Tuberculosis Treatment Outcome and Drug Resistance in Lambaréné, Gabon: A Prospective Cohort Study.

Despite overall global progress in tuberculosis (TB) control, TB remains one of the deadliest communicable diseases. This study prospectively assessed TB epidemiology in Lambaréné, Gabon, a Central African country ranking 10th in terms of TB incidence rate in the 2014 World Health Organization TB report. In Lambaréné, between 2012 and 2014, 201 adult and pediatric TB patients were enrolled and followed up; 66% had bacteriologically confirmed TB and 95% had pulmonary TB. The human immunodeficiency virus (HIV) coinfection rate was 42% in adults and 16% in children. Mycobacterium tuberculosis and Mycobacterium africanum were identified in 82% and 16% of 108 culture-confirmed TB cases, respectively. Isoniazid (INH) and streptomycin yielded the highest resistance rates (13% and 12%, respectively). The multidrug resistant TB (MDR-TB) rate was 4/91 (4%) and 4/13 (31%) in new and retreatment TB cases, respectively. Treatment success was achieved in 53% of patients. In TB/HIV coinfected patients, mortality rate was 25%. In this setting, TB epidemiology is characterized by a high rate of TB/HIV coinfection and low treatment success rates. MDR-TB is a major public health concern; the need to step-up in-country diagnostic capacity for culture and drug susceptibility testing as well as access to second-line TB drugs urgently requires action.

Malaria parasites form filamentous cell-to-cell connections during reproduction in the mosquito midgut.

Physical contact is important for the interaction between animal cells, but it can represent a major challenge for protists like malaria parasites. Recently, novel filamentous cell-cell contacts have been identified in different types of eukaryotic cells and termed nanotubes due to their morphological appearance. Nanotubes represent small dynamic membranous extensions that consist of F-actin and are considered an ancient feature evolved by eukaryotic cells to establish contact for communication. We here describe similar tubular structures in the malaria pathogen Plasmodium falciparum, which emerge from the surfaces of the forming gametes upon gametocyte activation in the mosquito midgut. The filaments can exhibit a length of > 100 µm and contain the F-actin isoform actin 2. They actively form within a few minutes after gametocyte activation and persist until the zygote transforms into the ookinete. The filaments originate from the parasite plasma membrane, are close ended and express adhesion proteins on their surfaces that are typically found in gametes, like Pfs230, Pfs48/45 or Pfs25, but not the zygote surface protein Pfs28. We show that these tubular structures represent long-distance cell-to-cell connections between sexual stage parasites and demonstrate that they meet the characteristics of nanotubes. We propose that malaria parasites utilize these adhesive "nanotubes" in order to facilitate intercellular contact between gametes during reproduction in the mosquito midgut.

Intermittent preventive treatment against malaria in infants in Gabon--a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Intermittent preventive treatment aims to maximize the protective effects of malaria chemoprophylaxis while minimizing the deleterious effects. METHODS: In Gabon, 1189 infants received either sulfadoxine-pyrimethamine (SP; 250 and 12.5 mg, respectively) or placebo at 3, 9, and 15 months of age. Children were actively followed-up until 18 months of age. RESULTS: In the intention-to-treat population at 18 months of follow-up, 84 children (17%) in the SP group had > or =1 episode of anemia, versus 108 (21%) in the placebo group (protective efficacy, 22% [95% confidence interval {CI}, -1% to 40%]; P=.06). In the intervention group, there were 66 episodes during 485 person-years at risk, compared with 79 episodes during 497 years in the placebo group (protective efficacy, 17% [95% CI, -24% to 45%; P=.36). The effects were similar at 12 months of follow-up. The study drug was safe and well tolerated. CONCLUSIONS: The intervention was efficacious, producing a reduction in risk for anemia but a smaller effect against malaria. It is a valuable additional tool to control malaria in a highly vulnerable age group. Remaining important questions are currently being addressed in further studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00167843.