Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05058885 |
| Other study ID # |
TMA2020CDF-3171. |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 2, 2022 |
| Est. completion date |
June 30, 2024 |
Study information
| Verified date |
April 2023 |
| Source |
University of Dschang |
| Contact |
Innocent Ali, PhD |
| Phone |
+237677021275 |
| Email |
dr.alinn[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Although Plasmodium vivax (P. vivax), one of the five malaria species causing parasites, has
the widest geographical distribution, it is rare in sub-Saharan Africa due to the absence of
a red blood cell receptor (Duffy antigen) in black Africans. Duffy-negative individuals are,
for the most part, therefore refractory to P. vivax infection and the Duffy-negative
phenotype is found at highest frequencies in Africa, whereas it is relatively rare elsewhere.
P. vivax has however, been observed as single infections in up to 5% of Duffy-negative
febrile patients in one health facility in Dschang, a region of low malaria transmission in
Western highlands of Cameroon. Whereas in the littoral South West and Southern forest of
Cameroon characterised by high malaria transmission, areas, there are contrasting molecular
evidence of human P. vivax infection. While important, the significance is limited from an
epidemiological point of view, concerning the source, transmission, distribution range of P.
vivax. There is thus a challenge in the true estimation of malaria burden, as well as the
attributable parasite species in infections occurring in the low transmission areas of
Western Cameroon. As a consequence, our understanding of the local epidemiology of malaria in
Western Cameroon warrants formal investigation. The current proposal is a multi-centre
observational study. Its purpose is to characterise the malaria species composition and
particularly exposure and burden of P. vivax across malaria endemic settings in Cameroon. It
will use multiplex serological methods based on quantitative suspension array on finger-stick
blood samples collected from febrile patients of ages 1-100 during two malaria transmission
seasons in different eco-climatic regions in Cameroon.
Description:
Type of study:
The current proposal is a multi-centre observational study in different eco-climatic regions
in Cameroon.
Study locations:
Dschang health district(Low transmission, highland) , Maroua (Sahel, high transmission) and
Bertoua-Batouri (East region, forest, perennial transmission).
Study period:
The study will be conducted over a period of 36 months beginning from June, 2021.
Study population:
In each selected health facility, children 1 year and above, and adult of both gender will be
eligible for participation.
Selection criteria: inclusion criteria, exclusion criteria.
Inclusion criteria:
1. Patient must be febrile (temperature >37.50 C or history of fever within 24 hours of
arrival to the hospital)
2. Patient must be aged 1 year or older
3. Both males and females alike
4. The patient must be able to sign a consent/assent form
5. The patient must be seeking care and be suspected of malaria infection
Non-inclusion criteria:
1. Patient less than 1 year
2. Patient not having fever
3. Patient not being suspected of malaria infection
Exclusion criteria:
1. Eligible patient who refuses consent to study procedures
2. Patient withdraws consent before or during the start of study procedures
3. Patient, who, for any reason, refuses that sensitive data should not be processed.
6) Recruitment strategies for the study population
Sample size and justification:
This study is a cross sectional study that will determine a point estimate of the
seroprevalence of parasite species, and in particular Plasmodium vivax in Cameroon. For this
reason, we calculated the sample size based on an estimate of Plasmodium vivax in febrile
patients as reported in a study in
2017((1)https://malariajournal.biomedcentral.com/articles/10.1186/s12936-017-1722-2), to get
the highest power to calculate the sample population size for use in our study. Using the
formula n = [DEFF*Np(1-p)]/ [(d2/Z21-α/2*(N-1)+p*(1-p)] in which DEFF=design effect=1, p
=Hypothesised percentage frequency of outcome factor in the population=25%, from above study,
d=confidence limit=5%, n=sample size, investigators calculated the for the study in three
sites to be 867 or 300 per site, taking into consideration a refusal rate 4%. The software
OpenEpi was used or the calculations (http://www.openepi.com/SampleSize/SSPropor.htm).The
primary outcome is the spatial seroprevalence of Plasmodium vivax among febrile patients in
the three epidemiological facies in Cameroon. For entomological component, WHO methods for
Human landing catch (HLC) will be used to catch mosquitoes in 12-15 houses in each of four
neighbourhoods over the periods corresponding to the beginning of malaria transmission, the
peak malaria transmission and at the end of the malaria transmission season.
8) Sample collection procedure:
In each selected health facility, febrile individuals 1 year and above will be eligible for
biological sample collection. Volunteers who have provided written informed consent/assent
will have a finger prick sampling (approximately 500μl). Four Dried Blood Spots (DBS, Whatman
903 Protein Saver) will be prepared for immunological and molecular assays.
Serological analysis
Six Plasmodium antigens will be used to screen patient samples: two P.f antigens (Merozoite
Surface Protein-1 19kD (MSP-1) and Apical Merozoite Antigen-1 (AMA-1), three P. vivax
antigens (PvMSP-1 and PvAMA-1, pvRBPII), one P. malariae (PmMSP-1) and one P. ovale (PoMSP-1)
selected on the basis of previous studies (20). Recombinant antigen will serve as a generic
protein to assess immunoglobulin G (IgG) non-specific binding. Antigens for other species of
malaria causing parasites are used in order to eliminate cross reacting sera and identify
co-infections from pure P. vivax infections.
Data analysis and management.
Data Management:
Field data will be entered into a password-protected database designed for the study through
hand held tablets at each study site. Primary data collection tool such as paper
questionnaires will be stored in metal cupboards with access control maintained by the
principal investigator of the study. Geographical location will be collected, but in the
dataset, it will be perturbed as well, by replacing with other coordinates which will not
distort the utility of the geolocation data and at minimum that the exact location of study
participants is not discernable.
Data analysis
Data will be cleaned centrally by visual inspection for outliers. The primary study outcome
for this will be the seroprevalence of P. vivax in the enrolled population of febrile
patients in different geo-ecological regions of Cameroon. The Bayesian analytical framework
using several different tools such as geographical positioning system, will be used to
characterise the spatial seroprevalence across different ecologies using individual and
geographical covariates in the model. The spatial software SaTScan will be used to identify
clusters of antibody responses against each antigen. The spatial analysis will be run
separately for each survey and spatial autocorrelation of clusters for each of the two survey
time points assessed using Moran's I in ArcGIS software, as done previously (22).
Age-adjusted antibody residuals from the regression model will be used for this analysis.
Risk factors for P. vivax infection will be assessed using mixed effect logistic regression
analysis with sampling site (health facility) considered a random effect variable. The
Microsoft Excel suite as well as the latest version of STATA or R-package will be used as the
statistical software.
Ethical considerations: potential risks, benefits, measures taken for data confidentiality
and respect for the privacy of participants
This is a minimal risk study that has an ethical clearance renewal from the IRB of the
Cameroon Baptist Convention health Services. This clearance will be renewed yearly until
close of study from the National Ethics Committee for Human Health Research (CNERSH). No
remuneration to participants will be made. Only de-identified datasets will be used for
analysis. At the end of the study, all hard copy materials and the study key will be
destroyed. This will follow local regulations that state a maximum of 15 years for data and
10 years for biological materials. The ethical committee requires that they be reached in
case a study participant feels his/her rights are being violated. In all information sheets
(of which the participant will have a copy), the mobile phone number of the responsible
contact of the ethical committee will be mentioned.
