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BackgroundDespite notable progress in the control and prevention of malaria in the Horn of Africa, the disease continues to cause significant morbidity and mortality in various regions of Ethiopia, and elsewhere in the region. The transmission of malaria is affected by genetic, sociocultural, and ecological factors. Lare is an Ethiopian district adjacent to the Ethio-South Sudan border, in Gambella region. The region currently has the highest prevalence of malaria in Ethiopia. This study assesses the burden and spatiotemporal patterns of disease transmission, including the effect of climatic factors on the occurrence of malaria, across an international border crossing. This understanding can assist in crafting informed programmatic and policy decisions for interventions.MethodsThis study was conducted in Lare district, Southwest Ethiopia, a temperate zone. A retrospective descriptive analysis was conducted using clinical service data collected between 2011 and 2021 from the 9 health facilities of the district. Both clinically diagnosed patients and those identified using microscopy and rapid diagnostic testing (RDT) were included in the study. Additionally, climate data was incorporated into analyses. Examples of analyses include malaria burden, positivity rate, incidence, species frequency, and an ANOVA to assess inter-annual case number and meteorological factor variation.ResultsBetween 2011 and 2021, a total of 96,616 suspected malaria cases were tested by microscopy or RDT, and 39,428 (40.8%) of these cases were reported as positive. There were 1276 patients admitted with 22 deaths recorded. There were further more significant fluctuations in positivity rates across years, the highest being 74.5% in 2021. Incidence varied from 18.0% in 2011 to 151.6% in 2016. The malaria parasite species most detected was Plasmodium falciparum, followed by a smaller proportion of Plasmodium vivax. The greatest proportions of P. falciparum cases were observed in 2018 and 2019, at 97.4% and 97.0% prevalence, respectively. There was significant seasonal variation in case number, the highest observed in July through September of each year. Climatic conditions of annual rainfall, temperature and humidity favored the increment of malaria cases from June until October.ConclusionThe study shows that the burden, i.e. morbidity and mortality (with fluctuating patterns) of malaria are still significant public health problems and can pose serious consequences in the district. This has implication for cross-border malaria transmission risk due to considerable border crossings. The predominant cause of the disease is P. falciparum, which causes severe complications in patients. The district has to prepare to deal with such complications for better patient care and outcomes.

Several essential cellular metabolites, such as enzyme cofactors, contain sulfur atoms and their biosynthesis requires specific thiolation enzymes. LarE is an ATP‐dependent sulfur insertase, which catalyzes the sequential conversion of the two carboxylate groups of the precursor of the lactate racemase cofactor into thiocarboxylates. Two types of LarE enzymes are known, one that uses a catalytic cysteine as a sacrificial sulfur donor, and the other one that uses a [4Fe‐4S] cluster as a cofactor. Only the crystal structure of LarE from Lactobacillus plantarum (LpLarE) from the first class has been solved. We report here the crystal structure of LarE from Methanococcus maripaludis (MmLarE), belonging to the second class, in the cluster‐free (apo‐) and cluster‐bound (holo‐) forms. The structure of holo‐MmLarE shows that the [4Fe‐4S] cluster is chelated by three cysteines only, leaving an open coordination site on one Fe atom. Moreover, the fourth nonprotein‐bonded iron atom was able to bind an anionic ligand such as a phosphate group or a chloride ion. Together with the spectroscopic analysis of holo‐MmLarE and the previously reported biochemical investigations of holo‐LarE from Thermotoga maritima, these crystal structures support the hypothesis of a reaction mechanism, in which the [4Fe‐4S] cluster binds a hydrogenosulfide ligand in place of the chloride anion, thus generating a [4Fe‐5S] intermediate, and transfers it to the substrate, as in the case of [4Fe‐4S]‐dependent tRNA thiolation enzymes. [ABSTRACT FROM AUTHOR]

Abstract Background Despite notable progress in the control and prevention of malaria in the Horn of Africa, the disease continues to cause significant morbidity and mortality in various regions of Ethiopia, and elsewhere in the region. The transmission of malaria is affected by genetic, sociocultural, and ecological factors. Lare is an Ethiopian district adjacent to the Ethio-South Sudan border, in Gambella region. The region currently has the highest prevalence of malaria in Ethiopia. This study assesses the burden and spatiotemporal patterns of disease transmission, including the effect of climatic factors on the occurrence of malaria, across an international border crossing. This understanding can assist in crafting informed programmatic and policy decisions for interventions. Methods This study was conducted in Lare district, Southwest Ethiopia, a temperate zone. A retrospective descriptive analysis was conducted using clinical service data collected between 2011 and 2021 from the 9 health facilities of the district. Both clinically diagnosed patients and those identified using microscopy and rapid diagnostic testing (RDT) were included in the study. Additionally, climate data was incorporated into analyses. Examples of analyses include malaria burden, positivity rate, incidence, species frequency, and an ANOVA to assess inter-annual case number and meteorological factor variation. Results Between 2011 and 2021, a total of 96,616 suspected malaria cases were tested by microscopy or RDT, and 39,428 (40.8%) of these cases were reported as positive. There were 1276 patients admitted with 22 deaths recorded. There were further more significant fluctuations in positivity rates across years, the highest being 74.5% in 2021. Incidence varied from 18.0% in 2011 to 151.6% in 2016. The malaria parasite species most detected was Plasmodium falciparum, followed by a smaller proportion of Plasmodium vivax. The greatest proportions of P. falciparum cases were observed in 2018 and 2019, at 97.4% and 97.0% prevalence, respectively. There was significant seasonal variation in case number, the highest observed in July through September of each year. Climatic conditions of annual rainfall, temperature and humidity favored the increment of malaria cases from June until October. Conclusion The study shows that the burden, i.e. morbidity and mortality (with fluctuating patterns) of malaria are still significant public health problems and can pose serious consequences in the district. This has implication for cross-border malaria transmission risk due to considerable border crossings. The predominant cause of the disease is P. falciparum, which causes severe complications in patients. The district has to prepare to deal with such complications for better patient care and outcomes.

In this paper, we propose a nonconcave penalized M-estimation of the least absolute relative errors (penalized M-LARE) method for a sparse multiplicative regression model, where the dimension of model can increase with the sample size. Under certain appropriate conditions, the consistency and asymptotic normality for the penalized M-LARE estimator are established. Simulations and a real data analysis are in support of our theoretical results and illustrate that the proposed method performs well. [ABSTRACT FROM AUTHOR]

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Several essential cellular metabolites, such as enzyme cofactors, contain sulfur atoms and their biosynthesis requires specific thiolation enzymes. LarE is an ATP-dependent sulfur insertase, which catalyzes the sequential conversion of the two carboxylate groups of the precursor of the lactate racemase cofactor into thiocarboxylates. Two types of LarE enzymes are known, one that uses a catalytic cysteine as a sacrificial sulfur donor, and the other one that uses a [4Fe-4S] cluster as a cofactor. Only the crystal structure of LarE from Lactobacillus plantarum (LpLarE) from the first class has been solved. We report here the crystal structure of LarE from Methanococcus maripaludis (MmLarE), belonging to the second class, in the cluster-free (apo-) and cluster-bound (holo-) forms. The structure of holo-MmLarE shows that the [4Fe-4S] cluster is chelated by three cysteines only, leaving an open coordination site on one Fe atom. Moreover, the fourth nonprotein-bonded iron atom was able to bind an anionic ligand such as a phosphate group or a chloride ion. Together with the spectroscopic analysis of holo-MmLarE and the previously reported biochemical investigations of holo-LarE from Thermotoga maritima, these crystal structures support the hypothesis of a reaction mechanism, in which the [4Fe-4S] cluster binds a hydrogenosulfide ligand in place of the chloride anion, thus generating a [4Fe-5S] intermediate, and transfers it to the substrate, as in the case of [4Fe-4S]-dependent tRNA thiolation enzymes., (© 2023 The Protein Society.)

Einleitung Die bayerische Landesarbeitsgemeinschaft multiresistente Erreger hat es sich zur Aufgabe gemacht, das Vorkommen dieser Erreger im gesamten bayerischen Gesundheitswesen zu reduzieren. Dieses Ziel kann nur erreicht werden, wenn die Einrichtungen des Gesundheitswesens gemeinsam an einem Strang ziehen und für die Umsetzung einheitlicher Strategien zur Bekämpfung multiresistenter Erreger sorgen. The Bavarian National Working Group Antibiotic Resistent Pathogens addresses to the task of reducing these pathogens in the bayarian health system. This aim can only be reached, if the institutions of the health system all pull together and take care to implement consistent strategies in the fight against pathogens with antibiotic resistance. [ABSTRACT FROM AUTHOR]