First TES in Djibouti: A Critical Milestone Amid Rising Regional Threats

Area of Science:

• Malariology
• Molecular Epidemiology
• Public Health

Background:

• Malaria control in the Horn of Africa is challenged by antimalarial drug resistance, diagnostic failures due to gene deletions, and the invasive *Anopheles stephensi* mosquito.
• Djibouti has used artemether-lumefantrine (AL) as first-line treatment since 2014, with no prior in-country therapeutic efficacy studies (TES).

Purpose of the Study:

• To assess the therapeutic efficacy of artemether-lumefantrine (AL) for uncomplicated *Plasmodium falciparum* malaria in Djibouti.
• To investigate the prevalence of resistance markers, gene deletions, and parasite genetic diversity in Djibouti.

Main Methods:

• A 28-day, single-arm therapeutic efficacy study (TES) was conducted in Djibouti City.
• Patients received directly observed artemether-lumefantrine (AL). Follow-up included clinical assessment, microscopy, rapid diagnostic tests (RDT), and qPCR.
• Molecular analyses assessed antimalarial resistance markers, *pfhrp2/3* gene deletions, parasite diversity, and identity-by-descent.

Main Results:

• The PCR-adjusted adequate clinical and parasitological response (ACPR) to artemether-lumefantrine (AL) was 98.6%.
• Widespread *pfhrp2/3* gene deletions (95.6%) compromised HRP2-based RDT sensitivity, while pLDH-based RDTs remained effective.
• Prevalence of key resistance markers was noted, including *Pf*CRT CVIET (90.9%), *Pf*DHFR AIRNI (40.2%), and *Pf*DHPS ISGEAA (72.2%).

Conclusions:

• Artemether-lumefantrine (AL) remains effective for malaria treatment in Djibouti.
• Widespread *pfhrp2/3* gene deletions necessitate improved diagnostics and highlight the need for integrated molecular surveillance.
• Persistent gametocytemia and resistance markers underscore the importance of transmission-blocking interventions, such as single-dose primaquine.