Genomic variations in polymyxin-resistant Pseudomonas aeruginosa clinical isolates and their effects on polymyxin resistance.

Infection with P. aeruginosa, one of the most relevant opportunistic pathogens in hospital-acquired infections, can lead to high mortality due to its low antibiotic susceptibility to limited choices of antibiotics. Polymyxin as last-resort antibiotics is used in the treatment of systemic infections caused by multidrug-resistant P. aeruginosa strains, so studying the emergence of polymyxin-resistant was a must. The present study was designed to define genomic differences between paired polymyxin-susceptible and polymyxin-resistant P. aeruginosa strains and established polymyxin resistance mechanisms, and common chromosomal mutations that may confer polymyxin resistance were characterized. A total of 116 CRPA clinical isolates from patients were collected from three tertiary care hospitals in China during 2017-2021. Our study found that polymyxin B resistance represented 3.45% of the isolated carbapenem-resistant P. aeruginosa (CRPA). No polymyxin-resistant isolates were positive for mcr (1-8 and 10) gene and efflux mechanisms. Key genetic variations identified in polymyxin-resistant isolates involved missense mutations in parR, parS, pmrB, pmrA, and phoP. The waaL and PA5005 substitutions related to LPS synthesis were detected in the highest levels of resistant strain (R1). The missense mutations H398R in ParS (4/4), Y345H in PmrB (4/4), and L71R in PmrA (3/4) were the predominant. Results of the PCR further confirmed that mutation of pmrA, pmrB, and phoP individually or simultaneously did affect the expression level of resistant populations and can directly increase the expression of arnBCADTEF operon to contribute to polymyxin resistance. In addition, we reported 3 novel mutations in PA1945 (2129872_A < G, 2130270_A < C, 2130272_T < G) that may confer polymyxin resistance in P. aeruginosa. Our findings enriched the spectrum of chromosomal mutations, highlighted the complexity at the molecular level, and multifaceted interplay mechanisms underlying polymyxin resistance in P. aeruginosa.

A public health achievement under adversity: the eradication of poliomyelitis from Peru, 1991.

The fight to achieve global eradication of poliomyelitis continues. Although native transmission of poliovirus was halted in the Western Hemisphere by the early 1990s, and only a few cases have been imported in the past few years, much of Latin America's story remains to be told. Peru conducted a successful flexible, or flattened, vertical campaign in 1991. The initial disease-oriented programs began to collaborate with community-oriented primary health care systems, thus strengthening public-private partnerships and enabling the common goal of poliomyelitis eradication to prevail despite rampant terrorism, economic instability, and political turmoil. Committed leaders in Peru's Ministry of Health, the Pan American Health Organization, and Rotary International, as well as dedicated health workers who acted with missionary zeal, facilitated acquisition of adequate technologies, coordinated work at the local level, and increased community engagement, despite sometimes being unable to institutionalize public health improvements.

Childhood immunization rates in rural Intibucá, Honduras: an analysis of a local database tool and community health center records for assessing and improving vaccine coverage.

BACKGROUND: Vaccines are highly effective at preventing infectious diseases in children, and prevention is especially important in resource-limited countries where treatment is difficult to access. In Honduras, the World Health Organization (WHO) reports very high immunization rates in children. To determine whether or not these estimates accurately depict the immunization coverage in non-urban regions of the country, we compared the WHO data to immunization rates obtained from a local database tool and community health center records in rural Intibucá, Honduras. METHODS: We used data from two sources to comprehensively evaluate immunization rates in the area: 1) census data from a local database and 2) immunization data collected at health centers. We compared these rates using logistic regression, and we compared them to publicly available WHO-reported estimates using confidence interval inclusion. RESULTS: We found that mean immunization rates for each vaccine were high (range 84.4 to 98.8 percent), but rates recorded at the health centers were significantly higher than those reported from the census data (p ≤ 0.001). Combining the results from both databases, the mean rates of four out of five vaccines were less than WHO-reported rates (p <0.05). Overall immunization rates were significantly different between townships (p=0.03). The rates by individual vaccine were similar across townships (p >0.05), except for diphtheria/tetanus/pertussis vaccine (p=0.02) and oral polio vaccine (p <0.01). CONCLUSIONS: Immunization rates in Honduras were high across data sources, though most of the rates recorded in rural Honduras were less than WHO-reported rates. Despite geographical difficulties and barriers to access, the local database and Honduran community health workers have developed a thorough system for ensuring that children receive their immunizations on time. The successful integration of community health workers and a database within the Honduran decentralized health system may serve as a model for other immunization programs in resource-limited countries where health care is less accessible.