Effect of Filarial Infection on Immune Responses in Latent Tuberculosis
| Status: | Recruiting |
|---|---|
| Conditions: | Infectious Disease |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 8/25/2018 |
| Start Date: | February 7, 2012 |
| Contact: | Thomas B Nutman, M.D. |
| Email: | tnutman@mail.nih.gov |
| Phone: | (301) 496-5399 |
Effect of Filarial Infection on Antigen-Specific Immune Responses in Latent Tuberculosis
Background:
- Lymphatic filariasis is an infection that is caused by small, thread-like worms. It is
spread by mosquitoes, and causes fever, chills, and headaches. If untreated, it can also
cause elephantiasis, a condition that leads to swelling of the arms, legs, breasts, and
scrotum. Treatment can eliminate the worms from the blood and reduce the risk of developing
elephantiasis. Researchers want to study people with latent tuberculosis (TB) who may or may
not be infected with filariasis. This study will look at the way that people with latent TB
fight infection with these worms.
Objectives:
- To study how the immune systems of people with latent TB react to filarial infection.
Eligibility:
- Individuals between 18 and 65 years of age who have latent TB and may or may not have
filarial infection.
Design:
- Participants will be screened with a physical exam and medical history. They will
provide a blood and stool sample to test for infection.
- Participants who do not have lymphatic filariasis but have another kind of intestinal
worm will be treated for the parasite. This will be their last study visit.
- Participants who have latent TB and lymphatic filariasis will be treated with the
standard treatment for the disease. They will come back for a second visit 6 months
later, and will provide another blood sample.
- Lymphatic filariasis is an infection that is caused by small, thread-like worms. It is
spread by mosquitoes, and causes fever, chills, and headaches. If untreated, it can also
cause elephantiasis, a condition that leads to swelling of the arms, legs, breasts, and
scrotum. Treatment can eliminate the worms from the blood and reduce the risk of developing
elephantiasis. Researchers want to study people with latent tuberculosis (TB) who may or may
not be infected with filariasis. This study will look at the way that people with latent TB
fight infection with these worms.
Objectives:
- To study how the immune systems of people with latent TB react to filarial infection.
Eligibility:
- Individuals between 18 and 65 years of age who have latent TB and may or may not have
filarial infection.
Design:
- Participants will be screened with a physical exam and medical history. They will
provide a blood and stool sample to test for infection.
- Participants who do not have lymphatic filariasis but have another kind of intestinal
worm will be treated for the parasite. This will be their last study visit.
- Participants who have latent TB and lymphatic filariasis will be treated with the
standard treatment for the disease. They will come back for a second visit 6 months
later, and will provide another blood sample.
Tissue-invasive helminth parasites infect close to 500 million people worldwide and are
associated with strong T helper (Th)2 responses and regulatory networks that downregulate
potentially protective Th1 responses. The two common tissue invasive helminth parasites are
Wuchereria bancrofti, that causes lymphatic filariasis and Strongyloides stercoralis, that
causes stronyloidiasis. Previous studies have shown that the intestinal helminth coinfection
is accompanied by lowered in vitro production of interferon-gamma and elevated production of
interleukin 10 in individuals with active pulmonary tuberculosis (TB). Our team has recently
shown that co-existent filarial TB infections down-regulate Th1 and Th17 responses, which are
necessary for protection against active TB.
The current study will compare immune responses to mycobacterial antigens in individuals with
latent tuberculosis (LTBI+) and concomitant helminth infection (Hel+), including those with
filarial (Fil+) and strongyloides (STR+) infection versus those with LTBI+ without
concomitant helminth infection (Hel-). Immune responses to mycobacterial antigens from
co-infected individuals will also be evaluated before and after treatment for helminth
infection. Individuals (n=4000) will sign a screening consent prior to undergoing any study
procedures. Every participant will have their medical history collected and will undergo a
physical exam and a tuberculin 2TU purified protein derivative (PPD) skin test; women of
childbearing potential will also undergo a urine pregnancy test, and those with positive test
results will be excluded from the study. Individuals with positive PPD skin test results (>
or = 5 mm) and no symptoms of active TB will have their blood drawn (5 mL) as part of the
screening procedures to confirm LTBI+ status, evaluate circulating filarial antigenemia,
determine Strongyloides status by ELISA, measure hematocrit levels, and for storage of serum
samples; those with PPD skin test results less than or equal to 5 mm will be excluded from
the study. Individuals with positive symptoms for TB will also be excluded from the study,
but sputum will be collected from them, and those with positive smears will be referred for
treatment. Individuals will be matched for age, gender, and geographic location, and they
will be assigned to one of two groups, LTBI+ Hel+ (n=100) or LTBI+ Hel- (n=100).
Within 3 months of screening, individuals will be asked to sign an on-study consent and will
undergo a second blood draw (10 mL) for immunological investigations and storage of serum
samples; women of childbearing potential will undergo a repeat urine pregnancy test, and
those with positive test results will be excluded from further study. Stool samples will also
be collected for microscopic evaluation of ova and parasites. LTBI+ Fil+ individuals will be
treated with a single standard dose of albendazole (400 mg) and single standard dose of
diethylcarbamazine citrate (300 mg), which are available through the National Programme for
the Elimination of Lymphatic Filariasis in India. LTBI+ STR+ individuals will be treated with
a single standard dose of ivermectin (12mg) and a single standard dose of albendazole
(400mg). These individuals will be asked to return 6 months after treatment to undergo a
third blood draw (10 mL) for additional immunological investigations and storage of serum
samples. LTBI+ Hel-individuals who test positive for other intestinal helminth infection will
be treated with a single standard dose of albendazole (400 mg).
associated with strong T helper (Th)2 responses and regulatory networks that downregulate
potentially protective Th1 responses. The two common tissue invasive helminth parasites are
Wuchereria bancrofti, that causes lymphatic filariasis and Strongyloides stercoralis, that
causes stronyloidiasis. Previous studies have shown that the intestinal helminth coinfection
is accompanied by lowered in vitro production of interferon-gamma and elevated production of
interleukin 10 in individuals with active pulmonary tuberculosis (TB). Our team has recently
shown that co-existent filarial TB infections down-regulate Th1 and Th17 responses, which are
necessary for protection against active TB.
The current study will compare immune responses to mycobacterial antigens in individuals with
latent tuberculosis (LTBI+) and concomitant helminth infection (Hel+), including those with
filarial (Fil+) and strongyloides (STR+) infection versus those with LTBI+ without
concomitant helminth infection (Hel-). Immune responses to mycobacterial antigens from
co-infected individuals will also be evaluated before and after treatment for helminth
infection. Individuals (n=4000) will sign a screening consent prior to undergoing any study
procedures. Every participant will have their medical history collected and will undergo a
physical exam and a tuberculin 2TU purified protein derivative (PPD) skin test; women of
childbearing potential will also undergo a urine pregnancy test, and those with positive test
results will be excluded from the study. Individuals with positive PPD skin test results (>
or = 5 mm) and no symptoms of active TB will have their blood drawn (5 mL) as part of the
screening procedures to confirm LTBI+ status, evaluate circulating filarial antigenemia,
determine Strongyloides status by ELISA, measure hematocrit levels, and for storage of serum
samples; those with PPD skin test results less than or equal to 5 mm will be excluded from
the study. Individuals with positive symptoms for TB will also be excluded from the study,
but sputum will be collected from them, and those with positive smears will be referred for
treatment. Individuals will be matched for age, gender, and geographic location, and they
will be assigned to one of two groups, LTBI+ Hel+ (n=100) or LTBI+ Hel- (n=100).
Within 3 months of screening, individuals will be asked to sign an on-study consent and will
undergo a second blood draw (10 mL) for immunological investigations and storage of serum
samples; women of childbearing potential will undergo a repeat urine pregnancy test, and
those with positive test results will be excluded from further study. Stool samples will also
be collected for microscopic evaluation of ova and parasites. LTBI+ Fil+ individuals will be
treated with a single standard dose of albendazole (400 mg) and single standard dose of
diethylcarbamazine citrate (300 mg), which are available through the National Programme for
the Elimination of Lymphatic Filariasis in India. LTBI+ STR+ individuals will be treated with
a single standard dose of ivermectin (12mg) and a single standard dose of albendazole
(400mg). These individuals will be asked to return 6 months after treatment to undergo a
third blood draw (10 mL) for additional immunological investigations and storage of serum
samples. LTBI+ Hel-individuals who test positive for other intestinal helminth infection will
be treated with a single standard dose of albendazole (400 mg).
- PARTICIPANT INCLUSION CRITERIA:
Individuals (18 to 65 years of age) who meet the following criteria are eligible to
participate in the study:
- Positive tuberculin PPD skin test result (>or equal to 5 mm) and IGRA+.
- Willingness to provide blood and stool samples for examination.
- Willingness to have samples stored for study participants only.
PARTICIPANT EXCLUSION CRITERIA:
Individuals are not eligible to participate if:
- Pulmonary symptoms suggestive of TB (cough >3 weeks in duration and/or intermittent
fever >1 week in duration and/or hemoptysis).
- Tuberculin skin test within the last 6 months prior to screening.
- Women who are pregnant or breastfeeding.
- Known documented cases of cancer, acquired immune deficiency syndrome, or other
immunosuppressive illness.
- History of any other illness or condition which, in the investigator s judgment, may
substantially increase the risk associated with the subject s participation in the
protocol, or it may compromise the scientific objectives.
- Consumption of DEC in the last one year prior to screening.
- EXCLUSION OF PREGNANT WOMEN:
- Pregnancy: Pregnant and lactating women will be excluded from the study because the
safety of DEC or ivermectin has not been adequately evaluated during pregnancy or
lactation, while albendazole is a Category C drug found to be teratogenic in animals,
and it poses a potential risk during breastfeeding.
- EXCLUSION OF CHILDREN: Children (<18 years of age) will not be included in this study
due to the fact the prevalence of filarial and strongyloides infection in children has
been found to be very low in South India.
We found this trial at
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Bethesda, Maryland 20892
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