid demonstrating rosette-shaped uterus in D. latum.

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copepods. The fish feed upon the small crustaceans ingesting the procercoid larvae. Within the freshwater

fish, the larvae develop into the infective larvae. D. latum infection occurs through the ingestion of poorly

cooked freshwater fish containing the plerocercoid larval form. D. latum matures to an adult tapeworm within

the human small intestine. Infection is usually asymptomatic, but mild gastrointestinal symptoms may occur

such as diarrhea, abdominal pain, fatigue, vomiting, or dizziness. Symptoms vary depending on the worm

burden and the host’s immune response to the organism. The tapeworm nutritional requirements may decrease

the host’s vitamin B12 level, resulting in megaloblastic anemia .

Laboratory diagnosis

Both eggs and proglottids may be found in patient’s feces. Visualization of the eggs is enhanced using a wet

preparation of the patient’s stool sample. Diagnosis is made by identification of the ovoid, operculated,

nyellowbrown eggs (58 to 75 μm by 40 to 50 μm) passed in abundance in the stool. They are sometimes

confused with the eggs of Paragonimus. The mature gravid proglottids are wider than long (3 × 11 mm), often

in chains, and contain a rosette-shaped central uterus (Figure 48).

Therapy

Humans infected with D. latum develop little or no protective immunity. Reinfection is common. Treatment

with praziquantel or niclosamide is effective and nontoxic. Subsequent stool specimens should be reexamined 6

weeks following treatment. The patient may require a vitamin B12 supplement if anemia develops.

Prevention

Prevention simply includes avoiding the consumption of raw fish. The larva stage is destroyed when food is

thoroughly cooked or frozen.

Dipylidium caninum

General characteristics

D. caninum, the cat or dog tapeworm (Figure 49), is a double-pored tapeworm consisting of many small

proglottids.

As the tapeworm matures, the proglottids separate and pass in the stool. They may be recognized on

Figure 49: Dipylidium caninum

tapeworm.

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the basis of their characteristic “cucumber seed” appearance when they are wet, as well as their resemblance to

a dried grain of rice. Adult tapeworms measure 10 to 70 cm in length. The scolex contains four suckers and an

armed rostellum. Egg packets may also be found in the feces of the host.

Pathogenesis and spectrum of disease

Ingestion of an infected flea may result in D. caninum infection. The flea is the intermediate host in which

infective cysticercoids develop; humans, dogs, and cats are the reservoir hosts. The larval stage of the egg is

ingested by a dog or cat and develops into cysticercoid larvae. The adult worm develops and matures within the

reservoir host. An infected human host will usually pass proglottids in a bowel movement or they may stick to

the skin around the anal area. Humans usually have very mild symptoms such as indigestion, appetite loss,

weight loss, perianal itching, persistent diarrhea, and vague abdominal pain. The severity of the disease is

dependent on the worm burden. Human infection is usually self-limited.

Laboratory diagnosis

Symptoms of Dipylidium infection are similar to those of pinworm infection; however, the treatments are very

different. The laboratory should confirm suspected infections. Proglottids (8 to 23 μm) may be seen in the stool.

D. caninum is also referred to as the “cucumber seed” tapeworm as previously described (see Figure 48). The

first sign of infection may be the appearance of seedlike particles in the stool or undergarments of the patient.

These particles are the egg-bearing segments of the tapeworm. Groups of egg packets may be found in the stool

The adult worms have a scolex with four suckers and a conical/retractile rostellum armed with four to seven

rows of small hooklets Patients may also develop a moderately elevated eosinophilia.

Therapy

D. caninum infection is usually asymptomatic and is self-limiting.When treated, praziquantel is typically

effective.

Prevention

To reduce the risk of infection, flea control of pets in the household will reduce exposure to humans via the

intermediate host. To limit the exposure to fleas by household cats, it is recommended to keep cats indoors to

prevent infection.

HYMENOLEPIS NANA

General characteristics

Hymenolepis nana, also known as the dwarf tapeworm, is very small in comparison to other tapeworms. The

organism may reach up to 4 cm in length. The proglottid contains a scolex with a short-armed rostellum. It is

the most common tapeworm with worldwide distribution. An intermediate host is not required, thus making

personto- person spread possible. An adult dwarf tapeworm can live within the host for approximately 4 to 6

weeks.