Format

Send to

Choose Destination
Malar J. 2019 Mar 12;18(1):76. doi: 10.1186/s12936-019-2716-z.

Persistence of chloroquine resistance alleles in malaria endemic countries: a systematic review of burden and risk factors.

Author information

1
Department of Pharmacology & Therapeutics, Makerere University, P.O. Box 7072, Kampala, Uganda. ocanmoses@gmail.com.
2
Africa Centre for Systematic Reviews and Knowledge Translation, Makerere University College of Health Sciences, P.O. Box 7072, Kampala, Uganda. ocanmoses@gmail.com.
3
Department of Psychiatry, Makerere University, P.O. Box 7072, Kampala, Uganda.
4
Infectious Disease Institute, Makerere University, P. O. Box 22418, Kampala, Uganda.
5
Department of Medical Microbiology, Makerere University, P.O. Box 7072, Kampala, Uganda.
6
Department of Medicine, Makerere University, P.O. Box 7072, Kampala, Uganda.
7
Africa Centre for Systematic Reviews and Knowledge Translation, Makerere University College of Health Sciences, P.O. Box 7072, Kampala, Uganda.
8
Albert Cook Library, Makerere University, P.O. Box 7072, Kampala, Uganda.
9
Clinical Epidemiology Unit, Department of Medicine, Makerere University, P.O. Box 7072, Kampala, Uganda.
10
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

Abstract

BACKGROUND:

Chloroquine, a previous highly efficacious, easy to use and affordable anti-malarial agent was withdrawn from malaria endemic regions due to high levels of resistance. This review collated evidence from published-reviewed articles to establish prevalence of Pfcrt 76T and Pfmdr-1 86Y alleles in malaria affected countries following official discontinuation of chloroquine use.

METHODS:

A review protocol was developed, registered in PROSPERO (#CRD42018083957) and published in a peer-reviewed journal. Article search was done in PubMed, Scopus, Lilacs/Vhl and Embase databases by two experienced librarians (AK, RS) for the period 1990-to-Febuary 2018. Mesh terms and Boolean operators (AND, OR) were used. Data extraction form was designed in Excel spread sheet 2007. Data extraction was done by three reviewers (NL, BB and MO), discrepancies were resolved by discussion. Random effects analysis was done in Open Meta Analyst software. Heterogeneity was established using I2-statistic.

RESULTS:

A total of 4721 citations were retrieved from article search (Pubmed = 361, Lilac/vhl = 28, Science Direct = 944, Scopus = 3388). Additional targeted search resulted in three (03) eligible articles. After removal of duplicates (n = 523) and screening, 38 articles were included in the final review. Average genotyping success rate was 63.6% (18,343/28,820) for Pfcrt K76T and 93.5% (16,232/17,365) for Pfmdr-1 86Y mutations. Prevalence of Pfcrt 76T was as follows; East Africa 48.9% (2528/5242), Southern Africa 18.6% (373/2163), West Africa 58.3% (3321/6608), Asia 80.2% (1951/2436). Prevalence of Pfmdr-1 86Y was; East Africa 32.4% (1447/5722), Southern Africa 36.1% (544/1640), West Africa 52.2% (1986/4200), Asia 46.4% (1276/2217). Over half, 52.6% (20/38) of included studies reported continued unofficial chloroquine use following policy change. Studies done in Madagascar and Kenya reported re-emergence of chloroquine sensitive parasites (IC50 < 30.9 nM). The average time (years) since discontinuation of chloroquine use to data collection was 8.7 ± 7.4. There was high heterogeneity (I2 > 95%).

CONCLUSION:

The prevalence of chloroquine resistance alleles among Plasmodium falciparum parasites have steadily declined since discontinuation of chloroquine use. However, Pfcrt K76T and Pfmdr-1 N86Y mutations still persist at moderate frequencies in most malaria affected countries.

KEYWORDS:

Chloroquine; Plasmodium falciparum; Policy; Re-emergence; Sensitivity

PMID:
30871535
PMCID:
PMC6419488
DOI:
10.1186/s12936-019-2716-z
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center