863lymphatic filariasis
TRANSCRIPT
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Lymphatic Filariasis
Dan Imler
Morning Report
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EPIDEMIOLOGY
W. bancrofti occurs in the following regions: sub-Saharan Africa, Southeast Asia, the Indiansubcontinent, many of the Pacific islands, andfocal areas in Latin America.
B. malayi occurs mainly in China, India, Malaysia,the Philippines, Indonesia, and various Pacificislands.
B. timori is limited to the Timor Island of
Indonesia. Within endemic regions, the infection has a focal
distribution that coincides with areas conducive tobreeding sites for the mosquito vector.
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EPIDEMIOLOGY
It is estimated that more than 120 million peopleworldwide are infected with one of these threemicrofilariae.
More than 90 percent of these infections are due to W.bancrofti, and the remainder are mostly due to B. malayi.
Estimates suggest that more than 40 million infectedindividuals are seriously incapacitated and disfigured bythe disease.
A study from India, which accounts for 40 percent of theglobal prevalence of infection, estimated that a minimumof $842 million is lost each year there, secondary totreatment costs and working days lost from filariasis.
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85% of Haitis population lives in areas at risk of LF transmission. According to a 2001 antigen survey, 117 of 133 communes are endemic for LF. In 2002, an estimated 2,130,000 people (30% of the total population) were thought to be infected.
The parasite responsible for LF in Haiti is Wuchereria bancroftispread mainly by Culexmosquitoes.
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EPIDEMIOLOGY
Adult worms are gradually acquired overyears, slowly accumulating and producingmicrofilariae in infected individuals.
Thus, the prevalence of microfilaremia inendemic communities increases with age.
After the third or fourth decade of life, most
people have been exposed and theproportion of infected individuals remainsrelatively constant.
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EPIDEMIOLOGY
New sensitive diagnostic tests reveal that lymphaticfilariasis is first acquired in childhood, often with as manyas one-third of children asymptomatically infected beforeage five
The risk of infection in childhood may be related to thematernal immune response during pregnancy. In onestudy of mother-newborn pairs, there was a 13-foldincreased risk of developing childhood Wuchereriainfection, compared to uninfected controls, if the motherhad active infection and there were absent filarial-
specific T cell responses in cord blood at birth. However, the risk of childhood filariasis was only five-fold
higher if there was evidence of T-cell specific immunity incord blood lymphocytes.
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EPIDEMIOLOGY
As with most helminth infections, the adultparasite does not replicate within the humanhost. Thus, the adult worm burden (as opposed
to the microfilarial burden) cannot increase oncean individual is no longer exposed to infectivelarvae, such as after leaving an endemic region.
Since the mosquito vectors are not efficienttransmitters of filariasis, a relatively prolongedstay in an endemic area is usually required forthe acquisition of infection.
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EPIDEMIOLOGY
Unlike most other mosquito-borne infections,several different mosquito species, including
Anopheles, Culex, Aedes, and Mansoniaspecies can serve as vectors for transmitting
filariasis. The geographic distribution of these mosquitoes
varies, and both urban and rural transmission ofdisease occurs.
In many tropical and subtropical areas, theprevalence of infection is increasing due toprogressive urbanization and increasedbreeding sites for the mosquito vectors.
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LIFE CYCLE
W. bancrofti, B. malayi, and B. timori are all acquired via the bite ofmosquitoes.
When mosquitoes bite humans, they deposit third-stage infectivelarvae into the skin.
These larvae travel through the dermis and enter local lymphatic
vessels. Over a period of approximately nine months, these larvaeundergo a series of molts and develop into mature adult worms,which range from 20 to 100 mm in length.
These adults reside in the lymphatics, generally several centimetersfrom lymph nodes. They survive for approximately five years(occasionally up to 12 to 15 years), during which time male andfemales worms mate and produce microfilariae.
Female parasites can release more than 10,000 microfilariae perday into the bloodstream. These microfilariae are also known asembryonic or first-stage larvae, and measure approximately 200 to300 m by 10 m.
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LIFE CYCLE
Mosquitoes, which bite infected individuals, cantake up these circulating microfilariae. Within themosquito, these embryonic larvae develop intosecond then third stage larvae over a period of
10 to 14 days. The mosquito is then ready to biteand infect a new human host, therebycompleting the life cycle.
The interval between acquisition of infective
larvae from a mosquito bite and detection ofmicrofilariae in the blood is known as theprepatent period. This interval is usuallyapproximately 12 months in duration.
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CLINICAL FEATURES
Most people infected with Brugian or Bancroftianfilariasis in endemic areas are asymptomatic, since thedevelopment of symptoms relates to the cumulativeacquisition of increasing numbers of worms.
Estimates suggest that at most one-third of infectedindividuals have clinical manifestations.
In endemic communities, clinical symptoms are notusually evident until adolescence or adulthood. Theclinical course of lymphatic filariasis includes threedistinct phases: asymptomatic microfilaremia, acuteepisodes of adenolymphangitis (ADL), and chronicdisease (irreversible lymphedema), which is oftensuperimposed upon repeated episodes of ADL.
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Acute adenolymphangitis
Acute adenolymphangitis (ADL) characteristically presents with thesudden onset of fever and painful lymphadenopathy.
Often there is retrograde lymphangitis, meaning that theinflammation spreads distally away from the lymph node group,which distinguishes it from the pattern typically associated with
streptococcal lymphangitis. ADL is thought to occur because of immune-mediated responses todying adult worms. It can manifest in a variety of locations, but theinguinal nodes and lower limbs are commonly involved.
The inflammation tends to resolve spontaneously after four to sevendays, but recurrences are frequent.
Recurrences are typically seen one to four times per year, but thenumber of attacks increases with increasing severity oflymphedema.
In addition, secondary bacterial infections can occur related to thebreakdown of skin barriers in edematous or elephantatic skin oroverlying intensely inflamed lymph nodes.
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Worms within Lymph Vessel
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Filarial fever
Another clinical syndrome is known asfilarial fever. This is characterized byacute, self-limiting episodes of fever, often
in the absence of any obviouslymphangitis or lymphadenopathy.
Because of the lack of associated
features, this syndrome is frequentlyconfused with other causes of fever in thetropics, such as malaria.
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Tropical pulmonary eosinophilia
Tropical pulmonaryeosinophilia is characterizedby nocturnal wheezing.
It is caused by an immunehyperresponsiveness tomicrofilariae trapped in thelungs and is typically seen
in young males.
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Chronic Lymphedema
Lymphedema, or swelling of a limb related to chronicinflammation of the lymphatic vessels, is a common latesequela of filarial infection.
When the lymph vessels in the inguinal region are
involved, swelling of the lower limb(s) ensues. When axillary lymph nodes are involved, swelling of the
upper limb(s) results.
Involvement of the breast can also occur in women.
Pitting edema is present early, but with more chronicinflammation, brawny edema and hardening of thetissues develops, eventually resulting inhyperpigmentation and hyperkeratosis.
When lymphedema is severe, it is often referred to as
elephantiasis.
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Chronic Lymphedema
The World HealthOrganization (WHO) hasdeveloped a system tograde the severity of
lymphedema. Grade I Pitting edema
that is reversible byelevating the leg
Grade II Nonpitting
edema that does notreverse with elevation ofthe extremity
Grade III Severeswelling with sclerosis and
skin changes
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Chronic Lymphedema
Chronic lymphatic disease canalso involve the genitalia,resulting in the development ofunilateral or bilateral hydroceles.
Hydroceles can be larger than 30cm in diameter but are usuallypainless unless complicated bybacterial infection.
Localization of adult worms in thelymphatics of the spermatic cordcan also lead to palpablethickening of the cord.
Lymphatic filariasis of the ovaryand mesosalpinx has also beenreported.
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DIAGNOSIS
Nonspecific test abnormalities Eosinophilia up to3000/microL
Blood examination for detection of microfilariae shouldbe performed in all individuals in whom the diagnosis of
filariasis is suspected. Bancroftian and Brugian filariasistend to show nocturnal periodicity. Blood should bedrawn between 10 p.m. and 2 a.m. because the greatestnumber of microfilariae can be found in blood during thispeak biting time of the mosquito vectors. The pattern ofperiodicity can be reversed by changing the patient's
sleep-wake cycle. Antibody tests Serologic tests for filarial antibodies
which detect elevated levels of IgG and IgE are available Antigen tests Different methods for detection of
antigen in the blood have been attempted using various
monoclonal antibodies.
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TREATMENT
Diethylcarbamazine DEC is not distributed for use inthe United States but can be obtained from the Centersfor Disease Control and Prevention (CDC) under anInvestigational New Drug (IND) protocol
Ivermectin Studies have established that ivermectingiven as a single dose in Bancroftian filariasis reducesmicrofilaremia by approximately 90 percent even oneyear after treatment
Albendazole has also been used in filarial infections.Prolonged courses of high dose albendazole have a
significant macrofilaricidal effect and result in a gradualdecrease in microfilarial levels.
Doxycycline Initial studies suggested that coxycycline,which has good activity against Wolbachia, leads tosterility of adult worms
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Mass drug administration This approach reduces both the transmissionof infection and disease morbidity. The hypothesis is that once populationshave been treated long enough, levels of microfilaremia will remain belowthat required to sustain transmission. This period has been estimated to befour to six years, corresponding to the usual reproductive lifespan of theadult parasite. Ideally, programs should focus on treating both adults andchildren.
Workers in Port-au-Prince clean
sea salt beforespraying it with adeworming drugand bagging it.The treated saltis then sold at a
loss to Haitians.
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Uptodate.com
Diagnosis, treatment, and prevention of lymphatic filariasis
Epidemiology, pathogenesis, and clinical features of lymphatic filariasis
NYtimes.com
Beyond Swollen Limbs, a Disease's Hidden Agony
http://www.nytimes.com/2006/04/09/world/americas/09lymph.html