Insights and efforts to control rabies in Zambia: Evaluation of determinants and barriers to dog vaccination in Nyimba district.

BACKGROUND: The current rabies control strategy in Zambia is based on dog vaccination, dog population control and dog movement restrictions. In Nyimba district of Zambia, dog vaccination coverage is low but the incidence of dog bites is high which places the community at risk of rabies infection. The renewed global interest eliminating rabies in developing countries has spurred interest to identify determinants and barriers of dog vaccination in an effort to reduce the overall disease burden. METHODOLOGY: A mixed methods cross sectional design was used in the study. This consisted of three parts: Evaluation of medical records regarding dog bite injuries, implementation and analysis of a household survey and in-depth review of key informant interviews. Data was collected into a Microsoft Excel database and subsequently transferred to STATA for descriptive, inferential and thematic analysis. RESULTS: Dog vaccination coverage overall was 8.7% (57/655), with 3.4% (22/655) in urban areas, 1.8% (12/655) in peri-urban and 3.5 (23/655) in the rural regions. Financially stable households were more likely to have their dogs vaccinated. Only 10.3% (31/300) of the respondents had vaccinated their dogs and these had a reliable source of income as 6% (18/300) were peasant farmers, 2% (6/300) were dependants whose guardians were financially stable and 2.3% (7/300) were in steady employment. Important barriers to dog vaccination included cost, limited awareness of vaccination program and access. CONCLUSION: Current rabies control strategies in Nyimba district, Zambia, appear quite limited. Improvements in the regional dog vaccination program may provide benefits. Enhancement of educational efforts targeting behavioural factors may also prove useful. Finally, the cost of dog vaccination can be reduced with scaled up production of a local vaccine.

Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan.

Purpose: We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients.Experimental Design: Sacituzumab govitecan was studied in patients with pretreated (median, 2; range, 1-7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate (ORR); duration of response, progression-free survival (PFS), and overall survival (OS) were secondary endpoints.Results: Sixty percent of patients showed tumor shrinkage from baseline CTs. On an intention-to-treat basis (N = 50), the ORR was 14% (17% for the 10-mg/kg group); the median response duration, 5.7 months; the clinical benefit rate (CBR ≥4 months), 34%; median PFS, 3.7 months; and median OS, 7.5 months. There was a suggested improvement in PR, CBR, and PFS with sacituzumab govitecan in second-line patients who were sensitive to first-line therapy, but no difference between first-line chemosensitive versus chemoresistant patients in the overall population. There was a statistically significant higher OS in those patients who received prior topotecan versus no topotecan therapy in a small subgroup. Grade ≥3 adverse events included neutropenia (34%), fatigue (13%), diarrhea (9%), and anemia (6%). Trop-2 tumor staining was not required for patient selection. No antibodies to the drug conjugate or its components were detected on serial blood collections.Conclusions: Sacituzumab govitecan appears to have a safe and effective therapeutic profile in heavily pretreated mSCLC patients, including those who are chemosensitive or chemoresistant to first-line chemotherapy. Additional studies as a monotherapy or combination therapy are warranted. Clin Cancer Res; 23(19); 5711-9. ©2017 AACR.

Therapy of Advanced Non-Small-Cell Lung Cancer With an SN-38-Anti-Trop-2 Drug Conjugate, Sacituzumab Govitecan.

Purpose Trop-2, expressed in most solid cancers, may be a target for antibody-drug conjugates (ADCs) in non-small-cell lung cancer (NSCLC). We studied sacituzumab govitecan (IMMU-132), a Trop-2 ADC, for the targeting of SN-38. Patients and Methods We evaluated IMMU-132 in a single-arm multicenter trial in patients with pretreated metastatic NSCLC who received either 8 or 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end points were safety and objective response rate (ORR). Progression-free survival and overall survival were secondary end points. Results Fifty-four patients were treated. In the response-assessable study population (n = 47), which had a median of three prior therapies (range, two to seven), the ORR was 19%; median response duration, 6.0 months (95% CI, 4.8 to 8.3 months); and clinical benefit rate (complete response + partial response + stable disease ≥ 4 months), 43%. ORR in the intention-to-treat (ITT) population was 17% (nine of 54). Responses occurred with a median onset of 3.8 months, including patients who had relapsed or progressed after immune checkpoint inhibitor therapy. Median ITT progression-free survival was 5.2 months (95% CI, 3.2 to 7.1 months) and median ITT overall survival, 9.5 months (95% CI, 5.9 to 16.7 months). Grade 3 or higher adverse events included neutropenia (28%), diarrhea (7%), nausea (7%), fatigue (6%), and febrile neutropenia (4%). One patient developed a transient immune response, despite patients receiving a median of 10 doses. More than 90% of 26 assessable archival tumor specimens were highly positive (2+, 3+) for Trop-2 by immunohistochemistry, which suggests that Trop-2 is not a predictive biomarker for response. Conclusion IMMU-132 was well-tolerated and induced durable responses in heavily pretreated patients with metastatic NSCLC. This ADC should be studied further in this disease and in other patients with Trop-2-expressing tumors.

Glycaemic Control and Associated Self-Management Behaviours in Diabetic Outpatients: A Hospital Based Observation Study in Lusaka, Zambia.

BACKGROUND: The control of diabetes mellitus depends on several factors that also include individual lifestyles. We assessed glycaemic control status and self-management behaviours that may influence glycaemic control among diabetic outpatients. METHODS: This cross-sectional study among 198 consenting randomly selected patients was conducted at the University Teaching Hospital diabetic clinic between September and December 2013 in Lusaka, Zambia. A structured interview schedule was used to collect data on demographic characteristics, self-management behaviours, and laboratory measurements. Binary logistic regression analysis using IBM SPSS for Windows version 20.0 was carried out to predict behaviours that were associated with glycaemic control status. RESULTS: The proportion of patients that had good glycaemic control status (HbA1c≤ 48 mmol/mol) was 38.7% compared to 61.3% that had poor glycaemic control status (HbA1c≥ 49 mmol/mol). Adherence to antidiabetic treatment and fasting plasma glucose predicted glycaemic control status of the patients. However, self-blood glucose monitoring, self-blood glucose monitoring means and exercise did not predict glycaemic control status of the patients. CONCLUSION: We find evidence of poor glycaemic control status among most diabetic patients suggesting that health promotion messages need to take into account both individual and community factors to promote behaviours likely to reduce nonadherence.

Glycaemic control in diabetic patients in Zambia.

INTRODUCTION: The glycaemic control status of diabetic patients affects the management of their disorder. We examined the glycaemic control and clinical factors that may influence the achievement of the glycaemic control targets among diabetic out-patients. METHODS: This was a hospital based cross-sectional study carried out at the University Teaching Hospital diabetic clinic in Lusaka, Zambia. A simple random sample of 198 consenting participants was selected from diabetic out-patients between September and December 2013. A structured interview schedule was used to capture socio-demographic data as well as needed clinical data from clients' medical records and laboratory results. Multivariate binary logistic regression analysis was carried out to examine factors that may be associated with the glycaemic control status of these diabetic patients. RESULTS: Overall (n = 198), mean (SD) age was 53.19 ± 13.32 years. Majority (61.3%) of the patients had poor glycaemic control status (HbA1c ≥ 49 mmol/mol). Insulin treatment (OR 0.13, 95% CI: 0.01 - 1.41), systolic blood pressure (OR 1.04, CI: 1.00 - 1.08) and fasting plasma glucose (previous; OR 0.81, CI: 0.72 - 0.90 and current; OR 0.85, CI: 0.78 - 0.93) were statistically significantly associated with glycaemic control. The poor glycaemic control observed in this study is similar to that reported in other published studies. CONCLUSION: We found evidence of poor glycaemic control in the study population suggesting need to explore the reasons for this. Association of Insulin, systolic blood pressure and fasting plasma glucose with glycaemic control further suggests the efficiency of traditional basic monitoring parameters which should be exploited in sharpening primary preventive strategies especially those that support lifestyle modification. Such efforts should also be integrated in all information, education and communication strategies that target but not limited to hospital based patients too.