28 research outputs found
Factors Associated with the Rapid and Durable Decline in Malaria Incidence in El Salvador, 1980-2017
A decade after the Global Malaria Eradication Program, El
Salvador had the highest burden of malaria in Mesoamerica, with
approximately 20% due to Plasmodium falciparum. A resurgence of
malaria in the 1970s led El Salvador to alter its national
malaria control strategy. By 1995, El Salvador recorded its last
autochthonous P. falciparum case with fewer than 20 Plasmodium
vivax cases annually since 2011. By contrast, its immediate
neighbors continue to have the highest incidences of malaria in
the region. We reviewed and evaluated the policies and
interventions implemented by the Salvadoran National Malaria
Program that likely contributed to this progress toward malaria
elimination. Decentralization of the malaria program, early
regional stratification by risk, and data-driven
stratum-specific actions resulted in the timely and targeted
allocation of resources for vector control, surveillance, case
detection, and treatment. Weekly reporting by health workers and
volunteer collaborators-distributed throughout the country by
strata and informed via the national surveillance system-enabled
local malaria teams to provide rapid, adaptive, and focalized
program actions. Sustained investments in surveillance and
response have led to a dramatic reduction in local transmission,
with most current malaria cases in El Salvador due to
importation from neighboring countries. Additional support for
systematic elimination efforts in neighboring countries would
benefit the region and may be needed for El Salvador to achieve
and maintain malaria elimination. El Salvador's experience
provides a relevant case study that can guide the application of
similar strategies in other countries committed to malaria
elimination
Disruption of γ-Glutamyl Leukotrienase Results in Disruption of Leukotriene D(4) Synthesis In Vivo and Attenuation of the Acute Inflammatory Response
To study the function of γ-glutamyl leukotrienase (GGL), a newly identified member of the γ-glutamyl transpeptidase (GGT) family, we generated null mutations in GGL (GGL(tm1)) and in both GGL and GGT (GGL(tm1)-GGT(tm1)) by a serial targeting strategy using embryonic stem cells. Mice homozygous for GGL(tm1) show no obvious phenotypic changes. Mice deficient in both GGT and GGL have a phenotype similar to the GGT-deficient mice, but ∼70% of these mice die before 4 weeks of age, at least 2 months earlier than mice deficient only in GGT. These double-mutant mice are unable to cleave leukotriene C(4) (LTC(4)) to LTD(4), indicating that this conversion is completely dependent on the two enzymes, and in some organs (spleen and uterus) deletion of GGL alone abolished more than 90% of this activity. In an experimental model of peritonitis, GGL alone is responsible for the generation of peritoneal LTD(4). Further, during the development of peritonitis, GGL-deficient mice show an attenuation in neutrophil recruitment but not of plasma protein influx. These findings demonstrate an important role for GGL in the inflammatory response and suggest that LTC(4) and LTD(4) have distinctly different functions in the inflammatory process