Non-specific Effects of Vaccination on Mortality and Morbidity

Anemia Clinical Trial

— NOVAC  

Official title:

The Non-specific Effects of Vaccination Related to Mortality and Morbidity in Nanoro Health and Demographic Surveillance System Cohort

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03176719
• Other study ID #: 2017-3339
• Status: Active, not recruiting
• Start date: June 17, 2017
• Est. completion date: December 31, 2018

Study information

• Verified date: August 2018
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

It has long been recognized that the positive effects of vaccination on childhood mortality cannot be solely attributed to a decline in the disease targeted by the vaccine. These so-called non-specific effects of vaccination have so far mostly been linked to mortality. However, it has been suggested that non-specific effects may also effect morbidity and nutritional status. This study aims to further explore the correlation between vaccination, susceptibility to infectious diseases (particularly malaria and bacterial infections), nutritional status and immunity.

With this prospective cross sectional study among healthy individuals in rural west-Africa we aim to address several research questions at the same time. This study will assess the influence of (time-point of) vaccination on morbidity, mortality and immune status among healthy individuals in a rural sub-Saharan African setting. Secondly, to explore the prevalence of subclinical malaria, iron deficiency anemia, sickle cell anemia and thallasemia among a healthy rural sub-Saharan African population. And finally to assess normal hemocytometry values among a healthy rural sub-Saharan African population.

Description:

A cross sectional study among healthy participants randomly selected from the population living in the Nanoro HDSS cohort to (a) study the relation between vaccination and morbidity (including hemoglobin levels, subclinical malaria and stunting) (b) perform hemocytometry in order to determine reference values for that population and estimate the prevalence and causes of anemia, using reference values from other Sub-Sahara Africa countries and industrialized countries.

In a cross sectional study among a healthy population in the Nanoro HDSS cohort, hemocytometry will be performed in order to define normal values for that population. In addition, hemoglobin levels can be related to the presence of iron deficiency, thalassemia and malaria and be corrected for important confounding factors, such as the family income, family composition, distance to a healthcare center and vaccination status. This study will allow to assess simultaneously the normal range of hemoglobin values, the prevalence of (different causes of) anemia, the prevalence of subclinical malaria parasitemia, as well as the influence of (timepoint of) vaccination on all these issues. It is hypothized that early vaccination with live attenuated vaccines has a protective effect against malaria and other severe infectious diseases and will result in a better nutritional status, a higher hemoglobin level and a higher threshold of subclinical parasitemia. The protective effect of early vaccination with live attenuated vaccines may be due to the long-term modulation of the immune system through epigenetic changes causing a right balance between the pro- and anti-inflammatory responses. Such balance can be determined by ex-vivo stimulation of whole blood by a variety of stimuli, including Mycobacterium tuberculosis and lipopolysaccharide from Escherichia coli, followed by measurement of ex vivo cytokine production. Previous studies among healthy volunteers in the Netherlands have shown that BCG is indeed capable to induce epigenetic changes and influence immune response by influencing various pathways including through genetic variations in mTOR, HK2, PFKP, GLS, and GLUD1/2 (ref).

The new Sysmex analysers are not only capable to determine hemocytometry, but are at the same time capable to detect malaria parasites directly. Interestingly, not only the asexual stages of the parasites are detected but the gametocytes as well. This may be very important as gametocyte carriers are known to play a crucial role in malaria transmission. Gametocytes are presently detected by light microscopy or by PCR, however these techniques are limited; the sensitivity of light microscopy is relatively low and PCR is too complex to perform in most rural sub-Saharan African settings. The new Sysmex hematology analysers are easy to operate at low costs and may as such become an important tool for malaria elimination programs. No data are presently available about gametocyte density in Burkina Faso in a large population, nor is the lower level of detection of gametocytes using the sysmex analyzers known.

This research has four main objectives :

1. To perform hemocytometry among a healthy rural Burkina Faso population selected from the Nanoro HDSS cohort, in order to determine reference values for that population.

2. To perform hemocytometry among a healthy rural Burkina Faso population selected from the Nanoro HDSS cohort, in order to estimate the prevalence and causes of anemia, using reference values from other Sub-Sahara Africa (SSA) countries and industrialized countries.

3. To study the relation between (timepoint of) vaccination and morbidity (including hemoglobin levels, subclinical malaria, bacterial infection and stunting) among a healthy rural Burkina Faso population selected from the Nanoro HDSS cohort. For this objective the population will be stratified by birth cohort.

4. To perform ex-vivo whole blood stimulation to assess differences in immune response between patientgroups with a different vaccination status, within a healthy rural Burkina Faso population selected from the Nanoro HDSS cohort

Seondary objectives

5. To assess the detection limit of gametocyte carriages for the new series Sysmex hematology analyzers.

6. To assess if Salmonella resides in blood as a reservoir for invasive infection among a rural Burkina Faso population selected from the Nanoro HDSS cohort.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1005
• Est. completion date: December 31, 2018
• Est. primary completion date: October 31, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Year and older

Eligibility

Inclusion Criteria:

• Healthy participants currently living in the Nanoro HDSS area, born before May 2016.

Exclusion Criteria:

• Current febrile illness,

• Current chronic illnesses, HIV, TB, renal failure, cardiac disease (if known)

• Patients that have participated in the RTSS vaccination trial from Glaxo-Smith-Kline at the same inclusion site.

Related Conditions & MeSH terms

• Anemia
• Bacteremia
• Malaria, Falciparum
• Malaria,Falciparum
• Salmonella Bacteraemia
• Vaccine Reaction

Intervention

Other:
• Venipuncture
Full blood count and leukocyte differentiation. Detection of malaria parasites and parasite differentiation to trophozoites, gametocytes and ringstages (XN-30) Detection of anemia, thallasemia and sickle cell anemia (XN-20) Ex-vivo stimulation of wholeblood with various stimuli. Read-out will be a spectrum of cytokines (ELISA) Circulating cytokines and inflammatory markers (ELIZA) DNA analysis to assess genetic variations determining pro- versus anti inflammatory response including mTOR, HK2, PFKP, GLS, and GLUD1/2. pan-Salmonella PCR Gametocyte PCR

Locations

Country	Name	City	State
Burkina Faso	Clinical Research Unit of Nanoro	Nanoro	Boulkiemedé

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	Clinical Research Unit of Nanoro

Country where clinical trial is conducted

Burkina Faso, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Salmonella PCR	Salmonella PCR on EDTA whole blood (ethical clearance not yet obtained, amendment in progress)	June 2017 - December 2017
Primary	Vaccination data	Vaccination data as recorded on the vaccination card	June 2017 - December 2017
Primary	Nutritional status (Z-score or BMI)	weight (kg), height (cm) and upperarm circumference (mm) leading to outcome measure on nutritional status: as appropriate Z-score or BMI	June 2017 - December 2017
Primary	History of disease	Recorded history of disease according to the participants health card	June 2017 - December 2017
Primary	Immunological profile	Cytokine levels, including IL-1b, IL-6, IL-10, IFN-gamma, TNF-alpha and IL-17, which will be assessed through ELISA. Measurement will be done on stimulated and unstimulated blood. Ex-vivo whole blood stimulation will be done with RPMI, LPS, MTB, Staphylococcus aureus, Candida albicans and Salmonella Typhimurium.	June 2017 - December 2017
Primary	Genetic immunological profile	DNA analysis to assess genetic variations determining pro- versus anti inflammatory response including mTOR, HK2, PFKP, GLS, and GLUD1/2.	June 2017 - December 2017
Primary	subclinical parasitemia	low level malaria infection detected by SYSMEX hematology analyzer XN - 30	June 2017 - December 2017
Primary	Anemia	Differentiation of different forms of anemia using SYSMEX hematology analyzers XN -20 and XN - 30	June 2017 - December 2017
Primary	Reference values for hemocytometry in a healthy rural population from Burkina Faso	Hemocytometry using SYSMEX hematology analyzers XN -20 and XN - 30	June 2017 - December 2017
Secondary	Gametocyte PCR	Gametocyte PCR on EDTA whole blood stored in RNA protect	June 2017 - December 2017