Background

In Kenya, the prevalence of alcohol use disorder (AUD) is close to 6%, but a notable treatment gap persists. AUD is especially pronounced among men, leading to negative consequences at both individual and family levels. This study examines the experiences of problem-drinking fathers in Kenya regarding previous treatment-seeking related to alcohol use. Experiences and dynamics of the family are also explored as they pertain to treatment-seeking experiences.

Methods

In Eldoret, Kenya, semi-structured qualitative interviews were conducted with 11 families with a male exhibiting problem drinking, his spouse, and one child. Thematic content analysis was used to examine themes related to barriers and facilitators to treatment.

Results

Participants only reported informal help received from family and community members; they exhibited little awareness of available formal treatments. Families were both deeply affected by alcohol use and actively involved in help-seeking. Indeed, fathers' experiences are described as help-accepting rather than help-seeking. Three overarching themes emerged from the results: poverty, people, and practices. Poverty could be a motivator to accept help to support one's family financially, but stress from lack of work also drove drinking behaviours. People were also crucial as both barriers and facilitators of help-accepting. Negative help strategies or peer influence deterred fathers from accepting help to quit. Positive motivation, social support, and stigma against drinking were motivators. Practices that were culturally salient, such as religiosity and gender roles, facilitated help acceptance. Overall, most help efforts were short-term and only lead to very short-term behaviour change.

Conclusion

Families and communities are active in help provision for problem-drinking men in Kenya, though results confirm remaining need for effective interventions. Future interventions could benefit from recognizing the role of family to aid in treatment-engagement and attending to the importance of poverty, people, and practices in designing treatment strategies.

Creatine deficiency disorders are inborn errors of creatine metabolism, an energy homeostasis molecule. One of these, guanidinoacetate N-methyltransferase (GAMT) deficiency, has clinical characteristics that include features of autism, self-mutilation, intellectual disability, and seizures, with approximately 40% having a disorder of movement; failure to thrive can also be a component. Along with low creatine levels, guanidinoacetic acid (GAA) toxicity has been implicated in the pathophysiology of the disorder. Present-day therapy with oral creatine to control GAA lacks efficacy; seizures can persist. Dietary management and pharmacological ornithine treatment are challenging. Using an AAV-based gene therapy approach to express human codon-optimized GAMT in hepatocytes, in situ hybridization, and immunostaining, we demonstrated pan-hepatic GAMT expression. Serial collection of blood demonstrated a marked early and sustained reduction of GAA with normalization of plasma creatine; urinary GAA levels also markedly declined. The terminal time point demonstrated marked improvement in cerebral and myocardial creatine levels. In conjunction with the biochemical findings, treated mice gained weight to nearly match their wild-type littermates, while behavioral studies demonstrated resolution of abnormalities; PET-CT imaging demonstrated improvement in brain metabolism. In conclusion, a gene therapy approach can result in long-term normalization of GAA with increased creatine in guanidinoacetate N-methyltransferase deficiency and at the same time resolves the behavioral phenotype in a murine model of the disorder. These findings have important implications for the development of a new therapy for this abnormality of creatine metabolism.