Rectal artesunate for severe malaria, implementation research, Zambia.

Objective: To determine whether the positive results of a single-district pilot project focused on rectal artesunate administration at the community level in Zambia could be replicated on a larger scale. Methods: In partnership with government, in 10 rural districts during 2018-2021 we: (i) trained community health volunteers to administer rectal artesunate to children with suspected severe malaria and refer them to a health facility; (ii) supported communities to establish emergency transport, food banks and emergency savings to reduce referral delays; (iii) ensured adequate drug supplies; (iv) trained health workers to treat severe malaria with injectable artesunate; and (v) monitored severe malaria cases and associated deaths via surveys, health facility data and a community monitoring system. Results: Intervention communities accessed quality-assured rectal artesunate from trained community health volunteers, and follow-on treatment for severe malaria from health workers. Based on formal data from the health management information system, reported deaths from severe malaria reduced significantly from 3.1% (22/699; 95% confidence interval, CI: 2.0-4.2) to 0.5% (2/365; 95% CI: 0.0-1.1) in two demonstration districts, and from 6.2% (14/225; 95% CI: 3.6-8.8) to 0.6% (2/321; 95% CI: 0.0-1.3) in eight scale-up districts. Conclusion: Despite the effects of the coronavirus disease, our results confirmed that pre-referral rectal artesunate administered by community health volunteers can be an effective intervention for severe malaria among young children. Our results strengthen the case for wider expansion of the pre-referral treatment in Zambia and elsewhere when combined with supporting interventions.

Use of rectal artesunate for severe malaria at the community level, Zambia.

OBJECTIVE: To determine whether the administration of rectal artesunate by trained community health volunteers before referral to a health-care facility reduces the case fatality rate of severe malaria in young children in hard-to-reach communities in Zambia. METHODS: We implemented a pilot project in Serenje District between July 2017 and July 2018. The project involved: (i) training community health volunteers to administer rectal artesunate to children with suspected severe malaria and refer them to a health facility; (ii) ensuring emergency transport with bicycle ambulances was available; (iii) ensuring adequate drug supplies; and (iv) ensuring health-care workers could treat severe malaria with injectable artesunate. Surveys of health facilities, volunteers and bicycle ambulance riders were performed near the beginning and end of the intervention period. In addition, data on severe malaria cases and associated deaths were obtained from health facilities and a community monitoring system. FINDINGS: In the year before the intervention, 18 deaths occurred in 224 cases of confirmed severe malaria among children younger than 5 years seen at intervention health facilities (case fatality rate: 8%); during the intervention, 3 of 619 comparable children with severe malaria died (case fatality rate: 0.5%). CONCLUSION: The administration of pre-referral rectal artesunate treatment to young children with severe malaria by community health volunteers was feasible, safe and effective in hard-to-reach communities in Zambia and was associated with a substantial decrease in the case fatality rate. The project's approach is highly adaptable and could be used in other countries with a high malaria burden.

Is "not just right experience" (NJRE) in obsessive-compulsive disorder part of an autistic phenotype?

OBJECTIVE: Harm avoidance (HA) and "not just right experience" (NJRE) have been proposed to be 2 core motivational processes underlying obsessive-compulsive disorder (OCD). The objective of this study was to explore whether NJRE demarcates a neurodevelopmental OCD subgroup distinct from HA related to autistic traits and/or to a broader phenotype of cognitive rigidity and sensory processing difficulties associated with an earlier age of OCD onset. METHODS: A correlational design investigated whether NJRE and HA are distinct entities in OCD and explored their relationship to autism spectrum disorder (ASD) traits measured by the Autism Quotient (AQ), sensory processing, set-shifting, and age of OCD onset in an OCD sample (N=25). RESULTS: NJRE was only moderately (r=.34) correlated to HA and not significant in this study. Consistent with predictions, NJRE was associated with sensory processing difficulties and an earlier age of OCD onset. No significant relationships were found between NJRE and ASD traits as measured by the AQ or set-shifting difficulties. CONCLUSIONS: These preliminary findings suggest a lack of evidence demonstrating NJRE as a manifestation of core autistic traits as measured by the AQ. However, NJRE was associated with sensory abnormalities and an earlier age of OCD onset. The role of NJRE as a developmental, and possibly neurodevelopmental, risk factor for OCD possibly warrants further investigation.

Biological and computational evaluation of resveratrol inhibitors against Alzheimer's disease.

It has been reported that beta amyloid induces production of radical oxygen species and oxidative stress in neuronal cells, which in turn upregulates ß-secretase (BACE-1) expression and beta amyloid levels, thereby propagating oxidative stress and increasing neuronal injury. A series of resveratrol derivatives, known to be inhibitors of oxidative stress-induced neuronal cell death (oxytosis) were biologically evaluated against BACE-1 using homogeneous time-resolved fluorescence (TRF) assay. Correlation between oxytosis inhibitory and BACE-1 inhibitory activity of resveratrol derivatives was statistically significant, supporting the notion that BACE-1 may act as pivotal mediator of neuronal cell oxytosis. Four of the biologically evaluated resveratrol analogs demonstrated considerably higher activity than resveratrol in either assay. The discovery of some "hits" led us to initiate detailed docking studies associated with Molecular Dynamics in order to provide a plausible explanation for the experimental results and understand their molecular basis of action.

How a Communication Intervention in Zambia Re-Oriented Health Services to the Needs of the Least-Supported.

Despite decades of training health workers in communication, complaints from clients and communities about poor health worker attitudes abound. This was found to be so in Zambia where the More Mobilizing Access to Maternal Health Services in Zambia (MORE MAMaZ) program was trying to ensure the inclusion of under-supported women in a community-based maternal and newborn health program in five intervention districts. Under-supported women suffer a disproportionate burden of child mortality and are poor users of health services. An exploratory small-scale qualitative survey involving nurses from training schools and health facilities found that nurses knew how to communicate well, but were selective with whom and in what circumstances they did this. In general, those who received the worst communication were under-supported and had low confidence-the very people who needed the best communication. An experiential training program was started to help health workers reflect on the reasons for their poor communication. The training was evaluated after 14 months using semi-structured interviews and focus group discussions with staff at participating health facilities. The results showed improved inclusion of under-supported women but also increased attendance generally for ante-natal clinics, deliveries and under-five clinics. Another outcome was improved communication between, and a sense of job satisfaction among, the health workers themselves. The program demonstrated an effective way to improve the inclusion and involvement of the least-supported women and girls. There are important lessons for other health programs that aim to operationalize the goals of the Global Strategy for Women's, Children's and Adolescent's Health, which include an emphasis on reaching every woman.

Rectal artesunate for severe malaria, implementation research, Zambia

Objective To determine whether the positive results of a single-district pilot project focused on rectal artesunate administration at the community level in Zambia could be replicated on a larger scale. Methods In partnership with government, in 10 rural districts during 2018­2021 we: (i) trained community health volunteers to administer rectal artesunate to children with suspected severe malaria and refer them to a health facility; (ii) supported communities to establish emergency transport, food banks and emergency savings to reduce referral delays; (iii) ensured adequate drug supplies; (iv) trained health workers to treat severe malaria with injectable artesunate; and (v) monitored severe malaria cases and associated deaths via surveys, health facility data and a community monitoring system. Results Intervention communities accessed quality-assured rectal artesunate from trained community health volunteers, and follow-on treatment for severe malaria from health workers. Based on formal data from the health management information system, reported deaths from severe malaria reduced significantly from 3.1% (22/699; 95% confidence interval, CI: 2.0­4.2) to 0.5% (2/365; 95% CI: 0.0­1.1) in two demonstration districts, and from 6.2% (14/225; 95% CI: 3.6­8.8) to 0.6% (2/321; 95% CI: 0.0­1.3) in eight scale-up districts. Conclusion Despite the effects of the coronavirus disease, our results confirmed that pre-referral rectal artesunate administered by community health volunteers can be an effective intervention for severe malaria among young children. Our results strengthen the case for wider expansion of the pre-referral treatment in Zambia and elsewhere when combined with supporting interventions.