Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu-Natal, South Africa.

Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that harbors the Philadelphia chromosome. Tyrosine kinase inhibitor (TKI) therapy has dramatically improved the survival of patients with CML. Nevertheless, 20%-40% of CML patients require changes in TKI therapy due to intolerance or drug resistance. A total of 30%-60% of resistant cases result from kinase domain (KD) mutations. There is currently no published data on CML KD mutations in South Africa. Methods: This retrospective, descriptive study collected data from 206 CML patients attending the King Edward Hospital Hematology clinic. Patient-based and mutation-based factors were analyzed using descriptive statistical analysis and Kaplan-Meier curves for survival analysis. Results: KD mutations were detected in 29.1% (n = 60 of 206). A total of 40 different KD mutations were detected, with unknown responses to TKI therapy in 65% (n = 26 of 40). A total of 57.7% (n = 15 of 26) of mutations with an unknown response, showed a response to specific TKIs in our study. Four patients had A399T mutations, of which two showed good responses to Nilotinib. Patients with I293N and V280M mutations showed good responses to Imatinib. G250E was most frequently detected. Despite M351T being one of six most commonly reported KD mutations globally, this mutation was not detected in our patient cohort. A total of 20.9% (n = 43 of 206) human immunodeficiency virus (HIV) positive patients were identified, of which 25.6% (n = 11 of 43) had KD mutations. HIV status showed no significant effect on mutational status or overall survival. Conclusion: The predicted response to TKI therapy was unknown in more than half of the KD mutations detected in our patient population. Additionally, eight patients with mutations with known responses to TKIs showed responses discordant to that expected. HIV status and KD mutations had no statistically significant effect on overall survival. Although some data were comparable to international publications, few notable differences warrant further investigation.

Response and remediation actions following the detection of Naegleria fowleri in two treated drinking water distribution systems, Louisiana, 2013-2014.

Naegleria fowleri causes the usually fatal disease primary amebic meningoencephalitis (PAM), typically in people who have been swimming in warm, untreated freshwater. Recently, some cases in the United States were associated with exposure to treated drinking water. In 2013, a case of PAM was reported for the first time in association with the exposure to water from a US treated drinking water system colonized with culturable N. fowleri. This system and another were found to have multiple areas with undetectable disinfectant residual levels. In response, the water distribution systems were temporarily converted from chloramine disinfection to chlorine to inactivate N. fowleri and reduced biofilm in the distribution systems. Once >1.0 mg/L free chlorine residual was attained in all systems for 60 days, water testing was performed; N. fowleri was not detected in water samples after the chlorine conversion. This investigation highlights the importance of maintaining adequate residual disinfectant levels in drinking water distribution systems. Water distribution system managers should be knowledgeable about the ecology of their systems, understand potential water quality changes when water temperatures increase, and work to eliminate areas in which biofilm growth may be problematic and affect water quality.