Impact of Parasitic Infections on Intestinal Epithelial Barrier and Immune Activation Among Persons Living With HIV in Lilongwe, Malawi
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Number of Participants With and Without Intestinal Parasitic Infection
研究概览
简要总结
The overall goal of this study is to determine if periodic de-worming of persons living with HIV in intestinal parasite-endemic regions will lead to decreased morbidity and mortality associated with HIV by reducing immune activation and intestinal damage associated with these diseases. The hypothesis for this project is that intestinal parasitic infections contribute to a modifiable pro-inflammatory state in persons living with HIV (PLWH).
Aim 1: Determine the prevalence of intestinal parasitic infections in PLWH receiving care at an HIV-treatment center in Lilongwe, Malawi using a highly sensitive multi-parallel stool PCR test. Hypothesis: highly sensitive stool PCR testing will demonstrate that disease burden of parasitic infection in PLWH in Malawi is higher than historically reported based on stool microscopy.
Aim 2: Determine the impact of parasitic infection on intestinal damage and immune activation by measuring sCD14, sCD163, and intestinal fatty acid binding protein (I-FABP) in PLWH. Hypothesis: plasma biomarkers reflecting intestinal damage and immune activation are elevated in those with HIV and parasitic co-infection compared with parasite-negative participants with HIV.
Aim 3: Determine the impact of eradication of parasitic infection on intestinal damage and immune activation by measuring sCD14, sCD163, and intestinal fatty acid binding protein (I-FABP) in PLWH before and after treatment of parasitic co-infection. Hypothesis: plasma biomarkers reflecting intestinal damage and immune activation are elevated in those with HIV and parasitic co-infection, and these biomarkers decrease with anti-parasitic treatment.
详细描述
This is a prospective study in which participants will be enrolled in outpatient HIV clinics associated with Kamuzu Central Hospital in Lilongwe, Malawi, where there are over 25,000 patients in care with over 90% virally suppressed on ART.
Any subject meeting inclusion criteria and lacking exclusion criteria who is currently receiving care at the clinics affiliated with Kamuzu Central Hospital or Bwaila Hospital will be eligible to participate in this study. After informed consent is signed, a total of 10ml of blood, 20g stool sample, and 20mL urine sample will be collected. Each participant will be asked a series of questions. Clinical variables including age, sex, CD4+ T-cell count, and CD4% will be collected from the participant's medical chart.
Stool samples will be processed by stool microscopy in the local UNC Project Malawi laboratory, and the remaining sample will be stored at -80 degrees Celsius (C) until transported to the Laboratory of Parasitology National School of Tropical Medicine Baylor College of Medicine in Houston, Texas for detection of 9 different parasites and quantification of parasite burden by stool qPCR. Blood samples will be collected in EDTA-blood collection tubes and centrifuged. Plasma will be frozen at -80 degrees C at UNC Project Malawi until transport to the National School of Tropical Medicine Baylor College of Medicine for determination of levels of immune activation and gut mucosal impairment (sCD14, sCD163, and I-FABP). Urine samples will be evaluated by microscopy to look for Schistosoma haematobium at UNC Project Malawi laboratory.
Multi-parallel real-time quantitative PCR (qPCR) performed on stool will evaluate for 9 different parasites including Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Schistosoma mansonii, Strongyloides stercoralis, Taenia solium, Trichuris trichiura, Entamoeba histolytica, and Giardia lamblia.
Participants that test positive for parasitic infection will be contacted and appropriate treatment administered according to the local standard of care. Albendazole single 400mg dose will be given for infection with Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Trichuris trichiura. Albendazole 400mg daily for 5 days will be given for Strongyloides stercoralis. Praziquantel single dose 40mg/kg will be given for infection with Schistosoma mansoni and Schistosoma haematobium. Praziquantel single dose 10mg/kg will be given to treat intestinal infection with Taenia solium. Metronidazole 500mg two times a day x5 days for Giardia lamblia and 500mg three times a day x7 days for Entamoeba histolytica.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
The participants and the study team will know the results of the tests, and thus will know the groups that the participants are in, since only the "parasite-positive" participants will receive treatment.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 18 years
- •currently living in Malawi
- •HIV-1 infection
- •on ART ≥ 1 year with undetectable HIV RNA level at the last evaluation
- •willingness to be treated with anti-parasitic therapy if infection with intestinal parasite is identified.
排除标准
- •Use of antibiotics other than prophylaxis with trimethoprim-sulfamethoxazole within 60 days of screening
- •Use of antiparasitic medication (ex- albendazole, praziquantel, metronidazole) in the last year
- •Inflammatory bowel disease
- •Gastrointestinal tract malignancy
- •Major intestinal surgery during prior 2 years
- •Coinfection with Mycobacterium tuberculosis
- •Pregnancy, breastfeeding mother, or planning pregnancy.
研究组 & 干预措施
Parasite-positive arm
Participants will be evaluated for intestinal parasitic infection by stool microscopy or stool PCR. If positive by either of these, the participant will be treated for the detected parasitic infection. The biomarker levels of this parasite-positive group will be compared to the parasite-negative group. Additionally the parasite-positive pre-treatment biomarker levels will be compared to the parasite-positive post-treatment levels.
干预措施: Antiparasitic medication (Drug)
结局指标
主要结局
Number of Participants With and Without Intestinal Parasitic Infection
时间窗: Baseline
The number of participants with and without parasitic infection was determined based on diagnostic tests utilized. Participants with a positive result by either stool microscopy or stool PCR were considered "parasite-positive". Participants negative by both diagnostic tests were considered "parasite-negative".
Mean Intestinal Fatty-acid Binding Protein (I-FABP) Levels
时间窗: Baseline
The level of I-FABP detected in plasma will be measured in all patients at the baseline visit. The mean level of I-FABP of the parasite-positive group will be compared to the mean level of I-FABP of the parasite-negative group (ng/mL) using Student's unpaired t-test.
Percent Change of sCD14 Levels Pre- and Post-treatment
时间窗: Baseline, 6 months after baseline visit
The level of sCD14 detected in plasma will be measured in all patients at the initial visit and the follow-up visit (µg/mL). The percent change of sCD14 from pre-treatment to post-treatment levels of the parasite-positive group will be compared to the percent change of sCD14 from pre- to post-treatment levels of the parasite-negative participants.
Mean Soluble CD14 (sCD14) Levels
时间窗: Baseline
The level of sCD14 detected in plasma will be measured in all patients at the baseline visit. The mean level of sCD14 of the parasite-positive group will be compared to the mean level of sCD14 of the parasite-negative group (µg/mL) using Student's unpaired t-test.
Mean Soluble CD163 (sCD163) Levels
时间窗: Baseline
The level of sCD163 detected in plasma will be measured in all patients at the baseline visit. The mean level of sCD163 of the parasite-positive group will be compared to the mean level of sCD163 of the parasite-negative group (ng/mL) using Student's unpaired t-test.
Percent Change of I-FABP Levels Pre- and Post-treatment
时间窗: Baseline, 6 months after baseline visit
The level of I-FABP detected in plasma will be measured in all patients at the initial visit and the follow-up visit (ng/mL). The percent change of I-FABP levels from pre-treatment to post-treatment of the parasite-positive group will be compared to the percent change of I-FABP levels pre- and post-treatment of the parasite-negative participants.
Percent Change of sCD163 Levels Pre- and Post-treatment
时间窗: Baseline, 6 months after baseline visit
The level of sCD163 detected in plasma will be measured in all patients at the initial visit and the follow-up visit (ng/mL). The percent change of sCD163 from pre-treatment to post-treatment levels of the parasite-positive group will be compared to the percent change of sCD163 from pre- to post-treatment levels of the parasite-negative participants.
次要结局
未报告次要终点