Chemoprophylaxis Delays Symptom Onset in Travelers Infected With Malaria

Malaria parasites
Malaria parasites
Researchers evaluated the effects of chemoprophylaxis among patients who were infected with malaria while traveling.

Chemoprophylaxis use was found to be associated with delayed symptom onset in patients who developed Plasmodium vivax or P ovale malaria infections after traveling to malaria-endemic countries, according to results of a study published in Clinical Infectious Diseases.

Data for this nested case-control study were sourced from the Malaria National Reference Centre database in France. Patients infected with malaria caused by either P vivax (n=247) or P ovale (n=615) after traveling to malaria-endemic countries between 2006 and 2017 were evaluated for illness characteristics and outcomes on the basis of chemoprophylaxis use. Researchers used multivariable logistic regression to assess the effect of chemoprophylaxis on the incubation period of the infection, the time between symptom onset and diagnosis, management, laboratory results, and the length of hospitalization.

Among patients infected with P vivax or P ovale included in the analysis, 30% and 47% received chemoprophylaxis, and 3% and 1% had severe disease, respectively. Patients included in the overall study population ranged in age between a median of 28 to 38 years and were predominantly men (range, 54.7%-73.4%). Most patients infected with P ovale had traveled to Western and Central Africa (range, 93.2%-95.0%), whereas those infected with P vivax had traveled to Southeastern Asia and the Western Pacific (range, 24.0%-37.3%), the Americas (range, 19.6%-29.8%), Southern and Eastern Africa (range, 15.2%-25.4%), and the Eastern Mediterranean (range, 0%-32.3%). Of patients with P vivax and P ovale infections who received chemoprophylaxis, poor adherence was noted in 59% and 56%, respectively, and the most common agents used included doxycycline, mefloquine, and atovaquone-proguanil.

Chemoprophylaxis use was found to be significantly associated with delayed symptom onset. For patients infected with P vivax, symptoms occurred after a median of 46 and 12 days among those who did vs did not receive chemoprophylaxis, respectively (P <.01). For patients infected with P ovale, symptoms occurred after a median incubation period of 67 and 15 days among those who did vs did not receive chemoprophylaxis, respectively (P <.001). Among the P ovale group, chemoprophylaxis use was associated with differing disease severity (P =.01), symptoms (P =.02), and hemoglobin levels (P <.001) compared with nonusers.


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In the multivariate analysis, chemoprophylaxis use was significantly associated with a 60-day or greater delay in symptom onset among patients infected with P vivax (adjusted odds ratio [aOR], 2.91; 95% CI, 1.22-6.95; P =.02), with similar results noted among those infected with P ovale (aOR, 2.28; 95% CI, 1.47-3.53; P <.001).

Further analysis was performed after stratification by type of chemoprophylaxis. Receipt of blood-stage agents, including doxycycline, mefloquine, chloroquine, or chloroquine-proguanil, was significantly associated with a 60-day or greater delay in symptom onset among patients infected with either P vivax (aOR, 3.54; 95% CI, 1.27-9.86; P =.02) or P ovale (aOR, 2.98; 95% CI, 1.85-4.80; P <.001).

Hemoglobin levels of 12 g/dL or less were associated with chemoprophylaxis use among patients infected with P ovale (OR, 1.76; 95% CI, 1.29-2.42; P =.005), but this association was attenuated after adjusting for covariates.

No biologic characteristics at diagnosis or management were associated with chemoprophylaxis use.

This study was limited by the fact that malaria surveillance programs in France are projected to capture 1 out of 2 cases, so these findings are not representative of all infections acquired during travel.

According to the researchers, “this work suggests that using chemoprophylaxis, especially doxycycline, mefloquine, chloroquine or chloroquine-proguanil, may delay the onset of symptoms” in patients with P vivax or P ovale malaria.”

Disclosure: Multiple authors declared affiliations with industry. Please see to the original reference for a full list of disclosures.

Reference

Le Goff M, Kendjo E, Thellier M, Piarroux R, Boelle P-Y, Jaureguiberry S; on behalf of the French National Reference Centre for Imported Malaria Study Group. Impact of chemoprophylaxis on Plasmodium vivax and Plasmodium ovale infection among civilian travellers: a nested case-control study with a counterfactual approach on 862 patients. Clin Infect Dis. 2022;ciac641. doi:10.1093/cid/ciac641