Short-term malaria reduction by single-dose azithromycin during mass drug administration for trachoma, Tanzania

Abstract

Single-dose mass drug administration of azithromycin (AZT) is underway to eliminate trachoma worldwide. Studies in Ethiopia showed a reduction in all-cause childhood deaths after administration. To examine the effect of single-dose AZ MDA on prevalent malaria infections in a large prospective cohort of children and parents in Dodoma Province, Tanzania, we quantified the temporal prevalence of malaria parasitemia by real-time PCR for 6 months after single-dose AZT. In the first month after treatment but not in subsequent months, Plasmodium falciparum infections were reduced by 73% (95% CI 43%-89%) in treatment versus control villages and differences remained significant (p = 0.00497) in multivariate models with village-level random effects. Genetic sequencing of P. falciparum ribosomal L4 protein showed no mutations associated with AZT resistance. AZT mass drug administration caused a transient, 1-month antimalarial effect without selecting for P. falciparum ribosomal L4 resistance mutations in a region with a 10-year history of treating trachoma with this drug.

Keywords: Tanzania; azithromycin; malaria; mass drug administration; parasites; prospective cohort study; single dose; trachoma.

Figure 1

Flowchart of participants in study of short-term malaria reduction by single-dose azithromycin (AZT) during mass drug administration (MDA) for trachoma, Tanzania, January 12–July 21, 2009. AZT MDA (village-wide) and study panels show that 90% of persons who were intended to receive AZT received this drug. Total study participants with ≈1,000 in each group, shown in the study panel, contributed samples that are shown in the real-time PCR panel at each sampling time. Percentages in the real-time PCR panel used values from the study panel as the denominator.

Figure 2

Effect of azithromycin (AZT) mass drug administration (MDA) in treatment and control villages by time in study of short-term malaria reduction by single-dose AZT during MDA for trachoma, Tanzania. January 12–July 21, 2009. Proportions of real-time PCR prevalent Plasmodium falciparum infections are shown in participants from treatment villages (solid line) and control villages (dashed line and circles). Error bars indicate 95% CIs from exact binomial tests.

Figure 3

Study villages and location of malaria cases at baseline, Tanzania, January 12–July 21, 2009. Study site included 8 rural villages in central Tanzania, Dodoma Province. Four azithromycin (AZ) treatment villages in southeastern Tanzania are indicated by yellow numbers 1, 3, 4, and 6. Four nearby control villages in northwestern Tanzania are indicated by white numbers 2, 5, 7, and 8. The background map was extracted from Google Earth (Google, Mountain View, CA, USA). Households are indicated by blue dots, malaria cases at baseline are indicated by red dots, and Dar es Salaam (capital) is indicated by the green dot.

Figure 4

Effect of azithromycin (AZT) mass drug administration (MDA) in treatment and control villages over space and time, Tanzania, January 12–July 21, 2009. AZT MDA control villages (2, 5, 7, and 8) are shown on the left, and AZT MDA treatment villages (1, 3, 4, and 6) are shown on the right. Survey periods at baseline and month 1 are shown within treatment and control groups. Baseline infection and prevalent infections at month 1 (red circles) and negative tests (white circles) are shown. Spatial odds of Plasmodium falciparum (P.f.) infection are shown in areas of high odds of infection (red) and areas of low odds of infection (blue). Ln kernel smoothers were used to show spatial odds.