Chiluria in a lymphatic filariasis endemic area
Araújo et al. BMC Res Notes
Chiluria in a lymphatic filariasis endemic area
Paulo Sérgio Ramos de Araújo 0 1 2
Valter Romão de Souza Junior 0 2
Anderson de Souza 0 2
Luciana de Barros Correia Fontes 0 2
Eduardo Brandao 1
Abraham Rocha 1
0 Federal University of Pernambuco , Av. Prof. Moraes Rego 1235, Recife, Pernambuco 50670‐901 , Brazil
1 Instituto Aggeu Magalhaes, FIOCRUZ , Av. Prof. Moraes Rego 1235, Recife 50670‐901 , Brazil
2 Federal University of Pernambuco , Av. Prof. Moraes Rego 1235, Recife, Pernambuco 50670‐901 , Brazil
Objective: To establish clinical and laboratory data of individuals presenting chyluria in endemic areas. Results: 75 individuals were studied. The majority were females with an average age of 45 years residing in the Metropolitan Region of Recife. The mean time between the beginning of the presentation of chyluria and the first care service in the Serviço de Referencia Nacional em Filarioses was approximately 5 years. The most frequent urinalysis changes were hematuria (27.6%), leukocytes (21.9%) and proteinuria (10.5%). The Addis test showed mean values of 155.43 E/min/mL of cylinders, 52,892 E/min/mL of erythrocytes and 291,660 E/min/mL of leukocytes. Among recorded cases, proteinuria had a mean value of 1372.80 mg/dL in 24 h, and the presence of lymphocytes in the urine was positive in 68.3%. Among lymphatic filariasis tests, immunochromatography was positive in 16.7%, there was circulating filarial antigen determined by detection of OG4C3 antibodies in 7.7% and microfilaremia in only 1/55.
Chyluria; Lymphatic filariasis; Wuchereria bancrofti
Lymphatic filariasis (LF), also known as elephantiasis,
occurs through infection by Brugia malayi, Brugia timori
and Wuchereria bancrofti [
]. It has been considered
a neglected disease, responsible for permanent or
longterm physical disabilities in more than 40 million people,
a considerable portion of a total of 120 million people
infected worldwide [
]. Endemic in 72 subtropical and
tropical countries, it is estimated that there are 947
million individuals at risk of infection in 54 countries [
Currently, according to the Pan American Health
Organization, there are 720,000 infected people in the
American continent, distributed in Guyana, Dominican
Republic and Haiti, and 9 million people living in areas
with a risk of contamination [
]. In Brazil, there is no
record of new autochthonous cases of MCF since 2014,
causing the Ministry of Health to start a program of
verification and elimination of LF, aiming the interruption of
its transmission [
Adult worms of Wuchereria bancrofti prefer the
lymphatic system, where they are able to live from 4 to
8 years [
]. Despite a tropism through lymphatic vessels,
the pathogenesis of the damage is still not completely
clear. It is known, however, that the presence of adult
worms in vessels and lymph nodes, mainly in the
pelvic region (legs and scrotum), breasts and arms, causes
damage to these structures, leading to lymphedema,
hydrocele, keruria and elephantiasis [
]. Although it
occurs in other clinical conditions, lymphatic fistulation
syndromes (lichen, kilocele, and lymphocele) are
considered strongly associated with this pathology in endemic
areas of LF.
Chyluria, or milky urine, is the presence of pylorus in
the urine, a fluid composed of lymph and chylomicrons
absorbed by lymphatic vessels, transported to the
thoracic duct and then drained into the subclavian vein.
Normally, lymphatic vessels do not communicate with
the urinary tract. When this occurs, the chylium escapes
into the urine, and the point of leakage may occur in the
kidney, ureter or bladder. The urine then acquires a
characteristically milky coloration [
It is believed that approximately 2–10% of
individuals with LF develop chyluria, which is the main parasitic
etiology of this clinical finding [
generally occurs several years after infection by Wuchereria
bancrofti and is characteristically intermittent [
]. As it
causes protein loss, its association with asthenia, weight
loss and malnutrition is common [
Study area, population and study design
A retrospective study was carried out, based on data
recorded in the records of the National Reference
Service in Filariasis of the Aggeu Magalhães Research
Center (CPqAM), a unit of the Oswaldo Cruz Foundation
(Fiocruz) in the State of Pernambuco, Recife, northeast of
Brazil. This service meets the demands of all regions of
There was respect for the universal principles of
Human Rights and Bioethics in Research. The project
was previously approved by Ethics Committee of
Instituto Aggeu Magalhaes. It was considered a census
sample of medical records of patients seen between 1996 and
In the analysis of the data, measurements of central
tendency, dispersion measures and statistical tests were
obtained, adopting a sampling error of 5%, with the aid
of the software Statistical Package for the Social Sciences
(SPSS), version 23. The Chi square test, Student’s t test,
and Fisher’s exact test were used to cross-analyze the
variables: gender, 24-h Proteinuria, Leukocytes, Casts, and
Among the 75 individuals studied, the majority were
females (45/75, 60%), with a mean age of 45.2 years
(minimum age of 14 and maximum age of 78 years).
The majority (94.7%) lived in the Metropolitan Region
of Recife (MRR). In descending order, participants lived
in Recife (34 cases, 45.4%), Jaboatão dos Guararapes
(13, 17.3%), Olinda (11, 14.7%), Paulista (9, 12%),
Camaragibe (2, 2.7%), Cabo de Santo Agostinho (1, 1.3%) and
São Lourenço da Mata (1, 1.3%). Among the cities in
the countryside of Pernambuco, Vitória de Santo Antão,
Caruaru and Riacho das Almas contributed with two
(2.7%), one (1.3%) and one (1.3%) cases, respectively.
The time elapsed between the first episode of
chyluria and the first care service in the SRNF was on average
74.5 months (minimum time of 1 month and maximum
of 456 months). Among the changes in urinalysis most
frequently found in medical records, hematuria (27.6%),
leukocyte (21.9%), cloudy appearance (14.3%), presence
of proteins (10.5%) and deposits (5.7%) were reported.
The mean value of cells and casts, through Addis test,
was 155.43 E/min/mL (minimum and maximum value of
2310 E/min/mL), mean value of red cells was 52,892 E/
min/mL (minimum value of 0.550 E/min/mL and
maximum value of 291,660 E/min/mL), and mean leukocyte
value was 33,058 E/min/mL (minimum value of 28.4 E/
min/mL and maximum value of 140,511 E/min/mL).
Among the 57 individuals who underwent 24-h
proteinuria, the majority (61%) presented changed values, with
an average value of 1372.80 mg/dL (minimum value of
0.257 mg/dL and a maximum value of 14,000 mg/dL).
Urinary lymphocytes were positive in most cases (68.3%).
Regarding the biomarkers for LF, the
immunochromatographic test (ICT) was positive in 16.7% of the cases. The
presence of circulating antigens OG4C3 was positive in
only 7.7% of the cases and microfilaremia was positive in
only 1/55 of the individuals.
Among the individuals studied, 45% (34/75) performed
ultrasonography (USG) of the abdomen and/or scrotal
pouch and/or lower limbs, and half (17/34) showed
echographic changes. Diffuse soft tissue lower limb edema,
hydrocele, scrotal pouch lymphangiectasis, unilateral
renal ectasia, and bladder echoes were the most
frequently described changes.
In the reported cases of pain and in relation to its
topography 10 patients (13.3% of the sample), there was
a significant difference (p < 0.05) between the female sex
(30% of those) and male (10%. According to Fisher’s exact
test there was also a significant association (p < 0.01)
between lymphocyte count and number of erythrocytes
in the urine.
In this study, we retrospectively reviewed the medical
records of 75 individuals living in an endemic area of LF.
Individuals complained of chyluria. There was a slight
predominance of women in the sample, while the
majority of studies had a higher proportion of men [
However, this may be related to the fact that women seek
more medical care. The mean age of the individuals at the
time of the first hospital visit was 45 years of age. In India,
Tandon et al.  described chyluria in patients with LF
in individuals aged 15–30 years [
], and this higher age
range in our sample may partly reflect a delay in care.
The diagnosis of LF has been based mainly on the
clinical expression of residents of endemic areas. Hydrocele
and lymphedema are the main clinical manifestations,
whereas chyluria is a less common presentation [
that manifests itself through milky-color urine
associated with flank pain, similar to ureteric cramps [
may be triggered by meals with high lipid contents. More
severe cases may result in malnutrition,
hypoproteinemia, immune dysfunction and hypercoagulability states
]. Chyluria may present an unpredictable clinical
course, including spontaneous remission in up to half of
the individuals .
Chyluria may still be a manifestation of tuberculosis
and deep mycoses, in addition to non-infectious causes
such as traumas, post-surgical status such as partial
nephrectomy and aorta-iliac by-pass, lymphatic
malformations, pelvic tumors, irradiation, pregnancy and
malformations such as stenosis of the thoracic duct [
All our patients underwent ultrasound examinations of
the abdomen, and none of them had obstructive causes
or the presence of tumors. However, we were not able to
perform other diagnostic tests to rule out other
Some biomarkers have been used for the diagnosis
of filarial infections and are able to detect microfilariae
and/or their antigens in peripheral blood, besides the
possibility of using ultrasound to identify adult worms
in lymphatic vessels [
]. Among the most common
diagnostic tests, the identification of microfilariae in
the peripheral blood, identification of W. bancrofti
antigens by an immunoenzymatic assay based on Og4C3
monoclonal antibodies and immunochromatographic
test (ICT) are highlighted [
]. The ICT card test
is a fast test performed by digital capillary punctures
where total blood is spread on a card impregnated with
filarial antigen markers, and the result is interpreted
by colorimetric reaction. Despite the easy execution of
the test, a negative result is not able to exclude filarial
infection as a cause of a chronic pathology, since filarial
antigens eventually become undetectable in a treated
infection even in a scenario of already installed
lymphatic damage [
]. In the studied population, only one
individual had microfilariae in the peripheral blood.
Among those who underwent ICT and Og4C3, only
16.7 and 7.7% presented positive results, which
corroborates with other studies describing a low sensitivity
of such tests in a scenario of late filarial infection and
already installed filarial morbidity [
The analysis of urine in patients with chyluria may
reveal the presence of chylomicrons and triglycerides.
The quantification of these elements is the most specific
and sensitive marker for diagnostic confirmation [
In our cases, the presence of hematuria (27.6%),
possibly due to the deposition of immunocomplexes in the
basal glomerular membrane and leukocytes (21.9%), was
observed through the Addis test. There was also
expression of an abnormal connection between the lymphatic
system and the urinary system [
]. Urine lymphocyte
screening was present in 63.3%, which is compatible with
data from the literature. Some studies have indicated
the presence of lymphocytes in the urine as an
important microscopic marker due to the formation of
venolymphatic fistulas leading to an increased pressure in
lymphatic vessels [
]. Protein concentration in the
24-h urine test presented mean values of 1372.80 mg/dL,
which may reflect a picture of nephritis by immune
complex deposition. However, this was not confirmed [
• The low proportion of individuals with chyluria and
residents of endemic LF areas with registered
protocols is a possible limitation of this study.
• We were not able to perform other diagnostic tests
to rule out other infectious causes.
ICT: immunochromatographic test; FIOCRUZ: Osvaldo Cruz Foundation.
All authors contributed equally. Conceptualization: PSRA, VRSJ, AS, LBCF, EB
and AR. Formal analysis: PSRA, VRSJ, AS, LBCF, EB and AR. Investigation: PSRA,
VRSJ, AS, LBCF, EB and AR. Writing—original draft: PSRA, VRSJ, AS, LBCF, EB and
AR. Writing—review and editing: PSRA, VRSJ, AS, LBCF, EB and AR. All authors
read and approved the final manuscript.
Availability of data and materials
The data that support the findings of this study are made available from by
the Instituto Aggeu Magalhaes.
The authors declare that they have no competing interests.
Consent for publication
Ethics approval and consent to participate
The study was submitted and approved by the Ethics Committee of Instituto
Aggeu Magalhaes for the publication of this work. A copy of the written
informed consent is available for review by the Editor‑in‑ Chief of this journal.
The authors declare that the procedures followed the regulations established
by the local Ethics Committee of the Instituto Aggeu Magalhaes and the Hel‑
sinki Declaration of the World Medical Association. Instituto Aggeu Magalhaes
hospital gave access to confidential patient medical records to the authors
and these records were anonymous.
There is no funding to report for this publication.
Springer Nature remains neutral with regard to jurisdictional claims in pub‑
lished maps and institutional affiliations.
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